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  • 1
    ISSN: 1420-908X
    Keywords: Key words: Neutrophil elastase — FR901277 — Paw edema — Hemorrhage — Pulmonary emphysema
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: A neutrophil elastase inhibitor FR901277 was examined for its inhibitory effect on degradation of natural substrate elastin in vitro, and on acute inflammatory states and pulmonary emphysema in vivo.¶Material and Treatment: Elastin-congo red was used as a substrate for elastin degradation assay. Paw edema in male C57BL mice (6 weeks old) and pulmonary hemorrhage in female golden hamsters (5 weeks old) were induced by topical injection of human neutrophil elastase (HNE). Pulmonary emphysema in male golden Syrian hamsters (10 weeks old) was provoked by intratracheal instillation of porcine pancreatic elastase. In all in vivo experiments, FR901277 was administered prior to elastase treatment.¶Methods: Elastin degradation by HNE was monitored spectrophotometrically with elastin-congo red. Foot swelling was measured by calipers. Pulmonary hemorrhage was assessed by hemoglobin concentration in bronchoalveolar lavage fluid. As emphysematous parameters, quasi-static lung compliance and vital capacity were measured.¶Results: FR901277 inhibited HNE-induced elastin degradation. Systemic treatment with FR901277 significantly inhibited paw edema and pulmonary hemorrhage. Intratracheal treatment with FR901277 significantly ameliorated changes in pulmonary function.¶Conclusions: These results suggest that FR901277 inhibits the elastase activity potently both in vitro and in vivo, and that elastase may play a role at least in part in pathogenesis of pulmonary emphysema.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Insulin ; insulin receptor substrate-1 ; phosphoinositide 3-kinase ; signal transduction ; phosphotyrosine ; enzyme activation ; conformational change ; Fao cells.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Phosphoinositide 3-kinase (PI3-kinase) plays a crucial role in insulin signal transduction. We studied the molecular mechanism of the insulin-induced activation of PI3-kinase in rat hepatoma Fao cells using an antibody against the 110-kDa catalytic subunit (p110) and two against the 85-kDa regulatory subunit (p85α). PI3-kinase activity increased 1.6-fold in anti-p85 immunoprecipitates after insulin stimulation, whereas it did not increase when cell lysates were first immunoprecipitated with anti-phosphotyrosine or anti-insulin receptor substrate-1 (IRS-1), then with anti-p85, suggesting that the PI3-kinase which associates with tyrosyl phosphoproteins including IRS-1 is responsible for the increase in kinase activity. The activated PI3-kinase molecules constituted 4–6 % of the total PI3-kinase, and their specific activity was 11–14 times higher than that of the basal state. Anti-p110 recognized the catalytically active form of p110, and immunoprecipitated p110 only after exposure to insulin. Hence, the epitope of anti-p110, P200–C215, seems to be included in the portion of p110, the conformation of which is changed by insulin stimulation. We conclude that, in response to insulin stimulation, only a small fraction of p85 in the PI3-kinase pool associates with tyrosyl phosphoproteins including IRS-1, and that the specific activity of p110 is increased presumably through a conformational change including the P200–C215 region. [Diabetologia (1996) 39: 515–522]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Insulin ; insulin receptor substrate-1 ; phosphoinositide 3-kinase ; signal transduction ; phosphotyrosine ; enzyme activation ; conformational change ; Fao cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Phosphoinositide 3-kinase (PI3-kinase) plays a crucial role in insulin signal transduction. We studied the molecular mechanism of the insulin-induced activation of PI3-kinase in rat hepatoma Fao cells using an antibody against the 110-kDa catalytic subunit (p110) and two against the 85-kDa regulatory subunit (p85α). PI3-kinase activity increased 1.6-fold in anti-p85 immunoprecipitates after insulin stimulation, whereas it did not increase when cell lysates were first immunoprecipitated with anti-phosphotyrosine or anti-insulin receptor substrate-1 (IRS-1), then with anti-p85, suggesting that the PI3-kinase which associates with tyrosyl phosphoproteins including IRS-1 is responsible for the increase in kinase activity. The activated PI3-kinase molecules constituted 4–6% of the total PI3-kinase, and their specific activity was 11–14 times higher than that of the basal state. Anti-p110 recognized the catalytically active form of p110, and immunoprecipitated p110 only after exposure to insulin. Hence, the epitope of anti-p110, P200-C215, seems to be included in the portion of p110, the conformation of which is changed by insulin stimulation. We conclude that, in response to insulin stimulation, only a small fraction of p85 in the PI3-kinase pool associates with tyrosyl phosphoproteins including IRS-1, and that the specific activity of p110 is increased presumably through a conformational change including the P200-C215 region.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology letters 162 (1998), S. 0 
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Prevotella intermedia, a putative periodontopathic microorganism, requires iron for growth. Hemoglobin can be a major source of iron for bacterial growth in vivo since it is present in the crevicular fluid collected from periodontitis sites. Experiments studying the growth of P. intermedia in iron-depleted Todd-Hewitt broth supplemented with human hemoglobin showed that the bacteria were able to utilize human hemoglobin as a source of iron. The uptake of iron from hemoglobin by P. intermedia appears to be initiated by the binding of hemoglobin to the bacteria as shown by direct binding studies using 125I-labeled human hemoglobin. Scatchard analysis of saturation binding data revealed that 125I-labeled human hemoglobin had a dissociation constant (Kd) of 2.53×10−8 M for the receptor on P. intermedia. Binding of labeled hemoglobin to P. intermedia was competitively inhibited by unlabeled human hemoglobin showing that the binding was specific. The ability of bovine hemoglobin, but not hemin or non-hemoglobin heme-containing compounds, to inhibit binding competitively suggested that the globin moiety of the hemoglobin molecule is recognized by the hemoglobin binding receptors.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Low-temperature luminescence and magnetoluminescence experiments have been performed on n-type modulation-doped lattice-mismatched InAsxP1−x/InP quantum-well wires. From these experiments we can obtain information about the conduction-band subband structure, the electron effective mass, and consequently the conduction-band density of states. The doping level is high enough to populate several subbands in the conduction band which become observable in the luminescence spectra. The low-temperature luminescence spectra contain a distinct signature of the Fermi level at the high-energy slope. The zero-field wire luminescence exhibits an energy blue shift due to lateral quantum confinement within the wire and strain energy enlargement of the optical band gap. We have determined the separate energy contributions to the blue shift by high-field magnetoluminescence experiments. We have also calculated the (nonuniform) strain distribution and the strain-induced band shift within the wires. The theoretical results agree well with the experimental data. The information obtained on the subband structure and the electron effective mass can be used to estimate the length of the space-charge region in the doped area and the 1D carrier concentration in the quantum-well wires, without using any electrical contacts. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Physics of Plasmas 6 (1999), S. 1562-1574 
    ISSN: 1089-7674
    Source: AIP Digital Archive
    Topics: Physics
    Notes: By means of a global mode analysis of ideal magnetohydrodynamic (MHD) modes for Mercier-unstable equilibria in a planar axis L=2/M=10 heliotron/torsatron system with an inherently large Shafranov shift, the conjecture for global mode in Mercier-unstable equilibria from local mode analysis [N. Nakajima, Phys. Plasmas 3, 4556 (1996)] has been confirmed and the properties of pressure-driven modes inherent to such three-dimensional systems have been clarified. The Mercier-unstable equilibria are categorized into toroidicity-dominant and helicity-dominant Mercier-unstable equilibria. In the toroidicity-dominant Mercier-unstable equilibria, the pressure-driven modes change from interchange modes for low toroidal mode numbers n〈M, to tokamak-like ballooning modes for moderate toroidal mode numbers n∼M, and finally to ballooning modes purely inherent to three-dimensional systems for fairly high toroidal mode numbers n(very-much-greater-than)M. In the helicity-dominant Mercier-unstable equilibria, the pressure-driven modes change from interchange modes for n〈M or n∼M, directly to ballooning modes purely inherent to three-dimensional systems for n(very-much-greater-than)M. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Physics of Plasmas 3 (1996), S. 2379-2394 
    ISSN: 1089-7674
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Transport processes and resultant entropy production in magnetically confined plasmas are studied in detail for toroidal systems with gyrokinetic electromagnetic turbulence. The kinetic equation including the turbulent fluctuations are double averaged over the ensemble and the gyrophase. The entropy balance equation is derived from the double-averaged kinetic equation with the nonlinear gyrokinetic equation for the fluctuating distribution function. The result clarifies the spatial transport and local production of the entropy due to the classical, neoclassical and anomalous transport processes, respectively. For the anomalous transport process due to the electromagnetic turbulence as well as the classical and neoclassical processes, the kinetic form of the entropy production is rewritten as the thermodynamic form, from which the conjugate pairs of the thermodynamic forces and the transport fluxes are identified. The Onsager symmetry for the anomalous transport equations is shown to be valid within the quasilinear framework. The complete energy balance equation, which takes account of the anomalous transport and exchange of energy due to the fluctuations, is derived from the ensemble-averaged kinetic equation. The intrinsic ambipolarity of the anomalous particle fluxes is shown to hold for the self-consistent turbulent electromagnetic fields satisfying Poisson's equation and Ampère's law. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-8798
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary.  We have previously reported that ingenol derivatives are highly potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in acutely infected cells. In this study, however, we have found that some ingenol derivatives strongly enhance the replication of HIV-1 in chronically infected cells at nanomolar concentrations. One of the derivatives could activate nuclear factor κB(NF-κB), a potent inducer of HIV-1 replication, through the activation of protein kinase C (PKC). Whereas another derivative, which affected neither PKC nor NF-κB, significantly enhanced HIV-1 replication, suggesting that a PKC-independent mechanism may also exist in ingenol derivative-induced HIV-1 upregulation.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2277
    Keywords: Key words Human hepatocytes ; Biliary epithelial cells ; Coculture ; Growth factors ; Bioartificial liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The application of primary hepatocytes in hybrid artificial liver systems has been hampered by the gradual loss of differentiated morphology and function in vitro. Therefore, we have established a coculture model of autologous human hepatocytes and biliary epithelial cells (BEC) in collagen gel in the presence of hepatotrophic growth factors. Furthermore, we examined the effect of hepatocyte cell perfusion in a woven multicompartment capillary membrane system. Normal hepatocytes isolated from human liver produced albumin for more than 2 weeks in serum-free media, and were further stimulated by conditioned medium. When cocultured with BEC, albumin secretion was greatly enhanced, suggesting that cellular interactions promote tissue-specific differentiation. When perfused in bioreactors, albumin levels were maintained at steady state for longer than 2 weeks. These data indicate that differentiation of primary hum hepatocytes can be maintained by coculture interactions and three-dimensional hybrid organ devices, providing appropriate growth factors and matrix for tissue regeneration.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1572-879X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The disproportionation of triethoxysilane was carried out in a fixed-bed flow reactor over the solids obtained by heat-treating calcium hydroxide at various temperatures. In the disproportionation, the reaction proceeding to completeness to afford silane and tetraethoxysilane occurs to far lesser extent: predominantly diethoxysilane is obtained together with tetraethoxysilane. Dimethoxysilane is obtained by the disproportionation of trimethoxysilane also over the heat- treated calcium hydroxide.
    Type of Medium: Electronic Resource
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