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  • 1
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  The β- d-endoglycosidase, heparanase, is emerging as an important contributor to the pathogenesis of proteinuria. The purpose of the present study therefore was to examine the role of heparanase in a model of accelerated anti-glomerular basement disease (anti-GBM).Methods:  Accelerated anti-GBM disease was induced and animals sacrificed at day 10 to establish heparanase expression using immunohistochemistry and western blot analysis. In addition, cortex was isolated from normal and diseased glomeruli to determine if mRNA levels altered with disease. A previously validated anti-heparanase antibody associated with proteinuria reduction, in a model of membranous nephropathy, was administered prior to disease induction to establish its impact on protein excretion in this model.Results:  At day 10 of anti-GBM disease, an increase in glomerular heparanase was shown using immunohistochemistry. Sequential staining studies revealed that this increase was associated with glomerular endothelial, epithelial cells and invading ED-1-positive inflammatory cells. RT-PCR revealed an insignificant 1.2-fold induction of mRNA at day 10 of disease. Western blot analysis of kidney cortex confirmed that the active 58-kDa heparanase species was restricted to diseased kidney at day 10. The inactive 65-kDa precursor, however, was found only in cortex derived from normal kidney. Proteinuria at day 10 of disease was significantly reduced, in the absence of altered rat anti-sheep antibody titres, after administration of a validated polyclonal anti-heparanase antibody (P 〈 0.05). Furthermore, sheep IgG deposition was not altered by administration of the anti-heparanase antibody.Conclusion:  These data suggest that heparanase contributes to the pathogenesis of proteinuria in a model of anti-GBM disease.
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  • 2
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The endoglycosidase heparanase is an important in the degradation of the extracellular matrix by invading cells, notably metastatic tumor cells and migrating leukocytes. Here we report the cDNA sequence of the human platelet enzyme, which encodes a unique protein of 543 amino acids, and the ...
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  • 3
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The four MPS-III sub-types are caused by deficiencies of four of the nine exoenzyme activities required for the lysosomal degradation of heparan sulphate5. Of the other five enzyme activities required, metabolic defects for three (MPS-I, -II and -VII), also involved in the degradation of dermatan ...
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  • 4
    ISSN: 1432-1939
    Keywords: Herbivory ; Tallgrass prairie ; Small mammals ; Invertebrates ; Plant communities
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A factorial field experiment was designed to test the effects of small mammals and above- and below-ground invertebrates on plant species richness and composition in native tallgrass prairie at Konza Prairie Research Natural Area, northeast Kansas. Over a 4-year period, Microtus ochrogaster densities were maintained by live-trapping in fenced plots, and invertebrate levels were reduced using the pesticides carbaryl for above-ground invertebrates and an organophosphate (isofenphos) for belowground invertebrates. ANOVA according to a split-plot design of plant species biomass data harvested in 1984 and 1986 revealed few significant effects of either small mammal densities or pesticide application. Of 54 species harvested from both sample dates, only 10 were significantly affected by either treatment. Analysis of species richness according to 8 life-form classes provided a clearer pattern of response than did biomass either by species or life-form class. For example, numbers of C4 grasses were reduced by increasing small mammal densities, whereas numbers of C4 annual forbs were lowest when above-ground herbivory was reduced. While consumers have been shown to have strong effects on successional communities, the few significant results observed in this study suggests that the manipulated levels of small mammals and insects had few effects on a mature tallgrass prairie.
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