Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We infused microgram quantities of active or inactive PMN elastase and cathepsin G into the renal arteries of rats. Both active and inactive elastase localized to the glomerular capillary wall equally, and in amounts that could be achieved physiologically in GN. However, elastase-perfused rats developed marked proteinuria (196 +/- 32 mg/24 h) compared with control rats receiving inactive elastase (19 +/- 2 mg/24 h, p less than 0.005). Similar results were seen with active and inactive cathepsin G. Neither elastase nor cathepsin G infusion was associated with histologic evidence of glomerular injury. We conclude that the PMN neutral serine proteinases elastase and cathepsin G can mediate marked changes in glomerular permeability in vivo due to their proteolytic activity, and thus, may contribute to the proteinuria observed in PMN-dependent models of GN.
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PMID:The human neutrophil serine proteinases, elastase and cathepsin G, can mediate glomerular injury in vivo. 304 4

A proliferative glomerulonephritis was induced in rats preimmunised with rabbit IgG by injecting a sub-nephrotoxic dose of rabbit anti-rat GBM IgG. All the rats developed a severe proteinuria within 2-5 days after the injection of anti-GBM IgG. At the same time, many mononuclear phagocytes infiltrated the glomeruli, the colloidal iron staining of the glomerular filtration barrier was altered, and the urinary excretion of laminin and of neutral proteinase strongly increased. However, the pattern and intensity of staining of different collagenous and non-collagenous BM glycoproteins were not modified, as shown by indirect immunofluorescence microscopy. The existence of a direct significant correlation between the proteinuria and the laminin urinary excretion, and between the latter and the urinary neutral proteinase activity suggests that lysosomal proteinase of mononuclear phagocytes may be involved in the damage of the GBM during the course of this experimental glomerulonephritis.
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PMID:Studies on the glomerular filtration barrier and on the urinary excretion of basement membrane glycoproteins during the accelerated model of nephrotoxic serum nephritis. 636 61

The role of the glomerular visceral epithelial cell in the physiologic turnover and pathologic breakdown of the glomerular extracellular matrix has remained largely unexplored. In this study a 98-kD neutral proteinase secreted by cultured rat visceral glomerular epithelial cells was shown to be a calcium, zinc-dependent enzyme secreted in latent form. In addition, the protein was heavily glycosylated and demonstrated proteolytic activity against Type I gelatin, Type IV collagen gelatin, and fibronectin. The similarity in molecular mass and substrate specificities to the 92-kD human matrix metalloproteinase-9 (MMP-9, or gelatinase B) suggested the identity of this activity, which was confirmed by immunoprecipitation and Northern blot analysis. The differences in molecular mass (98 vs. 92 kD) were not due to species-specific differences in glycosylation patterns, since cultured rat peritoneal macrophages secreted MMP-9 as a 92-kD enzyme. Furthermore, transfection of the human MMP-9 cDNA into rat glomerular epithelial cells yielded the 98-kD product. Using a specific monoclonal anti-MMP-9 antibody and in situ reverse transcription (ISRT) analysis of MMP-9 mRNA, the expression of this enzyme was evaluated in vivo. Normal rat glomeruli expressed little immunohistochemical or ISRT staining for MMP-9, while in rats with passive Heymann nephritis there was a major increase in MMP-9 protein and mRNA staining within the visceral epithelial cells. The temporal patterns of MMP-9 expression correlated with the period of proteinuria associated with this model, suggesting that a causal relationship may exist between GEC MMP-9 expression and changes in glomerular capillary permeability.
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PMID:Characterization of a glomerular epithelial cell metalloproteinase as matrix metalloproteinase-9 with enhanced expression in a model of membranous nephropathy. 861 33

A 39-year-old Japanese woman had been receiving propylthiouracil for 5 years for hyperthyroidism when she developed myalgia, scleritis, proteinuria, fever, and inflammation of the nose. Examination of a renal biopsy specimen showed focal segmental necrotizing glomerulonephritis. Indirect immunofluorescent staining showed a highly positive perinuclear pattern of anti-neutrophil cytoplasmic antibody (ANCA) in her serum. Enzyme-linked immunosorbent assay (ELISA) of the ANCA showed positivity for anti-proteinase 3, anti-myeloperoxidase, anti-leukocyte elastase, and anti-lactoferrin, but anti-cathepsin G and anti-lysozyme were negative. Because ELISA showed the titer of anti-leukocyte elastase antibody to be markedly elevated, we challenged this data by performing dot blot analysis. The patient's serum reacted with the native form, but not with denatured leukocyte elastase. Propylthiouracil-induced vasculitis was suspected. Symptoms abated within 2 weeks and all values of ANCA were reduced after the drug was withdrawn. Vasculitis is a rare side-effect of propylthiouracil therapy. Recently it was reported in association with ANCA. We present the findings of this patient and compare them with those described in 19 published cases of propylthiouracil-induced vasculitis associated with ANCA.
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PMID:Case of propylthiouracil-induced vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA); review of literature. 918 Dec 82