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)

A case of leukemic multiple myeloma with IgG-lambda type, which plasma cells in the peripheral blood and the bone marrow had large vacuolar inclusions is reported. A 67-year-old male was admitted because of bone pain. A diagnosis of leukemic multiple myeloma of IgG-lambda type was established, based on Bence Jones proteinuria (1.5 g/day), marked plasmacytosis in peripheral blood (63%) and bone marrow (90%), serum M-component (IgG-lambda type, 6.0 g/dl) and multiple osteolytic lesions. Most plasma cells in the bone marrow as well as in the blood had vacuolar inclusions in the cytoplasm which were 1-8 microns across and were negative with PAS and myeloperoxidase staining. Acid phosphatase reaction was distributed densely around vacuolar inclusions and sparsely within them in the form of fine granules. Ultrastructurally, most of the vacuolar inclusions were electron-lucent cytoplasmic spaces, encircled in a distinct limiting membrane, in which inner microvesicles were distributed diffusely. A few vacuoles showed fibrillary structures. These findings suggested that the lysosomal system might play a major role in the vacuolation of these plasma cells.
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PMID:[Vacuolar inclusions with multivesicular structure in leukemic multiple myeloma]. 132 2

We report a case of microscopic polyarteritis nodosa associated with myeloperoxidase-antineutrophil cytoplasmic autoantibodies (MPO-ANCA). A 38 year-old female was admitted to our hospital, because of proteinuria, recurrent pyrexia, polyarthralgia, abdominal pain and purpura. She had a history of severe pulmonary hemorrhage and 4 kg weight loss for 8 months. On admission perinuclear ANCA without cytoplasmic ANCA was detected by indirect immunofluorescence assay and MPO-ANCA was detected by enzyme linked immunosorbent assay. But anti-nuclear antibodies, immune complexes and anti-glomerular basement membrane antibodies were not detected. Renal biopsy showed necrotizing crescentic glomerulonephritis without immune deposits. Skin biopsy revealed leukocytoclastic vasculitis. Diagnosis of microscopic polyarteritis nodosa was made by these clinical and histological evidence of vasculitis. As renal failure progressed after admission, corticosteroid and cyclophosphamide administration were started. Renal function and other symptoms improved paralleled with decreased MPO-ANCA titer to normal values. It is suggested that MPO-ANCA may be closely related to the pathogenesis of microscopic polyarteritis nodosa and it may be a good serological marker for diagnosis and disease activity of this disease.
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PMID:[A case of microscopic polyarteritis nodosa associated with myeloperoxidase-antineutrophil cytoplasmic autoantibodies (MPO-ANCA)]. 136 30

Leukotriene B4 (LTB4) is the major 5-lipoxgenase product released during early experimental glomerulonephritis. To test its functional relevance, its actions in the normal rat kidney and its influence on renal function in the heterologous phase of mild nephrotoxic serum-induced glomerular injury were examined. Intrarenal administration of leukotriene B4 resulted in mild vasorelaxant and natriuretic responses which were shared by 12(R)-hydroxyeicosatetraenoic acid but not 12(S)-leukotriene B4 or 12(S)-hydroxyeicosatetraenoic acid, suggesting activation of a common recognition site with a requirement for 12(R) stereochemistry. The polymorphonuclear cell-specific activator, N-formyl-Met-Leu-Phe, stimulated leukotriene B4 production from isolated perfused kidneys harvested from nephrotoxic serum-treated rats to a significantly greater degree than from control animals treated with nonimmune rabbit serum. The renal production of leukotriene B4 correlated directly and strongly (r = 0.79, P less than 0.01) with renal myeloperoxidase activity, suggesting interdependence of leukotriene B4 generation and polymorphonuclear cell infiltration. In vivo, intrarenal administration of leukotriene B4 to rats with mild nephrotoxic serum-induced injury was associated with an increase in polymorphonuclear cell infiltration, reduction in renal plasma flow rate, and marked exacerbation of the fall in glomerular filtration rate, the latter correlating strongly with the number of infiltrating polymorphonuclear cells/glomerulus, whereas inhibition of 5-lipoxygenase led to preservation of glomerular filtration rate and abrogation of proteinuria. Thus, although devoid of vasoconstrictor actions in the normal kidney, increased intrarenal generation of leukotriene B4 during early nephrotoxic serum-induced glomerular injury amplifies leukocyte-dependent reductions in glomerular perfusion and filtration rates, likely due to enhancement of polymorphonuclear cell recruitment/activation.
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PMID:Functional significance of leukotriene B4 in normal and glomerulonephritic kidneys. 165 93

Neutrophils (PMNs) mediate injury in experimental glomerulonephritis (GN) in part via the release of reactive oxygen species, particularly hydrogen peroxide (H2O2). Recent kidney perfusion studies demonstrate that H2O2 can cause glomerular injury by reaction with halides in the presence of the PMN cationic enzyme myeloperoxidase (MPO) to form oxidants which can oxidize and halogenate tissue. We sought evidence for participation of the MPO system in a model of PMN-mediated immune complex (IC) GN. A PMN-dependent model of GN was developed in rats by perfusing the renal artery with concanavalin A followed by anticoncanavalin A antibody. PMN depletion abolished glomerular PMN infiltration and significantly reduced proteinuria (35 +/- 7 mg/day vs. 113 +/- 10, P less than 0.001). Rats that received Na125I (5.0 microCi) three and six hours following disease induction had more 125I incorporation in glomeruli and GBM at 48 hours than similarly treated rats that were PMN depleted (1200 cpm vs. 88 cpm, P less than 0.01). Glomerular iodination could not be demonstrated in a PMN-independent model of nephrotoxic nephritis induced with noncomplement fixing anti-GBM antibody. These data indicate that this model of PMN-mediated IC GN is associated with activation of the MPO-H2O2-halide system, which may participate in mediating glomerular injury.
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PMID:Participation of the myeloperoxidase-H2O2-halide system in immune complex nephritis. 282 92

Neutrophilic polymorphonuclear leukocytes can mediate glomerulonephritis by releasing reactive oxygen species such as H2O2. We have previously demonstrated that H2O2-mediated glomerular injury can be potentiated by reaction with polymorphonuclear leukocyte myeloperoxidase (MPO). When MPO was perfused into renal arteries of rats, it bound to the glomerular capillary wall due to its cationic charge. Subsequent perfusion with nontoxic concentrations of H2O2 and halides resulted in acute glomerular injury, halogenation of the glomerular basement membrane, and proteinuria. The studies reported here document the morphologic changes that accompany MPO-mediated glomerular injury. Acutely, there is severe injury to the endothelium with cell swelling and lysis. Within 10 minutes, a marked platelet influx occurs. Platelets frequently occlude capillary lumens and bind to areas of denuded glomerular basement membrane where platelet degranulation results. By 4 days, the platelet infiltration has ceased, and a reparative phase develops characterized by marked proliferation of resident endothelial cells and possibly mesangial cells. By 21 days postperfusion, the glomerular lesion had largely resolved. In contrast, control rats perfused with MPO alone, H2O2 alone, or buffered saline alone demonstrate minimal glomerular injury at all times studied. MPO-mediated glomerular disease results in endothelial and mesangial cell injury, activation of platelets, and a subsequent proliferative response. These morphologic changes resemble those seen in several forms of inflammatory and proliferative glomerulonephritis in man.
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PMID:Morphologic correlates of glomerular oxidant injury induced by the myeloperoxidase-hydrogen peroxide-halide system of the neutrophil. 283 32

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has been recently recognized in Graves' disease patients treated with propylthiouracil. We have experienced three adult cases of Graves' disease with main features being renal derangements. All three patients, who were between the ages of 22 and 82 years, had been treated with propylthiouracil for 2 to 5 years after a diagnosis of Graves' disease. After several weeks of upper respiratory tract infection or flu-like symptoms, they abruptly began to manifest proteinuria and hematuria concomitant with severe anemia. Their serum creatinine increased from normal levels to 1.2 to 3.6 mg/dL. Renal biopsy revealed crescentic glomerulonephritis without deposition of immune complexes (ie, pauci-immune type). Crescent formations were observed in 40% to 60% of the glomeruli in all three cases. The serum from the patients revealed positive perinuclear-ANCA and negative cytoplasmic-ANCA (C-ANCA) pattern, and myeloperoxidase (MPO)-ANCA titers were 120 to 502 ELISA Units/mL (normal, < 10 ELISA Units/mL). A withdrawal of propylthiouracil with or without immunosuppressive therapy ameliorated their renal derangements. Graves' disease patients should be placed under vigilant observation by monitoring their urinalysis and serum creatinine, especially when being treated with antithyroid drugs and when suffering from flu-like symptoms.
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PMID:Myeloperoxidase-antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis complicating the course of Graves' disease: report of three adult cases. 748 30

Wegener's granulomatosis (WG) is a granulomatous necrotizing vasculitis associated with the presence of ANCA, predominantly directed against proteinase 3 (PR3). The titres of ANCA correlate with disease activity and titre increases may precede disease exacerbations. Previously, we have shown that it is possible to induce autoimmune disease (systemic lupus erythematosus (SLE) and anti-phospholipid syndrome) in naive mice following active immunization with human autoantibodies, namely anti-DNA and anti-cardiolipin, respectively. The mice developed first anti-autoantibodies and, after about 4 months anti-anti-autoantibodies (Ab3), simulating auto-antibodies (Ab1) in their binding activities, and their presence was associated with the development of disease manifestations, characteristic of the human disease. So far, there is no good animal model for WG. In the current study we have immunized mice with human ANCA with the aim of inducing experimental WG. In two separate studies 30 mice were immunized in their footpads with autoantigen-purified IgG fraction (ANCA) from the sera of two patients with untreated WG, emulsified in Freund's complete adjuvant, followed 3 weeks later by ANCA injection in PBS. In the first experiment mice immunized with ANCA developed sterile microabscesses in the lungs after 8 months, and died after 8-15 months. In the second experiment, mice immunized with ANCA developed after 4 months mouse ANCA, with specificity both to PR3 and to myeloperoxidase, as well as anti-endothelial autoantibodies (AECA), as shown by radioimmunoprecipitation. Pathologically, the immunized mice developed proteinuria but not haematuria, and histological sections of the lungs demonstrated mononuclear perivascular infiltration, while diffuse granular deposition of immunoglobulins was noted in the kidneys. Our results point to a pathogenic role of ANCA in WG, and confirm the importance of the idiotypic network in the etiopathogenesis of autoimmune conditions.
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PMID:Immunization with anti-neutrophil cytoplasmic antibody (ANCA) induces the production of mouse ANCA and perivascular lymphocyte infiltration. 755 78

Although both ecto-ADPase and prostacyclin (PGI2) inhibit platelets and neutrophils, their action in acute glomerulonephritis is unknown. We tested the PGI2 analog Iloprost and 2chloroadenosine (2Cl-ADO), an analog of adenosine, the end product of nucleotidase activities, during anti-Thy1 nephritis. Rats received anti-Thy1 immunoglobulin G (5 mg/kg body weight, intravenously) and subsequently one subcutaneous injection of either 2Cl-ADO (10 mg/kg body weight; (n = 6) or Iloprost (1 mg/kg body weight; n = 6). Control rats received anti-Thy1 immunoglobulin G with saline (n = 6) or saline alone (n = 6). After 24 hours, kidneys were processed for light-microscopical evaluation. Proteinuria was studied in additional rats. Results showed that both drugs inhibited intraglomerular platelet activation (P < 0.005). 2Cl-ADO also reduced intraglomerular O2- production of neutrophils (P < 0.05), in contrast to Iloprost. Intraglomerular immunoglobulin G deposition, complement activation, neutrophil influx, and myeloperoxidase release were not affected by 2Cl-ADO or Iloprost. However, proteinuria was completely prevented by both drugs. It is concluded that PGI2 and nucleotidases are potentially able to attenuate this form of nephritis by inhibiting platelet activity, whereas nucleotidases also inhibit neutrophil activity in vivo.
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PMID:Attenuation of anti-Thy1 glomerulonephritis in the rat by anti-inflammatory platelet-inhibiting agents. 767 50

Although glomerular disease remains the most common cause of end-stage renal disease worldwide, major advances have been made recently in understanding the cellular and molecular mechanisms that mediate these disorders. The nephrotic syndrome in noninflammatory lesions such as minimal change or focal sclerosis and membranous nephropathy results from disorders of the glomerular epithelial cell that can be simulated in animal models by antibodies to various epithelial cell membrane epitopes. Clarification of how these antibodies affect epithelial cells to induce a loss of glomerular barrier function should substantially improve understanding of the pathogenesis of minimal change or focal sclerosis. In membranous nephropathy, proteinuria is mediated primarily by the C5b-9 complex through similar mechanisms that also involve glomerular epithelial cells as targets. Inflammatory glomerular lesions are induced by circulating inflammatory cells or proliferating resident glomerular cells. Understanding of how these cells induce tissue injury has also evolved considerably over the past decade. Neutrophil-induced disease involves leukocyte adhesion molecules in regulating neutrophil localization; proteases, oxidants, and myeloperoxidase in mediating injury; and platelets in augmenting these processes. The activated mesangial cell exhibits altered phenotype and proliferation with the release of oxidants and proteases. Mesangial cell proliferation may be initiated by basic fibroblast growth factor and is maintained by an autocrine mechanism involving platelet-derived growth factor. Transforming growth factor beta is important in the subsequent development of sclerosis.
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PMID:New insights into mechanisms of immune glomerular injury. 804 28

Although glomerular disease remains the most common cause of end-stage renal disease worldwide, major advances have been made recently in understanding the cellular and molecular mechanisms which mediate these disorders. Nephrotic syndrome in non inflammatory lesions such as minimal-change/focal sclerosis and MN results from disorders of the GEC which can be simulated in animal models by antibodies to various GEC membrane epitopes. Clarification of how these antibodies effect the GEC to induce a loss of glomerular barrier function should substantially improve understanding of the pathogenesis of minimal change/focal sclerosis. In MN, proteinuria is mediated primarily by C5b-9 through similar mechanisms that also involve the GEC as a target. Inflammatory glomerular lesions are induced by circulating inflammatory cells or proliferating resident glomerular cells. Understanding of how these cells induce tissue injury has also evolved considerably over the past decade. Neutrophil-induced disease involves leukocyte adhesion molecules in regulating neutrophil localization; proteases, oxidants, and myeloperoxidase in mediating injury and platelets in augmenting these processes. The activated mesangial cell exhibits altered phenotype and proliferation with release of oxidants and proteases. Mesangial cell proliferation may be initiated by basic fibroblast growth factor and is maintained by an autocrine mechanism involving PDGF. TGF-beta is important in the subsequent development of sclerosis. As understanding of these areas evolves, numerous new therapeutic strategies can now be devised, including agents which block or inhibit complement effects, oxidants, proteases, growth factors, and other cytokines. Appreciation of the role of several natural inhibitors of these mechanisms may also allow therapeutic manipulations that upregulate regulatory proteins, with a consequent therapeutic benefit.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mediation of immune glomerular injury. 830 38


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