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)

This presentation attempts to define the criteria for diagnosis of the suggested clinicopathologic entity of IgA nephropathy. Of 250 patients in whom renal biopsies with immunofluorescence, light and electron microscopic, and clinical data were available, 12 patients (4.8 per cent) showed predominance of IgA with localization mainly in the mesangium, a variable degree of mesangial cell proliferation, and increased mesangial matrix on light microscopy. Electron densities were restricted to the mesangium and paramesangial areas. IgA was accompanied by C3 only in two patients, by IgG and C3 in five, and by IgG, IgM, and C3 in five. Properdin was found in 11 of these 12 cases. There was a marked male predominance. All showed gross or microscopic hematuria and variable proteinuria. Ten had had normal renal function tests at the time of presentation, and there was no significant worsening of renal function in the 11 patients followed for six to 84 months after biopsy. No morphologic change was detected in two repeat biopsies six and seven years after the initial biopsies. These 12 patients appear to form a distinct clinicopathologic entity. They can only be separated from other glomerular disorders with IgA when the morphologic and clinical findings are considered in combination with the finding of diffuse IgA predominance on renal biopsy.
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PMID:IgA nephropathy. 85 15

Of 475 renal biopsles examined by immunofluorescence, IgA was seen located selectively in the glomerular mesangium of 18 patients. These patients were generally young men and had hematuria, only minimal proteinuria, and normal renal function. Glomerular lesions consisted of focal segmental capillary hypercellularity or sclerosis and mesangial thickening due to an increase in mesangial cells, matrix, and electron-dense deposits. Both IgG and C3 were frequently seen with IgA in the mesangium as was properdin in five of six cases, but C4, a component of the classical pathway of complement activation, was seen only infrequently. Serum IgA levels were elevated in many patients, but serum complement components were normal. These findings suggest a possible unusual immune pathogenesis with local mesangial binding and alternate pathway activation of complement.
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PMID:Immunoglobulin A nephropathy. 116 23

We demonstrated previously that B151K12 T cell hybridoma produces two distinct B cell differentiation factors, B151-TRF1 and B151-TRF2, capable of inducing differentiation of antigen-activated and unstimulated B cells into antibody-forming cells, respectively. In the present study we investigated the pathophysiologic relation of these factors with factors obtained from MRL/MP-lpr/lpr(MRL/lpr) mice and (C57BL/6 X DBA/2)F1 (BDF1) mice undergoing chronic graft-vs-host reaction (GVHR), representing a murine model of systemic lupus erythematosus with polyclonal B cell activation associated with the T cell hyperfunction. The functional and biochemical analyses revealed that B151-TRF2-like, but not B151-TRF1-like, activity was found in culture fluid supernatant (CFS) of lymphoid cells from MRL/lpr mice with lymphoproliferative syndrome. On the other hand, both B151-TRF1- and B151-TRF2-like activities were detected in CFS prepared from spleen cells of BDF1 mice undergoing chronic GVHR by the inoculation of parental DBA/2 spleen cells. Interestingly, spleen cells of BDF1 mice transferred with DBA/2 thymocytes preferentially elaborated B151-TRF1-like factor. Because BDF1 mice transferred with DBA/2 spleen cells but not with DBA/2 thymocytes developed a SLE-like syndrome exemplified by the appearance of Coombs' antibody and proteinuria, it seemed likely that production of B151-TRF2-like factor was closely associated with the onset of autoimmune disease. In fact, B151-CFS containing B151-TRF2 but not B151-TRF1 activity could induce a striking autoantibody production both in vivo and in vitro as detected by PFC responses of normal mice to bromelain-treated mouse red blood cells (BrMRBC). Moreover, it was demonstrated that in vitro anti-BrMRBC PFC responses induced by semipurified B151-TRF2 was markedly inhibited by addition of relevant anti-Ia antibody to the culture. Thus, the present study demonstrates that B151-TRF2 represents one of the B cell differentiation factors responsible for polyclonal B cell activation leading to autoantibody production.
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PMID:Polyclonal B cell activation by a B cell differentiation factor, B151-TRF2. III. B151-TRF2 as a B cell differentiation factor closely associated with autoimmune disease. 354 18

Laboratory examination of specimens from 123 consecutive renal biopsies performed at Victoria General Hospital, Halifax revealed six cases of mesangial deposition, predominantly of IgA, unassociated with systemic disorders. Immunohistologic examination showed deposits of only IgA in one specimen, IgA and IgG in two and IgA, IgG and IgM in three. Glomerular deposits of C3 were seen in five of the specimens, and properdin was seen in three. Glomeruli in all the specimens showed increased matrix and increased numbers of cells in the mesangium. Electron microscopy revealed deposits in the mesangium or capillary wall in all five of the specimens so studied. All six patients had proteinuria, four had microscopic hematuria, and three had hypertension; in one patient the disease progressed to renal failure.
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PMID:IgA nephropathy in adults: immunohistologic findings and clinical course. 389 Oct 58

The glomerular lesions induced in 10 chimpanzees infected with variable numbers of Schistosoma japonicum cercariae were studied by means of light and electron microscopy and fluorescent antibody technic. Ten animals served as controls; 5 were uninfected and 5 were only lightly infected. The animals were observed for periods ranging from 3 to 17 months, and by the time of sacrifice, all had developed advanced liver fibrosis. In general, the degree of glomerular injury was related to infection intensity and degree and duration of portal liver fibrosis. Some animals had terminal BUN elevation and slight proteinuria. By light and electron microscopy, in the initial stages, only part of the glomeruli were involved and exhibited mesangial matrix expansion and mesangial cell proliferation with intracellular hyaline droplets. At later stages, a larger number of glomeruli were affected and exhibited diffuse hypercellularity, glomerular basement thickening, mesangial sclerosis and less often, focal necrosis, crescent formation, synechiae and global hyalinization. In addition, there were discrete electron-dense deposits localized in the mesangial area in some glomeruli. Immunofluorescent studies utilizing antisera to chimpanzee gamma-globulin and complement (C3) and to human properdin disclosed only faint deposits of C3, apparently in mesangial areas. The association of hepatosplenic schistosomiasis and nephropathy, the possible role of schistosomal antigen and the mechanism(s) of such glomerular injuries are reviewed and compared with the disease in humans and other host species infected with Schistosoma.
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PMID:The nephropathy of experimental hepatosplenic schistosomiasis. 413 91

Forty-one out of 408 cases (or 10%) of primary glomerular disease had diffuse fine granular to arc-like short linear mesangial deposits of IgM by direct immunofluorescence. The IgM deposition was accompanied by C1q and/or C4 in the same locality in 29 cases, by C3 in 10, and by trace amounts of IgA in 6. Properdin-factor B was not detected. Fine granular electron dense deposits of low density were detected in the mesangium in all 41 cases by electron microscopy, usually as a discrete granular or arc-like pattern beneath the mesangial glomerular basement membrane and correlated well with the immunofluorescence findings. An immune complex disease with complement activation via the classical pathway is suggested. The ages of the patients varied from 2 to 58 years (average 23.8 years). A male predominance of 2.2:1 was identified. Serum IgM level was elevated in 46.7% of the cases. The majority (87.8%) of the cases manifested a nephrotic syndrome or relapse at time of biopsy, and the remaining cases experienced persistent or intermittent proteinuria. Among the 36 nephrotic patients, 22 cases (61.1%) demonstrated complete remission with steroid therapy, 9 cases (25%) were resistant, and 5 cases (13.9%) had partial remission. Complete and partial remissions were later achieved with cytotoxic drugs or methylprednisolone pulse therapy in 3 and 4 cases respectively in the steroid resistant patients. Frequent relapses occurred during the course in 22 out of 32 cases (68.8%) who had experienced complete or partial remission. Follow-up study after biopsy demonstrated that sustained complete remission was achieved with prednisolone with or without cytotoxic drugs and pulse therapy in only 14 (42.4%) of the 33 nephrotic cases who had been followed up for longer than 6 months, and six of them had had previous relapses. Pathologically, 56.1% of the patients showed mild to moderate increase in mesangial matrix and cellularity. Focal and segmental sclerosis was demonstrated in four cases (9.8%). However, minimal glomerular change was also common (34.1%). The patients with minimal change seemed to have a higher complete remission rate than patients with more evident glomerular alterations, although the difference was not statistically significant. This clinical and immunopathological study suggests that mesangial IgM nephropathy is an important disease in Taiwan, with a variable response to treatment and frequent relapses.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical and immunopathologic study of mesangial IgM nephropathy: report of 41 cases. 637 23

We experienced a female nephrotic patient associated with subacute bacterial endocarditis. Her proteinuria was completely normalized after antibiotic therapy and valve replacement. Immunofluorescence and an electron microscopic study of a renal biopsy specimen showed little evidence of immune complex in the glomeruli. Marked deposition of properdin in the glomeruli and the reduced level of serum complement may indicate involvement of the complement system in the pathogenic mechanism of massive proteinuria in this case.
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PMID:Nephrotic syndrome associated with subacute bacterial endocarditis (SBE): a case report. 757 Jun 80

Human proximal tubular epithelial cells (PTEC) incubated with normal human serum (NHS) were found to fix on their surface C3, properdin, terminal complement components and C5b-9 MAC neoantigen, but not C1q and C4, by immunofluorescence. Complement fixation was abrogated if PTEC were incubated with EDTA-treated NHS or C3-deficient human serum, but not with Mg EGTA-treated NHS or C1q-deficient human serum, showing the prevalent activation of the alternative pathway of complement. This event was followed by marked cytoskeleton alterations with disruption of the actin cortical network, redistribution of actin throughout the cytoplasm and formation of blebs, and by cell cytolysis. In addition, superoxide anion and hydrogen peroxide production and chemiluminescence response were detected in consequence of MAC insertion on PTEC plasma membrane. The dependency on MAC of the observed biological effects of complement fixation on PTEC surface was shown by using sera selectively deficient of terminal components of complement (C6 or C8), and therefore unable to form the C5b-9 MAC, and by restoring the ability to form MAC after addition of purified C6 or C8. The possible pathogenetic relevance of these observations in tubulointerstitial injury occurring in patients with complementuria due to non-selective proteinuria, is discussed.
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PMID:Alternative pathway activation of complement by cultured human proximal tubular epithelial cells. 816 33

We studied kidney biopsy specimens from three children with sickle cell anemia and microangiopathic glomerulopathy. One child also had cyanotic congenital heart disease. Laboratory evaluation revealed proteinuria and normal serum creatinine in all and normal serum complement in two of the three children at the time of biopsy. In all biopsies, glomeruli were enlarged with diffuse hypercellularity and focal segmental mesangial interposition; capillary loop lumens were congested with sickled erythrocytes. Immune labeling identified segmental immunoglobulin G, C3, and properdin over the glomerular capillary loop walls in each case. Ultrastructurally, the subendothelial zone of the glomerular basement membrane was widened with new lamina densa formation with focal mesangial interposition. The glomerular lesion we describe in these children may be due to endothelial injury related to the altered erythrocytes, glomerular hemodynamics, and the hypercoagulable state characteristic of sickle cell disease.
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PMID:Microangiopathic glomerulopathy in children with sickle cell anemia. 902 33

Activation of filtered complement products on the brush border of the tubular epithelium is thought to be a key factor underlying proteinuria-induced tubulointerstitial injury. However, the mechanism of tubular complement activation is still unclear. Recent studies on mechanisms of complement activation indicate a key role for properdin in the initiation of an alternative pathway. We hypothesized that properdin serves as a focal point for complement activation on the tubulus. We observed a strong staining for properdin on the luminal surface of the tubules in kidney biopsies from patients with proteinuric renal disease. In vitro experiments revealed dose-dependent binding of properdin to proximal tubular epithelial cells (PTEC), whereas no significant binding to endothelial cells was detected. Exposure of PTEC with normal human serum as a source of complement resulted in complement activation with deposition of C3 and generation of C5b-9. These effects were virtually absent with properdin-deficient serum. Preincubation of PTEC with properdin before addition of properdin-depleted serum fully restored complement activation on the cells, strongly suggesting a key role for properdin in the activation of complement at the tubular surface. In proteinuric renal disease, filtered properdin may bind to PTEC and act as a focal point for alternative pathway activation. We propose that this contribution of properdin is pivotal in tubular complement activation and subsequent damage. Interference with properdin binding to tubular cells may provide an option for the treatment of proteinuric renal disease.
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PMID:Complement activation by tubular cells is mediated by properdin binding. 1875 94


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