Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a means of studying mechanisms of response to injury in glomerulonephritis, glomeruli from normal sheep and rabbits and from sheep and rabbits with experimental crescentic glomerulonephritis have been isolated and grown in tissue culture. The cellular outgrowths from the normal and diseased glomeruli have been compared. The outgrowth of glomeruli from normal animals contained only two cell populations whose microscopic and ultrastructural appearances were of epithelial and mesangial cells. The same cells were also observed in the outgrowths of glomeruli from animals with crescenti nephritis but in addition a third population of cells was present in large numbers. These cells were identified as macrophages by their mobility, ultrastructure, phagocytic capacity, and presence of Fc receptors. Glomerular outgrowth from sheep with crescentic glomerulonephritis contained 170 +/- 20 (SEM) macrophages and outgrowths from rabbits with crescentic nephritis contained 64 +/- 6 (SEM) macrophages per glomerulus. We have previously observed large numbers of macrophages in the outgrowth of isolated glomeruli from humans with rapidly progressive crescentic glomerulonephritis. The predominance of the macrophage in cultures of glomeruli from both human and animal crescentic glomerulonephritis suggests that this is an important cell in the inflammatory reaction occurring in crescentic glomerulonephritis and may comprise a substantial proportion of the cells forming the crescent.
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PMID:Tissue culture of isolated glomeruli in experimental crescentic glomerulonephritis. 34 68

1. To elucidate the mechanisms by which cyclosporin A diminishes proteinuria, we studied 20 patients with severe nephrotic syndrome. Biopsy-established pathologies included minimal change disease (n = 5), membranous glomerulopathy (n = 6), membranoproliferative glomerulonephritis (n = 5) and focal segmental glomerulosclerosis (n = 4). Before, at the end of a 90 day course of cyclosporin A, and finally 1 month after stopping cyclosporin A we determined 24 h protein excretion. Measurements of glomerular filtration rate, effective renal plasma flow, fractional clearance rates of albumin and immunoglobulins with different charges and the transglomerular sieving of uncharged dextrans of broad size distribution were used to study the effects of cyclosporin A on renal perfusion and the glomerular filtration barrier. The findings were analysed with a theoretical model of solute transport. 2. Among the different forms of glomerulopathy the response to low-dose cyclosporin A (trough levels 32.0-36.9 ng/ml) varied markedly. In minimal change disease, proteinuria decreased from 9.5 +/- 3.1 to 1.3 +/- 0.2 g/24 h (mean +/- SEM, P less than 0.01). This response was due to restoration of the charge selectivity of the glomerular barrier. The depressed value of the glomerular permeability coefficient also returned to normal. Glomerular filtration rate, effective renal plasma flow and renal vascular resistance did not change. Proteinuria returned after stopping cyclosporin A, although it did not reach pretreatment levels. In membranous glomerulopathy, proteinuria fell from 9.9 +/- 1.5 to 1.8 +/- 0.3 g/24 h (P less than 0.01). Changes in protein excretion and dextran sieving were compatible with an increase in glomerular permselectivity and a decrease in filtrate flow through the 'shunt' pathway. Glomerular filtration rate was maintained, although effective renal plasma flow fell significantly. Proteinuria relapsed after stopping cyclosporin A. In membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis proteinuria did not respond to cyclosporin A, although cyclosporin A exerted important haemodynamic effects. 3. In minimal change disease and membranous glomerulopathy cyclosporin A exerts its beneficial effects on proteinuria through changes in the properties of the glomerular barrier, resulting in increased charge and size selectivity, respectively.
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PMID:Effects of cyclosporin A on glomerular barrier function in the nephrotic syndrome. 132 May 44

Effect of serine protease inhibitor Camostat Mesilate (Foipan) on primary glomerulonephritis and it's mechanism were evaluated. Forty-two patients having primary glomerulonephritis (13 cases of IgA nephropathy, 11 cases of membranous nephropathy and others), aged 18 to 81 years were selected for this study. At the start of our study, twenty-one patients had received other drugs (13 cases of dipyridamole and 13 cases of prednisolone). A control period of four weeks was established to confirm that the levels of proteinuria and renal functions were stable. Patients were orally administered with 600 mg of Camostat Mesilate per day for four weeks. Effect of Camostat Mesilate was judged by urinary protein excretion, hematuria, serum total protein, albumin, Ccr, creatinine and BUN. In order to reveal the mechanism of the effect laboratory data such as granulocyte elastase, CH50, C3, C4, fibrinogen, platelate factor 4, beta-thromboglobulin, thromboxane B2 and prostaglandin F1 alpha were evaluated before and after the treatment. Parameters were analyzed by using paired t-test. Mean (+/- SEM) urinary protein excretion reduced from 4.31 +/- 0.91 to 2.80 +/- 0.43 g/day (p less than 0.05), and score of hematuria decreased from 1.8 +/- 0.16 to 1.5 +/- 0.15. A significant decrease in urinary protein excretion was seen in membranous nephropathy and a significant decrease in hematuria was seen in IgA nephropathy. In combination therapy (dipyridamole, prednisolone) urinary protein excretion markedly decreased (p less than 0.05) and in Camostat Mesilate therapy score of hematuria markedly decreased (p less than 0.05). Camostat Mesilate had no effects on renal function assessed by Ccr, creatinine and BUN.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of protease inhibitor on primary glomerulonephritis and the mechanism of the effect]. 177 Jun 35

We recently reported evidence for the involvement of local cellular immune activation in the immunopathogenesis of human IgA nephropathy, particularly in cases of IgA disease featuring crescent formation. In the current study, using monoclonal antibodies, we investigated whether mononuclear cells bearing receptors for interleukin 2 (IL-2R+ MNC) were present within glomeruli or associated crescents in biopsies from patients with crescentic glomerulonephritis (greater than 60% crescents, N = 19), IgA disease with crescents (N = 9), or other types of proliferative glomerulonephritis with crescents (10 to 44%, N = 6), compared with normal control kidneys (N = 10). Biopsies were further classified into those showing active (cells, fibrin) (N = 15) or inactive (sclerosed) crescents (N = 19), to determine whether IL-2R+ MNC were particularly associated with active crescent formation. Few leucocytes were found within glomerular tufts of normal kidneys (2.4 +/- 0.7 cells/glomerular cross-section; mean +/- SEM). By contrast, in biopsies from patients with active crescentic glomerulonephritis, total intraglomerular tuft leucocytes were increased to 14.0 +/- 1.7 (P less than 0.01 vs. normal kidneys), largely due to increased numbers of intraglomerular monocytes (10.4 +/- 1.1, P less than 0.01) and T cells (3.7 +/- 0.6, P less than 0.01). Biopsies with active crescents also contained significantly increased numbers of intraglomerular tuft IL-2R+ MNC (4.0 +/- 0.7, 29% of total intraglomerular leucocytes), and there was a strong correlation between the numbers of intraglomerular IL-2R+ MNC and T cells (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activated (IL-2R+) intraglomerular mononuclear cells in crescentic glomerulonephritis. 205 38

Our previous immunohistologic studies with monoclonal antibodies (mAb) showed that glomerular and interstitial accumulations of mononuclear cells (MNC) were common features of many types of proliferative glomerulonephritis, especially crescentic glomerulonephritis. The current study examined a series of patients with crescentic IgA disease, since IgA disease in general has a highly variable course and the presence of crescents is one indicator of likely progression to end-stage renal failure. We compared the intraglomerular and interstitial infiltrates within biopsies from patients with crescentic IgA nephropathy (N = 5) versus those with noncrescentic IgA (N = 18), or normal controls (N = 10). Few leucocytes were found within glomeruli of normal (2.4 +/- 0.7 cells/glomerular cross section) (mean +/- SEM) or noncrescentic IgA disease biopsies (3.8 +/- 0.7), and no activated MNC bearing receptors for interleukin-2 (IL-2R) were detected. By contrast, in crescentic IgA disease, glomerular leucocytes were increased (5.1 +/- 0.6, P less than 0.01), due to increased monocyte (3.1 +/- 0.9, P less than 0.01) and T cell (1.4 +/- 0.4, P less than 0.01) infiltration, and IL-2R + MNC were then observed (1.2 +/- 0.5, P less than 0.05). Studies of interstitial cells showed small numbers of leucocytes within normal kidneys (101 +/- 16/mm2). Biopsies from noncrescentic IgA disease showed a fivefold increase in interstitial MNC infiltration (total leucocytes 565 +/- 105/mm2, P less than 0.01), due to an influx of T cells (283 +/- 59/mm2, P less than 0.01) and monocytes (120 +/- 32/mm2, P less than 0.01), and including a mean of 20% IL-2R+ MNC (114 +/- 29/mm2, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mononuclear cell activation and decreased renal function in IgA nephropathy with crescents. 236 7

1. The effects of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) on urinary protein excretion were examined in nine healthy subjects and 20 patients with primary glomerular diseases who had proteinuria of 1.0 g or more per day. Synthetic alpha-hANP was intravenously infused into supine subjects at a rate of 8.3 pmol min-1 kg-1 for 40 min. 2. Before alpha-hANP infusion, the plasma concentration of immunoreactive alpha-hANP was significantly higher in the patients with glomerulonephritis than in the normal subjects (44.3 +/- 8.7 vs 19.4 +/- 3.0 pmol/l, mean +/- SEM, P less than 0.01) and it showed a positive correlation with mean arterial pressure (rs = 0.84, P less than 0.001) and a negative correlation with creatinine clearance (rs = -0.50, P less than 0.01). 3. During infusion of alpha-hANP, although the urinary excretion of protein did not change significantly in the normal subjects, it increased from 0.6 +/- 0.2 to 3.0 +/- 0.8 mg min-1 m-2 (P less than 0.001) in the patients with glomerulonephritis. The urinary protein/creatinine ratio did not change significantly in the former (from 0.18 +/- 0.05 to 0.22 +/- 0.06; NS), whereas it rose from 3.25 +/- 0.94 to 7.62 +/- 1.31 (P less than 0.001) in the latter. 4. The urinary excretions of albumin and of alpha 1-, alpha 2-, beta- and gamma-globulins, which were electrophoretically analysed, all increased in eight nephrotic patients during or immediately after infusion of alpha-hANP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of alpha-human atrial natriuretic peptide on proteinuria in patients with primary glomerular diseases. 253 80

25 kidney donors who had undergone nephrectomy 1-11 years ago, 35 patients followed up for 13 years after poststreptococcal glomerulonephritis, and 44 controls were investigated for their capacity to increase their glomerular filtration rate after an acute oral load of 100-150 g of protein. Their mean baseline creatinine clearances (Ccrl, ml/min +/- SEM) were similar (controls 108.5 +/- 6.1; kidney donors 115.4 +/- 8.54; postacute nephritis 82.0 +/- 6.45), but the postmeal filtration rates (Ccr2) were significantly (p less than 0.05) lower in the two patient groups (kidney donors 137.4 +/- 11.60; postacute nephritis 90.3 +/- 5.30) than in the controls (161.5 +/- 9.39), as was the Ccr2/Ccr1 ratio (p less than 0.01, controls 1.58 +/- SEM 0.10; kidney donors 1.20 +/- 0.07; postacute nephritis 1.18 +/- 0.08). In normal individuals the degree of change was inversely related to the initial creatinine clearance and varied from 135.6% +/- 43.0 when Ccrl was less than 70 ml/min to 32.7% +/- 9.50 when Ccrl was 130 ml/min or higher. This relative response was decreased in kidney donors and postacute nephritis patients. Kidney donors and apparently normal postacute nephritis patients thus have diminished renal reserve capacity.
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PMID:Response to acute protein load in kidney donors and in apparently normal postacute glomerulonephritis patients: evidence for glomerular hyperfiltration. 286 91

Expression of the C3b/C4b receptor (CR1) on erythrocytes is decreased in patients with systemic lupus erythematosus (SLE) compared to normal individuals, and the CR1 antigen is absent from podocytes in severe diffuse proliferate nephritis of SLE. In the present study, we examined the relationship between the number of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes in non-SLE nephritis and other systemic inflammatory diseases by measuring the binding of 125I-labeled rabbit F(ab')2 and murine monoclonal IgG anti-CR1 antibodies to erythrocytes of normal individuals and patients in a French population. The number of binding sites for monoclonal anti-CR1 antibody on erythrocytes of 116 normal individuals was 743 +/- 22 (mean +/- SEM) with a range of 169-1,333, and the frequency distribution of this number in the population was bimodal. In 112 patients with SLE, the mean number of CR1 sites on erythrocytes was decreased to 62% of the mean for normal individuals (p less than 0.001). No correlation was found between CR1 expression on erythrocytes and the presence or immunohistopathological type of glomerulonephritis in biopsy specimens from these patients. The mean number of CR1 on erythrocytes of 29 patients with non-SLE glomerulonephritis was slightly decreased to 89% of the normal mean (p greater than 0.05), which could not be attributed to glomerular immune complex disease or vasculitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased expression of C3b receptor (CR1) on erythrocytes of patients with systemic lupus erythematosus contrasts with its normal expression in other systemic diseases and does not correlate with the occurrence or severity of SLE nephritis. 294 97

The acute phase of glomerular injury in a model of antiglomerular basement membrane, antibody-induced glomerulonephritis (antiGBM-GN) in rabbits was shown to be neutrophil-dependent using nitrogen mustard depletion studies. Administration of desferrioxamine (DFX) prevented the development of proteinuria in this model of renal injury [24 hr protein excretion (mean +/- SEM): antiGBM-GN/DFX = 16.2 +/- 2.9 mg compared with antiGBM-GN control = 271.5 +/- 92.2 mg, P less than 0.01]. Antibody binding levels, glomerular filtration rates, circulating complement and neutrophil counts, glomerular C3 deposition, and neutrophil infiltration did not differ between DFX treated and antiGBM-GN groups. In vitro assay systems to assess oxygen radical production [superoxide anion (O2-) and hydroxyl radical (OH.)] by neutrophils activated via the interaction of antiGBM antibody, GBM and complement were established. In these assays, DFX inhibited OH. production by immunologically-stimulated neutrophils (ISN) [nM diphenol/hr/10(6) cells, mean +/- SEM, ISN/DFX = 8 +/- 2 compared with ISN = 191 +/- 22, P less than 0.01] while production of O2- was not affected [nM O2-/hr/10(6) cells, mean +/- SEM, ISN/DFX = 29.1 +/- 4.3 compared with ISN = 32.6 +/- 2.5, P greater than 0.05]. These studies demonstrate that the iron chelator desferrioxamine can prevent neutrophil-dependent immune renal injury by interfering with neutrophil function. Treatment with the hydroxyl radical scavenger dimethylthiourea also significantly attenuated renal injury in antiGBM-GN. Together, the in vivo and in vitro data strongly suggest that neutrophil-dependent immunological renal injury is mediated via hydroxyl radical production by activated neutrophils within glomeruli.
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PMID:Hydroxyl radical mediation of immune renal injury by desferrioxamine. 302 99

Sera from 35 patients with biopsy-proven diffuse proliferative (WHO class IV) or membranous (WHO class V) lupus nephritis were analyzed for the presence and size of circulating immune complexes. Elevations of the C1q solid-phase assay (C1qSP) for immune complexes were found in sera from all patients with diffuse proliferative nephritis, with a mean +/- 1 SEM of 166.8 +/- 42.0 micrograms/AHG-equivalents/ml serum, and in 71.4% of the patients with membranous nephritis (83.1 +/- 26.7, p = 0.06). Using the WHO criteria for subclasses of membranous lupus nephritis, we also designated renal biopsies as nonproliferative (WHO classes Va and Vb) or proliferative (WHO classes IV and Vc). Employing the latter groupings, we observed significant differences between C1qSP results of patients with nonproliferative (30.3 +/- 8.8) and proliferative (172.8 +/- 36.8, p less than 0.001) lupus nephritis. These data suggest that the presence of C1q-binding material in serum is pathophysiologically related to proliferative glomerular lesions, and that levels of C1qSP binding reflect renal lesions in SLE patients. Sucrose density gradient ultracentrifugation was performed on each serum, and gradient fractions analyzed for C1qSP-binding and total IgG, using techniques to minimize losses of immune complexes. The predominant peak of C1qSP activity sedimented with the 6.6S monomeric IgG. The 6.6S C1q-binding IgG was increased only in 1 of 10 patients with membranous lupus nephritis without proliferative changes, and was elevated in 16 of 25 patients with proliferative lesions (WHO classes IV and Vc). A significant negative correlation was found between the presence of this C1q-binding material and subepithelial electron-dense deposits, suggesting that the presence of this material contributed to the absence of subepithelial immune deposits. Large-molecular-weight C1qSP-binding material was also present, mainly in sera from patients with proliferative lesions. Furthermore, highly positive correlations were found between immune deposits in interstitial blood vessels and peritubular areas, and the concentrations of C1qSP-binding IgG and rapidly sedimenting IgG in density gradient analysis. Overall, these findings are consistent with the hypotheses that circulating immune complexes contribute to the pathogenesis of glomerulonephritis and interstitial nephritis in patients with SLE, and that 6.6S C1q-binding IgG plays a role in the proliferative lesions of lupus glomerulonephritis.
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PMID:Relationship between renal pathology and the size of circulating immune complexes in patients with systemic lupus erythematosus. 310 94


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