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)

Mercuric chloride induces a transient systemic T-lymphocyte dependent autoimmune syndrome in Brown Norway rats. Two weeks after the first HgCl2 injection maximum serum levels of anti-GBM antibodies and nephrotic range proteinuria are detected. CyA treatment during HgCl2 administration completely prevented these autoimmune phenomena. Moreover, a prolonged unresponsiveness to HgCl2 was induced, lasting for at least 5 weeks after combined pretreatment with CyA and HgCl2. This unresponsiveness could not be adoptively transferred with peripheral lymphoid cells. Suppression of development of HgCl2-induced proteinuria was adoptively transferred with lymphoid cells from HgCl2-treated donors in remission phase. Unresponsiveness to HgCl2, induced by CyA plus HgCl2 pretreatment, could be broken by reconstitution with naive lymphoid cells. These results suggest that the tolerogenic effect of CyA in HgCl2-induced autoimmunity is not mediated by active suppression; instead, the observed unresponsiveness might be due to direct functional deletion of autoreactive T-lymphocytes. A serendipitous finding was the dissociation in time between synthesis of anti-GBM antibodies and development of proteinuria, suggesting a role for cellular effector mechanisms in the induction of proteinuria.
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PMID:Cyclosporin A induces long-term unresponsiveness in mercuric chloride-induced autoimmune glomerulonephritis. 318 May 13

In a telescoped model of antiglomerular basement membrane (GBM) antibody induced nephritis, Lewis strain rats were injected in the footpad with rabbit IgG on day 0 and then given a single intravenous injection of rabbit anti-rat GBM antibody on day 5. Proteinuria developed within 24 h and renal histology 7 days later showed a focal or diffuse proliferative glomerulonephritis. In this study rats treated as above were given Cyclosporin A (CyA) 20 mg/kg daily by intraperitoneal injection from day 0 or from day 5. Rats given CyA plus anti-GBM antibody developed extensive glomerular infiltration with polymorphs and glomerular thrombosis, lesions not seen with unmodified anti-GBM nephritis or in rats who received CyA alone. The mechanism by which CyA given prior to or at the onset of immunological insult in this model worsens glomerular injury is unclear.
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PMID:Cyclosporin A and anti-glomerular basement membrane antibody glomerulonephritis in rats. 325 90

Female Wistar rats were injected with (mouse) monoclonal antibodies (Moabs) of different IgG subclasses directed to rat thymocytes or rat tumor cells. Following intravenous injection of antithymocyte Moabs, glomerular binding of mouse IgG was observed during the first 4 days along the GBM and in the mesangium. No staining for mouse IgG was detected in anti-tumor Moab injected rats. Animals injected with IgG 2a anti-thymocyte Moab developed glomerulonephritis and a massive proteinuria in contrast to rats injected with IgG 1 Moab which is non-complement fixing. The glomerulonephritis lesion consisted of microaneurysms and focal and segmental proliferation. Deposits of complement and fibrin could be detected exclusively in rats injected with IgG 2a anti-thymocyte Moab during the whole observation period of 14 days. This is the first demonstration of overt glomerulonephritis lesions on the injection of monoclonal antibodies.
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PMID:Acute glomerulonephritis after intravenous injection of monoclonal anti-thymocyte antibodies in the rat. 352 13

It has been proposed that ingestion of large amounts of dietary protein leads to sustained renal hyperperfusion and progressive glomerulosclerosis in rats. This hypothesis was tested in dogs, with 75% reduction in renal mass, maintained for 4 years on either 56, 27, or 19% dietary protein. Twelve of 21 dogs survived 4 years, and death due to renal failure was not correlated to diet. Dogs fed 56 and 27% protein had increased GFR and CPAH before and after reduction of renal mass compared to the 19% group. A pattern of deterioration of renal function, including proteinuria, was not found in any diet group. Nine of 11 dogs, fed 56, 27, or 19% protein had minimal glomerular lesions, including mesangial proliferation, GBM irregularities, adhesions, and sclerosis. Two other dogs, fed 56% protein, had more severe glomerular lesions. No significant ultrastructural differences were found in glomeruli among the three diet groups. These results do not support the hypothesis that high protein feeding had a significant adverse effect on either renal function of morphology in dogs with 75% nephrectomy.
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PMID:Long-term renal responses to high dietary protein in dogs with 75% nephrectomy. 370 9

Twenty-eight patients aged from 18 mo. to 23 y. (at the onset of the diseases) affected by Alport's syndrome (AS), were studied during last 15 years. The mean time of observation was 10 +/- 0.7 years. Two cases progressed to renal failure at 15 and 21 years respectively, while 26 patients have normal renal function within the 2a decade of life. The diagnosis of hereditary nephritis (AS) was based on the following criteria: Existence of affected kindred. Perceptive deafness. Basal membrane ultrastructural abnormalities. A late exact diagnosis was made in some patients without ascertainable familiarity and without early ultrastructural glomerular study. Perceptive deafness occurred chiefly after 6-8 years of life, increasing the diagnostic difficulties. Isolated hematuria was present in 18 cases (64%) and associated proteinuria (or NS) in 10 (36%). Recurrent otitis media worsened the hearing loss in 5 cases (17.83%). An immuno-allergologic study was carried out because of the great frequency of allergic diseases, respiratory mainly. A significative decrease of plasmatic and secretory IgA was observed in those patients who underwent to recurrent otitis media. The features suggestive of AS in our patients, in addition to the familiarity, were gross haematuria in childhood and diffuse GBM splitting and splintering. Heavy proteinuria and nephrotic syndrome associated to early deafness and to male sex indicate a poor prognosis; but several females also can be affected by serious course of the disease.
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PMID:[Alport syndrome: 15-year follow-up in 28 cases]. 378 95

Most immune renal diseases are caused by the formation of immune complexes of antibody with either fixed glomerular antigens or exogenous non-renal antigens. Much progress has been made recently in understanding the ways by which these immune deposits form in glomeruli. Immune complex deposits of exogenous antigens may involve prior antigen localization in the glomerulus to initiate immune complex formation locally, or in situ. The type of glomerular lesion produced depends in large part on the site at which deposit formation occurs, which in turn determines what mediators of tissue injury are activated. The nature and quantity of immune reactants are also important. Subepithelial deposits may result from antibody binding to fixed epithelial cell-derived antigens or to exogenous antigens localized by direct interaction with glomerular anionic sites (cationic antigens) or with nonimmune cationic proteins bound to glomerular anionic sites (anionic antigens). Cationic antibody may also localize first, and deposits can form from subendothelial immune complex deposits dissociating to cross the GBM and re-form in a subepithelial distribution. Proteinuria induced by subepithelial immune deposit formation appears to be due to a direct effect of complement, probably involving membrane attack complexes, and independent of inflammatory cells. Intramembranous deposits form from anti-GBM antibody reacting with intrinsic GBM antigens. Subendothelial and mesangial deposits appear not to involve fixed antigens. Rather, they represent immune complexes containing exogenous antigens and antibody to the antigens. These complexes may result from the passive trapping of pre-formed immune complexes from the circulation or may form in situ by several different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunologic mechanisms of renal disease. 388 70

The effect of cyclosporin A (CYA) on the development of active and passive models of rat anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM-GN) was assessed. Active GN was induced by an intravenous injection of sheep anti-rat GBM globulin to preimmunized rats. After 5 days, a diffuse proliferative GN with proteinuria and linear GBM deposition of rat IgG was regularly observed. CYA treatment, commencing prior to preimmunization, significantly attenuated the glomerular lesion, reduced proteinuria, prevented linear deposition of rat IgG and reduced the serum titre of anti-sheep globulin antibody. However, treatment started after the antibody response was established failed to alter antibody production, its glomerular deposition or the outcome of the disease. CYA treatment did not effect passive anti-GBM-GN, occurring 24 h after intravenous administration of sheep anti-rat GBM globulin to unimmunized rats. Thus, CYA is able to block anti-GBM-GN when given prior to induction of disease, by preventing an active antibody response. However, it did not alter GN when the antibody response was well established, or when glomerular injury was passively induced.
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PMID:Effect of cyclosporin A on antibody-induced experimental glomerulonephritis. 388 77

To determine if the site of immune reaction could influence the mediation and morphological expression of glomerular injury in experimental anti-glomerular basement membrane (anti-GBM) nephritis and membranous nephropathy, we studied the events that followed the in situ reaction of rat antibody with antigen planted in either the GBM (especially the lamina rara interna) or in the subepithelial space (SE). Non-nephritogenic amounts of noncomplement-fixing sheep anti-GBM or anti-tubular brushborder antibody were injected into separate groups of rats to plant sheep IgG in the GBM and SE, respectively. Kidneys containing sheep IgG were then transplanted into naive recipients that were passively immunized with rat anti-sheep IgG. There was marked proteinuria after 2 days (antigen in GBM: 226 +/- 50.7; antigen in SE: 69 +/- 50.7 mg/24 hr) that was abrogated by prior depletion of complement in both groups (antigen in GBM: 10.2 +/- 1.7; antigen in SE: 14.3 +/- 8.7 mg/24 hr). When antigen was planted in SE, inflammatory-cell depletion with either anti-neutrophil (PMN) serum or lethal irradiation had no effect on proteinuria. In contrast, anti-PMN abolished proteinuria (12.0 +/- 5.6 mg/24 hr) and irradiation reduced it by 60% when antigen was in GBM. Glomeruli of kidneys with antigen in GBM were significantly larger and more hypercellular than those with antigen in SE after transplantation into immunized recipients. Endothelial cell injury and adherence of inflammatory cells to denuded GBM were prominent in the former (antigen in GBM), while glomeruli with antigen in SE showed only subepithelial deposits, adjacent slit-diaphragm displacement, and epithelial cell foot-process effacement. Thus, the reaction of antigen and antibody in glomeruli produced complement-mediated injury which was cell-independent when complex formation occurred on the outer aspect of the GBM but was cell-dependent when the same reagents reacted more proximally to the circulation. We therefore conclude that antigen distribution can critically influence the mediation and morphologic expression of immune glomerular injury and may, in part, account for variations in the clinical and histological manifestations of antibody-induced glomerular disease in humans.
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PMID:Influence of antigen distribution on the mediation of immunological glomerular injury. 389 65

The repeated administration of mercuric chloride to BN rats induces the production of anti-GBM. In the present paper, we describe the immunohistopathology and histopathology of the kidneys from mercuricchloride-treated rats. Direct immunofluorescence demonstrated bright linear deposits of immunoglobulins at the level of the GBM of the kidney. Light microscopy failed to reveal substantial glomerular changes, but electron microscopy demonstrated a spectrum of ultrastructural alterations of the glomeruli (including the detachment of endothelial cells from the GBM and the presence of electron-opaque deposits). In the aggregate, these findings are suggestive of membranous glomerulonephritis. We also investigated whether treatment with low doses of PG had any effect on the course of this experimental model of autoimmune renal disease. Two groups of mercuric-chloride-treated BN rats received different doses of DMPGE2. This resulted in significantly lower levels of circulating autoantibodies to the GBM, as well as a decrease in the amounts of rat immunoglobulins bound to the kidneys and an increase in proteinuria. On the other hand, there were no major differences in renal histopathology between rats treated with DMPGE2 and controls.
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PMID:Mercury-induced autoimmune glomerulonephritis in inbred rats. II. Immunohistopathology, histopathology and effects of prostaglandin administration. 391 30

In the rat, radiation injury to a kidney results in severe glomerular lesions, with only a moderate increase in proteinuria. The proteinuria, however, was found to be nonselective. There was no relationship between the degree and selectivity of the proteinuria. No change in the gross chemical composition of the glomerular basement membrane obtained from the irradiated kidney was observed when compared with the GBM of a) untreated control kidneys, b) kidneys obtained from sham operated rats, c) unilaterally nephrectomized and d) control kidneys of irradiated animals. In conclusion, no correlation could be established between the morphologic alterations of the glomerulus and the chemical or permeability characteristics of the membrane.
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PMID:Radiation nephritis. 3. Chemical, functional and morphologic correlates of the glomerular basement membrane. 472 96


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