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)

Administration of HgCl2 to the susceptible Brown-Norway (BN) strain of rats induces an autoimmune disease characterized by polyclonal B cell activation, increased serum levels of IgE and the occurrence of anti-glomerular basement membrane antibody-mediated glomerulonephritis. We have observed that the simultaneous administration to BN rats of normal human polyspecific immunoglobulins for therapeutic use (IVIg) with HgCl2 significantly decreased the occurrence and severity of proteinuria, and reduced serum IgE levels in diseased animals. Hypergammaglobulinaemia was potentiated in animals receiving HgCl2 and IVIg, compared with animals receiving HgCl2 alone. In vitro experiments indicated that F(ab')2 fragments from IVIg inhibited the binding to laminin of pathogenic anti-laminin antibodies from diseased rats, as did antibodies from the resistant Lewis strain of rats but not antibodies from susceptible BN rats. These observations suggest that IVIg may interfere with the immune regulatory mechanisms involved in mercury-induced autoimmune disease in an analogous fashion to the ability of IVIg to suppress the expression of certain pathological autoimmune responses in humans.
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PMID:Beneficial effect of human therapeutic intravenous immunoglobulins (IVIg) in mercuric-chloride-induced autoimmune disease of Brown-Norway rats. 201 3

Elevated urine mercury levels in two Asian brothers with the nephrotic syndrome led to the discovery of very high mercury concentrations in 7 out of 10 other family members. Mercury contamination was caused by gold refining in a garage at the home. Although childhood nephrotic syndrome is usually idiopathic, the proteinuria and the mercury inhalation were probably causally related in this family.
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PMID:Nephrotic syndrome in two members of a family with mercury poisoning. 213 88

In Brown-Norway (BN) rats mercuric chloride induces an autoimmune disease characterized by an increase in serum IgE concentration, and by the production of anti-glomerular basement membrane antibodies responsible for a glomerulonephritis with a heavy proteinuria. (i) This disease results from a B-cell polyclonal activation probably due to frequent anti-class II T cells. (ii) The self limitation observed in this model is associated with both a decrease in the frequency of anti-class II T cells and the emergence of CD8+ T cells able to suppress these autoreactive T cells. (iii) In Lewis (LEW) rats which do not develop autoimmunity, HgCl2 provokes the appearance of non-antigen-specific CD8+ T cells responsible for a depression of T-cell functions. The aim of this work was to test the effect of treatment with an anti-CD8 monoclonal antibody (MoAb) in both BN and LEW rats. Anti-CD8 MoAb-treated rats were effectively depleted in CD8+ T cells. However, neither the induction nor regulation phases of mercury-induced autoimmunity were modified in BN rats. Mercury-induced immunosuppression in LEW rats was abrogated; however, depletion in CD8+ T cells did not allow the disease to occur in that strain. Finally, CD8 depletion induced in normal BN rats the appearance of rare anti-class II T cells showing that these cells are normally present in that strain but negatively controlled by suppressor T cells.
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PMID:Role of CD8+ T cells in mercury-induced autoimmunity or immunosuppression in the rat. 213 55

The early renal excretion of mercuric mercury was studied in male BALB/c mice between 15 seconds and 30 min following a single intravenous injection of 3 mg HgCl2/kg body weight. The cytochemical Silver Amplification method applied at the light and electron microscopical levels showed mercury to be excreted by glomerular filtration and reabsorbed by proximal tubular epithelial cells by means of adsorptive endocytosis. Mercury was rapidly demonstrated in the lysosomal vacuome of proximal tubular epithelial cells. No uptake was observed from the peritubular side, and there was no evidence of tubular secretion of mercury. It is proposed that mercury is excreted in the form of mercury-protein complexes, assisted by the physiological proteinuria in mice, which is enhanced by mercury-induced damage to the glomerular structures.
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PMID:Renal handling of inorganic mercury in mice. The early excretion phase following a single intravenous injection of mercuric chloride studied by the Silver Amplification method. 286 44

Classically, the histological lesion observed in a drug-or heavy metal-induced nephrotic syndrome is membranous glomerulonephritis. We report two cases of "toxic" nephrotic syndrome with unusual histological features. One was secondary to mercury intoxication and the other, to D-penicillamine in a patient with rheumatoid arthritis. In both cases, renal biopsy revealed minimal glomerular changes. The proteinuria rapidly disappeared after exposure to the toxic agent was discontinued. Genetic factors and a disregulation of the immune system with lymphokine production may be responsible for these renal changes. This study demonstrates that renal biopsy is necessary in this clinical setting.
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PMID:[Lipoid nephrosis of toxic origin. 2 cases]. 294 17

The effects of methylprednisolone and of cyclophosphamide were tested in mercury-induced autoimmune disease in Brown-Norway rats. Survival, proteinuria, presence of antiglomerular basement membrane bound antibodies and of immune complex type deposits, amounts of circulating immune complexes, and total serum IgE were studied. Serum IgE represents the most sensitive marker in this drug-induced autoimmune disease. Methylprednisolone alone (1.5 mg/kg per day) affected the course of the disease only slightly. Cyclophosphamide (20 mg/kg every other day) given from day 0 completely prevented all the autoimmune manifestations, but the rats were profoundly immunosuppressed. The same protective effect was obtained with lower cyclophosphamide dosage (15 mg/kg on day 0 and then 2 mg/kg per day). More interestingly, cyclophosphamide given from day 10 or 15 (20 mg/kg twice a week or every other day), at a time when the disease was already expressed, resulted in partial or complete recovery, provided that the rats had not exhibited heavy proteinuria before initiation of treatment. Cyclophosphamide is therefore a powerful agent, able to prevent and even to reduce the consequences of polyclonal activation in this model.
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PMID:Effect of methylprednisolone and cyclophosphamide in mercury-induced autoimmune glomerulonephritis. 311 Jun 91

Mercury exposure and renal function parameters were examined in 68 dentists and 64 dental assistants. The levels of mercury in urine were low: only three individuals exceeded 20 micrograms/l. Increased excretion of urinary proteins and increased activity of urinary enzymes were observed. This enhanced prevalence of renal function changes appeared not to be related to the mercury urine level, age, sex, or smoking and drinking habits. Only for men was a positive relation between the level of mercury in urine and the activity of beta-galactosidase found. The proteinuria may be due to one or more potential nephrotoxic agents used in dental practice.
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PMID:Urinary mercury levels and early changes in kidney function in dentists and dental assistants. 313 45

Inbred Brown Norway (BN) rats treated with mercuric chloride develop autoantibodies to renal basement membranes and an immunologically mediated membranous glomerulonephritis. To date, this experimental rat model of chemically induced autoimmunity has been obtained only in the BN strain, whereas rats from 17 other strains were found to be resistant. This is a disadvantage for mechanistic studies, especially since BN rats have poor fertility. In the present paper we report that the same model can be obtained in another inbred strain of rats, the MAXX, which after exposure to mercury develop a glomerulonephritis characterized by the production of autoantibodies to renal basement membranes. The kinetics of the autoimmune response observed in MAXX rats, as well as the immunohistopathology, histopathology, and proteinuria, are similar to those previously described in BN rats. In addition, the MAXX strain is endowed with excellent fertility. Therefore, both rat strains can be used for comparative studies of the mechanisms of mercury-induced autoimmunity.
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PMID:Mercury-induced renal autoimmunity in the MAXX rat. 316 32

Proteinuria induced by chronic exposure to mercury and the relationship between urinary mercury and kidney damage were explored in rats using ultrafiltration concentration, gel chromatography, and transmission electron microscopy. The results showed that the primary site of damage was the proximal renal tubule and that the glomerulus was eventually involved. Of the tubular cell ultrastructures, the lysosome was the most sensitive to mercury, and there was a close relation between the excretion of urinary mercury and the mercury detoxication mechanism of the kidney. Many deposits were found in the endothelia and mesangia of the glomeruli. The results of the study showed that urinary mercury consisted of three components, that filtration through the glomeruli was an important source of urinary mercury, and that the mercury excreted from the renal tubules reflected the mercury-loading status of the kidney.
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PMID:Experimental study of proteinuria caused by chronic exposure to mercury. 327 May 13

The mechanism involved in glomerular fibrin deposition was investigated during mercuric chloride (HgCl2)-induced autoimmune glomerulonephritis in the Brown Norway rat. To ascertain whether the local hemostatic system was activated secondarily to the immunological conflict, the ability of glomerular lysates to induce coagulation in vitro was assessed in treated and control rats. Glomerular procoagulant activity (PCA) of HgCl2-injected rats was measured on day 12 (latent phase of the disease), day 20 (acme), and days 32 and 42 (recovery phase) after the first mercury injection. PCA rose 3-fold (p less than 0.02) at day 20 and then almost returned to control values. Proteinuria, PCA, and the incidence of glomerular fibrin deposits peaked concomitantly at day 20. Glomerular PCA was characterized as thromboplastin. The number of Ia positive cells detected by monoclonal OX-6 antibody was not different from the control number at any phase of the disease; the number of macrophages per glomerular section detected by electron microscopy at day 20 in HgCl2-injected rats was 1.80 +/- 0.60, versus 0.30 +/- 0.11 in the controls. No correlation was found between glomerular PCA and either the number of monocytes/macrophages or of Ia-positive cells present in the glomeruli. Since glomerular PCA was maximal at the onset of fibrin formation in the glomeruli and then decreased toward its basal level, and since the fibrin disappeared, it is concluded that increased production of thromboplastin by glomeruli, with activation of the extrinsic coagulation pathway, may contribute to intraglomerular fibrin deposition in HgCl2-induced glomerulonephritis.
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PMID:Enhanced glomerular procoagulant activity and fibrin deposition in rats with mercuric chloride-induced autoimmune nephritis. 347 99


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