Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of gold-induced autoimmunity and membranous glomerulopathy is not well understood. HgCl2 and D-penicillamine, other chemicals known to trigger membranous glomerulopathy in humans, induce autoimmune manifestations in Brown-Norway (BN) rats but not in Lewis (LEW) rats. These chemicals trigger T-cell clones which are specific for self class II molecules from the major histocompatibility complex and are probably responsible for the polyclonal B-cell activation observed. The aim of this work was to test the effects of aurothiopropanolsulphonate (ATPS) in BN and LEW rats. In BN rats, ATPS induced a polyclonal B-cell activation marked by lymphoproliferation, hyperimmunoglobulinaemia affecting mainly IgE, and by the production of numerous autoantibodies. A glomerulonephritis occurred, initially due to anti-glomerular basement membrane antibody deposition, and later to the formation of granular deposits, occasionally resulting in a typical membranous glomerulopathy. Self class-II-specific T-cells were found that might be responsible for the polyclonal B-cell activation. Lewis rats were free of glomerulopathy but, like BN rats, exhibited an interstitial nephritis and some degree of polyclonal B-cell activation. These findings demonstrate that, depending on the strain, ATPS triggers different B-cell clones inducing different degrees of autoimmunity.
Nephrol Dial Transplant 1991
PMID:Experimental gold-induced autoimmunity. 174 85

In order to study disease mechanisms and potential forms of therapy in glomerulonephritis, a model of experimental autoimmune glomerulonephritis (EAG) has been developed in the rat. We have examined the response of Brown-Norway (BN) rats to a single i.m. injection of collagenase-solubilised homologous (Sprague-Dawley, SD) or isologous (BN) glomerular basement membrane (GBM), with and without complete Freund's adjuvant (CFA). There was a dose-dependent circulating anti-GBM antibody response to all preparations of rat GBM. Animals given either antigen alone at a dose of 2 mg/kg developed circulating anti-GBM antibodies, which reached peak values by 6 weeks (63 +/- 5% following SD GBM; 53 +/- 8% following BN GBM), but did not develop glomerular deposits of IgG or nephritis. Animals given 2 mg/kg SD GBM in CFA developed greater concentrations of anti-GBM antibody by 6 weeks (122 +/- 20%) together with linear deposits of IgG on glomerular and tubular basement membranes (TBM), albuminuria (mean 7 mg/24 h), and variable focal segmental necrotising glomerulonephritis with mild interstitial nephritis. The same dose of BN GBM in CFA produced similar concentrations of circulating antibody (144 +/- 26%), with linear deposits of IgG on GBM but rarely TBM, little albuminuria, and variable mild focal glomerulonephritis. Other strains injected with SD GBM in CFA showed a variable circulating anti-GBM antibody response, which was similar to that of BN rats in PVG and DA rats but lower in LEW and WAG rats. Linear deposits of IgG on the GBM were detected in a proportion of PVG and DA rats, but not in LEW or WAG rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1991
PMID:Experimental autoimmune glomerulonephritis induced by homologous and isologous glomerular basement membrane in Brown-Norway rats. 192 7

Mercury-induced autoimmunity in Brown-Norway rats has been shown previously to be due to polyclonal activation of B lymphocytes, requiring the presence of T lymphocytes. Autoimmunity in that strain is characterised by the appearance of an autoimmune glomerulonephritis, by the production of a host of autoantibodies, and by an increase in total serum IgE. In the present study, T-cell deprived rats were tested to assess the role of T cells in the appearance of autoimmune abnormalities in vivo. It will be shown that both BN rnu/rnu and BN 'B' rats, who have virtually no T cells, do not develop autoimmunity following HgCl2 injections. In contrast BN 'B' rats reconstituted with normal T cells, and BN rnu/+ rats, exhibit autoimmune manifestations, including autoimmune glomerulonephritis, quite similar to those observed in Brown-Norway rats. These data demonstrate that T cells are essential for mercury-induced autoimmunity to occur in Brown-Norway rats.
Nephrol Dial Transplant 1987
PMID:Mercury-induced autoimmune glomerulonephritis: requirement for T-cells. 311 Jun 76

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.
Nephrol Dial Transplant 1987
PMID:Effect of methylprednisolone and cyclophosphamide in mercury-induced autoimmune glomerulonephritis. 311 Jun 91

Using an original technique permitting repeated plasma exchange in the rat, we have tested this therapeutic approach in animals actively immunised with horseradish peroxidase, and in rats with HgCl2-induced autoimmune glomerulonephritis. Plasma exchange effectively removes circulating IgG anti-horseradish peroxidase antibodies from the sera of immunised rats. When applied to the model of HgCl2-induced antiglomerular basement membrane glomerulonephritis in Brown-Norway rats, this technique is also remarkably effective. In these rats, proteinuria is abolished during the plasma exchange treatment period and no circulating antiglomerular basement membrane antibodies can be detected. These antibodies are, however, found in the ultrafiltrates of exchanged rats. Serum IgE, characteristically elevated in HgCl2-treated rats, is also markedly diminished in exchanged rats. Control rats treated with infusions of fresh frozen plasma or with heparin alone did not show any improvement in disease severity. These results suggest that plasma exchange alone can attenuate antiglomerular basement membrane nephritis in HgCl2-treated rats. This observation may be of relevance for the treatment of human antiglomerular-basement membrane-mediated glomerulonephritis.
Nephrol Dial Transplant 1988
PMID:Plasma exchange in a rat model of autoimmune glomerulonephritis. 314 Jan 25

In Brown-Norway rats HgCl2 induces an autoimmune disease due to a T-dependent B cell polyclonal activation. This disease is marked by the production of numerous antibodies including antiglomerular basement membrane (GBM) antibodies. Rats exhibit a biphasic glomerulopathy with heavy proteinuria. Initially anti-GBM antibodies are found linearly deposited; they precede the appearance of membranous glomerulopathy. Rats recover spontaneously even if HgCl2 injections are pursued, but mechanisms at play are unclear. We have assessed the effects of transplanting the spleen from a BN rat, either at the acme of the disease or at the time of convalescence, into naive BN rats, some of which were then injected with HgCl2. Transplantation of a spleen from HgCl2-injected rats at the acme of the disease dramatically protects BN rats from all the manifestations of the mercury disease. BN rats transplanted with a spleen from HgCl2-injected rats at the time of convalescence only exhibited a typical membranous glomerulopathy with heavy proteinuria but without circulating anti-GBM antibodies. Antilaminin antibodies were eluted from the glomeruli. This study shows that spleen cells from HgCl2-injected rats are able to confer tolerance to HgCl2-induced autoimmunity. It also shows that some B cell clones escape this tolerance. Finally, this study strongly suggests that membranous glomerulopathy, responsible for proteinuria in this model, is related to the presence of antilaminin antibodies.
Nephrol Dial Transplant 1993
PMID:Evidence for a role of antilaminin-producing B cell clones that escape tolerance in the pathogenesis of HgCl2-induced membranous glomerulopathy. 838 32

With the purpose of studying the curve of parathyroid response to variations of serum calcium during dialysis, we studied 20 patients on haemodialysis: 10 women and 10 men, with different forms of bone disease diagnosed by bone biopsy (adynamic bone disease, mild hyperparathyroidism, severe hyperparathyroidism). In all patients, we performed parathyroid stimulation by 4 h dialysis with 1 mEq/l of Ca2+ in the dialysate, and an inhibition test in another dialysis session with 4 mEq/l of Ca2+, with a 48 h interval. Ca2+ and intact parathyroid hormone (iPTH) were measured prior to dialysis and every hour subsequently, to obtain a Ca2+-iPTH for each patient. The analysis of the curves was made using Brown's four-parameter model. Stimulation and inhibition levels were similar in all groups, but basal iPTH and the response profiles obtained varied in the different histological groups. Basal, maximal and minimal iPTH were lower in adynamic forms than in the other two groups (P<0.04), and basal calcium was higher than basal calcium of severe hyperparathyroidism, expressing a basal inhibition status. In severe hyperparathyroidism, basal calcium was lower than the set-point, showing a permanent stimulation, and the slope was higher than in other groups, showing more sensitivity to serum calcium variations. The set-point of severe hyperparathyroidism was significantly higher than the set-point of mild and adynamic forms. In conclusion, the functional parathyroid study showed a different response in the different forms of renal osteodystrophy.
Nephrol Dial Transplant 1998
PMID:Are there any differences in the parathyroid response in the different types of renal osteodystrophy? 958 May 36

Brown tumors are focal bone lesions, encountered in patients with uncontrolled hyperparathyroidism. They can be located in any part of the skeleton. Clinically significant lesions in the craniofacial bones are rare. Craniofacial involvement may cause facial disfiguration and compromise social ease of the patient and normal functions, such as chewing, talking, and breathing. In this case report, we present a patient with a brown tumor of the craniofacial bones provoked by secondary hyperparathyroidism and review the last 10 years of craniofacial brown tumors associated with secondary hyperparathyroidism in the English literature.
Case Rep Nephrol Dial
PMID:Brown Tumors: A Case Report and Review of the Literature. 2706 94