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)

Further evidence implicating murine leukemia-like virus in the disorders of NZB mice was afforded by a study of antigens associated with murine leukemia virus (MuLV). MuLV group antigens were prevalent in extracts of spleen, kidney, and, to a lesser extent, thymus throughout a substantial portion of the life span of NZB mice as well as in extracts of lymphomas and sarcomas indigenous to the strain. G (Gross) soluble antigen, type-specific antigen, was first detected in plasma of untreated NZB mice at 3 months of age. G soluble antigen production increased thereafter in line with age, with 50% of reactions becoming positive at 5.3 months and 100% at 7 to 9 months. From months 3 to 9, the time-response curve for positive conversion of direct antiglobulin (Coombs) tests in untreated NZB mice corresponded closely to that for G soluble antigen production. Beyond the 9th month, G soluble antigen underwent elimination from the plasma of NZB mice, with positive reactions reduced to 50% at 13.3 months and to 0% at 18 months. G natural antibody was first detected in the serum of NZB mice at about 10 months of age and increased thereafter in line with age. The curves for G antibody production and G soluble antigen elimination bore a reciprocal relation to each other with crossover at 50% response occurring at 13.3 months. Significant proteinuria, a functional manifestation of membranous glomerulonephritis, became increasingly prevalent in female NZB mice as G soluble antigen was eliminated from plasma. Cumulative mortality of female NZB mice, mainly attributable to renal glomerular disease, increased in phase with G antibody production. MuLV group antigens were identified in the glomerular lesions by the immunofluorescence method. Positive conversion of direct antiglobulin tests was significantly delayed by vaccinating baby NZB mice with formaldehyde-inactivated cell-free filtrates of older NZB mouse spleens. The plasmas of vaccinated NZB mice with negative direct antiglobulin reactions at 4 to 7 months were likewise negative when tested for G soluble antigen. The 50% response time for G antibody production in the vaccinated NZB mice occurred at 7.3 months, that is, 6 months earlier than in untreated NZB mice. The collective findings implicate murine leukemia-like virus in the etiology of autoimmune hemolytic disease and membranous glomerulonephritis, as well as malignant lymphoma, of NZB mice and suggest that virus-specified cell-surface and soluble antigen is a factor in the immunopathogenesis of the renal disease and possibly also the autoimmune hemolytic disease.
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PMID:Further implication of murine leukemia-like virs in the disorders of NZB mice. 430 80

A soluble preparation of nucleoprotein (sNP), a complex of native deoxyribonucleic acid (DNA) and histones, was isolated from calf thymus nuclei and labeled with [(125)I]iodide. Isotope-labeled antigen ([(125)I]sNP) was used in a primary binding radioimmunoassay method to detect antibodies to both sNP and native DNA. Sera with antibody to native DNA reacted with the DNA moiety of sNP and bound [(125)I] sNP, but this binding was completely inhibited by addition of unlabeled native DNA. Antibody to sNP which reacted with DNA-histone complex was not inhibited in the radioimmunoassay by addition of unlabeled DNA. Thus, antibodies to sNP and native DNA could be detected and differentiated by use of a single isotopically labeled antigen. In systemic lupus erythematosus (SLE), sera with binding to [(125)I]sNP was present in 21/36 (58%) patients. The majority (18/21) had antibodies to sNP and native DNA present simultaneously, one had antibody only to sNP and two had antibody only to DNA. In contrast, patients with other connective tissue diseases rarely showed binding to [(125)I]sNP. Serial studies on SLE patients showed that high serum binding to [(125)I]sNP paralleled renal disease activity as reflected by the degree of proteinuria. A fall in binding was observed with subsidence of renal disease and reappearance of increased binding coincided with exacerbation. In these patients, antibodies to sNP and DNA appeared or disappeared pari passu suggesting that in addition to the previously demonstrated role of antibody to native DNA, antibody to sNP might also be implicated in the pathogenesis of immunologically-mediated tissue lesions such as SLE nephritis.
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PMID:Relationship between deoxyribonucleoprotein and deoxyribonucleic acid antibodies in systemic lupus erythematosus. 453 38

Defects in cellular communication are fundamental to the development of autoimmune disease. Modulation of immunoregulatory events can be mediated by cellular expression of Ia antigens. We have analysed, by flow cytometry, the Ia antigenic levels on cells from mice expressing the lpr gene and their congenic counterparts. Surface Ia expression is dramatically increased on bone marrow, thymus, lymph node and spleen cells from lpr mice even prior to characteristic lymph node and spleen enlargement. In addition, IL-2 production abnormalities occur in the low density Lyt 1 subset of Thy 1.2 positive cells of normal mice which may be the counterpart of the majority cell type of lpr lymphocytes. Treatment of lpr mice with low dose whole body irradiation (300 rad) decreases lymphadenopathy, autoantibodies, proteinuria and the resident Ia positive cell population while increasing survival. We conclude that lymphoid alterations induced by irradiation reflect a recovery of immunological control associated with suppression of autoimmune manifestations.
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PMID:Increased Ia expression, T lymphocyte subset abnormalities and autoimmunity in murine strains bearing the lpr gene. 643 11

The effects of thymus factor (TFX) and levamisole on the clinical picture and some indices of cellular immunity have been evaluated in 10 patients with nephrotic syndrome due to membranoproliferative glomerulonephritis Type I. The patients revealed decreased T-lymphocyte number and impaired responsiveness to phytohaemagglutinin (PHA) stimulation before treatment. An association between the slight diminution of proteinuria and the increase of E-rosette forming lymphocytes, increased responsiveness to PHA and return to normal of previously elevated B-cell percentages, was observed in four patients treated with TFX and one patients treated with levamisole.
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PMID:Effect of thymus factor and levamisole treatment in patients with persistent nephrotic syndrome. 660 17

Cardiotoxicity of doxorubicin, 2 mg/kg i.p. twice weekly in rats, was assessed by serial electrocardiography and electron microscopy. The toxic effects were markedly inhibited by ICRF-159, 50 mg/kg p.o. given 1 h before doxorubicin. The development of nephropathy characterized by proteinuria, hyperlipidemia and glomerular and tubular changes was significantly retarded, and the degenerative changes of peripheral nerves were markedly reduced. On the other hand, ICRF-159 enhanced the depressant effects of doxorubicin on bone marrow function. Doxorubicin reduced body weight gain, caused ascites, decrease in heart and thymus weight, and increase in liver and kidney weight. These changes were also inhibited or attenuated by ICRF-159 pretreatment.
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PMID:Inhibition of cardiotoxic, nephrotoxic and neurotoxic effects of doxorubicin by ICRF-159. 684 96

A local graft-versus-host reaction was established to elicit lymphoid hypertrophy in F1 hybrid PVG X Lew rats. cis-Di(amine)platinum(II) complexes were given i.p. on days 1--4 in divided doses. Overnight proteinuria and measurements of renal hypertrophy on day 5 reflected the nephrotoxicity of the test compound. Stomach weights indicated the peculiar effect on pyloric stasis causing gastric distension. Weights of thymus' and spleens together with lymph-nodes showed the lymphodepressant/immunosuppressive properties of platinum compounds. Structure activity relationships for immunosuppressant, nephrotoxic and gastric-distending activities were investigated with: (a) cis-diaquo, cis-hydroxyaquo- and cis-dichlorodi(amine)platinum(II) complexes; (b) dinuclear mu-dihydroxo-bridged di(amine)platinum(II) complexes; (c) carboxylatodi(amine)platinum(II) complexes. Nephrotoxicity was minimised (with retention of immunosuppressant activity) by (a) the use of certain N-substituted amines e.g. Dach, Me4en; (b) co-administration of selected adjuncts e.g. citrate, salicylate; (c) auxiliary treatment with a penicillin mixture (Triplopen). In vitro effects of some platinum(II) compounds on isolated rat kidney tubules were also investigated.
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PMID:cis-Platinum(II) amine complexes: some structure-activity relationships for immunosuppressive, nephrotoxic and gastrointestinal (side) effects in rats. 719 79

A 4-day drug schedule was used to explore the efficacy and simultaneous toxicity of cisplatin and 30 other platinum (II) amines given IP to PVG x Lew F1 hybrid rats at cumulative doses of 10-300 mumol/kg. Toxic effects monitored were stomach enlargement, kidney hypertrophy with tubular necrosis and proteinuria, evident visceral mucin, and lymphoid involution (thymus, spleen). Immunosuppressive effects were monitored as inhibition of the lymph node hypertrophy induced by grafting PVG spleen cells into each paw of F1 hybrids. No significant activity/toxicity was observed with 'platinum-(pyrimidine) blues'. N-alkyl derivatives of cisplatin were less active/toxic and some had no immunosuppressant effect, though they are reported as effective antitumour agents (in mice). mu-Hydroxobridged aminoplatinum (II) dimers were highly toxic, effective immunosuppressants and their toxicity profiles were distinct from the dihalo or diaquo diaminoplatinum species. 1,2-Diaminocyclohexane platinum derivatives showed a wide range of potency, all being much less nephrotoxic than cisplatin.
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PMID:Platinum drugs: combined anti-lymphoproliferative and nephrotoxicity assay in rats. 743 27

In a previous study, susceptibility for Trypanosoma brucei-related glomerulopathy in mice was shown to be dependent on non-major histocompatibility complex genes. Glomerular disease in this model could not be explained by the production of autoantibodies alone. In order to analyze which part of the defense system, in addition to the B-cell compartment, is involved in the development of this infection-related glomerular disease, groups of athymic (BALB/c rnu/rnu), splenectomized, or macrophage-depleted BALB/c mice were inoculated with T. brucei parasites. Polyclonal B-cell activation, invariably observed in infected BALB/c mice, was absent in BALB/c rnu/rnu mice. Glomerular disease in athymic mice, however, as defined by albuminuria and deposition of immune complexes, was not different from that seen in euthymic infected BALB/c mice. Splenectomy prior to inoculation of parasites led to a decreased incidence of albuminuria in 40% of the animals, whereas splenectomy 21 days after inoculation reduced albuminuria significantly, suggesting a role for spleen cells in the induction of glomerular disease. After macrophage depletion with liposome-encapsulated dichlorodimethylene-diphosphonate, infected BALB/c mice developed significantly higher albuminuria levels for a period up to 2 weeks after depletion. Therefore, it was concluded that the development of T. brucei-related glomerular disease is independent of thymus-matured T cells, while the involvement of macrophages in the development of proteinuria is inhibitory rather than disease inducing. Spleen cells other than thymus-dependent T cells, B cells, and macrophages should be investigated for their role in the pathogenesis of this glomerulopathy.
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PMID:T cells and macrophages in Trypanosoma brucei-related glomerulopathy. 791 96

Intravenous administration of human basic fibroblast growth factor up to 100 micrograms/kg/day to Sprague-Dawley rats caused changes in the kidneys that included enlargement, vacuolation, and karyomegaly of podocytes in glomeruli, dilatation and cast formation in tubules, thickening of the media in the lobular arteries, and hyperplasia of the epithelium of the papilla and collecting ducts. In cynomolgus monkeys there was hyperplasia of the parietal epithelium of Bowman's capsule in the glomeruli, tubular dilatation, and minimal arteriopathy. These changes were only seen at 100 micrograms/kg/day. The development and eventual recovery over time were investigated in a sequence of sacrifices. In monkeys the first changes were seen after 7 days of treatment, but in rats only after 16 days. In both species the changes had partially resolved after 30 days of recovery and were considered to return to normal after 60 days without treatment. The morphological changes were accompanied by functional alterations that included proteinuria and raised blood urea. Changes that occurred in other tissues including bone, red blood cells, adrenals, ovaries, liver, gall bladder, spleen, mesenteric lymph nodes, thymus, aorta, salivary glands, and injection site are not described in this paper.
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PMID:The histopathology of kidney changes in rats and monkeys following intravenous administration of massive doses of FCE 26184, human basic fibroblast growth factor. 811 25

Spontaneous anti-DNA antibodies in autoimmune mice have the characteristics of antibody produced by Ag-specific, clonally selective B cell stimulation. The nature of the somatically derived antibody V region structures recurrent among spontaneous anti-DNA antibodies suggests that DNA or DNA-protein complexes may provide the antigenic stimulus for autoimmune anti-DNA antibody. In order to test this hypothesis directly, we have immunized normal, nonautoimmune-predisposed mice with complexes formed with DNA and an immunogenic, DNA-binding peptide. The highly immunogenic peptide, Fus1, forms an internal domain of a 128-amino acid ubiquitin-fusion protein from Trypanosoma cruzi. DNA-Fus1 complexes formed with native calf thymus DNA induced anti-DNA antibody in normal, nonautoimmune-predisposed mice that is similar in isotype and specificity to spontaneous anti-DNA antibody in (NZB x NZW)F1 autoimmune mice. The progressive nature of the development of dsDNA specificity in the immunized mice was also analogous to what is observed in the spontaneous anti-DNA antibody response of autoimmune (NZB X NZW)F1 mice. DNA-Fus1 immunized mice that produced IgG that bound to dsDNA had low to moderate levels of proteinuria and glomerular deposits of IgG. This experimental immunization system may be useful for understanding the immunologic basis for autoimmunity to DNA.
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PMID:Antigen-specific induction of antibodies against native mammalian DNA in nonautoimmune mice. 839 48


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