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)

The effect of (-)15-deoxyspergualin (15-dsp), a new immunosuppressant which was originally separated from the culture filtrate of a strain of Bacillus laterosporus, was evaluated in this study. Various doses of 15-dsp were subcutaneously administered to New Zealand black/white F1 hybrid mice (B/WF1) four times a week starting at 14 weeks of age, just prior to the onset of nephropathy. The life span of the treated animals, studied at 0.6 to 6.0 mg/kg body weights, compared with the control mice was significantly prolonged by 15-dsp treatment (percent survival of the treated mice at 50 to 70 weeks of age was significantly higher than that of the control mice, except that of the 0.6 mg group at 60 wks of age, P less than 0.05 by Fisher's exact test). In the 6.0 mg group of mice, complete suppression of spontaneously progressive splenomegaly with decreased total spleen cells was observed at 24 through 36 weeks of age compared with the same-aged control group of mice (P less than 0.01). Absolute numbers of L3T4+ splenocytes determined by flow cytometry, as well as L3T4+/Lyt2+ ratio, were decreased, while in vitro interleukin 2 production by splenocytes induced with staphylococcal enterotoxin A was significantly enhanced. Serum IgG anti-ds DNA antibody levels, measured by radioimmunoassay in the treated mice, were significantly lower at 24 through 36 weeks of age than those in the control mice (P less than 0.01), and the incidence of significant proteinuria (greater than or equal to 100 mg/dl) in the 15-dsp group was lower at both 32 and 36 weeks of age (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lupus nephropathy in New Zealand F1 hybrid mice treated by (-)15-deoxyspergualin. 319 66

Untreated 9 to 11 month-old, female NZB/W F1 mice all died within six weeks (wks) after the occurrence of nephrotic range proteinuria (greater than or equal to 3 g/liter). Significant prolonged survival could be obtained in similar groups of animals either by weekly i.v. pulses of cyclophosphamide (CY, 25 mg/kg, 40% survival 20 wks after start of treatment) or by administering total lymphoid irradiation (TLI, 17 daily fractions of 2 Gy, 70% survival at 20 wks). All surviving animals in both groups showed remission of the nephrotic range proteinuria. In all treated mice, light microscopy examination of the kidneys revealed a decrease of inflammation and a stabilization of proliferation and sclerosis, yet immunofluorescence for IgM, IgG and C3 was not significantly altered. The better survival of the TLI- as compared to the CY-treated mice (P less than 0.001) was due to a lower incidence of lymphomas or viral infections. IgG anti-DNA auto-antibodies were significantly lowered by CY but not by TLI treatment. It is concluded that CY pulse therapy and TLI are both efficient treatment modalities for high grade lupus like NZB/W disease. In this model TLI is safer than CY when used in a dose regimen of 25 mg/kg/wk and interferes with the course of the disease without lowering the IgG anti-DNA antibodies.
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PMID:Treatment of murine lupus nephritis with cyclophosphamide or total lymphoid irradiation. 319 79

Systemic lupus erythematosus (SLE) is considered to be the quintessential autoimmune disease. It has not been possible to induce SLE in animal models by DNA immunization or by challenge with anti-DNA antibodies. We herewith report a murine model of SLE-like disease induced by immunization of C3H.SW female mice with a common human monoclonal anti-DNA idiotype (16/6 idiotype). Following a booster injection with the 16/6 idiotype, high levels of murine anti-16/6 and anti-anti-16/6 antibodies (associated with anti-DNA activity) were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens [Sm, SS-A (Ro), and SS-B (La)], and cardiolipin were noted. The serological findings were associated with increased erythrocyte sedimentation rate, leukopenia, proteinuria, immune complex deposition in the glomerular mesangium, and sclerosis of the glomeruli. The immune complexes in the kidneys were shown to contain the 16/6 idiotype. This experimental SLE-like model may be used to elucidate the mechanisms underlying SLE.
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PMID:Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype. 325 23

The effect of lysozyme on intraglomerular immune complex deposition was examined in NZB/W F1 mice undergoing unilateral nephrectomy. Unilateral nephrectomy enhanced the glomerular immune complex deposition and glomerular lesions, which were suppressed by repeated intraperitoneal injections of lysozyme, in spite of unaltered serum anti-DNA antibody titers. DNA binding to the glomerular basement membrane (GBM) examined in vitro and that to glomeruli examined in vitro were also suppressed by lysozyme. An increased survival rate and decreased proteinuria were also induced by this basic protein. The mechanisms of the ameliorative effect were studied in vitro. DNA was bound to the GBM only in the presence of serum, plasma, or fibronectin. A similar inhibitory effect on DNA binding was also obtained by another polycation, hexadimethrine, in place of lysozyme. The in vitro findings suggest that DNA binding to the GBM is mediated by fibronectin, and that lysozyme electrostatically inhibits this binding, thereby possibly reducing the in situ DNA-anti-DNA complex formation in the GBM.
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PMID:Inhibitory effect of lysozyme on the intraglomerular immune complex formation in lupus mice. 334 56

(2R,5R)-6-heptyne-2,5-diamine (MAP; MDL 72175), a potent irreversible inhibitor of L-ornithine decarboxylase (ODC), possesses immunosuppressive activities in vitro as the result of inhibition of lymphocyte polyamine biosynthesis. The effects of MAP were now studied in vivo in MRL-lpr/lpr female mice, an animal model for human systemic lupus erythematosus (SLE). Administration of MAP (0.2% in drinking water; drug intake: 0.25-0.35 g/kg body weight/day) to female mice for 15 weeks, starting 8 weeks after birth, reduced by 47% the number of spleen cells, retarded development of lymphadenopathy and, at that time, markedly prolonged the survival of the mice. At week 23, MAP reduced plasma IgG concentrations by 50% whereas, in contrast, those of IgM were elevated 1.5-fold. No statistically significant effects of MAP were observed on plasma levels of anti-DNA autoantibodies although serum anti-RNP and anti-Sm titres tended downwards during treatment. Neither glomerular lesions nor proteinuria were improved by MAP administration. Finally chronic administration of MAP for 45 weeks prolonged the median survival time from 29.75 to 35.5 weeks.
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PMID:Immunosuppressive effects of (2R,5R)-6-heptyne-2,5-diamine, an inhibitor of polyamine synthesis: II. Beneficial effects on the development of a lupus-like disease in MRL-lpr/lpr mice. 340 47

Pregnancy was encouraged in 15 B/W mice (Group 1) and the rate of development of FANA, anti-DNA antibodies, and proteinuria compared with that seen in 15 control mice (Group 2). The mean number of pregnancies for Group 1 mice was 5.2. No difference was seen in mortality rate or in the onset of serologic or urinary abnormalities between the 2 groups.
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PMID:The effect of pregnancy on disease development and mortality in B/W F1 mice. 343 May 21

A polyclonal activation of lymphocytes (PA) has been suggested to play a pathogenic role in autoimmune and immune complex diseases, particularly in mouse lupus. "DIAM 4," a cyclophosphazene derived drug, selected on the basis of its ability to modulate a PA has been used to treat female MRL/1, female NZBxNZW, and male BXSB mice. In these three strains of mice, the treatment was found to induce an inhibition of the PA, to prevent the increase of anti-DNA antibody levels and the simultaneous decrease of C3 levels, to prevent the appearance of proteinuria, the deposition of immune complexes in glomeruli, and the development of kidney lesions. Moreover in MRL/1 mice, lymphoproliferation was prevented. These results suggest that drugs able to modulate a PA might be efficient in the treatment of mouse lupus nephritis. Such a principle of immunomodulation might open the way to new possibilities of treatment of lupus and other immune complex diseases.
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PMID:Prevention of lupus diseases in MRL/1, NZBxNZW, and BXSB mice treated with a cyclophosphazene derived drug. 349 Mar 36

TI-31 (TEI-3096; 6-p-chlorobenzyl-5H-2,3,6,7-tetrahydro-5,7-dioxothiazolo[3,2-a]pyr imidine) is a novel immunomodulator. Various nephritic changes observed in female NZB/NZW F1 (B/W) mice with aging were suppressed by TI-31 when administered orally 5 times per week for 16 weeks at doses of 2, 10, or 50 mg/kg. It suppressed proteinuria, oliguria, the decrease of erythrocyte count, and increase of serum urea nitrogen, immune complex and anti-double-stranded DNA antibody levels. The anti-nephritic effect of TI-31 was confirmed by histopathological evaluation. TI-31 (10 mg/kg) could improve both the elevated polyclonal B cell activation and the depressed antibody response to sheep red blood cells in B/W mice, in comparison with age- and sex-matched BALB/c mice, without any effect on the antibody response in these normal mice. These findings indicate that TI-31 may inhibit B/W nephritis by regulating the antibody production through a mechanism different from that of anti-inflammatory drugs or immunosuppressants.
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PMID:Inhibitory effect of TI-31 on autoimmune nephritis in NZB/NZW F1 mice through regulation of the immune response. 349 22

A new method for measuring DNA antibody forming cells (DNA-AFC) using the enzyme-linked immunospot (ELISPOT) assay is described. This method uses enzyme-linked immunosorbent assay (ELISA) techniques applied to cells cultured on DNA-coated plates, which allows visual quantitation of spots representing imprints of specific antibodies from DNA-AFC. Specificity for DNA was confirmed by inhibition studies and lack of reactivity by anti-lysozyme hybridomas. Isotypes of IgG and IgM can be measured using the appropriate antisera in the assay. A study of 16 female (New Zealand black x New Zealand white)F1 ([NZB x NZW]F1) female mice showed significant correlation between age, rising blood urea nitrogen levels, and increasing proteinuria and increasing numbers of DNA-AFC. In contrast, the correlation between circulating antibodies to DNA (ELISA method) and clinical parameters of nephritis was not significant. Both the native DNA ELISPOT and the native DNA ELISA had similar significant linear correlations with age. This is the first report of use of the ELISPOT assay for measurement of DNA-AFC. The DNA-AFC measured by this method were specific and correlated with the presence of clinical nephritis in (NZB x NZW)F1 mice. This method should allow further study on the regulation of DNA-AFC in vitro and in vivo, and will be useful in the investigation of DNA-AFC and cellular mechanisms of autoimmunity.
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PMID:Detection of native and denatured DNA antibody forming cells by the enzyme-linked immunospot assay. A clinical study of (New Zealand black x New Zealand white)F1 mice. 353 Feb 55

A case of recurrent lupus nephritis in an 18-year-old girl with a renal transplant is described. Serological titer of ANA and Anti-DNA were low prior to renal transplantation following pulse therapy with methylpredonisolone and high dose oral predonisolone. A living related transplantation was performed after 6 months of hemodialysis. Maintenance immunosuppressive therapy consisted of predonisolone, mizoribine and cyclophosphamide. Graft function remained stable for one and half years after transplantation. Clinical recurrence was heralded by the development of proteinuria. If the serologic activities had been analyzed, the increase in ANA and Anti-DNA titers a few months before the onset of proteinuria might have predicted a possible histopathological recurrence. Fortunately, however, despite the histological and clinical recurrence of systemic lupus erythematosus, her renal allograft has continued to function fairly well.
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PMID:A case of recurrent lupus nephritis after renal transplantation. 354 85


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