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)

Fourteen-week-old female New Zealand B/W F1 mice were treated subcutaneously with 15-deoxyspergualin (DSP) at 0.3 mg-6.0 mg/kg body weight, 4 times/week. They were sacrificed at 36 weeks of age to determine the minimal effective dose as well as the lowest maximally effective dose without toxicity of DSP required to suppress the development of nephropathy. The life span of the animals was significantly prolonged with 0.6 mg/kg or more DSP. Additionally, glomerular (immuno)histological improvement of the kidney at 36 weeks was observed with 0.6 mg/kg DSP, although a higher dose was required to lower serum anti-DNA activity or to decrease proteinuria. In addition, DSP produced a decrease of L3T4+ splenocytes without affecting the number of Lyt 2+ cells, while the level of IL-2 generated in vitro was somewhat elevated. It may be concluded that DSP has a therapeutic range within an order of ten, but its exact mechanism of immunosuppression remains to be determined.
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PMID:Effect of 15-deoxyspergualin on lupus nephropathy in New Zealand black/white F1 mice. 156 87

The effects of the immunosuppressive agent CP 17193 on the development of spontaneous lupus disease in female NZBW F1 hybrid mice were investigated. Long term dosing with CP 17193 markedly delayed the onset of mortality but did not extend the long term survival of the mice. CP 17193 significantly inhibited immune complex deposition in the glomeruli of 30- and 35-week-old mice and also reduced the levels of proteinuria in the 35-week-old mice. There was a slight reduction in the levels of circulating antinuclear antibody to ds DNA in CP 17193-treated mice but this was not statistically significant. Studies on immune cell function of 35-week-old mice dosed with CP 17193 showed significant reduction in the total numbers of spontaneous polyclonal antibody producing cells. Analysis of the results revealed these effects to result from a marked reduction in total spleen cell numbers in CP 17193-treated mice. When results were expressed as activity per cell unit the differences between drug-treated and control mice were small. Spleen cells from mice given a shorter dosing schedule of 7 weeks with CP 17193 showed an augmentation of IL-2 production and responsiveness. These results show CP 17193 having interesting selective immunomodulating activity on the immunopathogenesis of spontaneous murine lupus disease. Furthermore, compounds with this profile of activity may have a potential role in the treatment of some autoimmune diseases.
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PMID:The effects of CP 17193, an immunosuppressive pyrazaloquinoline, on the development of spontaneous lupus disease in NZBW F1 hybrid mice. 163 62

To consider the mechanism of reduction of proteinuria by cyclosporine A (CYA) in the patient with intractable nephrotic syndrome, the effect of CYA on proteinuria and anionic sites (AS) of the glomerular basement membrane (GBM) was studied in puromycin aminonucleoside (PA) nephrotic rats. In addition the rats exogenously given human recombinant interleukin-2 (hrIL-2) every day repeated the same proteinuria were used. The PA nephrotic rats were made by single injection of PA 150 mg/kg excrete of urinary protein as compared 10 mg/day of urinary protein in the controls. The increase of urinary protein in the PA rats was inhibited by CYA10-20 mg/kg administrated orally from the day of PA injection for 15 days. To evaluate AS, the kidney were treated with a polyethyleneimine (PEI) staining method and the deposits in the lamina rara externa (LRE) of the GBM were counted on the electron micrographs. On the 15th day, in the PA rats, AS decreased greatly but were normal in the CYA-treated rats. On one hand, rats injected of hr IL-2 2.5 X 10(5)U/rat intraperitoneally for 14 days showed slight proteinuria on the 14th day, and the proteinuria was also inhibited by oral administration of CYA 25 mg/kg. As reduced in the rats treated with hrIL-2 as well as PA. The findings indicate that the proteinuria in the PA nephrotic rats and rats treated with hrIL-2 might result from reduction of AS and that the improvement of proteinuria in these rats by CYA might be due to the recovery of AS in the GBM.
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PMID:[Mechanism of reduction in proteinuria by cyclosporine A: effects on the glomerular anionic sites]. 222 90

Near-isocaloric diets with qualitative and quantitative differences in fat content have a profound influence on the manifestation and progression of the autoimmune syndrome that occurs in female MRL/lpr mice. In these animals, a high (9%) lipid intake resulted in a significantly higher mortality rate: 60% (saturated fat) and 75% (unsaturated fat) compared to 35% at 1 year for a group fed a diet low in fat. Furthermore, beginning at 7 months of age mice from both of the high fat diet groups exhibited a significantly higher incidence of proteinuria than mice in the low fat group. Immunologically, the group fed the high unsaturated fat diet had the highest incidence of anti-dsDNA autoantibodies, and the high saturated fat group had the poorest macrophage phagocytic function. The low fat diet preserved near 'normal' immune function in general, particularly IL-2 production. No significant differences were noted in either the production of rheumatoid factor or natural killer cell activity, irrespective of age or diet.
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PMID:Dietary fat influences the expression of autoimmune disease in MRL/lpr/lpr mice. 349 85

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

Groups of female MRL/MpJ-lpr/lpr mice received either saline or FK506 (tacrolimus; 2 mg/kg intraperitoneally) three times weekly, cyclophosphamide (CY; 20 mg/kg) once monthly, or both drugs from 8 weeks of age. Median survival for untreated and CY-treated mice was 26 weeks, and for FK506- and FK506 + CY-treated groups was > or = 44 weeks. Severity of skin lesions and lymph node hyperplasia was markedly reduced by the drug combination, whereas either drug alone was less effective. FK506 or CY alone delayed the onset of proteinuria, but by 24 weeks all of these animals were positive. In contrast, drug combination reduced the prevalence of proteinuria to < or = 60% throughout the 44 weeks of study. Sequential monitoring of peripheral blood lymphocytes revealed that combination therapy but not monotherapy markedly reduced the proportion of atypical CD3+ B220+ and CD3+CD4-CD8- T cells. Neither FK506 nor CY affected the reduction in IL-2 and IL-4 mRNA levels observed in lymph nodes of diseased animals compared with normals. Although the drug combination also did not affect IL-2 mRNA levels, IL-4 mRNA transcripts were increased six-fold compared with saline-treated controls. IL-10 and interferon-gamma (IFN-gamma) mRNAs were induced by FK506, CY and by the drug combination. Serum levels of anti-dsDNA antibodies were reduced in all treatment groups. These data demonstrate improved efficacy of combined T and B cell-directed immunosuppression in murine lupus, associated with marked inhibition of atypical T cells and selective augmentation of IL-4 within the affected lymphoid tissue.
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PMID:Combined effects of FK506 (tacrolimus) and cyclophosphamide on atypical B220+ T cells, cytokine gene expression and disease activity in MRL/MpJ-lpr/lpr mice. 753 8

Therapeutic effects of combined treatment with a Chinese medicine prescription, Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NYT) and suboptimal doses of prednisolone (PSL) on pathological findings of autoimmune-prone MRL/lpr mice were examined. Six-week-old MRL/lpr mice were treated orally with 1000 mg/kg of NYT, 0.5 or 2 mg/kg of PSL, 1000 mg/kg of NYT plus 0.5 or 2 mg/kg of PSL (combined treatment) or solvent only (control) six times per week. The rates of signs and symptoms of autoimmune disease (lymphadenopathy, proteinuria, dermatitis, loss of hair) were suppressed significantly in groups given PSL (2 mg/kg) alone, NYT alone and combined treatment with PSL (2 mg/kg) plus NYT (1000 mg/kg) compared with control, respectively, whereas treatment with PSL (0.5 mg/kg) alone did not inhibit their occurrence. ConA response and IL-2 production were also improved significantly in lymphocytes of mice given the combined treatment. Interestingly, treatment with NYT alone enhanced further the augmented IFN-gamma production in MRL/lpr mice but the combined treatment suppressed such an augmented production. The combined treatment dramatically reduced the level of anti-DNA antibodies in serum of MRL/lpr mice. By contrast, NYT alone treatment had no effect on autoantibodies production. These results suggest that combined treatment with NYT plus a suboptimal dose of PSL could be effective for systemic lupus erythematosus without severe side-effects.
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PMID:Combined treatment of autoimmune MRL/MP-lpr/lpr mice with a herbal medicine, Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to) plus suboptimal dosage of prednisolone. 784 56

The chemopreventive action of carotenoids on proteinuria and lymphadenopathy were examined in autoimmune-prone MRL-lpr/lpr (MRL/l) mice. They were fed a synthetic full-fed diet (16-18 kcal/mouse/day) with supplementation of beta-carotene or astaxanthin (0.19 mumoles/mouse, 3 times a week), and the development of lymphadenopathy and proteinuria were examined. MRL/l mice fed a full-fed diet without the supplementation of carotenoids or those fed a calorie-restricted (CR) diet (10-11 kcal/mouse/day, 60% calorie intake of full-fed mice) were employed as controls. CR dramatically delayed the development of proteinuria and lymphadenopathy, as reported previously. Carotenoids also significantly delayed the onset of these symptoms in MRL/l mice fed a full-fed diet. Carotenoids were half as effective as CR and astaxanthin, a carotenoid without provitamin A activity, which appeared to exert more significant preventive actions than beta-carotene in delaying the development of these symptoms. Similar chemopreventive actions of carotenoids were also demonstrated in MRL/l mice fed a regular diet (Lab Chow). CR has been shown to augment IL-2 production and to decrease serum prolactin levels in this strain, which may be related to its dramatic preventive action of autoimmunity. However, carotenoids did not affect IL-2 production nor prolactin levels in full-fed MRL/l mice. The chemopreventive actions of carotenoids observed in autoimmune-prone MRL/l mice may be attributed to yet unknown mechanisms, apart from their provitamin A activity or oxygen-quenching activity.
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PMID:Preventive action of carotenoids on the development of lymphadenopathy and proteinuria in MRL-lpr/lpr mice. 818 Mar 22

This study was designed to investigate the mechanisms by which marine lipids rich in long chain omega-3 fatty acids inhibit autoimmune disease and prolong the survival rate in female (NZB/NZW) F1 (B/W) mice, an animal model for human SLE. Nutritionally adequate semipurified diets containing at 10% either corn oil (CO) or fish oil (FO) were fed from 1 mo of age and were monitored for proteinuria and survival. Proteinuria was detected earlier and became progressively severe in CO-fed mice. The average life span was significantly shortened by the CO diet (266.7 days +/- 12.5), whereas FO extended the survival significantly (402.1 days +/- 26.1; p < 0.001). A cross-sectional study at 6.5 mo of age revealed an increased proliferative response to T cell mitogens including bacterial superantigens and decreased serum anti-dsDNA Ab titers in the FO group compared with the CO group. Furthermore, splenocytes from the FO group when stimulated with Con A had higher IL-2 and lower IL-4 production similar to that of young (3.5 mo) mice. Flow cytometric analyses of splenocytes revealed lower Ig+, higher lymphocyte endothelial cell adhesion molecule-1, and lower Pgp-1+ cells within CD4+ and CD8+ subsets in FO-fed mice. Also, elevated IL-2 and IL-4 and significantly higher TGF-beta 1 and lower c-myc and c-ras mRNA expression and higher TGF-beta 1 and significantly lower c-Myc and c-Ha-Ras proteins were detected in spleens of FO-fed mice. Fatty acid analysis revealed significantly higher linoleic (18:2 omega-6) and arachidonic (20:4 omega-6) acid levels in splenocytes of the CO-fed group and higher eicosapentaenoic (20:5 omega-3) and docosahexanoic (22:6 omega-3) acid levels in the FO-fed group, indicating that changes in membrane fatty acid composition may contribute to the altered immune function and gene expression during the development of murine SLE.
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PMID:Increased TGF-beta and decreased oncogene expression by omega-3 fatty acids in the spleen delays onset of autoimmune disease in B/W mice. 820 22

Assays of interleukin-1 (IL-1) and IL-2 were done in supernatants from phytohaemagglutinin-activated lymphocyte cultures from 10 children suffering from minimal-change nephrotic syndrome (MCNS) to assess their role in the aetiopathogenesis of this disorder. Increased levels of IL-1 and IL-2 had been found in supernatants from patients having MCNS compared with controls, suggesting a significant role of these cytokines in the immunopathogenesis of proteinuria in this syndrome.
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PMID:Pattern of interleukins in minimal-change nephrotic syndrome of childhood. 841 92


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