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)

Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis.
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PMID:Treatment of intractable lupus nephritis with total lymphoid irradiation. 387 90

A filtrable agent separable from transplantable malignant lymphomas of NZB/Bl mice was capable, upon inoculation into preweanling NZB/Bl mice, of inducing lymphoid cell hyperplasia, hypergammaglobulinemia, proteinuria, hypoalbuminemia, and pathological changes (focal membranous glomerulonephritis) of kidneys-renal functional and structural changes qualitatively similar to those of spontaneous occurrence in older NZB/Bl mice. Viruslike particles with close resemblance to the typical "C" type murine oncogenic virus particles were identified by means of electron microscopy in NZB/Bl mouse tissues and cells, including malignant lymphoma cells, benign lymphoid cells of thymus and spleen, epithelial cells of renal tubules, and extracellular sites. The relevance of these observations, the first of their kind dealing with NZB/Bl mice, is discussed in relation to the several immunopathological disorders which characterize this strain of mice.
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PMID:Immunopathology of NZB/BL mice. V. Viruslike (filtrable) agent separable from lymphoma cells and identifiable by electron microscopy. 428

The autoimmune manifestations of MRL-+/+ (MRL/n) and MRL/Mp-lpr/lpr (MRL/l) murine models of systemic lupus erythematosus (SLE) were successfully reversed following total lymphoid irradiation (TLI) therapy consisting of 8-12 daily fractions of 200 rad. Following radiotherapy the characteristic lymphadenopathy of MRL/l disappeared, proteinuria was 334 mg% compared to a peak of 2272 mg% in untreated controls, and the median survival time was prolonged to 423 days compared to 214 days in untreated mice. The albuminuria of TLI-treated MRL/n mice was 194 mg% compared to 1180 mg% in untreated controls. The survival of treated MRL/n mice was prolonged to a median of 389 as compared to 190 days in untreated controls. The effect of TLI on antiDNA antibodies in both MRL/l and MRL/n was less remarkable. However, the antiDNA activity reached normal levels in most long-living mice. The most impressive finding was complete reversal and/or prevention of the SLE-like glomerulonephritis in MRL/l mice as documented by light and electron microscopy. Immunomanipulation with TLI should be further evaluated as a possible treatment modality in intractable human autoimmune disorders.
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PMID:Successful treatment of autoimmune manifestations in MRL/l and MRL/n mice using total lymphoid irradiation (TLI). 633 70

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

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

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

Chronic graft-versus-host disease (GVHD) was induced in female (C57 B10S/DBA/2)F1 hybrid mice with two successive injections of lymphoid cells from parental DBA/2 strain. Serial bleedings of 27 GVHD mice were screened with a panel of antigens including the five histones H1, H2A, H2B, H3 and H4, 15 histone peptides, core particles, dsDNA, heat-shock proteins hsp70 and ubiquitin, a branched peptide of ubiquitinated H2A (U-H2A), poly(ADP-ribose) and SSB/La protein. The predominant IgG response to histone peptides was directed against regions 204-218 of H1, 1-25 of H2B and 1-29 of H4. GVHD mice also produced IgG antibodies to dsDNA and chromatin core particles as reported previously. IgG antibodies reacting with dsDNA appeared before antibodies to core particles and histones. Raised levels of antibodies to U-H2A, but not to monomeric ubiquitin, were also found. While the level of antibodies to dsDNA, histones and core particles decreased significantly before the appearance of proteinuria, suggesting their involvement in glomerular injury, the longitudinal pattern of anti-U-H2A peptide response was apparently not linked to the manifestation of lupus nephritis in GVHD mice.
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PMID:Antibodies to DNA, chromatin core particles and histones in mice with graft-versus-host disease and their involvement in glomerular injury. 795 35

One of the major complications after high-dose methotrexate (HDMTX) infusions is renal damage. We investigated the occurrence of proteinuria after HDMTX administration in children with pediatric malignancies (acute lymphoid leukaemia, osteosarcoma Burkitt's lymphoma). In the period 1989-1990 we gave 52 HDMTX courses to 24 children. During this period, prehydration and extra urinary alkalisation were performed only if the urinary specific gravity was over 1010 or if the urinary pH fell below 7. Using this schedule the mean values obtained for protein extraction were: before the therapy, 0.12 +/- 0.03 g/m2; on day 1 after MTX treatment, 0.38 +/- 0.06 g/m2; and on day 2 after the MTX infusion, 0.39 +/- 0.11 g/m2 (P < 0.01). A significant increase in proteinuria (> 0.2 g/m2 post- vs pretreatment) was detectable in 54% of the patients. In the period 1991-1992 we modified the hydration-alkalisation schedule to include i.v. prehydration for 18-24 h at 3 l/m2/day with a 0.45% NaCl-5% glucose solution along with sodium bicarbonate and posthydration for 72 h with the same solution. On this protocol the mean values determined for the urinary protein content were all in the normal range (pretreatment, 0.03 g/m2/day; day 1, 0.05 g/m2/day; and day 2, 0.08 g/m2/day). These findings were significantly different from the previous results (P < 0.05).
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PMID:Proteinuria due to suboptimal hydration with high-dose methotrexate therapy. 826 9

A 12-year-old boy was admitted to our hospital because of abnormal shadows on a chest radiograph, slight fever, and superficial lymphadenopathy. Laboratory examination showed anemia (Hb 9.9 g/dl) and hyperimmunoglobulinemia (IgG 5469 mg/dl) without M protein. A chest CT scan showed bilateral diffuse shadows and bilateral hilar lymphadenopathy. Biopsy specimens of an inguinal lymph node and a lung showed many lymphoid follicles with germinal centers, and marked infiltration of mature plasma cells in the interfollicular area without destruction of follicular structures. The polyclonality of the plasma cells was confirmed by immunohistochemistry. The patient was not treated because these results excluded malignant disease and he was asymptomatic. At the age of 17 years, he was admitted to our hospital again because of dyspnea and a tendency to bleed. Interstitial pneumonia, hyperimmunoglobulinemia (IgG 13900 mg/dl), and anemia (Hb 6.6 g/dl) were found, along with thrombocytopenia (2.5 x 10(4)/mm3) and proteinuria. The serum interleukin-6 level was high: 177 pg/ml. Bronchoalveolar lavage fluid contained many plasma cells. Therapy with corticosteroids and immunosuppressant medication was effective. Our diagnosis was plasma cell interstitial pneumonia as a manifestation of multicentric Castleman's disease.
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PMID:[Plasma cell interstitial pneumonia as a manifestation of multicentric Castleman's disease]. 934 Dec 83


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