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)

Primary plasma cell leukemia (PPCL) is a rare form of disease accounting for 1-2 percent of myelomas. Between September 1990 and November 2000, among 540 patients with myeloma studied, 24 fulfilled the criteria of PPCL (4.4 percent). We found high frequencies of female patients (62 percent), Bence Jones proteinuria (79 percent), anemia (88 percent), bleeding (54 percent), confusional syndrome (42 percent), weight loss (71 percent), hepatomegaly (25 percent), splenomegaly (21 percent), leukocytosis (62 percent), and thrombocytopenia (71 percent). High serum levels of creatinine, calcium, lactate dehydrogenase (LDH), and beta(2)-microglobulin were detected in 50 percent, 37 percent, 58 percent, and 71 percent, respectively. Four patients were treated with vincristine, melphalan, cyclophosphamide, prednisone, and adriamycin (VMCPA), 12 with vincristine, adriamycin, and dexamethasone (VAD), and 8 with M-80 (oral melphalan 80 mg/m(2) plus dexamethasone 40 mg/m(2)). There was a trend toward lower values of Karnofsky score (P=0.07) and higher values of LDH (P=0.2) in the VAD group. Other clinical characteristics were comparable among the three groups. Complete plus partial responses were achieved in one and six patients treated with VMCPA and M-80, respectively. All patients treated with VAD failed to respond to treatment. Patients receiving the M-80 regimen experienced higher platelet toxicity (P=0.05), vomiting (P<0.0003), and mucositis. Also, the need for red blood cell transfusions was higher in the M-80 group. Median overall survival was 60 days. Overall survival was better in patients achieving complete or partial response. In conclusion, our study illustrates that intermediate doses of melphalan plus dexamethasone are an effective chemotherapy regimen for this aggressive disease. Response to treatment is the only prognostic factor for survival in these patients.
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PMID:Intermediate doses of melphalan and dexamethasone are better than vincristine, adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of primary plasma cell leukemia. 1218 4

A 69-year-old man with proteinuria, hematuria and abnormal renal and hepatic function developed acute renal failure. His clinical and laboratory examinations showed splenomegaly, edema, anemia and polyclonal hypergammaglobulinemia with high IgG levels. Renal biopsy showed interstitial nephritis with predominant B cell and plasma cell infiltration without monoclonality. After corticosteroid treatment, the patient showed remission in clinical symptoms and laboratory findings. However, one year later, he developed mantle cell lymphoma (MCL) with typical lymphocyte markers of cyclin D1 and CD5. When evaluated retrospectively, this patient appeared to have multicentric Castleman's disease initially and developed MCL later.
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PMID:Acute interstitial nephritis with polyclonal B cell infiltration and development of mantle cell lymphoma. 1252 Nov 89

Retinoic acids, a group of natural and synthetic vitamin A derivatives, have potent antiproliferative and anti-inflammatory properties. Recently, retinoic acids were reported to inhibit Th1 cytokine production. We investigated the effects of retinoic acid on lupus nephritis in a model of NZB/NZW F(1) (NZB/W F(1)) mice. Three-month-old NZB/W F(1) mice were separated into two groups: one treated with all-trans-retinoic acid (ATRA; 0.5 mg i.p., three times weekly for 7 mo) and one with saline as a control. Compared with controls, ATRA-treated mice survived longer and exhibited a significant reduction of proteinuria, renal pathological findings including glomerular IgG deposits, and serum anti-DNA Abs. Splenomegaly was less marked in the treated mice than in controls. Transcripts encoding IFN-gamma, IL-2, and IL-10 in splenic CD4(+) T cells were significantly reduced in treated mice compared with controls. We conclude that treatment with ATRA in SLE-prone NZB/W F(1) mice significantly alleviates autoimmune renal disorder and prolongs survival; this may thus represent a novel approach to the treatment of patients with lupus nephritis.
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PMID:Retinoic acid reduces autoimmune renal injury and increases survival in NZB/W F1 mice. 1275 64

Chronic low-dose-rate gamma irradiation at 0.35 or 1.2 mGy/h prolonged the life span of MRL-lpr/lpr mice carrying a deletion in the apoptosis-regulating Fas gene that markedly shortens life due to severe autoimmune disease. Immunological modifications as indicated by a significant increase of CD8(+) T cells and a significant decrease of CD3(+) CD45R/B220(+) as well as CD45R/B220(+) CD40(+) cells were found in parallel with amelioration of total-body lymphadenopathy, splenomegaly, proteinuria, and kidney and brain syndromes.
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PMID:Prolongation of life span associated with immunological modification by chronic low-dose-rate irradiation in MRL-lpr/lpr mice. 1473 Oct 73

Coumestrol is a naturally occurring plant estrogen. As estrogen influences cellular and humoral immunity, and has known effects on murine models of lupus, we investigated the effect of coumestrol on disease expression in the NZB/W F1 mouse. Female NZB/W F1 mice were fed a "standard" rodent diet including soy proteins, a non-soy diet, or a non-soy diet with 0.01% coumestrol. Outcome measures included survival, autoantibody expression, immunoglobulin levels, proteinuria, renal histology and B cell immunohistochemistry, and renal mRNA expression. At 24 weeks, the treatment group had decreased prevalence of autoantibodies detected by immunofluorescence and less splenomegaly. At 39 weeks, the prevalence of autoantibodies was similar but the treatment group had less proteinuria. Overall, there was little effect of treatment on renal mRNA levels as assessed by gene array analysis, but functional ontology mapping revealed that genes encoding proteins involved in the immune response were most often affected. These results suggest that treatment with coumestrol may ameliorate some aspects of disease progression in this model of systemic autoimmunity.
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PMID:The effect of the phytoestrogen coumestrol on the NZB/W F1 murine model of systemic lupus. 1557 26

We analyzed the clinical features and prognostic factors for transformation of immunoglobulin Mrelated disorders (IgM-RDs) to malignant lymphoproliferative disease (MLD) in 83 patients with IgM-RDs. We studied 19 patients with type I cryoglobulinemias, 56 patients with type II cryoglobulinemias, 5 patients with peripheral neuropathies (PNs), and 3 patients with idiopathic thrombocytopenic purpuras. Fourteen patients with cryoglobulinemias presented with mild to moderate hepatomegaly with or without splenomegaly. Fourteen patients with type II cryoglobulinemias had arthralgias and/or vascular purpura (12 receiving corticosteroids), and 7 presented with PN. These latter patients and those with PNs without cryoglobulinemia were treated with steroids, cyclophosphamide, or polychemotherapy with/without plasma-exchange. Cumulative probability of evolution to MLD at 5 years was 15% (95% CI; 5%-25%). At a median of 62 months (12-195 months), 8 cases of IgM-RDs (8.4%) evolved to overt Waldenstrom's macroglobulinemia (n = 6), 1 case to non-Hodgkin's lymphoma, and 1 case to B-cell chronic lymphocytic leukemia. At univariate analysis, male sex (P = 0.02), IgM level > or = 3 g/dL (P < 0.0001), detectable Bence Jones proteinuria (P = 0.0005), lymphocytosis (P = 0.049), and high erythrocyte sedimentation rate (P = 0.003) significantly correlated with the evolution risk. Age, blood cell counts, b2-microglobulin level, degree of marrow lymphoplasmacytic infiltration, type of cryoglobulinemia, and hepatitis C virus positivity did not correlate with transformation. Although IgM-RDs represent a distinct clinical entity frequently requiring treatment in view of the IgM-related symptoms, their evolution probability and prognostic factors for malignant transformation seem to widely overlap those described for asymptomatic IgM monoclonal gammopathies.
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PMID:Clinical characteristics and outcome of immunoglobulin M-related disorders. 1579 61

MRL-lpr/lpr mice carry a deletion in the apoptosis-regulating Fas gene that markedly shortens life due to multiple severe diseases. In our previous study (Radiat. Res. 161, 168- 173, 2004), chronic low-dose-rate gamma irradiation of mice at 0.35 or 1.2 mGy/h for 5 weeks markedly prolonged the life span, accompanied by immunological activation. This report shows that extension of the irradiation period to the entire life of the mice at the same dose rates improved survival further. The 50% survival time for untreated mice, 134 days, was prolonged to 502 days by 1.2 mGy/h life-long irradiation. Also obtained were a time course and a radiation dose-rate response for the activation of the immune system as indicated by a significant increase in CD4+ CD8+ T cells in the thymus and CD8+ T cells in the spleen and also by a significant decrease in CD3+ CD45R/B220+ cells and CD45R/B220+ CD40+ cells in the spleen. Drastic ameliorations of multiple severe diseases, i.e. total-body lymphadenopathy, splenomegaly and serious autoimmune diseases including proteinuria, and kidney and brain-central nervous system syndromes, were found in parallel with these immunological activations, with lifelong low-dose-rate irradiation being more effective than 5-week irradiation at low dose rates.
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PMID:Further study of prolongation of life span associated with immunological modification by chronic low-dose-rate irradiation in MRL-lpr/lpr mice: effects of whole-life irradiation. 1579 98

Type I interferons are associated with lupus. Genes that are regulated by IFN-alpha are upregulated in pediatric lupus patients. Gene deletion of the IFN-alpha/beta receptor in experimental lupus-like NZB mice results in reduced disease activity. Conversely, IFN-beta is a well-established treatment in multiple sclerosis, another autoimmune disease. For determining whether IFN-beta treatment is harmful or beneficial in lupus, MRL-Fas(lpr) mice were injected with this type I IFN. Treatment was initiated in MRL-Fas(lpr) mice with mild and advanced disease. IFN-beta was highly effective in prolonging survival and ameliorating the clinical (renal function, proteinuria, splenomegaly, and skin lesions), serologic (autoantibodies and cytokines), and histologic parameters of the lupus-like disease in mice that had mild and advanced disease. Several underlying mechanisms of IFN-beta therapy involving cellular (decreased T cell proliferation and infiltration of leukocytes into the kidney) and humoral (decrease in IgG3 isotypes) immune responses and a reduction in nephrogenic cytokines were identified. In conclusion, IFN-beta treatment of lupus nephritis in MRL-Fas(lpr) mice is remarkably beneficial and suggests that IFN-beta may be an appealing therapeutic candidate for subtypes of human lupus.
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PMID:Interferon-beta: a therapeutic for autoimmune lupus in MRL-Faslpr mice. 1620 27

MRL/MpJ-Fas(lpr)/J (MRL/lpr) mice represent a well-established mouse model of human systemic lupus erythematosus. MRL/lpr mice homozygous for the spontaneous lymphoproliferation mutation (lpr) are characterized by systemic autoimmunity, massive lymphadenopathy associated with proliferation of aberrant T cells, splenomegaly, hypergammaglobulinemia, arthritis, and fatal immune complex-mediated glomerulonephritis. It was reported previously that steady-state mRNA levels for the chemokine (C-C motif) receptor 2 (Ccr2) continuously increase in kidneys of MRL/lpr mice. For examining the role of Ccr2 for development and progression of immune complex-mediated glomerulonephritis, Ccr2-deficient mice were generated and backcrossed onto the MRL/lpr genetic background. Ccr2-deficient MRL/lpr mice developed less lymphadenopathy, had less proteinuria, had reduced lesion scores, and had less infiltration by T cells and macrophages in the glomerular and tubulointerstitial compartment. Ccr2-deficient MRL/lpr mice survived significantly longer than MRL/lpr wild-type mice despite similar levels of circulating immunoglobulins and comparable immune complex depositions in the glomeruli of both groups. Anti-dsDNA antibody levels, however, were reduced in the absence of Ccr2. The frequency of CD8+ T cells in peripheral blood was significantly lower in Ccr2-deficient MRL/lpr mice. Thus Ccr2 deficiency influenced not only monocyte/macrophage and T cell infiltration in the kidney but also the systemic T cell response in MRL/lpr mice. These data suggest an important role for Ccr2 both in the general development of autoimmunity and in the renal involvement of the lupus-like disease. These results identify Ccr2 as an additional possible target for the treatment of lupus nephritis.
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PMID:Chemokine receptor Ccr2 deficiency reduces renal disease and prolongs survival in MRL/lpr lupus-prone mice. 1626 57

Rapamycin is a potent immunosuppressive drug currently used mainly for rejection prophylaxis in renal transplantation. The aim of this study was to determine the effect of rapamycin treatment on the development of nephritis in lupus-prone New Zealand Black/White F1 (NZB/W F1) mice. Twelve-week-old female NZB/W F1 mice were treated with rapamycin (3 mg/kg body weight) or saline once daily by oral gavage for 20 weeks. The severity of nephritis was assessed by clinical and biochemical parameters, renal histology, immunohistochemistry and gene expression studies. Rapamycin treatment markedly reduced proteinuria, improved renal function, decreased serum anti-double stranded DNA antibody levels and diminished splenomegaly. Kidney sections from saline-treated mice showed marked mesangial proliferation, tubular dilation with protein cast deposition and interstitial inflammatory cell infiltration. Rapamycin-treated mice had near normal renal histology, with marked reduction in glomerular immune deposition and the infiltration by T cells, B cells and macrophages. Rapamycin treatment was associated with down-regulation of intra-renal expression of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein. We conclude that rapamycin is highly effective in preventing the development of nephritis in NZB/W F1 mice. The beneficial effects of rapamycin are mediated through inhibition of lymphoproliferation and reduced MCP-1 expression.
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PMID:Rapamycin prevents the development of nephritis in lupus-prone NZB/W F1 mice. 1841 12


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