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 primary antiphospholipid syndrome and the antiphospholipid syndrome in systemic lupus erythematosus (SLE) patients (defined as secondary antiphospholipid syndrome) are characterized by the presence of anticardiolipin antibodies, thrombosis, thrombocytopenia, and recurrent fetal loss. To determine the role of anticardiolipin antibodies in the pathogenesis of antiphospholipid syndrome, monoclonal anticardiolipin antibodies were derived from mice in which experimental lupus was induced by a murine monoclonal anti-16/6 Id antibody. Two murine monoclonal anticardiolipin antibodies (2C4C2, 2C4D1) were generated and characterized. The 2C4C2, but not the 2C4D1, monoclonal antibody demonstrated remarkable lupus anticoagulant activity. Furthermore, these murine anticardiolipin monoclonal antibodies appear to recognize antigenic epitopes similar to those recognized by anticardiolipin antibodies found in sera of SLE patients. The monoclonal anticardiolipin antibody 2C4C2 was injected into naive female mice. Following immunization, the mice developed high titers of autoantibodies reacting with cardiolipin, DNA, nuclear extract, 16/6 and anti-16/6 Id, and anticardiolipin antibodies. As early as 8 weeks after immunization these mice exhibited significant leukopenia, thrombocytopenia, and proteinuria with immune complex glomerulonephritis. Moreover, mating of 2C4C2-injected mice with allogenic males resulted in low pregnancy rates and a low number of fetuses with a high percentage of fetal loss. These studies provide a new experimental model for secondary antiphospholipid syndrome demonstrating the role of anticardiolipin antibodies in the pathogenesis of this syndrome.
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PMID:Monoclonal anticardiolipin antibodies derived from mice with experimental lupus erythematosus: characterization and the induction of a secondary antiphospholipid syndrome. 768 61

No immunosuppression agent is as yet available that prevents the process of chronic allograft rejection, the most critical cause of late organ allograft loss. RS61443 (mycophenolate mofetil) inhibits de novo DNA synthesis as well as diminishes expression of cell surface molecules and antibody production. As these factors seem important in the pathophysiology of the chronic phenomenon, we investigated the effects of the agent in an established model of chronic rejection of kidney allografts in a F344-to-Lewis rat strain combination. All recipients were treated for the first 10 days after engraftment with low-dose cyclosporine (1.5 mg/kg/day) to reverse an initial acute rejection episode. Since functional and morphological changes do not become manifest in this model until after 12 wk, treatment with RS61443 (15 mg/kg/day, p.o.) was either initiated at the day of grafting (Gp 1) or 8 wks thereafter (Gp 2), and continued throughout the follow-up period. Non-RS61443-treated allografted rats receiving vehicle only (Gp 3) developed progressive proteinuria after 12 wk. Peak cellular infiltration (particularly macrophages in glomeruli and perivascular areas) at 16 wk was associated with densely expressed adhesion molecules (ICAM-1 on endothelium), cytokines and growth factors (TNF-alpha and TGF-beta in glomeruli and PDGF on arterial smooth muscle cells). Interstitial fibrosis, with tubular atrophy, glomerulosclerosis, and varying degrees of intimal proliferation and luminal obliteration of vessels, progressed thereafter. In vitro binding of MNC from naive animals to chronically rejecting allografted kidneys generally confirmed the immunohistological observations, peaking at 12 wk; this binding was significantly inhibited by mAbs against specific adhesion molecules (CD11a, CD18, and ICAM-1). Serum-allospecific IgG and IgM peaked at 1-2 wk after engraftment in the control recipients, decreasing thereafter. Although IgM declined to baseline after 12 wk, low levels of allospecific IgG persisted throughout the follow-up period. In contrast, recipient treatment with RS61443 (both Gp 1 and Gp 2) allowed the allografts to function normally throughout follow-up period. Proteinuria was virtually absent, and morphological and immunohistological manifestations of the chronic process were markedly diminished. In addition, treated recipients developed no significant side effects, including leukopenia, anemia, thrombopenia, nephrotoxicity, and hepatotoxicity. It appears that this agent can safely prevent the changes of chronic rejection of kidney allografts in this rat model.
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PMID:Effects of RS61443 on functional and morphological changes in chronically rejecting rat kidney allografts. 787 46

Induction of an experimental disease resembling murine systemic lupus erythematosus (SLE), has been achieved in mice by immunization with a human monoclonal anti-DNA antibody, bearing a common idiotype, designated 16/6 Id. In the present study we report the preparation of F(ab')2 proteolytic fragments of the human 16/6 Id mAb and the ability of the latter to induce experimental-SLE in mice. Following immunization with the F(ab')2 fragment, mice developed antibodies bearing the 16/6 Id, anti-16/6 Id and a variety of autoantibodies, similar to mice immunized with the whole 16/6 Id molecule. Serological manifestations of the disease such as leukopenia, proteinuria and renal damage, were developed following the immunization with the 16/6 Id F(ab')2 proteolytic fragments. These results demonstrate the pathogenic role of the F(ab')2 fragment that bears the 16/6 Id.
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PMID:Induction of experimental systemic lupus erythematosus in mice by immunization with the F(ab')2 fragment of the human anti-DNA monoclonal antibody carrying the 16/6 idiotype. 795 7

Experimental SLE can be induced in mice by immunization with a human mAb to DNA (16/6Id). Immunized mice develop Abs to the 16/6Id immunogen, DNA, and nuclear Ags. Subsequently, clinical manifestations of disease develop, including leukopenia, proteinuria, and immune complex deposits in the kidney. MHC class I Ags play a critical role in the induction of experimental SLE, as demonstrated by the finding that class I-deficient mice are resistant to disease induction. This finding suggested that agents that reduce MHC class I expression might mitigate experimental SLE in normal mice. These studies report that methimazole, which has been shown to repress class I transcription in some cell lines, reduces class I expression on PBLs in vivo and prevents the development of clinical manifestations of SLE in 16/6Id-immunized mice. These data suggest that methimazole, which has been used in the treatment of Graves' disease, may be useful in the clinical treatment of SLE and other autoimmune diseases.
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PMID:Methimazole prevents induction of experimental systemic lupus erythematosus in mice. 802 18

Because of the high rate of spontaneous remission, treatment of membranous nephropathy with prednisolone and chlorambucil is still controversial. The aim of this study was to give this therapy only to those patients at risk of developing renal insufficiency and to test the efficacy of a low-dose therapeutic regimen. Seventeen patients with more than 10 g protein excretion per day (mean 16.9) and/or a deterioration in renal function (mean serum creatinine, 162 mumol/l) were included. Serum total protein, serum lipids, proteinuria, serum creatinine, and blood pressure were measured, along with the diuretic and antihypertensive medication. The observation time before the start of treatment was 27 +/- 27 months. Steroids were given during months 1, 3, and 5 (methylprednisolone 3 x 500 mg intravenously) prednisolone 0.5 mg/kgBW daily per os for 1 week, then tapered by 0.1 mg/kg BW/week for 1 month). Chlorambucil was given during months 2, 4, and 6 at a dose of 0.12 mg/kgBW daily. At the end of treatment proteinuria had significantly decreased (mean of all patients, 7.8 +/- 1.4 g/d) in all patients. Six months after the end of treatment proteinuria was significantly lower than at baseline in 14 of 17 patients. Hypoproteinemia and hyperlipidemia had improved; diuretic and antihypertensive medication were reduced. Elevated serum creatinine decreased in 7 of 9 patients (pretreatment, 227 +/- 39 mumol/l; 6 months, 176 +/- 28 mumol/l). Nonresponders with respect to serum creatinine responded with respect to proteinuria. Regarding adverse effects, two patients complained of dyspepsia while taking steroids; during chlorambucil treatment two patients experienced nausea and lack of appetite, and one developed leukopenia (1600/microliters).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-dose prednisolone/chlorambucil therapy in patients with severe membranous glomerulonephritis. 804 74

Experimental SLE can be induced in susceptible mice by their immunization with the human monoclonal anti-DNA antibody that bears a major idiotype-16/6 Id. The SLE afflicted mice produce a variety of autoantibodies including anti-DNA antibodies. It was of interest to find out the effect of DNA on the induction of the experimental disease. To this end, mice were immunized with combinations of 16/6 Id and DNA. The results indicated that whereas mice primed with 16/6 Id developed high titers of antibodies to the 16/6 Id and a variety of autoantibodies typical to the experimental SLE, preimmunization of mice with ssDNA led to a reduction in the 16/6 Id specific antibodies and in the autoantibody titers. No significant differences could be detected in the clinical manifestations which are present in the mice with experimental disease (increased erythrocyte sedimentation rate, leukopenia, proteinuria and glomerular immune complex deposition) in all mice immunized with 16/6 Id including those pretreated with DNA. Thus, no direct correlation exists between the autoantibody levels and the clinical pathology, and probably other factors are involved in the development of the experimental disease.
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PMID:Inhibition of autoantibody production in experimental SLE by pre-immunization with DNA. 806 Nov 64

Experimental systemic lupus erythematosus (SLE) has been induced in mice by immunization with either a human anti-DNA mAb bearing a common idiotype (Id) designated 16/6 Id (antibody 1, Ab1) or with a murine anti-16/6 Id mAb (Ab2). In the present study a murine mAb (5G12-4, Ab3) that bears the 16/6 Id and binds to DNA was produced and was found to bind rabbit anti-16/6 Id sera and murine anti-16/6 Id mAb similarly to the human mAb 16/6 Id (Ab1). Moreover, mAb 5G12-4 was shown to share T cell epitopes with the human 16/6 Id mAb, since lymph node cells of mice immunized with the mAb 5G12-4 proliferated significantly to the human 16/6 mAb and vice versa. Following immunization of mice with the murine mAb bearing the 16/6 Id, antibodies to dsDNA, ssDNA, 16/6 Id, anti-16/6 Id, and to HeLa nuclear extract proteins were detected, similarly to those observed previously upon immunization with Ab1 or Ab2. Six months following the immunization, the mice exhibited leukopenia, increased erythrocyte sedimentation rates, and proteinuria. Examination of the kidneys of the mice disclosed immune complex deposits, thickening of the Bowman's capsule and glomerular necrosis. These results show the importance of the 16/6 Id network in the induction and progression of SLE in mice.
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PMID:The role of the 16/6 idiotype network in the induction and manifestations of systemic lupus erythematosus. 826 35

Experimental systemic lupus erythematosus (SLE) can be induced in mice by immunization with a human monoclonal antibody to DNA that bears a common idiotype (16/6Id). These mice generate antibodies to 16/6Id, antibodies to DNA, and antibodies directed against nuclear antigens. Subsequently, manifestations of SLE develop, including leukopenia, proteinuria, and immune complex deposits in the kidney. In contrast, after immunization with 16/6Id, mice lacking major histocompatibility complex (MHC) class I molecules generated antibodies to 16/6Id but did not generate antibodies to DNA or to nuclear antigen. Furthermore, they did not develop any of the above clinical manifestations. These results reveal an unexpected function of MHC class I in the induction of autoimmune SLE.
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PMID:Resistance of MHC class I-deficient mice to experimental systemic lupus erythematosus. 831 60

Plasma cell myelomas in horses have been reported infrequently. Data from 10 cases, 9 from the literature and 1 new case, are used to characterize the disease in the horse. Hot-blooded horses (7/10), specifically Quarter Horses (4/10), were most often affected. Median age at diagnosis was 11 years (range, 3 mo-22 yr) and both male (5) and female horses (5) were represented equally. Clinical findings included weight loss (6/8), anorexia (4/8), fever (4/8), limb edema (4/8), pneumonia (3/8), rear leg paresis/ataxia (3/8), epistaxis (3/8), palpable lymphadenopathy (2/8), and bone pain (2/8). Anemia (8/8) was present routinely, and in three horses, RBCs were macrocytic. Leukopenia (2/8), thrombocytopenia (2/8), and circulating plasma cells (3/8) were variable findings. Except for abnormal protein concentrations and hyponatremia (3), abnormal results from serum biochemical analysis including hypocholesterolemia (1), hypercalcemia (1), and azotemia (1) were reported infrequently. Hyperproteinemia (8/9), hypoalbuminemia (7/9), and hyperglobulinemia (8/9) were characteristic but not invariable findings. Monoclonal proteins (7/7) were detected in the alpha 2, beta, or gamma region by serum electrophoresis. The paraprotein's heavy chain, determined in four horses, was a subclass of IgG. Three horses had decreased concentrations of normal immunoglobulins. Variable proteinuria (trace to 4+) was detected by routine urinalysis in four of six horses. Bence Jones proteinuria was detected in one of five horses (heat precipitation) and monoclonal proteins were detected in two of three electrophoresed urine samples. Three of the horses had lytic bone lesions detected radiographically. Bone marrow aspirates were diagnostic in two of five horses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma cell myeloma in the horse. A case report and literature review. 833 11

In this study, we examined the progression of chronic Adriamycin (ADR) nephropathy in mild leukopenic rats and tried to define the possible relationship between tubulointerstitial lesions and proteinuria in this model. Chronic ADR nephropathy was induced by 2 doses of ADR (2 mg/kg) in 32 Sprague-Dawley rats. Eight of these were randomly assigned to cyclophosphamide treatment (50 mg/kg), given intravenously every week, to keep the blood leukocyte count constantly lower than 5,000/mm3. Serial parameters were followed for 16 weeks including clearance studies with iothalamate and p-aminohippurate and the analysis of urinary protein composition by: (a) an enzymatic assay for beta-glucosidase; (b) specific ELISA using antibodies against rat albumin and RBP, and finally (c) two-dimensional electrophoresis. ADR-treated rats rapidly (within 2 weeks) developed massive proteinuria which was in constant increment throughout the disease evolution in each single component (i.e., high and low molecular weight proteinuria, enzymuria) and developed renal insufficiency. At week 8, in ADR rats, glomerulosclerosis was mild whereas tubulointerstitial infiltrates predominated, characterized mainly by CD4+ T lymphocytes while CD8+ T lymphocytes were inconspicuous, and macrophages were only occasionally present. All such alterations had worsened after 16 weeks when the tubulointerstitial infiltration was associated with marked interstitial fibrosis and tubular atrophy. Leukopenia induced by cyclophosphamide was in all cases associated with a net amelioration of renal histopathology reducing tubulointerstitial infiltrates (by 40%) and glomerulosclerosis (33 +/- 5 vs. 52.2 +/- 7.5% sclerotic glomeruli) and also ameliorated glomerular filtration indexes (Cl 780 +/- 40 vs. 447 +/- 66 microliters/min/kg-1). In spite of these differences, albuminuria and urinary-retinol-binding protein were comparable at weeks 4, 8 and 16 in this group, while urinary beta-glucosidase was decreased at week 16 (p < 0.001) in cyclophosphamide-treated rats. No other qualitative changes in urinary proteins were detectable by 2-dimensional electrophoresis during the disease development. We concluded that chronic leukopenia prevents interstitial cellular infiltration by lymphocytes, interstitial fibrosis and slows down the decline of renal function typical of chronic ADR nephropathy. Glomerulosclerosis is also reduced in leukopenic rats without any appreciable changes in the urinary excretion of high molecular weight proteins deriving from the glomerulus. Finally, the improvement in tubulointerstitial alteration is associated with the reduction in urinary lysosomal enzymes. Tubulointerstitial alterations are implicated with a prominent role in the progression towards renal failure in chronic ADR glomerulopathy.
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PMID:Progression of chronic adriamycin nephropathy in leukopenic rats. 844 56


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