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 therapeutic effect of 15-deoxyspergualin (DSP) in old New Zealand Black/White F1 mice (B/W mice) with clinical nephropathy was studied and compared with cyclophosphamide (CY). The mice were treated with 0.05 ml phosphate-buffered saline, subcutaneously, four times/week, with DSP, 6 mg/kg body weight, s.c., four times/week, or with CY, 15 mg/kg, i.p., once a week, starting at the 28th week of age. They were serially semiquantitated for proteinuria, and serum IgG anti-dsDNA antibody was measured by ELISA. Spleen cell surface markers such as L3T4, Lyt2 and IgG were flow-cytometrically analyzed, and interleukin-2 (IL-2) activity in vitro was measured using CTLL cells. Kidney specimens were studied with light and immunofluorescence microscopy. The mice treated with either CY or DSP survived significantly longer than the control mice. L3T4+ cells in the DSP-treated mice at 40 weeks of age were significantly less than those in the 28-week-old control mice (p less than 0.05). In contrast, IL-2 generation in the three groups of mice showed no significant variations at 32-40 weeks of age. Serum anti-DNA antibody levels in both of the CY and DSP groups remained low and comparable with that in the 28-week-old mice, and the incidence of significant proteinuria decreased. Likewise, glomerular histology in the treated groups was improved compared with the 28-week-old control mice, and the deposition of IgG and C3 in the treated groups remained unchanged or further decreased. Accordingly, the renal (immuno)histological findings in the DSP group were quite comparable with or even better than those in the CY-treated mice. DSP may have suppressed the abnormal antibody production by modulating the T cell function(s), which is in contrast to the direct action against B cells due to CY.
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PMID:Reversal of established nephropathy in New Zealand B/W F1 mice by 15-deoxyspergualin. 204 19

Naturally occurring swine glomerulopathy was investigated and its glomerular tissue injury was compared with that of human IgA nephropathy. Mild proteinuria (30%) and microhematuria (17%) was found in 30 six-month-old swine. Serum creatinine level was 1.8 +/- 0.4 (mean +/- SD) mg/dl. Light microscopy (LM) disclosed diffuse or focal glomerulopathy with mesangial enlargement and hemispherical deposits in six-month-old swine. Electron microscopy revealed dense deposits in the mesangial, para-mesangial and sub-endothelium areas. On immunofluorescence+ (IF) staining findings, granular deposits of IgA (97%), IgG (97%), IgM (80%), C3 (100%), and mycoplasma hyorhinis (MH) antigen (90%) were found in the mesangial areas and along the capillary walls. One three-month-old pig and one five-year-old Goettingen mini pig were also found to have granular deposits of immunoglobulin and MH antigen in the glomerulus. In contrast, no glomerular lesion was found in all 4 new-born pigs and 4 fetal pigs by LM and IF study. In six-month-old swine anti-nuclear factor and anti-DNA antibody were negative, and no pathological lesion was found in the liver by LM. And IgA and MH antigen containing circling immune complexes were positive in sera by Raji cell assay, and moreover IgA and MH antigen was found co-depositing by the double stain techniques. These findings suggest that swine glomerulopathy is similar in appearance to human IgA nephropathy and MH antigen may contribute to the development of this nephropathy.
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PMID:[Study on the swine glomerulopathy resembling human IgA nephropathy]. 205 46

The precise pathogenesis of human diabetic kidney disease and the factors responsible for the susceptibility to it remain to be established. However, there is now evidence that renal disease clusters in families and that genetic factors are of central importance in determining liability. A predisposition to arterial hypertension has been suggested as playing a contributory role in the development of kidney disease. Genetically controlled hypertrophic processes may be implicated in the susceptibility to arterial wall damage and glomerular injury in diabetes. This suggestion derives from the observation that the fibroblasts of patients with diabetic nephropathy show a higher Na+/H+ antiport activity and a greater 3H-thymidine incorporation into DNA than fibroblasts of diabetic patients without nephropathy. The first sign of renal damage is the appearance of microalbuminuria and of a small elevation in arterial pressure, changes associated with significant mesangial expansion. Microalbuminuria is associated with abnormalities of lipoprotein profiles possibly as a consequence of insulin-resistance-induced hyperinsulinemia. It could be postulated that the environmental changes brought about by diabetes lead in susceptible individuals to increased systemic and intraglomerular pressure on the one hand and mesangial expansion on the other. These two processes would cause proteinuria and glomerulosclerosis. Lipid abnormalities would further aggravate the renal histological damage and, in combination with hypertension, contribute to the accelerated atherosclerosis typical of patients with diabetic kidney disease. A vicious circle would thus be triggered of reduction in renal function, more hypertension, more proteinuria, more glomerular obsolence, more hyperlipidemia and eventually end-stage renal failure or premature cardiovascular death.
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PMID:Mechanisms of diabetic renal and cardiovascular disease. 207 90

Hepatitis B virus carriers, a 30-year-old man (case 1) and a 31-year-old man (case 2), associated with nephrotic syndrome were treated with interferon-beta. The nephrotic syndrome did not respond to corticosteroid therapy. Their HBs-Ag, HBe-Ag and HBc-Ab were positive. Renal biopsies revealed membranous glomerulonephritis in case 1 and mixed membranous and proliferative glomerulonephritis in case 2. Direct immunofluorescence studies showed strong granular staining of the GBM with IgG and using sandwich technique with anti-HBe antiserum, granular deposits were seen throughout the GBM. Patients were administrated mainly 3-6 x 10(6) IU/day interferon-beta intravenously for four weeks. After transitory elevation of serum transaminase, HBe-Ag and DNA-polymerase have disappeared with development of HBe-Ab (seroconversion) about six months after the end of interferon-beta administration. Then nephrotic syndrome has recovered in incomplete remission after a year and a half follow-up. The secondary renal biopsy in case 1 showed less intense deposits of HBe-Ag along GBM. These facts suggest that the improvement of proteinuria is associated with the decrease in HBV replication due to interferon therapy.
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PMID:[Clinical and histological observation of HBV glomerulonephritis treated with interferon-beta]. 208 50

Experimental systemic lupus erythematosus (SLE) in mice can be induced by immunization either with a human monoclonal anti-DNA antibody bearing the 16/6 idiotype (16/6 Id) or with a mouse monoclonal anti-idiotypic antibody specific for the 16/6 Id. In the present report we investigated the pathogenic role of a monoclonal anti-La autoantibody in the induction and mediation of experimental SLE in mice. The monoclonal anti-La antibody was derived from a mouse in which experimental SLE was induced by immunization with the monoclonal anti-16/6 Id antibody. Following immunization with the anti-La antibody the mice produced antibodies to double-stranded DNA, single-stranded DNA, Sm, SS-A/Ro, SS-B/La, and ribonucleoprotein. Furthermore, even though the anti-La antibody does not express nor react with the 16/6 Id, the immunized mice produced high titers of anti-16/6 Id antibodies as well as 16/6 Id bearing antibodies. Four months following immunization the mice exhibited significant proteinuria, and kidney sections revealed immune complex deposits on the basement membrane of the glomeruli. These results suggest that anti-La autoantibodies are involved in the induction and mediation of SLE in mice.
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PMID:Induction of experimental systemic lupus erythematosus in mice by immunization with a monoclonal anti-La autoantibody. 208 87

Serum levels of 6 anti-DNA antibody idiotypes were measured in 65 consecutive patients with systemic lupus erythematosus (SLE) and 45 healthy subjects. Five of the 6 idiotypes were elevated in SLE sera compared to the normal controls (p less than 0.005). Analysis of the associations of the idiotypes with clinical, hematological, and serological characteristics revealed that significantly decreased serum levels of 3 idiotypes (103.1, 100, and 1305) were associated with nephritis and that one of these idiotypes (103.1) was also associated with discoid rash. An association of lowered levels of 3 idiotype markers (604, 1305, and 1400) was also observed with the presence of lupus anticoagulant and anticardiolipin antibodies. Serial studies in individual patients with SLE nephritis failed to show a close correlation of serum idiotype levels with the degree of proteinuria, creatinine clearance, anti-DNA antibody, or complement values. The association of decreased levels of specific idiotypes with the presence of nephritis, discoid rash, and antiphospholipid antibodies suggests the participation of these antibodies in the pathogenesis of disease.
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PMID:Association of anti-DNA idiotype markers with clinical and serological manifestations in patients with systemic lupus erythematosus. 210 45

Systemic lupus erythematosus (SLE) is considered a classical autoimmune disease that involves many biological systems. Similar to other autoimmune conditions, its etiology is multifactorial entailing genetic, environmental, hormonal, and immunologic factors. In this review we demonstrate that by using a pathogenic idiotype of anti-DNA autoantibodies, it is possible to explain some of the pathogenesis and diversity of clinical and serological manifestations reported by SLE patients. The 16/6 idiotype (Id) is a representative pathogenic idiotype of anti-DNA autoantibodies. The serum titers of 16/6 Id in SLE patients correlate with clinical activity of the disease, and are deposited in afflicted tissues in SLE patients. SLE was experimentally induced in naive mice after immunization with 1 microgram of the Id. The disease is characterized clinically (proteinuria), serologically (e.g., anti-dsDNA, anti-Sm antibodies), and by pathological findings (e.g., deposition of 16/6 Id in the kidneys). The condition can be induced by other human and mouse antibodies carrying the 16/6 Id, as well as by mouse antimonoclonal-16/6 Id and by T cell lines and clones specifically reactive with 16/6 Id. There are strain-dependent differences in susceptibility to the induction of systemic lupus erythematosus (SLE). Induction of SLE is directly correlated with the ability to respond to the 16/6 idiotype (or 16/6 Id)2 by anti-Id antibody production. It is easier to induce the disease in females, and it can be modulated by manipulation of sex hormones. Being able to identify the pathogenic idiotype allowed us to generate T suppressor (Ts) cells specific for the 16/6 Id. Treatment of mice with these T cells abrogated the disease. Our studies point to the importance of pathogenic idiotypes of autoantibodies in autoimmunity, which suggests that SLE may represent a dysregulation of a functional network of idiotypes-anti-idiotypes interactions among autoreactive B cells, T helper cells, and T suppressor cells.
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PMID:Pathogenic idiotypes of autoantibodies in autoimmunity: lessons from new experimental models of SLE. 214 Aug 6

To investigate the possibility of slowing down disease progression 27 patients with primary glomerular diseases unresponsive to steroids and cytotoxic drugs were treated with Defibrotide. This drug is a single stranded DNA fraction which has profibrinolytic and deaggregating properties and can promote the generation and release of prostacyclin from vascular tissue. Before treatment all patients showed proteinuria in excess of 1 g/day and 16 had a nephrotic syndrome (59%); 10 patients had serum creatinine above 1.6 mg/dl (37%) and 6 were hypertensive. After therapy a significant decrease in daily proteinuria was observed, although the reduction exceeded 50% of pre-treatment values in only 16 patients (59%). A progressive decrease in serum creatinine occurred in patients with abnormal renal function; serial measurement of renal plasma flow showed a progressive improvement with an average increase of 6 and 12%, after 1 and 3 months of treatment, respectively. These observations confirm the view that drugs improving endothelial function and renal hemodynamics can be of value in the treatment of chronic glomerular diseases and can contribute to the maintenance of renal function.
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PMID:Prevention of chronic glomerular uremia in steroid resistant glomerulonephritis. A clinical trial with a new antithrombotic agent. 220 92

Polyclonal B cell activation is an early feature of autoimmune disease in humans and mice with systemic lupus erythematosus. The contribution of polyclonal activation to the progression of autoimmunity is unclear, however, since it precedes the development of end-organ damage by months or years. To examine this issue, 109 autoimmune-prone (NZB X NZW)F1 X NZB backcross mice were hemi-splenectomized at 10 wk and the number and antigenic specificity of their Ig-secreting B cells quantitated by ELISA spot assay. Of the 61 mice that had polyclonally increased numbers of Ig-secreting cells/spleen, 31 died by 6 mo. In contrast, 0/48 backcross mice with normal numbers of Ig-secreting B cells at 10 wk died over the same period (P less than 0.001). Polyclonally activated mice also developed proteinuria earlier and more frequently than littermates with normal numbers of Ig-secreting cells (P less than 0.001). As adults, backcross mice with proteinuria expressed repertoires skewed towards the production of anti-DNA antibodies. At 10 wk these same mice expressed repertoires marked by polyclonal activation rather than preferential anti-DNA production. These findings indicate that autoimmune disease in SLE is accompanied by the autoantigen-driven production of autoantibodies but is preceded and predicted by polyclonal B cell activation.
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PMID:Polyclonal B cell activation in lupus-prone mice precedes and predicts the development of autoimmune disease. 221 9

Systemic lupus erythematosus is a multifactorial systemic disease in which genetic, immunologic, hormonal, and environmental factors may contribute to disease pathogenesis. Bacterial products (eg, bacterial lipopolysaccharide [LPS]) induce a lupuslike disease in normal mice and trigger an early and accelerated form of lupus nephritis in NZB/W mice. To investigate whether the mechanism by which LPS accelerates nephritis in the NZB/W mice involves interference with processing of immune complexes (IC), we administered LPS to NZB/W mice for 5 weeks and probed the kinetics of removal, liver uptake, and organ localization of a subsaturating dose of radiolabeled IC (2.5 mg of bovine serum albumin-antibovine serum albumin). Control NZB/W mice received vehicle (saline) alone. In NZB/W exposed to LPS, features of polyclonal B-cell activation (PBA) were enhanced, anti-DNA antibodies were raised, and a proliferative glomerulonephritis developed that was associated with renal insufficiency and substantial proteinuria. This LPS-accelerated nephritis could not be attributed to altered complement concentration, to altered blood cell carrier function, to delayed removal of pathogenic (large-sized) ICs from the circulation, to impaired liver uptake of ICs, or to enhanced localization of ICs in kidney. The findings indicate that transformation of nephritis is probably the result of LPS-induced PBA, that defective processing of pathogenic IC is not a contributory factor to nephritis, and that mechanisms other than passive renal localization of circulating ICs must be operative.
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PMID:Bacterial lipopolysaccharide transforms mesangial into proliferative lupus nephritis without interfering with processing of pathogenic immune complexes in NZB/W mice. 222 Oct 21


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