Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of ancrod, a defibrinating agent, on murine lupus glomerulonephritis in the male BXSB mouse was studied to determine the relationship between macrophage procoagulant activity (PCA), fibrin deposition and glomerulonephritis. Marked renal disease and fibrin deposition were noted by three months of age in control mice, whereas little or no disease was seen in ancrod treated mice until five months of age. Similar high titers of anti-DNA antibodies and renal deposition of IgG were seen in both groups of mice. PCA rose with age in both ancrod treated and untreated mice, although it was significantly higher in control animals than in the ancrod treated group. Furthermore, ancrod therapy resulted in a decrease in plasma PCA inducing activity (PIF) and a decrease in the effectiveness of PIF to induce PCA in peritoneal macrophages in vitro. No mortality was observed in the 20 ancrod treated mice, whereas 10 of 20 control animals died. We conclude that defibrination with ancrod delays the development of renal fibrin deposition and glomerulonephritis and improves survival in BXSB mice. This was associated with a decrease in plasma PCA inducing activity and with an inhibitory effect on PCA induction. These results suggest that PCA contributes to injury in murine lupus glomerulonephritis by promoting fibrin deposition.
 ...
PMID:Ancrod improves survival in murine systemic lupus erythematosus. 229 6

CBA/KlJms-lprcg/lprcg mice with a novel mutation producing systemic lymphoproliferation were investigated for their serological and histological characteristics. The mutant mice showed elevated levels of serum immunoglobulin, C1q-binding immune complexes and antibodies to nuclear antigens such as dsDNA and ssDNA and poly(ADP-ribose). In contrast, histopathological lesions, e.g. glomerulonephritis, vasculitis or interstitial pneumonitis, were not revealed by histological and immunofluorescent examinations, except for lymphocytic infiltration in various organs. These results suggest that this mutant mouse strain may provide a new animal model for autoimmunity. However, further investigations are required to clarify whether this strain is unique as compared with other well-known lupus-prone strains of mice with respect to serological and histological abnormalities and become to be a new model of systemic autoimmune disease.
 ...
PMID:Serological and histological characterization of the new mutant strain of lpr mice, CBA/KlJms-lprcg/lprcg. 230 30

A simple and reproducible method for the measurement of serum neutrophil clustering activity was developed. High clustering activity was found in 19/30 patients with active systemic lupus erythematosus (SLE), and 14/20 of those with severe disease flares. In contrast, 0/10 patients with quiescent SLE and 2/20 patients with rheumatoid arthritis had high neutrophil clustering activity. Particularly high clustering activity was found in patients with SLE with lupus glomerulonephritis and in certain patients with central nervous system disease. An inverse correlation was found between neutrophil clustering activity and peripheral blood neutrophil count in patients with SLE not treated with glucocorticoids, and clustering activity was high in all patients with low neutrophil counts in this group. A moderate correlation was found between neutrophil clustering activity and C1q binding circulating immune complexes. Non-steroidal anti-inflammatory drugs and glucocorticoids had little direct effect on neutrophil clustering activity.
 ...
PMID:A novel assay for neutrophil clustering activity of human sera: relation to disease activity and neutropenia in systemic lupus erythematosus. 231 Feb 27

Eighteen patients with lupus membranous nephritis were retrospective identified by reviewing the renal biopsy records of an active renal pathology service. Seven had minimally proliferative membranous nephropathy (World Health Organization (WHO) classes Va and b). Eleven had membranous nephropathy with superimposed changes of focal or diffuse proliferative glomerulonephritis (WHO Vc and d). After mean follow-up periods of 73 +/- 6 and 74 +/- 15 mo, respectively, one patient of seven from WHO Va and b and seven of 11 from WHO Vc and d reached end stage renal disease. The latter patients were distinguishable from the former only by the degree of superimposed proliferation on renal biopsy and not by blood pressure, antinuclear antibody, anti-double stranded DNA, or complement levels. These data stand in contrast to the widely held belief that lupus membranous nephropathy is relatively benign. The belatedness of this observation is partially due to imprecision in nosology for patients with lupus who have renal biopsies with "overlap" characteristics.
 ...
PMID:Lupus membranous glomerulonephritis: different prognostic subgroups obscured by imprecise histologic classifications. 232 50

The lupus of NZB/NZW F1 female mice is associated with immune complex glomerulonephritis and premature death. Cyclophosphamide and 15(S)-15 methyl PGE1 therapy halt disease progression. Fluorescein conjugated antibodies were utilized to label specific leukocytes and the subsets were quantitated using a Fluorescence Activated Cell Sorter. Normal outbred CD-1 female mice showed a decrease in absolute T and B cell numbers with age, but the ratio of T and B cells remained essentially constant through 9 months of age. By contrast the NZB/W female mice showed decreased numbers of total lymphocytes relative to CD-1 controls at all ages. Moreover relative to CD-1s, there was a far greater decrease in T cell numbers (7 x for NZB/W versus 2 x for CD-1) and B cell numbers failed to decrease with age. The characteristic decline in T lymphocyte numbers and relative increase in B cell numbers in NZB/W mice were corrected with cyclophosphamide and PGE1 therapy. However, there was no selective modification of T cell subsets (L3T4+ or Ly2+) with therapy. Our investigation suggests correction of the abnormal T/B cell ratio may be a useful marker of therapeutic activity in NZB/W mice.
 ...
PMID:Cyclophosphamide and 15(S)-15 methyl PGE1 correct the T/B lymphocyte ratios of NZB/NZW mice. 233 73

Little is known about endogenous systemic lupus erythematosus (SLE) plasma DNA even though it is the presumed precursor of DNA-containing immune complexes, thought to play a central role in lupus glomerulonephritis. DNA purified from SLE plasma formed discrete bands, corresponding to sizes of about 150-200, 400, 600, and 800 bp, closely resembling the characteristic 200 bp "ladder" found with oligonucleosomal (ON) DNA. By radiolabeling DNA while in whole plasma, the very small amounts present could be further characterized. All of 24 such specimens formed two or more discrete bands on 6% PAGE. Detergent treatment of plasma resulted in a DNA migration pattern similar to that of purified DNA, suggesting disruption of DNA-protein complexes. DNA purified from authentic ON and detergent-treated ON behaved similarly. A significant portion of DNA, labeled in SLE plasma could be specifically immunoprecipitated with monoclonal antihistone antibody as was the case with ON. These immunoprecipitates, when redissolved, exhibited the expected size distribution upon PAGE. It is concluded that DNA in SLE plasma occurs as a series of multimeric complexes, at least a portion of which is noncovalently bound to histone. These results are consistent with an ON-like structure for SLE plasma DNA as had been suggested by theoretical considerations and may have important implications for its immunologic behavior in SLE and perhaps other disorders.
 ...
PMID:Endogenous circulating DNA in systemic lupus erythematosus. Occurrence as multimeric complexes bound to histone. 236 27

The influence of oestrogen on the lupus disease in MRL/l mice has been investigated. Adult, castrated male and female MRL/l mice were administered with s.c. injections of 3.2 micrograms of 17 beta-oestradiol twice a week. The results clearly demonstrate that a relatively small dose of oestrogen is a potent accelerator of the lupus disease in this mouse strain. Thus, administration of oestrogen accelerates glomerulonephritis, lymphoproliferation and mortality. Our results also indicate that oestrogen exerts a dual effect on the immune system of MRL/l mice by depression of antigen-specific and mitogen-induced T cell responses as well as enhancement of polyclonal B cell activation and autoantibody formation. In addition, even short-term administration of oestrogen in the preclinical phase of the disease resulted in long-lasting effects as evaluated by reduced longevity and aggravation of renal disease.
 ...
PMID:Oestrogen is a potent disease accelerator in SLE-prone MRL lpr/lpr mice. 237 93

The present studies dealt with the pathogenesis of renal involvement in murine chronic graft-versus-host disease, which is a model for human systemic lupus erythematosus. The disease was induced in (C57BL10xDBA/2)F1 hybrids by injection of DBA/2 lymphocytes. The animals developed systemic disease accompanied by deposition of autoantibodies in the glomeruli and a lupus type of nephritis. Antibodies were eluted from glomeruli isolated during various stages of the disease by magnetic extraction from iron-perfused kidneys. For assessment of the specificity of the antibodies, we used indirect immunofluorescence, an enzyme-linked immunosorbent assay, and immunoblotting. In glomeruli from week 4, autoantibodies were found to be directed against several antigens, among which were the glomerular basement membrane component laminin and the glomerular enzyme dipeptidyl peptidase IV, whereas week 8 glomeruli also showed antibodies directed against nuclear antigens. Both laminin and dipeptidyl peptidase IV are known nephritogenic antigens occurring in renal tubular epithelial brush border preparations. Antibodies eluted from isolated glomeruli of diseased animals bound in a granular pattern along the glomerular capillary wall after in vivo transfer. Anti-renal tubular epithelial antibodies in the sera of diseased animals were affinity purified and injected into naive mice, which induced immune complex glomerulonephritis and proteinuria, thus confirming the nephritogenic role of these autoantibodies in this model.
 ...
PMID:Characterization and in vivo transfer of nephritogenic autoantibodies directed against dipeptidyl peptidase IV and laminin in experimental lupus nephritis. 239 30

The initial results of the treatment of 8 patients with idiopathic and lupus glomerulonephritis with immunovenin intact are reported. Previously the patients had been treated for a long time with combinations of corticosteroids, immunosuppressors and anticoagulants without effect. All patients had an well expressed nephrotic syndrome, 6 patients had initial chronic renal failure. The immunovenin intact treatment was carried out in three day courses of 85 mg/kg/24 h (a total of 250 mg/kg for one course). All patients received two courses of treatment. The patients were followed up for 3 to 30 months (mean 10.0 +/- 3.29). In 4 patients a full clinical remission was achieved. Two patients, after a satisfactory effect of the treatment, died from non-renal causes. The mechanisms of action of immunovenin intact are discussed.
 ...
PMID:[Treatment of chronic glomerulonephritis with high doses of intravenous immunoglobulin]. 239 19

The effect of 15-deoxyspergualin (DSP), a newly developed immunosuppressive agent, on the development of spontaneously occurring lupus glomerulonephritis in MRL-lpr mice was examined. Administration of the drug was initiated at the age of 13 or 17 weeks, when polyclonal B cell activation and lupus nephropathy were apparent or became prominent. Treatment with DSP for up to 19 weeks of age at a dose of 2 mg/kg twice a day or 5 mg/kg daily strongly suppressed the increment of IgG-producing cell numbers in the spleen and serum levels of immune complexes and anti-DNA antibodies. Glomerular histological score estimated by light microscopy and IgG and C3 deposition in renal glomeruli were improved, compared with untreated control mice. Thus, DSP was shown to suppress the progression of polyclonal B cell activation and lupus nephropathy in MRL/lpr mice. These results suggest that DSP may be used as a therapeutic agent for systemic lupus erythematosus.
 ...
PMID:Therapeutic effect of 15-deoxyspergualin on the progression of lupus nephritis in MRL mice. I. Immunopathological analyses. 239 13


<< Previous 1 2 3 4 5 6 7 8 9 10