Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complement-dependent cytotoxic activity against normal human peripheral blood lymphocytes was detected in 11 of 17 cryoprecipitates from the serum of patients with systemic lupus erythematosus (SLE). The lymphocytotoxicity was eliminated by treatment with 2-mercaptoethanol and iodoacetamide, and it was inhibited by antibody to human IgM but not anti-IgG. The titers of lymphocytotoxic activity in the cryoprecipitates were roughly proportional to the corresponding serum titers, but when they were normalized for IgM concentration it was apparent that selective concentration of lymphocytotoxic antibody occurred in the cryoglobulins. The relationship between cryoprecipitable lymphocytotoxicity and a number of laboratory and clinical parameters of SLE was studied. The amount of protein in the cryoprecipitates, which was greatest in patients with significant renal disease, correlated with a reduction of serum complement and the amount of antibody to DNA. However the lymphocytotoxic activity of the cryoglobulins did not correlate with the severity of SLE. The titer of lymphocytotoxic antibody was independent of a) the presence or absence of active lupus nephritis, b) the total protein or immunoglobulin content of the cryoprecipitates, c) serum complement levels, and d) the amount of circulating antibody to DNA. These findings cast doubt upon the pathogenetic significance of cryoprecipitable lymphocytotoxic antibody.
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PMID:Lymphocytotoxic antibody activity in cryoprecipitates from serum of patients with SLE. 108 25

Sera from patients with active systemic lupus erythematosus caused the retention of the radioactively labeled synthetic polynucleotide 14C-dAT on cellulose nitrate filters. The amount of 14C-dAT bound correlated with the presence of hypocomplementemia and active renal disease. Sera containing only anti-single-stranded DNA antibodies did not bind 14C-dAT but did bind 125I DNA from E coli that had been prefiltered to remove ssDNA contamination. Inhibition experiments also indicated the presence of antigenic differences between 14C-dAT and prefiltered 125I-E coli DNA. The data suggest that dAT carries one of the major antigenic specificities for antinative DNA antibodies in SLE, and that cellulose nitrate filtration fails to remove a significant proportion of contaminating single-stranded DNA determinants in non-synthetic DNA.
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PMID:Antibodies to dAT detected by membrane filtration. 108 27

Serum C4 and C3 concentration and binding of double-stranded-DNA (ds-DNA) were measured in sera from ninety-nine patients with systemic lupus erythematosus and clinical evidence of nephritis. C3 and C4 concentrations correlated poorly with ds-DNA binding. In sera from fifty-three patients, precipitating antibody was sought using the counterimmunoelectrophoretic technique. Precipitating antibody was detected on at least one occasion in 44% of the patients, and these sera with precipitating antibody showed higher binding of ds-DNA and lower C4 concentrations than those without precipitating antibody. In thirty-two patients, serial assessments of the activity of the renal disease were made using decline or improvement in glomerular filtration rate, degree of proteinuria, oedema and hypertension as indices of "activity". All patients were receiving immunosuppressive drugs. Active nephritis was rarely found in patients showing, at that time, a normal serum C4 or normal ds-DNA binding; but a raised ds-DNA binding or lowered serum C4 were found in both active and inactive nephritis. There was no correlation of activity with serum concentrations of C3, or the presence or absence of precipitating antibody. We conclude that measurements of serum-complement concentrations and binding of ds-DNA are of most use in the diagnosis of systemic lupus erythematosus, and that in patients with nephritis and taking immunosuppressive drugs, these tests are of limited use in guiding treatment.
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PMID:Disease activity in the nephritis of systemic lupus erythematosus in relation to serum complement concentrations. DNA-binding capacity and precipitating anti-DNA antibody. 108 78

Pulmonary function was measured in a group of 28 patients with systemic lupus erythematosus (SLE) who were free of pulmonary involvement at the time of the study. When compared with age and sex matched controls, the SLE patients had a pattern of restriction with reduced lung volumes and vital capacity. Diffusing capacity was reduced in proportion to the reduction in lung volume. This is felt to be most compatible with inapparent pleural thickening resulting in impaired lung expansion. There was no evidence of airway obstruction on maximal expiratory flow-volume curves. The effect of cigarette smoking in the SLE patients was a reduction in flows at low lung volumes, which was indistinguishable from the effects in the control smokers. Both SLE and control smokers had a significant reduction in DL/VA when compared with control nonsmokers. Pulmonary function was not influenced by the presence of renal disease.
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PMID:Pulmonary dysfunction in systemic lupus erythematosus without pulmonary symptoms. 108 64

Histologic classification of renal glomerular lesions in 46 patients with systemic lupus erythematosus revealed 17 as having either focal proliferative (10 patients) or minimal mesangial proliferative (7 patients) glomerulonephritis. Six of the 17 have progressed to a diffuse proliferative glomerular lesion on subsequent renal biopsies, 9 months to 5 years later. Five had clinical deterioration at the time of follow-up biopsies; currently one is undergoing hemodialysis and four others have decreased renal function. Although a comparison of those who progressed with those who are stable revealed greater proteinuria in some of those who progressed, no other clinical features of the initial illness were different in the two groups, nor were differences between the two groups noted on light microscopic examination of initial renal biopsies. However, ultrastructurally, electron-dense deposits, especially those subendothelial in location, were noted along glomerular capillary basement membranes more frequently and in greater number in those who progressed. These findings suggest that lupus patients with a mild proliferative glomerulonephritis may have clinical and histologic progression of the renal disease, and those who progress cannot be clearly defined by clinical or light microscopic features. Ultrastructural demonstration of subendotheial deposits suggests a greater likelihood of subsequent progressive disease.
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PMID:Progression from minimal or focal to diffuse proliferative lupus nephritis. 109 11

A study of renal biopsy specimens obtained in Senegal from 24 children and six adults with nephrotic syndrome showed two unusual varieties of nephropathy--namely, an extramembranous glomerulonephritis associated with hypocomplementaemia (four cases), a combination previously described only in systemic lupus erythematosus, and a "tropical nephropathy" (16 cases). The latter, though lacking the diffuse glomerular deposits of immunoglobulin described in quartan malarial nephropathy (Q.M.N.), showed a curious progressive and segmental glomerulosclerosis, characterized by a "flaking" or fibrillary splitting of the glomerular capillary wall, seen in Q.M.N. Serological evidence of malaria was lacking in a third of the childhood cases.
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PMID:"Topical nephropathy" and "tropical extramembranous glomerulonephritis" of unknown aetiology in Senegal. 109 12

One hundred ten patients with systemic lupus erythematosus (SLE) were classified into two groups, patients with central nervous system (CNS) or severe renal disease (usually associated with a poor prognosis) and patients without these manifestations, to define criteria for azathioprine therapy. Fifty-four of 68 patients with a poor prognosis received azathioprine. Azathioprine-treated patients showed improved long-term survival (72% vs 29%, P less than .005) and fewer hospitalizations (0.24/patient-years vs 0.89/patient-years, P less than .001). Azathioprine therapy in 19 of 42 patients with a good prognosis was associated with fewer hospitalizations (.02/patient-years vs .17/patient-years, P less than .05), but no decrease in maintenace prednisone requirement. Progression from a good to a poor prognosis was less frequent (1 of 20 vs 11 of 34, P = less than .05) among azathioprine-treated patients. Toxicity of azathioprine was minimal. Azathioprine therapy is indicated in patients with CNS or severe renal disease, and in patients whose prognosis was good with frequent hospitalizations or a maintenance prednisone requirement greater than 15 mg/day.
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PMID:Long-term maintenance therapy with azathioprine in systemic lupus erythematosus. 111 45

Female NZB/W mice develop a disease closely resembling human systemic lupus and serve as an animal model for therapeutic studies. Several previous studies have demonstrated the efficacy of different immunosuppressive drug regimens in the therapy of glomerulonephritis in NZB/W mice. After the onset of immune complex deposition, treatment with intermittent high doses of cyclophosphamide or daily low doses of the combination of cyclophosphamide, azathioprine, and methylprednisolone has been effective. The present study was designed to compare such effective regimens in mice early in the course of their renal disease versus mice late in the course of glomerulonephritis. One to three injections of high-dose cyclophosphamide during active immune complex deposition and early histologic changes were significantly effective in prolonging survival, whereas treatment late in the course of glomerulonephritis was less effective. Even more striking was the result of low-dose combination therapy. Daily treatment with cyclophosphamide, azathiprine, and methylprednisolone (C + A + M) effectively prolonged survival when started in mice 5 months old, but was of no benefit when started in those 8 months of age. In a concluding experiment, older mice were selected on the basis of degree of renal disease and studied with regard to proteinuria and survival. Those with mild renal disease responded to daily treatment for 6 months with C + A + M at 1 mg/kg of each drug, whereas those with advanced renal disease at the onset of therapy did not benefit.
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PMID:Therapeutic studies in NZB/W mice. III. Relationship between renal status and efficacy of immunosuppressive drug therapy. 111 49

Twenty renal biopsies from 13 patients with systemic lupus erythrematosus were examined in detail to assess the amount and distribution of electron-dense deposits. Results were correlated with clinical and histologic findings. Mesangial deposits were present when there were deposits in other areas. Subepithelial deposits were not associated with severe renal disease and tended to persist unchanged with time. Subendothelial deposits were not invariably associated with severe renal disease, but, when severe disease existed, large subendothelial deposits were found. These deposits disappeared with treatment and clinical improvement.
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PMID:Lupus Nephritis. Correlations between the clinical course and presence of electron-dense deposits. 112 9

Properdin deposition has been recognized in glomeruli of patients with acute and chronic nephritis and lupus nephritis, and low serum properdin levels have been found in these disorders. These findings suggest that properdin may be involved in the production of glomerular damage and that low properdin levels may be due to hypercatabolism. The study was designed to examine the metabolism of properdin in normal subjects and to look for an abnormality in five patients with systemic lupus erythematosus with renal involvement and in six patients with membranoproliferative glomerulonephritis or dense deposit disease (MPGN). Highly purified human properdin was prepared by elution from zymosan, followed by DEAE-cellulose and carboxymethyl-Sephadex chromatography, and labeled with 125I by the iodine monochloride method. Parameters of metabolism were determined by monitoring plasma and urinary radioactivity at frequent intervals after the intravenous injection of 1-2 muCi of labeled material. The fractional catabolic rate (FCR) of properdin in normal subjects was found to have a very narrow range of 0.78-1.0,% of the plasma pool per hour (mean 0.95%). In systemic lupus erythematosus, the FCR was regularly elevated with a range of 1.21-2.30% (mean 1.70%). In MPGN, FCR was elevated in three patients (1.22, 1.94, and 2.08%) and within or below the normal range in three (0.78, 1.00, and 1.00%). Properdin levels were reduced in two patients who had the highest FCR's noted in the study. Properdin synthetic rates in normals varied from 4.1 to 14.3 mug/kg per h (mean 9.1) and was not found to be reduced in any patient. Properdin catabolism was found to be normal in a patient deficient in the C3b inactivator. These studies show that properdin is hypercatabolized in patients with renal disease and that decreased properdin levels when they occur in these patients can be entirely explained on the basis of this hypercatabolism.
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PMID:Metabolism of properdin in normal subjects and patients with renal disease. 115 85


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