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)

This study shows that tritiated thymidine labeled DNA prepared from mammalian cells by the Marmur technique is a pure preparation of nucleic acid that is composed essentially of two populations of molecules. One molecular population consists of primarily double-standed nucleic acid, while the other population is of double-stranded nucleic acid with significant single-stranded regions. The double-stranded DNA with single-stranded regions can, depending upon the length of the single strand, behave as "native" DNA or "denatured" DNA on methylated albumin kieselguhr (MAK) column chromatography, Using MAK chromatography we have separated the DNA into a saltelutable fraction composed of primarily double-stranded molecules and an alkaline-elutable fraction containing double-stranded nucleic acid with variable length, single-stranded regions. Endonuclease enzyme removal of the single-stranded regions from the alkaline fraction DNA yield nucleic acid that behaves identically to the salt elutable DNA. Exonuclease removal of the single-stranded regions suggests they are located primarily at the ends of the molecules. Our data show that the alkaline-elutable DNA differs from salt-elutable DNA only in that the former has significant single-stranded regions. Sera of patients with systemic lupus erythematosus (SLE) selected for anti-DNA by hemagglutination bind significantly less to the alkaline fraction DNA than the sale fraction DNA. This difference in binding clearly does not represent simply an affinity for double-stranded vs. single-stranded nucleic acid since the alkaline fraction DNA contains predominately double-stranded nucleic acid. A model for antibody-DNA binding is suggested from the present data and information contained in the literature.
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PMID:Deoxyribonucleic acid strandedness. Partial characterization of the antigenic regions binding antibodies in lupus erythematosus serum. 12 88

Significant differences in both specificity and avidity of anti-DNA antibodies were observed in the sera of groups of patients with active systemic lupus erythematosus glomerulonephritis, active systemic lupus erythematosus without nephritis, and in IgG eluates obtained by DNAase digestion of isolated glomeruli from glomerulonephritic kidneys. With methylated albumin-kieselguhr fractionated 3H-HeLa DNA as a source of native or single-strand DNA antigen in a modified Farr assay, an increased level of antibody to native DNA was associated with active systemic lupus erythematosus, particularly active nephritis. The avidity of antinative DNA estimated from plots of the reciprocals of bound and free antigen according to the Sips distribution formula was significanly lower in active glomerulonephritis sera than in sera from patients with active systemic lupus erythematosus without nephritis. However, antinative DNA of uniformly high avidity was found in the glomerular eluates. Avidity of single-strand DNA antibodies did not differ in the various patient groups. The data stronly supprot a major role for high avidity antinative-DNA in DNA/antiDNA immune complex-induced glomerular injury in systemic lupus erythematosus.
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PMID:Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis. 29 48

Serum levels of carrier proteins, transferrin, ceruloplasmin and albumin were determined in patients with rheumatic disorders, along with serum levels of acute phase proteins, ceruloplasmin, alpha 1-acid glycoprotein and alpha 1-antitrypsin. Depressed levels of transferrin occurred in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Albumin was reduced in SLE and RA men. Acute phase reactants which are protective in inflammation were elevated in RA, osteoarthritis (OA), gout, pseudogout (PsG), and SLE. All of these rheumatic disorders show biochemical changes compatible with systemic inflammatory disease including gout and PsG which are considered local disorders and OA which is considered noninflammatory arthritis.
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PMID:Serum proteins--transferrin, ceruloplasmin, albumin, alpha 1-acid glycoprotein, alpha 1-antitrypsin--in rheumatic disorders. 31 26

A leukocyte migration inhibition test (LMIT) utilizing the agarose gel technique was performed with native DNA as an antigen in ten patients with systemic lupus erythematosus (SLE) and five normal subjects. Irrespective of disease activity, supernatants obtained at different time intervals during lymphocyte culture in eight patients with SLE showed significant alteration of migration, either enhancement or inhibition, of normal leukocytes. However, supernatants in the control experiments produced no significant alteration of migration. Polyacrylamide gel electrophoresis of supernatants obtained from the SLE group revealed that the inhibitory activity was present in the albumin region, whereas the enhancement activity was found in the beta-globulin region. These results indicate that the hitherto employed estimation of the leukocyte migration inhibition test based on the total activity of these two factors is insufficient for accurate evaluation of chemical mediators from sensitized lymphocytes and that the separation of these two factors may be important for a greater understanding of cellular immunity.
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PMID:Leukocyte migration inhibition test (LMIT) in systemic lupus erythematosus. 37 31

A solid phase radioimmunoassay was developed for detecting the quantity of double-stranded and single-stranded DNA antibodies in patients with systemic lupus erythematosus and other connective tissue diseases. The assay system employs a solid support 96-well, flex-vinyl microtiter plate to which bovine methyl albumin is layered, followed by denatured or native calf thymus DNA. A 1:80 dilution of patients' sera was added to respective wells followed by tritiated high affinity anti-IgG, -IgA, or IgM. Denatured DNA (single-stranded DNA) bound to methylated bovine serum albumin had less than 5% reannealment to the double-stranded form and provided a better substrate for Ab binding than double-stranded DNA, producing a linear binding curve. Of 58 patients diagnosed as having systemic lupus erythematosus (SLE), only 11 having active SLE had IgG antibody levels of greater than 5.0 microgram/ml to single-strand DNA. Renal involvement of some degree was found in all 11 with the high concentrations of IgG antibodies to DNA correlating with severe involvement. Patients with IgM antibodies to DNA alone had more benign types of SLE with little renal involvement. No abnormal levels of IgA Ab to either single-strand DNA or double-strand DNA were found in SLE patients' sera. Corticosteroid and/or immunosuppressant treatment caused a marked drop in the IgM Ab level to DNA within 10 days while IgG Ab to DNA remained high for up to 30 days. Quantitation of IgG and IgM Ab to single-strand DNA provides a useful method for diagnosing severe SLE with possible renal involvement and monitoring the course of the disease during therapy.
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PMID:Significance of levels of specific immunoglobulins to DNA in SLE patients' sera detected by solid phase radioimmunoassay. 42 67

Plasmapheresis together with immunosuppressive drug therapy has been used in the treatment of 17 patients with glomerulonephritis [Goodpasture's syndrome (4), systemic lupus erythematosus (4), mesangiocapillary glomerulonephritis (2), glomerulonephritis associated with cirrhosis (2), nonspecific mesangial proliferative glomerulonephritis (3), Henoch-Schoenlein purpura glomerulonephritis (1) and glomerulonephritis associated with infective endocarditis (1)]. Use of the Haemonetics Model 30 blood cell separator, exchanging two liters of plasma with 5% albumin in Hartmann's solution has provided a safe, effective but relatively expensive procedure, capable of producing a marked reduction of fibrinogen, complement components, anti-glomerular basement membrane antibody and immune complex concentrations. Removal of one or more of these factors is felt to be at least partly responsible for the improvement in renal function and clinical well-being demonstrated in patients with Goodpasture's syndrome, systemic lupus erythematosus and other forms of glomerulonephritis associated with the presence of circulating immune complexes.
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PMID:Plasmapheresis in glomerulonephritis. 50 88

The effect of conditioned medium on the biosynthesis and glycosylation profile of acute phase proteins secreted by the human hepatoma cell line Hep G2 was studied. Conditioned medium was prepared from nonactivated [CM-LPS(-)] and ex vivo lipopolysaccharide activated [CM-LPS(+)] monocytes from eight patients with active rheumatoid arthritis (RA), five patients with active systemic lupus erythematosus (SLE), and seven healthy subjects. The biosynthesis of albumin, alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor and the profile of glycosylation of proteinase inhibitor were analysed. CM-LPS(-) from patients with SLE had a similar effect to CM-LPS(-) from healthy subjects. In contrast, CM-LPS(-) from patients with RA had the same effect as CM-LPS(+) from healthy donors. A similar effect to that of CM-LPS(+) of healthy subjects was seen with CM-LPS(+) from patients with SLE and with CM-LPS(+) from patients with RA. The treatment of CM-LPS(+) with antibodies against interleukin 6 neutralised most of its ability to induce changes in the biosynthesis and glycosylation of acute phase proteins. Antibodies to interleukin 1 and tumour necrosis factor alpha had only a limited effect on the ability of CM-LPS(+) to induce changes of albumin and alpha 1-antichymotrypsin syntheses, whereas they had no effect on the biosynthesis and glycosylation of proteinase inhibitor. These results indicate that: (a) monocytes isolated from patients with active SLE and active RA have different capabilities of inducing alterations of acute phase proteins in vitro; (b) ex vivo activation of monocytes from patients with SLE leads to the full induction of its capabilities to change acute phase proteins, whereas the activation of monocytes from patients with RA has no additive effects; and (c) interleukin 6 seems to be a major cytokine involved in the regulation of the glycosylation pattern of acute phase proteins.
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PMID:Different capabilities of monocytes from patients with systemic lupus erythematosus and rheumatoid arthritis to induce glycosylation alterations of acute phase proteins in vitro. 137 63

A prospective study of systemic lupus erythematosus (SLE) patients under high doses of corticosteroid therapy (greater than 30 mg/day prednisolone) for a five-year period elucidated some risk factors of avascular necrosis of the femoral head (ANFH). A complete survey was performed on 62 patients, of whom nine patients developed ANFH during the period of study. The risk factors in the causation of ANFH were ascertained on the basis of characteristic clinical features of SLE, a typical pattern of laboratory data at the onset of ANFH, and the mode of glucocorticosteroid administration observed from a statistical point of view. The risk factors include stomatitis, drug-induced lupus, lupus erythematosus cell positive rheumatoid arthritis, interstitial pneumonitis, and thrombocytopenic purpura (characteristic clinical features); increased total cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, red blood cell, hemoglobin, and albumin/globulin; advanced renal failure (pattern abnormality of laboratory data); and a rash introduction of high-dose corticosteroid therapy (greater than or equal to 30 mg/day prednisolone) without corticosteroid preloading (mode of administration).
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PMID:Risk factors of avascular necrosis of the femoral head in patients with systemic lupus erythematosus under high-dose corticosteroid therapy. 155 61

A 17-year old-male presented with a 6-week history of weight loss, lassitude and calf pains. On examination he was very pale. Laboratory tests showed a very high erythrocyte sedimentation rate (155 mm in the first hour), anaemia (haemoglobin 10.1 g/dl), and a raised serum creatinine of 1.54 mg/dl. Microhaematuria (5-10 erythrocytes/microliter) and pronounced pyuria (500 leucocytes/microliter) were present, but the urine was sterile and there was no increase in albumin excretion. The serum IgG was raised to 75.7 g/l, suggesting an autoimmune disorder. Anti-nuclear antibodies (titre 1 : 1920) and anti-double-stranded DNA antibodies (31 U/ml) were present, while the serum complement C4 was decreased to 0.11 g/l. Renal histology showed an interstitial nephritis without glomerular involvement, while the bone marrow showed vasculitis accompanied by a prominent plasma-cell infiltrate. A diagnosis of interstitial nephritis associated with systemic lupus erythematosus was made, with asymptomatic cardiac and hepatic involvement. Renal function recovered rapidly with prednisolone therapy (initial dose 2 mg/kg.d). While glomerulonephritis is the most common lupus-associated renal disorder, isolated interstitial nephritis may occur in some cases, often with an absence of proteinuria.
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PMID:[Interstitial lupus nephritis]. 158 9

In previous studies we had shown that procainamide is metabolized to reactive metabolites by activated leukocytes, and evidence pointed to involvement of myeloperoxidase (MPO). In this study we examine the metabolism of procainamide by MPO/H2O2, in the presence and absence of chloride ion. In the absence of chloride ion, the metabolism was very similar to that seen with activated leukocytes. The major metabolite was formed by oxidation of the arylamine group to a hydroxylamine. In the presence of chloride ion, a much greater degree of metabolism occurred, and the major product (40% of the starting procainamide) was a reactive species that could not be isolated. This metabolite spontaneously rearranged to 3-chloroprocainamide, and from its mass spectrum and chemical reactions, we deduce its structure to be N-chloroprocainamide. The N-chloroprocainamide metabolite reacted very rapidly with reducing agents, such as ascorbate, and also reacted with protein such as albumin, the major product in both cases being procainamide. This metabolite also chlorinated phenylbutazone. When radiolabeled procainamide was oxidized by MPO/H2O2 in the presence of albumin, covalent binding of the radiolabel to albumin occurred, and binding was greater under conditions in which N-chloroprocainamide was formed. It is probable that the failure to observe N-chloroprocainamide, when procainamide is oxidized by activated leukocytes, is due to its rapid reaction with the cells. We propose that modification of neutrophils (or neutrophil precursors in the bone marrow) by these reactive metabolites is responsible for procainamide-induced agranulocytosis. In a similar manner, procainamide-induced lupus could be due to modification of monocytes by monocyte-generated reactive metabolites.
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PMID:N-Chlorination and oxidation of procainamide by myeloperoxidase: toxicological implications. 166 58


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