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

The effect of sera and IgG from 12 patients with systemic lupus erythematosus (SLE) on the endothelial cell (EC) procoagulant activity (PCA) was investigated in an in vitro thrombosis model. Six of the 12 SLE sera contained antiphospholipid antibodies (aPL). EC were stimulated for 8 h at 37 degrees C with or without 50 pM tumor necrosis factor (TNF) in culture medium containing 20% patient or control serum. Then the endothelial cell matrix (ECM) was isolated and subsequently exposed in a perfusion chamber to circulating normal whole blood, anticoagulated with low molecular weight heparin (LMWH). The PCA of the ECM was determined as the amount of generated fibrinopeptide A (FPA) in samples taken before and after perfusion. Furthermore, cross sections were made of the perfused matrix and analyzed for platelet adhesion and aggregate formation. All six aPL containing sera induced a small, but significant increase of ECM procoagulant activity. When added in combination with a low dose of TNF (50 pM), a synergistic enhancement of ECM procoagulant activity was found. The FPA generation was increased to 150-614% from the values obtained after stimulation with TNF and control serum. Also a shift towards the formation of larger platelet thrombi was observed. After stimulation with TNF and patient serum the surface of ECM covered with large aggregates (greater than 5 microns) was increased by 124-329% compared to the results obtained after stimulation with control serum and TNF. When patient sera were depleted from IgG the effects were strongly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Antiphospholipid antibody positive sera enhance endothelial cell procoagulant activity--studies in a thrombosis model. 144 Apr 92

The 1991 literature on septic arthritis included a concise review of adult septic arthritis, examples of pseudoseptic arthritis, and two interesting animal studies. One animal study examined the induction of acute synovitis by the intra-articular injection of bacterial endotoxin and the cytokines tumor necrosis factor-alpha, and interleukin-1 beta; and the other studied the effects of early and delayed synovectomy in the management of septic arthritis. The predispositions to septic arthritis can be divided into local joint abnormalities, systemic factors, or both. Examples of the local joint abnormalities include osteoarthritis of the hip and apatite-associated arthropathy. Septic arthritis in a patient with rheumatoid arthritis, in a patient with diabetes mellitus and hip arthropathy associated with hemochromatosis, or in a patient with acquired immunodeficiency syndrome and hemophilic arthropathy are examples of how systemic predisposition is coupled with local joint pathology to increase the vulnerability of the host to joint infection. Other examples of systemic disease that predispose to septic arthritis are systemic lupus erythematosus, hypogammaglobulinemia, and human immunodeficiency virus infection, as well as intravenous drug abuse. Unusual microorganisms causing septic arthritis in the adult include Achromobacter xylosoxidans, Moraxella catarrhalis, meningococci, and diphtheroids. Uncommon pathogenesis is represented by a case of intra-articular inoculation of Mycobacterium gastri into the small joint of the hand and a case of mixed bacterial infection of the hip resulting from an extension of a contiguous pelvic infection associated with trauma. Two cases of immune complex glomerulonephritis illustrate the extra-articular complications of septic arthritis: one due to group G streptococcus and the other due to pneumococcus. Finally, septic bursitis is reviewed from the community practice perspective.
 ...
PMID:Bacterial arthritis. 150 74

The production of different cytokines, namely interleukin-2, interleukin-1 and tumor necrosis factor-alpha produced by peripheral immunocompetent cells was evaluated in patients with systemic lupus erythematosus in active and inactive stage of the disease. The results obtained were compared to healthy controls. It has been found that lymphocytes from both groups of SLE patients produced similarly less interleukin-2 activity. Interleukin-1 activity of monocytes was significantly reduced only in patients with active stage of the disease, whereas tumor necrosis factor-alpha production was diminished even in cases of inactive SLE. The simultaneous detection of the above mentioned cytokines may indicate further details concerning immunoregulatory disturbances of systemic lupus erythematosus.
 ...
PMID:[Cytokine production in patients with systemic lupus erythematosus]. 160 83

Cells of the immune system synthesize prolactin and express mRNA and receptors for that hormone. Interleukin 1, interleukin 6, gamma interferon, tumor necrosis factor, platelet activator factor, and substance P participate in the release of prolactin. This hormone is involved in the pathogenesis of adjuvant arthritis and restores immunocompetence in experimental models. In vitro studies suggest that lymphocytes are an important target tissue for circulating prolactin. Prolactin antibodies inhibit lymphocyte proliferation. Prolactin is comitogenic with concanavalin A and induces interleukin 2 receptors on the surface of lymphocytes. Prolactin stimulates ornithine decarboxylase and activates protein kinase C, which are pivotal enzymes in the differentiation, proliferation, and function of lymphocytes. Cyclosporine A interferes with prolactin binding to its receptors on lymphocytes. Hyperprolactinemia has been found in patients with systemic lupus erythematosus. Fibromyalgia, rheumatoid arthritis, and low back pain patients present a hyperprolactinemic response to thyrotropin-releasing hormone. Experimental autoimmune uveitis, as well as patients with uveitis whether or not associated with spondyloarthropathies, and patients with psoriatic arthritis may respond to bromocriptine treatment. Suppression of circulating prolactin by bromocriptine appears to improve the immunosuppressive effect of cyclosporine A with significantly less toxicity. Prolactin may also be a new marker of rejection in heart-transplant patients. This body of evidence may have an impact in the study of rheumatic disorders, especially connective tissue diseases. A role for prolactin in autoimmune diseases remains to be demonstrated.
 ...
PMID:Prolactin, immunoregulation, and autoimmune diseases. 206 74

We report on the production of tumor necrosis factor (TNF)-alpha and TNF-beta by mitogen-activated peripheral blood lymphocytes or enriched monocyte subpopulations from human leukocyte antigen (HLA)-typed healthy subjects. The results indicate that HLA-DR2- and DQw1-positive donors frequently exhibit low production of TNF-alpha, whereas DR3- and DR4-positive subjects show high levels of TNF-alpha production. No correlation between TNF-alpha levels and HLA-A, -B, and -C genotype was found. The relevance of this quantitative polymorphism to the genetic predisposition to lupus nephritis in systemic lupus erythematosus (SLE) patients was investigated. DR2, DQw1-positive SLE patients show low levels of TNF-alpha inducibility; this genotype is also associated with an increased incidence of lupus nephritis. DR3-positive SLE patients, on the other hand, are not predisposed to nephritis, and these patients have high TNF-alpha production. DR4 haplotype is associated with high TNF-alpha inducibility and is negatively correlated with lupus nephritis. These data may help explain the strong association between HLA-DR2, DQw1 in SLE patients and their susceptibility to nephritis.
 ...
PMID:Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus. 210

The effect of 15 antiphospholipid antibody (APA) positive SLE sera, 13 APA negative SLE sera, 10 APA negative sera from patients with other connective tissue diseases (CTD) and 15 control sera on the expression of endothelial procoagulant activity (PCA) was studied. Endothelial cells (EC) were stimulated with tumor necrosis factor (TNF) and 20% serum for 4 hr and the surface PCA expression was measured. Without TNF, none of the sera stimulated PCA expression. With suboptimal TNF stimulation, 14/15 APA positive SLE sera, 7/13 APA negative SLE sera, 2/10 CTD sera and 2/15 control sera enhanced PCA expression. This stimulating effect resided in the IgG fraction and was associated with the presence of APA, but not with a history of thrombosis. Purified APA had no PCA stimulating activity. PCA expression was inhibited by cycloheximide and heat treatment (30 min, 56 degrees C) of serum. In conclusion, 21/28 (75%) SLE sera increase the TNF-induced endothelial PCA expression. Although this effect predominantly occurs with APA positive serum, a causative role of APA was not demonstrated.
 ...
PMID:Synergistic effect of low doses of tumor necrosis factor and sera from patients with systemic lupus erythematosus on the expression of procoagulant activity by cultured endothelial cells. 251 Mar 46

The degree of complement activation produced by hydrogen peroxide was estimated by the inhibition of serum homolytic activity (% IHA). Sera from patients with systemic lupus erythematosus and psoriasis vulgaris were resistant to hydrogen-peroxide-mediated complement activation. %IHA negatively correlated with ceruloplasmin level or catalase activity in systemic lupus erythematosus sera, but did not correlate with transferrin level. The addition of free metal ions, FeCl2 or CuCl2, promoted hydrogen-peroxide-mediated complement activation. These results suggest that hydroxyl radical is involved in complement activation and that the factors responsible for the insensitivity of pathological sera to H2O2 are catalase and ceruloplasmin in the sera. Human skin fibroblasts generate superoxide and tumor necrosis factor enhanced it, but interleukin-1 beta inhibited it. Normal serum cultured with fibroblasts for 24 h showed complement activation via catalase-inhibitable process, suggesting that hydrogen peroxide has an important role in fibroblast-mediated complement activation. It is speculated that fibroblasts and complement activation by oxygen radicals have an important role in inflammation and subsequent tissue damage at the site of skin lesion.
 ...
PMID:Possible role of H2O2-mediated complement activation and cytokines-mediated fibroblasts superoxide generation on skin inflammation. 255 Feb 83

Culture supernatants of B cells from patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in the active stage enhanced interleukin 2 (IL-2) dependent proliferation of CTLL A/J cells. This activity, designated B cell-derived growth-enhancing factor-2 (BGEF-2), was recovered by gel filtration of a molecular weight between 15,000 and 20,000. BGEF-2 itself did not show IL-2 activity nor IL-1 activity, and BGEF-2 activity was not detected in the following cytokines: Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 6 (IL-6). Furthermore, BGEF-2 was distinguishable from B cell-derived growth-enhancing factor described in a previous paper [Kang et al. (1987) J. Immunol., 139, 1154-1160]. BGEF-2 was produced by B cells from patients with RA or SLE only when the patients were in the active stage. BGEF-2 enhanced IL-2-dependent growth of peripheral blood T cells from patients with active RA, but did not enhance the growth of T cells from healthy volunteers. These results suggest that BGEF-2 is a B cell-derived lymphokine which plays an important role in the pathogenesis of RA and SLE.
 ...
PMID:IL-2 enhancing factor(s) in B cell supernatants from patients with rheumatoid arthritis or systemic lupus erythematosus. 262 61

Antibodies that bind to endothelial cells have been identified in patients with diverse forms of vasculitis and thrombosis. Sera from patients with systemic lupus erythematosus contain both complement-fixing antibodies and immune complexes that bind to cultured endothelial cells. Sera from patients with heparin-associated thrombocytopenia and thrombosis contain antibodies that react with heparin bound to the endothelium and cross-react with heparan sulfate synthesized by endothelial cells. Children with Kawasaki syndrome may develop cytolytic IgM antibodies that recognize surface antigens induced on endothelial cells by interferon-gamma, interleukin 1, and tumor necrosis factor. The presence of alloantibodies to tissue-restricted polymorphic antigens expressed by endothelial cells is frequently associated with thrombotic microvascular injury and hyperacute allograft rejection. Binding of antibodies and immune complexes to endothelial cells in vitro initiates platelet adherence, production of tissue factor, and secretion of plasminogen activator inhibitor. Antibody-mediated endothelial cell injury may play a role in other vascular disorders of unknown cause.
 ...
PMID:Disorders associated with antibodies to endothelial cells. 266 9

We studied the effects of recombinant murine tumor necrosis factor-alpha (TNF-alpha) on autoimmune disease in lupus-prone NZB/NZW F1 (B/W) mice. Treatment with TNF-alpha, begun after the onset of clinical disease, improved survival relative to control mice: at age 10 months, 92% of mice treated with TNF-alpha were alive compared with 42% of control mice (P less than 0.05). Administration of TNF-alpha delayed the progression of renal disease, but sustained therapy did not prevent the eventual development of severe nephritis. Despite the improvement in survival, treatment with TNF-alpha did not inhibit anti-dsDNA antibody production. However, it accelerated T lymphocytopenia and abolished natural killer cell activity. These observations suggest that TNF-alpha may retard murine lupus in B/W mice through effects on cellular rather than humoral mechanisms. Our findings also indicate that the beneficial effects of TNF-alpha cannot be sustained indefinitely by chronic therapy.
 ...
PMID:Chronic therapy with recombinant tumor necrosis factor-alpha in autoimmune NZB/NZW F1 mice. 275 98


1 2 3 4 5 6 7 8 9 10 Next >>