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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
8307537 [Antiphlogistic effect of salicylic acid and its derivatives]. 1993 Nov 30 An overview of the literature on the effects of salicylic acid and its derivatives with particular consideration being given to their antiinflammatory properties is presented. While acetylsalicylic acid, in common with most non-steroidal anti-inflammatory drugs, has a marked inhibitory effect on cyclooxygenase in vitro, salicylic acid only weakly inhibits this enzyme. Animal inflammation models, however, have shown that the two substances are comparable in terms of efficacy. It is therefore assumed that the antiinflammatory properties of salicylic acid and its derivatives are also based on prostaglandin-independent mechanisms. Both salicylates and salicylic acid are used for topical applications. Their penetration into deeper tissue layers, as also their efficacy after local application have been demonstrated in both animal studies and clinical trials.
7488278 Double-blind, placebo-controlled multicenter trial using chimeric monoclonal anti-CD4 anti 1995 Nov OBJECTIVE: To evaluate the clinical response to and safety of single and repeat doses of a chimeric anti-CD4 monoclonal antibody, cM-T412, in patients with rheumatoid arthritis (RA) concomitantly treated with a stable regimen of low-dose methotrexate. METHODS: Sixty-four patients with refractory RA, who were already receiving stable doses of methotrexate, were randomized into a multicenter, double-blind, placebo-controlled trial to receive 3 monthly treatments with either a placebo, or 5, 10, or 50 mg cM-T412, given intravenously. RESULTS: Using > or = 50% improvement in swollen joint counts as a criterion for clinical response, 13%, 13%, 18%, and 13% of patients receiving 50, 10, or 5 mg cM-T412, or the placebo, respectively, exhibited a clinical response at 3 months of therapy. Using > or = 50% improvement in tender joint counts as a measure of clinical efficacy at 3 months, 19%, 13%, 12%, and 6% of patients receiving 50, 10, or 5 mg cM-T412, or the placebo, respectively, exhibited a clinical response. "Flu-like" symptoms (fever, chills, rigor) within 24 hours of the infusion occurred more frequently in the groups receiving 50-mg (29%) and 10-mg (31%) doses of cM-T412 than those receiving 5 mg cM-T412 (12%) or the placebo (13%). Significant CD4+ T cell depletion occurred in the 50-mg group (mean of 353 CD4+ T cells/mm3 at 6 months versus 856 CD4+ T cells/mm3 at baseline). All patients were followed up for 12 months after the final treatment; no opportunistic infectious complications occurred. CONCLUSION: Treatment with cM-T412 in this cohort of RA patients who were also taking methotrexate was not associated with clinical efficacy or enhanced toxicity from infectious complications, despite significant peripheral CD4+ T cell depletion.
7907547 Thrombo-embolic and vascular complications in vasculitis syndromes. 1993 Dec The vasculitides are relatively rare diseases characterized by inflammation and necrosis of vessel walls and, hence, often complicated by vascular and thromboembolic manifestations. The causes and pathogenesis of most vasculitides are only partially known. However, in many there are strong implications of both immune-complex and cell-mediated pathogenetic mechanisms. Tissue ischaemia, thrombosis as well as mediators and end-products of vascular endothelial inflammation are thought to cause most of the vasculitic manifestations. Thrombo-embolic and cardiovascular manifestations and complications are most commonly found in the vasculitides with necrotizing vascular inflammation, i.e. Behçet's disease, Buerger's disease, Kawasaki's syndrome, polyarteritis nodosa and vasculitis of rheumatoid arteritis. The granulomatous vasculitides are less frequently complicated by thrombo-embolic manifestations. Vasculitis may also be an iatrogenic complication of a therapeutic intervention, such as an IC-mediated hypersensitivity vasculitis after streptokinase treatment or an anti-endothelial cell antibody-associated coronary vasculitis after heart transplantation.
7897233 Analysis of clonal CD8+ T cell expansions in normal individuals and patients with rheumato 1995 Apr 1 In the course of studying the circulating TCR repertoire in humans, we noted several individuals with an increase in the percentage of CD8+ T cells expressing a particular V region. In some cases, these CD8 expansions were dramatic, occupying over 40% of the total CD8 repertoire. Using a panel of mAbs to different TCR V regions, we found that over 30% of healthy adults (> 35 years of age) harbor an expansion that alters the peripheral blood CD8 TCR repertoire. A wide range of V regions were expressed by these expansions. Considering that the mAbs used cover only a portion of the V beta repertoire, the data suggest that over 70% of adults are likely to harbor such expansions. Junctional region sequencing showed that the CD8 subset expansions were clonal, and serial studies as long as 4 years showed that they persisted indefinitely. Expansions were not identified in the CD4 population. Discordant expression of one large V beta 6.7+ clone was found in one identical twin set, suggesting the possibility that an environmental exposure is involved in their generation and/or expansion. In one large family, we found five family members with a large CD8 subset expansion. Remarkably similar usage of J beta regions was noted, and two individuals demonstrated V beta 3-expressing clones with homologous CDR3 regions, differing by only one major substitution. The repertoire data from this family suggest that the T cell clones have arisen in response to a common Ag. Studies of patients with rheumatoid arthritis found a significantly increased frequency of circulating CD8 subset expansions that expressed a different V region repertoire compared with the healthy individuals studied. Overall, our results emphasize a frequent alteration in the human CD8 TCR repertoire, most likely related to an environmental exposure, in both healthy individuals and patients with rheumatoid arthritis. The presence of these expansions will be important to consider in any study of human TCR repertoire, and their implication for health and disease will be important to understand.
8655724 Chrysiasis after low-dose gold and UV light exposure. 1996 Feb We describe a case of chrysiasis in a 54-year-old woman. The diagnosis was confirmed by light microscopy, transmission electron microscopy, and radiographic microanalysis. The condition developed after a relatively low dose of gold. We propose that chrysiasis developed because of the patient's exposure to the intense UV light in Australia.
8789287 Modulation of proinflammatory cytokine release in rheumatoid synovial membrane cell cultur 1995 Jul While there is an extensive literature on cytokine regulation in vivo using human cell lines or peripheral blood monocytes, very little is known about cytokine regulation within the multicellular environment of inflammatory sites in vivo. We have previously shown that in rheumatoid synovial membrane cultures, a complex, but pathophysiologically relevant mixture of cells, the addition of a neutralizing anti TNF-alpha antibody inhibits the production of IL-1 and GM-CSF, indicating the presence of a cytokine 'cascade' in this inflammatory tissue. In this paper we demonstrate that the interactivities between cytokines in rheumatoid arthritis also extends to other cytokines, such as IL-6 and IL-8, and that within the IL-1 family it is IL-1 beta in particular which is downregulated by neutralizing TNF-alpha activity. The cytokine interactions are unidirectional, in that neutralization of TNF-alpha reduced IL-1 beta, IL-6 and IL-8 production, whereas treatment of the rheumatoid synovial membrane cells with a neutralizing concentration of the IL-1 receptor antagonist (IL-1ra) reduced IL-6 and IL-8 production but not TNF-alpha production. These results suggest a rationale for the profound anti-inflammatory effects and consequent clinical benefit noted in RA patients treated recently in clinical trials with a chimeric anti-TNF-alpha antibody in vivo.
8588127 Sera from patients with systemic lupus erythematosus demonstrate enhanced IgG binding to e 1995 Fluorescence flow cytometry and indirect immunofluorescence were used to detect circulating IgG antiendothelial cell antibodies (IgG-AECA) in the sera of patients suffering from rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). Pretreatment of endothelial cells with tumour necrosis factor alpha (TNF alpha), but not with interferon gamma (IFN gamma), increased the IgG binding from sera of some patients with active SLE. In contrast, no change in binding activity to cytokine-stimulated endothelial cells was observed in the RA and PSS sera. The results of this study suggested that the enhanced binding of IgG from the sera of patients with SLE to endothelial cells stimulated with TNF alpha may be due to the ability of this cytokine to increase the expression of potential antigens on the surface of these cells. Hence, TNF alpha may play a role in the immune-mediated vascular damage associated with SLE.
7545382 Expression of CD44 on rheumatoid synovial fluid lymphocytes. 1995 Jul OBJECTIVES: To investigate the involvement of the adhesion molecule CD44 in the homing of lymphocytes to synovial tissue, by examining the density of expression and molecular mass of CD44 on rheumatoid synovial fluid lymphocytes. METHODS: Twenty patients with rheumatoid arthritis were studied. Peripheral blood and synovial fluid lymphocytes were isolated by Ficoll-Hypaque sedimentation. CD44 expression was analysed by two colour flow cytometry of CD3 positive T lymphocytes with calculation of mean fluorescence intensity. Expression of activation markers M21C5, M2B3, interleukin (IL)-2 receptor and transferrin receptor was quantitated. In addition, CD44 molecular mass was examined by Western blot in six patients. RESULTS: CD44 expression was markedly increased on synovial fluid T lymphocytes of rheumatoid patients relative to peripheral blood lymphocytes from the same individuals. CD44 molecular mass on peripheral blood mononuclear cells was 88 kDa, but that on synovial fluid lymphocytes was only 83 kDa. CD44 expression correlated significantly with expression of activation markers M21C5, M2B3, and the IL-2 receptor. CONCLUSIONS: Alterations in density of expression or of the molecular mass of CD44 could contribute to local tissue injury, either directly by facilitating adhesion, or indirectly through effects on other adhesion molecules.
1732419 Engagement of major histocompatibility complex class II molecules by superantigen induces 1992 Feb 1 Cells in the rheumatoid synovium express high levels of major histocompatibility complex (MHC) class II molecules in vivo. We have therefore examined the ability of engagement of MHC class II molecules by the superantigen Staphylococcal enterotoxin A (SEA) to activate interleukin 6 (IL-6) and IL-8 gene expression in type B synoviocytes isolated from patients with rheumatoid arthritis. SEA had a minimal or undetectable effect on the expression of either gene in resting synoviocytes, as determined by Northern blot and specific enzyme-linked immunosorbent assay. However, induction of MHC class II molecule expression after treatment of synoviocytes with interferon gamma (IFN-gamma) enabled the cells to respond to SEA in a dose-dependent manner, resulting in an increase in both the level of steady-state mRNA for IL-6 and IL-8, and the release of these cytokines into the supernatant. IFN-gamma by itself had no effect on the expression of either cytokine. Pretreatment of the cells with the transcription inhibitor actinomycin D prevented the increase in cytokine mRNA induced by SEA, whereas cycloheximide superinduced mRNA for both cytokines after stimulation by SEA. Taken together, these results indicate that signaling through MHC class II molecules may represent a novel mechanism by which inflammatory cytokine production is regulated in type B rheumatoid synoviocytes, and potentially provides insight into the manner by which superantigens may initiate and/or propagate autoimmune diseases.
7495341 Increased levels of serum IgM antibody to staphylococcal enterotoxin B in patients with rh 1995 Sep OBJECTIVE: To investigate the role of superantigen in rheumatoid arthritis (RA) by assaying the serum levels of staphylococcal enterotoxin B (SEB) antibodies. METHODS: Serum IgG and IgM SEB antibodies were measured using an enzyme linked immunosorbent assay (ELISA), and confirmed by Western blot analysis. The T cell receptor V beta (TCR V beta) repertoire was analysed using the reverse transcriptase polymerase chain reaction. RESULTS: RA patients had increased levels of serum IgM SEB antibody compared with normal subjects, patients with systemic lupus erythematosus, Sjögren's syndrome, and Behçet's disease. The titres of rheumatoid factor (RF) showed no correlation with the levels of IgM SEB antibodies, and the levels of SEB antibodies were not inhibited by the addition of human immunoglobulin, or after absorption of RF. RA patients whose disease duration was less than 10 years had greater levels of serum IgM SEB antibodies than those with disease duration more than 10 years. The levels of IgM and IgG SEB antibodies in synovial fluid from RA patients were correlated with those in their sera. Western blot analysis detected IgM and IgG SEB antibodies as a band of approximately 30 kDa molecular size. The percentage of TCR V beta 2, V beta 5.2, and V beta 12 in phytohaemagglutinin stimulated peripheral T cells correlated significantly with the levels of serum IgM SEB antibody in RA patients. CONCLUSION: These results suggest that SEB, one of the superantigens, may have a critical role in the pathogenesis of RA.
8467296 Craniomandibular disorders in the geriatric patient. 1993 Winter This paper represents a general review of basic age-related changes that take place in the craniomandibular apparatus and the most frequently presenting conditions associated with craniomandibular disorders (CMD) in the elderly. The evaluation of geriatric patients with signs or symptoms of CMD must consider (1) normal age-related changes in the craniomandibular apparatus and their impact on both normal function and responses to stress; (2) the role of dentition status and dental prosthesis in CMD; and (3) the contribution of malignant disease, psoriasis, arthritic conditions, pseudogout, granulomatous vascular conditions, and metaplastic involvement of tissue to the pathosis of CMD. The clinician must also be aware of various effects of psychologic, sociologic, and biologic aspects of aging on the development of headache and atypical facial pain as components of CMD in the geriatric patient.
7589506 Bimodal distribution of proteinase 3 (PR3) surface expression reflects a constitutive hete 1995 Oct 23 Proteinase 3, which is known as an intracellular serine protease of neutrophils, was detected at the surface of a subpopulation of freshly isolated PMN. The proportion of PR3-positive and -negative PMN, observed by flow cytometry with anti-PR3 mAbs or ANCA autoantibodies, varies among individuals but is extremely stable for each individual over prolonged time periods. After PMN degranulation by FMLP with cyt. B, membrane PR3 expression increases but the proportion of low and high PR3-expressing cells remains stable. The existence of a subset of PMN which spontaneously expresses PR3 and varies among individuals, may be relevant to the pathogenesis of anti-PR3 ANCA autoantibody-related vasculitis.
7599436 Synovial and peritoneal macrophages in organoid culture. 1995 Apr Cultivation of macrophages and their progenitors has been very useful for elucidation of function, behaviour and morphology of these cells. The purpose of this contribution is to describe a new in vitro system (organoid, high density or micromass culture) which proved to be convenient for cultivation of macrophages derived from human synovial fluid and tissue and mouse peritoneal fluid. Using this method, highly differentiated and functionally active macrophages of marked purity and long maintenance (up to 2 weeks) could be obtained even after previous cultivation and subcultivation in monolayer culture. The macrophages were identified by electron microscopy and immunomorphology using HLA-DR-DP, CD-68 (markers for human macrophages), anti-human-polymorphonuclear leukocyte-gelatinase and F4/80 (a mouse macrophage surface marker). The significance of this method as a research tool in the study of cartilage degradation by macrophages in co-cultures is stressed.
1299712 Use of a different buffer system in the phenolic glycolipid-I ELISA. 1992 Dec By changing the buffer system in the phenolic glycolipid-I (PGL-I) enzyme-linked immunosorbent assay (ELISA) the sensitivity of the test was increased without altering its specificity. Using a Tris-HCl buffer, significant titers of > or = 1:300 were found in 53.1% of the sera in paucibacillary (PB) and 98.0% of the sera in multibacillary (MB) groups of patients. Titer levels were also significantly increased. In the PB group of patients with Tris-HCl, the highest titer detected was 1:1200; in the MB group of patients, 1:76,800. Through this modification of the buffer system a more sensitive test was obtained thereby increasing the detectable level of PGL-I antibodies in both the PB and MB groups of patients.
1474533 Clinical efficacy and safety of nabumetone in rheumatoid arthritis and osteoarthritis. 1992 Nov The efficacy and safety of nabumetone were evaluated in short term (up to 6 months), double blind, comparative trials and a longterm (up to 8 years), open label, noncomparative trial. In the short term trials, nabumetone was determined to be significantly more effective than placebo and as effective as naproxen and aspirin. The most common adverse effects that occurred were related to the gastrointestinal tract, nervous system, skin, and special senses. In the longterm trial, nabumetone was effective in 62% of patients, without complicating effects, for at least 1 year. This beneficial response was maintained in a fair percentage of patients for up to 5 years or more. The average treatment duration before withdrawal was at least 1.1 years. Therefore, most patients in the longterm trials experienced a beneficial response for a significant duration of therapy.
8149741 Comparison of the proteoglycanolytic activities of human leukocyte elastase and human cath 1993 In this study, we evaluated the in vitro and in vivo potency of human leukocyte elastase (HLE) and human cathepsin G (HCG) as proteoglycanases. In vitro evaluation was done using bovine nasal septum aggrecan and aggrecan/hyaluronan aggregate as substrates. Enzyme activity was assessed by the ability of the proteinases to abrogate the ability of aggrecan to aggregate with hyaluronan. In vivo activity of the proteinases was tested by injecting purified HLE and HCG intra-articularly into rabbit stifle joints and quantifying the levels of proteoglycan released into synovial fluids. On a molar basis, HCG was at least tenfold more potent than HLE as a proteoglycanase in vitro. Moreover, HCG was twofold more potent as a proteoglycanase in vivo. In contrast, HLE hydrolyzed elastin approximately 22-fold faster than HCG, but was only slightly more rapid than HCG when [3H]-transferrin was used as substrate. These data indicate that HCG is more potent than HLE as a proteoglycanase both in vitro and in vivo. Thus, HCG could be more important in the pathogenesis of rheumatoid arthritis than previously suspected.
8645252 An allel-specific abnormal transcript of the heat shock protein 70 gene in patients with m 1996 Feb 27 Stress-inducible 72-kDa heat shock proteins (HSP70) were encoded on genes in multiple chromosomes. The expression of mRNA transcribed from the gene (HSP70-1) on chromosome 6 was studied using reverse transcript polymerase chain reaction in peripheral blood mononuclear cells of patients with different diseases. The deletion of 29 bp occurred in 5' noncoding and subsequent 133 bp in coding sequences of HSP70 mRNA in patients with major depression (n = 18), while normal subjects (n = 10) and patients with schizophrenia (n = 5), essential hypertension (n = 3), rheumatoid arthritis (n = 7), and Graves' disease (n = 3) had normal mRNA. No such deletion occurred in genomic DNA and no protein was translated from deleted mRNA. The allel-specific abnormal transcript of the HSP70 gene on chromosome 6 thus may underlie the altered stress and/or immune response in major depression.
7562767 Monocyte-macrophage antigen expression on chondrocytes. 1995 Jul OBJECTIVE: To characterize chondrocytes in normal and arthritic joints and compare their phenotype to that of synovial macrophages present in rheumatoid joints. METHODS: Using an immunoperoxidase staining technique, we examined the presence and distribution of a number of leukocyte activation and differentiation antigens on samples of cartilage obtained from resected joints of normal controls and subjects with rheumatoid arthritis or osteoarthritis. RESULTS: Chondrocytes in each group were CD14+, CD68+, Thy-1+, CD11a+, CD18+, MAX.3-, and MAX.24-. Staining was variable for MAX.1 and CD45. HLA-DR and CD71 were expressed only on cells located in the superficial layer of rheumatoid cartilage. We found lower levels of expression of CD14 on chondrocytes in arthritic joints, whereas CD58 was expressed at higher levels. Surface expression of CD14 was confirmed on normal chondrocytes using flow cytometry and further supported by the detection of CD14 mRNA by polymerase chain reaction. CONCLUSION: Our findings demonstrate that chondrocytes express several antigens that are also found on monocytes and macrophages.
8934315 Relationship between polyethylene wear, pelvic osteolysis, and clinical symptomatology in 1996 Oct The purpose of this study is to assess the relationship between acetabular component polyethylene wear, pelvic osteolysis, and clinical symptoms to determine when operative intervention should occur and to predict the degree of difficulty of the revision. Fifty-four revisions of failed cementless acetabular components were performed in 52 patients. All cases demonstrated polyethylene wear radiographically, and in 43 cases (80%), osteolysis of the pelvis was seen. Symptoms of groin or buttock pain were seen in 45 of 54 cases (83%). Preoperative staging of the disease process included one patient with wear radiographically but neither symptoms nor lysis (stage I), 10 patients with wear and pain (stage IIA), 8 patients with wear and lysis but no pain (stage IIB), and 35 patients with wear, lysis, and pain (stage III). Patients in stages I and IIA could be revised with cementless components without structural allograft. Patients in stages IIB and III required structural allograft in 79% and cemented components in 53%. Cemented components were used when there was less than 50% contact between host-bone and prosthesis. Polyethylene wear alone (stage I) is an indication of impending failure, and when symptoms develop (stage IIA), revision should be undertaken. The development of radiographic lysis is a critical event, and as soon as osteolysis develops (stage IIB or III), revision should be undertaken immediately. From the perspective of the revision surgeon, there is great value in the early intervention for polyethylene wear and pelvic osteolysis.
1516259 Agalactosyl IgG in pristane-induced arthritis. Pregnancy affects the incidence and severit 1992 Sep The effect of pregnancy on the incidence and severity of pristane-induced arthritis was examined along with the glycosylation status of IgG during the ante-natal and post-partum periods. It was found that pristane-induced arthritis is prevented by pregnancy. In addition, the levels of agalactosyl IgG fall during pregnancy but rise to greater than normal within a few days of parturition, before resetting towards the norm shortly afterwards. Interestingly, the level of agalactosyl IgG correlates with the severity of arthritis. As previously reported IL-6 may be an important factor, not necessarily the only one, in the production of agalactosyl IgG. Here it is clearly demonstrated that the kinetics of IL-6 activity post-pristane injection parallels the kinetics of agalactosyl IgG production. In addition, the overshoot in agalactosyl IgG levels immediately post-partum coincides with a burst in IL-6 activity. It is considered that these changes in IgG glycoform levels, or the factors which control them, may be related to the mechanisms underlying prevention/remission of arthritis during pregnancy.