Browse

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

ID PMID Title PublicationDate abstract
1535616 Interleukin-1 receptor antagonist (IL-1ra) as a probe and as a treatment for IL-1 mediated 1992 Apr The natural human IL-1 receptor antagonist (IL-1ra) has been produced in a recombinant organism and has been used to study IL-1 action in vivo. The receptor antagonist mitigates the pathophysiology associated with animal models of ulcerative colitis through reducing IL-1 mediated neutrophil recruitment into the affected tissue. It also reduces joint swelling and damage in an animal model of rheumatoid arthritis, possibly by reducing IL-1 mediated synthesis of proteases by the synovial fibroblasts and chondrocytes of the joint. The receptor antagonist is not immunosuppressive in rodents, indicating that it is working by blocking the inflammatory reaction rather than any underlying defect in specific immunity.
1471433 ["Mobile occupational therapy" for rheumatic patients: development of the service, utiliza 1992 The development and utilization of occupational therapy as a home care service for patients with rheumatic diseases is examined. This new service was implemented in Schleswig-Holstein by local branch of the German League against Rheumatism, an organization devoted to the promotion of help and self-help for patients. The data for this study are based on standardized documentations within a comprehensive evaluation of model-intervention, and also accounting records. From July 1, 1986 until June 31, 1991, there were 1120 prescriptions issued by 293 physicians at 86 locations. 529 patients could be served with a total amount of 6778 time-units of care. The development of the service shows a slowly but steady and region wide growing acceptance by the practitioners and, accordingly, an increasing utilization associated with an increasing inclusion of non-rheumatic diagnoses. The supplies of support devices (included in 55% of all prescriptions) and braces (included in 26% of all prescriptions) are described separately, since patient counseling and assistance--particularly in connection with support devices and aids for everyday life--are of great importance.
8610477 Agranulocytosis in rheumatoid arthritis associated with long-term flucloxacillin for staph 1995 Agranulocytosis and septicaemia developing in a patient with rheumatoid arthritis after 3 years' intermittent treatment with diclofenac, cimetidine and flucloxacillin for staphylococcal osteomyelitis is described. Treatment with recombinant granulocyte-colony-stimulating factor and high-dose methylprednisolone had no effect on the neutropenia which resolved on stopping all drug therapy. Relapse of agranulocytosis followed reintroduction of flucloxacillin and cimetidine 3 months later.
7993713 Infectious arthropathies and other rheumatologic manifestations of infectious diseases. 1994 Sep Infectious agents have been implicated in the pathogenesis of many rheumatologic diseases. In most of these diseases, including those in which specific organisms are known to play a role, the details of pathogenesis remain incompletely defined. Recent studies have aimed to isolate bacterial and viral pathogens from patients with rheumatic diseases, efforts have been made to further define the host immune response to infection, and there have been attempts to develop improved methods of diagnosis and treatment of infectious diseases affecting the musculoskeletal system. This review discusses recent studies on the association of infection with illnesses affecting the joints and musculoskeletal system, with an emphasis on the rheumatic diseases of childhood.
1642652 Comparison of azathioprine, methotrexate, and the combination of both in the treatment of 1992 Aug OBJECTIVE: To compare the relative safety and efficacy of azathioprine (AZA), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). METHODS: Two hundred twelve patients with active RA were entered into a 24-week prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. RESULTS: One hundred fifty-eight patients finished 24 weeks of the study. There were no remissions seen but response rates were greater than 30% for all outcome measures. Combination therapy was not statistically superior to MTX therapy alone, but both combination therapy and MTX alone were superior to AZA alone when patients were analyzed by intent-to-treat and with withdrawals treated as therapy failures. If only patients who continued taking the therapy were analyzed, the mean improvement was greater for AZA therapy than for MTX, while the combination remained the most active. Adverse effects on the gastrointestinal tract and elevations of liver enzyme levels were the most frequent causes for discontinuations. CONCLUSION: Both combination therapy and MTX alone were superior to therapy with AZA alone for active RA but were not statistically different in their effect on outcome assessment.
1352152 The effect of cytokines on the expression of MHC antigens and ICAM-1 by normal and transfo 1992 We report the expression on synovial cells of cell surface molecules known to be involved in T cell activation by antigen presenting cells. Normal human synovial fibroblasts and a human synovial cell line transformed with the SV40 large T antigen were used for in vitro stimulation studies with recombinant cytokines. We demonstrate an increase in MHC-A, B, C expression in normal synovial cells in response to recombinant interferon gamma (r gamma IFN), tumour necrosis factor alpha and beta (rTNF alpha and beta) and interleukin-1 (rIL-1 alpha). Intercellular adhesion molecular-1 (ICAM-1) expression was increased in parallel with MHC Class I. The combination of r gamma IFN and rTNF alpha was additive in its effect on ICAM-1 expression. Northern blot analysis suggests that ICAM-1 expression in synovial cells is controlled at the level of transcription. In contrast, MHC Class II (HLA-DR) was only significantly induced by r gamma IFN. Other stimuli including interleukin-4 (IL-4), interleukin 6 (IL-6), granulocyte macrophage colony stimulating factor (GM-CSF) and prostaglandin E2 (PGE2) did not affect the expression of ICAM-1 or MHC Class I and II. Leucocyte function antigen 3 (LFA-3) expression was not affected by any of the stimuli tested. Immunoperoxidase staining of rheumatoid synovial tissue confirmed enhanced in vivo expression of ICAM-1 in rheumatoid arthritis. These changes are discussed in the context of T cell activation in inflammatory arthritis.
1430951 Limited arthrodesis for the rheumatoid wrist. 1992 Nov Limited arthrodesis of the proximal carpal row to the radius, synovectomy of the extensor tendons and the wrist joint, and a Darrach procedure were carried out in 25 unstable painful rheumatoid wrists that had ulnar shift and/or palmar subluxation of the carpus. The average follow-up period after the operation was 3 years. Satisfactory results were obtained with relief of pain, improved forearm rotation, and increased grip strength. The average degree of extension and flexion was reduced, respectively, 70% and 54% at follow-up compared with the preoperative range. Postoperative x-ray films showed deterioration in the lunocapitate joint in 12 wrists; however, the wrists remained stable and painless.
8670605 Unusual complications of cervical spine surgery for cervical myelopathy in rheumatoid arth 1996 Jul Cervical myelopathy is a recognized complication of rheumatoid arthritis and other inflammatory arthropathies. In a significant proportion of patients, surgical stabilization of the cervical spine offers the best opportunity for improvement of symptoms and long-term survival. We report two cases that illustrate some potential complications of cervical spine surgery and which also emphasize the need for vigilance when caring for patients in this group.
7516774 Adhesion molecules in the lymphoid cell distribution in rheumatoid synovial membrane. 1993 Summer The staining pattern of a group of adhesion molecules on the immunoreactive cells in the lining layer of lymphocytic infiltrates of the rheumatoid synovial membrane was studied, using monoclonal antibodies by immunoperoxidase staining method against LFA-1, VLA-4, VLA-5, ELAM-1, and ICAM-1. The cells of the lining layer were strongly ICAM-1+ and VLA-5+, suggesting (1) that ICAM-1 may function to facilitate the adhesion of ICAM-1 bearing type A cells to type B cells, and (2) that the lining cells may utilize VLA-5 for anchorage to fibronectin at the surface of the synovial membrane. In the lymphocyte-rich and transitional area, the endothelial cells of the postcapillary venules were both ELAM-1+ and ICAM-1+. ICAM-1 staining of mononuclear cells was weak in lymphoid aggregates, but strong in the transitional area, indicating a paucity of ICAM-1 bearing cells in the lymphocyte-rich areas. On the other hand, LFA-1 staining was very strong in the lymphoid aggregates and only moderate in transitional areas. This suggests that the large numbers of T4 cells in the lymphocyte rich areas are sufficiently activated to express substantial levels of LFA-1, and also that the LFA-1 molecule is an important receptor for emigration from postcapillary venules. In germinal center-like areas in lymphoid aggregates, most of the cells stained strongly for ICAM-1 and VLA-4, suggesting that the proliferation of B lymphocytes may be facilitated by LFA-1 and VLA-4 dependent T and B cell interaction. The VLA molecules stained in the transitional areas may provide appropriate adhesion and anchorage for the achievement of the variety of immune reactions which occur in these areas.
1281104 Noradrenergic and peptidergic innervation of secondary lymphoid organs: role in experiment 1992 Oct Noradrenergic (NA) and peptidergic nerve fibres are present in both primary and secondary lymphoid organs, distributing with the vasculature, trabecular and capsular smooth muscle, and within the parenchyma among cells of the immune system. NA nerve terminals directly abut lymphocytes and macrophages in spleen and lymph nodes. In these organs, norepinephrine has fulfilled the basic criteria for neurotransmission with cells of the immune system as targets. In vitro and in vivo studies have demonstrated NA modulation of primary and secondary antibody responses, cytotoxic T cell responses, natural killer cell activity, and proliferation and differentiation of both T and B lymphocytes. Substance P (SP) has been shown to modulate inflammatory responses, lymphocyte proliferation, and other immunologic reactivity. We investigated the role of NA and SP nerve fibres within lymph nodes in experimental allergic auto-immune arthritis in Lewis rats. Denervation of NA nerve fibres in popliteal and inguinal lymph nodes with 6-hydroxy-dopamine resulted in earlier onset and enhanced severity of arthritic changes as well as inflammation in bilaterally induced experimental arthritis, while denervation of SP nerve fibres in popliteal and inguinal lymph nodes with capsaicin resulted in delayed onset and diminished severity of the inflammatory changes ipsilaterally, and prevention of contralateral arthritic changes in unilaterally induced experimental arthritis. These findings suggest that NA and SP nerve fibres in lymph nodes can modulate the time course of onset and the severity of experimental arthritis in Lewis rats. These modulatory effects are distinctly different from the effects of NA and SP nerve fibres in the joints themselves.
1461781 [Rheumatic fever from 1960's to 1990's. Case records in 2 hospitals of the Lombardian area 1992 Jul An epidemiological study of rheumatic fever (RF) has been done. Incidence and prevalence of RF observed in Monza Hospital from 1964 to 1990 and in Como Hospital from 1980 to 1990 both show a progressive reduction. An exception to this trend was observed in 1986 in Monza in 1985 in Como. The percentage of carditis in pediatric age is high (60-70%), often associated with arthritis and chorea. However carditis clinical picture seems nowadays less severe, probably because in the past the diagnosis was delayed. Sice 1980 no death were observed due to RF or related cardiac involvement. Relapses and residual valvulopathies are significantly reduced only when penicillin prophylaxis was correctly performed.
8299714 Interleukin-1 and transforming growth factor-alpha: synergistic stimulation of metalloprot 1994 Feb Wound healing and other inflammatory processes are driven by a complex series of interactions among cells, the extracellular matrix, and secreted products of various cell types. Cytokines, such as interleukin-1 and transforming growth factor-alpha, are present at wound sites and contribute to the proinflammatory milieu of these sites. In the present study, we have investigated the effect of these cytokines, individually and in concert, on fibroblast expression of matrix metalloproteinases, which contribute to extracellular matrix remodeling, and of prostaglandin E2, which alters vascular tone and permeability. The metalloproteinases, procollagenase (matrix metalloproteinase-1) and prostromelysin (matrix metalloproteinase-3), are induced by exposure of dermal fibroblasts to interleukin-1, not stimulated by transforming growth factor-alpha, but are synergistically induced by the combination of cytokines. The 92-kDa type IV procollagenase (matrix metalloproteinase-9, progelatinase B), is also stimulated in synergistic fashion. Prostaglandin E2 is induced in rheumatoid synovial fibroblasts by interleukin-1 beta, not altered by transforming growth factor-alpha, and is synergistically released by the combination of the two cytokines. Fibroblast proliferation, which is also a component of normal wound healing, is also synergistically stimulated by the action of the two cytokines in concert. These results indicate that interleukin-1 beta and transforming growth factor-alpha synergize to elicit a number of phenotypic responses in fibroblasts which are relevant to normal wound healing and chronic inflammation.
7612033 End-stage liver disease developing with the use of methotrexate in heterozygous alpha 1-an 1995 Jul We report a case of cirrhosis developing in a man who was heterozygous for alpha 1-antitrypsin deficiency and who was receiving methotrexate for severe rheumatoid arthritis. The alpha 1-antitrypsin phenotype PiMZ has been associated with cryptogenic cirrhosis. Our patient had no biochemical or histologic evidence of chronic liver disease during the first year of receiving methotrexate. We postulate that the PiMZ state may result in enhanced susceptibility to methotrexate-induced hepatic toxicity and should be screened for if liver function abnormalities occur during methotrexate therapy.
8427516 Impact of disablement due to rheumatic disorders in a British population: estimates of sev 1993 Jan A survey of rheumatic disablement in the population has enabled the comparative impact of self reported causes of disability to be studied. One in three households in Calderdale, West Yorkshire, United Kingdom was screened in 1986 with a postal questionnaire (87% response rate), followed by in depth interviews with a sample of subjects reporting disability in conjunction with a rheumatic disorder (608 interviews). Severity of disablement was assessed using the physical independence handicap classification. The estimated prevalence of disability in conjunction with reported rheumatic disorders is 82/1000 population aged at least 16 years (95% confidence interval (CI) 77 to 87). Arthritis (mainly osteoarthritis) is the most commonly reported cause (47/1000 population; 95% CI 43 to 51), followed by back or neck disorders (25/1000; 95% CI 23 to 28), soft tissue disorders (18/1000; 95% CI 15 to 20), and rheumatoid arthritis (RA) (4/1000; 95% CI 3 to 5). A total of 30% reported more than one category of rheumatic disorder (mean number 1.3) and 63% reported non-rheumatic comorbidity. Current joint symptoms were reported by 98%, current antirheumatic drugs (including analgesics) by 70%, and severe pain by 62%. Overall 82% of subjects had seen their general practitioner in the past year, and 71% reported having attended an outpatient clinic; 26% reported current outpatient clinic attendance, and 15% a hospital inpatient stay during the previous year. Forty six per cent reported some dependence, with 12% reporting being dependent on a daily basis. Rheumatoid arthritis was the most disabling disorder with 73% dependent. Taking into account prevalence, osteoarthritis and back disorders are the most, and RA the least, common causes of dependence and incapacitating pain in the population. This challenges stereotypes and raises questions about the organisation and priorities for specialist services and for research.
8356999 Efficacy of nabumetone versus diclofenac, naproxen, ibuprofen, and piroxicam in osteoarthr 1993 Aug 9 The efficacy of nabumetone was compared with that of diclofenac, naproxen, ibuprofen, and piroxicam in patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in a randomized, controlled, open-label, multicenter trial. Patients > or = 18 years with clinical and radiographic evidence of OA or RA (functional class I, II, or III), who provided written informed consent, were eligible. To mimic real-life therapy, no washout phase preceded randomization. Eligible patients were assigned in a 3:1 ratio to receive nabumetone or a comparator NSAID for 12 weeks. Thus a total of 4,411 eligible patients were randomized to receive nabumetone (N = 3,315) or one of the comparator NSAIDs (N = 1,096). Initial daily doses were: nabumetone, 1,000 mg; diclofenac, 100 mg; naproxen, 500 mg; ibuprofen, 1,200 mg; piroxicam, 10 mg. Dosage increases were permitted after a 2-week trial period. All patients were evaluated at baseline, and at 4 and 12 weeks. Of all patients randomized, approximately 46% had RA and approximately 54% had OA. Demographic characteristics were similar for the nabumetone and comparator NSAID treatment groups. In OA, nabumetone was as effective as the comparator NSAIDs in the physician and patient global assessments of disease activity, in improving the Activities and Lifestyle Index, and in decreasing the degree of pain. There was no significant difference in the percentage of patients withdrawn for lack of efficacy when treated with nabumetone or one of the comparator NSAIDs. In contrast, nabumetone was significantly (p < or = 0.02) more effective than the comparator NSAIDs in RA patients for the global assessments of disease activity, pain relief, and improving the Activities and Lifestyle Index, primarily due to the poor response in the ibuprofen and piroxicam treatment groups. Furthermore, fewer nabumetone-treated RA patients (8.8%) withdrew for lack of efficacy than those treated with diclofenac (10.3%), naproxen (11%), piroxicam (13.5%), or ibuprofen (13.2%). In conclusion, in a large, randomized, open-label trial that mimicked real-life therapy, nabumetone was as effective as diclofenac, naproxen, piroxicam, and ibuprofen for the treatment of patients with OA. However, in RA, nabumetone was significantly more effective than the comparator NSAIDs, and fewer patients were withdrawn because of lack of efficacy.
8296641 ANCA with specificity for lactoferrin in systemic lupus erythematosus (SLE). 1993 Antibodies to lactoferrin were detected in about 20% of patients with SLE, irrespective of the presence of renal involvement and in 10% of patients with rheumatoid arthritis and in 19% of patients with scleroderma. We conclude that anti-lactoferrin antibodies may be found in different types of connective tissue disease. Their clinical significance in these diseases however remains to be elucidated.
8407906 Plasminogen activation stimulates an increase in intracellular calcium in human synovial f 1993 Oct 5 Both plasminogen (Pg) and urinary-type Pg activator (u-PA), but not tissue-type Pg activator (t-PA), bind to normal and rheumatoid arthritis (RA) human synovial fibroblasts in culture with high affinity and in a dose-dependent manner. Single cell intracellular Ca2+ responses to Pg and u-PA were studied using Fura-2 and digital imaging fluorescence microscopy. Pg activation by u-PA on the surface of RA synovial fibroblasts induces a significant rise in cytosolic free Ca2+ concentration ([Ca2+]i) within 90 s. Pg kringle 4 and the alpha 2,3-linked sialic acid in the carbohydrate chain bound to Thr245 are involved in mediating the increases in [Ca2+]i. This response is not observed in normal synovial fibroblasts, suggesting that RA synovial fibroblasts have altered responses to the binding and activation of Pg on their surfaces.
1320571 Enhanced expression of tumor necrosis factor receptor mRNA and protein in mononuclear cell 1992 Jul We previously proposed the hypothesis that the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) based on our observations that it is the dominant inducer of interleukin-1 (IL-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) production in RA synovial joint mononuclear (MNC) cells in culture. Since TNF-alpha acts via two membrane receptors, we have extended those studies to investigate the distribution of the p55 and p75 TNF receptors (TNF-R) in RA tissue. Surface receptor expression was quantitated by flow cytometry using monoclonal antibodies specific to the p55 (HTR-9) and the p75 (UTR-1) TNF-R. Both receptors were significantly increased on MNC isolated from the synovial membrane of RA patients compared to normal or RA peripheral blood MNC. Interestingly, the p75 TNF-R was increased both on large monocytic/macrophage-type cells and CD3+ lymphocytes. Furthermore, there was a significant increase in the proportion of CD3+ cells in RA synovial fluid expressing the p75 TNF-R, compared to matched peripheral blood MNC. In contrast to RA synovial MNC, p75 or p55 TNF-R expression was not significantly increased in osteoarthritis synovial MNC. In addition, Northern blot analysis indicated abundant expression of both p55 and p75 mRNA in RA synovial joint MNC. This was in contrast to normal peripheral blood MNC cells which contained little or no constitutive TNF-R mRNA; following stimulation with phytohemagglutinin and IL-2, a rapid and transient expression of both receptor mRNA was induced. These results, therefore, indicate that in RA synovial joint tissue there is up-regulation of both p55 and p75 TNF-R mRNA and surface protein expression, and with the presence of TNF-alpha in RA tissues, these results provide support to our hypothesis that TNF-alpha is of critical importance in the pathogenesis of RA.
1572405 Characterization and immunolocalization of a nucleolar antigen with anti-NOR serum in HeLa 1992 Jun We have used a serum from a patient with rheumatoid arthritis and found it to immunoblot with a 92- to 88-kDa protein doublet with an isoelectric point of around 7.5 after mono- and two-dimensional electrophoresis in whole HeLa cells. By means of immunofluorescence and immunoelectron microscopy we have found it to specifically react with the nucleolar fibrillar component. After quantitative analysis under the electron microscope, we have demonstrated a similar labeling both in the fibrillar centers and the dense fibrillar component, using two different gold-coupled markers. When transcription was inhibited under physiological conditions (mitosis) or after AMD treatment the antigen remained, as shown by immunoblotting and immunolabeling with anti-NOR serum. These biochemical characteristics, which coincide with those of the ribosomal transcription human upstream binding factor, together with the immunolocalization with anti-NOR serum, allow us to discuss the possible role of these antigens in rDNA transcription.
8800342 Multiple sclerosis and chronic inflammatory diseases. A case-control study. 1996 May INTRODUCTION: Disease associations may provide useful etiological leads in relation to diseases of unknown cause. MATERIAL AND METHODS: We conducted a hospital-based case-control study of 155 MS patients and 200 controls in Hordaland County, Norway to investigate the possible association between MS and autoimmune diseases. RESULTS: The MS patients had a statistically significant more frequent coexistence of rheumatoid arthritis, psoriasis, and goitre when compared to the controls (OR = 2.96; 95% CI 1.23-7.66). This difference persisted when analysing the definite MS cases separately (OR = 2.90; 95% CI 1.10-7.96). The familial occurrence of chronic inflammatory diseases was not significantly different in cases and controls. A significant increased risk to develop MS occurred in first degree relatives of MS patients (OR = 12.58; 95% CI 1.73-552). CONCLUSION: Acknowledging the low figures, the uncertain estimates with large confidence intervals, and thus the obvious role of chance in this study, the results might indicate that a generalized, genetically controlled problem of the immune system could result in aggregates of the reported diseases, all of which are partly characterized by aberrations of the immune system.