Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8448621 | Polyautoimmunity in a young woman. | 1993 Mar | A young woman with the HLA phenotype A1, A2, B5, B8, DR3, DR4 developed RA, idiopathic thrombocytopenic purpura (ITP), pernicious anaemia (PA), Hashimoto's thyroiditis (HT), systemic sclerosis (SS), pancreatic exocrine insufficiency (PEI) and coeliac disease (CD) before dying from vasculitic complications. A family study revealed RA, PA and insulin-dependent diabetes mellitus (IDDM) amongst her first degree relatives. Her case emphasizes the clinical and immunogenetic links between the autoimmune diseases. | |
| 8923355 | Recombinant soluble tumor necrosis factor receptor (p80) fusion protein: toxicity and dose | 1996 Nov | OBJECTIVE: To determine the safety and pharmacokinetics of recombinant human tumor necrosis factor receptor (p80) fusion protein (rhTNFR:Fc) administered as a single intravenous (iv) loading dose followed by subcutaneous (sc) maintenance injections twice weekly for one month in patients with refractory rheumatoid arthritis (RA). METHODS: Four dose groups were evaluated with 4 patients with RA per group: 3 received active drug and one received placebo injection. After each dose group completed 4 weeks of treatment, the patient who received placebo was allowed to receive the active drug for one month. After these 16 patients completed the study, 3 additional patients received the highest dose and 3 additional patients received the lowest dose in an open label study to obtain more safety data (total of 22 patients treated). RESULTS: There were no serious adverse effects. Drug related events include mild injection site reactions in 4 patients that did not necessitate discontinuation of the drug. There was no clearcut dose response among the treatment groups. At Week 4, there was 45% mean improvement in total pain and total joint scores in patients receiving active drug (n = 12), compared to 22% mean improvement in patients receiving placebo (n = 4). C-reactive protein (CRP) levels decreased substantially in patients treated with drug compared to placebo, 30 vs 13%, respectively. The decrease in CRP was most pronounced in the highest dose group. CONCLUSION: This initial experience with rhTNFR:Fc fusion protein in RA justifies further evaluation of this agent in a larger placebo controlled trial. | |
| 8031999 | Monocyte chemoattractant protein 1 and interleukin 8 production by rheumatoid synoviocytes | 1994 Mar | Activated synoviocytes are major effector cells in the pathogenesis of rheumatoid arthritis (RA) because of their capacity to secrete a variety of inflammatory mediators. Among these mediators, the chemotactic proteins monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8) are likely to contribute to the recruitment of inflammatory cells into the arthritic joint. We examined the effects of anti-rheumatic drugs on the MCP-1 and IL-8 production by cultured RA synoviocytes exposed to pro-inflammatory agonists. Both chemotactic cytokines were quantified by specific enzyme-linked immunosorbent assays (ELISA), and found to accumulate in the culture supernatants. Although the time course of formation was similar, the yield of IL-8 was three to 10-fold higher than that of MCP-1. Non-steroidal anti-inflammatory drugs inhibited the synthesis of prostaglandins, but did not influence the production and release of both chemotactic cytokines. Of three disease-modifying drugs tested, dexamethasone and gold sodium thiomalate (GST) inhibited the production of IL-8 and MCP-1, while methotrexate (MTX) was inactive. Dexamethasone reduced the production of MCP-1 and IL-8 by 20-65% and 60-80%, respectively, whilst GST inhibited MCP-1 and IL-8 synthesis in suboptimally, but not in optimally stimulated synoviocytes. Taken together, these results show that the production of MCP-1 and IL-8 is similarly affected by anti-rheumatic drugs and that dexamethasone is the most potent inhibitor suggesting that part of the anti-rheumatic action of glucocorticoids is due to prevention of accumulation of chemotactic cytokines acting on neutrophils and monocytes. | |
| 7965376 | [Efficacy of tonsillectomy for improving skin lesions of Pustulosis palmaris et plantaris- | 1994 Sep | In recent years, Pustulosis palmaris et plantaris (PPP) has been described as one of the representative second lesions of focal tonsillitis in Japan. We selected 289 cases of PPP, treated with bilateral tonsillectomy at our department over the past 12 years for this clinical evaluation. In 211 of those 289 tonsillectomy cases, follow-up was done for more than 3 months after operation. Prior to tonsillectomy, 196 cases suffered from PPP only, 90 cases had the complication of osteo-arthral lesions such as sterno-costa-clavicular hyperosteosis (SCCH), rheumatoid arthritis, and soon, whereas only 3 cases showed simultaneous lesions of Psoriasis vulgaris. The efficacy of tonsillectomy for improving the skin lesions was classified into 6 grades, mainly based upon individual evaluation by each patient as follows; disappeared, remarkably improved, improved, slightly improved, unchanged, and worsened. According to our 211 cases, post tonsillectomy improvement of skin lesions was very obvious, with disappearance occurring in 54.3% of cases and remarkable improvement in 21.4%. Age of onset and the duration from onset to tonsillectomy showed no association with effectiveness. However, the shorter the duration from onset to tonsillectomy, the fewer days were required for improvement of the skin lesions. The rate of improvement of PPP rose in conjunction with the number of days after tonsillectomy. We conclude that it requires 12 months, at minimum, to determine the efficacy of tonsillectomy as a treatment for PPP. | |
| 1374227 | Localisation and characterisation of substance P binding to human synovial tissue in rheum | 1992 Mar | The neuropeptide substance P is found in perivascular and free unmyelinated nerve fibres in human synovial tissue. Quantitative receptor autoradiography was used to show specific, high affinity (Kd = 0.75 (0.21), nmol/l (mean (standard error of the mean)), low capacity (Bmax = 27.8 (7.9) amol/mm2) binding sites for substance P Bolton Hunter-labelled with iodine-125 localised to vascular endothelial cells in human synovial tissue. The binding could be saturated, was reversible, and was dependent on the magnesium concentration. Unlabelled substance P and neurokinin A competitively inhibited specific binding with 50% inhibition at concentrations of 1.25 (0.21) and 175 (29) nmol/l respectively. Neurokinin B (mumol/l) and calcitonin gene related peptide (1 mumol/l) did not inhibit binding. These binding sites show characteristics of the neurokinin 1 tachykinin receptor subtype. This provides further evidence that substance P may play a part in the vascular control of human synovium and may influence inflammatory processes in joints. | |
| 8336307 | Absence of correlation between interleukin 6 and C-reactive protein blood levels in system | 1993 May | To investigate if the low C-reactive protein (CRP) response frequently observed in systemic lupus erythematosus (SLE) is related to an impaired expression of interleukin 6 (IL-6), considered its main inducer, we studied serum IL-6 and CRP levels in 37 patients with SLE and 22 with rheumatoid arthritis (RA). Results show that in contrast to CRP, IL-6 levels are significantly higher in SLE than in RA. A linear regression analysis shows a positive correlation between levels of these 2 molecules in RA but not in SLE. Similarly, levels of fibrinogen, another acute phase protein mainly induced by IL-6, did not correlate with IL-6 in SLE. Our results suggest an impairment of part of the acute phase response to IL-6 that might play a role in the pathogenesis of SLE. | |
| 8075277 | Community-acquired soft-tissue infections caused by Flavimonas oryzihabitans. | 1994 May | Flavimonas oryzihabitans has rarely been implicated in human infections. Previously reported cases of infections caused by this bacterium were nosocomially acquired. We report two cases of community-acquired soft-tissue infections due to F. oryzihabitans. It remains unclear how the patients were exposed to the organism. | |
| 8427509 | Bone mineral density in patients with recent onset rheumatoid arthritis: influence of dise | 1993 Jan | BACKGROUND: Generalised osteoporosis is often described in patients with rheumatoid arthritis (RA). The aim of this study was to evaluate disease related determinants of bone mineral density (BMD) in patients with RA. METHODS: Subjects were selected from a group of 147 patients with recent onset RA. Disease activity and functional capacity were studied prospectively in this cohort. Activity of the disease was assessed once every three months by various parameters, and functional capacity was measured with a health assessment questionnaire once every six months. Ninety seven patients consented to participate in the study. Bone mineral density was assessed with dual energy x ray absorptiometry in the lumbar spine, in a combined region of interest in the hips, and in Ward's triangle. Multiple linear regression procedures were used to analyse the data. RESULTS: Duration of RA was negatively associated with BMD at all three sites of measurement. The mean erythrocyte sedimentation rate in the six months before BMD measurement was negatively associated with BMD in the hip and in Ward's triangle. Other parameters of disease activity were not related to BMD. The mean health assessment questionnaire score in the 18 months before BMD measurement was negatively associated with BMD in the combined hip region only. Bone mineral density tended to be decreased when patients were compared with a normal reference group, especially in the femoral regions of interest. CONCLUSIONS: It is concluded that BMD may be affected in patients with recent onset RA by disease dependent mechanisms. Several factors have been suggested elsewhere as determinants of BMD in RA. The results of this study show that disease duration, disease activity, and functional impairment may, independently of each other, contribute to bone loss, especially in the proximal femur. | |
| 8523359 | Fatal pulmonary fibrosis complicating low dose methotrexate therapy for rheumatoid arthrit | 1995 Sep | We report the fatal disease course of 2 aged patients with rheumatoid arthritis (RA). Both had respiratory complaints after 10-15 weeks of treatment with methotrexate (MTX). After withdrawal of MTX, and despite the use of corticosteroids and ventilatory support, both died of respiratory failure. Post mortem examination showed extensive pulmonary fibrosis, bronchiolitis obliterans, and hyperplasia of type II pneumocytes. To our knowledge, this is the first report of fatal pulmonary fibrosis following short courses of low dose MTX therapy for RA. | |
| 7921751 | Detection of autoantibodies to the 90 kDa heat shock protein in systemic lupus erythematos | 1994 Oct | Expression of the highly conserved 90 kDa heat shock protein (Hsp90) is elevated in the peripheral blood mononuclear cells of approximately 25% of patients with SLE. Conflicting data have been published about the frequency of antibodies to Hsp90 with the previous methodology using a complex Western blot system. We now describe an ELISA to measure autoantibodies to Hsp90 and Hsp70 in SLE patients, healthy controls and patients with a variety of autoimmune rheumatic diseases. IgG and IgM antibodies were elevated in 26 and 35% of SLE patients, respectively. These results show autoantibodies to Hsp90 (but not Hsp70) are elevated in a significant proportion of patients with SLE (P < 0.025) compared to healthy controls; and that those with raised antibody levels were more likely to have renal disease and a low C3 level (P < 0.02). | |
| 7569815 | Sollerman hand function test. A standardised method and its use in tetraplegic patients. | 1995 Jun | A standardised hand function test based on seven of the eight most common hand grips is reported. The test consists of 20 activities of daily living. The test procedure and the method of scoring are described as is our evaluation of the validity and reliability of the test. Fifty-nine tetraplegic patients were evaluated using the test before reconstructive surgery to their hands. The test score correlated well with the accepted international functional classification of the patient's arm (r = 0.76, p < 0.001). The mean test score in the arms of patients lacking sensation was significantly lower than in those with tactile gnosis (O:1-3 compared with OCu:1-3, p < 0.001). | |
| 7807106 | Primary total knee arthroplasty in the elderly. | 1994 Oct | In a retrospective study, the authors investigated the outcome of primary total knee arthroplasty in patients aged 75 years or older. There is an increased risk of perioperative mortality and medical morbidity, but not surgical morbidity. The results were equal to the younger control group in terms of patient satisfaction, pain relief, stability, range of motion, residual degree of flexion contracture, and extension lag. Mobility was less impressive in the elderly group; factors included were ability to walk, use of walking aids, gait, ability to get out of a chair, and ability to climb stairs. | |
| 7506785 | ASAP total knee arthroplasty instrumentation: all six, all precise? | 1993 Oct | Thirty consecutive cases requiring total knee replacement (TKR) were treated using the Richards Tricon Total Knee System with ASAP (All Six, All Precise) instrumentation (Richards Medical Company, Memphis, TN, USA). Preoperative and postoperative overall coronal alignment were measured using long-leg anteroposterior X-rays. The femoral and tibial bone cuts in this plane were assessed using intraoperative films. The aim was to achieve a postoperative coronal tibio-femoral alignment of 7 degrees valgus. The mean preoperative alignment was 1 degree valgus (SD = +/- 13.5 degrees). A mean postoperative alignment of 8 degrees valgus was obtained (SD = +/- 5.6 degrees). The results obtained in this series suggest that the ASAP system with careful use simplifies the technique of total knee replacement while maintaining accuracy. | |
| 1411190 | [3 cases of polyarthritis treated with recombinant alfa interferon]. | 1992 May | Bilateral symmetrical polyarthritis occurred in three patients (2 males and 1 female), with no previous history of inflammatory rheumatologic disease, given alpha-interferon for 1 1/2, 7, and 10 months as treatment of chronic non A-non B hepatitis, myelofibrosis, and thrombocytopenia with myeloproliferative disorder, respectively. Joint manifestations developed 1 1/2, 3, and 10 months after initiation of alpha-interferon in a dosage of 3.10(6) U three times a week, 4.5.10(6) U per day, and 8.10(6) U three times a week. Polyarthritis persisted following withdrawal of alpha-interferon in the two last patients of whom one had rheumatoid nodules and positive rheumatoid serology and the other had scleritis, exanthema, and negative rheumatoid serology. Erosive rheumatoid arthritis was diagnosed after 28 months and 12 months, respectively, in two patients who required systemic corticosteroids with antimalarials (1 case) or azathioprine after failure of methotrexate (one case). Follow-up in the third case (12 months) is too short to allow differentiation of systemic lupus erythematosus (ANA: 1/1500 H with anti-DNA antibodies 58 U/ml) and chronic autoimmune hepatitis. Reports of chronic inflammatory rheumatologic disease during alpha interferon therapy are exceedingly few in number. In the cases reported herein, alpha-interferon may have either triggered or revealed the joint disease. To prevent occurrence of this complication, exclusion from alpha-interferon therapy of patients with autoantibodies or a positive history for clinical evidence of immune dysfunction may be considered. | |
| 8687266 | Resolution of a soft-tissue sarcoma in a patient with rheumatoid arthritis after discontin | 1996 Jul 22 | An 85-year-old woman with rheumatoid arthritis that was treated with azathioprine presented with a posterior thoracic soft-tissue mass. A computed tomographic scan demonstrated a large mass in the chest wall that extended into the pleural space and several pulmonary nodules that were consistent with metastatic disease. A fine-needle biopsy was performed, and a morphologic diagnosis of sarcoma was made. As the patient was relatively asymptomatic and the lesion was inaccessible to a surgical procedure, no therapy was recommended. Therapy with azathioprine was discontinued. One year later, the mass had resolved. To our knowledge, this is the first reported case of a soft-tissue sarcoma complicating azathioprine treatment of rheumatoid arthritis. | |
| 9099933 | Human monoclonal rheumatoid factors augment arthritis in mice by the activation of T cells | 1996 Jun | In order to investigate the in vivo role of rheumatoid factor (RF), the effects of the administration of human monoclonal (m) IgM-RF and IgG-RF on the development of arthritis in mice were examined. The administration of human mRFs into mice immunized with type II collagen (CII) markedly enhanced the clinical score and paw swelling. The severity of arthritic joint disease with a marked infiltration of lymphoid cells, proliferation of synovial membrane, pannus formation and destruction of articular cartilage was significantly enhanced in both groups receiving RF (RF-enhanced arthritis). Skin ulcers were also observed in some of these RF-enhanced arthritis mice, whereas no such signs were observed in CII-immunized mice without mRFs. Both IgM-RF and IgG-RF increased CII-specific IgG antibodies in circulation, and the severity of arthritis correlated with the production of high titres of anti-CII antibodies. In vivo treatment of RF-enhanced arthritis mice with an anti-CD4 MoAb or an anti-CD8 MoAb inhibited the induction and progression of arthritis in these mice. Administration of RF to severe combined immunodeficient (SCID) mice with arthritis developed by the transfer of spleen cells from CII-immunized mice, prolonged the arthritis and enhanced the severity. This murine model of RF-enhanced arthritis may provide a useful tool for analysing the pathogenesis of rheumatoid arthritis in RF-positive patients. | |
| 7799343 | Rheumatic manifestations in patients with myelodysplastic and myeloproliferative diseases. | 1994 Sep | OBJECTIVE: To evaluate the rheumatic complications in patients with myelodysplastic and myeloproliferative diseases. METHODS: A retrospective chart review of patients with a rheumatic disease and either a myelodysplastic or myeloproliferative disorder diagnosed on bone marrow examination. RESULTS: Nine patients were identified, 5 with myelodysplastic and 4 with myeloproliferative disorders. Polyarthritis was the most common rheumatic presentation, occurring in 6 patients with a positive rheumatoid factor in 4. Necrotizing vasculitis complicated the course in 3 patients. Autoantibodies and hypergammaglobulinemia were present in the majority of patients. CONCLUSION: There is an association between hematologic disorders caused by proliferation of bone marrow derived pluripotent stem cells and rheumatic disorders. | |
| 7482069 | [Pneumocystis carinii pneumonia associated with low dose methotrexate treatment for malign | 1995 Aug | Low dose pulse methotrexate (MTX) has become a widely used therapy for rheumatoid arthritis (RA) because of its good response rate profile. With the increased use of MTX, reports of opportunistic infections associated with MTX therapy have appeared. Fourteen cases of pneumocystis carinii (PC) pneumonia in patients receiving low dose MTX have been previously reported. Yet, no case of PC pneumonia associated with low dose MTX has so far been reported in Japan. We report the first case in Japan of PC pneumonia occurring in a patient with rheumatoid vasculitis who was receiving low dose MTX. A 70-year old woman with 13 year history of RA presented with 3-day history of rapidly aggravating dyspnea, dry cough and fever. She had been receiving MTX 7.5 mg/week for 2.5 months because of her vasculitis symptoms. She had also been receiving prednisolone 7.5 mg/day which had been successfully tapered from an initial dose of 15 mg/day. At the time of her presentation with respiratory symptoms, all of her vasculitis symptoms had been alleviated. A chest radiograph revealed diffuse interstitial shadowing bilaterally and bilateral hilar and right lower lung field infiltrates. Her arterial blood gas showed severe hypoxemia (PaO2 27.7 torr). Polymerase chain reaction assay of bronchoalveolar lavage fluid showed PC. Although the patient required ventilatory support for 9 days, she was successfully treated with trimethoprime-sulphamethoxazole and methylprednisolone pulse therapy. Eight months later, the patient was well with no evidence of vasculitis or respiratory symptoms. | |
| 8346465 | [Soluble IL-2 receptor levels in rheumatic diseases]. | 1993 Jun | We measured soluble interleukin-2 receptors (sIL-2R) in plasma and/or joint fluid (JF) from patients with rheumatoid arthritis (RA: 16 patients), Sjögren's syndrome (SS: 24 patients) and Behçet's disease (BD: 23 patients). Plasma sIL-2R levels were significantly higher in RA patients (956 +/- 994 U/ml, p < 0.01) and SS patients (1025 +/- 1112 U/ml, p < 0.01) than 20 healthy subjects (338 +/- 159 U/ml), but not significantly increased in BD patients (408 +/- 329 U/ml). sIL-2R levels higher than the mean of healthy subjects +2 standard deviations were observed in 3 BD patients (13.0%), 7 RA patients (43.8%) and 10 SS patients (41.7%). sIL-2R levels positively correlated with erythrocyte sedimentation rates and C-reactive protein levels in RA patients, or IgM levels in SS. There was no significant correlation between plasma sIL-2R levels and disease activity, clinical symptoms, or other laboratory parameters in BD patients. However, sIL-2R concentrations in the JF from 4 BD patients (1644 +/- 198 U/ml: p < 0.05) or 16 RA patients (3946 +/- 5424 U/ml: p < 0.01) were significantly higher than corresponding plasma sIL-2R concentrations. Above results indicate that lymphocytes are being activated in patients with RA or SS and in the inflammatory lesions of BD patients, while the whole immunologic activation are relatively lower in BD than RA and SS. | |
| 7911181 | Arthropathy in thalassaemia patients receiving deferiprone. | 1994 Jun 11 | The iron chelator deferiprone (L1) reduces tissue iron stores in iron-loaded patients. Three of sixteen patients treated with deferiprone developed joint pain and swelling without evidence of systemic lupus erythematosus (SLE). Articular cartilage, synovial hypertrophy and iron deposition, and synovial lining cell proliferation, with no inflammatory or allergic reaction, were observed on synovial exploration and biopsy. Symptoms resolved partly or completely during continued drug administration. We hypothesise that deferiprone-induced shifts of iron to synovium resulted in tissue damage, accelerated by free-radical formation during incomplete complexation of iron and this bidentate chelator. This deferiprone-associated symptom complex is not associated with drug-induced SLE, and does not progress in severity during continued therapy. |