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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
8639169 Cigarette smoking increases the risk of rheumatoid arthritis. Results from a nationwide st 1996 May OBJECTIVE: To test the hypothesis that cigarette smoking is associated with susceptibility to rheumatoid arthritis (RA) by comparing smoking history between twins with RA and their unaffected co-twins. METHODS: Interview questionnaires on smoking history were administered to 79 identical (monozygotic [MZ]) and 71 same-sex nonidentical (dizygotic, [DZ]) twin pairs who were discordant for RA, recruited from the Arthritis and Rheumatism Council Twin Study. Results were expressed as odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Although most twin pairs were concordant for smoking history, there was a strong association between ever smoking and RA in the MZ pairs (OR 12.0, 95% CI 1.78-513), with a similar trend observed in the DZ pairs (OR 2.5, 95% CI 0.92-7.87). CONCLUSION: The discordance in cigarette smoking history for individuals who are at presumed identical genetic risk for RA supports other data suggesting the role of smoking in disease susceptibility.
9098423 Frequency of HLA-DPB1 alleles in a Spanish population: their contribution to rheumatoid ar 1994 Apr HLA-DPB1 allele frequencies in 181 unrelated control individuals and 70 rheumatoid factor-positive RA patients from Seville (Spain) were determined using oligonucleotide typing methods. All frequencies shown concern the percentage of individuals positive for a certain allele. HLA-DPB1*0401 was the most common DPB1 allele in the healthy individuals, possessed by 65.7% of them. In addition to HLA-DPB1*0401, only the following alleles were found in normal subjects at frequencies greater than 10%: DPB1*0101 (15.5%), DPB1*0201 (12.2%), DPB1*0301 (16.6), and DPB1*0402 (29.3%). When HLA-DPB1 allelic frequencies were compared between seropositive RA patients and controls, a negative association for DPB1*0301 and DPB1*0401 was found in RA patients, although it failed to reach statistical significance after correction for the number of comparisons made. The other DPB1 alleles exhibited almost identical frequencies in both groups. However, when only DR4+ patients and controls were considered, the decrease in the frequency of the DPB1*0301 and DPB1*0401 alleles lacked statistical significance. On the other hand, when DR4- RA patients and controls were compared, the frequency of DPB1*0301 was found decreased significantly again, even more than in the whole group of patients.
8003057 Differential expression of two major cytokines produced by neutrophils, interleukin-8 and 1994 Jun OBJECTIVE: Neutrophils have been shown to produce interleukin-8 (IL-8) and interleukin-1 receptor antagonist (IL-1ra) in large amounts compared with other cytokines. Since IL-8 has a proinflammatory action whereas IL-1ra is antiinflammatory, our objective was to examine the relative levels of production of these cytokines by synovial fluid (SF) neutrophils isolated from patients with rheumatoid arthritis (RA). METHODS: We measured cytokine production using an enzyme-linked immunosorbent assay and analyzed messenger RNA accumulation in cells by Northern blot. RESULTS: SF neutrophils produced significantly more IL-8 and IL-1 beta, but significantly less IL-1ra, than peripheral blood neutrophils. CONCLUSION: These observations provide new information on the production of pro- and antiinflammatory molecules by neutrophils in the SF environment, and their possible role in RA.
7939730 Should methotrexate be used to treat early rheumatoid arthritis? 1994 Jun A number of studies show the efficacy of methotrexate (MTX) for rheumatoid arthritis (RA) in general. However, is there any reason to single this drug out for early RA? Mechanistically, it probably works differently in RA than in cancer, at least in part. Thus, in addition to dihydrofolate reductase-related effects, MTX inhibits aminoimidazocarboxamide transformylase, decreases leukotriene B4 production, and increases adenosine release at concentrations achieved with low-dose MTX regimens. Clinically, it is well tolerated over relatively long periods. Further, a recent meta-analysis of radiology studies shows that MTX compares favorably with intramuscular gold and is better than azathioprine. Toxicity remains a concern in treating early RA, particularly as pulmonary "hypersensitivity reactions" continue (1% to 7.6%), infections (both fungal and perioperative) are documented, and more cirrhosis is found. With all of the above in mind, the use of MTX seems reasonable but not necessarily uniformly appropriate and not yet proved for early RA. Studies of MTX in early RA, particularly in combination with other drugs, are only beginning.
8617976 Persistence of dominant T cell clones in synovial tissues during rheumatoid arthritis. 1996 May 1 In a previous study, we showed that the T cell repertoire is biased in the synovial membrane (SM) compared with peripheral blood during rheumatoid arthritis (RA). The same bias was observed in different joints from the same patient and seems to be the same over time. To discover whether this bias was due to expansion of a clonal subset resulting from activation by conventional Ag(s) or to polygonal stimulation by superantigen(s), we sequenced more than 650 TCRBV-D-J junctional regions from freshly isolated SM and peripheral blood of two DR4-RA patients. From each patient, two SM were obtained on the same day, and a third was obtained later. Several dominant clones were found in SM but not in peripheral blood. Some of them were found only at the first time point in anatomically different SM, the majority persisted over time, and others were detected only at the second time point. Analysis of the complementarity-determining region 3 (CDR3) showed a bias in TCRBD and amino acid usage. Valine, encoded by randomly inserted N nucleotides, was used by 45% of dominant clones compared with 18% in the control population (p less than 0.001). In addition, GXXG and TSG motifs were frequently observed in the CDR3 of these dominant clones. These data indicate a dynamic TCR selection process during the perpetuation phase of RA. The dynamic changes of dominant clones also suggest a determinant spreading mechanism during RA.
7478707 Scaling the affective domain of pain: a study of the dimensionality of verbal descriptors. 1995 Jul This study evaluated the multidimensional structure of affective verbal descriptors and investigated individual differences in the scaling of the descriptors. Patients with chronic low back pain, chronic headache and rheumatoid arthritis (25 per group) and 25 control subjects, matched for age and sex, made similarity judgements of a set of 12 verbal descriptors, e.g., awful, miserable. They also completed the Coping Strategies Questionnaire, the Hospital Anxiety and Depression Scale, McGill Pain Questionnaire Short Form, and a measure of verbal intelligence. The similarity data were subjected to individual differences multidimensional scaling (ALSCAL) and the resulting subject weights were related to group membership and the questionnaire data. The multidimensional nature of affective descriptors was confirmed. A 4-dimensional solution was identified: the first 3 dimensions were comparable with previous findings and labeled Tolerability, Focus of Attention and Minor Emotional Reaction. The 4th dimension was enigmatic and attributable to the back pain group. There were significant differences between the groups in their weighting of the dimensions and in their self-reported coping strategies. The results are discussed with reference to an earlier study and the degree of consistency across the studies is noted. Implications of the results for the conceptualisation and measurement of the affective domain of pain report are outlined.
1588747 [Improvement of ADL and quality of life ]. 1992 Mar Improvement of quality of life (QOL) of the patients with rheumatoid arthritis (RA) is very important. Practically, health status measurement (HSM) is beneficial to the assessment of QOL in arthritides, because the socioeconomical factor, one of 3 main factors in QOL, has numerous matters besides the medicine. There are many scales to assess health status so far, Health Assessment Questionnaire (HAQ) and Arthritis Impact Measurement Scales (AIMS) have been widely utilized because of their reliability, validity and sensitivity. We compared the health status in 105 of RA inpatients and that in 86 of RA outpatients by AIMS. Outpatients had significantly better physical status than inpatients. Our data showed a great discrepancy from that of Anderson. The reason for this discrepancy is presumably the differences in life style and daily activity between two countries. We are now trying to modify AIMS to fit Japanese.
7985137 [Therapeutic plasmapheresis in immune complex diseases]. 1994 We studied the dependence of the plasma protein and volume on the exfusion volume, type and composition of the substitution solution in 140 plasmapheresis procedures given to patients with immune thrombocytopenic purpura and bronchial asthma. The change of blood protein system corresponded to the procedure regime. The procedure does not entail adverse reactions if it removes up to 30% of the plasma circulating volume (replacement with salt solution), 50% of the plasma circulating volume (replacement with dextran solution) or 95% of that with replacement with albumin. We have tested 3 simple mathematic models for postplasmapheresis proteinemia and recommend the regression equation Ct = a0 + a1.Co as the most adequate model.
8324959 Alteration of synoviocytes by inflammation--the source of a persistent non-immunologic dri 1993 Mar A solid phase hybridization assay was developed to assess simultaneously the level of transcription of multiple genes in inflammatory tissues and in derivative cell lines. It involves binding of a labelled cDNA probe to plasmids containing cDNAs of the genes of interest in excess concentration applied to a nylon membrane in a dot blot format. After hybridization under stringent conditions, the blot is washed and counts enumerated. Levels of mRNA are compared between different samples by normalization to GAPDH. The results indicate that mesenchymal cells isolated from inflammatory synovia exhibit alterations in the pattern of gene expression which distinguish them from similarly isolated and cultured cells from non-inflammatory synovia. These patterns are sustained through multiple passages in tissue culture, suggesting that this may reflect a persistently altered state of fibroblast differentiation induced by exposure to an inflammatory milieu.
7570155 Distinctive radiological features of small hand joints in rheumatoid arthritis and seroneg 1995 Jul A series of patients with clinically early inflammatory joint disease due to rheumatoid arthritis, psoriatic arthritis and Reiter's syndrome were examined by plain film radiography and magnetic resonance imaging (MRI). The spin echo T1-weighted precontrast, T2-weighted, and, especially, T1-weighted postcontrast images demonstrated distinct differences in the distribution of inflammatory changes, both within and adjacent to involved small hand joints. Two major subtypes of inflammatory arthritis were shown, thus providing a specific differential diagnosis between rheumatoid arthritis and some patients with seronegative spondyloarthritis. In particular, all the patients with Reiter's syndrome who were studied, and half of those with psoriatic arthritis, had a distinctive pattern of extra-articular disease involvement. The need for a new classification of clinical subsets in psoriatic arthritis has been recently suggested. The present findings suggest that magnetic resonance imaging could be useful in such a reclassification of seronegative spondyloarthritis, as well as offering considerable potential for a reappraisal of pathogenesis and therapy. In this series, it was also noted that juxta-articular osteoporosis on plain film did not correlate with bone marrow oedema on MRI. Hence the aetiology of this common radiographic finding also merits further consideration.
1364609 [The amino acid-binding capacity of immunoglobulins in rheumatoid arthritis patients]. 1992 Jan A study is presented of the binding capacity of immunoglobulins with amino acids in 60 patients with rheumatoid arthritis of grade I and II activity. Results of the investigation revealed an increase of the binding capacity of immunoglobulins of all three classes with a high range of amino acids that depended directly on the activity grade of the pathological process.
8208627 [Cytokines, their receptors and inhibitors. Importance in laboratory diagnosis of rheumato 1993 The present paper reviews the literature on biological activities of human cytokines in homeostasis, as modulated by their secretion, expression of membrane-bound and soluble receptors as well as by means of other cytokines and specific inhibitors, respectively. The role of structure and properties of interleukins 1, 2, 6 and their receptors in pathophysiology and laboratory diagnostics of rheumatoid arthritis, is discussed. Methods of quantitative determination of cytokines are described.
8376420 Socket migration after Charnley arthroplasty in rheumatoid arthritis and osteoarthritis. A 1993 Sep Socket migration and rotation in the Charnley total hip replacement were evaluated by roentgen stereophotogrammetric analysis in 23 patients with rheumatoid arthritis and 23 patients with osteoarthritis. The two groups were matched with regard to age and sex. The follow-up time was two years. In the rheumatoid patients socket migration was most prominent in the proximal direction and averaged 0.6 mm at 24 months as compared with 0.1 mm in the osteoarthritic group (p = 0.0003). Within the rheumatoid group a preoperative acetabular protrusion in five patients was associated with increased migration and rotation in all directions. The increased proximal migration in rheumatoid arthritis was consistent (p = 0.0009) even after the exclusion of the five protrusion cases. In the rheumatoid patients there was a correlation between low body-weight and proximal migration, but there was no such correlation in the osteoarthritic group. Our results suggest that socket fixation is less secure in patients with advanced inflammatory arthritis.
8817757 Pneumocystis carinii pneumonia in rheumatoid arthritis patients treated with methotrexate. 1996 Jun Use of methotrexate to treat rheumatoid arthritis is associated with pulmonary adverse effects in 3% to 5% of cases. In addition to immunoallergic lung disease, bronchitis and pneumonia due to pyogenic organisms, opportunistic lower respiratory tract infections have been reported, including, to our knowledge, 18 cases of Pneumocystis carinii pneumonia. We report two new cases of P. carinii pneumonia in methotrexate-treated rheumatoid arthritis patients. One case occurred in a 62-year-old woman with a nine-year history of seropositive rheumatoid arthritis treated for the last seven months with methotrexate, 15 mg per week, and prednisone, 10 mg/d. The other patient was a 58-year-old woman who had been diagnosed with rheumatoid arthritis 18 months earlier and had been receiving 15 mg per week of methotrexate for eight months in combination with 12.5 mg of prednisone per day. Both patients had negative tests for the human immunodeficiency virus. Symptoms consisted of fever, cough and dyspnea, with interstitial infiltrates on chest films, hypoxia, and lymphopenia (700 and 600/mm3, respectively). The diagnosis was confirmed by bronchoalveolar lavage. Both patients recovered under treatment with trimethoprim-sulfamethoxazole. An analysis of the 20 cases of P. carinii pneumonia reported to date in methotrexate-treated rheumatoid arthritis patients demonstrated a number of characteristics: the rheumatoid arthritis was of recent onset in some cases (a few months in one patient); lymphopenia was present in two thirds of cases; one-third of patients were not receiving corticosteroid therapy; the dosage and duration of methotrexate therapy varied widely, from 5 to 30 mg per week and two to 48 months; and four patients died.
7486670 TNF alpha is an effective therapeutic target for rheumatoid arthritis. 1995 Sep 7 Rheumatoid arthritis is the most common of a number of diseases in which inflammation and tissue destruction is driven by an autoimmune process. Current therapy is inadequate, and this has prompted major research efforts, both in academia and industry, to understand more about the pathogenesis, and hence provide the rationale for new therapeutic strategies. Here we review our studies of cytokine expression and regulation in rheumatoid joints, which has culminated in demonstrating that TNF alpha blockade, using a chimeric (human IgG1/K, mouse Fv) anti-TNF alpha antibody, cA2, markedly ameliorates arthritis. This defines a therapeutic target for rheumatoid arthritis.
7529985 Expression of CD44 in normal and rheumatoid synovium and cultured synovial fibroblasts. 1994 Nov OBJECTIVE: To determine if expression of CD44, the principal receptor for hyaluronan, was altered in rheumatoid (RA) synovium and cultured rheumatoid synovial fibroblasts. METHODS: Synovium was obtained from normal adult human joints (n = 4) and from joints of patients with RA (n = 5). Specific monoclonal antibodies to CD44 were used in immunofluorescence of whole synovium and cultured synovial fibroblasts and in quantitative Western blotting and ELISA of CD44 in cultured synovial fibroblasts. RESULTS: CD44 was restricted to the lining layer in normal synovium but present, in reduced concentrations, throughout rheumatoid synovium. Cultured rheumatoid cells were 19% larger in area and showed far fewer and less extensive CD44-positive cytoplasmic extensions, together with reduced staining intensity compared with normal. Quantitative Western blotting normalised for cell protein showed a 75% reduction (normal = 1754 (835), rheumatoid = 409 (84) mean (SD) arbitrary units) in the amount of CD44 in rheumatoid cells compared with normal, and enzyme linked immunosorbent assay (ELISA) of cultured cell monolayers normalised for cell number indicated a 29% reduction (normal = 0.707 (0.110), rheumatoid = 0.504 (0.103), mean (SD) optical density at 405 nm). CONCLUSIONS: Rheumatoid synovial cells showed altered morphology and reduced CD44 expression compared with normal cells. CD44, by means of modulated associations with the cytoskeleton, may be involved in cell shape change.
8575711 [Synovectomy of the knee joint in rheumatoid arthritis. Follow-up studies]. 1995 Dec 10 A total of 156 synovectomies were performed to treat recurrent swelling of the knee joints in 148 patients with rheumatic diseases. The late results observed in 112 patients (72%) re-examined after an average follow-up period of 6.2 years are discussed. The subjective and objective findings in patients undergoing early surgery proved to be superior to those seen after late synovectomy. Also in comparison with a group of patients submitted to synoviorthosis, surgical synovectomy, in particular when carried out at an early stage, showed more favorable results. For this reason, should conservative treatment fail, and recurrent swelling of the knee joints persist, early surgical intervention ist recommended.
8052933 [A case of polyarthritis developed on the non-paralytic side in a hemiplegic patient]. 1994 Jun A 37-year old house wife who developed polyarthritis localized to contralateral to hemiplegic side was reported. The patient had been on the physical therapy program for right hemiplegia which occurred at the age of 33. The polyarthritis are chronic and showed significant responses to salazosulfapyridine. Her serum contained rheumatoid factor (RF) of high titer and hand X-ray showed characteristic erosive changes in PIP and MCP joints. Presence of morning stiffness, positive RF, bone erosion, isotope accumulation, HLA-DR4 and responses to DMARD are all consistent with a diagnosis of rheumatoid arthritis. Review of the literature revealed that fifteen patients had been reported in whom occurrence of neurological disorders and rheumatic conditions were described. In most of these patients including the present case, the rheumatic symptoms did not occur or subsided in the hemiplegic side of neurological disorders. Possible mechanisms of inactivation on rheumatic inflammation were discussed.
8990864 Liver cirrhosis due to methotrexate in a patient with rheumatoid arthritis. 1996 Dec A 49-year-old female with rheumatoid arthritis developed liver cirrhosis after a cumulative dosage of 6 g methotrexate (MTX). There were mild liver enzyme abnormalities, decreased liver synthesis function and possible signs of portal hypertension. After stopping MTX all laboratory abnormalities disappeared except for a mild thrombocytopenia. Risk factors and guidelines for monitoring liver toxicity during MTX treatment in rheumatoid arthritis are discussed.
7552077 How do second-line agents work? 1995 Apr The pathogenesis of rheumatoid arthritis remains unknown. Disease modifying anti-rheumatic drugs are commonly used to treat rheumatoid arthritis patients. Their use in rheumatoid arthritis was discovered serendipitously and their modes of action remain unknown. This article reviews current hypotheses on the mechanisms of action of established DMARDs. Most of them have anti-inflammatory properties and some are immunomodulators. We also discuss a number of novel agents which are potential new DMARDs.