Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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2774696 | Characterisation of soluble and cell associated phospholipase A2 from rheumatoid synovial | 1989 Jul | The hydrolysis of radiolabelled Escherichia coli phospholipids, and micellar dispersions of phosphatidylethanolamine and phosphatidylcholine, were used to characterise the phospholipase A2 activity in synovial fluid from patients with rheumatoid arthritis. Cell free fractions of synovial fluid contain a phospholipase A2 enzyme that preferentially releases [14C]oleic acid from E coli biomembranes (specific activity 291.3 (SEM 27.6) pmol/min/mg). This enzyme requires calcium and is optimally active at neutral pH. Purified dispersions of phosphatidylethanolamine are also readily degraded by the soluble enzyme, but it is not active against phosphatidylcholine. The substitution of [14C]oleic acid by [3H]arachidonic acid for the labelling of E coli allowed differentiation between the soluble phospholipase A2 and the cell associated phospholipase A2 present in sonicates of mononuclear cells and neutrophils from peripheral blood and synovial fluid. The cell associated phospholipase A2 preferentially releases [3H]arachidonic acid from E coli cardiolipin. In this paper the phospholipid substrate specificity of phospholipase A2 from rheumatoid synovial fluid, the optimal assay conditions for its detection, and a standardised expression of activity in terms of pmol per minute per mg of protein are established. | |
2772763 | Association of rheumatoid arthritis with HLA in three South African populations--whites, b | 1989 Sep 2 | The association between rheumatoid arthritis and HLA was studied in three South African populations: whites (N = 66), blacks (N = 33) and patients of mixed ancestry (Cape Coloureds) (N = 183). The antigens of the HLA-A, B, C, DR and DQ loci were detected by microlymphocytotoxicity assay and their frequencies in the three patient groups were compared with the corresponding frequencies in normal individuals of the same population group. HLA-DR4 was significantly associated with rheumatoid arthritis in whites (P less than 0.0001), blacks (P less than 0.001) and patients of mixed ancestry (P less than 10(-6]. The relative risk for HLA-DR4 was 3,2 in whites, 3,9 in blacks and 3,7 in patients of mixed ancestry. Other significant associations detected were with HLA-A2 in whites and HLA-B8 and DQw3 in patients of mixed ancestry. The constant association with HLA-DR4 seen in the different populations provides support for the suggestion that the HLA genes themselves are responsible for the genetic susceptibility to rheumatoid arthritis. | |
2420896 | Direct quantitation of activated C3 in human plasma with monoclonal anti-iC3b-C3d-neoantig | 1986 Apr 3 | We developed a microtiter solid-phase radioimmunoassay for quantitating C3 breakdown products (iC3b, C3dg, C3d) in human plasma with a unique monoclonal antibody specific for a neoantigen present on iC3b and C3d (MoAb 130). This monoclonal antibody reacts with a neoantigen which appears when C3b is converted to iC3b. The neoantigen is also present on the C3dg and C3d fragments derived from iC3b. The concentration of the neoantigen is elevated in the plasma of most patients with rheumatoid arthritis and systemic lupus erythematosus as compared to normal volunteers. Some patients with glomerulonephritis also had elevated concentration of the neoantigen in their plasma. | |
2046470 | Enzymatic activity and distribution of phospholipase A2 in human cartilage. | 1991 | Extracellular phospholipase A2 (PLA2) with proinflammatory activity has recently been discovered in synovial fluids in inflammatory arthritides. In the search for the sources of synovial fluid PLA2, human synovium and articular cartilage were found to contain large quantities of the enzyme. In rheumatoid arthritis (RA), PLA2 activity in synovium, superficial and deep layers of articular cartilage was 20 +/- 14 (SEM), 168 +/- 62 and 533 +/- 176 nmol/min/mg protein respectively. Corresponding values in osteoarthritis (OA) were 49 +/- 11, 569 +/- 109 and 1709 +/- 243 nmol/min/mg protein, all significantly higher (p less than .01) than in RA. Nasal septal cartilage contained much less PLA2, 19 +/- 5.6. PLA2 in human articular and nasal cartilage has sn-2 specificity, a neutral pH optimum and absolute calcium dependence. High PLA2 concentration in articular cartilage may imply that, at least in part, cartilage is the source of PLA2 in the joint space. Since RA cartilage and synovium have less PLA2 activity than the corresponding OA tissues, additional sources of PLA2 in RA synovial fluids are implicated. | |
2384498 | Total knee arthroplasty with the kinematic prosthesis. Results after five to nine years: a | 1990 Aug | A review of the results of 192 kinematic total knee replacements five to nine years after the operation showed that the results were still satisfactory. At the time of the review, the ages of the patients ranged from twenty-two to eighty-seven years. About half of the patients had rheumatoid arthritis and the other half, osteoarthrosis. About 90 per cent of the results were rated good or excellent, and the average range of flexion was 109 degrees. Radiolucency was present around 40 per cent of the tibial components, 30 per cent of the femoral components, and 60 per cent of the patellar components, but the lines were thin and not progressive. The complications included loosening of the patellar components in five knees, one fracture of the tibial tray with loosening of the patellar component, one fracture of the patellar component, and one dislocation of the patellar component. | |
3083339 | Sjögren's syndrome in children. | 1986 Feb | Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of the lacrimal and salivary glands; it eventually leads to keratoconjunctivitis sicca and xerostomia. The disease usually affects middle-aged women and is second to rheumatoid arthritis as the most commonly diagnosed connective tissue disorder. Surprisingly, only 31 cases have been reported in the pediatric population. The diagnosis should be considered, however, in children with a foreign body sensation in the eyes, chronic dryness of the eyes or mouth, or recurrent salivary gland enlargement. This has prompted us to describe our experience in treating five children with SS at Texas Children's Hospital, Houston. One 5-year-old child with no other evidence of connective tissue disease was diagnosed as having primary SS. The remaining four children either had juvenile rheumatoid arthritis or systemic lupus erythematosus in addition to SS, and the diagnosis of secondary SS was made. Other autoimmune disorders associated with SS include polyarteritis nodosa, scleroderma, and polymyositis. Interestingly, one child with secondary SS and chronic lymphocytic thyroiditis developed papillary carcinoma of the thyroid. Both forms of SS are probably more prevalent than the literature would suggest. Recognition of this fact is important if the immediate complications of corneal damage and severe dental decay are to be prevented. Symptomatic treatment with steroids, eyedrops, artificial saliva, and prophylactic fluoride treatments is available. With an adequate follow-up program the late morbidity associated with SS, such as malignant disease, can be minimized. | |
2498512 | Effects of galactose depletion from oligosaccharide chains on immunological activities of | 1989 Mar | We previously reported a decrease in the content of galactose residues in oligosaccharide chains of serum IgG from patients with rheumatoid arthritis, which was presumed to affect the 3 dimensional structure of CH2 domain. In the present study, we prepared the galactose depleted IgG (agalacto IgG) and characterized its immunological activities. Significant reduction in Clq binding and Fc receptor binding was observed in agalacto IgG. However, IgM rheumatoid factor binding and protein A binding were the same as with intact IgG. Our results implied the biological function of the carbohydrate moiety of human IgG. | |
2591122 | Humoral immunity and composition of immune complexes in patients with rheumatoid arthritis | 1989 Sep | IgE-containing circulating immune complexes (IgE-CIC) were determined with a 2.5% PEG-precipitation assay in 98 patients with classical or definite rheumatoid arthritis (RA). Of the 45 IgE-CIC positive sera, only 4 had elevated total serum IgE. IgE-CIC positive patients had more active disease than patients without IgE-CIC, as determined by their more swollen joints and higher Ritchie indices (p less than 0.04 and 0.02, respectively). Apart from IgE, other immunoglobulin isotypes, rheumatoid factor (RF) of the IgG-, IgA- and IgM-classes, C3 and antinuclear antibodies could be demonstrated in the IgE-containing PEG-precipitates. IgE-RF could not be demonstrated in serum or in IgE-CIC. Anti-IgE of the IgM-class (IgMaIgE) were frequently found (28/45 patients) in the IgE-positive PEG-precipitates. All 14 patients positive for IgGaIgE in the IgE-CIC were also positive for IgMaIgE in the CIC. As in the serum, there was a good correlation in the CIC between the level of IgGaIgE and the level of IgMaIgE (r = 0.64). The correlation between the respective levels of IgGaIgE and IgMaIgE in serum and in CIC was high (r = 0.93 and 0.79, respectively). On the other hand, only 1 patient was positive for IgAaIgE in the IgE-CIC. We conclude that IgE and aIgE of the IgM- and IgG-classes are frequently present in the immune complex form in RA and that they are correlated with the clinical activity of arthritis. | |
3359949 | Clinical experiences with the intramuscular injection of tiaprofenic acid in rheumatic dis | 1988 | The efficacy of intramuscular tiaprofenic acid (TA) was investigated in 3 separate studies: a multicentre open study involving 487 patients with various rheumatic conditions: an open study of 31 patients with active osteoarthritis of the knee; and an open comparative study with ketoprofen involving 30 patients with acute gout. In each of the studies tiaprofenic acid was given at a dose of 200mg intramuscularly twice daily for 5 days. In addition to clinical efficacy and tolerance, the time of onset and duration of the analgesic effect were also assessed. Significant improvements in both pain intensity and inflammation were seen in 60 to 70% of all patients in the 3 studies (p less than 0.0001). Benefits from tiaprofenic acid injection were noted within 60 minutes by about 47% of the patients with acute gout and about 85% of the whole group of patients enrolled in the multicentre study. The analgesic effect lasted from 8 to 12 hours in about 52% of the latter patients, and the overall effect was assessed as either good, very good or excellent in 62.5 to 100% of patients. Results from the comparative study with ketoprofen in acute gout patients showed a better and faster beneficial effect in the group receiving tiaprofenic acid. Thus the intramuscular administration of tiaprofenic acid at a dose of 200mg twice daily for 5 days to 533 patients with different rheumatic conditions resulted in good analgesic and anti-inflammatory activities with a rapid and sustained effect, and was also well tolerated. | |
3144941 | Combined suppressive drug treatment in severe refractory rheumatoid disease: an analysis o | 1988 Nov | A trial was designed to assess the effects of intramuscular sodium aurothiomalate or intravenous cyclophosphamide, or both, in combination with intravenous 'pulse' methylprednisolone in severe intractable rheumatoid arthritis. Thirteen patients with severe, active rheumatoid arthritis, unresponsive to conventional therapeutic regimens showed improvement in synovitis after receiving a single intravenous bolus of methylprednisolone (15 mg/kg). Early morning stiffness and Ritchie articular index remained improved over pretreatment values after 12 weeks. There was an early fall in the erythrocyte sedimentation rate, which returned to baseline levels by four weeks. A concomitant intravenous pulse of cyclophosphamide (1 g/m2 body surface area) given to eight patients did not confer any additional benefit. Six patients received sodium aurothiomalate, up to 100 mg intramuscularly a week, and in these patients the early improvement in synovitis induced by methylprednisolone was maintained. Thus between 12 and 24 weeks the Ritchie articular index, visual analogue pain score, erythrocyte sedimentation rate, haemoglobin, and immunoglobin G were significantly better in the patients treated with gold and methylprednisolone than in those treated with methylprednisolone alone, irrespective of whether they had received cyclophosphamide. Methylprednisolone pulse therapy given at the start of gold treatment results in early improvement in synovitis, maintained until the usual delay in achieving a therapeutic effect from gold has elapsed. | |
2921885 | The Quality of Well-being Scale. Applications in AIDS, cystic fibrosis, and arthritis. | 1989 Mar | The Quality of Well-being (QWB) Scale combines preference-weighted measures of symptoms and functioning to provide a numerical point in-time expression of well-being that ranges from zero (0) for death to 1.0 for asymptomatic optimum functioning. The QWB includes three scales of function: mobility, physical activity, and social activity. Each step of these scales is associated with preference weights. Preference adjustments for symptoms are also included. This paper describes how this general system was used to evaluate outcomes in three different clinical conditions: acquired immune deficiency syndrome (AIDS), cystic fibrosis, and arthritis. In one study, the QWB was administered to 31 patients participating in evaluation of azidothymidine (AZT) treatment for AIDS. The QWB system demonstrated substantial benefits of AZT treatment in comparison to placebo. In a second study, the QWB and a series of pulmonary function measures were administered to 44 patients with cystic fibrosis. The QWB was demonstrated to be significantly correlated with measures of pulmonary function, including FEV1 and maximal midexpiratory flow rate (MMEFR). In addition, there were significant associations between the QWB and measures of exercise tolerance. In the third study, the QWB and an arthritis-specific measure were administered to 83 arthritis patients before and after their treatment. The QWB was at least as capable of detecting clinical change in this population as was the disease-specific measure. For all three conditions, the QWB considered side effects and benefits of treatment in a common unit. Clinical trial data are cited to suggest that the QWB is a valuable outcome measure in arthritis treatment evaluation. We conclude that the QWB has substantial validity as a general health outcome measure and that the system can be used with different populations. | |
2443529 | Quantitation and antigenic characterization of bound C3 of circulating immune complexes in | 1987 Sep | In recent years defective function of the complement-mediated clearance of immune complexes (IC) has been reported in patients with immune complex disease. The defect has been found at different levels in the clearance system. An important event in this sequential system is the binding of C3-coated particles to C3 receptors on erythrocytes and phagocytes. This study focuses on immunochemical properties of IC-bound C3 that reflect the functional state of the molecule. Sera from patients with primary biliary cirrhosis (PBC), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) and from normal subjects were analyzed for their level of C3 precipitable in 2.7% (w/v) polyethylene glycol (PEG). The mean levels for the patient categories were significantly higher than that for the normal subjects. The immunochemical study revealed several differences among the different forms of PEG-precipitable C3. All forms expressed C3(D) antigens which are expressed by immune complex-associated and denatured forms but not by soluble physiological forms of C3. The expression of these antigens was proportionately lower for the complex-associated C3 of PBC compared to that of RA and SLE. Furthermore, employing monoclonal anti-C3(D) antibodies against the C3c and the C3d domain, distinct differences could be detected among all forms of PEG-precipitable C3. Sera from RA and SLE, in particular, contained PEG-precipitable C3 that exhibited distinctive immunochemical features with respect to these epitopes. | |
3308719 | Multicenter double-blind randomized clinical trial of imidazole salicylate versus ibuprofe | 1987 Aug | In a 24-week multicenter double-blind clinical trial, efficacy and safety of the novel nonsteroidal anti-inflammatory drug imidazole salicylate (750 mg t.i.d. per os) and ibuprofen (600 mg t.i.d. per os) were compared in 60 patients with classical or definite rheumatoid arthritis, randomly assigned to one of the two treatment groups. The patients improved significantly with both treatments in all the clinical parameters examined such as the duration of morning stiffness, grip strength of both hands, Ritchie's articular index and severity of joint pain. The systemic tolerability, assessed by hematological, liver and kidney function tests was excellent with both treatments. The incidence of side effects was overall fairly low with both drugs, and lower in the group treated with imidazole salicylate (23% vs. 33%). | |
3572936 | Salicylate toxicity in elderly patients with rheumatoid arthritis. | 1987 Feb | Using the American Rheumatism Association Medical Information System, we studied the effect of age upon salicylate toxicity in elderly patients with rheumatoid arthritis. Data were gathered from 545 patients by self-reported questionnaires for the 6 months and also the 7 days before the visit of interest. With one week data and weight adjusted doses in 253 patients in whom data were available, age related differences in lower gastrointestinal symptoms (p = 0.05) and tinnitus (p = 0.01) were found, despite the fact that elderly patients (E) took less salicylate than younger ones (y)--E [39.1 +/- 2.4 (SD) mg/kg/day] vs Y [49.8 +/- 3.89 mg/kg/day] (p = 0.02). Our data indicate a difference in salicylate dynamics among the elderly (i.e., increased toxicity in the face of decreased salicylate doses). | |
2952797 | Toxicity of longterm low dose D-penicillamine therapy in rheumatoid arthritis. Cooperative | 1987 Feb | After a controlled, double blind multicenter trial of D-penicillamine in the treatment of rheumatoid arthritis, 148 patients were followed for an additional year in an open label trial. Complications of longterm D-penicillamine included rash, gastrointestinal manifestations, proteinuria, bone marrow depression, myasthenia gravis, myositis, acute febrile reaction and pemphigus foliaceus. With the exception of one patient with myasthenia gravis, all adverse reactions resolved after withdrawal of D-penicillamine. While the complications of D-penicillamine therapy are usually dose related, these reactions can occur at any time and at any dose. Continued and frequent longterm monitoring of D-penicillamine therapy is required. | |
2539218 | Clinical applications of high-definition microfocal radiography. | 1989 Mar | Recent advances in technology have lead to the development of a high-definition microfocal X-ray unit allowing macroradiographic examination of different parts of the body at x 5 to x 10 magnification and with a high spatial resolution. Its applications in the study of a number of arthritides, metabolic and some other bone diseases are described in terms of early detection of diagnostic features. Emphasis is placed on the advantages of direct accurate measurement of these features, providing a precise evaluation of disease progression and response to therapy. | |
3521439 | [Deposits of immune complexes in rheumatoid nodule]. | 1986 | The classical histological features of rheumatoid nodules are similar to those of subcutaneous granuloma annulare and necrobiosis lipoidica. The same applied to the DIF images of these lesions. Rheumatoid nodules are more frequent in patients with high rheumatoid factor. Lesions of cutaneous vasculitis are a sign of severity associated with other extra-articular manifestations. Our results are consistent with those of other studies which demonstrated the presence of Ig and/or C deposits in vessels and sometimes at the dermis-epidermis junction. The deposits found in vessels are usually formed of IgM and C3, more rarely of IgG. Those found at the dermis-epidermis junction consist of IgG, IgM and C3. Immune complex deposits in the walls of venules represent the primary mechanism of leukocytoclastic vasculitis. The presence of such deposits on vessels with muscular wall in rheumatoid arthritis suggests an identical pathogenetic mechanism. No alteration of the basal membrane has been noted. The role of deposits at the dermis-epidermis junction has not yet been elucidated. | |
3353671 | [Assay of erythrocyte, platelet and serum superoxide dismutase, glutathione peroxidase and | 1988 Jan | The authors present a study of superoxide dismutase, catalase and glutathione peroxidase in hemolysis product, platelets and serum of 23 patients with rheumatoid polyarthritis and 11 healthy subjects. The nature of the treatment enables to divide the 23 patients into 3 groups: group I (8 cases): no treatment; Group II (7 cases): steroid therapy alone; group III (8 cases): basic treatment associated (3 cases) or not (5 cases) to steroid therapy. Statistical analysis shows no significant difference, whatever the environment and the treatment contemplated. The significance of these results is discussed and compared with literature data concerning only enzymatic activities and not the blood levels as in the present study. | |
2201818 | Pathophysiology of cytokines. | 1990 | Beside their therapeutic effects, cytokines are involved in pathologies such as IL-6 in myeloma tumor growth and bone resorption, BCGF in the proliferation of hairy cell leukemic cells, IL-2 in the capillary leak syndrome. For biotherapy to develop, it is necessary to understand both the beneficial and the deletorious effects of cytokines. | |
2525943 | Evaluation of the efficacy and comparative effects on gastric and duodenal mucosa of etodo | 1989 Aug | The therapeutic efficacy and upper gastrointestinal side effects of a twice daily dose of 300 mg etodolac and 500 mg naproxen were compared in 30 hospital out-patients with active rheumatoid arthritis. Drugs were taken for 4 weeks in a double-blind, randomized, parallel group, single centre study. Rheumatological, endoscopic and laboratory assessments were performed at the start and on completion of the study. Mucosal lesions developed in only three (20%) patients of the etodolac group and they all had low endoscopy scores, compared to eight (53%) patients of the naproxen group with significantly worse endoscopy scores (p less than 0.05). Lesions were asymptomatic in all but one patient (on naproxen), and the gastric antrum was the commonest region involved. Of the 11 patients who developed endoscopic abnormalities in both groups, seven (64%) were moderate to heavy smokers. Etodolac had a similar antiarthritic effect to naproxen, but it appears to be better tolerated by the upper gastrointestinal mucosa as shown by endoscopy. |