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

ID PMID Title PublicationDate abstract
6230449 Evidence for activated peripheral blood T-cells in rheumatoid arthritis. 1983 Dec We have previously demonstrated defective antigen specific T-suppressor (Ts) cell function in the peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA). Our study was designed to delineate whether diminished Ts activity is due to impaired interleukin (IL) dependent clonal expansion of Ts cells or to prior in vivo activation. Patients with recent onset of RA, or a disease flare, exhibited enhanced IL generation (IL-1 and /or IL-2). Increased proportions of active E-rosettes, elevated spontaneous production of IgM, and total immunoglobulin in mitogen free cultures were consistent with the concept of prior lymphocyte activation in vivo. Our results do not support defective clonal expansion of Ts cells as the basis of deficient IL generation, but do support the concept of in vivo activation of PBM cells in some patients with RA.
7373616 Clinical significance of synovial fluid total hemolytic complement activity. 1980 Mar Total hemolytic complement (CH50) was measured in 174 synovial fluids (SF) to determine its diagnostic and and prognostic value. SF CH50 was reduced relative to serum CH50 in 61% of patients with rheumatoid arthritis and 60% of patients with crystal-induced arthritis. There was no correlation of SF CH50 levels with disease duration, SF leukocyte count, presence of IgM rheumatoid factor, or radiologic evidence of erosions.
43824 [Azathioprine in rheumatology]. 1979 Dec 20 The indication for azathioprine (Imurek) has to be strictly adjusted, but amongst the immunosuppresive drugs it is without doubt the best tolerated substance and--provided that regular controls are carried out--is therefore also suitable for long-term treatment in practice.
3875632 Identification of immunostimulatory dendritic cells in the synovial effusions of patients 1985 Aug Dendritic cells in the circulation are leukocytes that are rich in Ia antigens and that actively stimulate T cell replication. We have identified dendritic cells in the joint effusions of patients with rheumatoid arthritis. By phase-contrast and immunofluorescence microscopy, synovial mononuclear cells contained 1-5% dendritic profiles that were rich in HLA-DR and DQ, had small amounts of C3bi receptor, and lacked a battery of monocyte and lymphocyte markers. These dendritic cells could be enriched to 60-80% purity by cytolytic depletion of monocytes and lymphocytes with a group of monoclonal antibodies (MAb) and complement. By transmission electron microscopy, the dendritic cell processes were bulbous in shape and lacked organelles. The cytoplasm had few lysosomes or endocytic vacuoles but contained a well-developed smooth reticulum that was comparable to that previously described in the Ia-rich interdigitating cells of lymphoid tissues. The growth of sodium periodate-modified T lymphocytes was used as a rapid quantitative assay of accessory cell function. Synovial mononuclear cells were some ten times more active than normal blood cells. Treatment with alpha-Ia MAb and complement ablated stimulatory function. In contrast, removal of monocytes (MAb, 3C10) or monocytes and B (MAb, BA-1) plus T (MAb, OKT3, or T101) lymphocytes did not significantly alter total activity, and the function per viable cell increased four- to eightfold. We conclude that rheumatoid arthritis synovial fluids contain cells that are comparable in function, phenotype, and structure to blood dendritic cells, although the frequency (1-5%) is 10 times greater in joints. The reason for their accumulation in the articular cavity is not known, but dendritic cells may be important in perpetuating the joint inflammation characteristic of this disease.
853126 Circulating complement breakdown products in patients with rheumatoid arthritis. Correlati 1977 May Quantitative determination of the small C3 breakdown product, C3d, was used to investigate complement activation in 45 plasma samples from 30 patients with rheumatoid arthritis (RA). The mean plasma C3e level in these samples (3.0 +/- 1.3 mg/100 ml) was significantly increased (P less than 0.001) as compared to patients with degenerative joint disease (0.9 +/- 0.4 mg/100 ml) and healthy blood donors (0.8 +/- 0.5 mg/100 ml). C3d levels were increased by more than s SD in 79% of RA samples. Plasma C3d levels were compared with C3d concentrations in synovial fluid. In most RA patients, the C3d levels were higher in synovial fluid than in plasma. A very significant correlation between plasma C3d levels and circulating immune complexes, as measured by determination of Clq binding activity (Clq BA), was observed (P less than 0.001). C3d levels were more elevated in RA patients with extra-articular disease manifestations (3.8 +/- 1.2 mg/100 ml) as compared to patients with joint disease alone (2.2 +/- 1.0 mg/100 ml). C3d levels and Clq BA were also significantly correlated (P less than 0.001) with the RA disease activity expressed by an index derived from sedimentation rate, joint score, and duration of morning stiffness. A close relationship between C3d levels, Clq BA, and the clinical activity further appeared during follow-up studies. The present observations suggest that a parallel but rather independent activation of the complement system may be induced by immune complexes in circulating blood and in the joint spaces during the course of rheumatoid arthritis.
161345 Diets deficient in copper and zinc? 1979 Dec Hospital diets, and, perhaps, diets in general may be low in copper and zinc, with the diets being lower in copper than zinc in comparison to requirements. Several human diseases or pathologic conditions of unknown etiology have similarities to findings in deficient animals. Thus nutritional status and metabolism of copper may be important in anemia, ischemic heart disease, rheumatoid arthritis, osteoporosis, multiple sclerosis and seborrheic dermatitis. Zinc may be involved in growth failure, acne, difficulties of labor, congenital abnormalities and wound healing. Whether or not dietary amounts of copper and zinc are involved in the etiology or the pathogenesis of these conditions can be determined by clinical investigation.
482843 [Study of cellular elements in synovial fluid in scanning electron microscopy]. 1979 Apr Scanning electron microscopy allows a tridimensional morphological study of the cellular elements of the pathological human synovial fluid. The cells are grouped into two populations: macrophage cells and round cells, whose differentiation is more difficult: polynuclears, lymphocytes and synovial cells. The combination of scanning electron microscopy and X-ray diffraction makes it possible to describe and indentify crystals of sodium urate and of triclinical, dehydrated calcium pyrophosphate.
108824 Antibodies against neurons in chronic Chagas' disease. 1979 Mar Severe qualitative and quantitative alterations of the autonomic system inervating the heart and other organs have been demonstrated in experimental and natural Chagas' disease. These facts led us to search for the presence of antibody to neurons in 230 chagasic sera by an indirect immunofluorescence technique. Our results indicated that 83% of the chagasic patients presented IgG antibodies and 7% IgM antibodies to neurons. All control sera were negative. The demonstrated antibody to neurons presented cross-reaction against neurons of the central and peripheral nervous system (sympathetic and parasympathetic) and also against neurons of different species.
947171 A new apparatus for measuring diameter changes of the rat paw and tibiotarsal joint. 1976 A new apparatus for the study of hind-limb inflammation in the rat is described. It measures with high precision the diameters of the hind paws and tibiotarsal joints at anatomically well defined reference points. Inflammation induced by subplantar carrageenin injection and by inoculation of adjuvant in the tail is accompanied by readily detectable and pronounced increases in diameters. Results obtained with this rapid and simple method are reliable and the method offers practical advantages over volume measurements.
6325344 Effect of antiinflammatory agents on neutrophil superoxide production in rheumatoid arthri 1984 Mar Granulocyte superoxide production by different stimuli was studied in 14 patients suffering from rheumatoid arthritis, and in four cases defective O(2) generation was shown. The effect of two chemically related drugs, such as indomethacin and oxamethacin, was also evaluated, since we have previously investigated the action of antiinflammatory agents on cell locomotion. Indomethacin did not affect O(2) production, whereas oxamethacin reduced significantly superoxide generation in PMNs from all subjects tested. Moreover, the extent of the effect was dependent on the stimulant used, being larger when the activation of O(2) generating system was induced by opsonized zymosan.
390674 A controlled trial of tiaprofenic acid versus ibuprofen in rheumatoid arthritis. 1979 Nov Tiaprofenic acid, 200 mg three times a day, was compared with ibuprofen, 400 mg three times a day, in 41 patients suffering from rheumatoid arthritis and already receiving nonsteroidal anti-inflammatory drugs in a double-blind controlled study. The degree of disability expressed as functional class was significantly improved on tiaprofenic acid. There were no other significant differences from initial values on either treatment in any other clinical measure of therapeutic efficacy. Side-effects were few and minor and there were no significant differences between the drugs in this respect.
1081725 Mitogens of B and T cells from peripheral blood in rheumatoid arthritis. 1975 Patients with rheumatoid arthritis (RA), 36 cases, and normal subjects, 49 cases were studied by lymphocyte cultures stimulated by phytohemagglutinin (PHA), Concanavalin A (Con A), pokeweed mitogen (PWM) and Con A convalently bound to Sepharose 4 B (Con A-S). The comparisons between the two groups showed a significant difference between the RA lymphocytes and the control lymphocytes stimulated by PHA and Con A. However, no statistical difference was found between the two lymphocyte populations stimulated by PWM and Con A-S. In order to determine the lymphocyte population stimulated by each mitogen, separation of B and T cells from peripheral blood was performed according to the ability for the T cell population to bind the sheep red blood cells (rosette-forming cells). The T cell-rich population was only stimulated by PHA, Con A and PWM. Although the T cell-depleted population showed no response to these mitogens, a response to Con A-S was elicited.
105740 Immunoelectrophoretic assay for synovial fluid C3 with correction for synovial fluid globu 1979 Mar Synovial fluid C3 was measured by electroimmunoassay. When C3 was expressed as mg/ml, the amounts found in Reiter's disease, psoriatic arthritis, gout, and systemic lupus erythematosus were significantly different from degenerative arthritis. When C3 was corrected for total protein, the levels for rheumatoid arthritis, Reiter's disease, psoriatic arthritis, and systemic lupus were significantly different from degenerative arthritis. When C3 was corrected for synovial fluid globulin, only rheumatoid arthritis and systemic lupus were significantly different from degenerative arthritis. Correction of C3 for globulin increases the difference between rheumatoid arthritis and degenerative arthritis. A proportion of gouty fluids with a relative decrease in C3 is demonstrated. It is argued that correction of C3 for globulin is more meaningful than correction for total protein. While many nonrheumatoid inflammatory effusions demonstrate split products of C3, the majority of fluids from patients with systemic lupus have none.
6602812 Clinical application of a new nephelometric technique to measure complement activation. 1983 Jul A new nephelometric technique to measure C3d as an indicator of complement activation, is described. C3d is isolated at high concentration of polyethyleneglycol (PEG), incubated with commercially available anti-C3d antiserum at a final concentration of 2.5% PEG and then measured in a Behring Laser Nephelometer. In contrast to previously available techniques our assay detects the low concentrations of C3d present in all normal subjects, which result from the continuous C3 catabolism occurring in vivo. We have also measured C3d blood concentrations in a large number of patients with diseases associated with complement activation. Raised C3d concentrations were found in 68% of rheumatoid arthritis, 57% of primary biliary cirrhosis, 38% of chronic active hepatitis, 100% of Gram-negative bacteraemia and 100% of malaria. The nephelometric technique has proved to be sensitive, economical and fast, and could be adapted for routine determination of C3d blood concentrations to monitor disease activity and response to treatment.
6789838 Cytotoxic chemotherapy for cancer in Felty's syndrome: role of lithium carbonate. 1981 Sep A 61-yr-old white man with Felty's syndrome, who had previously undergone splenectomy, presented for cytotoxic chemotherapy. Random granulocyte counts remained low, prohibiting the initiation of such treatment. A trial of lithium carbonate was instituted, resulting in prompt elevation of granulocyte counts into the normal range. Cytotoxic chemotherapy was then administered, and fluctuations of neutrophil counts similar to those of hematologically normal individuals were observed.
6840827 Neutrophil migration in response to chemotactic factors: effects of generation conditions 1983 Mar The effects of various chemotactic factor generation conditions and several chemotherapeutic agents on neutrophil migration were determined using in vitro assay systems designed as models for inflammatory processes occurring in the synovial cavities of patients with rheumatoid arthritis. The microtubule-promoting agent concanavalin A and the microfilament-disrupting agent cytochalasin B were shown in these systems to inhibit neutrophil migration towards zymosan-activated serum-derived chemotactic factors. Neutrophils, immunoglobulin G aggregates, and serum were required for maximum generation of comparable chemotactic factors. Insoluble immunoglobulin G aggregates with or without rheumatoid factor produced more chemotactic factor activity on interaction with neutrophils than soluble immunoglobulin G aggregates. Exposure of neutrophils to supratherapeutic levels of the nonsteroidal antiinflammatory agent aspirin decreased neutrophil response to chemotactic factors while exposure to the slow-acting or immunomodulating agents gold, D-penicillamine, or azathioprine had no effect on this neutrophil function. In vitro systems employing neutrophils, insoluble aggregates, and serum may offer useful means for assaying drug effects on important functional components of the rheumatoid inflammatory process.
6810477 An oral gold formulation in rheumatoid arthritis. A 12-month follow-up report. 1982 Aug 28 Oral gold(Auranofin; SKF) 6 mg/d has been used in an open study in 31 patients with active rheumatoid disease, 19 of whom have been on continuous treatment for 1 year. Four of these patients were considered to be in remission and 9 had a good clinical response to treatment. Four showed only minimal improvement and 2 did not improve at all. There were, however, no changes in the biochemical parameters of inflammation, e.g. haemoglobin concentration, erythrocyte sedimentation rate, platelet count and rheumatoid factor, or in renal and hepatic function. Of the 31 patients, 9 (29%) have discontinued treatment but only 3 (9.7%) because of side-effects. Minor side-effects have been fairly common, occurring in 19 patients (61%), and included skin rashes and pruritus, diarrhoea and loose stools, nausea, stomatitis and thrombocytopenia or leucopenia. Oral gold would seem to be a safer, less potent form of chrysotherapy than parenteral gold.
6883809 Association of rheumatoid factor with complement activation in rheumatoid arthritis and ot 1983 Aug Rheumatoid factor (RF) is a complement activating autoantibody. In rheumatoid arthritis (RA) the rate of catabolism of complement is closely related to the titre of RF. Therefore, we have examined whether these relationships are unique to RA or will be found in non-RA disorders in which RF may be found in the circulation. We studied patients with subacute bacterial endocarditis, leprosy, tuberculosis, and a variety of other rheumatic and vasculitic disorders. We found that in all the disorders examined the RF had a complement activating potential which was equivalent to that of the RF of RA patients. Furthermore in vivo activation of complement, as exhibited by the appearance of C3 degradation products, was significantly related to higher titres of haemolytically active RF in non-RA as well as the RA group. In these respects, therefore, the RF in RA and non-RA patients is indistinguishable. A possible survival value for RF is discussed.
6609700 Comparative study of piroxicam and ibuprofen in rheumatoid arthritis. 1983 Dec Piroxicam was compared with ibuprofen in a 8 weeks randomised open clinical trial in 31 patients (16 patients with piroxicam and 15 patients with ibuprofen) with rheumatoid arthritis. Piroxicam was given in a dosage of 20mg once daily and ibuprofen 400mg three times a day. Both drugs appeared to be equally effective and there were only few minor side effects in patients on either drug. The once daily administration gives piroxicam a clear practical advantage over ibuprofen.
773500 Azathioprine and penicillamine in treatment of rheumatoid arthritis: a controlled trial. 1976 May 1 Sixty-five patients, 33 receiving azathioprine and 32 receiving penicillamine, took part in a one-year, single-blind external-observer trial designed to compare the efficacy and toxicity of these two drugs in the treatment of rheumatoid arthritis. By six months there was a significantly greater rise in haemoglobin and fall in erythrocyte sedimentation rate among those receiving penicillamine, and by one year this difference remained only in the increase in haemoglobin levels. Fifteen patients, 10 on azathioprine and 5 on penicillamine, had to stop treatment because of side effects; 90 single side effects occurred, 48 in those on penicillamine and 42 in those on azathioprine. After one year both drugs were similar in efficacy and toxicity, but longer-term trials are needed. Both drugs were effective.