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

ID PMID Title PublicationDate abstract
2556902 Eicosanoid production in rheumatoid synovitis. 1989 Nov Leukotriene B4 (LTB4) synthesis in rheumatoid synovitis was studied using peripheral and synovial fluid polymorphonuclear leukocytes (PMNs) and rheumatic synovial lining cells. No differences were found in LTB4 synthesis between peripheral PMNs from healthy volunteers and rheumatoid arthritis patients. When peripheral and synovial PMNs from the same RA patient were compared, arachidonic acid-induced LTB4 synthesis in synovial fluid PMNs was increased 1.7-7.2 fold, whereas the response to Ca ionophore A23187 stimulation was similar. This suggests 5-lipoxygenase stimulating factor(s) in inflamed joints. Rheumatic synovial lining cells in a primary cell culture produced small amounts of LTB4, the concentrations being less than 0.1 per cent of those of prostaglandin E2 (PGE2). PGE2 synthesis in synovial cells was increased when arachidonic acid or interleukin-1 was added to the culture, whereas LTB4 production remained unaltered. The present results suggest that in inflamed joints LTB4 originates mainly from PMNs whereas synovial lining cells are the source for PGE2.
3135770 Purification and characterization of the 1q subcomponent of canine complement and its use 1988 Jun The complement subcomponent, C1q, was isolated from serum obtained from clinically normal dogs, using a rapid 2-step process involving affinity chromatography. Yield of C1q ranged from 8 to 10 mg/L of serum. Hemolytically active C1q had 3 protein bands after sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions and formed a single line of identity with rabbit anti-canine C1q. The amino acid composition of canine C1q was similar to that of human C1q and contained a high percentage of glycine. Isolated canine C1q was iodinated, and the fluid-phase binding assay was used to detect circulating immune complexes in dogs with systemic lupus erythematosus and rheumatoid arthritis.
2957387 Evaluation of anti-C1q capture assay for detecting circulating immune complexes and compar 1987 Aug An anti-C1q capture method kit (C1q-immunoglobulin G [IgG]) (Ortho Diagnostics, Inc., Raritan, N.J.) for measuring circulating immune complexes (CIC) was evaluated. The kit showed poor diagnostic sensitivity (P less than 0.005) for identifying CIC in patients with systemic lupus, rheumatoid arthritis, and bacterial endocarditis, as compared with polyethylene glycol-IgG and Raji cell tests (12, 24, and 24 positive, respectively, of 31 patients). Of the patients who were positive with the C1q-IgG test, 25% showed discrepancies when their results were compared with the polyethylene glycol-IgG and C1q-binding test results. Gel filtration chromatography of two of these discrepant sera showed the only peak of C1q-IgG activity to be associated with monomeric IgG (molecular weight, less than 200,000). We concluded that the kit method may be measuring substances other than CIC in some sera, because molecules of C1q attached to IgG should exhibit a molecular weight of greater than 500,000.
2673276 Dendritic cells in health and disease. 1989 Jun Cells with a dendritic morphology that are rich in surface class II histocompatibility antigens (Ia antigens) but lacking in other lymphocytes or monocyte markers constitute a small (less than 1%) proportion of circulating mononuclear cells, but in inflammatory joint effusions they comprise up to 7% of the mononuclear population. Their role as accessory cells in normal autologous and allogenic mixed leukocyte reactions is reviewed and the possible contribution of dendritic cells to intra-articular immunologic processes is considered.
2009650 Shoulder arthroplasty for rheumatoid arthritis. 1991 Apr Forty-two Designed After Natural Anatomy (DANA) total shoulder arthroplasties (Howmedica, Rutherford, New Jersey) were performed in 34 rheumatoid patients. Thirty shoulders in 23 patients were followed for a minimum of two years. Twelve of the 30 shoulders (40%) had significant rotator cuff tears. The average rating for pain improved from 3 points preoperatively to 8 points postoperatively for the overall group, and the average rating for function improved from 3 points preoperatively to 6 points postoperatively. Range of motion (ROM) improved substantially in patients treated with a regular glenoid component. Four patients were treated with hooded glenoid components designed to improve stability for shoulders in which the rotator cuff was deficient. In the rotator-cuff-deficient patients, pain and function improved; however, ROM was unchanged. Complications, including one acromial fracture and two loose glenoid components, required revision surgery.
3349680 Supracondylar fractures of the femur adjacent to resurfacing and MacIntosh arthroplasties 1988 Apr Twelve cases of supracondylar fracture of the femur in rheumatoid arthritis patients with previously implanted resurfacing or MacIntosh arthroplasty of the knee had long standing severe polyarticular rheumatoid arthritis (duration, ten to 41 years; mean 24.8 years). The fractures occurred following a long interval after implantation of the prosthesis (five to 204 months; mean, 92.3 months). Two fractures were treated by stable and two by unstable fixation; eight were treated nonoperatively. The fractures healed in a normal time with one exception, but the femur was shortened in ten cases (mean, 2.8 cm), and axially malaligned in nine. The ability to walk long distances decreased in eight cases and pain increased in seven; two prostheses were loosened and displaced. Because of the poor results of nonoperative management, internal fixation of these fractures is recommended in selected cases.
1914237 Identification of the major fibroblast growth factors released spontaneously in inflammato 1991 Oct Rheumatoid arthritis is characterized by chronic inflammation and proliferation of a number of important elements within the joint including the synovial fibroblasts. Elevated levels of a number of cytokines such as Il-1, IL-2, IL-6, interferon-gamma (IFN-gamma), transforming growth factor-beta and tumour necrosis factor-alpha (TNF-alpha) have been detected in the synovial fluid of patients with rheumatoid arthritis and other inflammatory arthritides. It seems likely that local release of such mediators may be responsible for the proliferation and overgrowth of connective tissue elements in these disorders. In order to ascertain whether there was evidence to suggest local production or release of fibroblast growth factors in the joint in inflammatory arthritis, and to determine their identity, cells were obtained from the synovial fluid of 15 patients with chronic inflammatory arthritides. All subjects' synovial fluid cells spontaneously released growth factor activity for fibroblasts. This was present in large amounts, being detectable in culture supernatants diluted to a titre of at least 1/625. By a series of depletion experiments using solid-phase bound antibodies to cytokines, it was possible to demonstrate that this activity was due to TNF-alpha and platelet-derived growth factor (PDGF). Thus, this study showed for the first time that functionally active PDGF was released from synovial fluid cells. Both PDGF and TNF-alpha appeared to contribute in approximately equal amounts to this fibroblast growth factor activity, and were synergistic in effect. Thus this study provides evidence for the local production and release of these two cytokines and suggests that together they are the dominant factors in fibroblast proliferation within the synovial cavity.
1765037 Individual differences in the day-to-day experience of chronic pain: a prospective daily s 1991 Explored the distribution and temporal patterning of daily pain reported by 47 patients with rheumatoid arthritis (RA) for 75 consecutive days. Approximately half the pain series were significantly positively skewed, trended significantly across the recording period, or both. One fourth of the sample had relatively painful "outlier" days that clustered together. Most series displayed a significant autocorrelation in pain intensity across successive days even when the series were detrended. Patients with more active disease had pain that was more intense but more predictable from day to day and reported fewer painful outlying days and briefer episodes of atypically severe pain. Patients describing themselves as more depressed on the Center for Epidemiological Stress Depression Scale also reported more intense pain across the recording period, independent of their level of disease activity and disability. Implications for daily process studies of RA pain are discussed.
3630669 Arthroplasty in tuberculosis of the knee. Two cases of missed diagnosis. 1987 Jun Active tuberculosis arthritis was diagnosed in two patients after they had undergone total knee replacement. Antituberculous therapy was successful.
3663263 Effects of dietary supplementation with marine fish oil on leukocyte lipid mediator genera 1987 Sep Twelve patients with active rheumatoid arthritis supplemented their usual diet with 20 gm of Max-EPA fish oil, daily, for 6 weeks. Following this supplementation, the ratio of arachidonic acid to eicosapentaenoic acid in the patients' neutrophil cellular lipids decreased from 81:1 to 2.7:1, and the mean generation of leukotriene B4 (with calcium ionophore stimulation) significantly declined by 33%. The mean neutrophil chemotaxis to both leukotriene B4 and FMLP significantly increased toward the normal range at week 6. The generation of 5-lipoxygenase products by calcium ionophore-stimulated monocytes was not significantly suppressed, but a significant decline (37%) in platelet-activating factor generation was noted at week 6. The modulation of these measures of leukocyte inflammatory potential suggests that fish oil supplementation may have an antiinflammatory effect.
3207381 Antibodies to type II and XI collagens: evidence for the formation of antigen specific as 1988 Dec Antigen specific and cross reacting antibodies to native and denatured types II and XI collagen were detected in the sera of rats immunised with either of these antigens. The antibodies from rats immunised with type XI collagen initially showed the strongest binding to the alpha 2(XI) chain of type XI collagen but later binding to the alpha 3(XI) chain was seen. Sera from patients with rheumatoid arthritis had antibodies that bound to both type II and XI collagens. Immunoblotting studies showed that most patients had antibodies which bound to the alpha 1(II) chain of type II collagen and to the alpha 3(XI) chain of type XI collagen. Some patients also had antibodies which bound to the alpha 1(XI) and to the alpha 2(XI) chains of type XI collagen. Thus antibodies to unique as well as to common epitopes on each of the two types of collagen molecule occur in some patients with rheumatoid arthritis.
2661582 Treatment considerations in the complicated rheumatoid hand. 1989 May The rheumatoid patient with complex involvement or multiple deformities of the hand and wrist can be a challenge to the hand surgeon. A systematic and orderly approach is used to formulate and execute a treatment plan that is realistic and that can result in modest, but significant improvement in overall hand function. The evaluation and treatment philosophy which is described can help turn a complicated and seemingly overwhelming situation into smaller components which can be treated in one or more surgical stages.
3778159 Comparison between arthroscopic and open synovectomy for the knee in rheumatoid arthritis. 1986 Ten surgical anterior capsulosynovectomies following Mori's four-block capsular incision technique in nine rheumatoid patients and 14 arthroscopic synovectomies utilizing a Wolf arthroscope with a large pituitary rongeur or a motorized intra-articular shaver in 11 patients were performed in our department. In three patients with bilateral involvement at nearly the same stage (III), we operated on the knees simultaneously, using open capsulosynovectomy on one side and arthroscopic synovectomy on the other side; we comparatively assessed the postoperative course, the subjective evaluation of the patients, and the follow-up results. Surgical intervention is milder in the arthroscopic operation, and postoperative knee pain during motion exercise is markedly less in the arthroscopically synovectomized knee. Although the postoperative management was more complex for open capsulosynovectomized knees, the results obtained at 1-2 months after synovectomy showed no significant difference between the two procedures.
3733796 Rheumatoid arthritis of the thoracic and lumbar spine. 1986 May We report seven cases of patients with seropositive rheumatoid arthritis in whom involvement of the thoracic and lumbar vertebrae occurred. Histological corroboration is presented in four. Pathological lesions comprised various combinations of paravertebral joint erosions, erosive discitis, anteroposterior and rotatory instability, major lumbar nerve root compression, and vertebral collapse. Specific radiological features are presented, enabling a distinction to be made between pure degenerative spondylosis and rheumatoid spondylitis. We submit that subcervical rheumatoid spondylitis is commoner than is generally believed, though less common than rheumatoid involvement of the cervical spine.
2784801 Increased polyamines may downregulate interleukin 2 production in rheumatoid arthritis. 1989 Apr Polyamines downregulate immune reactivity. RA is associated with decreased IL 2 production. In this study, we present evidence to suggest that excessive polyamines can contribute to the IL 2 deficiency in RA. Blocking polyamine production with inhibitors of ornithine decarboxylase results in increased IL 2 production by RA PBMC. Moreover, polyamine oxidase (PAO) inhibitors and catalase also increase IL 2 production by RA PBMC. This effect of PAO inhibition is monocyte mediated. After 3 d in culture, RA PBMC produce three times more IL 2 than do normal PBMC. This rise is prevented by exogenous spermidine but only in the presence of monocytes. The concentration of polyamines in RA PBMC and synovial fluid MNC is 2-20-fold higher than in normal cells. Thus, polyamines and their oxidation products downregulate IL 2 production by RA PBMC and may account for the decreased T cell effector function seen in this disease.
2611998 Abnormally-fucosylated serum haptoglobins in patients with inflammatory joint disease. 1989 Oct 16 The fucosylation of haptoglobins is altered in rheumatoid arthritis. In order to investigate the clinical usefulness of this finding, serum levels of abnormally-fucosylated haptoglobins (FHp) have been assessed in defined and matched groups of patients with different inflammatory joint diseases. FHp was elevated in 16/17 patients with active rheumatoid arthritis (RA); 1/20 patients with inactive rheumatoid arthritis; 1/11 patients with osteoarthritis; and 4/10 patients with seronegative polyarthritis. Raised FHp levels, therefore, are not disease-specific. There was no relationship between the duration of RA and the FHp level. The FHp expression in RA was also compared with other biochemical indices of disease activity. The degree of correlation between FHp and articular index, joint score and early-morning stiffness was very similar to that obtained for C reactive protein (CRP), and better than that obtained for erythrocyte sedimentation rate and haemoglobin. FHp, however, gives fewer false-positives than CRP in cases of inactive disease. until FHp can be measured more easily and cheaply, CRP estimation is still the biochemical test of choice in RA.
3810298 Somatosensory-evoked potentials in the evaluation of the unstable rheumatoid cervical spin 1986 Oct Median nerve somatosensory-evoked potential (SEP) examinations were performed in 24 consecutive patients with rheumatoid arthritis who had symptomatic cervical spine instability. Eighteen patients had C1-C2 instability: in ten, the subluxation was completely reducible, and in eight, the subluxation was irreducible, with or without superior migration of the odontoid process. Four patients had superior migration alone, and two had subaxial subluxation alone. Abnormal SEPs were found in seven patients overall. However, 58% of those patients with irreducible atlanto-axial subluxation and/or superior migration of the dens demonstrated abnormal cervical cord conduction latencies. Patients with these radiographic findings may be at a higher risk for the development of overt myelopathy.
3034780 Generation of superoxide by immunologically stimulated normal human neutrophils and possib 1987 Jun Rheumatoid synovial fluids generated significantly greater amounts of superoxide, lysosomal enzymes, and superoxide dismutase from neutrophils into extracellular fluid than osteoarthritic synovial fluids. Rheumatoid factors isolated from serum suppressed superoxide-generating activity of performed immune complexes, but did not suppress that of intermediate-sized immune complexes isolated from RA serum. Synovial fluid neutrophils has a greater capacity to generate superoxide and lower intracellular superoxide dismutase activity, compared with peripheral neutrophils of the corresponding patients. These results suggest that neutrophil superoxide release may be modulated, both by rheumatoid factor and by intracellular and extracellular superoxide dismutase.
1906940 Antigenicity and accessory cell function of human articular chondrocytes. 1991 Mar It is postulated that chondrocytes may be actively involved in the pathogenesis of inflammatory joint diseases, presumably by providing tissue specific antigens that may initiate or sustain autoimmune reactions. To investigate whether chondrocytes may also function as accessory cells in ongoing immune processes, mixed leukocyte-chondrocyte cultures and antigen presentation assays were studied. Freshly isolated and short term cultured HLA class II antigen (Ia) negative as well as gamma-interferon treated Ia positive chondrocytes were weakly or not stimulatory to allogeneic or autologous resting lymphocytes derived from either normal donors or patients with rheumatoid arthritis. In an antigen presenting system using tetanus toxoid, the majority of chondrocyte preparations tested induced an antigen driven response in HLA matched allogeneic or autologous resting T cells which, however, was much less when compared to blood monocytes. In contrast, using activated T cells derived from tetanus toxoid specific T cell lines, an efficient antigen presenting capacity could be demonstrated in both Ia positive and initially Ia negative chondrocytes. Interestingly, the latter population had acquired Ia antigens upon incubation with the T cell line.
2147952 Altered erythrocyte CR1 binding kinetics compensate for decreased binding capacity in rheu 1990 Aug Patients with rheumatoid arthritis have decreased numbers of CR1 per erythrocyte and decreased binding of immune complexes to erythrocytes. Overall erythrocyte immune complex binding activity depends on both the number and the binding kinetics of CR1. We measured kinetic parameters for the interaction between a complement-containing dsDNA:anti-dsDNA probe and erythrocytes in patients with rheumatoid arthritis and normal controls. The results indicate that: 1) the maximum quantity of immune complexes bound per erythrocyte was significantly decreased in rheumatoid arthritis compared with normal controls (p less than or equal to 0.009); 2) the steady state binding constant, Kss, and the association rate constant for binding of immune complexes to erythrocytes, ka, were significantly increased in rheumatoid arthritis versus normal controls (p less than or equal to 0.0001 and 0.002 respectively); 3) the dissociation rate constant for the release of bound immune complexes from erythrocytes, kd, was slightly smaller in rheumatoid arthritis but this difference was not statistically significant; and 4) the energies of activation for the association and dissociation reactions, Eaa, and Ead, did not differ between the two groups. These data confirm that while the maximum quantity of immune complexes bound per erythrocyte is decreased in rheumatoid arthritis, the association rate constants are larger and dissociation rate constants slightly smaller than those of normal controls. Changes in these kinetic parameters compensate for the decrease in the maximum quantity of immune complexes bound per erythrocyte.(ABSTRACT TRUNCATED AT 250 WORDS)