Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2893450 | The pharmacokinetics of sulphasalazine in young and elderly patients with rheumatoid arthr | 1987 | The clinical pharmacokinetics of enteric-coated sulphasalazine (Salazopyrin-EN) were studied after acute and chronic dosing in 20 patients with 'active' rheumatoid arthritis. 12 elderly (mean age 74.4 +/- 1 yr; range 71-83) and 8 young (mean age 40.5 +/- 1.4 yr; range 35-46) patients were given a single 2 g oral dose of sulphasalazine after an overnight fast. Serum and urine samples were collected at regular intervals over a 96 hour period for estimation of concentrations of sulphasalazine, sulphapyridine and its metabolites. This procedure was repeated after 17 days of continuous treatment with salazopyrin-EN 2 g daily in order to compare the drug's kinetics at 'steady-state'. Whilst the interindividual variation in kinetic parameters was large, age and acetylator status had a significant influence on a number of factors. The elimination half-life of sulphasalazine was prolonged in the elderly whilst renal clearance was increased in slow acetylators at 'steady-state'. The tmax and apparent volume of distribution of sulphapyridine were increased in the elderly after a single drug dosage but these differences disappeared with regular dosing. The Cmax, elimination half-life, 'steady-state' serum concentration, apparent volume of distribution and total clearance of sulphapyridine were all affected by acetylator status. We conclude that old age has only a minor effect on the body's handling of sulphasalazine and sulphapyridine but that acetylator phenotype plays a significant role in determining the 'steady-state' serum concentrations of sulphapyridine. This is likely to have practical implications with regard to some of the drug's adverse effects. | |
| 2188346 | [Management of children with chronic rheumatism. Similarities and differences with rheumat | 1990 Apr 10 | In France, about 3,000 children under 16 years of age suffer from juvenile chronic arthritis (JCA), whose management presents a problem. JCA covers several nosological entities. In 20% of the cases, a systemic form affecting the articulations in an inconstant way, and starting in the very young child, is observed. In 30% of the cases, a form with a polyarticular start is observed. This group is very heterogeneous and includes in particular early seropositive rheumatoid arthritis (RA), the little girls' polyarthritis with presence of antinuclear antibodies, and the little boys' rheumatisms HLA B27. Finally, in 50% of the cases, an oligoarticular form is observed, also expressed in greatly varying ways. In all cases, the evolution is unpredictable and the management of these children is different from that of adults. It must be noted that the treatments used in adults are rarely applied to children as JCA is a pathology which is quite different from RA. Several types of treatment can be administered by general route: non-steroidal antiinflammatory drugs (NSAIDs) and mainly aspirin, since few NSAIDs have a paediatric licence in France. However, the risks of intolerance at doses reaching up to 100 mg/kg are not negligible. Some NSAIDs can be used in older children. The slow acting drugs are dangerous in the systemic form of JCA. Their indication seem to be more appropriate in the polyarticular forms. In the oligoarticular forms, slow acting drugs are rarely proposed. Corticosteroids are prescribed in aspirin-resistant systemic forms only. Besides the complications observed in adults, the growth is stopped in a constant way.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1978810 | Clonal analysis of T cell infiltrates in synovial tissue of patients with rheumatoid arthr | 1990 Dec | To investigate the possibility of the presence of disease-relevant, antigen-specific immune reactions in rheumatoid arthritis (RA), clonal diversity of the T cells in the synovial tissue was examined. T cells were directly cloned by in vitro stimulation with phytohemagglutin and interleukin 2 from both the peripheral blood and inflammatory synovial tissue. Their clonotypes were defined by analyzing rearrangement patterns of T cell receptor (TCR) beta and gamma chain genes using Southern blotting. In total, 111 clones from the synovial tissue (four patients) and 45 from the peripheral blood (one patient) were studied. Although most of the clones were unique in their TCR gene rearrangement patterns, 2 clones from the synovial tissue of one patient had identical patterns. These 2 clones were CD3+, 4-, 8+. Since phenotypic analysis of 82 clones from the synovial tissues revealed that CD8+ T cell clones were less frequent (24%) than CD4+ clones, the clonal identity observed here in 2 clones may not be negligible. Furthermore, 1 CD8+ clone from the peripheral blood of the same patient also had the same clonotype. These results may suggest selective trafficking or proliferation of CD4-, CD8+ T cells in RA synovial tissue. | |
| 2532990 | Possible different mechanisms of B cell activation in systemic lupus erythematosus and rhe | 1989 Dec | To clarify the differential state of B cell activation in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), we investigated the expression of low-affinity receptor for IgE (Fc epsilon RII; CD23) on their peripheral B cells by a cytofluorometry using H107 (CD23) and Leu-16 (CD20) monoclonal antibodies. The percentage of CD23-negative B cells in total lymphocytes was significantly greater in both groups of patients than in normal subjects, suggesting the hyperactivity of late-phase B cells in both diseases. However, the increase of CD23-negative B cells in RA was brought about by the increased number of total B cells, although that in SLE was mainly based on the relative decrease of CD23-positive B cells. The number of IgD-positive B cells was decreased, and the number of colony-forming B cells was markedly increased in SLE patients. These observations indicate that a B cell abnormality is mainly qualitative in SLE but quantitative in RA. | |
| 2224402 | Patients with arthritis and anti-U1-RNP antibodies: a 10-year follow-up. | 1990 Oct | Five hundred and forty patients attending a rheumatology ward were screened for antinuclear antibodies (ANA) by indirect immunofluorescence (IFL). Seventy had a significant titre of ANA. Twenty-three had U1-ribonucleoprotein antibodies (U1-RNP-ab). The clinical findings in U1-RNP-ab-positive patients were consistent with mixed connective tissue disease (MCTD). Disease was more serious in the U1-RNP-ab-positive patients in terms of polyarthritis severity as well as mortality due to rheumatic disease. Thus, in this arthritis patient population, U1-RNP-ab positivity predicted an aggressive disease characterized by an erosive arthritis. | |
| 3260684 | Biological characterization of T cell-replacing factor in the synovial fluid of rheumatoid | 1988 Jun | The synovial fluid of patients with rheumatoid arthritis (RA) contains a biologically active factor which has the ability to replace T cells for the induction of antibody secretion by human blood lymphoid cells stimulated by pokeweed mitogen (PWM) in vitro. This factor, which will be referred to as RA-SF (synovial fluid), also has the capacity to act as a B cell-stimulatory factor of mouse splenic lymphocytes in the presence of lipopolysaccharide (LPS). Using a test system developed for the definition of interleukin 4 (IL-4), which is a B cell-stimulating lymphokine which preferentially activates the synthesis of selected Ig classes in mouse lymphoid cells, we have shown that RA-SF has properties similar to IL-4 in that it induces differentiation of antibody secretion in the LPS-pretreated mouse cell, but unlike IL-4, which gives IgG1 and IgE, it selectively induces IgG2b synthesis. The present study demonstrates that RA-SF has a biological activity that is reminiscent of other B cell-stimulating mouse lymphokines, but it is biologically distinct from IL-2, IL-4, and IL-5. Recent data also indicate that it is distinct from gamma interferon (IFN-gamma). Therefore, we conclude that the biological activity of RA-SF has properties in common with a T-cell replacing (TRF) and B-cell differentiation factor (BCDF) and probably represents yet another biological activity which so far lacks an experimental counterpart. The relevance of this factor for autoantibody synthesis is discussed. | |
| 2891462 | A three-year prospective study of systemic manifestation in rheumatoid arthritis. | 1987 Sep | Rheumatoid arthritis (RA) as a systemic disease can attack many other organs in addition to the joints. A variety of pathological lesions of the blood vessels are responsible for the extra-articular features (EAF). In the present study, we investigated firstly whether the presence of blood vessel changes in one organ--namely the skin--may indicate blood vessel pathology and, consequently, EAF in other organs. Secondly, we investigated the number of EAF in individual patients with RA, and observed whether this changed during the course of the disease. Fifty-one RA-patients (40 female, 11 male; ages had a mean of 49.5, minimum 19, maximum 73 years; mean duration of RA was 7.3, minimum 0.25, maximum 41 years) were included in the study. Punch biopsies from the posterior calf were examined immunohistologically for vessel wall immune deposits. Further, EAF were determined by means of instrumental clinical methods such as pulmonary function test, echocardiography, electromyography, and nerve conduction velocity measurement. At the first investigation 21/51 patients had skin vessel wall immune deposits (SVWID). Five patients--all showed SVWID at first investigation--died during the three-year investigation period, 10 patients could not be followed-up for unknown reasons; the skin biopsy of one patient could not be assessed. At the final investigation, we found SVWID in 11/35 patients. SVWID-positive patients had more EAF compared to SVWID-negative patients; this was true both, at the first investigation (1.85 EAF/patient vs 1.05 EAF/patient) and at the final investigation (1.91 EAF/patient vs 0.67 EAF/patient).(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3726548 | A distinct endothelial cell recognition system that controls lymphocyte traffic into infla | 1986 Aug 1 | Lymphocytes are essential mediators of normal tissue inflammatory reactions and of pathologic tissue damage in, for example, rheumatoid arthritis and other autoimmune diseases. In a study of the mechanisms controlling lymphocyte entry into sites of inflammation from the blood, the function and specificity of lymphocyte-endothelial interactions were examined in inflamed joint tissue (synovium) from patients with rheumatoid arthritis. Synovial high endothelial venules (HEV) supported the binding of normal peripheral blood lymphocytes in vitro. The characteristics of this binding, which were similar to those of lymphocyte-HEV interactions controlling lymphocyte migration into organized lymphoid tissues, included a requirement for calcium ions, a dependence on metabolic activity, and a preferential adherence of circulating lymphocytes as opposed to immature thymocytes. However, the binding of lymphocytes to synovial HEV was not inhibited by a monoclonal antibody to lymphocyte receptors for lymph node HEV, and synovial HEV failed to bind either lymph node HEV-specific or mucosal HEV-specific B lymphoblastoid cells. The results suggest that a lymphocyte-endothelial cell recognition system that is distinct from such systems in organized lymphoid tissues directs the extravasation of normal lymphocytes as well as pathologically important effector cells into inflamed synovium. | |
| 1916873 | [High dose 7S-immunoglobulin therapy in collagenoses. Clinical observations and effects on | 1991 Jun | Therapy with 7S-immunoglobulins in 8 patients with various connective tissue diseases led to a decrease of clinical disease activity. In vitro experiments showed that treatment induces change of B-cell function. Significant quantitative alteration of relative lymphocyte subpopulations did not occur. CRP, C3c, C4 and circulating immune complexes tended to normalization. | |
| 1750123 | Felty's syndrome in a Nigerian. | 1991 Jan | The first case of Felty's syndrome to be reported in a Nigerian, a fifty five-year-old woman who developed splenomegaly and leukopenia during the course of strongly seropositive rheumatoid arthritis of ten years duration is presented. her arthritis had lasted for about ten years, but she did not have the severe deforming disease known to be associated with Felty's syndrome. Radiologically there were no erosions and subcutaneous nodules were absent. She had a positive granulocyte specific anti-nuclear factor, cryoglobulins containing IgA and IgM and her polymorph-nuclear granulocytes showed evidence of impaired killing of staphylococci. | |
| 1862580 | [Felty's syndrome]. | 1991 Jul 8 | Felty's syndrome (FS) consists of the triad: rheumatoid arthritis (RA), leukopenia and splenomegaly. FS occurs in approximately 1% of patients with RA. In this syndrome, the risk of infection is increased and anaemia, thrombocytopenia and cutaneous ulcers are more frequently observed. The literature is reviewed on the basis of a case history. The pathogenesis is unknown but is probably multifactorial. Cell antibodies, increased occurrence of immune complexes, inhibited neutrophil production, altered neutrophil distribution and reduced neutrophil function have been observed. The main indication for treatment is present if the patient has severe neutropenia (less than 0.1 x 10(9)/l) and repeated infections. Various methods of treatment are available. The most important are: gold, low-dose methotrexate, lithium, methylprednisolone pulse therapy, penicillamine and splenectomy. According to the literature, conventional steroid treatment cannot be recommended. | |
| 2920840 | Degradation of type IX collagen by matrix metalloproteinase 3 (stromelysin) from human rhe | 1989 Feb 27 | The degradation of type IX collagen, a minor collagen in cartilage, was examined by treatment with three different types of matrix metalloproteinases (MMPs) purified from the culture medium of rheumatoid synovial cells. Neither MMP-1 (collagenase) nor MMP-2 (so-called 'gelatinase') could digest type IX collagen, but MMP-3 (stromelysin) readily degraded it into smaller fragments. This suggests that MMP-3 may be responsible for the pathological degradation and/or normal turnover of type IX collagen. | |
| 3131571 | Auranofin and gold sodium thiomalate in the treatment of rheumatoid arthritis: a one-year, | 1988 Feb 15 | In a 48-week, double-blind trial, 122 patients were randomly assigned to treatment with auranofin (60) and gold sodium thiomalate (GST) (62) at five centers. Both groups showed significant improvement (P less than 0.05) from baseline in parameters of disease activity. Results of the covariance analysis for all patients who completed the trial showed no significant differences (P less than 0.05) in efficacy between the two groups. The proportions of patients showing 50% or greater improvement in tender joints, swollen joints, activity index, severity of pain, general health rating, and erythrocyte sedimentation rate (ESR) were similar for both auranofin-treated and GST-treated patients who completed the 48-week trial. When all patients who entered the trial were evaluated, a slightly greater proportion of patients on auranofin had improved. Diarrhea occurred more frequently with auranofin (32%) compared to GST (19%), whereas rash and pruritus were twice as common in those patients treated with GST compared to those treated with auranofin. The withdrawal rate due to adverse reactions was 10% for auranofin vs 26% for GST. It was concluded that the efficacy of auranofin was comparable to that of injectable gold and was better tolerated, as evidenced by the lower withdrawal rate from adverse events for the auranofin patients. | |
| 3263239 | Decreased production of suppressive-B-cell factor by synovial membrane B-lymphocytes in rh | 1988 Jul | Suppressive-B-cell factor (SBF) is an autoregulatory B-cell lymphokine produced by heat-aggregated-IgG stimulated B-lymphocytes which suppresses polyclonal immunoglobulin production. SBF production by rheumatoid arthritis (RA) patients' peripheral blood B-lymphocytes inversely correlates with disease activity and in vitro rheumatoid factor production. To further define the role of SBF in the pathogenesis of RA, the present study measured SBF production by surgically-obtained synovial membrane mononuclear leukocytes. SBF production by RA synovial leukocytes was similar to the levels previously described for RA peripheral blood leukocytes. Both RA and osteoarthritis (OA) synovial leukocytes produced significantly less SBF than leukocytes obtained from otherwise healthy patients with plica. OA patients produced less SBF than RA patients, but the difference was not statistically significant. SBF values for combined RA patients and controls with OA or plica correlated with the degree of histological plasma cell infiltration providing further evidence for SBF production by cells of the B-lymphocyte lineage. Depletion studies also demonstrated that synovial SBF was produced by B-lymphocytes. The molecular weight (34,000) of synovial SBF was similar to the molecular weight of peripheral blood SBF. Decreased SBF production by RA synovial B-lymphocytes is a functional abnormality in RA which may contribute to the perpetuation of synovial rheumatoid factor production and chronic synovial inflammation. | |
| 2432961 | [Effect of a medium with a low serum content on protein synthesis and secretion and RNA an | 1986 Dec | Synthesis and secretion of protein, as well as synthesis of RNA and DNA by skin fibroblasts of patients with systemic sclerodermia (SSD) and rheumatoid arthritis (RA) upon prolonged culturing of fibroblasts in the medium with low (0.5-1%) serum content differ markedly in their direction and intensity from protein, RNA and DNA synthesis by skin fibroblasts of healthy donors (HD) and by fetal fibroblasts. It has been found that skin fibroblasts of patients with RA and SSD, as well as those of HD, secrete 75-80% of protein synthesized by fibroblasts de novo upon their culturing in DMEM medium with 1% human serum. Under the same conditions, on days 2-5 of culturing, RNA synthesis in the fibroblasts of patients with RA and SSD was increased 3-4-fold, while DNA synthesis was increased 2-3-fold. Collagenolytic and caseinolytic activity in the culture medium of skin fibroblasts from HD and patients with RA reached maximal levels on days 3-5. High protein secretion was observed in DMEM serum-free medium in the presence of vitamin mixture upon culturing skin fibroblasts of patients with SSD. The results obtained show that skin fibroblasts from HD differ in their functional activity from those of patients with rheumatic disorders. It might be suggested, therefore, that the mechanism of protein secretion plays an important role in the maintenance of constant intracellular protein levels in resting cells. | |
| 1969727 | DNA restriction fragment length polymorphism of HLA-DR2 haplotypes in normal individuals a | 1990 Mar | A strong association between HLA-DR4 and rheumatoid arthritis (RA) has been found in a number of populations. In contrast, the incidence of DR2 is decreased in patients with RA, suggesting that this specificity may confer some protection against the disease. A number of subtypes of DR2 have been defined by serology, by responses in mixed lymphocyte culture reaction, and, more recently, by restriction fragment length polymorphism. These subtypes of DR2 are in linkage disequilibrium with different subspecificities of DQw1. It is thus likely that the distribution of these subtypic DR,DQ haplotypes in DR2 positive patients with RA may be important in understanding the genetic basis of susceptibility/resistance to RA. In this paper a study of the subtypes of DR2,DQw1 haplotypes in 18 patients with RA, who required sodium aurothiomalate as a disease remitting drug, and unrelated healthy individuals is reported. Three subtypes of DR2 haplotypes, DRw15 (Dw2),DQw1.2(DQw6), DRw15(Dw12),DQw1.12(DQw6), and DRw16(Dw21),DQw1, AZH (DQw5), were analysed with a cDNA probe for the DQ beta gene. The data show that DR2 positive patients with RA carried either the DRw15(Dw2),DQw6 or DRw15(Dw12),DQw6 haplotype. No patient with RA was positive for the DRw16(Dw21),DQw5 subspecificity. In contrast, six of 29 (21%) normal healthy DR2,DQw1 positive individuals carried the DRw16(Dw21),DQw5 haplotype. These data together with earlier results on the distribution of the DR4,DQw7 haplotype in patients with RA support the hypothesis that DQB1 chain polymorphism may be important in determining susceptibility to severe RA. | |
| 3286539 | Ultrasound examination of haematomas after total hip replacement. | 1988 | We have used ultrasound after 84 total hip replacements to define the site and size of any haematoma present. Repeated examination after operation indicated when the haematoma had occurred. We have demonstrated that two suction drains were more effective than one in preventing haematomas around the prosthesis in the first week after operation. The early detection of a haematoma allows rational treatment which should reduce the risk of deep infection. | |
| 1721640 | The VLA-4/VCAM-1 pathway is involved in lymphocyte adhesion to endothelium in rheumatoid s | 1991 Dec 15 | Lymphocyte migration to inflammatory sites is an essential factor in the pathogenesis of chronic inflammation. An ensemble of adhesion receptors mediating lymphocyte-endothelial cell recognition and binding are thought to play a crucial role in this process. In the present study, we have explored the molecular basis of lymphocyte adhesion to endothelium in the synovial membrane of patients with rheumatoid arthritis. We established that the very late antigen-4 [VLA-4 (CD49d)] and the vascular cell adhesion molecule-1 (VCAM-1) are important mediators of binding to synovial endothelium of resting and, to a greater extent, of activated T lymphocytes, whereas the leukocyte-function associated antigen-1 [LFA-1 (CD11a/18)]/intercellular adhesion molecule-1 [ICAM-1 (CD54)] pathway is less important in this interaction. In contrast to its prominent role in lymphocyte interaction with endothelium in rheumatoid synovium, the VLA-4/VCAM-1 pathway does not significantly contribute to lymphocyte adhesion to peripheral lymph node high endothelial venule. Thus, the VLA-4/VCAM-1 pathway may be of primary importance in mediating lymphocyte adhesion to inflamed endothelium and in lymphocyte homing to rheumatoid synovium. | |
| 3698380 | Clinical results of the Oxford knee. Surface arthroplasty of the tibiofemoral joint with a | 1986 Apr | The Oxford method of knee arthroplasty replaces the femoral condyles with convex spherical metal components and relines the tibial plateaus with flat metal components. Free meniscal bearings of polyethylene, spherically concave above and flat below, lie between the fixed metal components, held in place by their geometry and ligamentous tension. Advantages of the design include: congruity of the articulating surfaces; unconstrained tibiofemoral movement; preservation of all the ligaments with facility to tension them accurately from a range of bearing thicknesses; minimal bone excision; applicability to unicondylar use. Laboratory studies showed that combined rolling and sliding at meniscofemoral and meniscotibial interfaces mimic normal joint kinematics and mechanics. One hundred twenty-five bicompartmental implants were followed for two to six years. Pain was relieved in 90%; mean flexion limit was 99 degrees and mean flexion deformity 7 degrees. Stability and alignment were recovered in nearly all joints. Six knees failed and were successfully arthrodesed (two) or converted to another prosthesis (four). Eight knees required revision to replace a dislocated bearing (five) or to recement a loose component (three). In knees with an intact anterior cruciate ligament, there were no failures and a low revision rate (4.8%). The prosthesis is proposed as a reliable and safe alternative to more invasive prostheses in rheumatoid and osteoarthritic joints in which the disease is still limited to the articular surfaces. | |
| 2608268 | [Total prosthesis implantation in the arthritic hip]. | 1989 Nov | In 11 patients, hip arthrodeses were converted to arthroplasties. The follow-up period ranged from 1 to 21 years. In some cases the patients' own assessment contrasted with the objective findings. No difference could be determined between previously arthrodesed and ankylosed hips. The duration of arthrodesis did not have an influence on the long-term results. It is interesting to note that in this group of patients the long-term survival rate proved to be slightly better than the overall survival rate for all patients with arthroplasties performed in our clinic. |