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

ID PMID Title PublicationDate abstract
10048531 Failure of the hinge mechanism of a trispherical total wrist arthroplasty: a case report a 1999 Jan We report a patient with rheumatoid arthritis who developed late catastrophic failure of the hinge mechanism of her trispherical total wrist arthroplasty. This was associated with synovitis secondary to wear debris from Titanium, cement, and polyethylene which produced exuberant flexor and extensor tendon synovitis and median nerve compression.
9032816 Serum levels of soluble CD44 variant isoforms are elevated in rheumatoid arthritis. 1997 Serum levels of soluble CD44 variant proteins including sequences encoded by exon v5 and exon v6 (sCD44v5, sCD44v6) were determined in patients with inflammatory rheumatic diseases: 56 with rheumatoid arthritis (RA+) and 31 with miscellaneous inflammatory rheumatic diseases (MIRD). There were very significantly higher serum levels of sCD44v5 and sCD44v6 in patients with RA+ than in those with MIRD (RA+ to MIRD: sCD44v5: 81 +/- 54 ng/ml to 33 +/- 13 ng/ml; sCD44v6: 237 +/- 124 ng/ml to 166 +/- 53 ng/ml; both P << 0.001). In RA+ elevated serum levels of sCD44v5 were correlated with the inflammatory activity of disease. In 17 patients with RA+ three or four follow-up measurements of sCD44v5 were performed within 6 months. The development of sCD44v5 serum levels reflected the clinical course of disease in the patients investigated.
9933086 Involvement of autoimmunity against type II collagen in the development of arthritis in mi 1999 Jan We previously reported that transgenic mice carrying the human T cell leukemia virus type I (HTLV-I) env-pX region (pX-transgenic mice) develop rheumatoid-like inflammatory arthropathy, and suggested involvement of autoimmunity in the pathogenicity. In this report, to elucidate pathogenesis of the arthritis, we investigated arthritogenic antigens in the joints. The TCR beta-chain variable region (Vbeta) repertoires in the lymphatic organs were normal in transgenic mice, however, specific Vbeta-positive T cells were expanded oligoclonally in the affected joints, suggesting that specific antigens, but not superantigens, were involved in the expansion of these T cells. These expanded T cells had the same TCR as those of lymph node T cells reactive to type II collagen (IIC). Moreover, these mice were susceptible to IIC-induced arthritis and oligoclonal T cells of the same Vbeta specificity as that found in spontaneously developed arthritic joint accumulated in the arthritic joints after immunization with IIC. These observations show that endogenous IIC is one of the arthritogenic antigens in the joint, suggesting tolerance break to this antigen in pX-transgenic mice.
9212381 Illness self-schemas in depressed and nondepressed rheumatoid arthritis patients. 1997 Jun This study examined the hypothesized illness self-schemas construct in persons with rheumatoid arthritis (RA). Biases in self-description, information processing, and schema-consistent illness behavior were examined in depressed and nondepressed persons with RA and compared with those of depressed and nondepressed controls. Major findings revealed that RA-depressed subjects exhibited pervasively negative self-description and biased processing of negative illness-related information. RA-nondepressed subjects demonstrated a bias for positive self-description and enhanced processing of positive illness-related information. Using regression analysis, the illness self-schema construct predicted unique variance in self-reported functional disability. Findings are reviewed in the context of previous research on self-schemas, chronic pain, and cognitive variables in chronic illness. Potential clinical implications and directions for future research are discussed. The illness self-schema construct has significant heuristic value which could guide further research on the psychosocial adjustment of individuals with chronic illnesses.
10415616 Melatonin influences interleukin-12 and nitric oxide production by primary cultures of rhe 1999 Jun 22 Because some of the clinical symptoms related to rheumatoid arthritis (RA) synovitis, such as joint morning stiffness and gelling, might be related to the effects exerted by the diurnal rhythmicity of the neurohormone melatonin (MLT) on synovial immune cell activation, we decided to evaluate the influence of MLT on the production of IL-12 and nitric oxide (NO) on primary cultures of RA synovial macrophages. Synovial macrophages were also prestimulated with lipopolysaccaride (LPS). Results were compared with those obtained on cultured human myeloid monocytic cells (THP-1). A significant increase in IL-12 (p = 0.01) was found in media of MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a significant decrease of IL-12 (p < 0.0001) was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to synovial macrophages treated with LPS alone. A significant increase in NO levels (p = 0.01) was found in MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a nonsignificant increase of NO levels was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to cynovial macrophages treated with LPS alone. Finally, a significant increase in IL-12 (p = 0.03) and NO (p = 0.002) concentrations was observed in media of MLT-stimulated THP-1 cells versus RMPI-treated controls. Our results therefore show that MLT induces IL-12 secretion and NO production by unstimulated cultured RA synovial macrophages and human monocytic myeloid THP-1 cells. The unexpected and opposite effects on IL-12 and NO production in RA synovial macrophages treated with LPS may be related to dose-dependent mechanisms exerted by MLT or to altered cell priming in RA macrophages; these are matters of our further research. This study strongly supports the role of MLT in immune response modulation and in particular suggests a close relationship between diurnal rhythmicity of neuroendocrine pathways, cytokine and reactive oxygen intermediate production by monocyte/macrophages, and synovial arthritis symptomatology, at least in RA.
9335630 The experience of rheumatoid arthritis pain and fatigue: examining momentary reports and c 1997 Jun OBJECTIVE: To evaluate the daily experience of patients with rheumatoid arthritis (RA) in an ecologically valid manner; Ecological Momentary Assessment (EMA) was employed. Diurnal cycles and within-day variation of self-reported pain and fatigue were examined as were relationships between pain, fatigue, daily stressful events, and sleep. METHODS: Thirty-five patients with RA were alerted with an electronic beep 7 times per day for 7 consecutive days. Assessments were recorded at each beep. Upon awakening each day, sleep information was reported. RESULTS: There were large individual differences in variation of pain and fatigue. Stressors were associated with increased pain but not fatigue. Subjects with poor sleep had higher levels of pain and fatigue. Diurnal cycles of pain and fatigue were found, yet were observed for only some patients (37% and 34%, respectively). CONCLUSION: The use of EMA deepens our understanding of the pain and fatigue experienced by RA patients. This method may help identify subgroups of patients who are highly "psychoreactive" to environmental stimuli and/or who have diurnal patterns to their symptoms. It may also be used to improve existing instruments.
9775023 [Importance of arthrodesis of the big toe combined with a metatarsal alignment according t 1998 Feb PURPOSE OF THE STUDY: The authors reviewed 70 cases of rheumatoid forefoot treated by Lelièvre, lateral metatarsal resection alignment, associated to first metatarsophalangeal joint arthrodesis. MATERIAL: Rheumatoid arthritis evolution was 20 years an average. It involved cortico-dependent polyarthritis in 48 per cent cases. Metatarsalgia were always present. METHODS: Mean follow up was 44 months (minimum 24 months) Results were analyzed according to Gainor. RESULTS: Foot pain disappeared in thirty two cases. Shoe wearing was normal 50 times. Arthrodesis fused 55 times. Lateral toes metatarsophalangeal joint space was satisfactory 28 times. Metatarsal divergence improved, 80 per cent of patients were satisfied in a subjective estimation and 85 per cent using Gainor's criteria. DISCUSSION: First-Metatarsophalangeal joint arthrodesis ensures permanent stability of the first ray and therefore an harmonious support distribution. The dorsal surgical approach allows an early weight bearing in cortico or immuno dependent patients. CONCLUSION: This technique keeps a low morbidity and ensures stable mid term results.
11273141 Detection of anti-nuclear antibodies from filter paper blood clots using indirect immunoen 2000 May BACKGROUND: The facilities to detect antinuclear antibodies (ANA) patterns in patients with systemic rheumatic diseases/connective tissue disorders (CTD) using indirect immunofluorescence (IIF) technique (the gold standard) are sparse; the technique is technically difficult and expensive. A simpler technique, such as the indirect immunoenzyme (IIE) which uses light microscopy, ought to be evaluated for widespread use in our setting. OBJECTIVE: To study the feasibility and relevance of IIE in demonstrating ANA patterns, both from serum and filter paper blood clots (FPBC), in patients with CTD. METHODS: In this pilot study, ANA were detected from sera and FPBC of 21 patients with proven CTD using IIE; paired FPBC and serum samples were simultaneously collected in 10 patients. All samples, coded randomly, were tested by IIE and IIF, along with positive and negative controls. RESULTS: Using IIE, the results of the ANA patterns obtained from FPBC eluates and sera were similar; homogenous (SLE-6, PSS-1, RA-4), speckled (SLE-8, PSS-2, Overlap CTD-1) and centromere (PSS-1). Four SLE patients showed mixed pattern; sensitivity of IIE for lupus was hundred percent. On comparing the results with the serum IIF, the Kappa statistic of agreement was 1 (perfect) and 0.4 (fair) for FPBC-IIF and FPBC-IIE respectively; the results matched between serum IIF and FPBC-IIE in 8 of the 10 paired samples tested. CONCLUSIONS: IIE can demonstrate ANA both from sera and FPBC. This pilot study besides demonstrating positive trends for further probe also creates an awareness for such a feasible technique. However a larger sample size would be required to carry out its evaluation as an alternative to IIF and as a screening technique.
10354515 Examination of the metabolic status of rat air pouch inflammatory exudate by high field pr 1999 May 31 High field proton (1H) NMR spectroscopy was employed to investigate the metabolic status of rat air pouch inflammatory exudates obtained subsequent to the induction of inflammation with carrageenan, and the 1H NMR profiles of these fluids were compared and contrasted with those of inflammatory human synovial fluid, rat plasma and human serum. The characteristic biochemical features obtained from 1H NMR analysis of these exudates consisted of (1) substantially elevated levels of lactate (11.40+/-1.46x10-3 mol dm-3 for samples collected at a time point of 24 h post induction) with little or no NMR-detectable glucose, data consistent with a hypoxic environment and consequent anaerobic metabolism in the inflamed air pouch, and (2) high levels of the ketone body 3-d-hydroxybutyrate, providing evidence for an increased utilization of fats for energy by lymphocytes, the predominant leucocytes present in this environment. These phenomena represent a pathological extreme of the abnormal metabolic status of inflammatory human synovial fluids.
10368792 Gender-specific medicine: the new profile of gynecology. 1999 Feb The science of gynecology is undergoing a change and is swiftly turning into a holistic discipline, i.e. gender-specific medicine. The rationale for this is that the hormones of the ovary not only are responsible for reproduction but also perform a number of extragenital functions that extend far into other disciplines, giving rise to a different frequency of diseases in women than in men. For example, females are five times more likely to be affected by rheumatoid arthritis than males, the same also holding true for autoaggressive conditions. This phenomenon may be accounted for by the fact that physiological auto-aggression is involved in the reproductive process. Similarly, there is a difference between women and men with regard to the sicca phenomenon, or to such disorders as connective tissue weakness, cellulite, venous conditions or hypercholesterolemia. A cause-related treatment of such problems is now available through specific endocrine therapy. That is why gynecologists in future will increasingly have to adopt an interdisciplinary approach.
9374927 Successful therapy with danazol in refractory autoimmune thrombocytopenia associated with 1997 Oct The objective was to assess the efficacy of therapy with danazol in refractory immune thrombocytopenia associated with different rheumatic diseases. Patients with severe immune thrombocytopenia (platelet counts < 40 x 10(9)/l) with a bone marrow biopsy showing megakaryocytes in normal or increased number and normal morphology were included if they fulfilled at least one of the following criteria: (a) thrombocytopenia refractory to prednisone (> or = 1 mg/kg/day during > or = 4 weeks); (b) patients requiring an unacceptably high dose of prednisone for > 2 months (prednisone dose > or = 20 mg/day); (c) no response to at least another drug besides corticosteroids. Other causes of thrombocytopenia were excluded. They were treated with danazol (100-200 mg q.i.d.) and followed for at least 12 months. Four patients diagnosed with systemic lupus erythematosus, two with rheumatoid arthritis and one with primary antiphospholipid syndrome met the inclusion criteria. All of them achieved acceptable platelet counts within the first 4 weeks of danazol therapy that allowed the prednisone dosage to be tapered. No important side-effects related to danazol therapy were observed. Danazol therapy seems to be a useful and well-tolerated treatment for refractory immune thrombocytopenia associated with different rheumatic diseases.
11036823 Metabolic activation stimulates acid production in synovial fibroblasts. 2000 Oct OBJECTIVE: In rheumatoid arthritis (RA), synovial fibroblasts express proteases such as collagenases or cathepsins and inflammatory cytokines at elevated levels and so contribute to the inflammatory degradation process. Extracellular matrix degradation and cathepsin activity is dependent upon the presence of an acidic milieu. We examined whether activated synovial fibroblasts secrete acidic components. METHODS: Synovial fibroblasts were isolated and immortalized to study the mechanisms of metabolic activation. Naïve and immortalized fibroblasts were activated with different cytokines. The responses were investigated by immunoblot to detect Egr-1 and by a cytosensor microphysiometer analysis to evaluate acid secretion. Basic gene expression patterns were investigated in naïve and immortalized cells by RT-PCR analysis. RESULTS: We found RA synovial fibroblasts respond to different cytokines associated with the pathomechanisms of RA including interleukin 1, basic fibroblast growth factor, platelet derived growth factor, and tumor necrosis factor-alpha, with metabolic activation and enhanced secretion of acidic components. In addition, naive and SV40 TAg immortalized fibroblasts rapidly release acidic components after stimulation with phorbol ester or ionomycin as well. CONCLUSION: Activated synovial fibroblasts not only express inflammatory cytokines and matrix degrading proteases that are associated with the pathomechanisms of RA, but upon stimulation may release acidic components that lower pH and consequently enhance cathepsin activity and collagen solubilization.
10971521 Expression of vascular endothelial growth factor by synovial fluid neutrophils in rheumato 2000 Sep Most of the leucocytes infiltrating rheumatoid synovial fluid (SF) are neutrophils capable of producing a variety of inflammatory mediators known to contribute significantly to the disease process during active RA. In the present study, we investigated the contribution made by SF neutrophils to the elevated levels of vascular endothelial growth factor (VEGF) seen in rheumatoid SF. Rheumatoid SF neutrophils were found to contain significantly larger amounts of both VEGF protein and its mRNA than peripheral blood neutrophils from either RA patients or healthy controls. Levels of cell-associated VEGF were well correlated with free VEGF in SF, which was significantly higher than in SF from osteoarthritis patients. Levels of SF neutrophil-associated VEGF also correlated with RA disease activity and cell surface integrin expression. Thus, SF neutrophil-associated VEGF may be considered an indicator of both local and systemic inflammation of RA, contributing to the neovascularization seen during RA synovitis.
11143903 Angiogenesis: general mechanisms and implications for rheumatoid arthritis. 2000 In rheumatoid arthritis, the vascular endothelium is among the key targets for circulating mediators of inflammation and controls the trafficking of cells and molecules from the bloodstream toward the synovial tissue. Local blood vessel proliferation allows the pannus to develop and grow, thereby promoting cartilage and bone destruction and joint remodeling. Angiogenesis, the production of new capillaries from preexisting blood vessels, is a key process in rheumatoid arthritis that involves multiple substances such as cytokines, chemokines, growth factors, cell adhesion molecules, proteinases, proteinase inhibitors, and matrix proteins. In animal models of arthritis, angiogenesis inhibitors have been found to improve clinical and radiological outcomes, opening up the possibility of therapeutic applications in humans. Before this possibility is realized, the steady accumulation of data on the mechanisms that regulate angiogenesis will have to continue until a clear picture of angiogenesis is formed.
11212151 CD4+,CD28- T cells in rheumatoid arthritis patients combine features of the innate and ada 2001 Jan OBJECTIVE: To determine whether CD4+,CD28- T cells, which are expanded in patients with rheumatoid arthritis (RA), express receptors that typically regulate the function of natural killer (NK) cells. METHODS: Expression of the NK cell surface molecules CD158, p70, CD94, CD161, and CD8alpha on T cell subsets was determined by multicolor flow cytometric analysis of peripheral blood mononuclear cells from 36 RA patients. Expression of CD161 on tissue-infiltrating CD4 T cells was determined by 2-color immunohistochemistry analysis of synovial tissue samples. RESULTS: Killer cell-inhibitory receptors (KIR) and killer cell-activating receptors (KAR) were exclusively expressed on CD4+,CD28- T cells, with the CD158b molecule being the most frequently detected isoform. A coordinated mechanism inducing KIR/KAR expression was suggested by similarities in the expression of CD158b on CD4 and CD8 T cells. CD4+,CD28- T cells were also positive for CD8-alphaalpha homodimers, another characteristic shared with NK cells. Of the C-type lectin NK cell receptors (NK receptors), CD94 was consistently absent, but CD161 was found on a CD4 T cell population that is significantly expanded in RA patients (P = 0.01). Involvement in disease of NK receptor-expressing CD4 T cells was suggested by the presence of CD4+,CD161+ T cells in follicular microstructures typical of rheumatoid synovitis. CONCLUSION: Patients with RA have an expanded and unusual subset of CD4 T cells that infiltrates the tissue lesions and is characterized by a deficiency of CD28, the expression of CD8-alphaalpha homodimers, and the expression of several types of HLA class I-recognizing NK receptors. CD4 T cells bearing NK receptors can bridge functions of the innate and adaptive immune systems, such as responsiveness to specific antigen, rapid release of interferon-gamma, cytotoxicity, independence from classic costimulatory pathways, and integration of multiple activating and inhibitory signals to control effector functions.
9224238 Surgery of the rheumatoid forefoot with special reference to the plantar approach. 1997 Jul The key to the understanding of rheumatoid forefoot deformities is the predominant joint involvement of the tibial side of the hindfoot, of the fibular tarsometatarsal joints, and the destruction especially of the metatarsal heads. Independent of these patterns, the predominant sources of pain and impaired function, and thus of surgical remedies, remains the metatarsophalangeal joints. The authors prefer forefoot arthroplasty consisting of a judicious resection of the metatarsal heads, plantar capsulorraphy, tenolysis and rerouting of the tendons, through a dorsomedial approach to the great toe basal joint, and through a transverse plantar approach with dermodesis (plastic resection of a plantar wedge of skin and subcutaneous tissue) for the lesser toes. This method yields excellent pain relief that does not deteriorate for at least 15 years. However, 1/2 of the nearly complete postoperative correction was lost again within 10 years, and barefoot walking again became more difficult. Reviewing the literature, one cannot detect a clearcut superiority of plantar versus dorsal approaches, nor of one surgical routine versus another.
9256029 [Antigenic epitopes recognized by autoantibodies to calpastatin in patients with rheumatoi 1997 Jun We have previously described that novel autoantibodies to calpastatin (endogenous inhibitor for calcium-dependent neutral protease, calpain) were detected in patients with rheumatoid arthritis (RA) and other disorders. Since calpain is thought to mediate inflammatory process and cartilage destruction, autoantibodies to its inhibitor protein, calpastatin, may be involved in the pathogenic mechanism of rheumatoid arthritis. In the present study, we analyzed antigenic epitopes reactive with autoantibodies to calpastatin and their clinical correlation. cDNA encoding the C-terminal 178 amino acids of human calpastatin (RA-6) was digested by restriction enzymes and ligated in to pEX expression vectors. These recombinant plasmids were tranfected into E. coli POP2136 and screened by colony blots using RA sera containing anticalpastatin antibodies and a mouse monoclonal antibody. RA patient sera recognized the C-terminus of domain IV (epitope C1 ; aa. 647-673) and C-terminus of domain III (epitope C2 ; aa. 496-571), whereas the mouse monoclonal antibody recognized an entirely different region containing the calpain-binding site (epitope B2 ; aa. 572-625). To evaluate epitope reactivity of patient autoantibodies, 15 RA sera containing anti-calpastatin were reacted with epitope fusion proteins. In immunoblotting, most RA sera recognized either C1 or C2 epitopes (67% and 40%, respectively), and only one patient recognized both epitopes. B2 epitope a more progressed and sever state of arthritis than those not reacting with C1. These results suggests that anti-calpastatin antibodies may play a role in the pathogenic mechanisms of RA and their epitope reactivity may be important for disease progression.
11465709 Induction of an invasive phenotype by human parvovirus B19 in normal human synovial fibrob 2001 Jul OBJECTIVE: To investigate the possible role of human parvovirus B19 as an etiologic agent in rheumatoid arthritis (RA), with particular emphasis on its ability to induce invasiveness in human synovial fibroblasts. METHODS: We established an experimental in vitro system in which normal primary human synovial fibroblasts were treated with or without parvovirus B19-containing human sera for 7 days. The fibroblasts were then tested for their ability to degrade reconstituted cartilage matrix using a well-characterized cartilage invasion assay system. RESULTS: Incubation with parvovirus B19-containing serum induced an invasive phenotype in normal human synovial fibroblasts. B19 serum-treated synovial fibroblasts exhibited an increase in invasion of up to 248% compared with the activity of fibroblasts in media alone, in contrast to B19-negative sera-treated synovial fibroblasts, which exhibited no significant change compared with that in media alone. In addition, preincubation of viremic serum with a neutralizing antibody to B19 abrogated the observed effect. CONCLUSION: These results provide direct evidence regarding the ability of parvovirus B19 to induce invasive properties in normal human synovial fibroblasts. Parvovirus B19 has been proposed as an etiologic agent of RA, and our data provide the first biologic link between exposure to B19 and phenotypic changes in normal human synovial fibroblasts.
11187380 [New drugs against rheumatoid arthritis. Improved treatment options place new demands on h 2000 Nov 29 During the present year more new drugs will be introduced for the treatment of rheumatoid arthritis than have been for several decades. In order to make the widening range of therapeutic options truly available in daily clinical care, certain changes will be required in the organization of treatment resources for rheumatic patients. Several articles in the present issue of Läkartidningen describe the new drugs. Besides introducing these new drugs, it is shown that combinations of "old" antirheumatic drugs (DMARD's) given in high doses and in an earlier phase of disease than previously also exert positive effects on disease course. Taken together, new strategies have been developed for the treatment of patients with RA. One such strategy, endorsed by the Swedish Rheumatology Association, is described in this paper, together with a description of a new national surveillance system for the new drugs.
11234268 [Quality of life in anxiety disorders in patients with rheumatoid arthritis]. 2001 Quality of life (QL) in patients with rheumatoid arthritis (RA) and anxious disorders was estimated according the scale of S. Roberts and M. Eliot. Anxious disorders were evaluated by RA patients' personality profile described by MMPI, Beck's questionnaire, Spilberger's test. In RA running for more than 5 years, QL tends to decrease, though subjectively the patients overestimate their QL. This leads to the loss of a direct correlation with psychological personality traits. The conventional treatment raises QL and restore the lost correlations. The persisting high level of anxiety and lowering of emotional functioning require administration of psychotropic drugs to improve adaptation of RA patients.