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ID PMID Title PublicationDate abstract
10566291 [Ultrasound patterns of rheumatoid and psoriatic arthritis in finger joints]. 1999 Jul PURPOSE: Rheumatoid and psoriasic arthritis involve proximal joints symmetrically and distal joints asymmetrically, respectively, the differential diagnosis between these two types of arthritis is not easy. Therefore we investigated which US signs could help the diagnosis and/or treatment of these conditions and compared them with radiographic patterns and articular and physical symptoms. MATERIAL AND METHODS: Fifty-one patients, 30 women and 21 men aged 19-42 years were enrolled in this study. Thirty patients had rheumatoid and 21 psoriasic arthritis. US of the skin and joints of the fingers was performed with a GE Sonora Logic 500 MD unit with 7.5 and 10 MHz scanheads. We studied the shape of articular bone heads, the intra-articular space distance and the thickness of extensor tendon and of the dermis and hypodermis covering it. These findings show the extent of damage in articular bone heads and intra-articular space and they indicate cutaneous and articular inflammation. US patterns were also compared with radiographic findings in all patients. RESULTS: US showed bone and joint and/or inflammatory damage in both types of arthritis. Articular bone heads had a bodkin-like appearance in proximal phalanges in rheumatoid arthritis, versus a hook-like appearance in distal phalanges in psoriasic arthritis. Inflammatory damage was indicated by intra-articular space thinning and by tendon, dermis and hypodermis thickening. These signs, confirmed radiographically, account for finger deformation and functional impairment, swelling and pain. CONCLUSION: US signs can help the diagnosis of rheumatoid and psoriasic arthritis. US can show inflammatory damage and the disease evolution.
10441840 The role of cytokines and growth factors in cartilage destruction in osteoarthritis and rh 1999 Jun Cartilage destruction in arthritis and osteoarthritis is linked to aberrant cytokine and growth factor expression in the affected tissues. It becomes clear that the balance of protective and destructive cytokines is more important for the net destruction than the absolute levels of destructive mediators. IL-1 is a key destructive mediator in arthritis and probably also in osteoarthritis. Production of the cartilage destructive enzyme stromelysin is linked to IL-1. In osteoarthritis, excessive formation of the growth factor TGF beta may contribute to cartilage lesions and osteophyte formation, in particular. Therapy should be aimed at neutralization of IL-1 and stimulation of safe anabolic growth factors for the articular cartilage, such as IGF-1 and the novel bone and cartilage derived morphogenetic proteins.
11641802 Paravertebral abscess formation and knee arthritis due to brucellosis in a patient with rh 2001 Oct OBJECTIVE: To report a case of Brucellosis causing severe joint and vertebra destruction in a patient with rheumatoid arthritis (RA). SETTING: Ankara, Turkey. CASE REPORT: A 47-year-old man with a known diagnosis of (RA) for 5 years developed paravertebral and epidural abscesses and vertebral fractures and nerve root compression due to brucellosis. The patient underwent surgery for L3-L4 vertebra stabilisation and medical treatment for knee arthritis. CONCLUSION: It is important to be aware of the possibility of brucellosis in endemic areas, even among patients with a known diagnosis of RA presenting with clinical pictures that may be confused with a flare-up of the RA itself. Steroids and NSAIDs may have the potential to mask disease manifestations.
10432311 Methotrexate inhibits the first committed step of purine biosynthesis in mitogen-stimulate 1999 Aug 15 The immunosuppressive and anti-inflammatory effects of low-dose methotrexate (MTX) have been related directly to inhibition of folate-dependent enzymes by polyglutamated derivatives, or indirectly to adenosine release and/or apoptosis and clonal deletion of activated peripheral blood lymphocytes in S-phase. In this study of phytohaemagglutinin-stimulated primary human T-lymphocytes we show that MTX (20 nM to 20 microM) was cytostatic not cytotoxic, halting proliferation at G(1). This stasis of blastogenesis was associated with an inhibition of purine ribonucleotide synthesis but a stimulation of pyrimidine biosynthesis, the normal mitogen-induced expansion of ATP and GTP pools over 72 h being restricted to concentrations of unstimulated T-cells, whereas the increment in UTP pools exceeded that of controls. Decreased incorporation of H(14)CO(3) or [(14)C]glycine into purine ribonucleotides, with no radiolabel accumulation in any de novo synthetic intermediate but enhanced H(14)CO(3) incorporation into UTP, supported these MTX-related effects. Exaggerated [(14)C]hypoxanthine salvage (which normalized the purine and UTP pools) confirmed the increased availability of 5-phosphoribosyl-1-pyrophosphate (PP-ribose-P) as the molecular mechanism underlying these disparate changes. These results provide the first substantive evidence that the immunosuppressive effects of low-dose MTX in primary blasting human T-lymphocytes relate not to the inhibition of the two folate-dependent enzymes of purine biosynthesis but to inhibition of the first enzyme, amidophosphoribosyltransferase, thereby elevating PP-ribose-P and stimulating UTP synthesis. Varying cell types or incubation conditions employed by other workers, especially malignant/activated cells with high basal metabolic rates, might mask the effects noted in primary human T-lymphocytes. The findings imply the involvement of low-dose MTX in the inhibition of T-lymphocyte proliferation and proliferation-dependent processes in rheumatoid arthritis.
9352605 Measurement of transcription factor c-fos and EGR-1 mRNA transcription levels in synovial 1997 The transcription factors Fos and EGR-1 are known to be involved in the regulation of the transcription of metalloproteinases and their specific inhibitors. Since the overexpression of metalloproteinases is responsible for the matrix degradation in rheumatoid arthritis (RA), exact analysis of transcription levels of c-fos and EGR-1 ex vivo may serve to monitor progression or remission of the disease activity in RA. Here we report on a method based on a quantitative reverse transcription polymerase chain reaction (RT-PCR) for rapid estimation of the transcription levels of the immediate early genes c-fos and EGR-1. Coamplification with suitable internal standards, easily generated by the use of hybrid primers, allows us to semiquantitatively measure c-fos and EGR-1 induction levels in low numbers of cultured cells or very small tissue samples obtained by synovial biopsy. The sensitivity of the method was 3.5 pg/ml for c-fos- and 10 pg/ml for EGR-1-specific cDNAs.
11252685 Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a systematic re 2001 Clinical experience suggests that fasting followed by vegetarian diet may help patients with rheumatoid arthritis (RA). We reviewed the available scientific evidence, because patients frequently ask for dietary advice, and exclusive pharmacological treatment of RA is often not satisfying. Fasting studies in RA were searched in MEDLINE and by checking references in relevant reports. The results of the controlled studies which reported follow-up data for at least three months after fasting were quantitatively pooled. Thirty-one reports of fasting studies in patients with RA were found. Only four controlled studies investigated the effects of fasting and subsequent diets for at least three months. The pooling of these studies showed a statistically and clinically significant beneficial long-term effect. Thus, available evidence suggests that fasting followed by vegetarian diets might be useful in the treatment of RA. More randomised long-term studies are needed to confirm this view by methodologically convincing data.
9228128 Radiographic results from the Minocycline in Rheumatoid Arthritis (MIRA) Trial. 1997 Jul OBJECTIVE: To assess radiographically determined disease progression in patients in the Minocycline in Rheumatoid Arthritis (MIRA) Trial. METHODS: A double blind, randomized, multicenter, 48 week trial of oral minocycline (200 mg/day) or placebo in 6 clinical centers in the United States. Patients include 219 adults with active RA previously receiving limited treatment with disease modifying drugs. Posteroanterior films of the hands from baseline and final visits, blinded for sequence, were read for erosions and joint space narrowing by trained observers. Outcomes included rate of disease progression (change/month) and percentage of patients with progression from baseline, newly involved joints, and newly erosive disease. RESULTS: Using intent-to-treat analyses, progression rates for erosions (0.11 +/- 0.42 minocycline, 0.17 +/- 0.41 placebo; p = 0.47) and joint space narrowing (0.16 +/- 0.55 minocycline and 0.23 +/- 0.71 placebo; p = 0.14) were similar. (Power 43% to detect a 50% difference.) Newly erosive joints occurred more frequently in the placebo group (44 vs 32%; p = 0.08), not a statistically significant difference. CONCLUSION: Radiographic measurement of disease progression using 4 measures failed to show a significant difference between minocycline and placebo treatment, although for all methods there was a trend toward treatment benefit, consistent with reported clinical results. A one year trial duration, high measurement variability, and slow rate of radiographic progression in this cohort may explain the low power to detect a treatment effect. The measurement that denoted "newly involved" joints was most sensitive in detecting change. In future trials longer term assessment (minimum 2 years) of radiographic changes and further comparison of measures of disease progression are warranted.
10323447 Magnetic resonance imaging-determined synovial membrane volume as a marker of disease acti 1999 May OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease-modifying antirheumatic drug (DMARD) therapy alone (11 patients) or DMARDs in combination with oral prednisolone (15 patients), were followed up for 1 year with contrast-enhanced MRI of the dominant wrist (months 0, 3, 6, and 12), conventional radiography (months 0 and 12), and clinical and biochemical examinations. Bone erosion (by MRI and radiography) and synovial membrane volumes (by MRI) were assessed. RESULTS: Significant synovial membrane volume reductions were observed after 3 and 6 months in the DMARD + prednisolone group, and after 6 and 12 months in the DMARD-alone group (P < 0.01-0.02, by Wilcoxon-Pratt analysis). The rate of erosive progression on MRI was highly correlated with baseline scores and, particularly, with area under the curve (AUC) values of synovial membrane volume (Spearman's sigma = 0.69, P < 0.001), but not with baseline or AUC values of local or global clinical or biochemical parameters, or with prednisolone treatment. In none of 5 wrists with baseline volumes <5 cm3, but in 8 of 10 wrists with baseline volumes > or =10 cm3, erosive progression was found by MRI and/or radiography, indicating a predictive value of synovial membrane volumes. MRI was more sensitive than radiography for the detection of progressive bone destruction (22 versus 12 new bone erosions). CONCLUSION: MRI-determined synovial membrane volumes are closely related to the rate of progressive joint destruction. Quantitative MRI assessment of synovitis may prove valuable as a marker of joint disease activity and a predictor of progressive joint destruction in RA.
9778218 HPRT- mutant T cells in the peripheral blood and synovial tissue of patients with rheumato 1998 Oct OBJECTIVE: To investigate the frequency and characteristics of hprt- mutant T lymphocytes in the peripheral blood and synovium of rheumatoid arthritis (RA) patients compared with controls, and to correlate these findings with disease parameters. METHODS: An hprt- T cell assay was performed on blood and synovial samples from 93 RA patients, 8 osteoarthritis (OA) patients, and 19 control subjects. T cell clones were studied by flow cytometry and evaluated for fibronectin adhesion. RESULTS: RA patients showed a 5-fold increase in the frequency of mutant T cells in the peripheral blood compared with that in control peripheral blood, and a further 10-fold increase in the mutant T cell frequency in synovial tissue. In OA patients, the synovium also had a significantly higher frequency of hprt- mutant T cells compared with the peripheral blood, but at a lower level than in the rheumatoid synovium. RA peripheral blood mutant T cell clones displayed elevated fibronectin adhesion and beta1 integrin expression, similar to that observed in the RA synovial T cell lines. CONCLUSION: The origin of the mutated T cells in the peripheral blood of these patients appears to be the inflamed synovium of RA, and to a lesser extent, of OA, where the cells are exposed to a mitogenic and genotoxic environment.
10589359 Combination DMARD therapy including corticosteroids in early rheumatoid arthritis. 1999 Nov A number of reports indicating the growing acceptance of simultaneous therapy with multiple disease-modifying anti-rheumatic drugs (DMARDs), as well as the use of more aggressive treatment measures in the early phases of disease to combat rheumatoid arthritis (RA), have appeared during the last decade. However, only a few randomized controlled clinical trials have been conducted on the use of DMARD combinations in early RA. We review these trials in this article. In two separate one-year studies combination therapy with sulphasalazine (SSZ) and methotrexate (MTX) seemed to offer no benefits compared to either drug used as monotherapy. On the other hand, the DMARD combinations so far proven to be superior to single DMARDs have initially also included a corticosteroid component. In the COBRA study (Combinatietherapie Bij Reumatoide Artritis) the combination of SSZ (2 gm/day), MTX (7.5 mg/week for 40 weeks), and prednisolone (Prd) (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day and stopped after 28 weeks) compared to SSZ alone (2 gm/day) resulted in significantly better clinical outcomes at week 28. Although the difference in clinical response between the treatment arms was lost at week 58, the progression of joint damage remained statistically significantly slower at week 80 in the patients initially assigned to the combination therapy. Furthermore, in the FIN-RACo trial (Finnish Rheumatoid Arthritis Combination Therapy Trial), therapy using a "tailored-steps" strategy with SSZ (1-2 gm/day), MTX (7.5-1.5 mg/week), hydroxychloroquine (300 mg/day), and Prd (up to 10 mg/day) yielded a significantly increased remission rate and less peripheral joint damage at two years than the single DMARD treatment strategy (initially SSZ 2 gm/day), with or without Prd. Adverse effects in both study arms were comparable. Two additional preliminary reports (in abstract form) suggest that intensive local therapy in the form of intra-articular injections added to single or combination therapy improves both local and systemic disease control, with increased remissions and less damage. Although still preliminary, these results should encourage the rheumatological community to treat selected RA patients with DMARD combinations from the very start.
11321132 Legionnaires' disease in a patient with rheumatoid arthritis. 2001 Mar A 62-year-old male with rheumatoid arthritis (RA) who was taking nonsteroid anti-inflammatory drug for controlling synovitis developed a flare of his arthritis, hepatitis, and pneumonia due to infection with Legionella pneumophila serotype 1. Adult respiratory distress syndrome (ARDS) occurred following the development of pneumonia. After the introduction of erythromycin and ventilator support with positive end expiratory pressure (PEEP), his condition stabilized and he recovered gradually. We suggest that L. pneumophila should be considered early in the differential diagnosis of pneumonia in RA patients due to their immunocompromised status.
11312373 Amelioration of rat antigen-induced arthritis by liposomally conjugated methotrexate is ac 2001 Apr OBJECTIVES: We examined the temporal changes in the expression of interleukin 1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the rat antigen-induced arthritis (AIA) model and investigated how their expression was modulated following disease amelioration by liposomally conjugated methotrexate (G-MLV). METHODS: On the day of arthritis induction (day 0), rats were treated with a single intra-articular injection of G-MLV, methotrexate (MTX), a dose of lipid equivalent to G-MLV (E-LIPO) or saline. On days 3 and 7 after disease induction, animals from each experimental group were killed. Joint tissue was examined histologically and for mRNA expression (IL-6, IL-1beta and TNF-alpha) using semiquantitative reverse transcription-polymerase chain reaction. RESULTS: There was no significant difference (ANOVA) in knee swelling between MTX-, E-MLV- or saline-treated animals from day 0 to day 7. By day 1, G-MLV significantly reduced knee swelling (1.94+/-0.12 mm; P<0.0001) compared with rats treated with MTX (3.17+/-0.18 mm). G-MLV treatment also significantly inhibited the histological progression of AIA. This reduction in disease severity was accompanied by a reduction in IL-1beta mRNA expression in synovial tissue extracts on day 3 and IL-6 mRNA expression on both day 3 and day 7. CONCLUSIONS: Liposomally conjugated MTX may exert its beneficial effects in experimental arthritis through IL-1beta and IL-6 inhibition.
11543695 Combination therapy with disease modifying anti-rheumatic drugs in rheumatoid arthritis. 2001 There is increasing interest in using combinations of two or more disease modifying anti-rheumatic drugs to treat rheumatoid arthritis. The use of such combinations is increasing in routine clinical practice. We have identified 18 well-conducted, randomised controlled trials of the use of combinations of disease modifying drugs, and a number of open studies that provide helpful supportive information. The 18 trials involved 2221 patients. Two trials reported strongly positive results, six reported moderately positive results and ten gave largely negative results. The combination of methotrexate, sulfasalazine and hydroxychloroquine appears to be effective with an acceptable level of adverse effects. There is also evidence that the combination of methotrexate and cyclosporin is advantageous. With both combinations, there appears to be further advantages from using corticosteroids in addition to the combination, although the evidence for this is incomplete. The use of other combinations is of less value, and in particular combinations involving parenteral gold, penicillamine and azathioprine are best avoided. Finally, there is growing evidence from randomised trials that the combination of anti-tumour necrosis factor (TNF) therapy with methotrexate is effective and well tolerated. We have identified four randomised controlled trials of the use of combinations of anti-TNF with methotrexate that all reported results favouring this combination. There is insufficient evidence to support the use of other combinations involving immunotherapies at the present time.
11039783 Clinical trials in the gene therapy of arthritis. 2000 Oct Gene therapy clinical trials raise important safety issues that complicate their design and require extensive preclinical testing. Human protocols for the treatment of arthritis and most other orthopaedic and rheumatologic indications are complicated additionally by the perception that they are largely acquired, nonlethal conditions. Taking these considerations into account, the first such human study used the local, ex vivo delivery of a gene whose product, the interleukin-1 receptor antagonist, has an outstanding safety profile. This gene was delivered to the metacarpophalangeal joints of postmenopausal women 1 week before these joints were removed during total joint replacement surgery. In addition to providing an additional safety cushion, the surgical removal of the genetically modified joints made available large amounts of tissue to examine for evidence of successful gene transfer and gene expression. This Phase I safety study was approved at the local and federal levels, and its funding was contingent on the establishment of an external monitoring board. This trial now has been completed and a Phase II, efficacy study is being planned. A similar study has begun in Dusseldorf, Germany and results from the first two patients are similar to the results of the American patients. Permission has been given for two additional human trials, one in the United States and one in the Netherlands, in which a gene encoding herpes thymidine kinase will be transferred to the joints of patients with rheumatoid arthritis who then will be administered gancyclovir. This procedure aims to treat the disease by producing a genetic synovectomy. Additional development of human gene therapies for arthritis and other orthopaedic and rheumatic conditions will be aided by the successful completion of these studies.
11709605 Development and validation of a self-efficacy scale for use in British patients with rheum 2001 Nov OBJECTIVE: Current arthritis self-efficacy scales have attracted some criticism. Therefore, the aim of this study was to develop and validate a measure of self-efficacy for use in British rheumatoid arthritis patients [Rheumatoid Arthritis Self-efficacy (RASE) scale]. METHODS: Phase I: item generation of self-management strategies by rheumatology professionals and patients to create a pilot RASE. Phase II: examination of the internal structure (n=88) using correlation coefficients and principal component analysis (PCA) to create the final RASE. Phase III: reliability in 23 patients. Phase IV: comprehension, construct validity and sensitivity to change in 48 rheumatoid arthritis patients undergoing a self-management programme, using correlation coefficients, PCA and inter-item correlation. RESULTS: Phase I: of 166 self-management items generated, 100 commonly cited items were selected for the pilot RASE. Phase II: using a correlation matrix and PCA, a 28-item RASE was created. Phase III: good 4-week reliability was seen (r=0.889, P<0.001). Phase IV: the final RASE was shown to be independent of mood, disease status and disability and weakly associated with other self-efficacy scales (r=0.313, P<0.05). The RASE was sensitive to change following an education programme (+5.167, P<0.025), and was associated with behaviour initiation (r=0.35, P<0.01). CONCLUSIONS: Careful construction means that the RASE examines beliefs in potential ability to perform tasks, rather than actual ability, performance or outcome expectancy. It shows good face validity and reliability, plus reasonable construct validity and sensitivity. Further studies are needed to support the validation of this new scale.
9599798 Lymphoma with regression after methotrexate withdrawal in a patient with rheumatoid arthri 1998 Apr We report a new case of large T-cell lymphoma in a rheumatoid arthritis patient under low-dose methotrexate (cumulative dose: 750 mg). Serologic tests for the Epstein-Barr virus were positive, and the viral RNA was demonstrated in the lymphoma cells. As in a few other cases reported in the literature, the clinical and laboratory test abnormalities resolved promptly after methotrexate withdrawal without anticancer therapy. The patient was still in complete remission at last follow-up four years later.
10796441 Azathioprine for rheumatoid arthritis. 2000 OBJECTIVES: To assess the short-term effects of azathioprine for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline up to and including July 1998 and Embase from 1988-1998. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials and controlled clinical trials comparing azathioprine against placebo in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: Data was extracted independently by two reviewers (CS, EB); disagreements were resolved by discussion or third party adjudication (MS). The same reviewers (CS, EB) assessed the methodological quality of the trials using a validated quality assessment tool. Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint. The pooled analysis was performed using standardized mean differences for joint counts, pain and functional status assessments. Weighted mean differences were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and for adverse reactions. The 95% confidence intervals (95% CI) are presented. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout, since no statistical heterogeneity was found. MAIN RESULTS: Three trials with a total of 81 patients were included in the analysis. Forty patients were randomized to azathioprine and forty-one to placebo. A pooled estimate was calculated for two outcomes. A statistically significant benefit was observed for azathioprine when compared to placebo for tender joint scores. The standardized weighted mean difference between treatment and placebo was -0.98 (95% CI -1.45, -0.50). Withdrawals from adverse reactions were significantly higher in the azathioprine group OR=4.56 (95% CI 1.16, 17.85). REVIEWER'S CONCLUSIONS: Azathioprine appears to have a statistically significant benefit on the disease activity in joints of patients with RA. This evidence however is based on a small number of patients, included in older trials. Its effects on long-term functional status and radiological progression were not assessed due to lack of data. Toxicity is shown to be higher and more serious than that observed with other disease-modifying anti-rheumatic drugs (DMARDs). Given this high risk to benefit ratio, there is no evidence to recommend the use of azathioprine over other DMARDs.
11083274 Activation, differential localization, and regulation of the stress-activated protein kina 2000 Nov OBJECTIVE: To investigate whether stress- and mitogen-activated protein kinases (SAPK/MAPK), such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK, are significantly activated in rheumatoid arthritis (RA) synovial tissue compared with their activation in degenerative joint disease; to assess the localization of SAPK/MAPK activation in rheumatoid synovial tissue; and to search for the factors leading to stress kinase activation in human synovial cells. METHODS: Immunoblotting and immunohistology by antibodies specific for the activated forms of SAPK/MAPK were performed on synovial tissue samples from patients with RA and osteoarthritis (OA). In addition, untreated and cytokine-treated human synovial cells were assessed for SAPK/MAPK activation and downstream signaling by various techniques. RESULTS: ERK, JNK, and p38 MAPK activation were almost exclusively found in synovial tissue from RA, but not OA, patients. ERK activation was localized around synovial microvessels, JNK activation was localized around and within mononuclear cell infiltrates, and p38 MAPK activation was observed in the synovial lining layer and in synovial endothelial cells. Tumor necrosis factor alpha, interleukin-1 (IL-1), and IL-6 were the major inducers of ERK, JNK, and p38 MAPK activation in cultured human synovial cells. CONCLUSION: Signaling through SAPK/MAPK pathways is a typical feature of chronic synovitis in RA, but not in degenerative joint disease. SAPK/MAPK signaling is found at distinct sites in the synovial tissue, is induced by proinflammatory cytokines, and could lead to the design of highly targeted therapies.
9153555 Selective activation of the JNK/AP-1 pathway in Fas-mediated apoptosis of rheumatoid arthr 1997 May OBJECTIVE: To evaluate the Fas-dependent signaling pathway, we examined the involvement of protein tyrosine phosphorylation and the DNA binding activity of AP-1 in rheumatoid arthritis (RA) cultured synovial cells. METHODS: The number of dead cells was counted after treatment with anti-Fas antibody in the presence of protein tyrosine kinase or phosphatase inhibitor. Protein tyrosine phosphorylation in synoviocytes after Fas ligation was examined by immunoblot and immunoprecipitation analyses. The DNA binding activity of AP-1 was examined by electrophoretic mobility shift assay. RESULTS: Treatment with the protein tyrosine phosphatase inhibitor, orthovanadate, significantly enhanced the apoptosis of RA synoviocytes after Fas ligation. Ligation of the Fas molecule on RA synoviocytes induced a rapid tyrosine phosphorylation of JNK (c-Jun amino-terminal kinase) and formation of the AP-1 transcription factor. CONCLUSION: Our results strongly suggest that the JNK/AP-1 signaling pathway is activated during the process of Fas-mediated apoptosis of RA synovial cells.
10969490 Anti-keratin antibodies in patients with rheumatoid arthritis. 2000 Jun As the proportion of patients with rheumatoid arthritis (RA) who have anti-keratin antibodies (AKA) varies in different ethnic groups, we studied its occurrence in a hospital populations with RA and its association with different disease variables. Sera from 84 consecutive patients with RA, 100 healthy controls and 85 disease controls (polyarticular juvenile rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis) were tested for AKA by an indirect immunofluorescence assay that used rat esophagus as substrate. The proportion of patients with RA who had AKA (47/84) was higher than in healthy controls (2/100; P < 0.001) and in disease controls (2/85; P < 0.001). The frequency of AKA positivity was higher among patients who had severe disease (P < 0.05) and rheumatoid factor. Anti-keratin antibody is present in 56 per cent of our patients with RA and is associated with severe disease.