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

ID PMID Title PublicationDate abstract
7554443 Thrombin receptor-mediated synovial proliferation in patients with rheumatoid arthritis. 1995 Sep Synovial cell proliferation is one of the pathological bases of rheumatoid arthritis (RA). Several cytokines including IL-1 and IL-6 and growth factors have been shown to be involved in the synovial cell proliferation in RA. Thrombin is a multifunctional protease and acts as a mitogen for several cell types through its specific receptor. To assess whether thrombin is involved in overproliferation of rheumatoid synovial cells, we measured the concentration of thrombin-anti-thrombin III (ATIII) complex (TAT) in synovial fluid obtained from patients with RA or osteoarthritis (OA). We also examined the effect of thrombin or thrombin receptor agonist peptide (TRAP) on cell growth of synovial cell clones (SCCs) established from an RA patient. The concentrations of TAT in the synovial fluid from patients with RA were significantly higher than in those with OA. Moreover, both thrombin and TRAP enhanced proliferation of synovial cells in vitro. We also characterized the expression of thrombin receptor mRNA by reverse transcription-PCR. The expression of mRNA for thrombin receptor was up-regulated by thrombin or TRAP stimulation. Thrombin receptor antigen was also detected on both SCCs and synovial tissue from RA patients by immunostaining using a monoclonal antibody against thrombin receptor. These findings indicate that thrombin may act as a mitogen for synovial cells through thrombin receptor and may play some role in synovial overproliferation and remodeling in RA.
8782147 Hydrocephalus and secondary syndrome of inappropriate antidiuretic hormone due to rheumato 1996 Jun We describe symptomatic hydrocephalus and secondary syndrome of inappropriate antidiuretic hormone as clinical manifestations of vertical atlantoaxial subluxation in a patient with severe rheumatoid arthritis. We found no reports of this association as a complication of rheumatoid cervical involvement. We discuss the difficulties of differential diagnosis and treatment in this patient.
8877931 Determination of stromelysin-1, 72 and 92 kDa type IV collagenase, tissue inhibitor of met 1996 Sep OBJECTIVE: To investigate the correlation between serum and synovial fluid (SF) concentrations of stromelysin-1 (MMP-3), gelatinases (MMP-2 and MMP-9), tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in patients with rheumatoid arthritis (RA) and to assess the role of these proteins in cartilage destruction and their clinical value as indicators of disease activity. METHODS: Enzyme linked immunoassays (ELISA) were used. SF and serum samples were collected simultaneously from 55 patients with RA. Radiographic (Larsen grade) and clinical evaluations were also done. RESULTS: There was significant correlation between SF concentrations of MMP-3 and MMP-9. In addition, there was significant negative correlation between SF concentrations of TIMP-2 and MMP-2, 3, and 9. The only correlation observed among MMP and TIMP in serum was that of MMP-3 with MMP-2. Significant correlation was also found between MMP-3 concentrations in the serum and SF. There were no significant correlations between radiological grade and concentrations of these proteins. Patients with mild to moderate functional disability showed significantly higher serum TIMP-1 concentrations than patients with severe disability. CONCLUSION: Extremely high concentrations of MMP-3 in SF of the patients with RA may contribute to its elevation in serum. It would seem that regulation of TIMP production depends upon the disease state and not the concentration of MMP. Discrepancies between concentrations of TIMP and MMP in SF may be responsible for cartilage destruction in RA.
1310815 T-cell receptor beta-chain gene rearrangements of T-cell populations expanded from multipl 1992 Feb In this study T-cell receptor (TcR) beta-chain gene rearrangements of T-cell lines prepared from multiple sites (n = 92) of synovial tissue derived from both knees of a patient with rheumatoid arthritis were analysed. In the majority of T-cell lines, dominant TcR beta-chain gene rearrangements were detected, involving C beta 1 as well as C beta 2. The dominant rearrangement patterns of T-cell lines from different tissue fragments showed significant variability, but some of the DNA restriction fragments were shared by T-cell lines from multiple sites in both knees. The latter observation suggests that identical T-cell clones may be present at different sites in the synovial tissue and in different joints. However, since many T-cell lines yielded different rearrangement patterns, these data also indicate considerable heterogeneity of T cells in the joints. Apart from theoretical implications, this TcR heterogeneity of T cells within an individual patient also has practical consequences for studies on synovial T cells obtained by biopsy.
8064738 Gold induced colitis and hepatic toxicity in a patients with rheumatoid arthritis. 1994 May We describe a case of severe colitis in a 40-year-old woman early in the course of intramuscular gold therapy for rheumatoid arthritis. Despite prompt withdrawal of gold, our patient required emergency laparotomy and bowel decompression. Incidental cholestatic hepatotoxicity, a further rare adverse reaction to gold, was also noted in our patient.
8978955 Plasma renin activity as a marker of renovascular injury in patients with rheumatoid arthr 1996 Nov OBJECTIVES: To assess whether plasma renin activity (PRA) in patients with rheumatoid arthritis (RA) and evidence of renal involvement (microhematuria) can serve as potential marker of renovascular injury. METHODS: PRA was measured at rest and following exercise. All nonsteroidal antiinflammatory drugs or other medications that might affect renin release were stopped at least ten days prior to PRA measurements. PRA was correlated with the number of dysmorphic erythrocytes present in the urine sediment as indicators of glomerular capillary injury (microhematuria). RESULTS: All patients with RA had a higher mean PRA than controls. Moreover, all patients with RA in whom microhematuria was present had a higher PRA than those without microhematuria. Simple and multiple regression analysis revealed a significant correlation between: a) PRA and rheumatoid factor levels; b) rheumatoid factor levels and the number of erythrocytes in the urine sediment; and c) PRA levels and the number of erythrocytes in the urine sediment. CONCLUSIONS: The observations indicate that increased PRA may occur in normotensive patients with RA and no clinical or biochemical evidence of renal involvement. This may reflect activation of the renin-angiotensin system. The positive correlation between enhanced PRA, rheumatoid factor levels and microhematuria in RA patients may indicate inflammatory injury of the glomerular microvasculature involving the juxtaglomerular apparatus.
8535640 Combining sulphasalazine and methotrexate in rheumatoid arthritis: early clinical impressi 1995 Nov The use of combinations of second line antirheumatic agents (SLAs) is increasing. There are several reasons for combination therapy, e.g. the unsatisfactory effects of single therapy. Strategies for combining SLAs are to begin with combinations, or to add one or more agents to another. The strategy of adding one agent to another is illustrated by a study of 40 patients having insufficient effect from sulphasalazine (SASP). Patients were randomized between methotrexate (MTX) and the combination of SASP and MTX. The patients were evaluated by a single observer in an open design. The follow-up was 24 weeks. The mean decrease in disease activity score was significantly greater and occurred earlier in the combination group. This favourable response was also present in the other efficacy variables. The incidence of toxicity was equal in both groups. These results support the strategy of adding MTX to SASP when combining these second line antirheumatic drugs.
8779261 [Sonography of the biceps tendon]. 1996 Mar 641 patients who had undergone ultrasonic investigation of the shoulder joint were reviewed retrospectively. Thirty-four cases (5.3%) with sonographic abnormalities of the biceps tendon or the soft tissue surrounding the biceps tendon were found. In 15 cases a synovitis or effusion of the bicipital (convexity of the transverse ligament) groove was found. Four times a mineralization of the transverse ligament (high echogenic zone with interruption of the humerus coticalis) was observed. In 10 cases rupture of the tendon (sagging of the transverse ligament) was diagnosed. One case was diagnosed as a subluxated biceps tendon (tendon riding on the lesser tubercle) and was misdiagnosed. Four cases with cysts of the biceps tendon were seen (well defined zone of low echogenity). Seven patients underwent surgery following unsuccessful conservative treatment and in all cases but one the ultrasonic diagnosis was confirmed. According to the experience of this investigation ultrasonic examination of the biceps tendon turned out to be an ideal imaging technique for screening of lesions of the long head of the biceps.
7983121 Total knee arthroplasty after patellectomy. 1994 Nov We compared the outcome of total knee arthroplasty in 19 patients who had had previous patellectomy with the results in a matched series of arthroplasties performed on knees in which the patella was intact. The mean follow-up was 63 months (21 to 114). In the study group, the outcome was poor in five patients. There was instability in the coronal plane in three patients and persistent pain in four. Three supracondylar fractures occurred. The overall complication rate was 36%. In the control group, pain was relieved in every case and there were no complications. Total knee arthroplasty has a higher complication rate and inferior results if the knee has undergone prior patellectomy.
8282535 Formation of DNA strand breaks by D-penicillamine and bucillamine in human lymphocytes. 1993 Sep DNA strand breakage by D-penicillamine and bucillamine, anti-rheumatic agents with thiol residues was evaluated in DNA unwinding assays. When incubating human peripheral blood lymphocytes with D-penicillamine or bucillamine in the presence of 8 microM CuSO4, numerous DNA strand breaks occurred and those depended on the production of hydrogen peroxide and were completely blocked in the presence of catalase. This phenomenon was reversible, and fragmented DNA was repaired in 8 to 24 h. Significant decreases in cellular NAD levels were observed at concentrations of D-penicillamine or bucillamine which could damage DNA. As extensive depletion of cellular NAD functionally inactivates lymphocytes, the formation of DNA strand breaks may have a role in the immunomodulating action of these anti-rheumatic drugs.
8712884 High prevalence of arthropathy in HTLV-I carriers on a Japanese island. 1996 Mar OBJECTIVE: To determine the aetiological relationship between human T cell leukaemia virus type-I (HTLV-I) and arthritis, by performing an epidemiological study of the inhabitants of Tsushima, an island northwest of the main island of Kyushu, Japan, which is an endemic area of HTLV-I. METHODS: A total of 7087 people underwent an annual health check, and those with arthropathy had further physical and radiological examinations by rheumatologists. The presence of HTLV-I antibody was determined by the particle agglutinin method, and integration of the proviral DNA in peripheral lymphocytes was confirmed by polymerase chain reaction. RESULTS: HTLV-I was positive in 26.1% of inhabitants; the incidence increased to 37.0% in patients with symptoms of polyarthritis. The prevalence of rheumatoid arthritis (RA) was significantly different between HTLV-I carriers (0.56%) and non-carriers (0.31%). The stage of bone destruction in HTLV-I carriers with articular symptoms was milder than that in RA patients without HTLV-I. The relative risk of HTLV-I infection for polyarthritis was 1.66 (p < 0.05). CONCLUSION: This is the first epidemiological report clarifying the association between HTLV-I and polyarthritis. Our results suggest that this viral infection has a relationship to RA.
8608359 Stability of health status measurement in rheumatoid arthritis. 1995 Dec Health status measures in rheumatoid arthritis that have been extensively validated for use in clinical trials are generally used also in correlative studies, e.g. to predict future health status. This application requires stability (repeatability of measurements). The purpose of our study was to determine the stability of commonly used health status measures. Two measurements at an interval of 6 months were then in 99 patients. High stability (alpha = 0.78 to 0.94) was observed for five biomedical measures (grip strength, walking time, platelet count, haemoglobin and erythrocyte sedimentation rate) and five self-report measures (mobility, self care, impact daily activities, anxiety and cheerful mood). Moderate stability (alpha = 0.65 to 0.72) was observed for joint scores, pain, C-reactive protein and depressive mood. The highly stable measures most adequately reflect individual differences, may be applied most reliably in correlative studies and appear to have the largest clinical utility with regard to long-term prediction of health status.
7732494 [Renal function after TKR in patients with rheumatoid arthritis who have chronic renal ins 1995 Feb Twenty three patients with RA who have chronic renal insufficiency were post operatively studied for changes in the renal function with TKR (total knee replacement). We evaluated the renal function by BUN, Creatine, PSP and Creatine clearance. The renal function has not grown worse in all cases. TKR is a safe operation for renal function with careful technique and management.
8757068 [Vasculitis in rheumatoid arthritis]. 1996 Jul 21 The frequency and histopathological characteristics of systemic vasculitis were studied in the autopsy material of 161 patients with rheumatoid arthritis. Systemic vasculitis was observed in 36 case (22.4%). In percentage of all cases with systemic vasculitis, the most frequently involved organs were the heart (66.7%), skeletal muscles (54.8%), and peripheral nerves (52%). The skin was involved only in about one third of 36 cases (36%). In most cases the arterioles and the small arteries were affected by vasculitis. Three types of vasculitis (non specific, fibrinoid necrotic, granulomatous) could be observed simultaneously in different vessels or combined in the same vessel. Different stages of inflammation could be found simultaneously, reflecting the relapsing nature of vasculitis. The frequency, the severity, and the recurrence of vasculitis are different aspects of the same phenomenon running usually parallel to each other in different organs and on different vessels. Vasculitis lead to local ischaemia and regressive changes depend on the number and size of the involved vessels. Systemic vasculitis led to death in 19 of 36 cases. Vasculitis was detected clinically in 7 of 36 cases. Exitus lethalis depend on the localization of the involved vessels. Vasculitis in the heart and brain are more life threatening, than that of localized to the skin.
8091868 [Side effects and efficiency of 15 mg and 25 mg methotrexate per week in chronic polyarthr 1994 May To examine the rate of side effects and the dose dependence of side effects 185 consecutive patients with active rheumatoid arthritis were randomized to receive 15 mg (group A) or 25 mg (group B) methotrexate (MTX) per week and studied prospectively over 12 months. Dose adjustments were performed according to tolerability and efficacy. With 168 patients eligible for evaluation the rate of withdrawal for any reason was 26% in group A and 27% in B. Withdrawal due to side effects occurred in 16% versus 18%, dose reduction due to side effects in 10% versus 9%. The higher dose was associated with a significantly higher rate of gastrointestinal side effects (28% vs. 17%, p < 0.05) and a tendency for more frequent elevations of transaminases. Other side effects were not dose dependent. A significantly higher rate of dose reduction due to improvement (35% versus 10%, p < 0.001), a more rapid decline of morning stiffness, and a higher number of patients reporting marked improvement are evidence in favour of higher therapeutic efficacy of the higher dose. In conclusion, an initial dose of 25 mg MTX/week is not associated with a higher rate of limiting side effects as compared with 15 mg/week. The efficacy of doses up to 25 mg/week should be examined in more detail.
1538096 Swanson silicone arthroplasty of the wrist in rheumatoid arthritis: a long-term follow-up. 1992 Jan Twenty-three Swanson silicone rubber implants in patients with stage III or stage IV rheumatoid arthritis were reviewed at an average of 72 months after surgery. Minimum follow-up in patients with unrevised implants was 44 months. Results were rated good or excellent in 48%, fair in 4%, and poor in 48%. Pain was the primary indication for surgery. Patient satisfaction and pain relief were achieved in 63%. Implant fracture occurred in 52%. Revision rate was 30%, including one recommended revision. Radiographic changes consistent with particulate synovitis were seen in 30%. Prosthesis settling and bony resorption were seen in more than 75% of the patients. Survivorship analysis demonstrated 42% survival at 77 months. Progressive clinical and radiologic deterioration was seen. Swanson silicone rubber implant is recommended only in the very low demand patient with stage III or stage IV rheumatoid arthritis and in those with insufficient bone stock to allow total wrist arthroplasty with a metal-on-plastic design.
7612047 Comparative analysis of cathepsin L, cathepsin D, and collagenase messenger RNA expression 1995 Jul OBJECTIVE: To compare the expression of cathepsin L, cathepsin D, and collagenase messenger RNA (mRNA) in synovial specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The expression of cathepsins L and D as well as collagenase mRNA in synovial tissues from 8 patients with RA, 6 patients with OA, and 2 patients with noninflamed joints was evaluated using in situ hybridization with digoxigenin-labeled RNA probes. RESULTS: Both RA and OA synovial tissue expressed cathepsins L and D as well as collagenase mRNA. The expression of the cathepsins was markedly higher in interstitial regions and, to some extent, in perivascular infiltrates of RA synovial tissue compared with OA specimens. CONCLUSION: Cathepsins L and D mRNA are expressed differently in RA and OA synovial tissues, supporting the concept that these enzymes may contribute to the influx of mononuclear cells into RA synovium. Moreover, the data reveal that the expression of collagenase and cathepsins in RA and OA synovial lining is otherwise largely similar, and suggest that the adhesion of synovial cells to cartilage mediates the invasive destructive process in RA.
1731807 Generation and characterization of two monoclonal self-associating IgG rheumatoid factors 1992 Jan OBJECTIVE: To study IgG rheumatoid factor (RF) from rheumatoid synovium. METHODS: We fused the K6H6/B5 human-mouse heterohybridoma with unstimulated rheumatoid synovial B cells to generate IgG-RF-secreting hybridomas. RESULTS: The RFs from 2 such hybridomas bound specifically to the Fc fragment of human IgG and self-associated to form immune complexes. Such immune complexes are a major characteristic of the pathogenic IgG-RFs in rheumatoid synovium. CONCLUSION: IgG-RF-secreting hybridomas have been obtained. Analyses may reveal the underlying mechanisms of the induction of IgG-RF.
9054050 [Regulatory R proteins and lipid peroxidation in rheumatoid arthritis]. 1996 Levels of R proteins (RP) and activity of lipid peroxidation (LPO) were measured in 209 patients with RA. It was noted that RP levels and LPO activity correlated with the activity of inflammation. A rapid RA progression was characterized by higher RP levels and LPO activity, while polyarthritis by more intensive RP metabolism and LPO. A comprehensive study of RP and LPO in RA patients may facilitate prognosis of the destruction rate.
7612043 Elevated levels of eosinophil major basic protein in the sera of patients with systemic sc 1995 Jul OBJECTIVE: To examine eosinophil activation, as reflected by evidence of eosinophil degranulation in the blood and affected tissues, in patients with diffuse and limited cutaneous forms of systemic sclerosis (SSc). METHODS: Levels of the eosinophil-derived major basic protein (MBP), a marker of eosinophil degranulation, were determined in sera from 46 SSc patients, from patients with rheumatoid arthritis and giant cell arteritis, and from healthy volunteers, and in bronchoalveolar lavage fluid from 4 SSc patients. Extracellular tissue deposition of MBP was evaluated in biopsy specimens from affected skin or lung of 11 SSc patients. RESULTS: Patients with diffuse cutaneous SSc (dcSSc) had elevated serum MBP levels compared with normal individuals (mean +/- SD 762 +/- 271 ng/ml versus 534 +/- 144 ng/ml; P = 0.0004). MBP levels were positively correlated with the extent of cutaneous involvement, and negatively correlated with pulmonary function and duration of disease (r = -0.20). By immunohistochemical analysis, modest extracellular MBP deposition could be demonstrated in involved skin in 7 of 10 biopsy specimens, and MBP staining was prominent in affected lung tissues in 2 patients. CONCLUSION: Eosinophil degranulation appears to be increased in some patients with dcSSc, as indicated by elevated serum levels of MBP and extracellular accumulation of MBP in the lung. Eosinophil granule proteins may contribute to the development of cutaneous and pulmonary fibrosis in SSc.