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ID PMID Title PublicationDate abstract
9167618 Expression of parathyroid hormone-related peptide in human osteoarthritis. 1997 Mar To evaluate the involvement of the expression of parathyroid hormone-related peptide gene in human articular cartilage pathology, we performed immunohistochemical staining and in situ hybridization on specimens of femoral head cartilage obtained from 15 patients with osteoarthritis, 11 with rheumatoid arthritis, and 12 control subjects. Parathyroid hormone-related peptide-positive chondrocytes were observed predominantly in degenerated lesions of osteoarthritic tissue and were less evident in rheumatoid arthritic samples, while the normal cartilage expressed little parathyroid hormone-related peptide. In addition, the level of parathyroid hormone-related peptide expression was clearly dependent on the degree of cartilage degeneration; cartilage tissues with moderate degenerative changes contained more positive chondrocytes compared with mildly or severely degenerated cartilage. In situ hybridization confirmed the localization of parathyroid hormone-related peptide protein and demonstrated intense expression of mRNA of the peptide in osteoarthritic samples. This is the first demonstration of parathyroid hormone-related peptide expression in chondrocytes from pathologic articular cartilage of humans. Our results suggest that parathyroid hormone-related peptide may be involved in the pathophysiology of osteoarthritis.
10857796 Primary association of tumor necrosis factor-region genetic markers with susceptibility to 2000 Jun OBJECTIVE: To determine whether tumor necrosis factor (TNF) polymorphisms are associated with susceptibility to rheumatoid arthritis (RA) independently of the HLA-DR shared epitope. METHODS: Fifty-two Spanish families with one or more affected members were typed for HLA-DRB1, TNF promoter polymorphisms, and TNFa and TNFb microsatellites. We performed an association analysis comparing transmitted versus not transmitted haplotypes, with or without shared epitope, to determine whether there is an independent effect of TNF genetic markers on RA susceptibility. RESULTS: TNFa6,b5 was significantly associated with susceptibility to RA. The haplotypes containing these markers were preferentially transmitted to the affected offspring, even if these haplotypes lacked the HLA-DR shared epitope. TNF promoter polymorphisms were not associated with susceptibility to RA. CONCLUSION: The data suggest that TNFa/b is an independent marker of RA susceptibility, pointing to a genetic role of the TNF region in the pathogenesis of RA.
10606357 Expression of myeloid related proteins (MRP) 8 and 14 and the MRP8/14 heterodimer in rheum 1999 Dec OBJECTIVE: Myeloid related proteins (MRP) 8 and 14 and the heterodimer MRP8/14 are myeloid differentiation markers present on infiltrating tissue macrophages in inflammation but not on resident tissue macrophages. We determined the pattern of expression of MRP8, MRP14, and the MRP8/14 heterodimer (27E10 antigen) in rheumatoid arthritis (RA) synovial membrane (SM). METHODS: SM samples were obtained from patients with RA at joint replacement surgery or at arthroscopy and patients without joint disease (healthy subjects) and immunostained for MRP8, MRP14, 27E10 antigen (MRP8/14 heterodimer), and CD68. Positive cell staining was measured by quantitative analysis. RESULTS: SM from 8 patients with RA, including 7 who had paired samples from both adjacent to the cartilage-pannus junction (CPJ) and an area remote from the CPJ, and 2 healthy controls were analyzed. In RA, CD68+ cells accumulated in greater numbers adjacent to the CPJ than remote from the CPJ [mean +/- standard error of the mean (SEM) 488+/-103 and 286+/-76 cells/mm2, respectively; p = 0.01]. SM lining layer (LL) MRP8, MRP14, and 27E10 staining was observed predominantly adjacent to the CPJ and only in patients with active disease. Minimal or absent LL MRP staining was observed in non-CPJ sections. Synovial sublining layer (SL) MRP8, MRP14, and 27E10 staining was also observed only in patients with active disease, but in contrast to the LL, SL staining was observed predominantly in sections remote from the CPJ. CONCLUSION: MRP antigens, representing activation markers on SM macrophages, were observed predominantly in the LL of sections adjacent to the CPJ samples. These original observations suggest altered activation and differentiation of lining layer macrophages at the site of maximal cartilage destruction in RA.
9263147 Efficacy of low load resistive muscle training in patients with rheumatoid arthritis funct 1997 Aug OBJECTIVE: To determine the effect of a low load resistance exercise training program on muscle strength, functional outcome, and cardiovascular endurance. METHODS: Forty-nine patients, 37 women and 12 men between the ages of 35-76 yrs (mean 60.5 yrs), with definite rheumatoid arthritis (RA) functional class II and III (mean disease duration of 10.5 yrs) were randomly assigned to exercise and control groups for a 12 wk resistive muscle training program. A circuit weight bearing form of training was incorporated using light loads with high repetitions. A video tape demonstrating the exercises was given to all exercising participants to enable them to continue the program at home at least 3 times per wk with a biweekly self-report evaluation. Baseline and post-intervention evaluations included joint activity, muscle strength, endurance, functional outcome, and self-report. Cardiovascular fitness measured by treadmill time, anaerobic threshold and peak oxygen consumption (VO2) in this group were assessed at baseline and 12 wks. RESULTS: A significant improvement at 12 wks was noted in the exercise group for self-reported joint count (p = 0.02), number of painful joints (p = 0.004), HAQ (p = 0.012), sit-to-stand time (p = 0.02), grip strength (p = 0.05) knee extension 60 degrees (p = 0.03), Arthritis Impact Measurement Scales dexterity (p = 0.02), and time to anaerobic threshold (p = 0.03). Significant improvement in the exercise group compared to the control group was noted for self-reported joint count (p = 0.02), night time pain (p = 0.05), and sit-to-stand time (p = 0.02). Increase in treadmill time was not statistically significant nor was a change in peak oxygen consumption (VO2) noted. Abnormalities on initial treadmill screening were detected in 2 of 49 asymptomatic patients. They were excluded from the study and subsequent workup revealed significant coronary artery disease. CONCLUSION: Low load resistive muscle training increased functional capacity as reported by patients and is a clinically safe form of exercise in functional class II and III RA. Screening this population for dormant coronary artery disease is recommended.
11333345 Combination therapy in rheumatoid arthritis. 2001 May It has become clear that early suppression of rheumatoid arthritis disease activity is important in preventing progressive joint destruction and functional decline. To achieve this goal, many rheumatologists today advocate a more aggressive approach, using combinations of classic disease-modifying antirheumatic drugs-often including methotrexate-or new drugs. During the last 2 years, the combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone has been demonstrated to be more beneficial than monotherapy in patients with early rheumatoid arthritis. In addition, the superior efficacy of the combination of new tumor necrosis factor-alpha blocking agents plus methotrexate to methotrexate alone in patients with chronic disease is very promising. Most studies of combination therapy focus on the efficacy of a combination compared with monotherapy, rather than on the efficacy of a treatment strategy. Although these studies of combination therapy provide useful information about the possible synergistic action of combinations of drugs, many questions remain unanswered, and studies evaluating different treatment strategies are needed before a new approach can be suggested.
10857781 Differential expression pattern of membrane-type matrix metalloproteinases in rheumatoid a 2000 Jun OBJECTIVE: To study the expression of messenger RNA (mRNA) for different membrane-type matrix metalloproteinases (MT-MMPs) and compare their expression pattern in rheumatoid arthritis (RA) and normal synovium. METHODS: Polymerase chain reaction (PCR) with specific primers was performed to analyze the presence of MT1-, MT2-, MT3-, and MT4-MMP in synovial tissue and synovial fibroblasts from 10 patients with RA and 4 subjects without arthritis. In addition, in situ hybridization with digoxigenin-labeled RNA probes was used to investigate the expression pattern of MT-MMPs in the synovium of these subjects. MT-MMP-expressing cells were characterized by immunohistochemical double labeling with anti-CD68 monoclonal antibodies. RESULTS: Reverse transcription-PCR revealed the expression of MT1-, MT2-, MT3-, and MT4-MMP mRNA in all tissues and cell cultures examined. However, in situ hybridization showed considerable differences in the expression pattern of the different MT-MMPs in RA synovium. MT1- and MT3-MMP mRNA were highly expressed in both the lining and the sublining layer, with more intense staining in the lining. Immunohistochemical double labeling demonstrated the presence of mRNA for MT1-MMP in fibroblasts and macrophages, as well as in osteoclast-like cells at sites of bone resorption. Expression of MT3-MMP mRNA was seen in fibroblasts and some macrophages. Expression of MT2- and MT4-MMP was characterized by staining of only a few CD68-negative fibroblasts, and no differences could be found between the lining and sublining. Normal synovial samples showed only limited staining for all MT-MMPs. CONCLUSION: Our results indicate a role for MT1-MMP not only in the matrix degradation by fibroblasts, but also in osteoclast-mediated bone resorption in RA. Given the ability of MT1-MMP to activate MMP-2 and MMP-13, the findings also point to a cooperation between fibroblasts and macrophages in degrading cartilage and bone. While MT3-MMP is also intensely expressed in RA synovium, MT2- and MT4-MMP appear not to be involved in rheumatoid joint destruction.
11413159 Severe inflammatory arthritis and lymphadenopathy in the absence of TNF. 2001 Jun It has been postulated that TNF has a pivotal role in a cytokine cascade that results in joint inflammation and destruction in rheumatoid arthritis (RA). To evaluate this, we examined the response of TNF-deficient (Tnf(-/-)) mice in two models of RA. Collagen-induced arthritis (CIA) was induced by injection of chick type II collagen (CII) in CFA. Tnf(-/-) mice had some reduction in the clinical parameters of CIA and, on histology, significantly more normal joints. However, severe disease was evident in 54% of arthritic Tnf(-/-) joints. Tnf(-/-) mice had impaired Ig class switching, but preserved T cell proliferative responses to CII and enhanced IFN-gamma production. Interestingly, CII-immunized Tnf(-/-) mice developed lymphadenopathy and splenomegaly associated with increased memory CD4(+) T cells and activated lymph node B cells. Acute inflammatory arthritis was also reduced in Tnf(-/-) mice, although again some mice exhibited severe disease. We conclude that TNF is important but not essential for inflammatory arthritis; in each model, severe arthritis could proceed even in the complete absence of TNF. These results call into doubt the concept that TNF is obligatory for chronic autoimmune and acute inflammatory arthritis and provide a rationale for further studies into TNF-independent cytokine pathways in arthritis.
9068286 Antiperinuclear factors are present in polyarthritis before ACR criteria for rheumatoid ar 1997 Feb OBJECTIVE: To show that antiperinuclear factor (APF) may be useful for the diagnosis of rheumatoid arthritis at a time when the American College of Rheumatology (ACR) criteria are not yet fulfilled. METHODS: Testing for APF-IgG (1:100 threshold) and rheumatoid factors (RF) was done in 60 patients with polyarthritis of recent onset during a three year follow up. RESULTS: At the end of the study, 21/40 rheumatoid arthritis were positive for RF and 31/40 for APF, including 18/40 cases (45%) in which ACR criteria were not yet fulfilled. CONCLUSIONS: APF are useful in the diagnosis of early rheumatoid arthritis.
10984135 Distribution of tenascin-X in different synovial samples and synovial membrane-like interf 2000 The distribution of tenascin-X (Tn-X) was investigated in synovial samples from rheumatoid arthritis (RA), osteoarthritis (OA) and knee injuries, and in synovial membrane-like interface tissue (SMLIT) from aseptic loosening of total hip replacement (THR). An affinity purified rabbit antiserum against Tn-X was applied in avidin-biotin-peroxidase complex method. Double immunofluorescence labeling was used to assess the spatial relationship of Tn-X and Tn-C. All samples showed Tn-X immunoreactivity. Strong staining appeared in the lining and lining-like layers of RA and SMLIT samples, respectively. An intensive immunoreactivity was also found in pannus tissue in RA, and around multinucleate giant cells and polyethylene wear debris in SMLIT. Staining intensity/extent varied significantly in different samples in the following rank order: SMLIT, RA, OA, knee synovium membrane. Double labeling revealed two patterns of Tn-X/Tn-C distribution, reciprocal and co-localization. Our results suggest that Tn-X is an essential component of normal synovial membrane, and that inflammatory mediators may increase local Tn-X production. Tn-X distribution is not always reciprocal to that of Tn-C.
11138338 Factors affecting depression and anxiety in female Japanese patients with rheumatoid arthr 2000 Nov OBJECTIVE: In this study, we attempted to identify which background factors were the most important indicators regarding such psychological problems as depression and anxiety in female rheumatoid arthritis (RA) patients. METHODS: Among female RA patients aged 20 and older, who visited the outpatient clinic, and who met the Revised Criteria of the American Rheumatism Association for RA (ARA1987), 101 Class I and II patients were selected as subjects for the present study. Specially designed questionnaires and psychological tests were given to those subjects who had given their written consent for such testing, and a stepwise multiple logistic regression analysis was carried out on the 85 patients who returned all written forms. Those factors affecting psychological problems at a significance level of 5% or less were identified. RESULTS: It was shown that among sociodemographic factors, "a decrease in the frequency of going out socially after having RA" and "a higher education" worked as significantly associated variables for depression, while "a decrease in the number of friends after having RA" served as a significantly associated variable for trait anxiety. Significantly associated variables for state anxiety included "a decrease in the frequency of going out socially after having RA" and "a willingness to join an RA study group". CONCLUSION: The present study demonstrated that factors related to social interactions were significantly associated with depression and anxiety in Class I and II female RA outpatients.
10451060 Anti-p53 antibodies are rarely detected in serum of patients with rheumatoid arthritis and 1999 Aug OBJECTIVE: To detect evidence of abnormalities of the p53 protein in autoimmune diseases. Mutation of the p53 protein may inhibit apoptosis and thereby lead to cancer and possibly play a role in the pathogenesis of autoimmune diseases. METHODS: Serum antibodies to p53 are detected in 30 to 50% of patients with cancer who have p53 mutations. Using an ELISA, we determined the prevalence of anti-p53 antibodies in the serum of 106 patients with rheumatoid arthritis (RA), 72 patients with primary Sjögren's syndrome (SS), and 14 patients with lymphoma complicating SS. The presence of anti-p53 antibodies was also measured in the synovial fluid of 16 patients with RA. Positive sera by ELISA were confirmed by immunoprecipitation. RESULTS: Serum anti-p53 antibodies were detected in 2 of 106 patients with RA. The synovial fluid of one of these 2 patients was also studied and was positive. Anti-p53 antibodies were not detected in the other synovial fluids. Serum anti-p53 antibodies were not detected in 72 patients with primary SS alone, but were present in 2 of 14 patients with lymphoma complicating SS. CONCLUSION: Our results suggest that if p53 mutations have any role in the pathogenesis of some autoimmune diseases, they are rarely associated with the presence of anti-p53 antibodies in patients with RA. In patients with SS, the presence of serum anti-p53 antibodies might be an indirect sign of the development of a lymphoma.
10615977 Radiolunate arthrodesis: A procedure for stabilising and preserving mobility in the arthri 1999 Nov We carried out arthrodesis of the radiolunate joint in 46 wrists (38 patients) for pain and ulnar translation of the carpus because of rheumatoid (42) or psoriatic arthritis (4). At follow-up, three patients had died and in three (1 bilateral) an additional midcarpal arthrodesis had been undertaken. The remaining 32 patients (39 wrists) were evaluated after a mean of five years. The clinical results were good with a mean visual analogue score of 8.3 for pain, 7.2 for hand function and 9 for overall satisfaction. Except for palmar flexion, mobility was equal to or better than before operation. Radiologically, there was deterioration of the midcarpal joint with an increase in the Larsen score from 1.8 to 2.7 (p < 0.001), some decrease in carpal height and recurrence of carpal translation. Radiolunate arthrodesis gives good clinical results at five years although there is some deterioration radiologically.
9782601 [Vitamin E in therapy of rheumatic diseases]. 1998 Aug Over the past years, antioxidants, and particularly vitamin E, have received considerable attention in the treatment of human diseases. In rheumatology, interest has been given to the treatment and prevention of rheumatoid arthritis and osteoarthritis. However, the concept of using antioxidant nutrients as potential remedies is not new. As early as the sixties, first case reports have described beneficial effects of vitamin E in the therapy of osteoarthritis. Nonetheless, most of the following studies were not conducted properly, thus, not allowing valid inferences about the efficacy of vitamin E. Newer studies with sound methodology have shown a beneficial effect in rheumatic diseases, mainly in the reduction of pain. This paper reviews current and past studies about vitamin E in the treatment of rheumatic diseases.
11766500 [Diagnostic imaging of inflammatory rheumatic joint diseases. Part II: techniques and axia 2001 Dec 3 Imaging of inflammatory disorders of the spine and sacro-iliac joints is important for the diagnosis, prognosis, and evaluation of therapy. Conventional radiography still constitutes the basic imaging modality, but supplementary computed tomography (CT) and especially magnetic resonance imaging (MR-scanning) may provide additional important information. The radiation dose by CT must be taken into account. It is therefore expected that MR-scanning, which is without known risks, will increasingly become the method of choice when the information obtained by conventional radiography is inadequate.
10966367 Acute compartment syndrome following revisional arthroplasty of the forefoot: the dangers 2000 Aug A case of acute compartment syndrome of the forefoot after revisional arthroplasty of the forefoot is presented. Shortening of the compartments due to bony resection and extensive dissection due to previous scarring may have predisposed to the pathological condition. Prompt decompression based on clinical grounds prevented any long term sequelae. Allowance must be made for the concomitant use of local anaesthetic procedures which may obscure the clinical picture.
10857784 Dysregulated intracellular Ca2+ stores and Ca2+ signaling in synovial fluid T lymphocytes 2000 Jun OBJECTIVE: Peripheral blood (PB) T cells from rheumatoid arthritis (RA) patients proliferate poorly to mitogen, a change that is related to decreased intracellular Ca2+ ([Ca2+]i) signaling after T cell receptor (TCR) stimulation. We hypothesized that this was, in part, due to the effect of mediators of inflammation and predicted that greater changes in [Ca2+]i signaling would be seen in synovial fluid (SF) T cells. We also examined the mechanisms underlying the altered [Ca2+]i signals. METHODS: Paired PB and SF T cells from patients with chronic inflammatory arthritis were stimulated with mitogen to assess the magnitude of the [Ca2+]i signal in cell populations by fluorometry, the pattern of the [Ca2+]i signal in individual cells in a single-cell ion-imaging system, and the spatial distribution of Ca2+ within intracellular organelles. RESULTS: There was a significantly smaller [Ca2+]i signal after phytohemagglutinin protein stimulation of SF T cells (peak rise in [Ca2+]i signal PB versus SF 200 nM versus 180 nM; P < 0.05). In single SF T cells, a change in the pattern of the [Ca2+]i signal and a reduction in the number of responding cells was seen. These changes were a magnification of those seen in RA PB compared with control PB T cells. The contribution of Ca2+ release from intracellular stores to the final [Ca2+]i signal in PB and SF T cells was equal, but there was a significant increase in the Ca2+ remaining in the endoplasmic reticulum (ER) in SF T cells after TCR activation (PB versus SF 6 nM versus 19 nM; P < 0.05). Non-ER Ca2+ stores were not similarly affected. CONCLUSION: We found abnormalities in the magnitude, pattern, and spatial distribution of [Ca2+]i signaling in T cells from SF of patients with chronic inflammatory arthritis. A reduction in the number of responding SF T cells may partly explain some of our observations. However, we propose that the observed redistribution of SF Ca2+ stores may underlie the altered [Ca2+]i signaling, thus making these cells hyporesponsive to mitogen. The inflammatory environment of the joint and the late stage of differentiation of SF T cells are both likely to contribute to these changes in [Ca2+]i signaling, resulting in aberrant T cell function and promotion of disease chronicity.
10822686 [The ultrasonography of the capsular ligamentous apparatus of the knee joint in the early 1999 Jul With the purpose of finding out informative value of the ultrasound investigation designed to study the capsular and ligamentous apparatus of the knee joint in its instability during the early stages of rheumatoid arthritis and correlating clinical symptoms with ultrasonographic findings an examination was done of twenty joints of patients in early stages of rheumatoid arthritis presenting with clinical signs of anterior-medial instability. Sonography confirmed the presence of instability and permitted the qualitative assessment of its degree to be done. The method allows us to disclose relative incompetence of the anterior-medial sector of the knee joint in those patients presenting with early stages of rheumatoid arthritis, which is one of causes of instability, with the cruciate and lateral ligaments remaining uninjured. Ultrasonography makes it possible to perform a quantitative assessment of the degree of instability of the joint irrespective of the clinical test used and experience of the orthopedist.
9572638 Weighting for joint surface area improves the information provided by a reduced 28-joint a 1998 The objective of our study was to examine whether weighting for joint surface area or recording of simultaneously tender and swollen joints increases the association of a reduced 28-joint articular index with clinical and outcome parameters. In a cross-sectional study we examined 61 consecutive outpatients with RA fulfilling the American Rheumatism Association 1987 revised criteria. Tender, swollen, and simultaneously tender and swollen joints were recorded. The association of 28- and 68-joint articular indices with clinical and outcome parameters were estimated with nonparametric correlation analyses. Weighting for joint surface yielded consistently increased correlation of clinical and outcome parameters with swollen and tender and swollen but not with tender joint counts. The correlation of the 28-joint articular and 68-articular indices with these parameters were similar. In conclusion, weighting for joint surface notably improves the information provided by swollen joint counts, whereas it does not appear to improve the information provided by tender joint counts.
10403281 Characterization of collagenase 3 (matrix metalloproteinase 13) messenger RNA expression i 1999 Jul OBJECTIVE: To study the localization and cell type-specific expression of collagenase 3 messenger RNA (mRNA) in the synovial membrane, its regulation in primary synovial fibroblasts, and the correlation with systemic markers of inflammation and radiographic damage in rheumatoid arthritis (RA). METHODS: The expression of collagenase 3 mRNA was characterized by Northern blot analysis, reverse transcriptase-polymerase chain reaction, and in situ hybridization. Immunohistochemical detection of cell type-specific antigens was used in combination with in situ hybridization of collagenase 3 mRNA to characterize the cellular origin of collagenase 3 mRNA expression. RESULTS: Collagenase 3 mRNA was detected in synovial membrane specimens of 21 of 36 RA patients (58%) and correlated with an increase in erythrocyte sedimentation rate (P<0.05) and C-reactive protein levels (P<0.005). Collagenase 3 mRNA was localized in fibroblast-like cells of the lining and sublining layers, and at the synovial membrane-cartilage interface. Four of 10 primary synovial fibroblast cell cultures showed basal expression of collagenase 3 mRNA, which was stimulated 2-4-fold upon interleukin-1beta or tumor necrosis factor alpha treatment and, in contrast to interstitial collagenase mRNA, 5-10-fold by increasing the intracellular level of cAMP. The stimulation by cAMP analogs was completely abolished by protein kinase A inhibitors. CONCLUSION: Some RA patients show collagenase 3 mRNA expression in the synovial membrane, which correlates with elevated levels of systemic markers of inflammation in these patients. In synovial fibroblasts, the expression of collagenase 3 and interstitial collagenase mRNA is differentially regulated by distinct protein kinase signal transduction pathways.
9325068 Characterization of adhesion molecule expression in the pathogenesis of homologous collage 1997 Oct We have investigated the inflammatory cell infiltrates and adhesion molecule expression in the synovial fluid (SF) and synovial membranes (SM) of rats with homologous collagen-induced arthritis. Immunohistochemical staining revealed that the majority of the cells in the SF were granulocytes, expressing CD11b and CD11c. In SM, the majority of the cells were monocytes/macrophages. CD49d and CD49f were expressed mainly in the erosion zone in SM, and ICAM-1 was expressed in the lining layer, in the capillaries, and in the erosion zone. In SF 7% of the cells were ICAM-1 positive. CD2 was more abundant in SM than in SF. These findings might explain the difference in granulocyte counts between SF and SM. CD49d and CD49f expression might retain lymphocytes and monocytes in SM, while granulocytes not expressing CD49d and CD49f are not retained.