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ID PMID Title PublicationDate abstract
11808983 Novel pro-inflammatory interleukins: potential therapeutic targets in rheumatoid arthritis 2001 Dec Among potential targets for nonspecific anti-inflammatory immunointervention, three pro-inflammatory interleukins (ILs) have recently been found to play a pivotal role in rheumatoid arthritis (RA). IL-15 has both chemoattractant and proinflammatory properties and may promote bone destruction. IL-17, a product of T lymphocytes, has proinflammatory effects and induces production of metalloproteinases such as MMP-1. IL-18 not only has proinflammatory, angiogenic, and chemoattractant effects but also promotes cartilage destruction. These cytokines are potential targets for specific or nonspecific anti-inflammatory therapy. Thus, blocking IL-15 by its receptor reduces the severity of experimental collagen-induced arthritis (CIA). In this model, IL-17 levels fall after administration of anti-inflammatory cytokines such as IL-4 or IL-13. Finally, monoclonal anti-IL-18 antibodies prevent streptococcal cell wall arthritis, and IL-18 binding protein, which is a naturally occurring IL-18 inhibitor, prevents CIA.
10853185 The Marshall R. Urist Young Investigator Award. Orthopaedic applications of gene therapy. 2000 Jun Gene therapy offers new possibilities for the clinical management of orthopaedic conditions that are difficult to treat by traditional surgical or medical means. To bring the potential of this novel technology into the clinic, a research program was initiated that aimed to identify orthopaedically useful genes and develop methods for delivering them to suitable sites under conditions in which gene expression remains at therapeutic levels for the appropriate periods of time; this program is now 10 years old. Rheumatoid arthritis was selected as the lead disease. Preclinical studies evaluating the local and systemic delivery of numerous different genes by in vivo and ex vivo methods in murine and lapin models led to the development of a human gene therapy protocol for arthritis. In this protocol, a gene encoding the human interleukin-1 receptor antagonist protein is transferred to the metacarpophalangeal joints of female patients with rheumatoid arthritis. The first patient was treated this way in July 1996. This is not only the first orthopaedic application of human gene therapy, but also the first use of gene therapy approved for a nonlethal disease. In addition to providing additional therapeutic options for the treatment of rheumatoid arthritis, the experimental data from this study suggest that gene transfer approaches may improve the treatment of osteoarthritis, the repair of cartilage, ligaments, tendons, menisci, intervertebral discs and bone, and the management of disorders such as osteoporosis and osteogenesis imperfecta. They also show promise as a means for developing novel and improved animal models of orthopaedic diseases. If the current rate of progress continues, wide clinical application of gene therapy in various orthopaedic indications should occur within the next 5 to 10 years.
9918236 Effects of actarit on synovial cell functions in patients with rheumatoid arthritis. 1999 Jan OBJECTIVE: Actarit (4-acetylaminophenylacetic acid), developed in Japan, has been shown to be effective for suppressing disease activity of rheumatoid arthritis (RA). We analyzed effects of actarit on synovial cell functions in patients with RA for insight into the clinical application of this medication. METHODS: RA primary synovial cells were co-cultured with actarit at 10(-4)-10(-7) M. Their subsequent proliferative responses and proinflammatory cytokine and matrix metalloproteinase (MMP) production at the mRNA and protein levels were measured. Effects of actarit on adhesion molecule expression were analyzed by immunofluorescence flow cytometry and cell-cell binding assay. RESULTS: Spontaneous tumor necrosis factor-alpha and interleukin 1beta secretion by primary synovial cells of patients with RA was reduced by actarit at therapeutic concentrations (10(-5)-10(-6) M). In contrast, actarit also suppressed MMP-1 production by the primary synovial cells. In addition, actarit down-regulates CD44 and intercellular adhesion molecule 1 expression on fibroblast-like synovial cell lines, and very late antigen 4 expression on CD14+ macrophage-like synovial cells resulted in the inhibition of lymphocyte adhesion to RA synovial cells. CONCLUSION: The results suggest that actarit acts on RA synovial cells to reduce cell-cell interactions with autologous synovium infiltrating lymphocytes and to inhibit proinflammatory cytokine and MMP production, leading to amelioration of symptoms of RA.
11304666 Old and new drugs used in rheumatoid arthritis: a historical perspective. Part 1: the olde 2001 Mar Rheumatoid arthritis is the paradigmatic immune-mediated inflammatory arthropathy and may be of comparatively recent, New World origin. Apart from the symptom-relieving nonsteroidal anti-inflammatory drugs, whose natural congeners have been in use since antiquity for musculoskeletal pain and inflammation, only a dozen drugs or drug classes--the disease-modifying antirheumatic drugs--are currently in common use in rheumatoid arthritis. Development of these drugs has been a notable achievement of the 20th century. Some were developed serendipitously (glucocorticoids, antimalarials), some were the product of faulty reasoning (gold, D-penicillamine), and others were applied for plausible reasons but whose mechanism remains unproven (sulfasalazine, methotrexate, minocycline). A minority were originally applied on the basis of actions that remain germane to the pathophysiology of rheumatoid arthritis as currently understood (azathioprine, cyclosporine, leflunomide, infliximab, etanercept). Among the latter are the more recently introduced and effective agents. The practical use of these drugs is determined by efficacy-toxicity considerations, which have also driven the recent development of the cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs.
11928230 [Stromelysin-1 in inflammatory disease: significance, specificity, and regulation elements 2001 Stromelysin-1 or matrix metalloproteinase-3 (MMP-3) is a key enzyme of the degradation of the extracellular matrix in rheumatoid arthritis. MMP-3 is indeed induced by pro-inflammatory cytokines and may in turn activate other metalloproteinases. MMP-3 is a synovial parameter reflecting the local inflammatory reaction induced by inflammatory cytokines. It is not specific for rheumatoid arthritis nor for the erosive capacity of an arthropathy, which does not exclude its role in articular degradation. Serum MMP-3 is increased in diseases characterized by synovitis but also by steroid therapy. Although it is not disease-specific, serum MMP-3 could be useful as a synovial-derived marker of local inflammation in rheumatoid arthritis, in parallel to CRP which is a systemic marker of inflammation. Furthermore, early determination of serum MMP-3 could constitute a new tool predictive of the disease activity and the therapeutic response in rheumatoid arthritis.
10612068 Nonsurgical management of the foot and ankle affected by rheumatoid arthritis. 1999 Dec Rheumatoid arthritis frequently affects foot and ankle function, leading to pain, difficulty with ambulation, and disability. The purpose of this article is to describe common foot and ankle deformities associated with rheumatoid arthritis and present state-of-the-art nonsurgical management strategies. Physical impairments thought to be commonly associated with limitations of function and practical interventions for alleviating those impairments or reducing the impact of the impairment on ambulation are identified. Examples of rehabilitation interventions discussed include prescription footwear, custom and premolded foot orthoses, hindfoot orthoses, ankle-foot orthoses, shoe modifications, therapeutic exercises, and patient education. Early and aggressive attempts at prevention, delay, or correction of foot and ankle pathomechanics related to rheumatoid arthritis may play a key role in helping patients maintain an active ambulatory lifestyle.
10796461 Auranofin versus placebo in rheumatoid arthritis. 2000 BACKGROUND: Auranofin is an oral gold compound used for the treatment of rheumatoid arthritis RA. The use of auranofin has declined in the past few years, perhaps due in part to conflicting results from different studies. OBJECTIVES: To estimate the short-term efficacy and toxicity of auranofin for the treatment of (RA) SEARCH STRATEGY: We searched MEDLINE and EMBASE up to December 1998, the Cochrane Controlled Trials Register (CCTR) version 4, 1998, and the Cochrane Musculoskeletal Group Specialized Register. A hand search was also done of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing auranofin against placebo in patients with RA DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed using a validated assessment tool (Jadad 1996). Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain and global assessments. The weighted mean difference (WMD) was used for ESR. Toxicity was evaluated with pooled odds ratios for withdrawals and adverse reactions. A chi-square test was used to assess heterogeneity among trials. In the presence of heterogeneity, random effects models were used. Otherwise, the data was pooled assuming fixed effects. MAIN RESULTS: A statistically significant benefit was observed for auranofin when compared to placebo for tender joint scores, pain, patient and physician global assessments and ESR. The SMD between treatment and placebo was -0.39 (95% CI -0.54, -0.25) for tender joint scores, -0.08 (95% CI -0.22, -0.07) for swollen joint scores, and the WMD was -4.68 (95% CI -6.59, -2.77) for pain scores and -9.85mm (95% CI -16.46, -3.25) for ESR. Withdrawals from adverse reactions were 1.5 times higher in the auranofin group OR = 1.52 (95% CI 0.94, 2.46) but this result was not statistically significant. Patients receiving placebo were three times more likely to discontinue treatment because of lack of efficacy than patients receiving auranofin: OR=0.31 (95% CI: 0.21, 0.44). REVIEWER'S CONCLUSIONS: Auranofin appears to have a small clinically and statistically significant benefit on the disease activity of patients with RA. The beneficial effects appear to be modest compared to drugs such as methotrexate or parenteral gold. Its effects on long term health status and radiological progression are not clear at this time.
10812493 Reduction in serum leptin and IGF-1 but preserved T-lymphocyte numbers and activation afte 2000 Mar OBJECTIVE: To assess the clinical, immunological and hormonal effects of carbohydrate restriction in rheumatoid arthritis (RA) patients via the provision of a ketogenic diet. METHODS: Thirteen RA patients with active disease consumed a ketogenic diet for 7 days, providing the estimated requirements for energy and protein whilst restricting their carbohydrate intake to < 40 g/day. This was followed by a 2-week re-feeding period. Clinical and laboratory evaluations were carried out on days 0, 7 and 21. Changes in serum glucose, beta-hydroxybutyrate (beta-HB), leptin, insulin-like growth factor-1 (IGF-1) and cortisol were also measured at these time points. To study CD4+ and CD8+ lymphocyte responses, mitogen stimulated T-cell activation was assessed in heparinised whole blood via flow-cytometric analysis of CD69 expression. RESULTS: After the 7-day ketogenic diet, there were significant increases in serum beta-HB and cortisol, and significant decreases in body weight, the total lymphocyte count, serum leptin, IGF-1 and glucose. However, with the exception of morning stiffness, there were no significant changes in any of the clinical or laboratory measures of disease activity, or in early T-lymphocyte activation and the absolute numbers of CD4+ and CD8+ cells. CONCLUSION: In RA patients several of the metabolic and hormonal responses to a ketogenic diet, such as a fall in serum IGF-1 and leptin, resemble those which occur in response to acute starvation. However, the clinical and immunological changes which occur in response to acute starvation do not take place with a ketogenic diet and thus may be dependent upon energy and/or protein restriction.
10648022 Foot deformities in rheumatoid arthritis and relevance of disease severity. 2000 Jan OBJECTIVE: To investigate foot deformities in rheumatoid arthritis (RA) in relation to the disease severity. METHODS: Radiographs of 100 weight bearing feet of 50 patients who had had RA for >10 years (mean 13.5 years) were studied. The patients were classified into 2 study groups according to the severity of disease. We measured hallux valgus angle (HVA), intermetatarsal angle between first and 2nd (M1/2), and intermetatarsal angle between first and 5th (M1/5) on anteroposterior (AP) radiographs, as well as calcaneal pitch (CP) and first metatarsal pitch (MP) on lateral radiographs. The differences in these angles between the 2 groups (Inter-group study) and the correlations among angles within each group (Intra-group study) were examined. RESULTS: Inter-group study showed significant differences between the 2 groups for all variables. Intra-group study, on the other hand, showed no correlation between variables of the 2 deformities, i.e., splaying of forefoot (M1/2 and M1/5) and flattening of longitudinal arch (CP and MP). Only HVA correlated with the splaying (M1/2 and M1/5) in both study groups. CONCLUSION: Disease severity is related to the progression of foot deformities in RA, but the flattening and the splaying are not correlated with each other. We believe that foot deformities should be treated properly and early, especially for patients who are expected to have severe disease.
9221406 [Quantitative analysis of radiologic progression in rheumatoid arthritis: controversies an 1997 Mar Rheumatoid arthritis (RA) is a chronic inflammatory disease with symmetrical polyarthritis as the major feature. Persistent inflammation leads to largely irreversible joint damage which can be seen radiographically. Radiographs depict the progression of joint damage and alterations, which are one of the major parameters of RA evolution. Delayed radiologic progression is a good indicator of the success/failure of long-term drug treatment, but the quantitative analysis of changes over time and the reliability of scoring systems remain difficult steps. This paper focuses of the main current scoring systems, with an emphasis on the following four: Larsen method and its modification by Kayle, Sharp method and its modification by van der Heijde. The scoring method--be it grading, counting, or weighted counting--did not appear to influence reliability or repeatability, while the radiologist's training and the film reading technique were critical to identify disease progression accurately. Our data consistently suggest the paired reading method as the most suitable for radiologic progression assessment in RA. The radiologic studies of 62 patients with early RA after 7 years' follow-up showed joint damage in 82% of patients. The average annual progression rate of the total radiologic score obtained with Sharp method, summing erosions and joint space abnormalities, was faster in the earlier years of the disease (8.8 units/year) than later on (4.9 units/year) (p < 0.01). From the trialist's point of view, these results imply that disease duration is a critical feature for RA treatment outcome.
10520445 Basic therapy for rheumatoid arthritis: nonsteroidal anti-inflammatory drugs. 1999 Aug Nonsteroidal anti-inflammatory drugs (NSAIDs) are often the initial treatment for rheumatoid arthritis. NSAID-induced inhibition of cyclooxygenase-2 (COX2) and cyclooxygenase-1 appears to correlate with clinical efficacy and toxicity, respectively. Newer NSAIDs with greater COX2 selectivity offer the promise of less toxic therapy.
11034719 Penicillamine for treating rheumatoid arthritis. 2000 OBJECTIVES: To estimate the short-term effects of D-penicillamine for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register (issue 3, 2000) and Medline up to and including August 2000 and Embase from 1988-2000. 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 D-penicillamine against placebo in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed independently by two reviewers (CS, EB) and checked by a third (MS) using a validated quality assessment tool (Jadad 1996). Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint and stratified according to D-penicillamine dosages: low (<500mg/day), moderate (500 to <1000mg/day) and high (1000 mg/day or greater). Data was abstracted by one reviewer and checked by a second (CS, MS). The pooled analysis was performed using the standardized mean difference for joint counts, pain and global assessments. The weighted mean difference was used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and adverse reactions. 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: Six trials were identified, with 425 patients randomized to D-penacillamine and 258 to placebo. A statistically significant benefit was observed for D-penicillamine when compared to placebo for all three-dose ranges and for most outcome measures including: tender joint counts, pain, physician's global assessments and ESR. The standardized weighted mean differences between treatment and placebo in moderate doses were -0.51 [95% CI -0.88, -0.14] for tender joint counts, -0.56 (95% CI -0.87, -0.26) for pain and -0.97 (95% CI -1.25, -0.70) for global assessment. The difference for ESR was -10.6 mm/hr. Similar results were observed for the higher dose group. Total withdrawals were significantly higher in the moderate and high dosage D-penicillamine groups (OR=1.63 and 2.13 respectively), mostly due to increased adverse reactions (OR = 2.60 and 4.95 respectively), including renal and hematological abnormalities. REVIEWER'S CONCLUSIONS: D-penicillamine appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. Its efficacy appears to be similar to that of other disease modifying anti-rheumatic drugs (DMARDs), but with a significantly higher toxicity. Its effects on long-term functional status and radiological progression are not clear from this review.
9041933 Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation t 1997 Feb OBJECTIVE: To define variations in the cellular infiltrate and in the expression of monokines in synovial tissue (ST) from rheumatoid arthritis (RA) patients with different durations of disease and different levels of disease activity. METHODS: The immunohistologic features of synovial biopsy specimens from 31 patients with early RA (< 1 year) and 35 patients with longstanding RA (> 5 years) were compared. The possible associations between these features and local disease activity, as measured by the score for pain in the biopsied knee joint were also evaluated. RESULTS: The immunohistologic features were not dependent on disease duration. We found a positive correlation between the scores for knee pain and the semiquantitative scores for the number of macrophages, as well as the expression of interleukin-6 and tumor necrosis factor alpha, whereas the correlation with the scores for CD4+ T cells was negative. Multivariate analysis showed that these correlations were highly statistically significant (P < 0.003). CONCLUSION: The results do not support the view that inflammatory mechanisms in the synovial tissues of RA patients differ between early and late stages of the disease. The findings presented here are consistent with the concept that early RA is the result of a synovitis process of longer duration and that macrophage-derived cytokines play an important role in maintaining the clinical signs of inflammation.
10415630 Can we use steroid hormones to immunomodulate rheumatic diseases? Rheumatoid arthritis as 1999 Jun 22 This review discusses the available clinical trials in which steroids have been used in the (adjuvant) treatment of rheumatoid arthritis. Glucocorticosteroids have a positive effect on symptoms and signs of inflammation, but probably not on structural damage. Therefore glucocorticosteroids should be used as part of a long-term treatment strategy, including disease modifying drugs. Preventive measures regarding osteoporosis and peptic ulcer disease are now possible, and an active screening for potential adverse effects is advisable. The benefit of adjuvant treatment with sex hormones is limited. Estrogens have a slight positive effect in postmenopausal women on disease activity and bone mass. Androgens have a slight positive effect in men and postmenopausal women, especially on general well-being and bone mass.
9308521 Swanson proximal interphalangeal joint arthroplasty in patients with rheumatoid arthritis. 1997 Sep One hundred thirty-eight Swanson proximal interphalangeal replacements were implanted in patients with rheumatoid arthritis, of which 99 implants were available for average 5.8 years followup. Pain was severe in 1%, moderate in 4%, slight in 28%, and not present in 67%. The average preoperative active arc of motion was 38 degrees, and postoperative 29 degrees. Ten fractures were found, and were revised. Of 45 patients assessed, 45 (100%) reported the ability to feed themselves, 43 (96%) to button their clothes, and 42 (93%) to write. There was sclerosis of bone around 78% of the implants and resorption adjacent to 12% of the implants. Survivorship analysis showed that 81% of implants were not revised at 9 years.
8995045 Pain behavior, spouse responsiveness, and marital satisfaction in patients with rheumatoid 1997 Jan Although the pain behavior of some diagnostic groups has been shown to be reactive to social influences, the reactivity of pain behavior in a rheumatoid arthritis (RA) population remains an open question. The authors in this article combined laboratory and self-report assessment techniques to examine the extent to which the pain report and behavior of 52 RA patients was susceptible to influence of social factors within the marital unit. The authors' findings suggest that (a) different types of spouse responsiveness (e.g., solicitous, punishing) may be viewed differently by the RA population than more general chronic pain populations; (b) the patient's perception of spouse responsiveness is a significant predictor of the pain behavior, whereas the spouse's perception of these same behaviors is not; and (c) the patient's perception of the spouse's responsive behavior adds significantly to the prediction of pain behavior over a model based on "disease impact" variables alone.
9821101 Miliary tuberculosis presenting as tenosynovitis in a case of rheumatoid arthritis. 1998 Sep A 77-year-old woman with a seropositive nodular rheumatoid arthritis and vasculitis, who was treated with high doses of corticosteroids and intravenous cyclophosphamide, developed miliary tuberculosis that was heralded by a tenosynovitis in her right wrist. A 1-year course of anti-tuberculous therapy resulted in complete resolution of the tenosynovitis and disseminated infection.
11219390 Activation of synovial fibroblasts in rheumatoid arthritis: lack of Expression of the tumo 2000 AIMS: PTEN is a novel tumour suppressor which exhibits tyrosine phosphatase activity as well as homology to the cytoskeletal proteins tensin and auxilin. Mutations of PTEN have been described in several human cancers and associated their invasiveness and metastatic properties. Although not malignant, rheumatoid arthritis synovial fibroblasts (RA-SF) exhibit certain tumour-like features such as attachment to cartilage and invasive growth. In the present study, we analyzed whether mutant transcripts of PTEN were present in RA-SF. In addition, we used in situ hybridization to study the expression of PTEN messenger (m)RNA in tissue samples of RA and normal individuals as well as in cultured RA-SF and in the severe combined immunodeficiency (SCID) mouse model of RA. Synovial tissue specimens were obtained from seven patients with RA and from two nonarthritic individuals. Total RNA was isolated from synovial fibroblasts and after first strand complementary (c)DNA synthesis, polymerase chain reaction (PCR) was performed to amplify a 1063 base pair PTEN fragment that encompassed the coding sequence of PTEN including the phosphatase domain and all mutation sites described so far. The PCR products were subcloned in Escherichia coli, and up to four clones were picked from each plate for automated sequencing. For in situ hybridization, digoxigenin-labelled PTEN-specific RNA probes were generated by in vitro transcription. For control in situ hybridization, a matrix metalloproteinase (MMP)-2-specific probe was prepared. To investigate the expression of PTEN in the absence of human macrophage or lymphocyte derived factors, we implanted RA-SF from three patients together with normal human cartilage under the renal capsule of SCID mice. After 60 days, mice were sacrificed, the implants removed and embedded into paraffin. RESULTS: PCR revealed the presence of the expected 1063 base pair PTEN fragment in all (9/9) cell cultures (Fig.1). No additional bands that could account for mutant PTEN variants were detected. Sequence analysis revealed 100% homology of all RA-derived PTEN fragments to those from normal SF as well as to the published GenBank sequence (accession number U93051). However, in situ hybridization demonstrated considerable differences in the expression of PTEN mRNA within the lining and the sublining layers of RA synovial membranes. As shown in Figure 2a, no staining was observed within the lining layer which has been demonstrated to mediate degradation of cartilage and bone in RA. In contrast, abundant expression of PTEN mRNA was found in the sublining of all RA synovial tissues (Figs 2a and b). Normal synovial specimens showed homogeneous staining fo PTEN within the thin synovial membrane (Fig. 2c). In situ hybridization using the sense probe gave no specific staining (Fig. 2d). We also performed in situ hybridization on four of the seven cultured RA-SF and followed one cell line from the first to the sixth passage. Interestingly, only 40% of cultured RA-SF expressed PTEN mRNA (Fig. 3A), and the proportion of PTEN expressing cells did not change throughout the passages. In contrast, control experiments using a specific RNA probe fo MMP-2 revealed mRNA expression by nearly all cultured cells (Fig. 3B). As seen before, implantation of RA-SF into the SCID mice showed considerable cartilage degradation. Interestingly, only negligible PTEN expression was found in those RA-SF aggressively invading the cartilage (Fig. 3c). In situ hybridization for MMP-2 showed abundant staining in these cells (Fig. 3d). DISCUSSION: Although this study found no evidence for mutations of PTEN in RA synovium, the observation that PTEN expression is lacking in the lining layer of RA synovium as well as in more that half of cultured RA-SF is of interest. It suggests that loss of PTEN function may not exclusively be caused by genetic alterations, yet at the same time links the low expression of PTEN to a phenotype of cells that have been shown to invade cartilage aggressively. It has been proposed that the tyrosine phosphatase activity of counteracting th actions o protein tyrosine kinases. As some studies have demonstrated an upregulation of tyrosine kinase activity in RA synovial cells, it might be speculated that the lack of PTEN expression in aggressive RA-SF contributes to the imbalance of tyrosine kinases and phosphatases in this disease. However, the extensive amino-terminal homology of the predicted protein to the cytoskeletal proteins tensin and auxilin suggests a complex regulatory function involving cellular adhesion molecules and phosphatase-mediated signalling. The tyrosine phosphatase TEP1 has been shown to be identical to the protein encoded by PTEN, and gene transcription of TEP1 has been demonstrated to be downregulated by transforming growth factor (TGF)-beta. Therefore, it could be hypothesized that TGF-beta might be responsible for the downregulation of PTEN. Low expression of PTEN may belong to the features that distinguish between the activated phenotype of RA-SF and the sublining, proliferating but nondestructive cells.
10343468 Cutaneous mucinous nodules associated with proliferating synovitis of rheumatoid arthritis 1999 Apr Rheumatoid arthritis (RA) is occasionally associated with specific or non-specific cutaneous conditions. In this report, we describe unusual cutaneous nodules arising on the skin overlying the inflamed joints of two patients with RA. The nodules were histopathologically characterized by mucinous granulation tissue associated with neutrophilic infiltration and proliferation of starry-shaped mesenchymal cells. The affected joints of both cases showed synovitis with synovial tissue hyperplasia due to RA. Because hyaluronic mucin, which is the major component of synovial fluids, was deposited in the nodules, intradermal inoculation of synovial cells seemed to be responsible for the nodular development. The nodules of one patient spontaneously resolved in several months. We are unaware of any report describing similar cases. Such nodules should be included as a cutaneous complication of RA, distinct from neoplasias.
10374284 [DNA typing for HLA-DR and HLA-DQ alleles in Chinese patients with rheumatoid arthritis]. 1997 Apr We analysed the associations of DR and DQ alleles with rheumatoid arthritis (RA) in Han nationality of China. PCR-RFLP technique was used to determine DRB1, DQA1 and DQB1 alleles in 35 unrelated patients with RA and 100 healthy controls from the Hans. The frequency of DR4 was 51.4% in RA patients and 24.0% in the healthy controls (P < 0.01, RR = 3.30). Subtyping of DR4 revealed no differences in the relative distributions of the DR4 alleles between the RA group and the controls, which both were predominated by DRB1 * 0405 allele, but there was a significant increase in the absolute frequency of DRB1 * 0405 in RA patients compared with the healthy controls (31.4% vs 12.0%, P < 0.01). DQ4 (DQB1 * 04) was also increased both in the RA patients compared with the healthy controls (37.1% vs 10.0%, P < 0.001) and in DR4+ RA patients compared with DR4+ healthy ones (72.2% vs 41.6%, P = 0.0376). Further analysis showed that the haplotype DR4-DQ4 was associated with RA (RR = 5.17, P < 0.001), and that the DR4(+)-DQ4+ patients had more severe disease than the DR4- patients. These results suggest that DR4, mainly the DRB1 * 0405, is associated with RA in Han nationality, and DQ4 may play a role in DR4 conferring susceptibility to RA. The DR4-DQ4 haplotype could be taken as a predictive marker for disease severity.