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

ID PMID Title PublicationDate abstract
7738940 Upper limb lymphatic function in inflammatory arthritis. 1995 Feb OBJECTIVE: To determine the effect of inflammatory arthritis on lymphatic function in the upper limb. METHODS: Lymphoscintigraphy was used to measure lymphatic drainage in the upper limbs of 3 groups of patients: Group 1, inflammatory arthritis and edema (N = 10); Group 2, inflammatory arthritis and no edema (N = 18); and Group 3, healthy controls (N = 11). RESULTS: Lymphatic drainage was reduced significantly in Group 1 but was the same in Groups 2 and 3. Multiple regression analysis failed to show any effect of arthritis on lymphatic drainage. CONCLUSION: Inflammatory arthritis alone does not impair lymphatic drainage in the upper limbs. The results suggest that the presence of edema is primarily attributable to an unrelated abnormality influencing lymphatic function.
7833884 [Search of papillomavirus genome in synovial membranes and rheumatoid nodules]. 1994 IgG antibodies to rat esophagus stratum corneum are highly specific for rheumatoid arthritis and have been recently shown to be directed against human (pro)filaggrin. Although the mechanisms underlying the loss of tolerance of B lymphocytes for filaggrin remain unelucidated, a role of infection with the human papillomavirus has been suggested on the basis of the following facts: 1) the protein exhibiting the greatest molecular homology with filaggrin is papillomavirus-encoded; 2) human papillomavirus proteins bind to cytoskeletal proteins; 3) human papillomavirus replication is enhanced by friction and rheumatoid lesions predominantly develop in areas subjected to friction, as shown by the distribution of rheumatoid nodules; 4) the rheumatoid pannus resembles a benign tumor. The objectives of this study were to look for the human papillomavirus genome in six synovial membrane specimens and two rheumatoid nodule specimens from rheumatoid arthritis patients with disease durations of more than ten years and in 20 synovial membrane specimens collected during surgical procedures in osteoarthritis patients. The methods used were polymerase chain reaction with papillomavirus-specific primers. The papillomavirus genome was not detected in any of the 28 specimens. A role for the human papillomavirus in the pathogenesis of rheumatoid arthritis cannot be ruled out on the basis of these findings because filaggrin is expressed in other tissues, including the thymic medulla epithelium. In addition, the primers used in this study may have been inappropriate.
1567489 An electronic method for measuring joint tenderness in rheumatoid arthritis. 1992 Apr OBJECTIVE: To test the precision of a new electronic method for measuring joint tenderness. METHOD: Joint tenderness was measured in 30 patients with rheumatoid arthritis, using an electronic dolorimeter. The results were compared with joint tenderness counts, which were made according to the American Rheumatism Association (ARA) methods. RESULTS: The intra-observer variability using the electronic method was significantly decreased compared with the conventional ARA joint tenderness counts. CONCLUSION: The electronic method is more efficient for use in clinical trials than is the conventional ARA joint tenderness count.
8775704 Marmor modular knee plateau positioning and prosthesis survival in 55 knees with rheumatoi 1996 In a long-term follow-up of 55 Marmor knee arthroplasties in patients with rheumatoid arthritis operated on between 1975 and 1977, the radiologically visible indicator wire was used to identify the position of the tibial components. The survival rate of the prostheses at 15 years was 0.71, and the revisions were evenly distributed over the observation period of 16 years. No significant relationship was found between the slope of the tibial components postoperatively and the survival of the prostheses. However, a postoperative valgus angle of the leg of 3 deg or more tended to increase the risk of revision (RH = 2.7, 95% CL = 0.8-8.9). The patient's sex, affected side or weight did not influence prosthesis survival.
8230006 Aberrant control of galactosyltransferase in peripheral B lymphocytes and Epstein-Barr vir 1993 Aug It is now well established that hypogalactosylation of IgG is a molecular marker for rheumatoid arthritis (RA). However, the mechanism for the alteration of the galactosylation status has not been resolved. We compared the galactosyltransferase activities of anti-CD19 selected peripheral B lymphocytes of healthy subjects and patients with RA using ovalbumin as the acceptor substrate. In addition, certain samples of lymphocytes were assayed after Epstein-Barr virus (EBV) transformation and, also, the ability of bovine milk galactosyltransferase to galactosylate IgG in vitro was examined. Our results indicate that there is a significant difference between the galactosyltransferase activities of rheumatoid and control peripheral B lymphocytes and that EBV transformation causes a variable increase (15-1225%) in galactosyltransferase activity, over that present in the peripheral B lymphocytes from which the transformed cells were derived. Also the ubiquitous "lactose synthetase" type galactosyltransferase (EC 2.4.1.38) will galactosylate normal native IgG at concentrations of 500 mU/ml in vitro. We conclude that there is no evidence from our study for an IgG specific galactosyltransferase and that galactosyltransferase is an enzyme that is aberrantly modulated in peripheral B lymphocytes and EBV transformed B lymphoblasts derived from patients with RA.
7924049 Imaging techniques for glenohumeral arthritis and glenohumeral arthroplasty. 1994 Oct A thorough history and physical examination can usually determine the cause of a painful shoulder. In most cases, the diagnosis and cause of glenohumeral arthritis are fairly obvious. Imaging studies such as radiographs, computed tomography (CT), arthrography, ultrasonography, and magnetic resonance (MR) imaging are used to confirm and further define the pathologic process. Early in the development of glenohumeral arthrosis, subtle radiographic findings may suggest the diagnosis when the symptoms are mild. Later in the progression of joint destruction, imaging studies are crucial to the planning of prosthetic arthroplasty. Subsequent to arthroplasty, imaging studies can identify existing or potential problems that might correlate with the clinical course. Recent advances in musculoskeletal imaging, such as CT, ultrasound, and MR imaging, enable the physician to confirm or document anatomic pathology that was previously only inferred. There has been a corresponding increase in the use of imaging modalities. Concurrently, cost has become a major concern, and its limitation or reduction a priority of current and future medical care. Consequently, the knowledge gained from further research, education, and clinical experience must promote appropriate use and enable doctors to avoid sophisticated imaging when the results will not influence the course of treatment. The radiographic evaluation of glenohumeral arthrosis the use of imaging techniques in planning prosthetic glenohumeral arthroplasty, and the role of imaging in followup evaluations of prosthetic arthroplasty are discussed. The preferred approaches to these subjects are presented and clinical cases are used to highlight the important and interesting principles.
1582126 Influence of rheumatoid synovial fluid and cells on proteoglycans in human cartilage expla 1992 Mar We have studied the effects of cell-free rheumatoid synovial fluid (RASF) and the conditioned medium (CM) from these cells on the proteoglycans (PGs) of normal human cartilage and the influence which piroxicam might have on these processes. Both RASF and the CM from RASF cells enhanced the PG release from the cartilage explants. The effects of the above mentioned fluids on the cartilage PG content depended on the metabolic state of the cartilage i.e. correlated inversely with the PG synthesis. Whether this was due to the presence of anabolic and catabolic factors in these fluids is discussed. Piroxicam had no adverse effect on the PGs of human cartilage in vitro. Piroxicam prevented the cartilage PG depletion when it was induced by the CM from RASF cells.
7720133 [IL-1 beta mRNA expression in patients with rheumatoid arthritis]. 1994 Oct Using arthroscopy techniques, 6 synovia samples from patients with rheumatic diseases were obtained. Of these, 2 patients had rheumatoid arthritis (RA), 2 had meniscus damage (MD), 1 had osteoarthritis (OA), and 1 had osteochondritis (OC). Using the guanidinium isothiocyanate method, total RNA from synovia was extracted, and 18S and 28S sedimentation bands (rRNA) were separated by electrophoresis. Plasmid containing the 1.3kb cDNA of IL-1 beta were extracted from E. coli by alkaline lysis. Subsequent digestion with XHO1 and then separation on gel isolated the 1.3kb cDNA for use as a probe. The probe was then labeled with 32P-dATP by nicktranslation and hybridized to the synovial RNA extract. The autoradiograph showed that in 4 cases of non-RA, the IL-1 beta cDNA did not hybridize to the synovial mRNA extract. An intense hybridization band was visible for mRNA from one RA case. The clinical and laboratory parameters and X-rays of both knees and wrists of this case were all abnormal, and a rthroscopic findings showed pathological rheumatoid changes of synovium. In addition, this patient did not receive any DMARDs treatment for the RA. The other RA case did not have any hybridization bands. However, this patient did receive DMARDs treatment, and the RA went into remission. The Northern blot result above suggests that IL-1 beta mRNA expression in synovia is negative in non-RA cases and in cases where RA is in remission after DMARDs treatment. In the case with clinically active RA, IL-1 beta is highly expressed, as evidenced by the intense hybridization band.
8352236 Decreased affinity and number of transferrin receptors on erythroblasts in the anemia of r 1993 Jul In anemia of chronic disease (ACD) in rheumatoid arthritis (RA) a decreased iron uptake and transferrin binding by erythroblasts are postulated to play a pathophysiological role. To examine whether this is related to changes in transferrin receptor expression by erythroblasts, we studied bone marrow from 5 healthy controls, 5 nonanemic RA patients, and 9 RA patients with ACD. Bone marrow mononuclear cells were incubated with increasing concentrations of 125I-transferrin and specific binding data were analyzed by the method of Scatchard. The number of transferrin receptors on erythroblasts from RA patients with ACD was significantly lower as compared to nonanemic RA patients (P < .05) and controls (P < .02). The affinity of the transferrin receptor tended to be lower in ACD. These preliminary data may indicate that transferrin receptor expression by erythroblasts is impaired in ACD. Since the rate of erythroid iron uptake is mainly determined by the number of transferrin binding sites, this may explain a decrease in erythroblast iron availability in ACD in RA.
7725811 [Chronic polyarthritis and carpal tunnel syndrome. Results of follow-up]. 1995 Jan Between July 1974 and December 1989, carpal tunnel-syndromes (CTS) were operated on in 903 hands of 746 patients. 147 of these patients (191 hands) were suffering from chronic inflammatory joint diseases. In 11 patients CTS was the first sign of rheumatoid arthritis (R.A.). The hands showed intraoperatively in 44.8% (n = 86/191) an extensive tenosynovitis with an aggressive infiltration. In 19% (n = 36/191), we had to extend the obligate tenosynovectomy on the flexor tendon parts of the fingers and ligaments (28 hands). 21 articulosynovectomies on the wrist or finger joints were performed. In 6 hands (8.0%) tendon ruptures were repaired. A questionnaire was completed for 107 of 147 patients (72.8%) (with 145 operated hands). Clinical (77 hands) and electromyographical examinations (49 hands) were performed an average of 5.1 (0.7-15) years postoperatively. 20 patients (13.6%) died, 20 could not be traced. In 86% (n = 125/145) of the patients we achieved relief of pain and a marked reduction of neurological deficits. 96.3% of the patients were content. The improvement of function of the hand after surgical intervention is of a great benefit for the patient with R. A. The overall risks of the procedure are low (complications 14%; no recidivism). Therefore, we recommend surgery in early stages after a confirmed diagnosis or a reasonable suspicion.
8508557 Effect of gonadal steroids on the production of IL-1 and IL-6 by blood mononuclear cells i 1993 Mar Sex hormones have profound effects on immune responses and may influence the outcome of autoimmune diseases such as rheumatoid arthritis (RA). We investigated the effect of gonadal steroids on the production of interleukin-1 (IL-1) and IL-6, cytokines believed to be important in the pathogenesis of RA. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy male donors and male patients with RA, and were stimulated with lipopolysaccharide (LPS) in the presence of different concentrations of 17-beta-estradiol, progesterone or testosterone. In studies of cells from normal male donors, 17-beta-estradiol at pharmacological concentrations (> or = 10(-6) M) enhanced IL-1 and IL-6 secretion as well as the production of cell-associated IL-1. Progesterone and testosterone at similar concentrations inhibited IL-1 secretion but had no significant effect on IL-6 secretion or on the production of cell-associated IL-1. In studies of male RA donors, 17-beta-estradiol failed to enhance IL-1 or IL-6 secretion and progesterone failed to inhibit IL-1 secretion. The inhibitory effects of testosterone, however, appeared to be similar to that in normal donors. It is suggested that 17-beta-estradiol may promote IL-1 and IL-6 production and release, while gestation hormone, progesterone, and testosterone may inhibit IL-1 release in vivo. These data may partly explain the gender and age differences in the incidence of RA and the development of the disease in men with low and androgen levels.
8929774 Bilateral fast MR imaging of the rheumatoid wrist. 1996 Jan To evaluate the structural changes in the carpal tunnel and possible intrinsic median nerve damages in RA patients, quantitative bilateral magnetic resonance imaging (MRI) of the wrists was performed by means of a fast imaging sequence. Thirty-three women with RA and 42 controls were examined. The length of the carpal tunnel, the carpal tunnel volume/wrist volume (CTV/WV) ratio and the signal intensity of the nerve were calculated in both groups, bilaterally. The CTV/WV ratio was 0.12 in the patients and 0.11 in the control group (p = 0.007). A negative association was found between disease duration and carpal tunnel volume/wrist volume ratio (p = 0.049). Mean distal latency in the right motor median nerve was 3.0 +/- 0.4 msec (patients) and 3.4 +/- 0.6 msec (controls) (p = 0.002). Mean values in the right sensory branch were 1.2 +/- 0.1 msec (patients) and 1.4 +/- 0.3 (controls) (p = 0.01). The lack of association between the size of the carpal canal and neurophysiological parameters found in this study may suggest a possible protection of the median nerve by the increased canal size in patients with RA.
8367198 Dual CD45RA, CD45RO positive T-lymphocytes within rheumatoid arthritic joints. 1993 Apr This report documents the presence of an expanded population of dual CD45RA, CD45RO positive T cells (up to 91% of T cells) in the rheumatoid joint. Cells from peripheral blood (PB) and synovial fluid (SF) were analysed by dual immunofluorescence labelling. Synovium from a separate patient population was analysed by single and dual immunoenzyme staining of serial sections. Dual CD45RA, CD45RO positive T cells were found in PB (up to 74%), SF (up to 91%) and synovium. This was associated with a lack of early activation antigens (4F2, interleukin-2 receptor, transferrin receptor) but increased HLA-Class II antigens (HLA-DR, -DP, -DQ) in SF compared with PB. This intermediate activation phenotype may support the hypothesis that T cell activation or reactivation occurs within the rheumatoid joint.
8733440 Divergent effects of methotrexate on the clonal growth of T and B lymphocytes and synovial 1996 Apr OBJECTIVE: To define the mechanisms whereby methotrexate (MTX) manifests its effects in patients with rheumatoid arthritis. METHODS: T and B cells from peripheral blood and rheumatoid synovial tissues, synovial adherent cells, and the human fibrosarcoma cell line HT1080 and its mutant (defective in an enzyme in the nucleotide salvage pathway) were tested for clonal growth when cultured with MTX. Normal human fibroblasts and those with a deficiency in a salvage pathway were cultured with MTX in the presence or absence of purine and pyrimidine bases. RESULTS: Clonal growth of T and B cells, but not synovial cells, was inhibited by clinically relevant concentrations of MTX. Slowly proliferating fibroblast lines were resistant to MTX, whereas their rapidly proliferating counterparts were not. However, mutant fibroblast lines deficient in a salvage pathway were sensitive to MTX despite slow proliferation. Similarly, while skin fibroblasts were resistant to MTX, germline mutant fibroblasts deficient in a salvage pathway were sensitive to small concentrations of MTX. CONCLUSION: T and B lymphocytes, but not synovial cells, may be the target of MTX in vivo. Resistance to MTX may be associated with slow proliferation and the ability to synthesise nucleotides via salvage pathways. MTX can inhibit proliferation of even slowly growing cells by restricting the supply of nucleotides obtained via a salvage pathway, by removal of purine and pyrimidine bases, or by inducing a deficiency in a salvage pathway. It may be possible to manipulate the therapeutic effect of MTX by adjusting the amounts of purines and pyrimidines available to the cells in vivo.
1458695 Terminal complement complex in synovial tissue from patients affected by rheumatoid arthri 1992 Sep The C5b-9 complex (Terminal Complement Complex-TCC) is the final product of the terminal complement pathway. In this study, using the monoclonal antibody MCaE11 (specific for a C9 neoantigen) and an immunohistochemical technique, we examined the TCC deposits in synovial tissues from 4 patients affected by rheumatoid arthritis (RA) and 6 patients affected by osteoarthritis (OA). Synovial tissues from 8 patients affected by acute joint trauma were examined as controls. Furthermore, plasma TCC levels were measured in 44 RA patients and 51 controls, using the above mentioned antibody and a sandwich ELISA. Eight synovial fluids were also included in this study. Abundant TCC deposits were detected in the cytoplasm of the synovial lining cells and of large stromal mononuclear cells in all the RA and in 3 out of 6 OA synovial tissues characterized by histological signs of inflammation. No TCC deposits were found in non-inflamed synovial tissues from patients with joint trauma. In agreement with previous observations, the TCC plasma levels found were significantly higher in RA patients than in controls, but no difference was seen between patients with active and non-active disease. The mean TCC level was significantly higher in the synovial fluid than in the plasma, but no correlation emerged between these two series of values. This study shows that: a) the plasma level of TCCs cannot serve as an indicator of disease activity in RA; b) the TCC deposits in synovial tissue correlate well with the extent of inflammatory synovitis, irrespective of whether the synovitis is rheumatoid or osteoarthritic in nature.
7751165 Meta-analysis reveals association between most common class II haplotype in full-heritage 1995 Jan The association of RA with the alleles at the HLA system was tested among Pima and Tohono O'odham Indians (Pimans) of the Gila River Indian Community of Arizona. Serologic class I (HLA-A, -B, and -C) alleles were typed in 51 individuals with RA and in 302 without RA. Serologic class II (HLA-DR, DQ; DR52 DR53) alleles were typed in a subset of 47 with RA and 147 without RA. Molecular subtypes of DR3X6, DRB1*1402, and *1406 were determined in 29 individuals, 16 with RA and 13 without RA. Among the cases with RA, 46 of 47 had the serologic antigen HLA-DR3X6, as did 140 of 147 of those without the disease. However, this association was not statistically significant because of the high prevalence of the antigen in the controls. Data from Pimans were analyzed with similar results from the Tlingit and Yakima Indians. A meta-analysis employing the Mantel-Haenszel procedure, stratified by tribe, revealed a statistically significant association between the most common haplotype, DRB1*1402 DQA1*0501 DQB1*0301 DRB3*0101, and RA (summary odds ratio = 2.63, 95% confidence interval = 1.08, 6.46). There was also a statistically significant difference in the genotype distributions of one class I locus, HLA-C, between those with and without RA (chi 2 = 12.4, 5 df; p = 0.03). It is concluded that the association with the most common class II haplotype in full-heritage Native Americans might help explain their high prevalence of RA.
1485816 Methotrexate treatment of rheumatoid arthritis: is a fortnightly maintenance schedule enou 1992 Dec In 15 patients with rheumatoid arthritis who were in clinical remission the weekly regimen of methotrexate treatment was changed to fortnightly without a change in dose. A total of 13 patients completed a 12 month trial. No change in clinical or laboratory parameters occurred. There was no change in the use of analgesics or non-steroidal anti-inflammatory drugs and the patients remained in remission. Two patients had to be withdrawn after two and four months respectively because of a flare in disease activity. It is suggested that in most patients with rheumatoid arthritis who are treated with methotrexate and whose disease activity is stable a fortnightly regimen can be permitted without affecting drug efficacy.
8409646 Immuno-reactive human epidermal growth factor (h-EGF) in rheumatoid synovial fluids. 1993 Sep The immuno-reactive human epidermal growth factor (h-EGF) level, measured by a sensitive enzyme immunoassay, was significantly higher in synovial fluids or synovial tissue extracts from 89 patients with rheumatoid arthritis (RA) than in those from 53 patients with osteoarthritis. RA synovial immuno-reactive h-EGF was predominantly of a low molecular weight form (LMW h-EGF) on gel filtration chromatography. Furthermore, in the RA group, the synovial immuno-reactive h-EGF correlated positively with C-reactive protein, an acute-phase reactant, in the blood examination and with synovial immunoglobulin M. These results suggest that synovial h-EGF is specifically produced by RA synovium from the initial stage of arthritis, and that the measurement of synovial h-EGF serves as an early indicator to appraise the RA activity. A pathogenesis of RA including growth factors and growth inhibitory factors are discussed.
8833063 The future use of biologic therapies in combination for the treatment of rheumatoid arthri 1996 Mar The complexity of the immune system, exemplified by the pleiotropic effects of many cytokines and the redundancy of regulatory networks controlling immune responses, suggests that single therapeutic interventions will offer transient or less than clinically meaningful benefit. Theoretically, combination therapy using 2 or more biologic agents will modulate important symptomatic and objective manifestations of rheumatoid arthritis (RA). Data from animal models suggest that use of biologic agents in combination can be synergistic and may alter the severity and course of disease. Although combinations of biologic agents have yet to be used in human disease, successful examples employing immunosuppressive agents exist: cyclosporin (CsA) with methotrexate in patients with persistent active RA, as well as azathioprine and/or mycophenolate mofitil with CsA in organ transplantation and acute graft rejection. There are many arguments against the use of combination biologic therapies including acute infusion related toxicities, infection, malignancy, autoimmune manifestations, and expense. While caution dictates that phase I-II clinical trials be performed in patients with longstanding, refractory disease, subsequent trials should be conducted in patients with earlier, more responsive disease. Successful combination biologic therapies must afford sufficient duration of benefit (at least 6, preferably 12 months), cost comparable to approved 2nd line agents, ease of treatment, and an acceptable safety profile.
8285001 [Intrapelvic migration of a total hip prosthesis in rheumatoid arthritis]. 1993 The authors discuss the risk of mechanical loosening and protrusion of a cemented endoprosthesis of the hip joint after operation which is one of the few possibilities of palliative treatment in patients with rheumatoid arthritis. They deal in particular with specific features of surgical approaches whereby they select a modified method described by Eftekhar which makes it possible to resolve even severe grades of intrapelvic migration of the socket of a total endoprosthesis. The authors discuss possible complications which can be prevented if the relationship of intrapelvic structures to the protruded prosthesis is elucidated before operation. In a group of 1268 patients operated there were three with intrapelvic migration of a total endoprosthesis of the hip joint.