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ID PMID Title PublicationDate abstract
7631138 TNF inhibitors are produced spontaneously by rheumatoid and osteoarthritic synovial joint 1995 Jul We have proposed the hypothesis that tumour necrosis factor alpha (TNF-alpha) has a pivotal role in the pathogenesis of rheumatoid arthritis, based on in vitro observations that in RA synovial joint cell cultures removal of TNF-alpha, inhibited other potentially pathogenic cytokines such as the equally proinflammatory cytokine interleukin 1 (IL-1) and the macrophage activating factor, GM-CSF. Here we describe that in both rheumatoid (RA) and osteoarthritic (OA) synovial cultures there is a homeostatic mechanism to regulate the activities of TNF-alpha. This concept is based on several observations. First in these synovial joint cell cultures the substantial discrepancy between the levels of bioactive and immunoreactive TNF-alpha indicates the presence of an inhibitor. Second, TNF binding proteins are produced spontaneously, which are the soluble variants of surface p75 and p55 TNF receptor. The amount of soluble TNF receptors (sTNF-R) produced varied between cultures; p75 sTNF-R was more abundant than p55 sTNF-R (as detected by ELISA), and both were produced at higher levels by RA synovial joint cells in culture, compared to OA cultures. These TNF binding proteins act as endogenous inhibitors of TNF-alpha, since blocking their activity in synovial joint cell culture supernatants with MoAb to p55 and p75 sTNF-R enhanced their cytotoxic activity in the TNF bioassay. The regulation of production of these sTNF-R in synovial joint cell cultures is important as the balance between TNF-alpha and sTNF-R production may determine the outcome of the inflammatory process.
1462123 Spontaneous in vivo gene transcription of interleukin-2, interleukin-3, interleukin-4, int 1992 Dec Rheumatoid synovial T lymphocytes were investigated for the presence of mRNA for the cytokines interleukin-2, -3, -4, -6, interferon-gamma, the interleukin-2 receptor (CD25) and the proto-oncogene c-myc. The isolated RNAs were analysed by dot blot and Northern blot hybridization. Our results show that synovial T lymphocytes from patients with rheumatoid arthritis (n = 12) had spontaneous in vivo gene transcription of interleukin-2 (93%), interleukin-4 (67%), interleukin-6 (92%), interleukin-2 receptor (92%) and the proto-oncogene c-myc (67%). Only a few of the RA patients had synovial T cells with increased expression of mRNA for interleukin-3 (25%) and interferon-gamma (25%). The amounts of mRNA for the various cytokines and activation molecules produced by the rheumatoid synovial T lymphocytes were in most instances comparable to those of normal peripheral blood T lymphocytes activated in vitro by the mitogen phytohaemagglutinin. The data thus indicate that the synovial T lymphocytes are activated in vivo in the majority of rheumatoid arthritis patients.
8940667 Musculoskeletal disorders: genitourinary medicine perspective. 1996 Oct The association of musculoskeletal disorders and genitourinary symptoms is reviewed. Reactive arthritis, Sjögren's syndrome and rheumatoid arthritis can present with a variety of genitourinary symptoms. Similarly sexually transmitted diseases including gonorrhoea, syphilis, HIV and other viral infections can affect the musculoskeletal system. Reiter's syndrome may be a consequence of a sexually transmitted infection although its presentation can suggest that also in post-dysenteric cases. The fact that conditions may present to various medical specialties requires doctors outside departments of GUM to allow their patients an opportunity and the time to discuss sexual matters.
8282813 Expression and functional significance of alternatively spliced CS1 fibronectin in rheumat 1994 Jan Expression of fibronectin (FN) isoforms containing CS1, a 25-amino acid sequence present within the alternatively spliced IIICS region of FN, has been analyzed in rheumatoid arthritis (RA) synovium. Unexpectedly, CS1-containing FN variants were exclusively found on endothelium but not extracellular matrix (ECM) of RA synovium. Lumenal expression of CS1 on RA endothelial cells, as observed by electron microscopy, correlated with inflammation in RA, since normal synovium expressed little CS1 without appreciable decrease in ECM FN. CS1 expression on human endothelial cells was further shown by FN mRNA analyses. In adhesion assays on frozen RA synovial sections, T lymphoblastoid cells expressing functionally activated alpha 4 beta 1 integrin specifically attached to the intravascular surface of RA endothelium. Binding was abrogated by both anti-alpha 4 integrin and CS1 peptides. Our observations suggest direct involvement of CS1-containing FN in recruitment of alpha 4 beta 1-expressing mononuclear leukocytes in synovitis, and provide basis for therapeutic intervention in RA.
7656398 [IgG RF analysis of supernatant of cultured synovia in patients with rheumatoid arthritis] 1995 Apr We used Enzyme Linked Immuno-Sorbent Assay (ELISA) to measure IgG RF of supernatant of cultured knee synovia in 45 patients with various rheumatic diseases (Harvest time for the supernatant was 1,4,7,14,28 days). 25 cases of patients with osteoarthritis (OA) and non-synovitis (Non-S) were regarded as the negative control. IgG RF was positive in 4 of 12 patients with rheumatoid arthritis (RA), whose IL-1 bioactivity is also high. Meanwhile these 4 patients had not received disease-modifying anti-rheumatic drugs (DMARDs) and their clinical and laboratory parameters were active. IgG RF was negative in other groups. It is suggested that humoral factor such as IgG RF and cytokine such as IL-1 may play the synergistic role in the pathogenesis of RA and DMARDs may suppress these two kinds of pathological factors.
8326109 [Perforated and pre-perforated ulcer in rheumatoid polyarthritis]. 1993 The authors report a case about relapsing corneal ulceration in a patient with rheumatoid arthritis. Treatment of such perforated and preperforated corneal ulcers is a difficult task. The poor visual outcome of an emergency penetrating keratoplasty leads to the use of other methods (conjunctival flaps, corneal graft, keratopatch, tissue adhesive). This case report stresses the importance of preserving the anatomy of the eye allowing in a record time the performance of corneal graft. The use of immunosuppressive drugs is also discussed because of the existence of a rheumatoid arthritis with eye involvement.
8752735 [Clinical significance of serum soluble interleukin-2 receptor (sIL-2R) determination in p 1996 Jun It has been recently shown that soluble interleukin-2 receptor (sIL-2R) is related to the pathogenesis of autoimmune diseases. We determined serum levels of sIL-2R in patients with rheumatoid arthritis (RA). Fifty-three patients (3 males and 50 females from 35 to 70 years old) and sex- and age-matched 50 healthy subjects were included in this study. The sIL-2R concentrations positively correlated with Lansbury index of RA (r = 0.602, p < 0.01). There was a significant correlation between sIL-2R levels and the prevalence of CD3+.HLA-DR+ lymphocytes (r = 0.420, p < 0.01).
8151591 Joint impairment is strongly correlated with disability measured by self-report questionna 1994 Jan OBJECTIVE: To determine how well self-report functional ability reflects the impairment due to the arthritic process in rheumatoid arthritis (RA) and how much it is affected by other factors of health status. METHODS: We examined the relationships between self-report measures such as the Health Assessment Questionnaire (HAQ) and Arthritis Impact Measurement Scales (AIMS) and measures of impairment such as the Keitel function test (KFT), which is intended to reflect the degree of functional limitation of the joints, grip strength and radiological destruction as well as anxiety and depression in a population-based series of RA. RESULTS: First, the HAQ and AIMS had a high correlation coefficient (r = 0.89, p < 0.0001). Second, the above measures of impairment were more significant predictors of self-report functional measures than, for example, mental health perceptions. The AIMS scales also correlated well with the corresponding physical function of the KFT. CONCLUSION: Patients' self-report functional ability in RA reflects their physical impairment due to the arthritic joint disease and is less influenced by other factors such as emotional adjustment.
8308770 The effects of nonsteroidal antiinflammatory drug therapy in early rheumatoid arthritis on 1993 Nov OBJECTIVE: Cell surface molecules can be shed by activated T lymphocytes and measured in serum to assess in vivo T cell activation. To evaluate the relationship between these serum markers and disease activity in rheumatoid arthritis (RA), we determined levels of soluble interleukin 2 receptor (sIL-2R), CD4 (sCD4), and CD8 (sCD8) in sera from a well characterized group of 26 patients with active RA treated with a nonsteroidal antiinflammatory drug (NSAID) alone. METHODS: A retrospective, blinded determination of sIL-2R, sCD4, and sCD8 levels in serum samples from patients with early, active RA participating in 2 trials of NSAID therapy. Commercially available enzyme linked immunosorbent assays were employed. Data analysis included nonparametric techniques and correction for multiple comparisons. RESULTS: The patients with RA had significantly elevated levels of sIL-2R at baseline compared with age matched healthy controls. During NSAID therapy, mean sIL-2R levels among responders decreased to lower levels while nonresponder levels increased, although these trends did not reach statistical significance. Patients with RA did not differ from controls in baseline measures of serum sCD4 or sCD8 levels. Moreover, the serum sIL-2R, sCD4, and sCD8 levels among patients did not vary significantly from their baseline measures during NSAID therapy, irrespective of response. CONCLUSION: Our results suggest that elevated levels of serum sIL-2R in early RA likely reflect generalized immune system activation, not always associated with elevated serum sCD4 or sCD8 levels or varying with other measures of disease activity in RA.
8630113 Elevated levels of the soluble form of bone marrow stromal cell antigen 1 in the sera of p 1996 Apr OBJECTIVE: Bone marrow stromal cell antigen 1 (BST-1) is a novel glycosyl phosphatidylinositol-anchored ectoenzyme, which is overexpressed on bone marrow stromal and synovial cell lines derived from patients with rheumatoid arthritis (RA). To investigate the pathophysiologic roles of BST-1 in RA, we established an enzyme-linked immunosorbent assay (ELISA) system to detect the soluble form of BST-1 (sBST-1) and examined levels of sBST-1 in the sera of RA patients. METHODS: Concentrations of sBST-1 in sera from healthy donors and from patients with RA, osteoarthritis, Sjögren's syndrome, and systemic lupus erythematosus were measured with the ELISA. RESULTS: In 7% of the RA patient samples (10 of 143), concentrations of serum sBST-1 were higher (approximately 30-50-fold) than in non-RA samples. Serum sBST-1 concentrations showed no correlation with age, C-reactive protein level, or rheumatoid factor level. All RA patients with high concentrations of serum sBST-1 had severe disease with involvement of several large joints. CONCLUSION: We believe the measurement of serum sBST-1 may have prognostic value, but further analysis is necessary to clarify the clinical significance of elevated sBST-1 in RA.
8961588 Subcutaneous granuloma annulare in a patient with rheumatoid arthritis and diabetes mellit 1996 Nov A case is reported of multiple subcutaneous nodules over the forehead and scalp of a 67-year-old male with moderately severe seropositive rheumatoid arthritis and corticosteroid-induced diabetes mellitus. The histology was initially reported as consistent with a rheumatoid nodule, but on review, was regarded as typical of subcutaneous granuloma annulare (SCGA). The nodules resolved spontaneously within 4 months, which is also in keeping with SCGA. A brief review of the relevant literature is presented.
7744125 Clinical performance of etodolac in patients with osteoarthritis and rheumatoid arthritis. 1994 The effectiveness of etodolac in the treatment of patients with osteoarthritis (OA) and with rheumatoid arthritis (RA) has been well documented in controlled clinical trials. The superiority of etodolac, 300 mg twice daily, over placebo has already been established in short-term trials involving patients with OA. During long-term treatment, significant (p < 0.05) improvement was observed in patients with OA and RA as measured by a variety of efficacy parameters. In comparative studies for OA, etodolac was more effective than conventional indomethacin; naproxen, sustained-release diclofenac, and piroxicam were comparably effective. The newer sustained-release formulation of etodolac is as effective as the conventional etodolac formulation when used to treat patients with OA and those with RA.
8109833 Optimizing combination chemotherapy for rheumatoid arthritis. 1993 Nov 30 A potential approach toward rational decision making when using combinations of DMARDs has been presented. This approach combines knowledge of DMARD mechanisms of action, kinetics, and toxicities to look for "nonoverlapping" combinations. When using this approach to predict responses and comparing them to studies that have been done, some encouraging results were obtained. Nevertheless, as exemplified by the combination of D-penicillamine and hydroxychloroquine, this approach is not infallible. The use of refinements of such rational choices, however, should be continued in an effort to improve the chances of success and decrease the costs of testing drug combinations.
1286129 Gold concentrations in blood fractions of patients with rheumatoid arthritis treated with 1992 Sep Gold levels in the plasma and blood cells of patients treated with the gold drug Myocrisin (sodium aurothiomalate) were determined by atomic absorption spectrometry. There is a correlation between whole blood gold and plasma gold concentrations which is different for smokers and non-smokers. Most cellular gold is associated with the membrane and is present in concentrations approximately equivalent to the number of reactive sulphydryl groups on the exofacial surface of the cell. Since gold would be expected to react with SH groups and since these groups are vital for cellular function, a possible role for gold in modifying cellular metabolism is indicated.
1445447 Calcium-dependent cysteine proteinase (calpain) in human arthritic synovial joints. 1992 Nov OBJECTIVE: To study the roles of calpains in the synovial joint in rheumatoid arthritis (RA) and osteoarthritis (OA) and to verify the hypothesis that calpains present in the synovial fluid come from the synovium. METHODS: We performed immunohistochemical, biochemical, and immunoblotting analyses for calpains in synovial tissues, synovial cell cultures, and synovial fluids. RESULTS: Immunohistochemical staining of RA synovium demonstrated specific cytoplasmic staining of cells in the synovial lining layer, storomal fibroblasts, and endothelial cells. OA synovium showed almost the same intensity and distribution of calpain staining. DEAE-cellulose chromatography of RA and OA synovial extracts and synovial fluids showed a peak of caseinolytic activity attributable to calpain, as well as an inhibitory peak of calpastatin, a specific inhibitor protein of calpains. Immunoblotting using the anticalpain antibody from the calpain peak of RA and OA synovium and synovial fluid showed identity with the heavy subunit of calpain (80 kd). Similarly, calpain existed in the same form (80 kd) in conditioned media (supernatant) obtained from synovial cell cultures, as well as in the synoviocytes. The total specific activity of the 2 calpains in the synovial fluid of RA patients was higher than that of calpastatin. CONCLUSION: The findings suggest that the extracellular appearance of calpains could be due to the secretion of these proteins from the synovial cells and that calpains may play a role in cartilage damage of RA and OA that occurs in synovial joints.
8895145 Autonomic nervous system function in rheumatoid arthritis. A controlled study. 1996 Oct OBJECTIVE: To study cardiovascular autonomic nervous functions in patients with rheumatoid arthritis (RA) compared with controls and to investigate fasting and meal stimulated pancreatic polypeptide (PP) in RA and its possible associations with autonomic functions and disease activity. METHODS: Forty-three women meeting the American Rheumatism Association 1987 diagnostic criteria for RA and 61 healthy controls were studied. Blood pressure recordings and cardiovascular heart rate studies were performed. PP was measured by radioimmunoassay. RESULTS: Cardiovascular reflexes were equal in the 2 groups, but the patients had significantly higher fasting plasma PP level with mean log10 value of 0.94 pmol/l (SD = 0.38) compared with 0.68 pmol/l (SD = 0.35) in the controls (p = 0.0006). Mean log10 plasma PP increase 30 min after the meal was 1.80 pmol/l (SD = 0.42) for the patient group and 1.47 pmol/l (SD = 0.40) in the controls (p = 0.0001). Feeding caused a mean PP increase of 1.85 (SD = 0.42) for the patients and 1.44 (SD = 0.42) in the controls 60 min postprandially (p = 0.0001). Multiple regression and correlation analysis showed no association between PP and disease activity. CONCLUSION: The higher basal and postprandial PP in the RA group indicates a relationship between the disease and PP by unknown mechanisms.
7553032 [A case of rheumatoid arthritis complicated with salazosulfapyridine-induced aplastic anem 1995 Feb A 64 year-old woman with rheumatoid arthritis was admitted to our hospital because of general fatigue. She noticed polyarthralgia 8 months prior to the admission and diagnosis of rheumatoid arthritis was made. Administration of salazosulfapyridine (1.0 g/day) was started 6 months before the admission. Complete remission of rheumatoid arthritis was obtained in 2 months and blood cell counts showed normal values at that time. The results of laboratory tests included hemoglobin; 8.6 g/dl, white blood cell count; 1,900/mm3 with a differential of 19% neutrophils, 77% lymphocytes, and 4% monocytes; platelets were 21,000/mm3. A bone marrow aspiration and biopsy were performed. There were reduced numbers of myelocytes, erythroblasts, and megakaryocytes indicating aplastic anemia. Salazosulfapyridine was discontinued. Prednisolone, anabolic steroid and granulocyte-colony stimulating factor (G-CSF) were administrated. In spite of these therapy, recovery of peripheral blood cell counts have not been observed and supporting therapy including red cell and platelets transfusion have been continued. To our knowledge, this is the first case report which describes occurrence of aplastic anemia in patients with rheumatoid arthritis treated by salazosulfapyridine.
7892020 Effect of light and season on pain and depression in subjects with rheumatic disorders. 1994 Nov The clinical and neurochemical association between depression and season noted in seasonal affective disorder (SAD) has suggested that clinical pain might also be linked to season, perhaps through similar neurochemistry or the known association of depression with pain. We investigated the pain-light season/dark season hypothesis in 2523 rheumatic disease outpatients by examining VAS Pain and VAS Global Severity scores, as well as levels of depression and functional disability. No clinically significant difference in pain severity between season (or individual month) was noted for the consecutive outpatients at their first clinic visit, nor in sub-analyses using paired light and dark season visits. A slight trend toward increased pain severity in lighter months by about 3% compared to darker months was identified. No effect of season was seen on depression scores. In a subset of patients with high depression scores, rheumatoid arthritis and osteoarthritis patients, respectively, reported 16% and 7% greater pain scores in light compared to dark months, but fibromyalgia patients had stable scores. Season does not appear to play an important role in pain and/or depression in rheumatic disorders.
8697660 TAP2D is associated with HLA-B44 and DR4 and may contribute to rheumatoid arthritis and Fe 1996 Jan OBJECTIVES: TAP2 transporter gene polymorphisms have been ascertained in patients with rheumatoid arthritis (RA) and Felty's syndrome (FS) to determine whether particular alleles of this gene are disease associated. METHODS: TAP2 dimorphisms at amino acid positions 379, 565 and 665 were detected using ARMS-PCR in 89 RA patients, 24 FS patients and 64 control subjects. TAP 2 alleles were assigned from these results. RESULTS: The frequency of one particular allele, TAP2D, was increased in both RA (OR 2.6, 95% CI 1.2 - 5.8) and FS (OR 3.9, 95% CI 1.4 - 10.7). When individual amino acid polymorphisms were compared between patients and controls, isoleucine at position 379 (present in TAP2D and TAP2C) was significantly increased, indicating that this dimorphism itself may be associated with RA (OR 5.0, 95% CI 2.4 - 10.2) and FS (OR 5.0, 95% CI 1.91 - 3.2). DISCUSSION: The presence of TAP2D was greatly increased in HLA-B44/DR4 positive RA (83%) and FS (67%) patients. These frequencies were appreciably higher than in the HLA-B44/DR4 controls (11%), suggesting that linkage disequilibrium alone may not explain the increase in TAP2D frequency in patients and that this allele may represent an additional risk factor in these conditions.
8000738 Prevalence of selected autoantibodies in different elderly subpopulations. 1994 Dec We have evaluated the prevalence of selected autoantibodies commonly utilized in rheumatologic practice in different elderly subpopulations grouped according to their clinical status. RF, ANA, double-stranded DNA antibodies, and antibodies to extractable nuclear antigens (ENA) were measured in the serum of all participants using standardized laboratory assays. One hundred and fifty-nine elderly subjects were enrolled, of whom 63 were classified as successfully aging elderly, 62 were ambulatory chronically ill residents of a nursing or Veterans home and 34 were patients attending an RA clinic. Prevalence of autoantibodies were compared to healthy adult blood donors. There was no statistically significant increase in autoantibodies in successfully aging elderly compared to healthy young controls. RF, ANA and ENA antibodies were significantly increased in only the chronically ill and RA sufferers. Antibodies to nDNA were absent in all groups. We conclude that autoantibodies commonly utilized in rheumatological practice are not globally non-specifically increased as a result of aging, but increase in prevalence in chronically ill elderly. Therefore assessment of health status is necessary to evaluate the clinical significance of these autoantibodies in the elderly.