Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2802797 | Anionic salivary proteins associated with connective tissue disorders: sialated tissue kal | 1989 Sep | Parotid saliva was collected from 32 patients with rheumatoid arthritis, 10 with systemic lupus erythematosus, three with mixed connective tissue disease, 12 with progressive systemic sclerosis, two with primary Sjögren's syndrome, and four with Raynaud's syndrome. Tissue kallikreins were measured by radioimmunoassay, and saliva samples were subjected to isoelectric focusing followed by immunoblotting or silver staining. The results showed that the saliva of patients with connective tissue diseases contained increased amounts of immunoreactive tissue kallikrein. In addition, there was an increase in the multiple forms of anionic tissue kallikreins, resulting mainly from a shift in their distribution towards that of higher sialic acid content and lower isoelectric point. These changes were most obvious in patients with systemic lupus erythematosus. Novel or unusual glycosylation may explain the occurrence of increased amounts of anionic salivary proteins in connective tissue diseases. | |
| 3464214 | Sleep and musculoskeletal pain. | 1986 Sep 29 | Chronic musculoskeletal pain and fatigue of "fibrositis syndrome" are associated with a physiologic arousal disorder within sleep, the alpha (7.5 to 11 Hz) electroencephalographic, non-rapid-eye-movement sleep anomaly. In this nonrestorative sleep disorder, pain and mood symptoms may be mediated by psychologic distress (e.g., following a nonphysically injurious industrial or automobile accident), noxious environmental stimuli (e.g., noise), physiologic disturbance (e.g., sleep-related myoclonus, painful inflamed joints, i.e., rheumatoid arthritis), and altered central nervous system metabolism (e.g., disordered brain serotoninergic functions). Because such heterogeneous agents influence this hitherto poorly understood nonarticular rheumatic syndrome, the descriptive term "rheumatic pain modulation disorder" is suggested. | |
| 1770364 | Autologous bone grafting for medial tibial defects in total knee arthroplasty. | 1991 Dec | Seventeen posterior stabilized Insall-Burstein knee arthroplasties were implanted in severely deformed varus knees with large medial tibial bony defects. The defect was filled with an autologous bone graft obtained from the same knee and fixed with one or two screws. The patients were reviewed during an average follow-up period of 4 years (range, 2-8 years). The graft was completely united in 14 cases (82%), with bony trabeculae crossing the interface. Fibrous union occurred in three cases (18%). There was no evidence of graft necrosis or collapse. The results were classified as excellent in 10 knees (59%), good in 6 (35%), and poor in 1 (6%), which was revised for femoral loosening. The importance of meticulous technique and correct component positioning is emphasized. | |
| 2028334 | Posterior occipitocervical fusion. A preliminary report of a new technique. | 1991 Mar | A new technique for occipitocervical fusion is described. The fixation of the upper cervical spine with plates and screws avoids the possible disadvantages of the commonly used wiring technique. By the establishment of a rigid fixation between the occiput and upper cervical spine with a combination of plates and screws, especially with transarticular atlantoaxial screw fixation, reliable, multidirectional, and immediate stability is achieved. The clinical picture and analysis of 14 patients with a variety of pathologies of the upper cervical spine is presented. The satisfactory outcome and solid bony fusion in all 14 patients and the absence of severe complications encourages the continued use of this technique of occipitocervical fusion. | |
| 2676901 | A new fluorescent mitochondrial antibody: disease association. | 1989 Sep | The case notes of 34 patients whose sera contained an antibody giving an unusual immunofluorescent staining pattern were reviewed. This antibody designated M2(1) gave a slightly different pattern of staining on composite sections of rat liver, kidney and stomach from the primary biliary cirrhosis associated M2 antimitochondrial antibody. Anaemia was present in 10 patients, endocrine disease in 7 patients and autoimmune liver disease in 6 patients. We did not find the presence of M2(1) antibody to be of specific diagnostic significance. Although the M2(1) antibody is rare, caution is required in order to avoid confusion between this antibody and the M2 antimitochondrial antibody of primary biliary cirrhosis. | |
| 3528080 | Colour development of immunogold-labelled antibodies for light microscopy. | 1986 | We describe an improvement of the immunogold technique, which is based on the colour development of silver-intensified immunogold signals. This method (referred to as the coloured-SIG technique) was found to be as sensitive as the silver-intensified immunogold method and more sensitive (in two of the three tested systems) than immunoenzymatic procedures, such as the peroxidase/antiperoxidase technique or the avidin-biotin system. The coloured SIG-method results in either a magenta-red or a cyan-blue final reaction product. Therefore, this new improvement of the immunogold technique should be useful in double-staining methods, immunoblot methods and conventional immunostaining methods. | |
| 3780048 | Pepsinogen--an immunoglobulin binding artefact in 'collagen' preparations. | 1986 Sep | It has previously been shown that extracts of human articular cartilage, many many of which contain type II collagen, react with heat-aggregated immunoglobulin and artificially prepared immune complexes. Sera from patients with rheumatoid arthritis and psoriatic arthritis, but not from patients with inflammatory bowel disease, react with these extracts. There are two distinct patterns of binding, either as low molecular weight immune complexes or as free antibody directed against collagen. Aggregate-binding activity identified in extracts of human articular cartilage following pepsin digestion was found to be distinct from collagen in its salt solubility. Further purification of this aggregate-binding factor by SDS gel electrophoresis has shown it to be an artefact resulting from the binding of small immune complexes to pepsinogen present in the pepsin preparation used to digest the cartilage. | |
| 1948446 | [Sex hormones and calcium regulating hormones in rheumatoid arthritis]. | 1991 Jun | Rheumatoid arthritis (RA) occurred frequently in women. Exogenous estrogen has been reported to alleviate the symptoms of patients with RA. But the implications of sex hormones and immunological abnormalities in RA remain to be elucidated. Therefore, we measured sex hormones (LH, FSH, estradiol, testosterone and prolactin), bone metabolic markers (midregion and carboxy terminal mainly recognized PTH1-84, intact PTH1-84, bone GLA protein and alkaline phosphatase), bone mineral, in lumbal bone with quantitative tomography (QCT) and with of cortex with microdensitometry in 52 females with RA and 46 females with osteoarthritis (OA) as a control group. Sex hormones and bone metabolic markers were analyzed as independent variables of serum LH, FSH and estradiol levels, using one way analysis, in patients with RA and OA. The more increased serum FSH and LH levels were, the more decreased serum estradiol levels were in both RA and OA groups, when they were considered as independent variables. These results indicate that the secretory function of pituitary and ovary axis hormones are normally enacted in RA. On the other hand, when the sex hormones of the patients under 53 years of age were studied in both groups, serum FSH adn LH showed significantly higher levels, while serum estradiol levels revealed decreased tendency in RA, compared with these in RA. Thus the pituitary ovary secretory function in patients with RA was suggested to be disturbed in early stage of age, indicating that the sex hormones would be partly implicated in calcium and bone metabolism in patients with RA. | |
| 2143370 | Analysis of impaired in vitro immunoglobulin synthesis in rheumatoid arthritis. | 1990 Jul | Decreased immunoglobulin production in pokeweed mitogen driven lymphocyte cultures has been reported in rheumatoid arthritis (RA). Here various activators and experimental designs have been used to determine the contribution of B cells, T cells, or monocytes to this low response. Sixty patients with RA and paired controls were studied at the onset of disease and again six months later. Concentrations of IgA, IgG, and IgM in cultures of RA peripheral blood mononuclear cells stimulated with thymus dependent activators were already decreased at the onset of the disease. Six months later RA mononuclear cells produced even lower concentrations of immunoglobulin. In contrast, stimulation with a T cell independent activator showed that RA B lymphocytes had retained normal potential to synthesise immunoglobulin. Poor helper function was indicated by costimulation experiments and cultures of mixed mononuclear cells from patients and controls. This notion was supported also by the fact that phytohaemagglutinin induced interleukin-2 production by RA mononuclear cells was less than half of the control values. Nonspecific suppressor activity was similar in RA and controls. Monocyte functions were normal when tested by addition of indomethacin or 2-mercaptoethanol to the mitogen activated cultures. The defect in mitogen stimulated immunoglobulin production in vitro of RA mononuclear cells thus was more pronounced with time and probably reflects impaired mediator associated help in the differentiation of B lymphocytes into immunoglobulin secreting cells. | |
| 2481874 | Epstein-Barr virus and rheumatoid arthritis: cellular and molecular aspects. | 1989 | Several lines of research have indicated a possible association of the Epstein-Barr virus and rheumatoid arthritis (RA). The earliest evidence suggested that RA patients develop a stronger humoral immune response to EBV nuclear antigens (EBNA) which may in part account for the increased titers of antibody to the RA nuclear antigen (RANA). It was then pointed out that mononuclear cells from RA patients may be impaired in their capacity to control EBV infection. This may be related to a decrease in the production of IFN gamma and a consequence of monocyte-derived inhibitory activities. These cellular defects, however, are not specific for RA and may rather be the result of chronic inflammatory responses. These findings and the lack of increased virus presence in RA tissues did not provide a strong basis for a possible association of EBV and RA. A new concept for this association is now being tested on the basis of the sequence homology between the genetic RA susceptibility determinant HLA DR4 and the EBV glycoprotein 110. | |
| 1754748 | Anaemia in elderly patients. Incidence and causes of low haemoglobin concentration in a ci | 1991 Sep | Haemoglobin concentration was determined in all patients (530) over 70 years of age in a general practice in Oslo during an eight month period. 72 had anaemia and were investigated further. Iron deficiency was found in 13 patients and was most often caused by gastrointestinal blood loss. Chronic diseases, particularly chronic infections and rheumatoid arthritis, were responsible for anaemia in 34 patients. Renal failure caused anaemia in 14 patients. In 10 patients we found no explanation for the anaemia. Nine patients with a previously undiscovered disease were found, six of whom could be offered some kind of treatment. We conclude that anaemia in elderly patients in general practice is often caused by chronic diseases. The main cause of iron deficiency is blood loss, and routine prescription of iron is not justified in this age group. The therapeutic benefit from routine measurement of haemoglobin concentration is small and the test should be used selectively. | |
| 2115418 | Analysis of immunoglobulins secreted by hybridomas derived from rheumatoid synovia. | 1990 Jun | Twenty-six IgG-secreting and eight IgM-secreting hybridomas were derived from the synovia of two patients with rheumatoid arthritis (RA). Hybridomas were obtained by fusing a heteromyeloma cell line, SPAZ-4 with synovial mononuclear cells that were not deliberately stimulated in vitro. Over 96% of the IgG-secreting hybridomas produced antibodies which belonged to the IgG1 subclass and showed lambda light chain predominance; the latter was not seen in IgM antibodies, where kappa light chains dominated by 3:1. All IgG antibodies were cationic. Synovial B cells were not exposed to extrinsic stimuli prior to fusion, therefore these results reflect the state of B cell activation and differentiation in vivo. Our results indicate that IgG-secreting B cells in the RA joint are under a selective influence which is, as yet, unidentified. One out of eight IgM-secreting and two out of 26 IgG-secreting hybridomas produced rheumatoid factors (RF). The IgM-RF specificity for IgG heavy chain subclasses was determined and showed that the monoclonal bound to IgG1, IgG2 and IgG4 but not IgG3 with exception of IgG3 Goe of the G3m (st) allotype, a profile typical of specificity for the Ga epitope. This monoclonal also distinguished a determinant in the Fc region of human IgG which was not present in rabbit IgG. The overall frequency of RF-secreting hybridomas we observed indicates that B cells committed to RF production in the synovium of a seropositive and a seronegative RA patient is below 10%. | |
| 2114442 | T cell regulation of collagen-induced arthritis in mice. I. Isolation of Type II collagen- | 1990 Jul 15 | After immunization with native type II collagen (CII), susceptible strains of mice (H-2q) develop a polyarthritis that mimics rheumatoid arthritis. Although the underlying mechanisms are still undefined, T cells and particularly CD4+ lymphocytes seem to play a crucial role in the initiation of collagen-induced arthritis. To investigate whether CD8+ cells may participate in the pathogenesis of the disease, we have generated lines and clones of cytotoxic T cell hybridomas reactive to CII by fusion of lymph node and spleen cells from bovine native CII-primed C3H.Q (H-2q) mice and the AKR-derived thymoma cell line BW 5147. Clones were selected for their ability to lyse syngeneic macrophages pulsed with bovine native CII in an Ag-dependent manner. The two hybrid clones that were characterized, exhibited cell surface phenotypes of cytotoxic cells and reacted with CII purified from various species. However, each of them recognized different determinants on the CII molecule. P3G8 clone was specific for an epitope shared by CII and type XI collagen, whereas P2D9 clone reacted with CII and type IX collagen. Both hybridomas recognized CII-pulsed targets in association with H-2Kq molecules. These data indicate that the two CII-specific cytotoxic clones recognize different epitopes that are shared by other articular collagens and will allow us to test their influence on the development of arthritis in vivo. | |
| 2688083 | Auranofin (SK&F) in early rheumatoid arthritis: results from a 24-month double-blind, plac | 1989 | In a 2-year, randomized, double-blind Nordic multicentre trial, auranofin was compared with placebo in early (disease duration less than or equal to 2 years), active rheumatoid arthritis (RA). Efficacy and safety were analysed in 67 patients receiving auranofin and 65 receiving placebo. Life table analysis demonstrated a significantly higher withdrawal rate due to insufficient therapeutic effect in the placebo group, whereas more patients dropped out due to side effects in the auranofin group. More auranofin than placebo patients (35 vs. 24) completed the 2 years. Clinical and inflammatory activity improved in both groups, but consistently more so in the auranofin group, in spite of the greater consumption of local steroids and NSAIDs in the placebo group. The most frequent side effects leading to withdrawal in the auranofin group were cutaneous and gastrointestinal reactions. The study demonstrated that most patients exhibit improvement in clinical signs and symptoms and about half of all patients with early RA continue to take auranofin for at least 2 years. | |
| 1904330 | Soluble CD4 in patients with rheumatoid arthritis and osteoarthritis. | 1991 Jul | An ELISA was used to measure the soluble form of the leukocyte surface antigen CD4 (sCD4) in the sera and synovial fluids (SF) of patients with rheumatic diseases. Patients with rheumatoid arthritis (RA) had raised levels of sCD4 in both their sera and synovial fluid compared to age-matched healthy controls. In patients with osteoarthritis levels of sCD4 in SF and sera were lower than in RA but higher than in sera of healthy individuals. Mononuclear cells from the synovial fluid of RA patients were found to produce spontaneously high levels of sCD4, but autologous blood cells only produced comparable levels after in vitro stimulation with mitogenic lectin. In individual RA patients with active disease, serial sCD4 levels fell preceding clinical improvement. In three patients where serum sCD4 levels fell and clinical improvement occurred, subsequent small increases in serum sCD4 preceded increased clinical disease activity by up to 5 days. Synovial fluid levels of sCD4 correlated positively with soluble interleukin 2 receptor levels but no correlation was found with sCD8 levels. We conclude that the release of sCD4 reflects the involvement of T helper cells and macrophages in the pathogenesis of joint inflammation, especially in RA. | |
| 2823754 | Viral antibody titers. Comparison in patients with multiple sclerosis and rheumatoid arthr | 1987 Dec | Higher titers of antibodies to measles virus envelope antigens, hemolysin and hemagglutinin, Epstein-Barr virus (EBV) capsid antigen and nuclear antigen, and rubella virus hemagglutinin were demonstrated in serum samples of patients with multiple sclerosis and rheumatoid arthritis than in age- and sex-matched control subjects. A significant correlation was observed between antibodies to measles and rubella viruses both in patients with multiple sclerosis and rheumatoid arthritis, but such a correlation was not observed between antibodies to EBV and measles or rubella viruses. Whether elevated levels of antibodies to EBV are due to reactivation of the virus, or elevated levels of antibodies to all the enveloped viruses result from cross-reactions between viruses and host tissue, or perhaps reflect defects in immunoregulation, needs further investigation. | |
| 3102124 | A method for serum C1q based on its hydroxyproline content. | 1987 Mar | The radial immunodiffusion assay overestimates the C1q in serum. Here we describe a convenient, accurate procedure for measuring C1q in 250 microL of dialyzed serum. This method is based on our previous findings that all C1q in serum precipitates with the euglobulin fraction and that all other serum proteins containing hydroxyproline are excluded from this fraction. Because C1q is 4.3% hydroxyproline, the concentration of C1q in serum can therefore be calculated from the hydroxyproline content of the euglobulin fraction. The procedure, all done in the same tube, consists of precipitating the euglobulin fraction, digesting it with HClO4, and converting hydroxyproline to the corresponding pyrrole, which is extracted with toluene and measured by absorbance at 560 nm. | |
| 2068542 | Effects of a hydrosoluble bacterial extract from Escherichia coli (OM-89) on cytokine prod | 1991 | OM-89 is a bacterial extract from escherichia coli, proposed as an immunomodulating drug for the treatment of rheumatoid arthritis (RA). Since immunological mechanisms may play a role in its action, the immunological effects of OM-89 were evaluated in vitro on peripheral blood mononuclear cells (PBMC) derived from healthy subjects and RA patients. Results indicated that in the absence of OM-89, production of the monokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) is increased, while that of the lymphokines interleukin-2 (IL-2) and interferon-gamma (IFN-gamma is decreased by phytohemagglutinin (PHA)-stimulated PBMC from RA patients as compared with PBMC from healthy subjects. In the presence of PHA, OM-89 enhanced the production of IL-1 beta, TNF-alpha, IL-2, and IFN-gamma. IL-1 beta and IL-2 curves obtained using increasing amounts of OM-89 did not differ depending on the source of PBMC. By contrast, in the presence of increasing amounts of OM-89, TNF-alpha secretion significantly higher and IFN-gamma secretion significantly lower with PBMC from RA patients compared to PBMC from healthy subjects. These data indicate that OM-89 acts on monocytes and T cells directly and/or indirectly and suggest a possible clinical activity by OM-89 in RA relative to its immunological properties. | |
| 1697741 | Effects of capsaicin on the metabolism of rheumatoid arthritis synoviocytes in vitro. | 1990 Aug | The effects of capsaicin, the ingredient of hot pepper, on rheumatoid arthritis synoviocytes have been studied. Capsaicin was shown to have a direct action on the metabolism of synovial cells. Thus at 10(-6) mol/l and at higher doses DNA synthesis was restored to the control level. Capsaicin at both doses induced an increase in the synthesis of collagenase and at the lower concentration (10(-8) mol/l) only of prostaglandins. These results indicate that the different effects of capsaicin on cellular proliferation and on metabolic activities are dependent on dose. The responses seen in rheumatoid arthritis synoviocytes in vitro might not be mediated by tachykinins if the synovial tissue is still able to produce neuropeptides in the absence of neuronal afferents. These results suggest that capsaicin, in addition to its direct action on the afferent nervous fibres and the consequent release of tachykinins, may also have a direct action on the cells. The mechanisms by which capsaicin stimulates DNA synthesis and production of collagenase and prostaglandin E2, in a manner dependent on dose, remain to be determined. | |
| 16788633 | Cytotoxic and immunologic effects of methotrexate in psoriasis. | 1990 Nov | Based on recent experience that Cyclosporin A, an immunosuppressive drug, produces marked improvement in psoriasis, possible immunomodulatory activities of methotrexate (MTX) have been reviewed to look for alternate mechanisms of MTX action in psoriasis. It is generally considered that the therapeutic results of MTX in psoriasis are related to a direct effect on epidermal cell hyperplasia through inhibition of DNA synthesis. Several studies in the literature now suggest possible effects of MTX on the immune system of psoriatics as well as in animal models that may have some pathogenic similarities to psoriasis. In psoriatics receiving MTX, neutrophil chemotaxis is suppressed, resulting in a possible alteration in the potential pathologic activity of neutrophils commonly found in lesional skin. MTX does improve both psoriatic and rheumatoid arthritis. Animal studies of the latter using adjuvant arthritis and graft vs host disease (GVHD) have indicated several possible mechanisms for MTX that affect these processes. In GVHD, MTX selectively destroys cycling CD8+ cells, and in adjuvant arthritis the activation of macrophages is prevented by inhibition of T-cell function. While MTX generally has not been clinically utilized as an immunomodulatory drug for immunologically related diseases, it may, nonetheless, have selective actions that could be specific for some diseases. MTX and Cyclosporin A could work mechanistically in similar ways but at different steps in the activation of T cells and macrophages. It may be that the major direct effect of MTX on epidermal cell proliferation is complemented or even mediated by subtle immunoregulatory effects on the melange of cells in the affected skin and the systemic immune response. |