Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2294239 | Bladder leiomyosarcoma following cyclophosphamide therapy for lupus nephritis. | 1990 Jan | We report 2 cases of leiomyosarcoma of the bladder that occurred after long-term cyclophosphamide chemotherapy for lupus nephritis and rheumatoid arthritis. One patient had a tumor at the end of an 11-year course of chemotherapy and 1 approximately 7 years after completing a 7-year course of chemotherapy. Patient 1 underwent left partial cystectomy and patient 2 underwent cystectomy with ileal conduit urinary diversion. In patient 1 the tumor was a typical leiomyosarcoma and patient 2 had a myxoid variant. Both patients were free of disease at 4 months and 3 years, respectively. Whereas previous reports of the carcinogenic effects of cyclophosphamide have been questioned, since the induced tumors occurred in patients being treated for other neoplasms (lymphoproliferative and myeloproliferative disorders), the disease in both of our patients followed cyclophosphamide therapy for nonneoplastic disorders. | |
| 2816285 | Associated disorders in myasthenia gravis: autoimmune diseases and their relation to thyme | 1989 Oct | The prevalence of myasthenia gravis (MG) in the counties of Hordaland and Sogn & Fjordane on January 1, 1984 was 9.6 per 100,000 inhabitants. Other autoimmune diseases were found in 11 out of 48 MG patients. The occurrence of autoimmune thyroiditis (5 patients, 10.4%) and systemic lupus erythematosus (4 patients, 8.3%) in the MG patients was clearly higher than that reported in the general population. Rheumatoid arthritis was found in 2 patients (4.2%). The autoimmune diseases were mainly recorded among the nonthymectomized MG patients. In addition to those with definite diseases of autoimmune nature, 3 other MG patients had thyroid antibodies and 1 had antinuclear factor without clinical evidence of autoimmune disease. Seven MG patients (14.6%) had unspecific arthralgia during active periods of MG. Two MG patients had ankylosing spondylitis. | |
| 2508447 | Biochemical characterization of soluble phospholipase A2 from rheumatoid synovial fluid. | 1989 Jun | Radiolabeled E. coli, Phosphatidylethanolamine (PE) and Phosphatidylcholine (PC), were used to characterize the phospholipase A2 (PLA2) activity in synovial fluid (SF) from rheumatoid arthritis (RA) patients. Cell-free fractions of SF contain a PLA2 enzyme that preferentially releases [14C]oleic acid from E. coli, requires calcium and is optimally active at neutral pH. Purified PE, but not PC is also readily degraded by the soluble enzyme. A cell-associated PLA2 present in sonicates of SF mononuclear cells and neutrophils preferentially releases [3H]AA from E. coli. These studies suggest the presence of at least two different enzymes with activity of PLA2 in rheumatoid SF. | |
| 2853449 | Effect of polymorph derived oxidants on IgG in relation to rheumatoid factor binding. | 1988 | Immunoglobulin G from rheumatoid patients is denatured around the hinge region. This has been proposed as an explanation for the presence of circulating autoantibodies to IgG in these patients. It has previously been suggested that oxygen radicals (OR) derived from activated polymorphs may play a role in denaturation in vivo. Using sera from rheumatoid patients and age-matched controls in a modified ELISA technique, we have investigated the potential for polyclonal rheumatoid factors (RF) to bind to OR denatured IgG. Three model systems were used to generate OR in vitro: (a) purified PMN s activated by the cell surface stimulant PMA, (b) radiolysis of IgG in solution to generate specifically the superoxide radical and, in a separate system, the hydroxyl radical, (OH.), (c) purified myeloperoxide in the presence of H2O2 and halide ions. RESULTS: 1. The binding of both IgA and IgM RF s to PMN denatured IgG increased dose dependently for seropositive sera only. 2. The OH. radical but not the superoxide radical significantly increased the binding of IgA and M RF, again only for seropositive sera. 3. The myeloperoxidase enzyme system did not increase RF binding. 4. IgG incubated with elastase was not found to be a better antigen than native IgG. These results indicate that IgG is denatured by OR released from activated PMN, thereby producing an antigen for polyclonal RF s. | |
| 2212003 | Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 | 1990 Oct | Accumulating evidence implicates a central role for synovial T cells in the pathogenesis of rheumatoid arthritis, but the activation pathways that drive proliferation and effector function of these cells are not known. We have recently generated a novel monoclonal antibody against a rheumatoid synovial T cell line that recognizes an antigen termed UM4D4 (CDw60). This antigen is expressed on a minority of peripheral blood T cells, and represents the surface component of a distinct pathway of human T cell activation. The current studies were performed to examine the expression and function of UM4D4 on T cells obtained from synovial fluid and synovial membranes of patients with rheumatoid arthritis and other forms of inflammatory joint disease. The UM4D4 antigen is expressed at high surface density on about three-fourths of synovial fluid T cells and on a small subset of synovial fluid natural killer cells; in synovial tissue it is present on more than 90% of T cells in lymphoid aggregates, and on approximately 50% of T cells in stromal infiltrates In addition, UM4D4 is expressed in synovial tissue on a previously undescribed population of HLA-DR/DP-negative non-T cells with a dendritic morphology. Anti-UM4D4 was co-mitogenic for both RA and non-RA synovial fluid mononuclear cells, and induced IL-2 receptor expression. The UM4D4/CDw60 antigen may represent a functional activation pathway for synovial compartment T cells, which could play an important role in the pathogenesis of inflammatory arthritis. | |
| 2461346 | A unique monoclonal antibody derived from a lupus-prone mouse with multiple bindings to au | 1988 Sep | Monoclonal anti-poly(ADP-ribose) (MRP-2) was primarily a product of a hybridoma selected by binding to poly(ADP-ribose) from an autoimmune MRL/Mp-lpr/lpr (MRL/1) mouse. Detailed examination revealed that anti-poly(ADP-ribose) monoclonal IgMK antibody bound not only to left-handed Z-DNA and single-stranded (ss) DNA but also to a conformational epitope formed by histone and double-stranded (ds) DNA. A reconstitution study revealed that association of dsDNA with histone H3 plus H4 was essential for their binding to MRP-2 monoclonal antibody. MRP-2 monoclonal antibody acted as a rheumatoid factor (RF). Since some monoclonal or polyclonal human serum antibodies of rheumatoid arthritis (RA) or mixed connective tissue disease (MCTD) have been reported to recognize shared epitopes of denatured IgG and DNA-histone (nucleosomes), this MRP-2 monoclonal antibody with the similar activity derived from a lupus-prone mouse will be useful for the studies on the etiology of autoantibodies associated with RA, MCTD and systemic lupus erythematosus (SLE). | |
| 1849807 | The perinuclear factor, a rheumatoid arthritis-specific autoantigen, is not present in ker | 1991 Apr | Rheumatoid arthritis patients have antibodies in their serum directed against the perinuclear factor, a protein component present in keratohyalin granules in the cytoplasm of human buccal mucosa cells. The anti-perinuclear factor (APF) can only be detected by an indirect immunofluorescence test performed on fresh buccal mucosa cells from 'selected donors'. To obtain a more reliable antigen source and to gain more insight into the origin and nature of the perinuclear factor we attempted to culture perinuclear factor-containing buccal mucosa cells. Here we describe the successful culturing of such cells, which, however, did not contain keratohyalin granules nor the perinuclear factor. By adding the phorbol ester 12-o-tetradecanoylphorbol-13-acetate (TPA) we were able to induce keratohyalin granules in both cultured primary buccal mucosa cells and a squamous carcinoma cell line of the cheek (SqCC/Y1). These induced keratohyalin granules do contain the protein profilaggrin, which in vivo, in fresh buccal mucosa cells, co-localizes with the perinuclear factor. However, we were not able to demonstrate the presence of the perinuclear factor, not even after induction of terminal differentiation of the cultured cells nor after Epstein-Barr virus infection. Our results suggest that the perinuclear factor, in contrast to profilaggrin, is not an integral component of buccal mucosa cells. | |
| 2554826 | Autoantibodies to recombinant lipocortin-1 in rheumatoid arthritis and systemic lupus eryt | 1989 Oct | Corticosteroids may mediate some of their anti-inflammatory effects via induction of a specific 38 kD protein, lipocortin-1. Autoantibodies to lipocortin-1 were measured by enzyme linked immunosorbent assay (ELISA) in 90 healthy subjects and in 63 patients with rheumatoid arthritis (RA), 36 with systemic lupus erythematosus (SLE), 26 with polymyalgia rheumatica, and 13 with chronic airways disease. Sixteen patients with RA receiving prolonged, high steroid doses (prednisolone greater than 7.5 mg/day) had raised IgM antilipocortin-1 levels, while 19 patients with RA untreated with steroids had normal levels. This association was independent of disease activity. In SLE, raised antilipocortin-1 levels were associated with active disease and were independent of steroid treatment. Antilipocortin-1 antibody levels were not raised in patients with polymyalgia rheumatica and chronic airways disease. Thus steroid treatment alone appears insufficient to induce antilipocortin-1 antibodies, unless an underlying autoimmune state is also present. In RA, antilipocortin-1 antibodies may impair anti-inflammatory actions of steroids and render some patients 'steroid resistant'. | |
| 3318429 | Nabumetone in the treatment of active adult rheumatoid arthritis. | 1987 Oct 30 | One hundred patients were entered in a six-month, double-blind comparison of 1,000 mg nabumetone once daily and 250 mg naproxen twice daily. Forty-two patients in each arm of the study were evaluable for efficacy; all were evaluable for safety. There was a low incidence of adverse experiences during this study, with no patients withdrawing from the study because of side effects from either drug. Efficacy was equal, with both compounds sharing the same degree and rate of improvement. All of the patients completing the double-blind phase were then switched to open-label treatment with nabumetone. The dosage of nabumetone was gradually increased. At the end of one year, 84 patients remained in the study (52 taking 1,000 mg per day, 23 taking 1,500 mg, and nine taking 2,000 mg). This gradual increase has continued, and, at this time, 61 patients remain in the study (seven taking 1,000 mg per day, 24 taking 1,500 mg, and 30 taking 2,000 mg). There have been very few side effects. From this study, it can be concluded that nabumetone is at least as effective as naproxen and, even at higher doses, had an acceptable safety profile for extended use in patients with rheumatoid arthritis. | |
| 2894754 | Rheumatoid arthritis: a pharmacologic overview. | 1988 Mar | Numerous drugs are available for the treatment of rheumatoid arthritis. The nonsteroidal anti-inflammatory drugs differ in structure and pharmacokinetics, and they rarely act synergistically. The disease-modifying antirheumatic drugs include gold compounds, penicillamine, hydroxychloroquine and sulfasalazine. Useful immunosuppressive and cytotoxic agents include methotrexate, azathioprine and cyclophosphamide. Costicosteroids find their greatest use in short courses. | |
| 1805774 | Non steroidal anti-inflammatory drugs. Risk factors versus benefits. | 1991 Dec | NSAIDs can still provide significant symptom relief in patients with many forms of arthritis. Nevertheless, they need to be used judiciously and a careful watch kept for adverse reactions. | |
| 2361972 | [Osteosynthesis of the greater trochanter using a plate and cables in total hip arthroplas | 1990 Apr | The authors suggest a new system of osteosynthesis of the greater trochanter using a plate and cables. The surgical technique is simple in its realisation which allows 94.4% bone-union of the greater trochanter and almost immediate partial weight bearing by the patient. 61 patients were studied after a minimum of one year and only one case of non-union was observed. The authors recommend this technique especially in difficult arthroplasties (obesity, dysplasia) and in revision total his replacement. The trochanteric approach facilitates the extraction of the prothesis, bone cement, and reconstruction of the acetabulum. This technique may be used systematically in arthroplasties using trochanterotomy. | |
| 3039647 | [Expression of T-lymphocyte antigens by serum B lymphocytes in rheumatoid polyarthritis]. | 1986 Nov | Molecules recognised by the monoclonal antibodies Leu 1 - OKT 1 - Mid 5 (CD5 molecules) were originally shown on human T cells and are equivalent to Lyt-1 molecules in the mouse. These surface molecules are detectable on some human B cells, but are weakly expressed. We have therefore tested the effects of the tumour-promoter, phorbol myristic acetate (PMA) on expression of these molecules on B cells. Sheep red blood cell rosette-depleted lymphoid organ or blood cells from 8 controls and 10 rheumatoid arthritis (RA) patients were examined fresh and cultured with PMA for 48 hours and the cells stained with Leu 1 or Mid 5 by indirect immunofluorescence. Cells were analysed by UV microscopy or flow cytometry. More RA blood B cells were positive for Leu 1 than normals before culture. Following incubation with PMA, the percentage of positive cells increased in all cell populations (1-49% in RA patients and 5-26% in controls). There was no difference in the expression of Leu 1 on Kappa--or lambda--positive cells before and after culture in PMA. Leu 1 positive cells were under-represented in Epstein-Barr virus-driven cell lines. | |
| 1776120 | Heat-shock proteins and autoimmunity in humans. | 1991 | T cells and antibodies against self and non-self hsp are present in both patients and healthy controls. T cells responding to hsp65 can be involved in autoimmune diseases, this was demonstrated for two site-specific animal autoimmune diseases: AA in Lewis rats and diabetes (IDDM) in NOD mice. In human ReA there is evidence for a direct stimulation of joint T cells by antigens of the organisms causing the infection which precedes the joint inflammation. The individual antigens of the triggering bacteria still have to be defined, but hsp65 may be of importance since this is one of the molecules recognized by synovial T cells in ReA patients. In RA there are no clear data implicating an infection in the initiation of joint inflammation, but mycobacteria have been suggested to be involved. We have discussed experimental findings which are in favor of, or in contradiction with, a role of mycobacterial antigens--particularly hsp65--in the etiology of RA. T cells recognizing hsp65 and other mycobacterial antigens are present in the joint, but there is no indication for a specific involvement of one or a limited set of (myco)bacterial antigens in the pathogenesis of RA. | |
| 3081411 | Investigation of auranofin-induced diarrhoea. | 1986 Jan | Gastrointestinal function was assessed in six patients with rheumatoid arthritis who had developed diarrhoea on treatment with Auranofin. With the administration of Auranofin whole gut transit time decreased markedly (to 50% or less of control values) in five of six patients. The speed of passage of intestinal contents through the colon was certainly increased but attempts to assess transit through the upper gastrointestinal tract failed because the breath hydrogen method gave inconclusive results. There was no evidence of colitis and in all cases biopsy of the rectal mucosa appeared normal by light microscopy. In the five patients with rapid intestinal transit faecal weight increased more than two-fold (range +44 to +335%) although in only three cases were the changes sufficient to cause an increased frequency of bowel action. Overall the concentration of sodium in faecal water increased three-fold (mean values rose from 10.6 to 38.3 mmol/l). There were no significant changes in the concentrations of either potassium or chloride but bicarbonate was reduced. Faecal pH fell from a mean value of 7.5 (range 6.8-7.9) to a mean value of 6.4 (range 6.0-7.4). In the three patients who developed overt diarrhoea and in two others taking Auranofin the intestinal uptake of 51Cr-EDTA was increased on average three-fold and there was a similar change in the ratio of the absorption of lactulose/mannitol. The mean clearance of alpha-1-antitrypsin from the circulation into the gastrointestinal tract was doubled. These data indicate an increase in intestinal permeability. In contrast the absorption of vitamin B12 was unaffected and there was no significant change in the excretion of faecal fat although one patient developed mild steatorrhoea. Thus in a selected group of subjects with rheumatoid arthritis the administration of Auranofin caused diarrhoea in association with a reversible defect in intestinal permeability but without significant change in the absorption of nutrients. | |
| 2937138 | Rheumatoid synovial dendritic cells as stimulators in allogeneic and autologous mixed leuk | 1986 Feb | Dendritic cells were isolated from peripheral blood, synovial fluid, and synovial tissue of patients with rheumatoid arthritis and from peripheral blood of healthy blood donors on the basis of semiadherence to plastic surfaces. The cells were compared with autologous peripheral blood monocytes with respect to their stimulating capacities in allogeneic and autologous mixed leukocyte reactions (MLR). Dendritic cells from the various compartments stimulated allogeneic T cells 6-14 times more than monocytes did. Dendritic cells also stimulated autologous T cells 10-24 times more than monocytes did. Evidence in favour of the dendritic cell as the major stimulating cell type in MLR was also found in mixed experiments in which various ratios of dendritic cells and monocytes were used as stimulator cells. Furthermore, the activating structures on the dendritic cells seem to be major histocompatibility complex class II antigens, since anti-HLA-DR antibodies inhibited the responses. The results, especially from the autologous MLR, indicate that dendritic cells are important accessory cells for the various immune responses in rheumatoid inflammation. | |
| 2232043 | Diclofenac-associated hepatotoxicity. | 1990 Nov 28 | Diclofenac sodium, a phenylacetic acid-derived nonsteroidal anti-inflammatory drug (NSAID) recently released in the United States, was associated with the development of significant hepatitis in seven patients, with one associated death. Signs and symptoms developed within several weeks of initiation of drug use and generally resolved 4 to 6 weeks following discontinuation of use of the drug. The only patient rechallenged with the drug developed a recurrence of her hepatic abnormalities. In one patient, fatal, fulminant hepatitis developed despite early withdrawal of the drug. Review of the European literature disclosed three additional fatalities associated with diclofenac therapy. It is unclear whether the incidence of hepatotoxicity is higher with this drug compared with other nonsteroidal anti-inflammatory drugs. Careful patient monitoring is advised, and prompt discontinuation of the drug is suggested when signs or symptoms of liver disease develop. | |
| 1717250 | Two-dimensional electrophoresis of human parotid salivary proteins from normal and connect | 1991 Jul | Two-dimensional electrophoretic analysis of human salivary proteins using immobilised pH gradients in the first dimension, thin-layer gradient horizontal sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the second, and modified staining procedures has resulted in a substantial improvement in their resolution. Unlike carrier ampholyte-based techniques, immobilised pH gradients prevent the loss of proteins of pI greater than 8; accordingly, basic components, including basic proline-rich proteins, can now be resolved. A two-dimensional map showing the locations and identities of most of the major proteins has been constructed. Narrow-range pH gradients can be constructed to give increased resolution of proteins of particular interest. By means of a pH 3.5-5.0 gradient, the abnormal salivary proteins associated with connective tissue disorders were found to be a highly heterogeneous group of pI approximately 3.75-4.75 and Mr approximately 32,000; although low levels occurred in some normal individuals, there was less heterogeneity (pI approximately 3.75-4.25). The technique should form a base for future structural, functional, and clinical studies on human salivary proteins. | |
| 2501058 | Increased renal tubular cell excretion by patients receiving chronic therapy with gold and | 1989 Jul | Using rheumatoid arthritis patients who were receiving gold as models, we evaluated the renal effects of the chronic administration of very low doses of a nephrotoxic drug. The heavy metal gold has been shown to increase urinary enzyme excretion when it is given in usual doses for the treatment of rheumatoid arthritis. It is not clear whether the increased urine enzyme excretion caused by long-term drug therapy represents injury to the kidney or whether it is merely an effect of the drug. Urinary N-acetyl-beta-glucosaminidase and renal tubular cell excretion rates were measured in 19 patients who were receiving chronic treatment with gold and with nonsteroidal anti-inflammatory drugs for rheumatoid arthritis, in 10 patients who were receiving nonsteroidal anti-inflammatory drugs, and in 8 healthy control subjects. No subjects showed evidence of kidney disease. Both renal tubular cell and enzyme excretion rates were elevated in the gold-treated group. This showed that there was increased renal tubular cell turnover in this group, which suggests low level renal tubular injury and not merely an effect of the usual dose of gold. | |
| 2317110 | Phenotypic and genotypic analysis of mononuclear cells from patients with Felty's syndrome | 1990 Feb | Phenotypic and genotypic characteristics of the peripheral blood mononuclear cells in nine patients with Felty's syndrome have been examined. One patient had an increased number and percentage of peripheral blood mononuclear cells with the phenotype CD3+ Leu-7+ CD16+ and showed a clonal rearrangement of the T cell receptor B chain gene. The remaining eight patients all showed a germline configuration of the T cell receptor B chain gene. In two patients an increased proportion of CD3+ Leu-7+ CD16- peripheral blood mononuclear cells (45 (SD 11)% of peripheral blood mononuclear cells) were found, while the remaining six patients had proportions of CD3+ Leu-7+ cells similar to those of patients with uncomplicated rheumatoid arthritis. These data confirm that patients with Felty's syndrome are heterogeneous, with at least three different peripheral blood mononuclear cell phenotypic subsets. One subset is characterised by a clonal expansion of an unusual lymphocyte subpopulation, another by polyclonal expansion, and the third subset has the same proportions of peripheral blood mononuclear cells as patients with uncomplicated rheumatoid arthritis. |