Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2824488 | Transcription from the stromelysin promoter is induced by interleukin-1 and repressed by d | 1987 Dec 5 | The stromelysin gene encodes a potent tissue-degrading proteinase whose activity is important in tissue-remoldeling processes such as wound healing, the inflammatory reaction, rheumatoid arthritis, tumor invasion, and possibly embryonic development. In light of the ability of interleukin-1 to amplify, and ability of glucocorticoids to attenuate the inflammatory response, we tested interleukin-1 and dexamethasone for regulatory effects on stromelysin gene expression. We report that interleukin-1 induces the stromelysin gene, and dexamethasone diminishes the level of induction by interleukin-1, epidermal growth factor, phorbol ester, and cAMP elevation (elicited by cholera toxin). Similar responses are conferred upon a chloramphenicol acetyltransferase coding sequence by a 700-base pair stromelysin 5'-flanking fragment, implying transcription regulation by sequence elements in this region. | |
| 3110943 | Long-term efficacy and safety of auranofin: a review of clinical experience. | 1986 | Auranofin (AF) is the first oral gold therapy developed for the treatment of rheumatoid arthritis (RA). Since the drug was introduced in 1982, more than 100,000 patients have been treated with AF. Controlled clinical trials prior to introduction included more than 5,000 patients, some of whom received AF for more than 7 years. At the recommended dose of 6 mg/day, AF therapy results in a lower total body burden of gold than does injectable gold (IG). However, comparative studies indicate that the clinical effect of AF is comparable to that of IG. Adverse events that occur during AF therapy tend to be mild and of short duration, often resolving with continued therapy or temporarily reduced dosage. Most adverse events occur during the first few months of therapy, and the incidence diminishes over time. Data on 134 patients who received AF for more than 5 years demonstrate a sustained therapeutic effect and no cumulative toxicity from long-term therapy. In 18 comparative trials, 1,053 patients with RA received either AF (527 patients) or IG (526 patients) for up to 36 months. At 1 year, similar proportions of patients in the AF and IG groups had 50% or greater improvement in various parameters of disease activity. Safety analysis showed that AF was significantly better tolerated than IG. The rate of withdrawal because of adverse events was about twice as great in the IG group as in the AF group, both at one year (14% vs. 31%, p less than 0.05) and for the duration of the trials (18% vs. 34%, p less than 0.05). This suggests that the benefit-to-risk ratio is more favorable with AF. | |
| 3293969 | Nabumetone. A preliminary review of its pharmacodynamic and pharmacokinetic properties, an | 1988 May | Nabumetone is a new non-steroidal anti-inflammatory drug advocated for use in the symptomatic treatment of rheumatic and inflammatory conditions. Unlike most other drugs of its class it is non-acidic and a prodrug, which after absorption forms an active metabolite. Published data suggest that nabumetone 1 to 2g daily is comparable with therapeutic dosages of aspirin, diclofenac, ibuprofen, indomethacin, naproxen and sulindac for the treatment of pain and inflammation associated with rheumatoid arthritis, osteoarthritis and acute soft tissue injuries. While nabumetone produced fewer side effects than aspirin, results have generally shown tolerability to be similar to that of other nonsteroidal anti-inflammatory drugs. If further definition of its efficacy and tolerability relative to other non-steroidal anti-inflammatory drugs confirms these initially favourable results, then nabumetone would appear to offer a useful alternative in the treatment of painful rheumatic and inflammatory conditions. | |
| 2515016 | Long-term outcome with gold thiosulphate and tiopronin in 200 rheumatoid patients. | 1989 Nov | Two hundred rheumatoid patients were prospectively studied over a five-year period. One hundred and three received tiopronin (T) and 97 were treated with gold thiosulphate (GTS). At the end of the five-year period, similar percentages of patients dropped out because of lack of efficacy or because of major toxicities. Likewise, the percentages of patients still receiving the original drug in the two drug regimens at the 5th year of follow-up were 27.8% (GTS) vs. 25.2% (T), respectively. | |
| 3003163 | Human recombinant interleukin 1 stimulates collagenase and prostaglandin E2 production by | 1986 Feb | The pathogenesis and progression of rheumatoid arthritis involves the production of biologically active lymphokines and monokines. Of these, interleukin 1 (IL-1) has been somewhat of a controversial molecule because it seems to evoke various biological responses in several different tissues. In these studies we demonstrate that three biological properties of human monocyte-derived IL-1 (T-lymphocyte activation and human synovial cell prostaglandin E2 and collagenase production) co-purify. The complementary DNA for the prominent pI 7 form of human IL-1 was expressed, purified, and tested. Any controversy now appears resolved since homogeneous recombinant human IL-1 stimulates prostaglandin E2 and collagenase from human synovial cells as well as activates T cells in vitro. | |
| 1892140 | Nonsteroidal anti-inflammatory drug-associated gastropathy: incidence and risk factor mode | 1991 Sep | PURPOSE: The most prevalent serious drug toxicity in the United States is increasingly recognized as gastrointestinal (GI) pathology associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The incidence of serious GI events (hospitalization or death) associated with NSAID use was therefore prospectively analyzed in patients with rheumatoid arthritis (RA) and patients with osteoarthritis. PATIENTS, METHODS, AND RESULTS: The study consisted of 2,747 patients with RA and 1,091 patients with osteoarthritis. The yearly hospitalization incidence during NSAID treatment was 1.58% in RA patients and was similar in all five populations studied. The hazard ratio of patients taking NSAIDs to those not taking NSAIDs was 5.2. The incidence in osteoarthritis may be less. The risk of GI-related death in RA patients was 0.19% per year with NSAIDs. Multivariate analyses assessing risk factors for serious GI events were performed in the 1,694 (98 with an event) RA patients taking NSAIDs at the predictive visit. The main risk factors were higher age, use of prednisone, previous NSAID GI side effects, prior GI hospitalization, level of disability, and NSAID dose. A rule is presented that allows estimation of the risk for the individual patient with RA. CONCLUSION: Knowledge of the risk factors for NSAID-associated gastropathy and their inter-relationships provides a tool for identification of the patient at high risk and for initiation of appropriate therapeutic action. | |
| 2109075 | Experimental evidence of the benefit of misoprostol beyond the stomach in humans. | 1990 Feb | Nonsteroidal antiinflammatory drugs (NSAID) cause inflammation of the small intestine in 60 to 70% of patients receiving these drugs for more than 6 months. The importance of the inflammation lies in the associated complications of blood and protein loss and in the occasional development of unique small intestinal strictures requiring surgery. The pathogenesis of the inflammation is unknown. However, increased intestinal mucosal permeability due to NSAID appears to be a prerequisite; increased permeability allows exposure of the mucosa to lumenal toxins, which results in neutrophil chemotaxis and, hence, inflammation. In a study assessing the possible protective effect of misoprostol on indomethacin-induced increased small intestinal permeability, 12 volunteers underwent combined absorption/permeability tests prior to and following administration of misoprostol and/or indomethacin. Indomethacin increased intestinal permeability significantly as assessed by 51Cr-EDTA/L-rhamnose urine excretion ratio, and concomitant administration of misoprostol produced a significant protective effect. These results conform to the suggestion that NSAID-induced changes in intestinal permeability may be due to an imbalance between mucosal prostaglandins and leukotrienes. Longterm studies of the coadministration of misoprostol with NSAID are indicated to assess whether this agent reduces the severity of NSAID enteropathy. | |
| 2805494 | A metal-backed, rotating-bearing patellar prosthesis to lower contact stress. An 11-year c | 1989 Nov | A congruent-contact, metal-backed, rotating-bearing patellar prosthesis has been used clinically over an 11-year period. The features of this implant include a congruent-contact, rotating bearing attached to a thin metallic anchoring plate fixed to the bone by cruciate fixturing fins. The device was initially used with methylmethacrylate and later used as a cementless, porous-coated, ingrowth fixation implant. The benefits of congruent contact with mobility to adjust its tracking position during flexion and extension help to eliminate axial shear stresses at the bone-prosthesis interface and lower the contact stresses at the bearing-metal interface to improve wear properties. Prostheses were implanted in 515 knees over a period of six months to 11 years. Of these 515 knees, 331 patellar prostheses have been followed for 24 to 132 months (mean, 73 months). Of that group of 331 implants, 141 were cemented and 190 were cementless. Specific complications involving the use of this implant were as follows. One intraoperative vertical midpatellar fracture in a cemented case went on to uneventful healing with an excellent result. Two displaced postoperative transverse midpatellar fractures (0.39%) occurred in two revision total knee arthroplasties that involved major lateral releases. One of those was a cemented revision and required removal of the implant and a partial patellectomy to gain an excellent result. In the other, a noncemented revision, the patient lacks 45 degrees of quadriceps extension and has a poor result following traumatic fracture at three years postsurgery. One patellar dislocation (0.19%) occurred in a 270-pound, osteoarthritic man in whom undersized components were used. No polyethylene wear-through, separation from the metal anchoring plate, or implant breakage was seen in this series. Overall, the performance of this congruent-contact, metal-backed, rotating-bearing patellar prosthesis indicates the prosthesis can provide long-term function and stability with few short-term or long-term complications. | |
| 1825808 | Identification of a population of large granular lymphocytes obtained from the rheumatoid | 1991 Mar | In this study, we phenotypically characterized large granular lymphocytes (LGL) among the synovial fluid mononuclear cells obtained from rheumatoid arthritis (RA) patients. Cytochemical and flow cytometric studies revealed an increased percentage of LGL in the synovial fluid mononuclear cells obtained from patients with RA compared to those without RA. Flow cytometric analysis revealed an expanded population of cells expressing a rare phenotype: CD3 +/CD16+. While these cells are seen in very low percentages in normal individuals (less than 2%) and have been reported in T cell lymphoproliferative disorders. In 20/30 RA patients studied, these cells constituted from 20 to 80% of the total synovial fluid mononuclear cells. Furthermore, studies of synovial fluids with greater than 20% CD3 +/CD16+ cells failed to show significant cytolytic activity even after incubation with recombinant interleukin-2, while fluids with less than 20% CD3 +/CD16+ cells possessed normal cytolytic activity. Studies of matched blood and fluid in eight patients with RA demonstrated a significantly increased percentage of CD3 +/CD16+ cells in synovial fluid compared to peripheral blood. Modulation and adsorption studies did not provide evidence that the CD16 antigen present on these CD3 cells was due to passive adsorption of soluble CD16 antigens. Thus, while the relevance of these cells in the pathogenesis of RA is not clear, this report identifies CD3 +/CD16+ cells in a disease state other than T cell lymphoproliferative disorders. | |
| 2462048 | Characterization of human synovial mast cells. | 1988 Sep | Human synovium obtained at arthroplasty from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were characterized by assessing mast cell morphology, content and function. Histological studies confirmed significant numbers of mast cells in both RA and OA synovium. Electron microscopic data support the morphologic similarity between human synovial mast cells and human mast cells in lung and intestine. Likewise, synovial mast cells do not appear to be functionally different from pulmonary or intestinal mucosal mast cells. Mast cell suspensions with a cellular histamine content of 4.3 +/- 0.5 pg/cell (mean +/- SEM) released histamine following provocation with anti-IgE and calcium ionophore but not compound 48/80, f-met peptide or bradykinin. Prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) were also released in response to anti-IgE. Auranofin inhibited anti-IgE provoked histamine, PGD2 and LTC4 release while gold sodium thiomalate, cromolyn and indomethacin had no effect on histamine release. Theophylline inhibited anti-IgE induced histamine release only at concentrations greater than or equal to 10(-3) M. Our study argues against functional or morphologic mast cell heterogeneity of human intestinal, lung and synovial origin and suggests that mast cells may have a pathogenic role in both RA and OA. | |
| 2438080 | Caeruloplasmin, prealbumin and alpha 2-macroglobulin as potential indices of disease activ | 1987 Mar | Caeruloplasmin (Cp), prealbumin and alpha 2-macroglobulin (alpha 2-M) concentrations in serum were compared in rheumatoid arthritis (RA), osteoarthrosis, ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome, Behçet's syndrome, SLE and normal controls. Cp was significantly elevated (p less than 0.01) in all disease groups except for Reiter's syndrome and SLE. Prealbumin was only significantly depressed (p less than 0.01) in RA. The most notable elevation in alpha 2-macroglobulin occurred in Reiter's syndrome. However, these differences were generally still within the normal range, and hence these proteins are unlikely to offer alternative indices of disease activity suitable for monitoring the the progress of seronegative arthropathies. | |
| 3951729 | [Eosinophilic granuloma of the stomach associated with polyarthritis]. | 1986 Feb 18 | Eosinophilic granulomas of the stomach, also known as inflammatory pseudotumours, are infrequently occurring lesions characterised histologically by local capillary and fibroblastic proliferation with infiltration of eosinophilic cells. This condition is benign and appears as a polypoid mass with or without ulceration. A case of association of a polyarthritis with a eosinophilic polypoid gastric granuloma is described. This was subsequently removed by endoscopic polypectomy. | |
| 1949833 | [Changes in the serum pepsinogen level during therapy with acemtacin retard as a measure o | 1991 | Early indications of the development of gastroduodenal lesions can be obtained with the radioimmunological determination of pepsinogen I in serum. The influence of the non-steroidal anti-inflammatory drug Acemetacin in depot form on the course of the pepsinogen levels in serum was examined during 14 day therapy. Mean and median of pepsinogen I in the whole group of 26 patients did not increase significantly. Likewise no increases of the single pepsinogen levels in serum were seen in 85%. Only 4 patients showed increases of about 20 to 27% compared with the initial values. These results indicate that Acemetacin with prolonged action is well tolerated and has only mean influence on the integrity of the mucosa. | |
| 2166768 | Possible role of Epstein-Barr virus infection in cutaneous T-cell lymphomas. | 1990 Sep | Although cutaneous T-cell lymphoma (CTCL) is a neoplastic helper T-cell disorder of unknown etiology, prolonged antigenic stimulation has been postulated to contribute to the development of this disease. Because Epstein-Barr Virus (EBV) infection has been associated with several different lymphomas, the sera of 21 CTCL patients were examined for antibodies to EBV antigens. By using complement immunofluorescence (CIF) techniques, 13 of 21 CTCL patients had detectable antibodies to Epstein-Barr Nuclear Antigens (EBNA), whereas only five of 20 control psoriatic patients were CIF positive. When immunoblot analysis was employed, all 21 of the CTCL patients had antibodies to the EBV antigens, EBNA, whereas only 12 of the control patients had detectable antibodies to these antigens. In addition, three of 21 CTCL patients had antibodies to the EBV-associated antigen, rheumatoid arthritis nuclear antigen (RANA), as determined by double immunodiffusion, whereas none of the control sera contained anti-RANA antibodies. These results indicate that antibodies against EBV antigens are found with a higher frequency and concentration in patients with CTCL when compared to controls and suggest that EBV products might serve as a possible stimulus for the development of this malignant disease. | |
| 1941813 | Phenotypic characteristics of T cells interacted with synovial cells. | 1991 Aug | We demonstrated the phenotypic characteristics of T cells interacted with synovial fibroblast-like cells. A small percentage of peripheral blood T cells adhered to synovial fibroblast-like cells. When synovial cells were treated with interferon-gamma or interleukin-1 beta, the percentage of T cells that adhered to the treated cells markedly increased in comparison with the value for untreated synovial cells. The kinesis of T cell adherence to treated synovial cells differed from that of HLA-DR antigen expression on synovial cells. T cell adherence was not blocked by mouse monoclonal anti-HLA-DR and anti-HLA-ABC antibodies. The phenotypes of the adherent and nonadherent T cells were investigated with a flow cytometer. The CD29 + subset was more adhesive than the CD45RA + subset to IL-1 beta-stimulated synovial cells. The proportions of high density lymphocyte function associated antigen (LFA)-1 alpha and LFA-1 beta were greater in the adherent than in the nonadherent T cells, and the mean fluorescence intensities of LFA-1 alpha, LFA-1 beta and CD2 molecules on adherent T cells were significantly higher than those on nonadherent T cells. Our results support the concept that an interaction between infiltrating lymphocytes and synovial cells occurs in the synovium, resulting in the initiation and perpetuation of immune responses in synovial tissue in rheumatoid arthritis. | |
| 3501721 | Inhibitor of interleukin-2 synthesis and response in rheumatoid synovial fluid. | 1987 Dec | We studied the effects of a factor present in rheumatoid arthritis (RA) synovial fluid (SF) on interleukin-2 (IL-2)-dependent cell proliferation and on the production of IL-2 by mitogen-stimulated peripheral blood mononuclear cells. RA SF suppressed the responsiveness of a mouse T cell line (HT-2) to IL-2, indicating that it contained an inhibitor of the IL-2 response. When RA SF was fractionated by Sephadex G-200 gel filtration, the inhibitory activity was detected mainly in fractions with a molecular weight of approximately 150,000, but was also found in a 15-19-kd fraction. Removal of IgG from the 150-kd fraction, by means of an anti-IgG affinity column, did not reduce the activity of the fraction, nor was activity found in the eluted IgG. The inhibitory fractions reduced mouse thymocyte proliferative responses to IL-1 in the presence of phytohemagglutinin, and reduced the production of IL-2 by human peripheral blood mononuclear cells, but did not inhibit IL-1-induced human foreskin fibroblast proliferation; this suggests that the factor was not an IL-1 inhibitor. The inhibitory activity of the RA SF factor was blocked by an antibody against an inhibitor of IL-2 that was purified from a culture of the human monocytic leukemia cell line, THP-1. This finding also supports the conclusion that RA SF contains an IL-2 inhibitory factor. The observed inhibition of both IL-2 synthesis and IL-2 response suggests that the target of the inhibition was the T lymphocyte. | |
| 2427092 | Characterization and functional studies of rheumatoid synovial mast cells. Activation by s | 1986 Aug | Microscopic analysis of synovial specimens from 35 patients with rheumatoid arthritis (RA) and 7 patients with osteoarthritis revealed mast cell hyperplasia in perivascular regions, in fibrous interstitial areas, and clustered around the periphery of lymphoid aggregates. Metachromatic staining, immunofluorescence studies, and ultrastructural analysis revealed a single population of connective tissue-type mast cells with surface IgE receptors. Total extractable histamine of synovial tissue was 4.15 +/- 2.30 micrograms/gm (n = 8) for RA synovium and 0.53 +/- 0.23 microgram/gm (n = 7) for OA synovium. Mast cell secretion was assessed and specific release of histamine from RA synovial mast cells was observed following stimulation with anti-IgE (32.3%), compound 48/80 (40.1%), calcium ionophore A23187 (25.2%), and a partially purified lymphokine with histamine-releasing activity (23.9%). | |
| 2939096 | Silicone implants. | 1986 May | Infection has not been considered in this article with each individual implant. The incidence is low indeed. In the only publication concerned primarily with the topic of infection following silicone implant surgery, Millender et al. reviewed 2105 implants of varying kinds. There were ten infections, seven of which were with Staphylococcus aureus. The onset was remarkably late--17 days after surgery on average. In seven cases the implant had to be removed and the eventual result was good, being likened to that obtained after an excisional arthroplasty. Reviewing the complications that occur with the various implants, it becomes evident that there are three primary concerns--fracture, subluxation, and synovitis. Fracture occurs primarily in the wrist and the metacarpophalangeal implants. The incidence of fracture in the wrist implant is 8.6, 9.4, and 19.8 per cent, giving an average of the means of 12.6 per cent. In the metacarpophalangeal joint, the incidence with the Swanson design is variously 1.9, 26.2 and 21 per cent, the average of the means being 16.4 per cent. The Niebauer design is reported as having a fracture rate of 29.7 and 38 per cent, for an average of the means of 33.9 per cent. The somewhat lower incidence of fracture of the wrist implant is offset by the fact that, in contrast to the situation with the smaller joint, the fracture is almost always symptomatic, requiring treatment. Largely for this reason, silicone wrist arthroplasty is limited mainly to the rheumatoid patient, being little used for post-traumatic arthritis. Subluxation of implants occurs mainly with the carpal replacements. The incidence in independent reports are 56.5 and 50 per cent, for an average of the means of 53.3 per cent with the scaphoid; 20, 20, and 50 per cent for an average of the means of 30 per cent with the lunate; and 5.3, 10, 11.2, 29, and 32 per cent for an average of the means of 17.5 per cent with the trapezium. In the case of the trapezium, excision of a portion of the trapezoid, supplemented where necessary by ligament reconstruction to support the first metacarpal, appears to give the hope of lowering the incidence of subluxation to an acceptable level. With the lunate, preservation of an anterior shell may give satisfactory results but judgment should await longer term studies of larger groups. The scaphoid implant gives most cause for concern, both because the incidence is high and because the solutions offered have either failed or are too recent to judge and perhaps too radical to accept.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 2450710 | IgE rheumatoid factors: quantification in synovial fluid and ability to induce synovial ma | 1988 Feb | IgE rheumatoid factor activity was found to be significantly elevated (P less than 0.01) using an ELISA assay when paired synovial fluid and sera from 13 patients with active RA were compared to ten control samples. Synovial fluid IgE RF activity was higher than predicted by diffusion alone in 7/11 (64%) of the RA synovial fluids studied when coefficients of diffusion were determined. The specificity of IgE RF activity as measured by the ELISA was confirmed using immunoaffinity chromatography. Mast cells, obtained by enzymatic dispersion of rheumatoid synovial tissue, were sensitized with sera containing either IgE antibodies directed against ragweed or IgE with RF activity. Histamine was released upon challenge with anti-IgE antibodies (33.2% +/- 11), ragweed antigen E (34.6% +/- 11), or aggregated gamma globulin (47.6% +/- 17.9). No histamine release was observed if antigen challenge occurred in the absence of appropriate sensitization, with C3 anaphylatoxin, or after immunoadsorption of IgE from sera containing IgE RF activity. | |
| 2078956 | Sterile corneal ulceration after cataract extraction in patients with collagen vascular di | 1990 Oct | We report the occurrence of sterile corneal ulceration in 11 eyes of eight patients with collagen vascular diseases and dry eyes after cataract extraction with intraocular lens implantation. Keratolysis occurred after both extracapsular and intracapsular cataract extraction and appeared unrelated to the type of intraocular lens. Despite aggressive lubrication and other medical treatment, including systemic immunosuppressive agents, penetrating keratoplasty was often required. Although all eyes were saved, visual outcome was usually poor. The histopathologic finding of polymorphonuclear leukocytes localized near the areas of corneal dissolution provides evidence for the role of polymorphonuclear leukocyte-derived collagenase as a contributing factor in the pathogenesis of sterile corneal ulceration in these patients. |