Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3266031 | Interleukin-6 (IL-6) in synovial fluid and serum of patients with rheumatic diseases. | 1988 | Interleukin-6 (IL-6) is a monokine with a number of biological activities, which are intimately related to inflammatory responses. We have measured IL-6 levels in synovial fluid (SF) and serum (Se) of patients with rheumatic diseases. SF-IL-6 levels were a thousand-fold higher than corresponding Se levels and a positive correlation was found between SF and Se levels suggesting that Se-IL-6 is derived from IL-6 produced in the joint. Se levels of IL-6 were also positively correlated to C-reactive protein (CRP) levels, supporting the in vitro experiments showing that IL-6 stimulates hepatocytes to produce CRP. Finally we observed a positive correlation between SF-IL-6 levels and the local activity score. | |
| 2521453 | 1,25-dihydroxyvitamin D3 potentiates the in vitro inhibitory effects of cyclosporin A on T | 1989 Jan | Treatment of rheumatoid arthritis (RA) with cyclosporin A (CsA) has been successful, but the adverse effects of the drug have limited its use. We investigated the capacity of another immunosuppressive agent, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], to augment the effects of CsA on in vitro T cell functions. Exposure of CD4+ cells from RA patients or from normal subjects to either molecule alone resulted in a dose-dependent inhibition of phytohemagglutinin stimulation and interleukin-2 (IL-2) production that was more pronounced in cells from RA patients than in cells from normal subjects. Moreover, the action of CsA and 1,25(OH)2D3 on RA patient T cell functions in vitro was synergistic. Thus, in the presence of the vitamin D3 metabolite, only one-hundredth the concentration of CsA was required to produce the same effect on IL-2 production as that produced by CsA alone. IL-2 receptor expression was also reduced by the addition of both drugs. In contrast, IL-1 production by RA monocytes was not affected by CsA and 1,25(OH)2D3, either together or alone, and addition of IL-1 did not restore the ability of CD4+ cells from RA patients to secrete IL-2. Exogenous IL-2 reversed a large part of the inhibitory effect induced by both CsA and 1,25(OH)2D3, indicating that the immunosuppressive properties of these agents are mediated by the inhibition of IL-2 secretion. This synergy between 2 molecules that are biochemically very different suggests the existence of one or several sites of interaction that take place during the early stages of T cell activation. | |
| 3213662 | Realignment and surgical fixation of atlanto-axial and subaxial dislocations in rheumatoid | 1988 | One hundred consecutive patients with atlanto-axial dislocation(s) were subjected to posterior occipito-cervical fusion and followed up to 16 1/2 years postoperatively (mean: 4 1/2 years). The mean age at surgery was 60.3 years. At the time of follow-up, 45 patients had died, mostly due to cardiopulmonary disease. Out of the 100 patients, 67% showed a major improvement and in an additional 14% there was a slight or moderate improvement. Some patients with a stable fusion later developed subaxial dislocation(s) necessitating an anterior fusion which in patients with RA is difficult due to poor bone quality. MRI revealed pannus formation around the odontoid peg in many patients, in several to such a degree that cord compression was evident. Following the posterior fixation, the pannus disappeared or was reduced which may at least partly explain the generally favourable operative outcome following the fixation procedure. Early occipito-cervical fusion appears to prevent further vertical dislocation or upwards migration of the odontoid which is a more severe condition, and does not appear to result in increased incidence of subsequent subaxial dislocation(s). Such luxation(s) pose a technically difficult problem since the quality of the patients' own bone usually does not permit a common anterior fusion procedure with autologous graft. In such cases with cord compression, acrylic cement may be used to obtain a normalized realignment. | |
| 2705507 | The proinflammatory effect of intra-articular injection of soluble human and venom phospho | 1989 Apr | The proinflammatory effects of intra-articular injection of purified phospholipase A2 from snake venom and rheumatoid synovial fluid were studied in rats. Purified soluble phospholipase A2 (PLA2) in concentrations ranging from 1000 to 20,000 units/ml, was injected intra-articularly. Histologic parameters examined were cell and protein content of synovial fluid, subsynovial cellular infiltration, synovial lining cell hyperplasia, bone erosion, and peri-articular soft tissue infiltration. Single intra-articular injections of PLA2 resulted in an acute inflammatory infiltrate of the subsynovium with maximal changes seen 2 to 6 hours after injection. Acute inflammatory changes were dose-dependent. Joints injected repeatedly at 24-hour intervals showed prominent synovial lining cell hyperplasia, maximal at 96 hours. Human synovial and snake venom PLA2s were equipotent at inducing both the acute and chronic articular changes. These changes were not seen in joints injected with inactivated PLA2. It is concluded that soluble PLA2 causes time- and dose-dependent acute inflammatory changes after a single intra-articular injection and synovial lining cell hyperplasia in response to repeated exposure to PLA2. The experimental proliferative synovitis in this model may correlate with features of acutely inflammed joints bathed in synovial fluids containing high levels of PLA2 in patients with rheumatoid arthritis. | |
| 3075178 | Calcitonin versus cimetidine or De-Nol in gastric ulcer treatment. An endoscopically contr | 1988 | 110 patients with benign gastric ulcer and concomitant joint diseases (rheumatoid arthritis, osteoarthrosis) were treated in a comparative short-term clinical trial to assess the relative efficacy of calcitonin (daily 100 MRC of salmon calcitonin intramuscularly), cimetidine (daily 1000 mg orally) and colloidal bismuth subcitrate (De-Nol-four times a day in doses of 5 ml diluted with 15 ml of water). Groups of patients were comparable according to age, sex, duration of ulcer disease, smoking habits, gastric acid secretion and mean ulcer size. The ulcer healing was controlled endoscopically after 2 and 4 weeks of the treatment. There was no significant difference in the ulcer healing rate between three groups neither after 2 weeks (calcitonin-36.7% of healed ulcers, cimetidine-37.5% and De-Nol-35.0% nor after 4 weeks respectively (76.7%, 72.5% and 77.5%). In the calcitonin group a gradual joint pain relief was observed in 84% of patients who complained arthralgia. The moderate side effects (headache, nausea, flush) were observed only in the patients treated with calcitonin (8 subjects). We suggest that calcitonin may be considered as a valid anti-ulcer drug in the peptic ulcer patients with concomitant rheumatological diseases especially with osteoporosis. | |
| 1776991 | Antibodies to tubulin and microtubule-associated proteins. A study in diabetes mellitus, s | 1991 Oct | We report the results of a study of serum antibodies to proteins of the nerve cytoskeleton in patients with Type I and Type II diabetes mellitus, both with and without clinical signs of diabetic neuropathy. In contrast to previous reports, elevated levels of antibody to tubulin or glycated tubulin were not associated with either diabetes or diabetes with related neuropathy. Similarly, clinical evidence of neuropathy in patients with diabetes did not relate to increased levels of antibody to native or glycated microtubule-associated proteins (MAPs). The levels of antibody to MAPs and glycated MAPs were higher in control subjects over the age of 45 years compared with younger control subjects. Increased levels of antibody to tubulin and glycated tubulin were found in the sera of patients with systemic lupus erythematosus, but not rheumatoid arthritis. | |
| 3260837 | HLA-DR-associated isotype-specific regulation of antibody levels to mycobacteria in rheuma | 1988 Apr | Using sera from 75 healthy donors, 68 rheumatoid arthritis (RA) patients, and 85 tuberculosis (TB) patients, we have examined the level of antibody of the three major classes binding to seven mycobacterial species, and to three control antigens. The major findings are that IgM binding to mycobacteria is reduced in RA patients who have HLA-DR7 (P = 0.008 for M. tuberculosis antigen), and that IgA binding to mycobacteria is reduced in RA patients who have HLA-DR2 (P = 0.007 for M. tuberculosis; P = 0.0004 for M. nonchromogenicum). These associations were not seen in TB, and were restricted to these antibody isotypes. We believe this is the first report of isotype specific Class II MHC-associated regulation of antibody levels in man. A possible interpretation of our data is that patients bearing these haplotypes are recognizing suppressor epitopes common to all the mycobacterial species tested. Since DR2 and DR7 have recently been shown to be associated with a significantly reduced risk of RA, our findings are compatible with the view that changes in immune responsiveness to mycobacterial antigens, or to autoantigens which cross-react with them, are relevant to RA. | |
| 3765223 | [Diclofenac-Na--an alternative treatment possibility in therapy-resistant calcium oxalate | 1986 Jul | In a prospective study, the influence of sole Diclofenac-Na therapy (3 X 25 mg Rewodina, Voltaren) on the calculus recurrence rate of eight frequently relapsing and therapy resistant calcium-oxalate stone patients is analysed. During a period of one year's treatment, the recurrence rate could be reduced by 73.2%, from 123 to 33 calculi. Serious side effects, changes in blood serological parameters and various urine components were not observed. The course of passages of calculi was improved by reduced pain and rapid passage. The paper summarizes all results of calcium-oxalate stone treatments with nonsteroidal antiphlogistics known so far. In the opinion of the authors, the present successful Diclofenac-Na treatment offers a novel possibility of influencing therapy resistant stone-formers over long periods. | |
| 1829302 | [Acetabular convexity--a specific addition to total endoprosthetic hip replacement]. | 1991 Mar | Between 1. 1. 1977 and 30. 6. 1988, 1470 total hip prostheses were implanted at the 1st Orthopedic Clinic in Bad Abbach/Regensburg. In 101 cases (82 patients, average age 54.8 years) the acetabular convexity was built up at the same time. This is considered indicated if the acetabulum is too shallow and thus provides insufficient lateral or dorsolateral countersupport. The main area of indication is dysplasia-coxarthrosis and congenital dislocation of the hip, destructive coxitis in chronic polyarthritis or juvenile chronic arthritis, and loosened prostheses. The material used for building up the convexity is a block of corticocancellous bone, which is fixed ventrolaterally to dorsolaterally to the ilium by osteosynthesis. Autologous material was used in 88 cases and homologous material in 13. Sixty-one patients with a total of 77 built-up convexities were followed up. In 92.2% a bony bridge between the corticocancellous block and the rising branch of the ilium was fund. The method described is a valuable addition to replacements in case of extreme hip joint changes and replacement operations. In the authors' opinion it has considerable advantages over supporting shells and similar materials. | |
| 3261188 | Gram-negative bacteria, HLA-B27 and inflammatory bowel disease. | 1988 | Lymphocytes from 48 IBD patients including nine with HLA-B27 were examined for their capacity to absorb Y.enterocolitica 0:9 antiserum. They possessed a range of absorption ability which was unconnected with HLA-B27 status. Samples of lymphocytes from 28 AS patients, 10 RA patients and 28 normal control subjects were included for comparison. The significance of the findings is discussed. | |
| 2805829 | Elevated BAL fluid histamine levels and parenchymal pulmonary disease in rheumatoid arthri | 1989 Nov | To determine the amount of histamine in BAL fluid in subjects with RA and to ascertain if elevated histamine levels were associated with parameters of active pulmonary disease, we measured BAL fluid histamine levels in 31 subjects with RA and 36 normal subjects. The subjects with RA had a significantly greater mean BAL histamine level than the normal subjects, (313 +/- 154 pg/ml vs 18 +/- 8 pg/ml; p less than 0.05). When the subjects with RA were divided into three groups based on chest radiograms (1 = normal; 2 = pleural disease only; 3 = interstitial or nodular disease), we found that subjects in group 3 had significantly lower values for TLC and D. Subjects in group 3 also had higher percentages of BAL neutrophils and eosinophils and higher BAL histamine levels (group 1, 115 +/- 52 pg/ml; group 2, 30 +/- 30 pg/ml; and group 3, 1,182 +/- 709 pg of histamine per milliliter). Moreover, BAL histamine levels were negatively correlated with TLC (r = -0.46; p = 0.01) and FVC (r = -0.45; p = 0.01) and positively correlated with BAL neutrophils (r = 0.6; p = 0.0003) and BAL eosinophils (r = 0.89; p = 0.0001). These data suggest that the BAL histamine level may be a useful marker to determine the activity of pulmonary disease in RA. | |
| 3350348 | Neck pain in the elderly: common causes and management. | 1988 Apr | Neck pain is common in the elderly. An outline of the relevant anatomy and pathological conditions which affect the cervical spine and an approach to diagnosis are presented. Intrinsic causes of pain arise in the vertebral column itself--arthritis, discogenic disorders, trauma, tumors, and infection; in the cervical musculature--myofascial pain syndrome, torticollis, and whiplash; and in the spinal cord from tumors. Differentiation of these causes from extrinsic causes of neck pain will enable the appropriate management protocols to be implemented. Many of these problems can be treated effectively at the primary care level. Guidelines for specialist referral are suggested. | |
| 1659460 | Characterization of a gelatinase from human rheumatoid synovial fluid cells. | 1991 Aug | A metalloproteinase with a specificity for gelatin was isolated from serum-free medium of cultures of rheumatoid synovial fluid. The enzyme showed all the properties of a leukocyte gelatinase. In addition to gelatin this proteinase cleaved the synthetic substrate dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg (Dnp-peptide) rapidly, while casein was a much poorer substrate. This proteinase showed no enzymatic activity against collagen type I, was secreted in a latent form and could be activated by trypsin or organomercurial compounds, such as mersalylic acid or 4-aminophenyl-mercury acetate. The latent enzyme had an apparent molecular mass of 130,000-150,000 estimated by gel filtration or 97,000 by electrophoresis on polyacrylamide gel containing sodium dodecyl sulphate. When analysed by immunoblotting the enzyme was recognized by antibodies raised against human polymorphonuclear leukocyte gelatinase. Although we found synovial fibroblasts to be largely present in the cell cultures we could not detect any fibroblast gelatinase activity. | |
| 2777241 | Eosinophilic products lead to myocardial damage. | 1989 Sep | Eosinophils have been associated with endomyocardial fibrosis. However, their effect on the myocardium and the reactions they elicit have not been emphasized. We describe four patients with extensive myocardial eosinophilic infiltration with and without endomyocardial fibrosis. Patients with a short duration of disease had eosinophilic infiltrates, myocardial eosinophilic abscesses containing granular eosinophilic material, and/or Charcot-Leyden crystals with and without profuse histiocytic and giant cell reaction with granuloma formation. In the early phase, the granular eosinophilic material can be visualized by the Luna stain and/or by electron microscopic examination. In patients with a long duration of symptoms, well-developed granulomas and profuse fibrosis are seen and eosinophilic material may not be visualized. Toxic eosinophil granular protein may be involved in the development of these lesions. | |
| 1673814 | [Effect of sulfasalazine and its metabolites on prostaglandin and leukotriene liberation f | 1991 | The effects of sulfasalazine (SASP) and its metabolites sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA) were investigated on release of prostaglandins (PG) and leukotrienes (LT) from synovial tissue of 37 patients with osteoarthritis, chondrocalcinosis and rheumatoid arthritis. Calcium ionophore A23187 significantly increased the release of PGE2, 6-keto-PGF1 alpha, LTB4, and LTC4 from human synovial tissue irrespective of the underlying joint disease. SASP inhibited release of LTC4 and increased release of PGE2. On the other hand, 5-ASA and SP inhibited the release of all eicosanoids measured. The effective concentrations of SASP and SP were found to be in the range which can be reached during SASP therapy. On the other hand, blood and synovial fluid levels of 5-ASA are considerably lower than those which inhibit eicosanoid synthesis in vitro. While nonsteroidal anti-inflammatory drugs, which are used for symptomatic therapy of rheumatoid arthritis, inhibit cyclooxygenase only, SP, the active metabolite of the second line anti-rheumatic drug SASP, inhibits both PG and LT release. Inhibition of LT synthesis by SASP and SP could contribute to the second line efficacy of SASP therapy in rheumatoid arthritis. | |
| 3547657 | Gold lung: recent developments in pathogenesis, diagnosis, and therapy. | 1987 Feb | Gold lung is a hypersensitivity pneumonitis to gold-containing compounds. It can be distinguished from rheumatoid lung by its subacute or acute onset, diffuse interstitial and/or alveolar filling pattern on chest roentgenogram, presence of lymphocytes on BAL with an inverse helper/suppressor ratio, and response to withdrawal of gold and/or corticosteroid therapy. Other in vitro assays of gold hypersensitivity using peripheral blood lymphocytes are only sporadically positive and, therefore, of limited value in making the diagnosis. Physicians prescribing organic gold compounds should elicit pulmonary complaints throughout the duration of therapy. When patients receiving gold therapy present with signs and symptoms consistent with an acute or subacute hypersensitivity pneumonitis, the gold therapy should be withheld and a diagnostic workup initiated. | |
| 3538948 | [D-penicillamine and collagen]. | 1986 | D-penicillamin is widely used for the treatment of various diseases, such as cystinuria. Wilson's disease or rheumatoid arthritis. It is an osteolathyrogenic agent. This effect may explain some side-effects such as fetal dysplasias, wound healing defects, skin lesions, obliterative bronchiolitis, auto-immune abnormalities. Conversely the collagen effects of D-Penicillamin explain its use in various fibrosis states such as progressive systemic sclerosis, liver or lung fibrosis. | |
| 1712684 | T cell interactions in active rheumatoid arthritis: insights from the human autologous mix | 1991 Jul | The autologous mixed lymphocyte reaction (AMLR) represents the activation, proliferation and differentiation of T cells in response to signals from autologous non-T cells. Using monoclonal anti-Leu8 antibody to isolate subpopulations of human CD4+ and CD8+ T cells, we have investigated the role of these subpopulations in the T cell activation cascade during the course of AMLR. In normal subjects, CD4+Leu8+ cells are necessary for the initiation of the AMLR response, and sequentially lead to activation and proliferation of both CD4+Leu8- cells and CD8+Leu8+ cells. The activated CD8+Leu8+ cells, in turn, induce CD8+Leu8- cells to generate proliferation of the latter cells. Soluble mediators could be involved in the T cell activation cascade induced by the AMLR. Patients with active rheumatoid arthritis have a profound defect in the AMLR. Further analysis indicates that rheumatoid arthritis CD8+ T cells are markedly defective as responding cells in the AMLR. The impaired AMLR response by CD8+ cells cannot be reconstituted with AMLR-derived supernatants from normal T cells. The data suggest that the defective CD8+ T cell function may contribute to the pathogenesis of the disease. | |
| 2258613 | Analysis of IL-1 and TNF-alpha gene expression in human rheumatoid synoviocytes and normal | 1990 Dec 15 | Human IL-1 alpha, IL-1 beta, and TNF-alpha mRNA expression was examined in peripheral blood monocytes (PBM) from normal individuals and in primary synoviocytes isolated from patients with rheumatoid arthritis by Northern blot and in situ hybridization. Cells cultured in the presence or absence of LPS were analyzed using in vitro synthesized 35S-labeled sense or antisense RNA probes to determine the relative abundance and the cell type expressing each of the mRNA for these potent inflammatory mediators. The results indicated that 72% of the LPS-stimulated PBM expressed detectable levels of IL-1 alpha mRNA, 89% IL-1 beta mRNA, and 10% TNF-alpha transcripts. Thus, the majority of activated PBM produced both IL-1 alpha and IL-1 beta. Experiments combining immunofluorescence for IL-1 beta protein with in situ hybridization for TNF-alpha mRNA demonstrated that monocytes expressing TNF-alpha mRNA also produced IL-1 beta. Primary synoviocytes from four patients with RA were also examined for the mRNA expression of each cytokine. Northern blot analyses of total RNA isolated from 0 to 72 h after LPS- or mock-stimulation showed that IL-1 beta mRNA was the most abundantly expressed, followed by TNF-alpha. In situ hybridization revealed that IL-1 beta and TNF-alpha transcripts were detected exclusively in synovial tissue macrophages. IL-1 alpha mRNA was not detected in these cultures by either method. | |
| 3383437 | Methyltransferase and phospholipase A2 activity in the cell membrane of neutrophils and ly | 1988 May 13 | Phospholipid methylation and phospholipase A2 activation in the membrane of neutrophils and lymphocytes, which participate in the induction of cell activation, were assessed in patients with Behçet's disease, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). [3H-methyl] incorporation and phospholipase A2 activity of neutrophils from active cases of Behçet's disease and RA were significantly increased compared with normal controls. In lymphocytes from the patients with active Behçet's disease and RA, a significant increase in methyltransferase activity and a marked enhancement of phospholipase activity were found. A modest increase in these two membrane phospholipid enzyme activities was observed in lymphocytes of patients with active SLE. In addition, these enzyme activities were significantly enhanced in normal leukocytes preincubated with serum from patients with active SLE and malignant RA. The potentiated functions of neutrophils and lymphocyte abnormalities in the patients tested thus seem to be at least partly due to an increase in these enzymatic activities in the cell membrane. |