Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2803323 | Electron microscopic analysis of sequential liver biopsy samples from patients with rheuma | 1989 Oct | We used electron microscopy (EM) to analyze 52 biopsy samples from 22 patients who were receiving long-term weekly oral doses of methotrexate (MTX) for the treatment of rheumatoid arthritis. Forty-eight biopsy samples were obtained after 2-6 years of continuous treatment, and 4 samples were obtained before treatment was begun. Specimens were graded for neutral fat, secondary and tertiary lysosomes, and smooth endoplasmic reticulum (SER) in hepatocytes, and for collagen in the perisinusoidal space (Disse's space). We examined the correlations between the EM findings and the light microscopic (LM) findings in the same biopsy specimens, and between the EM findings and the results of simultaneous monthly measures of aspartate transaminase, alkaline phosphatase, bilirubin, and albumin levels, as well as history of alcohol consumption before MTX treatment and monthly assessments of clinical status during the course of treatment. The presence of collagen was minimally increased in these sequential biopsy samples, whereas fat, lysosomes, and SER were decreased. The SER decrease was statistically significant. EM findings of collagen in the space of Disse did not correlate with early fibrotic changes observed with LM. Thus, after as long as 6 years of weekly oral treatment with MTX, hepatic ultrastructural changes are minimal and are not clinically significant. The use of EM for sequential biopsy studies allows the quantitation of long-term hepatic changes that may be more limited than the impression gained after LM analysis. | |
| 1768159 | Inactivation of the elastase inhibitory activity of alpha 1 antitrypsin in fresh samples o | 1991 Dec | The proteinase inhibitory ability of alpha 1 antitrypsin was measured in 23 samples of rheumatoid arthritis synovial fluid, eight osteoarthritic synovial fluids and nine normal control serum samples. For each sample a detailed kinetic analysis was performed with porcine pancreatic elastase as the target proteinase. Samples were stored for less than 24 hours at 4 degrees C before analysis, which does not significantly alter the proportion of inactive alpha 1 antitrypsin. In rheumatoid synovial fluid the elastase inhibitory ability was disproportionately depressed relative to the immunochemically determined concentrations of alpha 1 antitrypsin. | |
| 2612117 | Anticardiolipin antibodies in patients with rheumatoid arthritis. | 1989 Dec | Anticardiolipin antibodies (ACA) were assayed by ELISA in 73 patients with rheumatoid arthritis. Twelve (16.48%) patients showed levels of ACA three standard deviations above the value of the control group and were considered positive; these patients were compared to the group with ACA within the normal levels regarding the following clinical and laboratorial characteristics: spontaneous abortions, central nervous system involvement, systematization and activity of disease, alterations in platelet counts, presence of antinuclear antibodies and rheumatoid factor. Significant statistical association could be demonstrated between systematization and presence of antinuclear antibodies (ANA) and positiveness to ACA (IgG, IgM or both). These findings might indicate that ACA in patients with RA could have relevance to morbidity of disease or perhaps to its pathogenesis. | |
| 3092816 | Induction of mammalian stress proteins by a triethylphosphine gold compound used in the th | 1986 Aug 14 | In vitro exposure of cultured human, murine and rat cells to pharmacologic concentrations (10(-8) to 10(-6) M) of auranofin, 2,3,4,6,-tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S- triethylphosphine gold(I) (Ridaura), a gold containing compound approved for the treatment of rheumatoid arthritis, results in the induction of several stress proteins. The enhanced synthesis of two polypeptides, p32 and p34, was particularly prominent. A similar response was observed in freshly collected human monocytes challenged with auranofin. In addition, oral administration of auranofin to rats induced enhanced synthesis of a 32-kDa protein in peritoneal exudate cells analyzed ex vivo at various times following drug treatment. These data suggest that increased synthesis of p32 and p34 might participate in mediating certain aspects of auranofin pharmacology. | |
| 2357201 | [Follow-up of patients with knee endoprostheses of the orthopedic clinic of the Dresden "C | 1990 Jan | A report is given about an examination of 143 knee prostheses which were implanted between 1973 bis 1983. After biomechanic points of view the used prostheses were divided in four types. Very good to good results were found there in 70-80% of cases. Most positive results were reached by the so called sledge prostheses. In 44% of cases there were observed complications. The rate of complications is about 12% higher by patients whose basic disease is pcP. | |
| 2138877 | Analysis of lymphocyte subsets of bone marrow in patients with rheumatoid arthritis by two | 1990 Mar | Lymphocyte subsets defined by monoclonal antibodies were investigated in bone marrow and peripheral blood of 17 patients with rheumatoid arthritis (RA); 13 patients with osteoarthritis or aseptic necrosis served as controls. Patients with RA were found to have a raised OKT 4/8 ratio both in bone marrow and peripheral blood in comparison with the controls. Furthermore, bone marrow of RA showed a lower percentage of OKT 8+ T cells than that of controls. The percentage of HLA-DR+ T cells was higher in bone marrow than in peripheral blood of RA, though a slightly lower percentage was detected in bone marrow than in peripheral blood of controls. Thus T cell subsets in bone marrow of RA differ significantly from those of controls. Patients with RA had a higher OKT 4/8 ratio and a higher percentage of HLA-DR+ T cells in bone marrow than controls, suggesting that T cell subsets in bone marrow of RA are in an immunologically activated state and that T cell subsets are affected by rheumatoid inflammation in bone marrow of RA. | |
| 3148711 | Multiple cytokine activities and loss of interleukin 2 inhibitor in synovial fluids of pat | 1988 Nov | Attempts to detect immune mediators in rheumatoid arthritis synovial fluids (RA-SF) by bioassays have yielded conflicting results, and so we analyzed the immune reactions occurring within rheumatoid joints using monospecific immunoassays for cytokines such as interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2) and gamma interferon (gamma-IFN). Furthermore, we examined the IL-2 inhibitors to clarify the immunoregulatory mechanism in the lesion. SF from active RA contained a significant amount of IL-1 beta and IL-2 but not gamma-IFN. In contrast IL-2 inhibitor activity was depressed in RA-SF regardless of clinical disease activity. Our results suggest that cytokine overproduction and deficiency of inhibitory signals may result in the overactivity of cytokines and the overactivity may participate in the joint lesions of RA. | |
| 2439090 | The immunologic detection and characterization of cartilage proteoglycan degradation produ | 1987 May | Antibodies were used in radioimmunoassays with gel chromatography to detect the hyaluronic acid-binding region, core protein, and keratan sulfate of human cartilage proteoglycan in the synovial fluids of patients with rheumatoid arthritis, juvenile rheumatoid arthritis, and osteoarthritis. All fluids contained proteoglycan that was mainly included on Sepharose CL-4B; this result indicates cleavage of proteoglycan (which is normally excluded). The hyaluronic acid-binding region was the smallest and most commonly detected fragment. It was relatively free of keratan sulfate and core protein, and it could sometimes bind to hyaluronic acid. Other larger fragments containing core protein and/or keratan sulfate were detected in every fluid. | |
| 3104558 | Immunoglobulin-producing cells in labial salivary glands of patients with rheumatoid arthr | 1986 Nov | The distribution of immunoglobulin-producing cells within labial salivary glands from normal individuals (n = 7) and patients with rheumatoid arthritis (n = 10) and systemic lupus erythematosus (n = 9) was studied using morphometric and indirect immunoperoxidase methods. Cell counts revealed a significant increase in the density of IgG cells within glands from both patient groups compared with glands from normal individuals. No significant differences in the density of IgA- or IgM-producing cells between the 3 groups were observed although large individual variations were apparent. Histomorphometric studies showed an increase in the lymphoid compartment and a decrease in glandular elements within glands from the 2 patient groups. When data for all specimens were pooled a significant positive correlation was obtained between the percent area of stromal lymphoid tissue and density of IgG and IgM cells. | |
| 3067924 | A comparative analysis of two dosing strategies of flurbiprofen in rheumatoid arthritis: a | 1988 Dec | Forty patients with classic or definite rheumatoid arthritis were entered into a double-blind, randomized, multiple crossover, sequential trial comparing two doses (300 mg vs 150 mg per day) and two dosing schedules (b.i.d. vs t.i.d.) of flurbiprofen. Clinical assessments (Ritchie Index, grip strength, walking time, physician and patient global assessments) were made at baseline and at biweekly intervals during the next six weeks of active treatment. Overall there were no statistically significant differences either between the two dosage levels or the dosing schedules. This study demonstrates the utility of the sequential trial design in assessing drug efficacy. The data confirm a lack of difference between the two doses of flurbiprofen selected and suggest that twice-daily dosing with flurbiprofen is similar in efficacy to thrice-daily dosing. | |
| 3293863 | Cellular immune responses to cartilage components in rheumatoid arthritis and osteoarthrit | 1988 Jan | Proliferative responses of peripheral blood mononuclear cells of rheumatoid or osteoarthritis patients and normal controls stimulated with cartilage components were studied. Two components not studied in previous cellular studies, matrix proteins (fraction A4) and lipoproteins, were used as well as whole extract of cartilage, native and denatured collagen, and proteoglycans. In general, osteoarthritis cells responded less well than the other two groups; this was statistically significant for fraction A4-matrix protein (normal p less than .02, rheumatoid arthritis p less than .025). Fraction A4 sterilized by filtration rather than irradiation gave higher responses in both arthritic groups, but not controls. Antigenic alteration by radiation may explain this difference and, perhaps, the low level of proliferation to all the components seen. The possible role of such cell-mediated responses in chronic arthritis is discussed, and the current and previous reports of cartilage component-induced cellular responses are reviewed. | |
| 2900853 | The association of DNA variants at or near the IgH locus with rheumatoid arthritis. | 1987 Aug | DNA samples from 78 patients with classical or definite rheumatoid arthritis (RA) and 132 healthy controls were analysed by the Southern blotting method, using two DNA probes: the first to the immunoglobulin mu heavy-chain switch region (S mu), in conjunction with the SstI restriction endonuclease, and the second to the D14S1 region, in conjunction with the HindIII restriction endonuclease. The homozygous phenotype for the 6.9 kb S mu fragment was decreased in the patient group (7.8%) compared to controls (19.1%) (P = 0.04). The homozygous phenotype for the 10.3 kb D14S1 fragment was increased in the patient group (38.5%) compared to controls (21.2%) (P = 0.02). The increase was more pronounced in the DR4-positive patients (51.2%) (P versus DR4-positive controls = 0.009). These results suggest that genes on chromosome 14 are involved in the genetics of RA. | |
| 2113103 | Cost-effectiveness of misoprostol for prophylaxis against nonsteroidal anti-inflammatory d | 1990 Jul 4 | Patients who take nonsteroidal anti-inflammatory drugs (NSAIDs) are at increased risk of upper gastrointestinal tract bleeding, which may be prevented with prophylactic prescription of misoprostol. Using data from the literature, we estimated rates of gastrointestinal tract bleeding in NSAID users, direct medical costs, years of life lost, and cost-effectiveness of a 1-year course of misoprostol in three clinical populations of NSAID users: all users, users aged 60 years or older, and users with rheumatoid arthritis. The incremental cost-effectiveness ratios for misoprostol as primary prevention were $667,400 per year of life saved for all NSAID users; $186,700 per year of life saved for users aged 60 years or older; and $95,600 per year of life saved for users with rheumatoid arthritis. Misoprostol as secondary prevention for those who continued to take NSAIDs despite having had an episode of gastrointestinal tract bleeding in the previous year was associated with incremental cost-effectiveness ratios less than $40,000 per year of life saved in all patient groups. We conclude that misoprostol is costly as primary prevention for NSAID-induced gastrointestinal tract bleeding in the groups examined but may be cost-effective as secondary prevention in patients with a proved history of gastrointestinal tract bleeding. | |
| 3582479 | Salicyl phenolic glucuronide pharmacokinetics in patients with rheumatoid arthritis. | 1987 | The pharmacokinetics of salicyl phenolic glucuronide (SPG) and other salicylic acid (SA) metabolites were studied at three aspirin dosage regimens in eight patients with rheumatoid arthritis. Each patient received 1, 2 and 4 g enteric coated aspirin (ASA) daily in ascending order. At the end of each 2-week dosage period, plasma and urine were collected over a dosage interval for the estimation of various pharmacokinetic parameters. With increasing ASA dosage, mean clearance of SA to SPG was approximately constant (1.8 +/- 0.3, 1.7 +/- 0.2, and 1.5 +/- 0.2 ml/min at 1, 2 and 4 g/day, respectively) when related to plasma concentrations of total SA. The percentage of the ASA dosage recovered in urine as SPG increased from 5.2 +/- 1.1 to 7.1 +/- 1.1 to 10.5 +/- 1.7 at 1, 2 and 4 g/day, respectively. It was concluded, however, that the conversion of SA to SPG is saturable, since the mean clearance of SA to SPG decreased when calculated with respect to the plasma concentration of unbound SA (13.4 +/- 1.6, 11.0 +/- 1.4, and 6.6 +/- 1.9 ml/min at 1, 2 and 4 g/day, respectively). The kinetics of the formation and excretion of salicylurate and the excretion of gentisate were similar to those found in previous studies. | |
| 1948096 | The efficacy and safety of low-dose corticosteroids for rheumatoid arthritis. | 1991 Aug | Low-dose corticosteroids (defined as less than or equal to 10 mg/d of prednisone or equivalent) are used increasingly for the management of rheumatoid arthritis. They are frequently substituted for nonsteroidal antiinflammatory drugs (NSAIDs), particularly in patients with gastrointestinal or other intolerance to NSAIDs, or as "bridge therapy" while patients await the benefits of delayed-acting, disease-modifying agents. Despite their clinical acceptance, published data concerning efficacy are meager. Adverse effects to low-dose corticosteroids are not so frequent nor so severe as those that occur with higher doses. Nevertheless, alterations in glucose metabolism, cutaneous atrophy, cataracts, and glaucoma are common. Osteoporosis, steroid-myopathy, a steroid-withdrawal syndrome, and dysfunction of the hypothalamic-pituitary-adrenal axis appear in some patients. Osteonecrosis, gastrointestinal, cardiovascular, infectious, or neurological complications probably do not occur. Fetal wastage, prematurity, or congenital malformations have not been proven with this dosage. | |
| 3716509 | [Diagnostic and prognostic significance of so-called rheumatoid vasculitis--2]. | 1986 Mar 15 | 51 patients with rheumatoid arthritis and high rheumatoid factors (mean titres 928) underwent examination for the demonstration of an extraarticular organ manifestation within the scope of the cooperation between the Department of Medicine of the Karl-Marx-University Leipzig and the Institute for Rheumatology of the Academy of Medical Sciences of the USSR in Moscow. The frequency of nodous rheumatism (about 60%) is comparable with the frequency of polyneuropathy. In 20% of the patients a systemic muscle atrophy, a hepatomegaly as well as a Raynaud-syndrome were stated. By means of skin biopsy in 28% perivascular infiltrates were found. Altogether in 6 patients (12%) a participation of the lungs and the pleura, respectively, could be proved. Only rarely a clinically manifest heart disease caused by the rheu-we we found an pericardial effusions in 3 cases. In systemic manifestation, such as myositis, participation of the eyes or vasculitis of the digital arteries with necrosis, were only sporadically to be established. Among 22 patients we found an pericardial effusions in 3 cases. In systemic manifestation in most cases increased parameters of activity were found. From the practical point of view apart from increased titers of the rheumatoid titres and circulating immune complexes (C1q-BT) increased concentrations of the C-reactive protein are prognostically significant. The presence of high rheumatoid factor titres alone as well as the isolated presence of rheumatic nodes must not always be connected with an unfavourable prognosis. When severe extraarticular manifestations are present a possibly early, intensive occasionally extracorporeal treatment is indicated. | |
| 3134690 | [Prospects in the treatment of rheumatoid polyarthritis]. | 1988 Apr 30 | Searching for new long-term treatments of rheumatoid arthritis (RA) is taking now different turns. It is a matter of trying molecules presenting a structural analogy with products considered as effective, either products with a more or less specific immuno-modulating ability, or natural substances involved in the immuno-pathological process of the RA. Among them, thymus hormone and interferon gamma have been the subject of controlled studies with results which are encouraging enough to pursue the investigations. Immunoglobulins of placental origin, the use of which has been justified by the frequent remissions of the disease during pregnancy, have given encouraging results. Finally, cyclosporin, in spite of its effectiveness, results in undesirable effects leading to a redefinition of its use. These studies require additional studies, especially long-term ones, in order to verify that these substances represent a definite improvement over the medications currently in use. | |
| 3041137 | Carboxypeptidase N (kininase I) activity in blood and synovial fluid from patients with ar | 1987 Sep 7 | Carboxypeptidase N (CPN, kininase I) and kininase II (angiotensin converting enzyme) activities were measured simultaneously in blood plasma and synovial fluid in patients suffering from rheumatoid arthritis (RA), psoriatic arthritis (PA) and osteoarthritis (OA) and in the plasma of normal volunteers. CPN levels (defined as the rate of hydrolysis of furylacryloyl-Ala-Lys) in blood were modestly increased and correlated with erythrocyte sedimentation rate in RA and PA. Based on the hydrolysis of synthetic substrates, CPN activity was much higher than kininase II activity in synovial fluid (SF). SF kininase activities were always inferior to the blood levels in all patients and were correlated with the logarithm of SF leukocyte counts, an indicator of the intensity of inflammation. In addition, CPN and albumin levels in SF were highly correlated when expressed as a percent of the plasma concentrations. Biochemical properties of CPN in crude SF confirmed its similarity to blood CPN. Polymorphonuclear leukocytes derived from inflammatory SF did not release CPN. It is concluded that kininases diffuse from the blood into SF through increased vascular permeability and that CPN could be a major metabolic pathway for kinins in this form of exudate. CPN leads to the formation of des-Arg kinins, selective agonists of the B1 receptors for kinins. | |
| 2797695 | [Results of treating the residual manifestations of uveitis of rheumatic and rheumatoid et | 1989 | The effect of a complex health resort treatment including eye applications of medical mud from the Sax lake has been studied in 100 patients (172 eyes) with residual effects after uveitis of rheumatic and rheumatoid etiology. Besides improvement of the general patient's state, the treatment provided a rise of visual functions, reduction of recurrences in remote terms. This effect can be, to a great extent, explained by antiinflammatory, resolving and desensitizing action of medical mud. The positive results obtained allow to recommend this method of treatment in conditions of a health resort and outside it (imported medical mud). | |
| 3746056 | Possible involvement of prostaglandin endoperoxides in cartilage-synovial interactions. | 1986 Jun | The depletion of proteoglycans in cartilage matrix is the beginning of cartilage breakdown. Prostaglandins and related compounds might play an important role in inhibition of cartilage metabolism under arthritic conditions. Prostaglandin endoperoxides, intermediate metabolites of arachidonic acid, are more potent chemical mediators than prostaglandins, but their action can only be demonstrated in cartilage co-incubated with synovial tissue, because they are short-lived and active only within a small restricted space. Human rheumatoid synovialis highly inhibited sulfation of cartilage matrix co-incubated. The inhibition of cartilage metabolism was released by indomethacin added to the co-incubating system, showing its responsiveness to indomethacin. The magnitude of inhibition was time-dependent and substantially greater than that by prostaglandin in cell-free rheumatoid synovial culture media. The results suggest a possible involvement of prostaglandin endoperoxides in potent inhibition of cartilage metabolism under arthritic conditions. |