Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2406713 | Rheumatoid arthritis. Practical use of medications. | 1990 Feb 15 | The treatment of rheumatoid arthritis is undergoing steady change as new medications are approved and new regimens are attempted. Once the diagnosis is ensured, therapy should include appropriate rest, physical and occupational therapy, involvement of the family or a supportive caregiver, and, most important, participation of the patient. If the disease is not terribly aggressive, therapy with nonsteroidal anti-inflammatory drugs is appropriate initially. If no response is obtained within 2 to 3 weeks, a new dose or different nonsteroidal agent is recommended. In many patients, aspirin, particularly if enteric-coated, is successful and very cost-effective. Disease-modifying antirheumatic drugs (DMARDs) are sometimes being used earlier in disease than previously. Hydroxychloroquine sulfate (Plaquenil Sulfate), auranofin (Ridaura), or sulfasalazine (Azulfidine, S.A.S.-500) is sometimes effective for early rheumatoid arthritis. For patients with more aggressive disease, intramuscular gold is the drug of first choice, and it is the only one that has been shown to decrease the rate of formation of new erosions. Significant toxic reactions occur in 30% to 40% of patients, however. D-penicillamine (Cuprimine, Depen) and azathioprine (Imuran) can be used if intramuscular gold is unsuccessful. Methotrexate (Rheumatrex Dose Pack) is the newest DMARD approved for treatment of rheumatoid arthritis. Its onset of action is rapid, and it is an effective anti-inflammatory agent. Its toxicity in patients with rheumatoid arthritis is not yet fully understood, however. Combination therapy with DMARDs is in its infancy, but such treatment is likely to become more prevalent in the future. | |
| 2423091 | Stimulation of neovascularization by human rheumatoid synovial tissue macrophages. | 1986 Apr | Synovial tissue from patients with rheumatoid arthritis was enzymatically dissociated, and single cell suspensions were fractionated into subpopulations by centrifugation on continuous Percoll gradients. Five fractions (F1-F5) with densities of 0.991-0.998 gm/ml, 0.998-1.042 gm/ml, 1.042-1.062 gm/ml, 1.062-1.082 gm/ml, and 1.082-1.180 gm/ml, respectively, were prepared. F3 consistently contained the highest number of macrophages, while F2 and F4 contained substantially fewer macrophages. Macrophages present in F2, F3, and F4 were enriched by differential adherence to fibronectin-coated collagen gels. These macrophage-enriched cell preparations were found to be Fc and C3 positive, esterase positive, and peroxidase negative, to stain positively with anti-HLA-DR, anti-Leu-M3, OKM1, and OKM5 monoclonal antibodies, and to show characteristic features of macrophages by electron microscopy. Macrophages from F3 consistently induced neovascularization in rat corneas, while equal numbers of macrophages from F2 and F4 did not. Fibroblastic synovial cells and cells that did not adhere to fibronectin-coated collagen gels did not induce neovascularization. Within the rheumatoid synovium, there appears to be a major subpopulation of macrophages capable of inducing neovascularization, a process vital to the development of the rheumatoid synovial pannus. | |
| 3426290 | Xanthine oxidoreductase is present in human synovium. | 1987 Nov | It is postulated that the mobile inflamed joint may be subject to cyclical ischaemic reperfusion injury. Xanthine oxidoreductase is an enzyme thought to contribute to oxidative reperfusion injury, and the detection of this activity in human synovium is described. Three normal and five rheumatoid tissues were assayed with a carbon-14 radioassay detecting the conversion of [14C]xanthine to [14C]uric acid. Rheumatoid synovia contained 0.67-305 microU/g tissue (n = 5), while normal synovia contained 1.2-5.0 microU/g tissue (n = 3). | |
| 2323105 | Anti-class II beta-chain antibodies in the serum and synovial fluid of rheumatoid arthriti | 1990 May | Sera and synovial fluid (SF) from rheumatoid arthritis (RA) patients were evaluated for anti-HLA class II beta-chain antibodies using single and two-dimensional immunoblots. The antibodies from RA sera and SFs which reacted with class II beta-chain determinants were predominantly IgM and IgA with minimal IgG. This reactivity was also present in SFs from other rheumatic diseases. Anti-class II beta-chain antibodies were also shown to be present simultaneously in RA sera and SF. | |
| 3042078 | Antibodies to Klebsiella and Proteus microorganisms in ankylosing spondylitis and rheumato | 1988 | Antibodies to Klebsiella oxytoca and Proteus mirabilis in 21 active ankylosing spondylitis (AS), 13 active rheumatoid arthritis (RA), 19 inactive RA patients and 18 healthy controls were measured using enzyme-linked immunosorbent assay (ELISA). Elevated anti-Klebsiella antibodies were demonstrated in active AS patients compared to active RA (p less than 0.01), inactive RA patients (p less than 0.001) and controls (p less than 0.005). When measuring antibodies to Proteus, active RA patients showed higher levels of antibodies compared to active AS patients (p less than 0.005) and healthy controls (p less than 0.05). Further investigations are required to assess the role of Klebsiella and Proteus microorganisms in AS and RA respectively. | |
| 3382265 | Urinary proteoglycan degradation product excretion in patients with rheumatoid arthritis a | 1988 Jun | The excretion of sugar components of glycosaminoglycans in the urine was investigated in 19 healthy controls, 27 patients with rheumatoid arthritis, and 24 with osteoarthritis. Both groups of patients excreted significantly more glucosamine, galactosamine, and mannose than the controls. The total uronic acid excretion, also, was higher in the two groups than in the healthy subjects. The possibility of using this method for the long term follow up of rheumatoid arthritis and osteoarthritis and the response to treatment is discussed. | |
| 2447181 | Identification of the DRw10 DR beta 1-chain allele as encoding a polymorphic class II majo | 1988 Jan 15 | Although the polymorphic human Ia epitope recognized by monoclonal antibody 109d6 typically is expressed by DRw53 beta 2 chains, the epitope was shown to be encoded by distinctive DR beta 1 chains of a DRw10 haplotype in three unrelated DR4-negative individuals with rheumatoid arthritis. No evidence of a DR beta 2 (DR beta 4) chain molecule was found to be encoded by this haplotype. Using two-dimensional gel analysis and partial radioactive N-terminal microsequencing, the DR and DQ products were characterized in the heterozygous members of a family in which the segregation of both varieties of DR beta chains specifying the 109d6 epitope was demonstrated. The expression of the epitope on the DR beta 2 chain, but not on the DR beta 1 chain, was abolished by preventing N-linked glycosylation, although in both molecules the epitope was not altered by neuraminidase digestion. The potential structural bases of the serologic cross reactions of DRw10 are discussed, as are the possible implications of the findings for the definition of susceptibility to rheumatoid arthritis. | |
| 3594990 | Hinged knee replacement in revision arthroplasty. | 1987 Jul | Fifty-two Stanmore hinged knee replacements were used as revision arthroplasties for failed arthroplasties. The patients were followed for a mean of 44.7 months. On clinical examination, 23% had good, 48% fair, and 29% poor results. Worst results were achieved when revising bulkier or more constrained primary knee joints. Two patients exhibited radiologic evidence of loosening, but at the latest follow-up examination no patients had clinical evidence of loosening. There was an infection rate of 4%. In view of the poor results and the advent of a new generation of knee arthroplasty devices, hinged knee implants may have only a limited place in revision arthroplasty. | |
| 3494687 | In vitro effect of alpha-interferon on mononuclear cells of normal and autoimmune patients | 1987 | The effect of lymphoblastoid interferon (IFN-alpha) on cell-mediated and humoral immunity was studied in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The base-line natural killer (NK) and antibody dependent cytotoxic cell (ADCC) activity was higher than normal in individuals with RA. The NK and ADCC activities were tested after IFN-alpha pretreatment and the augmentation of NK and ADCC activity was less in these patients than in normals. Lymphoblastoid IFN inhibited antigen induced T-cell proliferation in SLE to a lesser extent than in normal individuals. Finally, the addition of lymphoblastoid IFN was also less effective at suppressing in vitro polyclonal antibody formation by mononuclear cells from patients with SLE than from normals, with enhancement observed in some patients at the lower IFN-alpha concentrations tested. | |
| 2476268 | Coordinate expansion of 'fetal type' lymphocytes (TCR gamma delta+T and CD5+B) in rheumato | 1989 Aug | In the blood of 10 patients with rheumatoid arthritis (RA), the number of TCR gamma delta+T cells and CD5+B cells was 5.5% +/- 4.38 and 34.3% +/- 20.62 (mean +/- s.d.), respectively. In 12 patients with primary Sjögren's syndrome (SS) the mean +/- s.d. of these T and B cell subpopulations was 4.75% +/- 3.85 and 38.75% +/- 22.68. These values were significantly increased as compared with the circulating T and B cells from 22 healthy subjects in whom TCR gamma delta+T cells were 2.09 +/- 1.01 (P less than 0.001 for RA; P less than 0.004 for SS) and CD5+B cells were 18.09% +/- 4.47 (P less than 0.001 for RA and SS). This increase was not influenced by disease activity. Furthermore, there was a marked correlation (P less than 0.001) between the levels of TCR gamma delta +T cells and CD5+B cells. This novel finding of coordinate elevated levels of lymphocytes with fetal phenotypes in RA and primary SS suggests an immunological imbalance that may have implications in these diseases. | |
| 3209328 | Family history of autoimmune disorders and cancer in multiple myeloma. | 1988 Sep | To explore genetic mechanisms that might underlie the relation observed between multiple myeloma and rheumatoid arthritis, we examined the occurrence of autoimmune disorders in first-degree relatives of myeloma cases and controls. There was a significant excess of rheumatoid arthritis (OR = 3.7; 95% CI = 1.0-13.1) among the relatives of cases compared with controls, as well as an increased occurrence of systemic lupus erythematosus and pernicious anaemia. An excess of certain cancers was also observed among family members, including leukaemia and cancers of the breast, endometrium, and oral cavity and pharynx, but none of the excesses were significant. These findings deserve further evaluation in larger population-based studies. | |
| 2843297 | Free radicals, immunoglobulins and complement as mediators of inflammation. | 1988 Apr | There is evidence for both oxygen-centred free radicals and products of complement activation acting as mediators of inflammation. Evidence for the generation and reaction of free radicals at sites of inflammation can only be indirect and circumstantial due to their very transient nature. Evidence for complement activation in several inflammatory conditions, including rheumatoid arthritis is strong. These mediator classes individually possess a range of potential proinflammatory activities. Their effects may be linked through the formation of immune complexes and the activation of polymorphonuclear leukocytes. Their actions will also be linked with and modulated by the activities of other mediators mentioned only briefly in this chapter. The relative importance of the different mediators in any particular inflammatory condition is difficult to ascertain. The importance of free radicals and complement will be better understood when drugs specifically and unequivocally aimed at their control are identified. This potential for therapeutic advances in the treatment of inflammatory disorders has yet to be realized. | |
| 2185910 | HLA antigens in Yugoslav population with rheumatoid arthritis. | 1990 Mar | The antigens of HLA-DR locus were determined in 127 patients with rheumatoid arthritis and in 175 healthy persons. The frequency of HLA-DR1 antigen was discovered in 45% of the patients and in 22.3% of the examinees from the control group (p less than 0.001). The relative risk is 2.84. 69% of the patients were seropositive. The HLA-DR4 antigen was found in 34% of the patients and in 21% of the healthy examinees (p less than 0.05). The relative risk is 1.91. The rheumatoid factor was determined in 70% of the patients with this antigen. | |
| 3515527 | A double-blind placebo-controlled evaluation of fenflumizole in rheumatoid arthritis. | 1986 | Twenty-eight patients with active classical or definite rheumatoid arthritis were randomly allocated to treatment with fenflumizole 200 mg or 100 mg or placebo daily in a 2-week double-blind placebo-controlled study. Three patients dropped out and 25 patients completed the study. Ten patients received fenflumizole 100 mg daily, 7 patients received fenflumizole 200 mg daily and 8 patients received placebo. Clinical and laboratory assessments before and during the study revealed that in patients treated with fenflumizole, grip strength, morning stiffness and walking time improved significantly. No improvement could be seen in the placebo group. No side effects attributable to fenflumizole were observed during the study. | |
| 2724251 | Comparison between 3 diagnostic criteria for mixed connective tissue disease. Study of 593 | 1989 Mar | We tested patients with a well defined connective tissue disease (CTD) against 3 different sets of criteria for mixed connective tissue disease (MCTD). Included were 200 patients with systemic lupus erythematosus (SLE), 80 with MCTD, 100 with rheumatoid arthritis (RA), 80 with scleroderma, 53 with dermato/polymyositis (DM/PM) and 80 with primary Sjögren's syndrome (SS). The 3 sets of criteria fared similarly in capturing nearly all MCTD patients. They also were similar in ruling out most of the other CTD except for 11 patients with SLE, 36 with scleroderma, 13 with DM/PM and 3 with SS who fulfilled the category of possible MCTD included in the set of criteria proposed by Sharp. Because the set of criteria we proposed includes only 5 clinical manifestations (edema of the hands, synovitis, myositis, Raynaud's phenomenon, and acrosclerosis) whereas the other 2 sets include 15 and 13, respectively, it would seem that the 5 included in our criteria are core manifestations of MCTD. Of the 80 patients with MCTD 32 had all 5, 38 had 4, and 10 had 3 of these manifestations. The sensitivity of 3 or more of these clinical criteria for MCTD was 100%, whereas the specificity which, with the clinical criteria was 91.8%, rose to 99.6% with the presence of anti-RNP antibody. However, because testing of our criteria was made internally, they should be further tested, along with the other 2 sets of criteria by unrelated groups of clinical investigators, perhaps in a multicenter study. | |
| 3232037 | Proresid in the long-term treatment of rheumatoid arthritis. | 1988 | Drug withdrawal rate and reasons for treatment termination were studied in a retrospective life-table analysis of patients with rheumatoid arthritis prescribed Proresid, a semisynthetic podophyllotoxin derivative. Two years after starting with Proresid medication, half of the patients were still on treatment. After 5 years the termination rate had risen to 71%. Gastrointestinal side effects were the most common reason for abandoning medication. The results are compared with those found in other studies of similar desing. It is concluded that Proresid is a valuable and well-tolerated disease-modifying drug for long-term treatment of rheumatoid Arthritis. | |
| 2829280 | The metabolism of synthetic leukotriene B4 in synovial fluid and whole human blood. | 1987 Sep | The metabolism in vitro of synthetic leukotriene B4 (LTB4) in synovial fluid from rheumatoid arthritis and osteoarthritis patients and in whole blood from these same patient groups and from normal volunteers has been studied. A linear relationship existed between a plot of the time of incubation of samples with LTB4 and the percentage of the initial concentration of LTB4 at each time point. The slope of this line, the rate constant for metabolism, has been used to compare different samples. LTB4 was metabolised more rapidly in the synovial fluid of rheumatoid arthritis patients than osteoarthritis patients. Furthermore, LTB4 was metabolised more rapidly in the blood of rheumatoid arthritis patients than either osteoarthritis patients or normal volunteers. These differences in metabolism correlate with the polymorphonuclear leukocyte (PMN) and albumin content of samples. It is suggested that binding of LTB4 to albumin in vivo will in part determine the available concentration of LTB4 in inflammatory lesions. | |
| 2842805 | Measurement of sulfidopeptide leukotrienes and their metabolism in human synovial fluid of | 1988 Jun | Leukotriene (LT)C4 in the synovial fluid of patients with osteoarthritis deformans (OA) and rheumatoid arthritis (RA) was measured by radioimmunoassay (RIA) after extraction with Sep-Pak C18 cartridge. The amounts of immunoreactive LTC4 (i-LTC4) in samples from patients with OA and RA were not significantly different, being 0.198 +/- 0.018 pmol/ml (n = 11) and 0.179 +/- 0.016 pmol/ml (n = 12), respectively. After separation by high performance liquid chromatography (HPLC) and measurement by RIA, the levels of other sulfidopeptide LTs, such as LTD4 and LTE4, in synovial fluid from patients with RA were found to be significantly higher than those in fluid from patients with OA. The leukocyte number in synovial fluids did not correlate with the i-LTC4 level. The metabolic activities of these synovial fluids were determined by incubating them with 3H-LTC4 and then separating sulfidopeptide LTs by HPLC. The conversion of LTC4 to LTD4 in synovial fluids of patients with OA and RA were similar, but the dipeptidase activity converting LTD4 to LTE4 was higher in fluid from patients with RA. It is suggested that a high level of LTE4 may contribute to exudation of synovial fluid, since LTE4 increases vascular permeability. | |
| 3408829 | Anaemia in patients with arthritis: are simple investigations helpful? | 1988 Aug | The level of haemoglobin, serum iron, total iron binding capacity and ferritin were measured in patients with rheumatological conditions who were anaemic at the time of upper gastrointestinal endoscopy. These parameters were similar in patients with or without lesions of their upper gastrointestinal tract, and in patients with a positive or negative faecal occult blood result. Lesions of the upper gastrointestinal tract were not more frequent in patients with a microcytic anaemia when compared to those with a normocytic anaemia, nor were they found more frequently in patients with a positive faecal occult blood test. Lesions visible at upper gastrointestinal endoscopy are not an important cause of microcytic anaemia in patients with arthritis. The finding that patients with normocytic anaemia are more likely to proceed to lower bowel examination than patients with microcytic anaemia is a reflection of the difficulty in interpretation of these simple haematological tests and showed they were unhelpful in determining which patients warrant investigation of the lower bowel. The frequency of further investigation of the lower bowel was significantly reduced by a positive endoscopy report, irrespective of the nature of the lesion, but was not significantly increased by finding faecal occult blood. We suggest that patients with arthritis selected for investigation of possible gastrointestinal blood loss should follow an organized plan of investigation that includes examination of both upper and lower bowel, and which should proceed uninfluenced by pro tem results. Unfortunately the selection of patients for such further investigation is hampered by a lack of simple discriminatory tests. | |
| 2143127 | Induction of bone resorbing activity by normal and rheumatoid arthritis T cells. | 1990 Aug | We studied the role of T cells in the production of osteoclast activating factor (OAF) using anti-CD3 MAb as a specific T cell activator. OAF activity was totally inhibited by anti-IL-1 beta. Peripheral blood mononuclear cells (PBMNC) from normal subjects produced more OAF than did PBMNC from rheumatoid arthritis (RA) patients. Mononuclear cells (MNC) from RA synovial fluid produced less OAF than did RA peripheral blood. We conclude that (i) specific T cell stimulation induces OAF production which may be attributed to interleukin 1 (IL-1) activity, (ii) the inhibition by anti-IL-1 beta of OAF production following anti-CD3 stimulation suggests that the T cell signal is being transmitted to the macrophage, and (iii) RA MNC are deficient in T cell-mediated OAF production. |