Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1982890 | Association of HLA-DR antigens with disease severity in Japanese patients with rheumatoid | 1990 Aug | Twenty eight Japanese patients with rheumatoid arthritis (RA) were tested for HLA-DR antigens to investigate genetic influence on disease severity and prognosis. The severity of RA was assessed by clinical, laboratory and radiological indexes. HLA-A, B, C and DR typing was performed using sera described at the 3rd Asia and Oceania Histocompatibility Workshop. HLA-DR4.1 was significantly higher in RA patients (50%) compared with controls (27.6%). HLA-DRw53 was also higher in RA patients, although DRw52 was lower in those than controls. When the relationship between HLA-DR antigens and the clinical severity of RA was investigated, the patients with HLA-DR4 had a severer disease than DR4 negative patients. In contrast, HLA-DR2 positive patients had significantly better functional scores than DR 2 negative patients. We next investigated specific genes likely to be directly involved in the pathogenesis of RA. Although the new restriction fragment length polymorphisms (RFLPs) were found in DR2 positive patients, no association was found between the RFLPs and the clinical severity of RA. Furthermore there were no differences in the frequencies of the RFLPs in HLA-DR4 positive patients compared with DR4 negative patients. It may be concluded that the severity of RA appears to be influenced by several different genes or molecules rather than by a single gene or gene product linked to HLA-DR2 or DR4. | |
| 3572937 | Toxicity of methotrexate in rheumatoid arthritis. | 1987 Feb | Seventy-two patients with rheumatoid arthritis had been treated with pulse weekly oral methotrexate with a mean followup of one year. Minor side effects (oral ulcers, transient elevation of liver enzymes, nausea, vomiting) were present in 46 patients (63.8%), whereas major side effects (severe infection, cytopenia, respiratory failure, seizures, gastrointestinal bleeding) were present in 7 (9.7%), 2 of whom died. Patients with major side effects had shorter disease duration and increased frequency of extraarticular manifestations as compared to those with no side effects. No association between a particular clinical or genetic variable and occurrence of side effects to methotrexate was found. | |
| 3757358 | Uncemented acetabular cups in dysplastic and protrusio acetabuli. | 1986 Sep | Total hip arthroplasties using the Ring uncemented polyethylene to metal system were carried out in 84 hips with either protrusio or dysplasia of the acetabulum. The results of the operation, the stability and function of the acetabular implant, and radiologic changes in the medial wall of the acetabulum in the protrusio hips were assessed over a two- to five-year follow-up period. Annual assessment over the follow-up period showed that an excellent functional result was achieved in all patients. Six of the eight hips with severe protrusio showed an increase in the thickness of the medial acetabular wall one year from the time of operation. Lack of bony cover over the lateral surface of the acetabular cup in the dysplastic hips did not have any adverse effect on the stability and function of these hips. | |
| 2389044 | Rheumatoid knee: role of gadopentetate-enhanced MR imaging. | 1990 Sep | Physical examination is often insufficient in distinguishing between joint effusion and inflamed synovium in the knee joints of patients with rheumatoid arthritis. The authors prospectively evaluated the role of intravenously administered gadopentetate dimeglumine in distinguishing between these two conditions. Fourteen patients with classic rheumatoid arthritis were examined first by a rheumatologist and then by means of magnetic resonance (MR) imaging with T1- and T2-weighted sequences. T1-weighted images were also obtained following the intravenous administration of gadopentetate dimeglumine. T1-weighted images obtained prior to contrast material administration demonstrated an identical low-intensity signal from both effusion and inflamed synovium, and T2-weighted images demonstrated increased signal intensity in both cases. Intravenous administration of gadopentetate dimeglumine allowed distinction between effusion and abnormal synovium, with the effusion remaining of low signal intensity and the synovium demonstrating enhancement and increased signal intensity. The authors conclude that the use of gadopentetate allows distinction between synovial thickening and joint effusion in the knee, which may affect treatment decisions. | |
| 1849716 | Neutrophils isolated from the synovial fluid of patients with rheumatoid arthritis: primin | 1991 Mar | The oxidative metabolism of neutrophils isolated from the bloodstream and synovial fluid of 16 patients with rheumatoid arthritis was compared by measuring the ability of neutrophils to generate luminol dependent chemiluminescence and to secrete O2-. Measurements of receptor mediated--that is, N-formyl-methionyl-leucyl-phenylalanine stimulated--activation or receptor and second message independent--that is phorbol myristate acetate stimulated--activation showed that synovial fluid neutrophils had biochemical characteristics to suggest that they had been either up-regulated (primed) or down-regulated (activated) in vivo. These conclusions were confirmed by comparison of these responses with the changes in oxidative metabolism observed during in vitro priming and activation of control neutrophils: synovial fluid neutrophils possessed lower levels of myeloperoxidase than paired bloodstream cells, and unlike bloodstream cells could not be primed in vitro. These data thus suggest that synovial fluid neutrophils have been exposed to both priming and activating agents within rheumatoid joints. | |
| 2053914 | The impact of rheumatoid arthritis on the household work performance of women. | 1991 Jun | We conducted a study to assess whether and to what degree household work disability exists in women with rheumatoid arthritis (RA) and to examine the role of health versus family and personal factors as predictors of household work disability. In addition, the participation of other family members and paid employees in household work was evaluated. One hundred forty-two women with RA and 58 female friends/neighbors completed questionnaires which assessed household work performance and health, family, and personal variables. Performance was measured in 4 ways: the current amount of time spent on household work, the proportion of the household work done, and the changes in time and proportion since just before the onset of RA. Functional status was measured via the Health Assessment Questionnaire. Pain, anxiety and depression, and general health perception were measured via the Arthritis Impact Measurement Scales. The results indicate that household work disability exists in women with RA, but is substantial only in women with moderate-to-severe disease. In families in which the wife/mother has moderate-to-severe RA, the other family members spend 7 hours more per week on household work than in control families, but there was no increase in the use of paid household employees. Health factors were the strongest predictors of household work disability, but family and personal factors also had significant effects. Household work disability in women with moderate or severe RA merits more attention because of the importance of household work to family functioning and the negative effects that changes in this area can produce. | |
| 2662917 | Seronegative rheumatoid arthritis, rheumatoid factor cross reactive idiotype expression, a | 1989 Jun | The major rheumatoid factor cross reactive idiotype (RCRI), defined by prototypic monoclonal rheumatoid factors (RFs), is expressed as a dominant idiotype by pokeweed mitogen induced plasma cells obtained from seropositive (RF+) patients with rheumatoid arthritis (RA). Some patients who meet clinical diagnostic criteria for RA set by the American Rheumatism Association fail to express RFs at any time during their clinical course. To determine if seronegative (RF-) patients with RA, so designated by the latex fixation, Rose-Waaler classic binding assays, or a RF enzyme linked immunosorbent assay (ELISA), express the RCRI in the absence of detectable RFs we examined pokeweed mitogen plasma cells from these patients by indirect immunofluorescence. In addition, we used an inhibition ELISA to detect RCRI bearing molecules in the sera of RF- patients with RA. Five of 10 RF- patients with RA had a high prevalence of RCRI+ plasma cells (16-49% of total pokeweed mitogen plasma cells in culture). Six of 20 RF- patients with RA had high serum concentrations of molecules marked by the RCRI, equivalent to 21-110 micrograms/ml of RCRI+ reference monoclonal IgM RF. Four of five patients who expressed the RCRI in high prevalence in pokeweed mitogen plasma cells, also demonstrated high concentrations of RCRI in their sera detected by inhibition ELISA. There was significant concordance of RCRI expression determined by the two different assays. Four RF- patients with RA who expressed RCRI in their whole sera had hidden RFs detected in their 19S and, in one case, 7S serum fraction. Detection of RF related molecules in whole sera by the expression of RCRI in RF- patients with RA identifies a subgroup of RF- patients with RA who possess hidden RFs. Some RF- patients with RA can express the major RCRI in pokeweed mitogen plasma cells and in their sera and therefore are related to patients with prototypic Waldenstrom's macroglobulinaemia, who produce RCRI+ 19S IgM monoclonal RFs. | |
| 3375772 | [Mechanism of Felty's syndrome and long-term course]. | 1988 Mar 15 | The authors report 18 cases of Felty's syndrome followed, in an average, for 5 years (1 to 12 years). There were 3 deaths, 9 patients are in complete remission, 6 others still show signs of the disease: splenomegaly (4 cases), leucopenia (1 case) and only one complete Felty's syndrome. Steroid therapy has proved to be effective regardless of the mechanism of the neutropenia specified in 9 cases by an isotopic study. Prognosis and infectious risk are difficult to determine but the overall course was rather favorable. | |
| 1656449 | The T-cell-receptor repertoire in the synovial fluid of a patient with rheumatoid arthriti | 1991 Oct 1 | We have analyzed the T-cell-receptor repertoire expressed in the synovial fluid of a patient with rheumatoid arthritis by using an inverse polymerase chain reaction. Total RNA was isolated from Ficoll-purified mononuclear cells and converted into circularized double-stranded cDNA. Specific amplification of alpha- and beta-chain variable regions (V alpha and V beta) was achieved with inverted alpha- and beta-chain constant region (C alpha and C beta) primer pairs, and the amplification products were cloned into phage vectors. A total of 78 alpha and 76 beta clones were sequenced, and 67 and 72 productively rearranged alpha and beta genes were identified, respectively. Thirty-one V alpha, 33 alpha-chain joining region (J alpha), 29 V beta, and 12 beta-chain joining region (J beta) gene segments were found in the productively rearranged clones, indicating that the T-cell repertoire expressed in the synovial fluid of this RA patient is highly heterogenous and polyclonal. Comparison of peripheral blood and synovial fluid repertoires showed that the most abundant V beta sequences, V beta 2.1 and V beta 3.1, were enriched in the inflamed joint by a factor of 2 to 3. It is possible that T cells expressing these V beta gene segments, which recognize bacterial superantigens, play a role in the disease. | |
| 2377900 | Magnetic resonance imaging of the craniocervical junction in rheumatoid arthritis: value, | 1990 | The cervical spine is the second most common location for manifestation of rheumatoid arthritis (RA). Symptoms are typically related to involvement of the craniocervical junction. Unfortunately, conventional radiographic examination is often unable to demonstrate that RA is the cause of such symptoms. Magnetic resonance imaging (MRI) provides an unique opportunity to visualize nerves, connective tissue, and bone in all planes without the use of contrast agents. These features suggest that MRI could provide important information related to RA of the cervical spine. The possibilities and limitations of MRI were therefore evaluated in 60 patients with cervical RA. The main objective of this study was to correlate symptoms and clinical findings with MRI results to establish indications for this imaging procedure. | |
| 2800735 | [Development of a new quantitative rheumatoid factor test]. | 1989 Jul | A new simple identification of rheumatoid factor on nitrocellulose was developed that allows quantitative detection. Verification of the results was done by comparison with the established Waaler-Rose-Test and Latextest: Correlation coefficient of linear regression for Latextest rLR = 0.717 and for Waaler-Rose-Test rLR = 0.665; Spearman rank correlation coefficient for Latextest rs = 0.798 and for Waaler-Rose-Test rs = 0.700. The interday and intraday variations showed good results. The histograms for different patient groups showed significant distributions. The nitrocellulose-test satisfies ARA-criterium No. 6. | |
| 3337927 | Significant changes in Ritchie scores. | 1988 Feb | A study was designed to establish the reliability of assessing joint tenderness in rheumatoid arthritis. Reliability both within and between observers was measured and the 95% confidence intervals (CI) for a change in score calculated. Forty-two patients were assessed by two metrologists over a 14-week period using three subjects per week. Results showed close agreement within and between metrologists. The 95% CI for repeat measures by the same metrologist was +/- 8.5 and +/- 12 by a different metrologist. Taking a change of 5 in the score as clinically significant, the 95% CI for a clinically significant change would be +/- 14 with one observer and +/- 17 when a different observer repeated the assessment. It is recommended that other centres should establish their own CI for a change in scores when undertaking clinical trials. | |
| 2565707 | HLA class II DR, DQ, and DP restriction fragment length polymorphisms in rheumatoid arthri | 1989 Apr | HLA class II restriction fragment length polymorphisms (RFLPs) were studied in 43 individuals with established seropositive rheumatoid arthritis (RA) and in a group of healthy controls. All patients and controls were tissue typed for HLA-A, B, and DR antigens. Rapid, initial screening for RA associated RFLPs was conducted by pooling DNA samples from 11 HLA-DR4 positive patients with RA and comparing the RFLP patterns with those seen in a pool of DNA samples drawn from 11 HLA-DR4 positive healthy controls. Candidate RA associated RFLPs were examined in our full panel of patients with RA and controls. In most cases the RFLPs detected showed no significant association with RA. An exception was a 13.0 kb DraI DQ beta associated RFLP, which, when HLA-DR4 positive patients with RA and controls were considered alone, showed a weak positive association with susceptibility to RA. This RFLP was not associated with known DR, DQ, or Dw specificities. These results show a distinct paucity of class II RA associated RFLPs but may indicate a role for DQ beta genetic variation in the aetiology of RA. | |
| 2476386 | Southern blot analysis of HLA-DP gene polymorphisms in Caucasoid rheumatoid arthritis (RA) | 1989 | Despite extensive analysis of the incidence of HLA-DR and HLA-DQ allele frequencies in defined autoimmune disease groups, there is very little information available on HLA-DP allele frequencies. This is largely because HLA-DP typing has until recently been restricted to primed lymphocyte typing (PLT). However, allelic polymorphism of the HLA-DP subregion can now be studied by Southern blot analysis or genotyping with DPA1 and DPB1 probes. By direct counting of allele-specific DNA fragments, we have analyzed the frequencies of five major DP genotypes (DPw1, DPw2, DPw3/6, DPw4, and DPw5), in a large number of Caucasoid rheumatoid arthritis (RA) patients (n = 74), and controls (n = 91). The predicted frequency of DP alleles in both patient and control groups was comparable to PLT-determined DP allele frequencies in normal Caucasoids. However, the gene frequency of DPw4 was increased in the RA patients, with 51% of the patients studied scoring as DPw4, 4 homozygotes. With the exception of one possible combination (DPw5 and DRw6) in the controls, no significant linkage disequilibrium was detected between DP and DR alleles in either patient or control groups. Thus the prevalence of DPw4 in the RA patients is independent of any disease association with the DR loci, and may represent a new class II association with RA. | |
| 3135572 | Results of a multicenter placebo-controlled double-blind randomized phase III clinical stu | 1988 | In a multicenter placebo-controlled double-blind randomized clinical study, 91 patients with rheumatoid arthritis were given 28 days' treatment with recombinant interferon-gamma (50 micrograms daily for 20 days, then 50 micrograms each second day up to day 28, given by subcutaneous injection). The aim of the study was to provide a methodologically clear demonstration of the efficacy of treatment with interferon-gamma, using criteria that could be handled by statistical tests. Evaluatable documentation was available for 79 patients, of whom 40 were treated with the active compound. The principal criterion for the statistical evaluation of the therapeutic success was improvement of the Ritchie "joint pain index" or Lansbury "joint pain index" by at least 30% within 28 days. The chi-square test showed superiority of the interferon arm over the placebo arm with an error probability of alpha less than 1%. In addition, efficacy of interferon-gamma was demonstrated in respect of practically all parameters investigated. The frequency of side-effects, including febrile reactions, was the same for the active compound and the placebo. During interferon treatment the daily maximum body temperature was raised by 0.3 degrees C on average, but was below 37.2 degrees C at all times. | |
| 2715941 | Pharmacokinetics of low-dose methotrexate in rheumatoid arthritis patients. | 1989 Feb | The pharmacokinetics and bioavailability of low-dose methotrexate (MTX) (10 mg/m2) were evaluated in 41 subjects who had definite or classical rheumatoid arthritis as defined by the American Rheumatism Association criteria. Subjects received 10 mg/m2 (to the nearest 2.5 mg) of MTX in a single oral dose and a single intravenous (iv) dose one week apart. Serum concentrations for this low-dose regimen were monitored using a radiochemical ligand binding assay. The results indicate the MTX is cleared from the plasma at a rate of 84.6 mL/min/m2. The terminal half-life was approximately 6 h. The volumes of distribution at steady state and for the central compartment were 22.2 and 13.5 L/m2, respectively. The mean residence time in the body, in the systemic circulation, and in the periphery were estimated to be 4.7, 3.0, and 1.7 h, respectively, with a peripheral single-pass mean transit time of 6.0 h and an intrinsic mean residence time in the periphery of 7.9 h. The mean absorption time was 1.2 h and the oral bioavailability was 0.70. The ratio of synovial fluid concentration to serum concentration 4 and 24 h after a dose was found to be approximately 1.0, indicating that at least within that time range serum and synovial fluid concentrations are approximately equal. Because of conflicting results and insufficient data from previous high-dose pharmacokinetic studies, it is difficult to say whether or not low-dose MTX pharmacokinetics differs from those of high-dose MTX. | |
| 3579389 | Renal impairment associated with non-steroidal anti-inflammatory drugs. | 1987 Mar | We have compared the renal function on admission and discharge of 22 patients routinely admitted to our rheumatology ward. None had previously diagnosed renal failure. Of 11 patients in whom we stopped long term non-steroidal anti-inflammatory drug (NSAID) therapy, all showed a rise in creatinine clearance (Ccr) after three to 28 days. In contrast, a control group comprising 11 similar patients who continued to receive NSAIDs showed no significant change. Recent work has suggested that it is possible to identify patients at risk of developing nephrotoxic side effects with NSAIDs. Based on these criteria (but excluding age alone as a risk), six patients from the first group and 10 from the second group would have been without risk. We infer from this that asymptomatic, reversible impairment of renal function is common, and that the potential clinical benefit from the use of NSAIDs should be balanced against this predictable toxicity. | |
| 2085056 | Rheumatic diseases in Neolithic and Medieval populations of western Switzerland. | 1990 Nov | An investigation of three groups from ancient populations (Neolithic, Early Middle Ages, Middle Ages) was performed on 273 adult skeletons. Despite unequal preservation of the remains, a study of a series of large joints and spinal segments permitted some conclusions: rheumatoid arthritis, ankylosing spondylitis, and osteoarthrosis of large joints (hip, knee, shoulder) were not found. The main findings were: osteoarthrosis in spinal zygapophyseal joints (particularly at cervical level); intervertebral osteochondrosis (particularly at the cervical and lumbar levels); Schmorl's nodes (particularly at the thoracic and lumbar levels); enthesopathic osteophytes (particularly in the spine, iliac crest, patella, and calcaneus). Such deformities seemed more frequent in the Middle Ages than in the Neolithic period. | |
| 3584885 | Tendon ruptures and median nerve damage after Hamas total wrist arthroplasty. | 1987 May | This article describes complications due to an incorrectly positioned Hamas-designed total wrist prosthesis in a 68-year-old woman with rheumatoid arthritis. At operation the median nerve was found to be directly impinged upon by the rim of the distal portion of the prosthesis. There were divisions of the superficialis tendon to all four fingers, the profundus tendon to the index finger, and partial division of the profundus to the long finger. The prosthesis was removed, and the wrist stabilized with a Steinmann pin in the radius and the second metacarpal. | |
| 3495174 | Immunological aspects of the anemia of rheumatoid arthritis. | 1987 May | In order to investigate the cause of the anemia concomitant with rheumatoid arthritis (RA), we examined, using the erythroid colony assay of human bone marrow colony-forming units-erythroid (CFU-e) and burst-forming units-erythroid (BFU-e), the effects of the patients' serum and peripheral blood T lymphocytes on the CFU-e-derived colonies. The counts of erythroid colonies of RA patients were markedly lower than those of human control subjects [CFU-e: control 152.9 +/- 30.6 (n = 19), RA 51.1 +/- 13.6 (n = 7), t = 7.66567, p less than 0.01; BFU-e: control 25.2 +/- 5.9 (n = 5), RA 12.6 +/- 2.6 (n = 7), t = 4.574, p less than 0.01]. The serum from two out of seven RA patients slightly inhibited the formation of CFU-e-derived colonies of human control subjects (t = 2.31, 0.05 less than p less than 0.1); however, the serum from the other five RA patients did not significantly inhibit human control erythroid colony formation as compared with human control serum (t = 0.981, 0.3 less than p less than 0.4). On the other hand, peripheral blood T lymphocytes of the patients markedly inhibited the formation of CFU-e-derived colonies of the control subjects as compared with peripheral blood T lymphocytes from human control subjects (t = 4.24, p less than 0.01). The above-mentioned results suggest that the peripheral blood T lymphocytes of RA patients might play a role as one of the causes of the concomitant anemia of RA patients. |