Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1567559 | Regulation of synovial cell growth by polypeptide growth factors. | 1992 Apr | In vitro, rheumatoid arthritis (RA) synovial cells display several of the characteristics of neoplastic and virally transformed cells. The recent observation that synovial cell cultures, derived from collagenase digests of synovial membranes from RA patients, proliferate in serum-free medium suggests that these cells have the capacity to synthesize those factors essential for their growth. Direct immunocytochemical staining and Western analysis have identified transforming growth factor-beta (TGF-beta) band and basic fibroblast growth factor (FGF) in the cytoplasm of RA and normal synovial cells in long-term culture. Greater amounts of each growth factor were found in RA, as compared with normal synovial cell lysates. Western analysis identified a single TGF-beta band in RA and normal synovial cell lysates. Four bands were identified by Western analysis on RA synovial cell lysates probed with monoclonal antibodies recognizing bFGF, whereas only two bands (which co-migrated with human native recombinant bFGF) were identified in normal cell lysates probed with these antibodies. Gene expression analysis using PCR identified mRNA transcripts encoding TGF-beta 1 and FGF-2 (bFGF), but not TGF-beta 2 in all cell cultures studied. Taken together, these data indicate that cultured synovial cells co-express TGF-beta 1 and multiple isoforms of hFGF. These data further strengthen the concept that both polypeptide growth factors are involved in the regulation of synovial cell growth. | |
| 8762279 | [Pleuropulmonary manifestations of rheumatoid arthritis]. | 1996 May 18 | Respiratory complications are important morbidity and mortality factors in rheumatoid arthritis. Either the disease itself, secondary effects of necessary drugs, or infections favored by the relative immunosuppression resulting from the disease and therapy can affect all the respiratory structures: airways, lung parenchyma, vessels, chest wall, respiratory muscles. The combined efforts of rheumatologists and pneumologists are required for correct management. | |
| 8535653 | Joint erosions and patients with early rheumatoid arthritis. | 1995 Nov | The development of changes on X-rays in patients with rheumatoid arthritis (RA), as described in the literature, is presented. Prospective studies on patients with early disease show that approximately 75% of the patients have joint erosions. The majority of patients develop the first erosions during the first 2 yr of the disease. The rate of progression, expressed as newly eroded joints or increase in radiographic damage, is highest during the early years of the disease. Joints in the feet erode earlier than those in the hands. Moreover, more joints are affected in the feet than in the hands. Exact data on the involvement of large joints are scarce, but the progression of RA in small and large joints correlates well. Over half of the patients develop an involvement of the cervical spine during the first 10 yr of the disease. The percentage of patients with cervical subluxation increases steeply with disease duration. | |
| 8406247 | Surgical treatment for mild deformities of the rheumatoid forefoot by partial phalangectom | 1993 Jul | Thirteen patients (14 feet) were treated for mild rheumatoid forefoot deformities with lesser toe partial proximal phalangectomies and partial syndactylizations. Eleven patients (85%) were reviewed at an average of 8 years postoperatively. The results were completely satisfactory in four patients, satisfactory with minor reservations in three patients, satisfactory with major reservations in one patient, and unsatisfactory in three patients. The major cause of reservations and lack of satisfaction was metatarsalgia. Seven patients (64%) reported that their activities were limited by intermittent metatarsalgia. Four patients (36%) considered the cosmetic appearance of the forefoot to be unsatisfactory. All but one patient required some form of shoewear modification. Based on this study, we believe the indications for this procedure are limited. These include rheumatoid patients with mild forefoot deformities without significant metatarsalgia or ongoing disease who have failed nonoperative treatment. Relative contraindications to this operation appear to include the recent onset of rheumatoid arthritis, active disease, significant metatarsalgia, and strong cosmetic concerns regarding outcome. In borderline clinical decisions that involve whether or not to leave or excise the lesser metatarsal heads, they probably should be excised to decrease late metatarsalgia. | |
| 1483306 | Calcium pyrophosphate deposition disease: description in defleshed skeletons. | 1992 Nov | The osseous appearance, skeletal distribution, and distinguishing features of calcium pyrophosphate deposition disease (CPPD) were delineated in a population of 2906 contemporary defleshed skeletons. The limitations of routine x-ray and clinical examination were transcended in this study of defleshed bones. The nature of the disease was clearly identified and preconceived notions (based on the "shades of black and white" of the conventional x-ray technique) were examined on the basis of the actual osseous impact. Epidemiologic assessment of this disease allowed it to be distinguished from rheumatoid and other erosive forms of arthritis. Analysis of the "pseudo-rheumatoid" subgroup of CPPD provided clear criteria for distinguishing the disease from rheumatoid arthritis. Characterization of the nature and epidemiology of osseous alterations in a contemporary skeletal population permitted the development of a standard for recognition of CPPD in skeletal populations and for clarification of the nature of associated pseudo-erosions. | |
| 8448612 | A clinical and radiological study of back pain in rheumatoid arthritis. | 1993 Mar | Five hundred and three patients with RA were questioned about the symptom of back pain. Chronic back pain, lasting more than 3 months, occurred in 33 per cent of the group. A group of 100 back pain patients were studied in more detail using a structured questionnaire, clinical examination and radiology. Ninety-four of these patients had low back pain. Particular clinical patterns (such as that of the facet syndrome) were sought but no clear characteristics were found. Fifty-two lumbar spine X-rays were available from the RA population and these were compared to 52 age and sex matched X-rays from outpatients with chronic mechanical low back pain. Significant differences between these groups radiologically were a higher frequency of osteoporosis and a higher frequency of disc narrowing without associated osteophytes in the RA population. This study differs from previous reports which found other characteristic radiological features of RA of the lumbar spine (spondylolisthesis, facet erosions, and vertebral fracture), a discrepancy possibly resulting from the use of a control group having low back pain. | |
| 1505113 | Human platelets in synovial fluid. A focus on the effects of growth factors on the inflamm | 1992 Mar | The alpha granules of platelets are a major storage site for peptide growth factors. The inflamed synovial fluid of rheumatoid arthritis contains a high number of platelets as well as platelet-derived growth factors. These platelets may apparently be acted upon to release their alpha granule-located substances. It can thus be suggested that platelets present in the synovial fluid express growth factors of significance to the local inflammatory responses of rheumatoid arthritis. | |
| 8261056 | Accelerated nodulosis and systemic manifestations during methotrexate therapy for rheumato | 1993 Mar | OBJECTIVES: Methotrexate is successfully used in the treatment of arthritis but little is known about its effects on extra-articular manifestations of rheumatoid arthritis. We focused this work on the incidence and clinical course of extra-articular manifestations during long-term treatment with methotrexate. METHODS: The effect of methotrexate on extra-articular manifestations was investigated in 176 patients with rheumatoid arthritis who had obtained, in a prospective study, a good clinical response to methotrexate (10 mg/week) taken for 33 months (range 4-68). RESULTS: Before taking methotrexate, 44 patients (25.1%) had extra-articular manifestations: nodules (n = 40) and vasculitis (n = 9). With methotrexate, nodulosis and vasculitis were stable in 31 cases, improved in 3 and worsened in 10 (23%). Among the 132 patients without extra-articular manifestations before methotrexate therapy, 15 (11%) developed accelerated nodulosis preferentially located on the fingers, 7 had a vasculitis and 3 a pericarditis during methotrexate therapy. Extra-articular manifestations occurred between 1 and 24 months of initiating methotrexate therapy. Rheumatoid factor was positive in 88% of the patients with extra-articular manifestations. No relationship was noted between extra-articular manifestations and HLA type or antinuclear antibodies. In 3 out of 4 patients who developed accelerated nodulosis while taking methotrexate, the addition of hydroxychloroquine (400 mg/day) resulted in a significant reduction in the number and size of the nodules within 3 to 10 months after starting combined therapy. CONCLUSION: These data suggest that methotrexate is not effective in the treatment of extra-articular manifestations in rheumatoid arthritis and that nodulosis may occur in about 11% of patients taking methotrexate therapy for rheumatoid arthritis. The combination of hydroxychloroquine and methotrexate may have a beneficial effect on nodulosis that needs to be evaluated. | |
| 8712883 | Factors associated with the development of vasculitis in rheumatoid arthritis: results of | 1996 Mar | OBJECTIVE: To investigate those characteristics of patients with rheumatoid arthritis (RA) that are associated with the development of rheumatoid vasculitis (RV). METHODS: Demographic and clinical data of 69 patients who had been diagnosed as having RV were compared with those of 138 contemporaneous control patients with RA who were not suspected to have vasculitis. Vasculitis was confirmed histologically in 96% of the subjects with RV. RESULTS: Variables associated with the development of RV were: 1) male gender, presence of increased serum concentrations of rheumatoid factor, joint erosions, subcutaneous nodules, number of disease modifying antirheumatic drugs previously prescribed, treatment (ever) with D-penicillamine or azathioprine; 2) presence of nail fold lesions and any other extrarticular feature one year before the time of diagnosis of RV; 3) treatment with corticosteroids at the time of diagnosis of RV. CONCLUSIONS: The development of RV is associated with male gender, extra-articular features, and a severe course of RA as indicated by the presence of joint destruction and need for intensive treatment with antirheumatic drugs. The strongest association was found with the presence of increased concentrations of rheumatoid factor. | |
| 8254878 | [Anesthetic management of a patient with hyperkalemic tubular acidosis]. | 1993 Nov | We experienced the anesthetic management of a 72-year-old female with hyperkalemia, metabolic acidosis and renal insufficiency, undergoing right total hip replacement for rheumatic arthritis. She had been treated with nonsteroidal anti-inflammatory drugs (NSAIDs) for last several years. Anesthesia was maintained with isoflurane 0.2-1.0% and nitrous oxide in oxygen supplemented with vecuronium. Continuous infusion of prostaglandin E1 0.05-0.10 microgram.kg-1 x min-1 and bolus infusion of 7.0% NaHCO3 during the operation were useful in controlling blood pressure, improving hyperkalemia and maintaining renal function. Postoperatively, she was diagnosed to have hyperkalemic tubular acidosis due to interstitial nephritis induced by NSAIDs. | |
| 7974025 | [The indications for the use of salazosulfapyridine in rheumatoid arthritis patients]. | 1994 Aug | In an attempt to clarify the background of patients with rheumatoid arthritis (RA) who should be treated with salazosulfapyridine (SASP), a tree classification of responders and non-responders to SASP was developed by analyzing 88 RA patients administered with SASP, according to factors such as clinical findings, autoantibody and HLA antigen. Five clinical features were associated with increased efficacy of SASP: male sex, duration of illness of less than 10 years, initial use of SASP, negative RA test and negative antinuclear antibody. In the tree classification for SASP, there were 3 groups of responders: male sex, female sex + initial use of SASP + negative RA test, and female sex + previous treatment with disease-modifying antirheumatic drugs (DMARDs) +negative antinuclear antibody + negative RA test, while there were 5 groups of non-responders: female sex + previous treatment with DMARDs + negative antinuclear antibody + positive RA test with HLA DR9 or A24 + DR9, and female sex + previous treatment with DMARDs +positive antinuclear antibody with HLA A24, DR9 or A24 + DR9. The new tree classification for the efficacy of SASP in the present study facilitated clear distinction of responders and non-responders to the drug. | |
| 8335337 | [Imaging in rheumatoid arthritis]. | 1993 Jun | The radiographic changes of rheumatoid arthritis (RA) consist of periarticular soft tissue swelling, osteoporosis, symmetric narrowing of the joint space associated with marginal or central erosions. Conventional radiography is the basic imaging method in RA due to its high impact on differential diagnosis. MRI and bone scintigraphy are second line imaging methods in early stages of arthritis. Hypervascularized pannus can noninvasively and in a detailed way be depicted using intravenously applied Gadolinium-DTPA. Follow-up examinations of the clinical and radiographic findings are adequate in advanced stages. Additional sonography and computed tomography are supplementary methods. | |
| 8848738 | The cervical spine in rheumatoid arthritis: relationship between neurologic signs and morp | 1996 Feb | OBJECTIVE: Comparison of clinically observed neurologic long tract signs in a heterogeneous group of patients with rheumatoid arthritis (RA), with morphologic abnormalities of the cervical spine as depicted on radiographs and magnetic resonance (MR) images. DESIGN: The patients were prospectively assigned to one of three classes on the basis of their neurologic status. Lateral cervical spine radiographs and sagittal T1-weighted and gradient echo images were performed. The qualitative MR features evaluated were erosion of the dens and atlas, brain stem compression, subarachnoid space encroachment, pannus around the dens, appearance of the fat body caudal to the clivus, and the signal intensity of the pannus. The quantitative imaging parameters were the cervicomedullary angle and the distance of the dens to the line of McRae. PATIENTS: Sixty-three consecutive patients with RA and subjective symptoms, especially neck or occipital pain, and/or clinical objective signs consistent with a compromised cervical cord were included in this study. RESULTS AND CONCLUSIONS: Damage documented with radiographs and MR imaging in patients with RA is often severe, even in those without neurologic signs (class 1). None of the abnormalities confined to the atlantoaxial level correlated significantly with neurologic classification. Subarachnoid space encroachment anywhere in the entire cervical spine did correlate significantly with neurologic classification. | |
| 7783057 | The correlates of health perceptions in rheumatoid arthritis. | 1995 Mar | OBJECTIVE: Although measures of health perceptions have been routinely incorporated into assessments of individuals with rheumatoid arthritis (RA), the relationships of other characteristics of these individuals to their health perceptions is not fully understood. We describe the cross sectional associations of sociodemographic, disease, and functional status characteristics with perceived health in individuals with RA. METHODS: This description was generated through a 2-phase secondary data analysis using 2 statistical approaches: recursive partitioning of the sample and standard multivariate logistic regression techniques. RESULTS: Both methodological approaches identified education, race, depression, and physical activity as important correlates of self-assessed health in RA. Each approach, in its own way, also identified an interactive effect between physical activity and education and between depression and race in these models. CONCLUSION: An individual's sociodemographic, disease, and functional status characteristics form a complex model of the correlates of health perceptions of individuals with RA. | |
| 8431213 | Increased production of soluble CD23 in rheumatoid arthritis, and its regulation by interl | 1993 Feb | OBJECTIVE: To assess CD23 status in rheumatoid arthritis (RA) patients, as defined by the levels of CD23 expression on peripheral blood mononuclear cells (PBMC), the levels of soluble CD23 (sCD23) in sera, and the production of sCD23 by PBMC cultures and its regulation by interleukin-4 (IL-4). METHODS: CD23 expression as determined by double fluorescence-activated cell sorter analysis and sCD23 production as determined by immunoradiometric assay were investigated in 24 RA patients and 21 controls. Soluble CD23 was measured in sera and supernatants of PBMC, activated with polyclonal activators (pokeweed mitogen [PWM] or Staphylococcus aureus Cowan strain 1, [SAC]) used either alone or in combination with IL-2 or IL-4. RESULTS: The percentage of B cells expressing CD23 and serum levels of sCD23 were increased in patients with RA. IL-4 was a potent inducer of sCD23 production in supernatants, whereas IL-2 was inactive. Costimulation with SAC or PWM did not increase the effect obtained with IL-4 alone. When sCD23 levels in RA and control supernatants were compared, spontaneous production was found to be increased in RA PBMC: This difference from control values was even more pronounced when sCD23 levels in PBMC and purified B cells in response to IL-4, either alone or in combination with SAC or PWM, were tested. In the same supernatants, the increased secretion of sCD23 induced by IL-4 was associated with an inhibitory effect of IL-4 on Ig production, a phenomenon that was more pronounced in RA PBMC than in controls. CONCLUSION: CD23 status in RA is characterized by increased expression of CD23 on B cells, increased production of sCD23 in sera and supernatants, and increased sensitivity of RA PBMC and B cells to IL-4. | |
| 8129777 | Differential distribution of intercellular adhesion molecules (ICAM-1, ICAM-2, and ICAM-3) | 1994 Feb | OBJECTIVE: Cellular adhesion and differentiation molecules (CAMs) may play a role in the recruitment and retention of inflammatory cells into rheumatoid arthritis synovial tissue (RA ST). In order to determine if certain CAMs are up-regulated in RA ST compared with normal ST, we studied the distribution of intercellular adhesion molecules (ICAMs) 1, 2, and 3 in ST. We also studied the MS-1 antigen since it is preferentially expressed on discontinuous endothelia, such as those found in RA ST; MS-1 is also expressed differentially upon cytokine activation of cells in vitro or in pathologic conditions in situ. Thus, we postulated a possible similarity between MS-1 and ICAM-1 expression in inflamed ST. METHODS: Immunohistochemical analysis was used to determine the distribution of ICAMs and MS-1 in ST from 10 patients with RA, 10 with osteoarthritis (OA), and 4 normal individuals. RESULTS: ICAM-1 expression was found on significantly more RA ST endothelial cells compared with normal cells, as well as on RA ST macrophages and lining cells. ICAM-2, also found on endothelial cells, showed no differential staining pattern. ICAM-3 was present on RA ST macrophages and lining cells as well as on some RA and OA endothelial cells. The MS-1 antigen was present on most RA and OA ST endothelia, lining cells, and macrophages. ICAM-1 expression and MS-1 expression in the lining layer were positively correlated in both RA and OA. CONCLUSION: ICAM-1, while found mainly on endothelial cells, is up-regulated on RA ST macrophages and lining cells, suggesting a role for these cells in the infiltration and tissue damage seen in the RA ST: ICAM-3, which is present mainly on normal resting leukocytes but not on normal endothelium, is expressed by some diseased ST leukocytes and endothelial cells. MS-1 is also found on the RA ST specialized, fenestrated endothelium, on macrophages, and in the lining layer. These results suggest that the differential expression of ICAMs and MS-1 in RA ST compared with normal ST might play a special role in the pathogenesis of RA. | |
| 7783053 | Synthesis and degradation of hyaluronate by synovia from patients with rheumatoid arthriti | 1995 Mar | OBJECTIVE: Hyaluronate degradation was analyzed in cultures of healthy tissue and tissue obtained from patients with rheumatoid arthritis. METHODS: Arthritic and healthy synovial tissues were incubated in culture with [3H]glucosamine. Labelled hyaluronate was extracted and its size determined by gel filtration. The production of low molecular weight hyaluronate was analyzed by pulse-chase experiments. Radical production was measured by a cytochrome C reduction assay. RESULTS: Healthy tissues and some arthritic tissues that did not contain significant amounts of granulocytes produced high molecular weight hyaluronate. In contrast, arthritic tissue infiltrated with granulocytes released low molecular weight hyaluronate. Pulse-chase experiments suggested that hyaluronate was degraded in these arthritic tissues. Exogenous hyaluronate was degraded only by intact tissue, but not by cells in culture obtained from synovial membranes of synovial fluids. Hyaluronate degradation was accompanied by massive oxygen radical production. Radical scavengers protected hyaluronate from degradation in synovial tissue. Some protection was achieved by superoxide and catalase or by methionine and complete protection by the iron chelators diethyltriaminepentacetic acid or deferoxamine mesylate. CONCLUSION: Degradation of hyaluronate in arthritic synovial tissue may be inhibited in tissue culture by radical scavengers. | |
| 8100702 | Second line (disease modifying) treatment in rheumatoid arthritis: which drug for which pa | 1993 Jun | OBJECTIVES: The objectives were to assess (a) the comparative merits of commonly used disease modifying drugs in the treatment of rheumatoid arthritis (RA) and (b) the influence of age, gender, and disease duration on the outcome of treatment. METHODS: Collected analysis (meta-analysis) was performed on results obtained during the first year of treatment in 1140 patients with RA treated with gold, penicillamine, sulphasalazine, or auranofin from a single centre. RESULTS: Gold, penicillamine, and sulphasalazine performed similarly, with about 60% of patients continuing to receive each of these drugs for at least one year. Neither gender nor age had an influence on the response to treatment, but patients with a longer disease duration showed a greater tendency to stop treatment. The median percentage improvement was 33% in visual analogue pain score and 50% in erythrocyte sedimentation rate. CONCLUSIONS: Routine use of these drugs should at least equal these results. Any new drug should either be substantially less toxic or at least as efficacious. | |
| 8948289 | Parathyroid hormone-related peptide in synovial fluid and disease activity of rheumatoid a | 1996 Nov | To understand the clinical role of parathyroid hormone-related peptide (PTHrP) in rheumatoid arthritis (RA), we analysed the circulatory and synovial fluid (SF) concentrations of the N- and C-terminal regions of PTHrP (N- and C-PTHrP) in RA (n = 38), osteoarthritis (OA, n = 45) and control (n = 11) subjects. The SF level of C-PTHrP was markedly higher in RA compared with control and OA groups, while no differences in circulatory C-PTHrP were present among the three groups. In contrast, the SF level of N-PTHrP was marginally higher in OA patients. C-PTHrP levels in SF correlated significantly with CRP, ESR and SF IL-1 receptor antagonist. To identify the mechanism of elevated PTHrP levels in SF, immunohistochemistry and in situ hybridization of synovial membrane (SM) were performed in each subject. Overexpression of PTHrP was identified in the sublining cells within papillary proliferated SM of RA patients only. Our results indicate that C-PTHrP produced from SM into SF reflects the disease activity in RA. | |
| 7944637 | Circadian rhythm of serum interleukin-6 in rheumatoid arthritis. | 1994 Aug | OBJECTIVES: To test the hypothesis of a diurnal variation in circulating levels of interleukin-6 (IL-6) and/or tumour necrosis factor-alpha (TNF-alpha) in rheumatoid arthritis and other inflammatory connective tissue diseases. METHODS: Serum levels of IL-6 and TNF-alpha were measured at three hour intervals from 7:30 to 22:30 in 48 patients with different rheumatic diseases as well as ten healthy controls. In four of the patients with rheumatoid arthritis, serum IL-6 levels were measured before and after one week of treatment with prednisolone 15-20 mg daily. RESULTS: IL-6 and TNF-alpha could not be detected in serum from healthy controls. However, serum IL-6 levels were substantially increased in patients with rheumatoid arthritis. Furthermore, patients with rheumatoid arthritis showed a statistically significant circadian variation in levels of IL-6. Peak values appeared in the morning and low values in the afternoon and evening. In contrast, levels were low and stable in other connective tissue diseases. Levels of TNF-alpha were low in patients with rheumatoid arthritis and high in patients with other connective tissue diseases, but without circadian rhythm. After treatment with prednisolone, levels of serum IL-6 decreased significantly, but the circadian rhythm remained. CONCLUSIONS: The circadian rhythm of circulating IL-6 might correspond to the circadian rhythm of symptoms in rheumatoid arthritis. The diurnal variation of IL-6, and possibly other cytokines, might explain the conflicting results previously reported on the inter-relationship between circulating IL-6 levels and disease activity in rheumatoid arthritis. |