Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8657998 | [Felty syndrome: a therapy-resistant variant of chronic rheumatoid arthritis? 2 case repor | 1996 Apr 16 | Felty's syndrome is a rare but serious extra-articular manifestation of rheumatoid arthritis. Morbidity as well as mortality are increased on account of greater susceptibility to infectious agents. We report on two patients suffering from Felty's syndrome who were successfully treated by cyclophosphamide. A review of the literature with special regard to treatment of Felty's syndrome is given. | |
| 1472834 | Bucillamine (a new therapeutic agent for rheumatoid arthritis) induced nephrotic syndrome: | 1992 Nov | Two cases of nephrotic syndrome during bucillamine treatment were encountered in 1989 in our hospital; both patients had suffered from rheumatoid arthritis for 2 years. They had received 200 mg bucillamine orally per day for 3-4 months before the onset of the nephrotic syndrome. Discontinuation of bucillamine led to complete remission of the nephrotic syndrome within 1 year. Bucillamine is a new therapeutic agent for rheumatoid arthritis developed in 1982 in Japan. Since 1985, 14 cases of nephrotic syndrome, including the two cases reported here have been reported. We review these cases and discuss the pathogenesis. | |
| 8674148 | Oral tolerance: mechanisms and possible role in inflammatory joint diseases. | 1996 Feb | Decreased systemic immune responsiveness to a specific antigen following exposure to that antigen by the enteric route is termed 'oral tolerance.' Oral tolerance is revealed when attempts are made to parenterally immunize the host to the same antigen that was previously administered orally or intragastrically. A similar phenomenon is also seen following antigen exposure via the nasal mucosa and a related phenomenon is seen following antigen exposure in the upper respiratory tract. There has been a marked renewal of interest in the mechanisms that underlie oral tolerance because of its potential role for preventing and treating autoimmune and inflammatory diseases and IgE-mediated allergic disorders. The specific factors that determine whether or not the host develops mucosal tolerance to an antigen administered by the mucosal route are also of substantial importance for those involved in mucosal vaccine development. Furthermore, putative abnormalities in the ability of the host to develop mucosal tolerance may play a pathogenetic role in certain autoimmune and allergic diseases and disorders. Several well-defined immunological mechanisms mediate oral tolerance. These include the induction, following mucosal antigen exposure, of regulatory populations of T-cells that can down-regulate specific immune responses (e.g. DTH) via the production of specific cytokines (e.g. TGF-beta 1, IL-10 and IL-4). In addition, clonal anergy, clonal deletion and antibody-mediated suppression can be shown to play a role in the induction and maintenance of mucosal tolerance in several experimental systems. In animal studies, the onset of collagen-induced, adjuvant-induced, antigen-induced and pristane-induced arthritis has been delayed and the severity of ongoing disease diminished following feeding collagen type II. Mucosal tolerance has been clearly demonstrated in humans and clinical studies have been undertaken to treat rheumatoid arthritis using a similar approach. Results of initial clinical studies in rheumatoid arthritis indicated a modest improvement and further studies are ongoing in this and other autoimmune diseases (e.g. multiple sclerosis, autoimmune uveitis and insulin-dependent diabetes). This approach, if successful, could offer a new and novel therapeutic modality for preventing autoimmune and allergic disorders, and modulating ongoing disease. | |
| 7538096 | [Normal synoviocytes and synoviocytes from osteoarthritis and rheumatoid arthritis bind ex | 1995 Apr | Extracellular matrix proteins are increased in inflammatory synovitis. We showed previously that the in situ expression of the corresponding extracellular matrix receptors (beta 1-integrins) is enhanced in synoviocytes (SC) of synovitis of different etiology (16). To investigate the adhesion of SC to extracellular matrix proteins, we examined the attachment of SC from normal and inflamed synovia to fibronectin, tenascin, laminin and collagen type IV. Compared to normal SC and SC of osteoarthritis, SC of rheumatoid arthritis showed an increased binding to tenascin, laminin, fibronectin and collagen type IV, suggesting a distinctive interaction of SC and extracellular matrix proteins in rheumatoid arthritis. Furthermore, the increased binding of SC of rheumatoid arthritis to extracellular matrix proteins may play a role in tissue remodelling associated with rheumatoid arthritis. | |
| 1432999 | Cyclosporine and chloroquine synergistically inhibit the interferon-gamma production by CD | 1992 Sep | OBJECTIVE: To investigate synergistic interaction between cyclosporine (Cy) and chloroquine (Chl) in an in vitro system, with regard to interferon-gamma (IFN) production by OKT3 activated T cell clones. METHODS: CD4+ and CD8+ T cell clones, derived from synovial tissue of a patient with rheumatoid arthritis (RA) were activated with plastic coated OKT3 monoclonal antibody in the presence or absence of various concentrations of Cy, Chl and their combinations. After 24 h of incubation the supernatants were assayed for IFN by ELISA: RESULTS: Cy as well as Chl were able to completely inhibit in a concentration dependent fashion the IFN production by CD4+ and CD8+ T cell clones. Combinations of Cy and Chl, which in themselves give minor inhibition of IFN production, were able to inhibit in a synergistically enhanced fashion the production of IFN by these clones. The synergy was formally proven by the construction of isoboles. This synergy was most pronounced when drug concentrations were used which individually gave minor inhibition of IFN production. CONCLUSION: We conclude that the results of our in vitro experiments may give rise to further investigation of the promising combination of Cy and Chl in the treatment of RA. | |
| 8303435 | Cervical spine surgery in rheumatoid arthritis: improvement of neurologic deficit after ce | 1993 Dec | Ninety of 110 consecutive patients with rheumatoid deformities of the cervical spine surgically treated had associated neurologic deficits. Fifty-five patients had atlantoaxial subluxation. In this group, there were 16 Ranawat Class I patients (normal), 21 Class II (weakness, hyperreflexia, dysesthesia), 13 Class IIIA (paresis and long-tract findings but can ambulate), and five Class IIIB (quadriparesis and inability to ambulate). After C1-C2 stabilization, 94.8% improved at least one class. Twenty-two patients had AAS-SMO (atlanto-axial subluxation and superior migration of the odontoid) only one before surgery was Class I, five Class II, eight Class IIIA, and eight Class IIIB. Seventy-six percent improved at least one class after surgery. Nineteen had isolated subaxial subluxation (SAS). Three were Class I, two Class II, nine Class IIIA, and five were Class IIIB. After surgery, 94% improved at least one class, and all were ambulating. Fourteen had combined AAS-SMO-SAS deformities. There were no Class I patients, only four Class II, four Class IIIA, and six Class IIIB. After surgery, 71% improved. The four deaths that occurred in the immediate postoperative period were Class IIIB. Fifteen patients had worsening or recurrence of their symptoms. Thirteen of these were related to the later development of subaxial subluxation. Neurologic symptoms and recovery were related to severity of the deformity. Those with SMO had greater neurologic deficits and worse results. In general, neurologic recovery is encouraging even in the IIIB patient. Earlier surgery should be done, however, particularly before SMO develops, if possible.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 8403807 | 1H-nuclear magnetic resonance studies of human synovial fluid in arthritic disease states | 1993 Sep | 1. A 1H-n.m.r. method was used to measure concentrations of valine, alanine, lactate, acetate, hyaluronan and lipids in synovial fluid obtained, during the normal course of examination from the knee joints of patients attending rheumatology and orthopaedic clinics. Fluid was available from 16 patients with osteoarthritis, 18 patients with rheumatoid arthritis, four patients with meniscal tear and one patient each with systemic lupus erythematosis, mono-arthritis, synovitis and loose bodies. Four normal specimens were obtained for comparison. 2. Valine, alanine and acetate levels all showed a normal Gaussian distribution, reflecting the distributions within the serum of the sample population. 3. Lactate concentrations divided into two distinct patterns. At concentrations below 2.5 mmol/l the lactate levels showed a Gaussian distribution, reflecting the distribution in normal serum. The normal synovial fluid specimens belong to this distribution. Above 2.5-3.0 mmol/l, lactate levels were asymmetric in distribution with a long tail at higher concentrations. These high levels of lactate can be explained by the generation of lactate through anaerobic metabolism within the synovial cavity. This metabolic process is triggered by a general inflammatory condition such as in rheumatoid arthritis. 4. The distribution of n.m.r.-observable lipid concentrations in rheumatoid arthritis and osteoarthritis each shows a normal distribution and the mean concentration is significantly higher in rheumatoid arthritis. 5. An increased n.m.r.-observable hyaluronan concentration is associated with an inflammatory situation. 6. It is concluded that raised levels of lactate and n.m.r.-observable hyaluronan and lipids are useful markers to aid the clinical distinction between rheumatoid arthritis and osteoarthritis.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1581372 | Activity-induced pain in rheumatoid arthritis functional class II and its relations with d | 1992 Mar | One aim of this study was to describe inflammatory activity, joint destruction, work status, and demographic factors in a group of 69 American Rheumatism Association functional class-II rheumatoid arthritis patients: 56 women and 13 men, mean age 54 years (SD 11), mean symptom duration 14 years (SD 11). Another aim was to determine correlations between activity-induced pain and other variables. Patients were assessed with Ritchie's articular index, Larsen's radiologic index, and laboratory tests. Deformity in hands and knee joints, and grip strength, were determined. Results from earlier investigations of functional impairment and psychosocial capacity were also used. Of the patients, 4% had high inflammatory activity. Joint erosions were found in between 4% (knee joints) and 55% (wrists) of the joints examined. Of the patients aged less than 65, 43% were working. Activity-induced pain was related with work status (p = 0.0002). It also correlated significantly (p less than or equal to 0.01) with inflammatory activity (r(s) = 0.34), but not with joint destruction (r(s) = 0.21). | |
| 1486748 | Treatment of rheumatoid arthritis with anti CD4 monoclonal antibody. Open study of 25 pati | 1992 Dec | Twenty-five defined severe RA patients (pts) (17 F, 8 M) were treated in an open study with a CD4 murine monoclonal antibody (Mab) (B-F5 clone, IgG1). Mab's daily dose was 10 mg (1 pt), 15 mg (2 pts), 20 mg (17 pts), 30 mg (4 pts) and 50 mg (1 pt) for 10 days. Tolerance was fair. Clinical improvement occurred during treatment period or within the first month in all but 2 patients, irrespective of Mab dosage. Improvement duration was variable (1 to 12 months), half of the patients still show signs of improvement at month 4. Biological parameters (CRP) improved parallel to the clinical. At day 180, 25% of the patients showed a reduction of 50% or more of the initial CRP values. There is no modification of RF titers, renal and hepatic parameters. Sequential evaluation showed a decrease of B, TCD3, CD4, CD8 lymphocytes and monocytes two hours after Mab infusion and return to baseline in 20 hours. Xenogenic immunization occurred in 6 patients without influence upon clinical response. These modifications are moderate and transient and do not account for the more prolonged effect in some cases, nor do they offer any prediction of further clinical response. | |
| 8136466 | Hormones in self tolerance and autoimmunity: a role in the pathogenesis of rheumatoid arth | 1993 | Recent studies indicate that pituitary hormones play an important role in immunoregulation. The evidence that endocrine abnormalities are associated with, and may contribute to the development of autoimmune disease is reviewed and discussed. Patients suffering from rheumatoid arthritis show a number of endocrine abnormalities that indicate altered pituitary function. The decreased bioactivity of prolactin and possible inadequate glucocorticoid response to inflammation found in patients may have an etiological role in rheumatoid arthritis. The further clarification of the possible role of endocrine factors in the etiology of autoimmune disease is needed urgently. | |
| 7652463 | Serum cytokines in patients with rheumatoid arthritis. Correlation of interferon gamma and | 1995 | Serum cytokines such as interleukin 1 beta (IL-1 beta), interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF alpha) were measured in 40 patients with rheumatoid arthritis (RA). In the 40 patients studied, serum IL-1 beta was detected in 5 patients, IFN-gamma in 10 patients, and TNF alpha in 20 patients. The IL-1 beta-positive group showed increased values of activity indices compared to the IL-1 beta-negative group. Values of serum IFN-gamma correlated well with the number of peripheral blood lymphocytes and CD3+ cells and with the percentage of CD3+ CD26+ cells. Values of serum TNF alpha correlated positively with the number of peripheral blood monocytes and the percentage of CD3+ HLA-DR+ and CD3+ CD25+ cells. These results indicated that serum IL-1 beta in RA patients reflects the activity of RA, while the serum IFN-gamma and TNF alpha in RA patients may be related to circulating activated lymphocytes and monocytes, respectively. | |
| 8881465 | [Rheumatoid aortic insufficiency. Apropos of a case treated by mechanical valve replacemen | 1996 Jun | Rheumatoid valve lesions have been described for a long time in the literature. The authors report a case of rheumatoid aortic incompetence presenting with complete heat failure and treated semi-urgently by mechanical valve replacement. The pathological lesions observed on the aortic valves were pathognomonic of rheumatoid arthritis. Transthoracic echocardiography should be systematically proposed in the context of severe rheumatoid arthritis looking for valvular heart disease. | |
| 1618422 | [Ultrastructure of the long flexor and extensor tendons of the hand in rheumatic tenosynov | 1992 May | Tendon ruptures are a frequent problem in patients affected by rheumatoid arthritis. The aim of the present study was to further characterize the known macroscopic changes of tendon tissue by micromorphological methods. Flexor and extensor tendon samples (n = 28) in rheumatoid arthritis were investigated by light- and transmission electron microscopy. In all cases, marked alterations in fibril architecture and structure were found. The fibril diameter showed a higher variability (range = 20-490 nm, x = 98.9 nm, s = 49.1 nm) in comparison with the control group of normal tendons (range = 20-290 nm, x = 119.0 nm, s = 34.9 nm). The average distance between the major bands in rheumatoid arthritis was reduced (from 57.3 nm down to 54.8 nm). Rare minor bands were detected. Oxytalan and mature elastic fibres were destroyed. These findings suggest that a causal correlation exists between altered matrix substructure and insufficient function of the tendon tissue in rheumatoid arthritis. | |
| 7758062 | Efficacy and safety of auranofin in patients with active early rheumatoid arthritis. | 1995 Jan | The efficacy and safety of auranofin, an oral gold compound, were investigated for the treatment of patients with active early rheumatoid arthritis (RA). The 48 patients enrolled in the study had RA that satisfied the diagnostic standards set in 1987 by the American College of Rheumatology, was of less than 5 years' duration, and was of stage I or II and class 1 or 2 according to the Steinbrocker system. Auranofin 3 mg was administered orally twice daily for 12 months. All patients also received nonsteroidal anti-inflammatory drugs as a basic therapy. Some patients also received steroids, although the dose was limited to < 5 mg/d prednisolone equivalent. No other disease-modifying antirheumatic drug (DMARD) was administered. On the first day of the trial and after 3, 6, and 12 months of treatment, clinical symptoms, modified Lansbury index, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and the patients' assessments of severity of pain, judged using a visual analog scale, were evaluated. All of these measurements had improved significantly after 12 months of treatment. Moreover, no adverse events were observed during the treatment period. Therefore, the results confirm that auranofin is an effective and safe DMARD and is useful as a first-line therapy in the treatment of patients with RA. | |
| 8279269 | Relation between intra-articular temperature of the arthritic temporomandibular joint and | 1993 Oct | Arthritic temporomandibular joints were investigated for intra-articular temperature and joint fluid content of calcitonin gene-related peptide. Eleven patients (16 joints) with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or chronic unspecific polyarthritis or monarthritis participated in the study. The intra-articular temperature varied between 35.5 and 37.5 degrees C, with a mean of 36.5 degrees C. The concentration of calcitonin gene-related peptide varied between 7.5 and 749.0 pmol/l, with a mean of 108.6 pmol/l. There was a positive correlation between the intra-articular temperature and the joint fluid concentration of calcitonin gene-related peptide. The plasma level of the peptide was on an average 5% of the joint fluid level. | |
| 7481584 | Scoring of synovial membrane hypertrophy and bone erosions by MR imaging in clinically act | 1995 | MRI-scores of synovial membrane hypertrophy and bone erosions of the RA-wrist are introduced. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) and conventional radiography (CR) of the wrist were performed in 16 patients with rheumatoid arthritis (RA) and 3 healthy controls. A MRI-score of synovial membrane hypertrophy was obtained by summation of gradings of synovial hypertrophy in 6 regions of the wrist. The score was significantly higher in wrists with than in wrists without clinical signs of active arthritis. The score was 0 in all healthy controls. Each bone of the wrist was assessed by MRI and CR with respect to bone erosions. Bone erosions were detected by MRI in 14 wrists in contrast to only 6 wrists by CR. In all patients the erosions were more numerous on MRI. The introduced methods may be useful quantitative measures of synovitis and early joint destruction in RA. | |
| 8068493 | Pharmacokinetics and pharmacodynamics of hydroxychloroquine enantiomers in patients with r | 1994 | Hydroxychloroquine, a slow acting antirheumatic drug, is administered as the racemic mixture. Blood concentrations of the two enantiomers of hydroxychloroquine were measured in two studies, one study of eight patients, in whom blood and urine concentrations were measured during the first 6 months of therapy with rac-hydroxychloroquine, and one of 43 patients who had received rac-hydroxychloroquine therapy for at least 6 months. In the latter study rheumatoid disease activity was also measured. The pharmacokinetics of hydroxychloroquine were found to be enantioselective. The concentrations of (-)-(R)-hydroxychloroquine were higher than those of the (+)-(S)-antipode in all patients at all time points, although the ratios of the two enantiomers did display a two to three fold variability between patients. Both total and renal clearance were greater for the (+)-(S)-enantiomer. From the observational, cross-sectional study design used, it was not possible to differentiate concentration-effect relationships of the two enantiomers. The 11-fold range of drug concentrations swamped any effect of variability between patients in enantiomer proportions. Blood concentrations of both enantiomers were significantly higher in groups of patients with less active disease. | |
| 1280847 | T-cell receptor-major histocompatibility complex genetic interactions in rheumatoid arthri | 1992 Nov | Rheumatoid arthritis (RA) is a complex multifactorial illness. It is proposed that multiple genes involved in immune recognition interact to produce a state of genetic susceptibility for RA. The role of HLA and T-cell receptor and other background genes is discussed, with an emphasis on their role in shaping the T-cell repertoire. | |
| 8507217 | Expression of monocyte chemotactic and activating factor in rheumatoid arthritis. Regulati | 1993 Jun | OBJECTIVE: To investigate whether monocyte chemotactic and activating factor (MCAF) contributes to the accumulation of macrophages in the joints of patients with rheumatoid arthritis (RA). METHODS: MCAF was measured by radioimmunoassay. MCAF gene expression was determined by Northern blotting and reverse-transcriptase polymerase chain reaction. Recombinant human MCAF was injected into rabbit joints to evaluate the effect of MCAF on infiltration of macrophages. RESULTS: High levels of MCAF were detected in synovial fluid from patients with RA. Cells freshly isolated from synovial fluid expressed MCAF messenger RNA (mRNA). Fibroblast-like synoviocytes were found to express MCAF mRNA and to secrete MCAF in response to interleukin-1 (IL-1) and tumor necrosis factor in vitro. IL-1 also promoted MCAF gene expression in rabbit synovial tissue in vivo. MCAF caused marked infiltration of macrophages in rabbit synovial tissue. CONCLUSION: Our findings suggest that MCAF may contribute to the accumulation of macrophages in inflamed rheumatoid joints. | |
| 8519117 | Triple arthrodesis in rheumatoid arthritis. | 1993 Jul | Fifty-five patients with rheumatoid arthritis were treated with 65 triple arthrodeses of the hindfoot from March 1975 through July 1985. Twelve patients (12 procedures) have died, and follow-up evaluation could not be completed on three patients (four procedures), leaving 40 patients (49 procedures) available for clinical and roentgenographic evaluation. There were 32 women and eight men, with an average age at the time of surgery of 50 years. The follow-up period averaged five years. Standard operative technique involved medial and lateral incisions with staple fixation and local bone grafting. Correction of deformity was performed with closing wedge osteotomies. All patients had moderate to severe pain preoperatively and difficulty with ambulation. Postoperatively, 94% of the patients had significant pain relief and 83% had complete pain relief. Ambulatory status was improved in 80% of the patients. Ninety percent were at least community ambulators at the time of review, whereas more than half the patients were limited to household ambulation preoperatively. Complications included four superficial wound infections, all of which responded to local care. One patient required revision surgery for pseudarthrosis, and three patients had progression of ankle disease and required pantalar arthrodeses. There was no significant progression of fore-foot or knee symptoms, however, and there was no progression of ankle symptoms in patients whose hindfeet were corrected to 0 degrees-10 degrees valgus. Triple arthrodesis in the rheumatoid population has a high union rate. Pain relief and ambulation improvement can be expected. |