Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
10946311 Type IIA secretory phospholipase A2 up-regulates cyclooxygenase-2 and amplifies cytokine-m 2000 Sep 1 Human type IIA secretory phospholipase A2 (sPLA2-IIA) is induced in association with several immune-mediated inflammatory conditions. We have evaluated the effect of sPLA2-IIA on PG production in primary synovial fibroblasts from patients with rheumatoid arthritis (RA). At concentrations found in the synovial fluid of RA patients, exogenously added sPLA2-IIA dose-dependently amplified TNF-alpha-stimulated PGE2 production by cultured synovial fibroblasts. Enhancement of TNF-alpha-stimulated PGE2 production in synovial cells was accompanied by increased expression of cyclooxygenase (COX)-2 and cytosolic phospholipase A2 (cPLA2)-alpha. Blockade of COX-2 enzyme activity with the selective inhibitor NS-398 prevented both TNF-alpha-stimulated and sPLA2-IIA-amplified PGE2 production without affecting COX-2 protein induction. However, both sPLA2-IIA-amplified PGE2 production and enhanced COX-2 expression were blocked by the sPLA2 inhibitor LY311727. Colocalization studies using triple-labeling immunofluorescence microscopy showed that sPLA2-IIA and cPLA2-alpha are coexpressed with COX-2 in discrete populations of CD14-positive synovial macrophages and synovial tissue fibroblasts from RA patients. Based on these findings, we propose a model whereby the enhanced expression of sPLA2-IIA by RA synovial cells up-regulates TNF-alpha-mediated PG production via superinduction of COX-2. Therefore, sPLA2-IIA may be a critical modulator of cytokine-mediated synovial inflammation in RA.
10898074 Elevation of only one rheumatoid factor isotype is not associated with increased prevalenc 2000 OBJECTIVE: To analyse the relationship between different rheumatoid factor (RF) isotype patterns and the prevalence of RA. METHODS: Serum samples, collected between 1973 and 1983 from nearly 14,000 randomly selected individuals, were screened for elevation of RF. In 1987, 173 RF positive and 156 matched RF negative participants were evaluated clinically. RESULTS: Participants with elevation of only one RF isotype, most commonly IgM, did not have significantly higher prevalence of RA than the RF negative controls. Of the 17 RF positive individuals who were diagnosed with RA, 14 (82%) had a combined elevation of IgM and IgA RF. CONCLUSION: In contrast to a combined elevation of IgM and IgA RF, elevation of only one RF isotype may not be a significant risk factor for the development of RA.
9725064 Analysis of rising from a chair after total knee arthroplasty. 1998 The relationship between the range of motion following total knee arthroplasty (TKA) and the height of chairs when rising from a seated position was analyzed. Forty-six TKA subjects were evaluated; 16 had osteoarthritis, 30 had rheumatoid arthritis. Subjects were divided into two groups based on their degree of knee flexion (average: 96.0 degrees; range: 75 degrees to 135 degrees; group 1 contained 24 subjects with < 100 degrees of flexion and group 2 contained 22 subjects with > 100 degrees of flexion) in order to evaluate the acceptable knee flexion angle required for comfortably rising from a chair. To evaluate the flexion-extension angle of the knee and hip joints, three goniometers, a large reaction force plate, and a switch sensor on the chair surface to detect the initiation of rising were used. One chair had a height equal to the subjects' lower leg length, while the height of the second chair was 120% of the subjects' lower leg length. Analysis showed that TKA patients with less knee flexion (< 100 degrees) required a high angular velocity of the hip and excessive swing velocity to lift the trunk forward than did those with a larger degree of knee flexion (> 100 degrees). We concluded that a minimum of 100 degrees of postoperative flexion is desired and that a higher chair is more suitable for TKA patients.
9644738 [Neopterin: laboratory marker of cellular immunity activation in rheumatoid arthritis]. 1998 AIM: Measurement of neopterin in the serum of patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: 59 patients with verified RA diagnosis (22 cases of joint lesion stage I-IIa, 27 of stage IIb-IIIa, 10 of stage IIIb-IV established roentgenologically, 48 patients were seropositive by IgM-rheumatoid factor) were examined for concentrations of serum neopterin and C-reactive protein (CRP). The activity and prognostic factors were characterized by modified Wilke method, the severity index was calculated. 100 healthy donors served controls. RESULTS: Immune inflammation in RA develops with growing neopterin concentration in the serum. This concentration well correlates with inflammation activity and intensification of systemic symptoms. CONCLUSION: Neopterin measurements may be important for determination of inflammation activity in RA. Further efforts should be made to ascertain relationships between neopterin hyperproduction and disturbances of cellular immunity in RA, clinical value of neopterin assays compared to the other laboratory evidence, feasibility of using neopterin levels to define prognosis and efficacy of on-going therapy.
11468900 [Effects of shaft length of finger joint prostheses on tension distribution in the bone]. 2001 May In order to investigate the influence of stem length in finger joint prostheses on stress in the surrounding bone area, finite element (FEM) calculations of finger bones before and after prosthetic replacement of metacarpophalangeal joints with cementless implants of different stem length were performed. CT scans of the metacarpal bone and proximal phalanx before and after implantation of a prototype of a noncemented semiconstrained implant for the MP joint, which has been developed to replace metacarpophalangeal joints destroyed by rheumatoid arthritis, were analysed. The FEM calculations showed comparatively decreased differences of the von-Mises stress after implantation of intramedullary stems reaching the middle of the diaphysis. At the metaphysis of the metacarpal head we found an increase of the von-Mises stress of 1.3 MPa (Mega Pascal = 10(6) Pa), an increase of 18.9 MPa around the shortest prosthesis and a decrease of 21.4 MPa around the prosthesis with the longest stem.
11081009 Differences by sex in correlates of work status in rheumatoid arthritis patients. 1999 Dec OBJECTIVE: To examine differences by sex in correlates of work status in rheumatoid arthritis (RA) patients seen in rheumatology clinical settings. METHODS: Associations of demographic factors, occupation, duration of RA, and scores for disease and psychological scales with work status according to sex were examined in a cross-sectional study of 960 RA patients, aged 18-64 years, of whom 451 were working and 254 were work-disabled. Comparisons of characteristics were conducted by logistic regression between working and work-disabled, and between working and not working subjects. RESULTS: For both men and women, the odds of work disability increased with age, duration of RA, nonwhite race, and scores indicating high levels of functional disability, pain, and helplessness. Work-disabled women were more likely than working women to have less than a high school education or a nonprofessional occupation, compared with little association of these variables with work disability in men. Unmarried men were more likely to be work-disabled than working, while marital status was not associated with work disability in women. Differences by sex in the associations of pain and helplessness scores with work disability were also observed. Similar results were observed in associations of these characteristics when the outcome was coded as working versus not working. CONCLUSIONS: These findings indicate some differences between men and women with RA in correlates of work disability that may help to more effectively target interventions. A patient's sex should be an important consideration in studies of work disability due to arthritis.
11411957 Treatment of rheumatoid arthritis by oral administration of bovine tracheal type II collag 2001 May We evaluated the efficacy and safety of orally administered bovine tracheal type II collagen (CGII) in the treatment of rheumatoid arthritis (RA). Twenty RA patients received 0.5 mg/day of CGII for 12 weeks. Eighteen of them had improvements in the clinical parameters studied (swollen and tender joint counts, 15-m walking time, duration of morning stiffness, and physician's global assessment of disease activity). Anti-CGII antibodies were positive in 57% and rheumatoid factor (RF) in 71% of the patients with a short history of RA ( < or =2 years), whereas only 23% of those with long histories (>2 years) presented autoantibodies to CGII and 38% had positive RF. After the treatment, four patients showed reduced RF levels and all those with detectable serum tumor necrosis factor alpha (TNF-alpha) experienced its return to normal or levels below those at study entry. Although a placebo effect cannot be discounted, the oral administration of bovine tracheal CGII induced clinical benefits in 90% of the patients, without the side effects usually associated with treatment. This is the first study showing that feeding CGII can induce reductions in RF and TNF-alpha. The data justify further controlled studies to assess the long-term efficacy of this treatment approach.
9592862 Elderly onset rheumatoid arthritis and polymyalgia rheumatica: ultrasonographic study of t 1998 The glenohumeral joints of 32 patients (aged 60 or above) were examined using ultrasonography. Thirteen patients were suffering from characteristic polymyalgia rheumatica (PMR) symptoms. In contrast 19 other patients initially had similar complaints, but were diagnosed as having elderly onset rheumatoid arthritis (EORA) upon development of typical symptoms. Ultrasound examination revealed glenohumeral joint inflammation in 61% (8 out of 13) of the patients with PMR and 63.2% (12 out of 19) of the patients with EORA. These findings suggest that a subgroup of patients with PMR and EORA suffers from shoulder joint inflammation and this synovitis/bursitis/intraarticular effusion might play an important role in the understanding of their symptoms. We conclude that overlapping forms of PMR and a predominate rheumatoid factor negative subgroup of EORA might exist and should be further characterized.
11429548 TACI-ligand interactions are required for T cell activation and collagen-induced arthritis 2001 Jul Interactions of the tumor necrosis factor superfamily members B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) with their receptors-transmembrane activator and CAML interactor (TACI) and B cell maturation molecule (BCMA)-on B cells play an important role in the humoral immune response. Whereas BCMA is restricted to B cells, TACI is also expressed on activated T cells; we show here that TACI-Fc blocks the activation of T cells in vitro and inhibits antigen-specific T cell activation and priming in vivo. In a mouse model for rheumatoid arthritis (RA), an autoimmune disease that involves both B and T cell components, TACI-Fc treatment substantially inhibited inflammation, bone and cartilage destruction and disease development. Thus, BLyS and/or APRIL are important not only for B cell function but for T cell-mediated immune responses. Inhibition of these ligands might have therapeutic benefits for autoimmune diseases, such as RA, that involve both B and T cells.
9819549 [Analysis of immune disorders in patients with rheumatoid arthritis and heart involvement] 1998 Jul Examinations of 121 patients with rheumatoid arthritis (RA) included immunological testing for antinuclear antibodies (ANA), lymphocyte blastogenesis test, and leukocyte migration inhibition test and functional cardiological examinations (ECG and EchoCG). RA patients with positive ANA test (n = 43) more often developed immune disorders: the titer of rheumatoid factor was higher and antibodies to type I collagen were more often detected; this was paralleled by decreased cellular immunity and macrophage formation in spontaneous lymphocyte blastogenesis test. The same group more often had ECG and EchoCG deviations. A conclusion is made about a probable role of immune disorders in the development of cardiac disease.
10764936 Objective auscultation for traditional chinese medical diagnosis using novel acoustic para 2000 Jun The goal of this work is to propose novel acoustic parameters of voice for the purpose of providing a quantitative analysis of auscultation in traditional Chinese medical diagnosis. There is rare amount of available literature related to this topic. Four novel acoustic parameters, the average number of zero-crossings, the variations in local peaks and valleys, the variations in first and second formant frequencies, and the spectral energy ratio, are presented to analyze and identify the characteristics among non-vacuity, qi-vacuity, and yin-vacuity subjects. Among these acoustic parameters, two temporal parameters, the average number of zero-crossings and the variations in local peaks and valleys, outperformed other parameters in classifying both non-vacuity and deficient subjects. The spectral energy ratio was adequate for the classification between qi-vacuity and yin-vacuity patients. This research is a first step in an ongoing effort to modernize the auscultation in traditional Chinese medical diagnosis.
10895376 Palindromic rheumatism: effect of dietary manipulation. 2000 May OBJECTIVE: Evaluation of the contribution of dietary components in triggering the attacks of palindromic rheumatism (PR), and the effect of dietary manipulation on the frequency and severity of PR attacks. METHODS: Sixteen patients (10 males, 6 females) were diagnosed as having PR during 1994-8 in one center. Their mean age was 45 +/- 6, duration of symptoms prior to diagnosis was 4 +/- 1.4 years, and frequency of PR attacks were 3.1 +/- 1.8/month. All patients were instructed to make a list of the food that was consumed daily and to specify the dates of PR episodes. Data were evaluated after a period of 2-4 months in each patient. RESULTS: In 5 patients (31%) there was an association between episodes of PR and certain foods that were consumed within 36 hours prior to PR episodes. These were fish (2 patients), eggs, canned vegetables and processed cheese (each in one case). Elimination of the relevant food from each patient's diet resulted in complete cessation of the PR attacks in two of the cases, while the other three had milder, infrequent attacks. Four patients were rechallenged with the offending food. In all cases it resulted in recurrence of the PR attacks. No association between PR episodes and prior consumption of certain foods could be documented in the other 11 patients. CONCLUSIONS: In some PR patients ingestion of certain foods, specific for each case, can trigger the typical attack. It is suggested that this association should be looked for in any PR patient, as elimination of the offending food from the diet may help in preventing the PR attacks.
11508576 Tumor necrosis factor-alpha (TNF-alpha) converting enzyme contributes to production of TNF 2001 Aug OBJECTIVE: Expression and function of tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) in synovia of patients with rheumatoid arthritis (RA) were examined to investigate posttranslational regulation of TNF-alpha production by TACE in RA. METHODS: Expression of TACE protein was evaluated by immunohistochemistry. Cytokines and soluble cytokine receptors were measured by ELISA. TACE mRNA was detected by RT-PCR. The enzymatic activity of TACE was measured using TACE-specific fluorogenic substrate. RESULTS: Expression of TACE at protein level in synovial tissue (ST) of patients with RA was significantly stronger than that of patients with osteoarthritis (OA). In RA, TACE was mainly expressed in CD68+ macrophage-like synovial cells. ST from 9 of 9 RA and 3 of 8 OA patients expressed TACE mRNA. RA ST cells possessed significantly higher TACE-like enzymatic activity than OA ST. A synthetic TACE inhibitor significantly reduced the release of TNF-alpha and p75 TNF receptor from RA ST cells. CONCLUSION: TACE is an important regulator of the secretion of TNF-alpha from synovia of patients with RA.
11196542 Epstein-Barr virus, methotrexate, and lymphoma in patients with rheumatoid arthritis and p 2001 Jan OBJECTIVE: Rheumatoid arthritis (RA) and primary Sjögren's syndrome (SS) are associated with an increased risk of lymphoma. Epstein-Barr virus (EBV), a ubiquitous herpes virus, has been linked etiologically to lymphoma in patients with RA and primary SS. Recently, methotrexate (MTX) has also been linked to the development of these lymphomas. We investigated the frequency of EBV in lymphoma tissue of patients with RA and primary SS and the association of MTX with lymphomagenesis. METHODS: Twenty-three patients with RA and 9 with primary SS with a history of lymphoma were identified by writing to all Arthritis Foundation member rheumatologists in Washington State. Formalin fixed, paraffin embedded tissue blocks were then requested from pathology laboratories. Lymph nodes from 5 RA patients without lymphoma were also studied. In situ hybridization using a biotinylated EBER-1 oligonucleotide probe was used to detect EBV in tissue sections. Positive and negative laboratory controls were used to ensure procedural integrity. RESULTS: Specimens from 21 RA patients were obtained, with 2 subsequently excluded due to specimen quality. Specimens from 6 patients with primary SS were obtained. In situ hybridization for EBV was positive in 5/19 (26%) RA patients and 1/6 patients with primary SS. In the nonmalignant lymph nodes no patient showed EBV. One primary SS and 12 RA patients were known to be taking MTX at the time of lymphoma diagnosis. Of the EBV positive RA lymphoma patients, 4/5 were receiving MTX at the time of diagnosis. These results show that EBV is present in lymphoma tissue of some patients with RA and very few with primary SS. CONCLUSION: EBV is over-represented in the lymphomas of patients with RA, but whether MTX plays a role in predisposing patients with RA and primary SS to the development of lymphoma, perhaps by influencing behavior of EBV, remains unclear.
10784522 Microsatellite analysis in rheumatoid arthritis synovial fibroblasts. 2000 May OBJECTIVES: Rheumatoid arthritis (RA) is a chronic disease characterised by irreversible destruction of the affected joints. As aggressive transformed-appearing synovial fibroblasts are commonly found at the site of invasion of the rheumatoid synovium into the adjacent cartilage and bone, the presence of microsatellite instability (MSI) and expression of mismatch repair enzymes as a possible mechanism in the alteration of these cells was examined. METHODS: DNA was extracted from the synovial fibroblasts and blood of 20 patients with long term RA undergoing joint replacement, and the presence of MSI was studied at 10 microsatellite loci. In addition, immunohistochemistry was performed to evaluate the expression of the two major mismatch repair enzymes (hMLH1 and hMSH2) in rheumatoid synovium. RESULTS: MSI could not be detected in any of the fibroblast cell populations derived from the 20 different rheumatoid synovial samples. In addition, strong expression of mismatch repair enzymes could be seen in numerous cells, including fibroblasts, throughout the synovium. CONCLUSIONS: Applying the currently used and established markers for MSI, the data show for the first time that MSI does not appear to have an important role in alteration of rheumatoid synovial fibroblasts into an aggressive phenotype. On the other hand, strong mismatch repair enzyme synthesis in rheumatoid synovium supports the hypothesis of continuing DNA repair, presumably due to long term, inflammation induced DNA damage.
11328838 Retain or sacrifice the posterior cruciate ligament in total knee arthroplasty? A histopat 2001 May BACKGROUND: The decision whether to retain or resect the posterior cruciate ligament in total knee arthroplasty is at present determined clinically by preoperative radiological variables focusing upon the amount of joint destruction, and subsequent soft tissue contractures. However, these variables give only indirect information on the histological integrity and proprioceptive properties of the posterior cruciate ligament. METHODS: Twenty posterior cruciate ligaments, obtained during total knee arthroplasty, were evaluated histologically to study the relation between the degree of preoperative radiological joint destruction, structural integrity of the posterior cruciate ligament and the neurological integrity of the targeted tissue. Eleven patients had osteoarthritis and nine patients rheumatoid arthritis. Haematoxylin and eosin, Alcian blue (mucoid degeneration), elastica von Gieson, Gomori (elastic fibres and collagen), and immunohistochemical staining for neural structures were used. RESULTS: In all but one of the posterior cruciate ligaments, morphologically intact neural tissue was present in the peritendineum of the ligaments. Structural integrity of the collagen framework was present in only seven posterior cruciate ligaments. These cases all had grade three or four radiological joint destruction. In 13 of the specimens a certain degree of mucoid degeneration of collagen was present. All patients with grade five radiological knee joint destruction displayed mucoid degeneration and irregularity of the posterior cruciate ligament fibres. CONCLUSION: Because of the extensive architectural and probably functional damage of the posterior cruciate ligament in patients who have grade five radiological knee joint destruction, retention of the posterior cruciate ligament in knee prosthesis should not be advocated.
11594227 [Should indications for amniotic membrane transplantation be altered in concurrent rheumat 2001 Sep BACKGROUND: Amniotic membrane transplantation (AMT) shows good results in corneal epithelial defects or ulcerations. However, in patients with rheumatoid arthritis (RA) these corneal defects represent a somewhat greater challenge. We address the question whether AMT has to be indicated differently in RA patients. PATIENTS AND METHODS: We retrospectively analysed 25 AMTs performed between October 1998 and August 2000 in 22 patients for corneal epithelial defects and ulcerations. In 8 patients (11 AMTs) RA was present (group A) and no RA (group B) was found in 14 patients (14 AMTs). RESULTS: Epithelial closure could be achieved in 24/25 cases after a mean of 24.9 days. In 15/25 cases the epithelium remained closed over a minimum of 3 months (successful AMT). In group B, 12/14 AMTs (85.7%) were successful, but only 3/11 AMTs (27.3%) were successful in group A. DISCUSSION: In addition to the pronounced keratoconjunctivitis sicca, immune-mediated inflammatory aspects are suspected to be the reason for the poor results of AMT in RA patients. But as alternative surgical procedures (e.g. keratoplasty) implicate specific problems in RA, we believe that after failure of conservative treatment AMT is a reasonable procedure for corneal defects even in RA patients.
10079586 Multicentric reticulohistiocytosis: a mimic of gout and rheumatoid arthritis. 1999 Mar Multicentric reticulohistiocytosis is a rare cutaneous-articular disease that may mimic more common disorders such as rheumatoid arthritis or tophaceous gout. In one fourth of patients, it is a paraneoplastic process. This brief overview is aimed at physicians who care for patients with polyarthritis, to alert them to distinctive features that differentiate multicentric reticulohistiocytosis from the common arthritides.
10614754 Ten-year follow-up of silicone arthroplasty of the metacarpophalangeal joints in rheumatoi 1999 Dec In resection arthroplasty of destroyed metacarpophalangeal joints stabilisation with a silicone spacer is regarded as the gold standard. In 28 patients with rheumatoid arthritis (34 hands) 102 arthroplasties of the metacarpophalangeal joint were assessed a median of 10 years postoperatively (range 8.7-12.5). All patients reported pronounced subjective relief of pain, and in three quarters function of the hand had improved. The median active range of movement decreased from 40 degrees (range 10 degrees-90 degrees) preoperatively to 35 degrees (range 5 degrees-85 degrees) postoperatively. Ulnar deviation was corrected from a median of 35 degrees (range 0 degrees-60 degrees) preoperatively to 10 degrees (range 0 degrees-40 degrees) postoperatively. The extension deficit was improved from a median of 35 degrees (range 10 degrees-80 degrees) before surgery to a median of 10 degrees (range 0 degrees-30 degrees) at follow up. Grip strength remained unchanged. Radiological examination showed surrounding osteolysis in 89% of the implants and 28% had broken. The well-known discrepancy between fair clinical and good subjective results with distinct radiological findings such as osteolysis was therefore confirmed. Material fatigue and sharp bony edges that result from osteolysis may be the cause of the relatively common implant fractures and ulnar deviation in this long-term follow-up.
10587546 The relative proportions of secreted interleukin-2 and interleukin-10 determine the magnit 1999 Dec OBJECTIVE: To investigate the mechanisms of the deficient proliferative responses by rheumatoid arthritis (RA) peripheral blood T cells to the recall antigen tuberculin purified protein derivative (PPD). METHODS: The concomitant production of interleukin (IL)-2, IL-10 and lymphocyte proliferation were studied by enzyme-linked immunosorbent assay and [(3)H]thymidine uptake, respectively, in 12 normal controls and eight RA patients. RESULTS: An inverse correlation was found between IL-10 production and proliferation to PPD. The proliferative response was shown to be critically affected by the IL-2:IL-10 ratio so that absolute levels of secreted IL-2 or IL-10 correlated non-significantly with lymphocyte proliferation. CONCLUSION: The deficient T-cell proliferation in RA peripheral blood mononuclear cells is related to the relative proportions of IL-2:IL-10 rather than the absolute amounts secreted.