Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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16960936 | Insufficient endogenous control of tumor necrosis factor-alpha contributes to temporomandi | 2006 Sep | OBJECTIVE: To investigate whether pain and tissue destruction in the temporomandibular joint (TMJ) of patients with rheumatoid arthritis (RA) are influenced by plasma levels of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) or the soluble receptor TNFsRII. METHODS: Fifty-one patients with RA were included. TMJ resting pain intensity, pain intensity upon mandibular movement, tenderness to palpation, pressure-pain threshold, and presence of anterior open bite were assessed. Venous blood was obtained for analysis of TNF-alpha, TNFsRII, and inflammatory markers. RESULTS: A total of 29 patients had TMJ pain and 22 patients had anterior open bite. In the group of patients with TMJ pain, 12 had anterior open bite and 17 did not. In the patients without TMJ pain 10 patients had anterior open bite and 12 did not. Patients with or without anterior open bite did not differ regarding any investigated variable. Plasma TNF-alpha and TNFsRII were positively correlated in the total patient sample. TNFsRII was negatively correlated with degree of anterior open bite in patients with TMJ pain but positively correlated with TMJ pressure-pain threshold in patients with elevated plasma TNF-alpha. CONCLUSION: Our results indicate that insufficient systemic endogenous control of TNF-alpha seems to contribute to TMJ pain and tissue destruction in RA. | |
16980807 | Effects of regular exercise on pain, fatigue, and disability in patients with rheumatoid a | 2006 Oct | Rheumatoid arthritis (RA) is a major health problem in Korea. To explore the effects of regular exercise on pain, fatigue, and disability, a descriptive study was conducted in 435 Korean patients with RA. Exercisers were defined as those who are currently exercising more than 3 times a week, for at least 20 minutes, and for more than 6-consecutive months after being diagnosed with RA. The primary finding was that exercisers had significantly less fatigue and disability compared with nonexercisers. Results suggest that regular exercise has advantages for patients with RA to decrease fatigue and disability. | |
15971434 | Is there a rationale to using leflunomide in early rheumatoid arthritis? | 2005 May | The efficacy of leflunomide in the treatment of early rheumatoid arthritis (RA) patients might be attributed to the fact that it acts at several levels, including the anti-inflammatory and anti-destructive pathways. This is in addition to its inhibition of the L-dihydro-orotate dehydrogenase (DHOH) enzyme and pyrimidine de novo synthesis which decreases cell proliferation and more specifically early activated CD4+ T cells, as well as monocyte interaction with T cells leading to cytokine and anticytokine production. Recent studies clearly indicate the rationale of an early administration of leflunomide in RA patients, particularly in the light of the results of previously reported clinical studies showing its rapid onset of action when compared to other DMARDs. The early efficacy and safety of leflunomide in patients with early RA is sustained over a long period, and the long-term safety profile of leflunomide does not seem to be different from that observed in phase III trials. | |
15709923 | Rheumatoid disease and the heart: from epidemiology to echocardiography. | 2005 Jan | Rheumatoid disease (RD) is a common chronic inflammatory condition associated with progressive joint destruction. Sufferers of RD experience reduced life expectancy, reflected in the increased standardised mortality rates reported in several studies over the last 50 years. Most studies indicate that the increased mortality affecting this population is mainly due to cardio-vascular disease. Epidemiological data have revealed an increased risk of developing ischaemic heart disease and heart failure in RD. The increased risk of ischaemic heart disease may result from traditional risk factors but data suggest that RD may confer risk independently. Although pericardial involvement, valvopathy and myocarditis are the most well-recognised cardiac manifestations of RD, and constitute a rheumatoid heart disease, these features are relatively benign. The current prevalence of rheumatoid heart disease in the era of early administration of disease-modifying therapy requires evaluation. | |
17105852 | S100A4 is expressed at site of invasion in rheumatoid arthritis synovium and modulates pro | 2006 Dec | The metastasis-associated protein S100A4 promotes the progression of cancer by regulating the remodelling of the extracellular matrix. The expression of S100A4 in vivo is shown and the functional role of S100A4 in the pathogenesis of osteoarthritis and rheumatoid arthritisis is explored. The expression of S100A4 in rheumatoid arthritis, osteoarthritis and normal synovial tissues was determined by immunohistochemistry. The expression of matrix metalloproteinase (MMP) mRNA was measured in rheumatoid arthritis and osteoarthritis synovial fibroblasts treated and untreated with S100A4 oligomer by real-time polymerase chain reaction. Levels of released MMPs were confirmed by ELISA in cell culture supernatants. S100A4 protein was expressed in rheumatoid arthritis and osteoarthritis synovial tissues, in contrast with normal synovium. S100A4 up regulated MMP-3 mRNA in rheumatoid arthritis synovial fluid, with a peak after 6 h. This resulted in release of MMP-3 protein. MMP-1, MMP-9 and MMP-13 mRNA were also up regulated in synovial fluid, but with different kinetics. MMP-14 mRNA showed no change. Thus, S100A4 protein is expressed in synovial tissues of patients with rheumatoid arthritis and osteoarthritis in contrast with healthy people. It induces the expression and release of MMP-3 and other MMPs from synovial fluid. The data suggest that S100A4-producing cells could be involved in the pathogenesis of osteoarthritis and rheumatoid arthritis, including pannus formation and joint destruction. | |
15696560 | Development and assessment of indicators of rheumatoid arthritis severity: results of a De | 2005 Feb 15 | OBJECTIVE: To develop a set of indicators for assessing the severity of rheumatoid arthritis (RA) through medical records. METHODS: A list of 47 potential indicators of RA was reviewed by an expert Delphi panel of 6 rheumatologists. The Delphi method is a formal approach for gathering expert opinion. The 47 potential indicators included items from the following 5 categories: radiologic and laboratory findings, clinical and functional status measures, extraarticular manifestations, prior surgical history, and medications. The panelists rated the potential indicators' relationship to RA disease severity. Each panelist rated each indicator on a scale of 0-6, in which 0 indicated no relationship at all with severe RA and 6 indicated a perfect relationship with severe RA. After a baseline set of ratings, a literature review was distributed to the panelists along with the panel's initial mean ratings and the ranges. The panelists then met to discuss the literature and rerate all indicators. RESULTS: After repeat ratings and review of relevant literature, the panel rated 28 of 47 (60%) potential indicators as having a strong or very strong relationship to severe RA. These 28 indicators were drawn from all 5 categories of potential indicators. There was agreement among the panelists on ratings for 41 of 47 indicators. Agreement was defined as a range of scores among the panelists =3. CONCLUSION: A Delphi panel of rheumatologists agreed that data generally available in medical records may serve as potential indicators of severe RA. | |
15878905 | Dendritic cells, Fc{gamma} receptors, and Toll-like receptors: potential allies in the bat | 2005 Nov | Recent findings suggest an important role for Fcgamma receptors and Toll-like receptors expressed by dendritic cells (DC) in the pathogenesis of rheumatoid arthritis (RA). Possibly, DC behaviour might be tuned to counteract the misbalanced immune system in RA. Understanding the precise mechanisms that determine the skewed immune response in RA may provide new clues for the therapeutic use of DC in RA. | |
16249225 | Prevalence and predictors of disability in valued life activities among individuals with r | 2006 Jun | OBJECTIVE: To identify the prevalence of disability in a wide range of life activities and identify factors associated with such disability using the Verbrugge and Jette disablement model as a framework. METHODS: Data were from a panel study of 548 individuals with rheumatoid arthritis, interviewed annually by telephone. Valued life activity (VLA) disability was assessed using a 26-item scale rating difficulty in carrying out each activity. Three types of summary measure were calculated: activities unable to perform, activities affected, and mean difficulty. Subscale scores were also calculated, corresponding to obligatory, committed, and discretionary activities, as defined in the disablement model. Disease status measures were examined as predictors of VLA disability using multiple regression analyses. RESULTS: Half the subjects were unable to do at least one VLA. Approximately 2%, 31.3%, and 40.2% were unable to do at least one obligatory, committed, and discretionary activity, respectively. Almost all (95%) reported at least one VLA affected by rheumatoid arthritis; 68.4%, 91.4%, and 92.5% reported at least one obligatory, committed, and discretionary activity, respectively, affected. Disease status measures were robust predictors of VLA disability, accounting for 22-47% of the variation in VLA disability (with one exception). Adding the health assessment questionnaire (HAQ) to these models increased (p<0.0001) all model R2 values. HAQ score mediated the effects of many disease measures, consistent with the disablement model. CONCLUSION: VLA disability was common, with more disability noted in committed and discretionary than obligatory activities. Because VLA disability has been linked to psychological wellbeing in previous studies, identification of factors that may protect against such disability is important. | |
17013437 | [Comparation of levels of anxiety and depression in patients with autoimmune and chronic-d | 2006 Jul | Scientific research on rheumatic diseases was often focused on the link between psychological features and disease. Depression and anxiety are frequently observed with an higher incidence among rheumatic patients in comparison to general population. In autoimmune diseases, such as rheumatoid arthritis, an important role for psychiatric symptoms could be played by the alteration of cytokines levels. In the chronic-degenerative diseases, psychological factors such as stress and depression, can be involved in perception of pain. OBJECTIVE: We aimed at evaluating in a sample of 50 patients (25 with rheumatoid arthritis and 25 with osteoarthritis) levels of pain, anxiety and depression. METHODS: We evaluated two group of patients with rheumatic disease, group A (25 with Rheumatoid Arthritis, mean age = 45.1; DS =15.24) and group B (25 with osteoarthritis, mean age = 54.3; DS =14.74) by clinic examination and with the following tests, SF-MPQ, HAQ, HAM-A, HAM-D. RESULTS: We found in group A higher levels of depression and anxiety but lower levels of pain, which was more expressed in group B. CONCLUSION: Depression and anxiety were observed with an higher prevalence in patients with autoimmune disease, whereas pain was stronger in patients with osteoarthritis, a degenerative disease. We could explain this phenomenon considering the aetiopathology of the two conditions. As regard to autoimmune disorders, these symptoms may reflect the direct effect of cytokines on the central nervous system. As far as it concerns chronic-degenerative diseases, anxiety and depression are usually considered "reactive" to pain, not "constitutive". | |
16542469 | Epstein-Barr virus and rheumatoid arthritis: is there a link? | 2006 | Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic, destructive, debilitating arthritis. Its etiology is unknown; it is presumed that environmental factors trigger development in the genetically predisposed. Epstein-Barr virus, a nearly ubiquitous virus in the human population, has generated great interest as a potential trigger. This virus stimulates polyclonal lymphocyte expansion and persists within B lymphocytes for the host's life, inhibited from reactivating by the immune response. In latent and replicating forms, it has immunomodulating actions that could play a role in the development of this autoimmune disease. The evidence linking Epstein-Barr virus and rheumatoid arthritis is reviewed. | |
16760256 | Changes in synovial tissue Jak-STAT expression in rheumatoid arthritis in response to succ | 2006 Dec | BACKGROUND: Modulation of Jak-STAT signalling may provide an effective therapeutic strategy in inflammatory arthritis (IA). OBJECTIVE: To examine the effect of successful disease-modifying antirheumatic drug (DMARD) treatment on the expression of Jak-STAT in a cohort of patients with active rheumatoid arthritis. METHODS: Synovial tissue biopsy specimens from 16 patients with active rheumatoid arthritis, taken before and after initiation of DMARD treatment, were examined for the presence of janus kinase (Jak)3, signal transducer and activator of transcription (STAT)1, STAT4 and STAT6 expression using immunohistochemistry. RESULTS: Successful treatment with DMARDs results in reduction in STAT1 expression in the lining, and STAT1 and STAT6 in the sublining of rheumatoid arthritis synovial tissue. Although the overall expression of STAT4 and Jak3 was not significantly altered by DMARD treatment, there was a significant reduction in the expression of the STAT4 and Jak3 bright cells, thought to be an activated dendritic cell subpopulation. CONCLUSION: Results show that Jak3, STAT1, STAT4 expression and STAT6 sublining expression decrease in response to successful treatment of rheumatoid arthritis with standard DMARDs. Therefore, altering the expression of these pathways may represent an alternative treatment option, either through promoting up-regulation of inhibitory pathways, or suppressing inflammatory paths. | |
15893712 | Peptidylarginine deiminase type 4, anticitrullinated peptide antibodies, and rheumatoid ar | 2005 Apr | Anticitrullinated peptide antibodies seem to be one of the most clinically reliable serologic markers for rheumatoid arthritis (RA). A genetic approach revealed that one of the citrullinating enzymes has a RA-susceptible variant. Peptidyl citrullination alters the chemical character of peptides and, subsequently, their antigenicity as well. This change in antigenicity of self-peptides seems to invoke citrulline-related autoimmunity. Although the precise physiologic role of citrullination is still unknown, accumulating data indicate that citrullination has a definite role in biologic phenomena, along with other posttranslational protein modifications, such as methylation and phosphorylation. In RA synovial tissue, two of five PADI isotypes are known to be expressed, and their expression is regulated at multiple steps: transcription, translation, intracellular localization, and activation/inactivation of PADI proteins. Further investigations on citrulline and PADIs from various aspects will provide a more profound understanding of RA-related autoimmunity. | |
16544921 | [Diagnosis of early arthritis]. | 2005 Dec 15 | The diagnosis of early arthritis is often difficult even though it is an important issue. A step-by-step clinical examination is necessary to make the diagnosis of "joint emergency": an infection must be suspected when fever is associated with arthritis. Then, classification of early arthritis will be carried on with a special attention to rheumatoid arthritis when the rheumatism is persistent and erosive. However, arthritis might be undifferentiated for several months to years; such an explanation should be given to the patient. A tight follow-up is necessary. | |
16881356 | [Pro- and antioxidant blood system in patients with rheumatoid arthritis and systemic lupu | 2006 | AIM: To estimate the levels of prooxidants (malonic dialdehyde-MDA and nitric oxide-NO), Zn, activity of antioxidant enzymes (superoxide dismutase--SOD and glutathione peroxidase--GPO) in the blood of patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). MATERIAL AND METHODS: Pro- and antioxidant system was assessed in 45 RA patients and 32 SLE patients by content of MDA estimated by reaction with thiobarbituric acid, NO (Boehringer Manheim kits, Germany), Zn (Unicam SP 190/191, Great Britain), activity of SOD and GPO (kits Ransod, Ransel; Randox, Great Britain). RA activity was evaluated by DAS index, SLE--by SLEDAI. RESULTS: MDA and NO concentrations were found elevated while SOD and GPO activity low in RA and SLE. The level of Zn was subnormal in RA. The activity of RA and SLE did not influence the above indices significantly. CONCLUSION: RA and SLE patients have high levels of prooxidants (MDA and NO) whereas their antioxidant enzymes (SOD and GPO) activity was low. This may promote oxidant stress. | |
16650587 | Depression in rheumatoid arthritis patients: demographic, clinical, and psychological pred | 2006 May | OBJECTIVE: To confirm the prevalence of depression in a sample of rheumatoid arthritis (RA) patients; to identify the most significant predictors of depression in RA and to explore patients attitudes to medication in relation to depression. METHODS: A cross-sectional survey was used to collect data from 134 RA patients (77% female, 23% male). Participants were divided into depressed and nondepressed groups based on their scores on the Center for Epidemiological Studies-Depression (CES-D) scale. Discriminant analysis was conducted to identify the predictors that would best categorise patients into those two groups. RESULTS: Twelve predictors correctly classified 80% of patients into depressed or nondepressed groups. The strongest predictors of depression were high tension and low self-esteem followed by the perceived impact of RA, fatigue, passive coping, pain, and physical disability. Other predictors included medication effectiveness and importance as well as perceived lack of control over pain. CONCLUSION: Both physical and psychological factors have an impact on depression in RA. The key predictors identified in this study need to be considered within the regular RA management as possible cues to depression development. | |
16252848 | Raising rheumatoid factor cutoff helps distinguish rheumatoid arthritis. | 2005 Jun | The presence of rheumatoid factor (RF) is one of the clinical criteria for the diagnosis of rheumatoid arthritis (RA). The cutoff point of RF assays is usually based on a reference level obtained from normal subjects in the same population as the patients. We evaluated 63 rheumatoid arthritis (RA), 25 other arthritis patients and 110 blood donors. Their rheumatoid factors (RF) ranged from < 9.9 to 2,264, < 9.9 to 262, and < 9.9 to 66 mIU/ml, respectively. The sensitivity at different cutoff points of 15, 20, and 25 mIU/ml was 92.1%, 90.5%, and 88.9%, respectively. The specificity at the same cutoff points was 81.5%, 84.4%, and 85.2%, respectively. Having minimally sacrificed the sensitivity, we recommend using a higher RF cutoff to increase specificity. | |
16049375 | Effect of pyrimethamine in experimental rheumatoid arthritis. | 2005 Aug | BACKGROUND: Recent evidence has shown that the antimalarials are useful drugs in the treatment of various rheumatic diseases. The present study was designed to test the therapeutic effect of pyrimethamine (PYR) in collagen-induced arthritis (CIA). MATERIAL/METHODS: CIA was induced in Lewis rats. The intraperitoneal administration of PYR and methotrexate (MTX) were started on day 25 post-immunization and continued until final assessment on day 35. During this period, clinical examination was performed intermittently. Anti-C II Ab and nitric oxide (NO) synthesis were measured. The paws and knees were then removed for histopathology and radiography assay. The biocompatibility of PYR and MTX were assessed using a fibrosarcoma cell line. RESULTS: Data showed that i.p. injection of pyrimethamine to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed reduced inflammatory cell infiltrate in the joints of treated rats, and tissue edema and bone erosion in the paws were markedly reduced following PYR therapy. Moreover, our radiography results paralleled our histological findings. Cytotoxicity analysis of PYR showed greater tolerability compared with MTX. Treatment with PYR significantly diminished nitric oxide formation in treated rats compared with untreated controls. CONCLUSIONS: Our findings shed light on the therapeutic efficacy of pyrimethamine in experimental rheumatoid arthritis compared with a choice drug (methotrexate), which may recommended it as a second-line drug in the treatment of rheumatoid arthritis. | |
17165004 | Rheumatoid nodulosis during methotrexate therapy in a patient with rheumatoid arthritis. | 2006 | We report a 62-year-old man with rheumatoid arthritis (RA) who developed nodulosis after methotrexate (MTX) treatment. The epithelioid cells of nodules were positive for matrix metalloproteinases (MMP)-2, MMP-3, MMP-9, and Ki67. The synovial tissues obtained from the same patient were negative for MMP-3, MMP-9, and Ki67. This study demonstrated that MTX-induced nodules are different from synovial tissues in terms of MMP expression, suggesting the presence of different pathologic mechanisms and differential MTX susceptibility. | |
16870099 | Extra-articular manifestations of rheumatoid arthritis: results of a university hospital o | 2006 May | OBJECTIVE: Presence of extra-articular manifestations (EAM) in rheumatoid arthritis (RA) is associated with more severe disease and increased mortality. Prevalence of EAM may vary in different geographic areas and in different ethnic populations. In this study we investigated the frequency of EAM in 526 RA patients from a single university hospital in Turkey. METHODS: The hospital records of patients who had been diagnosed as RA in Hacettepe University Department of Rheumatology between the years 1988 and 2003 were retrospectively evaluated. There were 73 males and 453 females, and mean age of the patients was 48.0 +/- 12.3 years. The mean follow-up period was 4.8 +/- 4.1 years. Three hundred and fifty-nine patients were rheumatoid factor (RF) positive (68.3%). RESULTS: The overall frequency of EAM was 38.4% (202 patients). The most common EAM was rheumatoid nodules (18.1%). Sicca symptoms, pulmonary findings, Raynaud's phenomenon, livedo reticularis, carpal tunnel syndrome, vasculitis, amyloidosis, and Felty syndrome were present in 11.4%, 4.8%, 3%, 4.8%, 2.8%, 1.3%, 1.1%, and 0.3% of the patients, respectively. Overall EAM and rheumatoid nodules were significantly more common in RF positive patients than RF negative patients. The frequency of rheumatoid nodules was significantly higher in males than in females. CONCLUSION: The prevalence of EAM in Turkey is higher than East Asia and Africa, and lower than UK and North America. Excluding secondary Sjögren's syndrome, our results are similar to other Mediterranean populations like Italy. | |
16167165 | Hand deformity in Parkinson's disease: case report. | 2005 Sep | Hand and foot deformities were originally described in Parkinson's disease (PD) in 1864, although their pathogenesis still remains to be clarified. Typical hand deformities are flexion in metacarpopharyngeal joints and hyperextension in interphalangial joints, sometimes accompanied by ulnar deviation. Unlike rheumatoid arthritis (RA), there is no swelling and stiffness in joints. In this report, a case that was previously misdiagnosed as RA due to deformities in the hand and whose PD was detected upon presentation to our clinic is presented, and the differential diagnosis of the disease is discussed. |