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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7839155 | Rheumatic diseases in African blacks. | 1994 Oct | Contrary to previous belief, there is increasing evidence that a broad spectrum of rheumatic diseases do affect African blacks. Although properly conducted epidemiological studies have yet to be performed, reports of population surveys from a variety of sub-Saharan African countries indicate that diseases such as rheumatoid arthritis (RA), gout, and the connective tissue diseases are observed, although some differences in clinical presentation may occur as a result of cultural, racial, and socioeconomic factors. Rheumatoid arthritis is common in some parts of Africa and less common in others. In particular, a significantly lower prevalence of RA in rural areas compared with urban cohorts has led to the hypothesis that environmental factors associated with urbanization may be involved in disease pathogenesis. A similar hypothesis has been suggested for hyperuricemia and gout. Clinical features of disease may also be different in Africans when compared with other population subgroups such as with systemic lupus erythematosus although this may be artefactual as different accessibility to health care and referral practices may result in only the more severe cases coming to medical attention (eg, lupus nephritis). Immunogenetic factors may reduce the prevalence of some conditions such as the spondyloarthropathies. Although the association between HLA-DR4 and RA holds true in Africans, the same is not so for the association of HLA-B27 with ankylosing spondylitis (AS). The prevalence of HLA-B27 in African blacks is 10 times less than Caucasian populations, in part accounting for the low prevalence of spondyloarthropathies, although its association with AS is low. Other conditions such as human immunodeficiency virus (HIV)-related arthropathies appear to be an increasing medical problem. The panepidemic of acquired immunodeficiency syndrome in Africa has resulted in an increased awareness of the different types of arthritis that may be associated with HIV. These are similar to those reported in other parts of the world, although risk factors are different in Africa where heterosexual transmission is a more common cause than homosexual transmission or i.v. drug usage. Information on other rheumatic diseases such as osteoarthritis and soft tissue rheumatism are slowly emerging. Rheumatic manifestations of the infectious diseases, which are endemic in Africa, remain a uniquely fascinating aspect of rheumatology practice on the African continent. Therefore, African countries will increasingly be a continued valuable source of clinical material for comparative studies to help elucidate factors that influence the development of rheumatic diseases. | |
8016605 | [Fulminant purpura in Still's disease and bacteremia with Xanthomonas maltophilia and coag | 1994 May 28 | We describe the case of a 31-year-old man with a long history of juvenile rheumatoid arthritis who was admitted to the hospital because of painful purple skin lesions on hands and feet. On admission he presented the classical picture of "purpura fulminans" with extensive acrocyanosis and large blisters on the lower limbs which evolved into symmetrical peripheral gangrene. Laboratory findings revealed activated intravascular coagulation and bacteremia with coagulase-negative staphylococci and Xanthomonas maltophilia which was thought to be catheter-related. His condition improved markedly under therapy with antibiotics, intravenous heparin, iloprost and intensive local debridement including amputation of several toes. Coagulation studies two months after the acute phase of the disease revealed chronic activated coagulation with a significant protein S deficiency. Clinical findings, etiology, significance of impaired coagulation and therapeutic action in "purpura fulminans" are discussed. | |
1439846 | Timed treatment of the arthritic diseases: a review and hypothesis. | 1992 Oct | Evidence has been accumulating regarding the importance of biological rhythms in the diagnosis and treatment of a variety of diseases and disorders. Increasingly, the arthritides have shown statistically quantifiable rhythmic parameters. Included in the latter group are joint pain and joint size. In addition, a number of drugs used to treat rheumatic diseases have varying therapeutic and toxic effects based on the time of day of administration. Among these drug classes are nonsteroidal antiinflammatory drugs, glucocorticoids, and a number of cytostatic agents. In the last group of agents, experience in treating malignant disease suggests that time-specified treatment may reduce the toxic effects of low-dose cytostatic treatment of rheumatoid arthritis (RA) and related diseases. This article reviews that evidence and suggests a rationale for the timed treatment of RA with methotrexate. | |
1338598 | [Anti-polynuclear neutrophil cytoplasmic antibodies of the perinuclear type or p-ANCA]. | 1992 | Some neutrophil cytoplasmic auto-antibodies produce perinuclear immuno staining of alcohol-fixed neutrophils called P-Anca pattern. These autoantibodies show chiefly reactivity with myeloperoxidase in Elisa but other specificities have been detected (elastase, cathepsin, lactoferrin). These P-Anca anti-MPO are more frequent with renal angiitis but P-Anca (anti-MPO negative) are associated with other diseases without renal failure (rheumatoid arthritis, Gougerot-Sjogren and ulceritis colitis). | |
8685451 | [Monoarthritis]. | 1995 Dec | By definition, monoarticular arthritis means one-joint involvement, even though, in fact, such a condition is often an oligoarthritis because as many as two or three separate joints will be involved. Arthritis is often limited and may regress, so that it is frequently misdiagnosed. Sometimes, a monoarticular condition may be a polyarthritis onset (i.e., rheumatoid arthritis). Monoarticular arthritis can be caused by many factors, such as infections (septic arthritis), nonspecific inflammatory processes (reactive arthritis), crystals deposition (gout, CPPD crystal deposition disease), trauma, neoplasm (pigmented villonodular synovitis), immunologic conditions (amyloidosis) and hormonal changes (parathyroid disease). Its onset is usually acute and sometimes dramatic, with fever, pain and joint swelling, so that a decision must be made promptly to stop rapid illness evolution and to prevent the irreversible destruction of cartilage and bone (especially in septic arthritis). Diagnostic studies are performed with mono-bilateral radiographs of the joint. Radiographic findings (i.e., soft tissue swelling, joint effusion, widening and thinning of joint spaces, bone erosions and destruction of bone surface) are typical of the disease, but some findings (e.g., type of evolution and progression), laboratory tests, synovial biopsy and arthroscopy can differentiate infectious from inflammatory forms. Scintigraphy can depict isotopic joint uptake, before articular abnormalities are demonstrated with radiography, thanks to its high sensitivity; nevertheless, because of its low specificity, scintigraphy may miss some kinds of lesions (including osteoarthritis) and cannot easily differentiate osteomyelitis from septic arthritis. CT and MRI play a secondary, though not negligible, role, especially to study such deep infections as psoas abscesses, which may mimic arthritides. | |
8870116 | Health-related quality of life after total hip replacement. | 1996 Aug | Total hip replacement (THR) is a commonly performed orthopedic procedure with an increasing rate of utilization. It is performed to relieve symptoms of pain and help restore the loss of function that follows advanced hip diseases, including osteoarthritis, rheumatoid arthritis, and avascular necrosis. Although there are numerous studies evaluating patient outcomes after THR with respect to physical functioning and pain relief, relatively few studies have specifically evaluated changes in health-related quality of life (QOL). We reviewed a total of 20 studies that evaluated changes in QOL after THR. Results of all studies were consistent in showing beneficial and often dramatic improvements in QOL after elective THR. These improvements were most likely to occur within the first 3 to 6 months after THR. Future research should assess the impact of both patient-level predictors and the role of various surgical approaches in contributing to successful outcomes after THR. | |
1417127 | Uridine diphosphoglucose dehydrogenase activity in synovial lining cells in the experiment | 1992 Aug | Uridine diphosphoglucose dehydrogenase (UDPGD) is the enzyme responsible for the production of uridine diphospho(UDP)-glucuronate, an essential monosaccharide in the biosynthesis of hyaluronan, which is found in high concentrations in normal synovial fluid. Synovial lining cells have been implicated in the synthesis of hyaluronan, but the degree to which they are adapted metabolically to this function in normal and inflamed synovium has not been established. Using a quantitative cytochemical method it was shown that synovial lining cells from chronically inflamed rabbit synovium had significantly lower UDPGD activity per cell than the lining cells of normal synovium. These findings suggest that the lining cells of normal non-inflamed synovium may be enzymatically adapted for the synthesis of hyaluronan and that this may be an indication of a specific role of synovial lining cells in the maintenance of normal joint function. | |
1578179 | Circulating immune complex in bilharzial arthropathy. | 1992 Apr | Using the enzyme-linked immunosorbent assay (ELISA), the immune complex (IC) level was estimated in sera of 100 individuals grouped as follows; Group 1: 40 cases with bilharzial arthropathy. Group II: 20 cases with bilharziasis. Group III: 20 cases with rheumatoid arthritis. Group IV: 20 apparently healthy individuals. IC level was also estimated in synovial fluid of 4 cases with knee joint effusion. A significant increase in IC level in cases with bilharzial infection (with or without arthropathy) was noticed. This was higher in intestinal than in urinary bilharziasis. Further more IC level was significantly higher in cases of bilharzial arthropathy than in cases with bilharziasis alone. The IC level in synovial fluid was higher than in serum with a positive correlation. The role of IC as a causative agent in the pathogenesis of bilharzial arthropathy is clearly discussed. | |
8948295 | Natural remission in inflammatory polyarthritis: issues of definition and prediction. | 1996 Nov | This paper reports the frequency and predictors of remission (no arthritis on examination and no treatment with second-line drugs or steroids within the previous 3 months) in 358 patients with early inflammatory polyarthritis (IP) referred to the Norfolk Arthritis Register. Two years after referral, 91 patients (25%) were in remission, 32 of whom had also been in remission at 1 yr. Remission rates were twice as high in patients with undifferentiated inflammatory polyarthritis at baseline as in those who satisfied criteria for rheumatoid arthritis. To identify predictors of remission, a logistic regression model was developed on a random two-thirds of the patients and validated on the remaining one-third. Remission at 2 yr was associated with male gender and fewer than six tender joints at baseline. However, even the best-fitting model was not sensitive enough to be useful clinically. Thus, amongst patients with early IP in the community, remission rates at 2 yr are low. Further, it was impossible, using simple clinical measures, to predict those patients whose arthritis would resolve. | |
8287593 | IgG glycosylation in autoimmune-prone strains of mice. | 1994 Jan | The relationship between increased levels of IgG oligosaccharide chains lacking galactose (G0) and the development of rheumatoid arthritis is unclear. In order to further our understanding of the observed correlation between raised serum G0 and arthritis, we have studied G0 levels in arthritis-prone and non-susceptible (i.e. non-arthritis-prone) mice and the effects on G0 of mycobacterial antigens, which have been postulated to play a role in the early events leading to the development of arthritis. We have shown that different age-matched mouse strains have characteristic 'resting' levels of G0 which (in six out of seven strains of mice) increase with age. We have also shown that these increases can be enhanced by immunization of arthritis-prone strains of mice with an adjuvant containing mycobacteria (Freund's complete adjuvant (FCA)), suggesting that deflects in the ability to regulate these G0 changes may be related to susceptibility to arthritis. | |
8613699 | Dissection of the pathologies induced by transmembrane and wild-type tumor necrosis factor | 1996 Apr | With increasing awareness that seemingly diverse immune-mediated diseases involve similar pathogenetic mechanisms, and the identification of a growing number of key effector molecules, it is becoming possible to design and generate effective transgenic models for such diseases. Tumor necrosis factor (TNF) plays a prominent role in immune and host defense responses and there is strong evidence that abnormal TNF production contributes to disease initiation and progression in rheumatoid arthritis, systemic inflammatory response syndrome, diabetes, multiple sclerosis, and many other immune-mediated disorders. The generation of TNF transgenic mice, in which TNF production is deregulated, has provided us with direct evidence that, in vivo, this cytokine can indeed trigger the development of such complex disease phenotypes. Transgenic mice that have been engineered to overexpress human or murine TNF molecules in peripheral joints, T cells, or neurons of the central nervous system represent important animal models for human rheumatoid arthritis, systemic inflammation, and multiple sclerosis, respectively. In addition to establishing a central role for TNF in such diseases, these animal models have already proved valuable for identifying additional important disease-effector molecules, and for gaining an insight into the complex in vivo mechanisms that are involved in disease pathogenesis. For example, in the case of arthritis, TNF has been found to transmit its pathogenic effects entirely through interleukin-1, which may therefore represent an additional important target for therapeutic intervention in the human disease. In summary, TNF transgenic models of human disease are expected to serve as important in vivo tools for defining details of disease pathogenesis, potential targets for therapeutic intervention and for evaluating the possible involvement of additional genetic and environmental factors on the disease state. | |
1506256 | Bromide toxicosis (bromism) in a dog treated with potassium bromide for refractory seizure | 1992 Aug 1 | A 4-year-old German Shepherd Dog was evaluated because of chronic hind limb lameness and recurrent seizures. Diagnostic evaluation of the dog confirmed rheumatoid arthritis and idiopathic epilepsy. The rheumatoid arthritis was treated with prednisone and piroxicam. The seizures were treated with phenobarbital plus clonazepam. The seizures were refractory and potassium bromide was substituted for clonazepam. The dog was reevaluated 4 months after initiation of potassium bromide treatment because of recurrence of arthritis signs. During hospitalization, the dog had neurologic signs, which progressed from depression to recumbency and stupor. Anisocoria, muscle pain, and hyporeflexia were noticed. Bromide toxicosis was diagnosed on the basis of toxic serum bromide concentration (2.7 mg/ml; therapeutic range, 1.0 to 2.0 mg/ml). Following cessation of potassium bromide treatment, the neurologic signs resolved. The seizures recurred 6 weeks after potassium bromide was discontinued. Bromide treatment was reinitiated at half the initial dosage. After 6 weeks, the serum bromide concentration was 1.9 mg/ml, and no seizures had been reported by the dog's owners. Therapeutic serum bromide concentrations in dogs has been reported to be 0.5 to 2.3 mg/ml. The serum bromide concentration at which toxic signs are expected is variable in human beings because individuals differ in their tolerance of the drug. Clinical trials are necessary to determine the toxic serum bromide concentrations in dogs. This case of bromism in a dog suggests that the dosage of potassium bromide should be based on serial measurement of serum bromide concentrations. | |
9069110 | Inflammatory joint disease: the role of cytokines, cyclooxygenases and reactive oxygen spe | 1996 Dec | Cytokines are known to have a key role in the onset and development of inflammatory joint disease, including rheumatoid arthritis and osteoarthritis. The effects of some cytokines on the cells and tissues involved in inflammation of the joint are well catalogued, but recent discoveries of new cytokines, and interest in intracellular signalling molecules, have thrown new light on the way in which cytokines mediate the cellular responses that lead to inflammation. Here, recent work on the roles of cytokines, cyclooxygenases, nitric oxide and other reactive oxygen species, in the cellular pathways that lead from cytokine receptor to inflammation, are discussed. | |
7871204 | [Clinical significance of heat shock proteins. Influence of heat shock proteins on the pat | 1994 | The presentation shows the survey of diseases the pathogenesis of which might be connected with the existence of Heat Shock Proteins (HSPs). We discuss the data referring to the influence of the HSPs upon the occurrence and progression of the following diseases: systemic lupus erythematosus, reactive arthritis, rheumatoid arthritis, insulin dependent diabetes mellitus, schizophrenia and Alzheimer's disease. There is also indicated a possible activity of HSPs in the pathogenesis of neoplasia, organ ischaemia and inflammation or degeneration. | |
7794974 | Arthritis hand function test: inter-rater reliability among self-trained raters. | 1995 Mar | OBJECTIVE: The purpose of this project was to examine the inter-rater reliability of the Arthritis Hand Function Test (AHFT), a new instrument for measuring hand strength and dexterity in adults with arthritis. METHODS: Six occupational therapists (two at each of three sites) trained themselves as AHFT administrators using the test manual and training videotape. They recruited 30 adult subjects (10 at each site) with rheumatoid arthritis or osteoarthritis affecting the hands. There were 21 women and 9 men in the sample (mean age, 57.5 years; average time since diagnosis, 14.8 years). Subjects were tested twice, once by each rater from that site. RESULTS: Inter-rater reliability ranged from 0.45 to 0.99 (Pearson r). Because subjects were tested twice, AHFT scores were examined for an order effect. Although scores on all strength items declined by the second test session, and improved for all dexterity items, only the aggregate applied dexterity score showed significant change across all three sites (P = 0.002, 0.001, and 0.031, respectively). CONCLUSIONS: These results suggest the AHFT is a reliable instrument for measuring hand strength and dexterity that requires minimal training on the part of occupational therapist raters. | |
8060762 | Biologic agents in the therapy of inflammatory rheumatic diseases, including therapeutic a | 1994 May | As a result of a better understanding of the mechanisms that underlie diseases such as rheumatoid arthritis, biologic agents have been used increasingly in the therapy of inflammatory rheumatic diseases. Monoclonal antibodies directed against either cell surface constituents mainly on CD4+ T cells or cytokines such as tumor necrosis factor-alpha, fusion toxins reactive with cell activation membrane markers, and cytokine inhibitors, have been shown to be safe and possibly efficacious in open trials. At present, most ongoing studies are focused on the treatment of refractory rheumatoid arthritis and lupus nephritis. Open therapeutic trials are followed by double-blind placebo-controlled phase II and III studies, which are necessary to prove the efficacy of the various biologic agents. Open trials, however, already have shown that only a short decrease in the inflammatory activity of arthritis can be induced and that anti-idiotypic and human anti-mouse antibodies are induced even when humanized monoclonal antibodies are used. Nevertheless, a significant improvement in the available therapeutic repertoire for the treatment of inflammatory rheumatic diseases is expected. | |
19078064 | The arthritis of primary biliary cirrhosis: clinical features and associated immune proces | 1996 Aug | We have performed a survey to determine the percentage of patients with primary biliary cirrhosis (PBC) and arthritis followed at Geisinger Clinic, a rural tertiary care center. We have assessed the clinical features of the arthritis, delineated any signs that suggest the diagnosis of asymptomatic PBC in patients with arthritis, and explored coexisting immune diseases.From January 1988 through November 1993, 36 patients with PBC were identified from a computer search of the Geisinger Gastroenterology Clinic database. These records were reviewed for clinical information of an associated arthritis, other autoimmune processes, and demographic information.Twenty-five percent of the patients with PBC had an inflammatory arthritis. Two patients had classic, seropositive rheumatoid arthritis with erosions and nodules. The remaining seven patients had a predominantly symmetrical, nonnodular inflammatory arthritis involving both large and small joints. Tenosynovitis was the most common presenting rheumatic feature. Sjögren's syndrome, Raynaud's phenomenon, and hypothyroidism were more common in the subgroup of PBC patients with arthritis.A diagnosis of PBC should be considered in any patient presenting with tenosynovitis or an unexplained inflammatory arthritis, especially in the setting of Raynaud's phenomenon and signs of Sjögren's syndrome. | |
7888786 | Detection of Epstein-Barr virus and cytomegalovirus genome in white blood cells from patie | 1995 Mar | The role of infectious agents in the pathogenesis of autoimmune diseases has long been a matter of debate. This study investigated the possible role of Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) infections in the pathogenesis of autoimmune diseases by an attempt to demonstrate the presence of the viral genome in the leukocyte of 21 juvenile rheumatoid arthritis (JRA) patients, 20 childhood-onset systemic lupus erythematosus (SLE) patients, and 20 age-matched normals, using polymerase chain reaction (PCR) and DNA probes. The results showed: (1) there was no difference in serum IgG anti-EBV antibody titers among three groups; (2) the EBV PCR-positive rates for JRA and SLE patients and normal controls were 5% (1/21), 10 (2/20), and 0% (0/20), respectively; (3) the HCMV PCR-positive rates for JRA and SLE patients and normal controls were 33% (7/21), 25 (5/20), and 10% (2/20), respectively, and (4) the HCMV-positive rate was 25% for JRA patients with steroid treatment and 33% for those without steroid treatment. It is, therefore, concluded that: (1) the data do not support the participation of EBV and HCMV in the pathogenesis of childhood-onset SLE and JRA; (2) steroid therapy does not increase the frequency of HCMV infection in JRA patients, and (3) immunoincompetence might be one of the major factors contributing to increased susceptibility to HCMV infection in JRA and SLE patients. | |
8662835 | Thiazolidine diones, specific ligands of the nuclear receptor retinoid Z receptor/retinoid | 1996 Jun 7 | Rat adjuvant arthritis is a chronic T cell-dependent autoimmune disease with many similarities to rheumatoid arthritis. We have identified a class of thiazolidine diones with high potency in suppressing chronic inflammation and joint destruction in this experimental model. The lead compound CGP 52608 (1-(3-allyl-4-oxothiazolidine-2-ylidene)-4-methylthiosemicarbazone) exhibits antiarthritic activity at daily oral doses between 0.01 and 1 mg/kg and was shown to specifically activate the retinoid Z receptor/retinoid acid receptor-related orphan receptor alpha (RZR/RORalpha) in low nanomolar concentrations. This receptor is a novel member of the superfamily of ligand-inducible transcription factors, and we have recently identified the pineal gland hormone melatonin as a natural ligand. Structure-activity relationship studies with 13 closely related analogues of CGP 52608 revealed a striking correlation between RZR/RORalpha activation and antiarthritic activity. We therefore suggest that nuclear signaling via RZR/RORalpha is a key mechanism in mediating the antiarthritic effects of these thiazolidine diones and may open a novel therapeutic approach for the treatment of rheumatoid arthritis and other autoimmune diseases. The existence of a nuclear melatonin receptor may lead to a better understanding of the immunomodulatory actions of melatonin. | |
7631133 | Female preponderance for development of arthritis in rats is influenced by both sex chromo | 1995 Jul | Autoimmune arthritis was induced after a single injection of the non-immunogenic adjuvant (avridine) or with autologous rat type II collagen. Females of two different rat strains, DA and LEW, were found to be more susceptible than males. To investigate further the mechanisms behind the female preponderance, we selected the avridine induced arthritis model. This is known to be a chronic joint-specific disease which is T-cell dependent and associated with MHC genes and, therefore, is an appropriate model for rheumatoid arthritis. To address the possibility of sex chromosome involvement, reciprocal F1 hybrids were produced. Female (DAxLEW)F1 rats were found to be more prone to arthritis than their male counterparts. This difference could be explained, at least partly, by the influence of sex chromosomes since reciprocal (LEWxDA)F1 rats showed no sex linkage. However, the sex linkage was more pronounced in normal rats when compared to castrated (DAxLEW)F1 rats indicating a role for sex hormones in conjunction with the sex chromosome-linked effect. Both oestrogen and testosterone had a suppressive effect on the development of arthritis. The findings presented here suggest the presence of a sex chromosome gene, which mediates its function only in the presence of sex hormones and is associated with a female preponderance for development of arthritis. |