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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7899827 | Subclass distribution of IgA and IgG antibodies against Clq in patients with rheumatic dis | 1995 Apr | To obtain insight into the immunoregulatory mechanisms in patients with different rheumatic diseases, the occurrence and the subclass distribution of IgA and IgG antibodies against Clq (anti-ClqAb) was determined. In patients with systemic lupus erythaematosus (SLE) the highest frequency of increased serum levels of IgG anti-ClqAb were found, whereas IgA anti-ClqAb were predominantly present in patients with ankylosing spondylitis (AS) and patients with rheumatoid arthritis complicated by vasculitis (RV). In all the IgA anti-ClqAb positive AS and RV patients the antibody reactivity involved the IgA1 subclass while the IgA2 subclass was found in 47% of the patients. Further characterization of the IgA anti-Clq binding activity in sera of AS patients revealed that both subclasses of IgA anti-ClqAb were predominantly polymeric; the binding of both IgA subclasses with solid phase Clq was inhibitable by aggregated fluid phase Clq; we found no detectable interference of rheumatoid factor in the test system for the measurement of IgA anti-ClqAb. In patients with SLE the IgG anti-ClqAb reactivity was mainly of the IgG2 and IgG3 subclass, whereas in the same patients the IgG anti-tetanus toxoid response was not restricted to these subclasses. The predominance of IgG2 and IgG3 subclass of anti-ClqAb in sera of SLE patients, suggests a skewing of the anti-ClqAb response. The observation that the IgA anti-ClqAb of both subclasses is predominantly polymeric in nature and the notion that polymeric IgA is associated with activation of inflammation cascades, suggests that IgA anti-ClqAb may contribute to tissue damage. | |
8349791 | Adenoviral-mediated gene transfer to rabbit synovium in vivo. | 1993 Aug | Currently, treatment for rheumatoid arthritis and other inflammatory arthropathies is often ineffective in ameliorating the progression of the disease, particularly the invasive destruction of cartilage and bone by rheumatoid synovium. Multiple aspects of this inflammatory process are mediated by the synovial lining cells (synoviocytes). Genetic modification of these cells in vivo represents a potential method for the treatment of these conditions. In this report, we describe a novel technique for the genetic transduction of synovial lining cells in vivo using recombinant adenoviral vectors and intraarticular injection techniques. Purified high titer suspensions of a recombinant adenoviral vector containing the gene for Escherichia coli beta-galactosidase (AdCMVlacZ) were directly injected into the hind knees of New Zealand white rabbits. Synovial tissues were then examined for transgenic lacZ expression using a combination of in situ staining for beta-galactosidase activity, immunohistochemical staining, and transmission electron microscopy. High efficiency gene transfer and lacZ expression was observed in both type A and type B synoviocytes throughout the articular and periarticular synovium of the rabbit knee, with continued expression of transgenic lacZ detected for > or = 8 wk after infection. | |
1307628 | [Comparable evaluation of serological diagnostic tests (ELISA, IFA and PA methods) for the | 1992 Nov | We have evaluated the usefulness of the enzyme-linked immunosorbent assay (ELISA), indirect fluorescent antibody assay (IFA) and particle agglutination (PA) method as serological screening tests for Lyme-borreliosis. Serum samples obtained from two patients with Lyme-borreliosis showed marked high antibody titers for Borrelia burgdorferi when measured by these methods. Of the serum of 368 healthy members of the Self-Defense Force in north-eastern Japan screened for the antibody to B. burgdorferi, 8.4%, 3.7%, 4.6% were found positive by the ELISA, IFA, and PA method, respectively. However, Western blot analysis of these "positive" sera demonstrated no identical bands to those seen in the serum from the patients with Lyme-borreliosis. While 85% and 15% of Treponema pallidum hemagglutination test (TPHA)-positive sera (20 samples) showed a false-positive reaction by the ELISA and IFA method, respectively, no cross-reaction to the anti-B. burgdorferi antibody was observed in these sera by the PA method. The analysis of the serum of the patients with autoimmune diseases (rheumatoid arthritis; 11 cases, systemic lupus erythematosus; 46 cases) by the ELISA and PA methods resulted in a cross-reaction to some extent, which suggested that the antibodies produced by autoimmune mechanisms such as the anticardiolipin antibody can cause a cross-reaction to the anti-B. burgdorferi antibody. These findings indicate that the PA and ELISA rather than the IFA method should be recommended for rapid and conventional screening of Lyme-borreliosis and that serum "positive" for the anti-B. burgdorferi antibody determined by these tests should be confirmed by Western blot analysis to negate the cross-reactions. | |
8927346 | [Cyclosporin-A therapy in autoimmune diseases]. | 1996 Sep 1 | The author surveys the action of cyclosporin, its advantages over conventional immunosuppressive drugs and its side effects. This paper lists comparative research showing autoimmune diseases in which cyclosporin has been used as well as data confined to disease causality. It touches on almost all autoimmune diseases, and details rheumatoid arthritis, lupus erythematosus disseminatus, and the treatment of kidney disease, giving a review of the ideal usage of cyclosporin during laboratory and clinical testing and the reasons for dosage modifications. In organ transplants, it is necessary to determine the serum level of cyclosporin. In autoimmun diseases cyclosporin's effectiveness and side effects cannot be determined on the basis of blood serum level. Dose modifications should be based on serum creatinine levels and on diastolic blood pressure. On the basis of the literature and on his own experience, the author emphasizes the potential for new perspectives in drug usage. This is particularly true for Sandimmun-Neoral. His group for example has been the first to use Cyclosporin A to treat Polyglandular autoimmune syndrome and Henoch Schönlein disease and has achieved excellent results. | |
8767930 | [Growth hormone therapy in childhood. Growth hormone therapy in small children without gro | 1996 Jun 10 | The availability of unlimited amounts of recombinant human growth hormone (rhGH) has now made it possible to investigate its growth-promoting effect in children in whom growth hormone production is not deficient. In girls suffering from the Ullrich Turner syndrome, treatment with rhGH increases final height by some 6 to 8 cm. An increase in growth rate has also been observed in children with renal insufficiency, and in children with intrauterine growth retardation. Favourable results have also been reported in children receiving glucocorticoids for such chronic conditions as rheumatoid arthritis, and in youngsters with hypochondroplasia. In a further group of children with various disorders an improvement in the growth rate has been observed, although nothing can yet be said about the outcome in terms of final height. To achieve an increase in growth rate, pharmacological doses of growth hormone higher than those used in children with growth hormone deficiency are necessary. For this reason, the risk of unwanted side effects might be higher than in the latter. | |
8812700 | Activation of T Cells by Autoantigen Immobilized by Specific Antibodies. | 1996 Jun | A convenient microtiter-plate assay that uses immobilized antibody to capture specific antigens for presentation to T cells has been developed. Initial experiments used KLH as the antigen, immune antisera and draining lymph node cells from immunized NOD mice as the source of antibody and T cells, and spleen cells from naive NOD mice as the source of antigen-presenting cells (APCs). The resulting proliferation of the T cells was shown to be antibody- and antigen-specific, suggesting that the APCs had internalized and processed the captured antigen, presenting it to the T cells in the form of peptide/MHC complexes. The approach was also tested for an autoimmune disease as part of an effort to identify autoantigens responsible for the proliferation of T cells in the synovial fluid of rheumatoid arthritis patients. When immunoglobulin from autologous synovial fluid was captured on plates coated with anti-human immunoglobulin antibodies, the addition of HLA-DR4 peripheral blood mononuclear cells as APCs and synovial fluid-reactive HLA-DR4-restricted T-cell clones resulted in significant proliferation, indicating that the specific antigen in the crude synovial fluid was human immunoglobulin. This response was also shown to be antigen-specific and HLA-DR4-restricted. This assay format should permit the definition of autoantigens by capturing with antibodies to crude autoantigen extracts, followed by the addition of the appropriate APC and T-cell populations. | |
8784934 | Anti-inflammatory drugs and myorelaxants. Pharmacology and clinical use in musculoskeletal | 1996 Jun | Anti-inflammatory agents and myorelaxants are the cornerstone of pharmacologic management of musculoskeletal disease. Combinations of these drugs are recommended for the treatment of muscle spasm and injury, whereas anti-inflammatory agents alone are used to treat inflammatory pain such as rheumatoid arthritis. Choosing the most effective regimen for patients with pain can be difficult. This article reviews the pharmacology and clinical use of these agents to define how to use these medications better. | |
8692572 | [Hindfoot arthrodesis]. | 1996 Apr | Arthrodesis of the hindfoot is indicated in congenital foot deformity of young adults, in posttraumatic arthrosis of the subtalar joint following calcaneus fractures, in idiopathic, isolated arthroses of hindfoot joints, in rheumatoid arthritis and in deformities of the longitudinal arch of the foot. Common and useful combinations are the triple-arthrodesis and the arthrodesis of the subtalar and the calcaneocuboid joint, in particular if both joints are affected by calcaneus fractures. Arthrodesis of the subtalar and the talonavicular joint are often performed as isolated procedures. The three-dimensional structure of the hindfoot articulations may impede perfect contact of the bone surfaces in combined arthrodeses. Various fixation methods are in use. Follow-up examination of 52 arthrodeses after 11.1 years revealed good, symptomatic improvement in most patients. However, complete bony union was achieved in only 47 percent, and this was due to insufficient stabilization of the arthrodesis in many cases. In view of comparable rates of pseudarthroses in the literature, we advocate stable internal fixation with screws or bone staples. | |
7495156 | [Patient education--a contribution to improvement of long-term management of patients with | 1995 Jul | Patient education has been recognized as an important tool in the therapy and the rehabilitation of patients with chronic rheumatic diseases. An increasing body of literature refers to favorable effects of patient education. Patient education improves coping with disease, reduces pain and depression and decreases arthritic "helplessness". Therefore, patient education should be a part of the comprehensive care for the rheumatic patient. The patient education group (Arbeitskreis Patientenschulung) of the German Society of Rheumatology (Deutsche Gesellschaft für Rheumatologie) has been initiated to develop a general concept of patient education in rheumatology and to elaborate various patient education programs. The patient education program for rheumatoid arthritis is described as a model for further patient education programs. It consists of six group sessions (modules). The program is conducted by an interdisciplinary team. A group leader is in charge of the program. Train-the-trainer courses should improve the quality of the program. Currently, the patient education group develops education programs for patients with systemic lupus erythematodes and related collagen diseases, spondyarthritis patients, patients with fibromyalgia and rheumatic children and their parents. | |
7790516 | Massage therapy for infants and children. | 1995 Apr | Data are reviewed on the effects of massage therapy on infants and children with various medical conditions. The infants include: premature infants, cocaine-exposed infants, HIV-exposed infants, infants parented by depressed mothers, and full-term infants without medical problems. The childhood conditions include: abuse (sexual and physical), asthma, autism, burns, cancer, developmental delays, dermatitis (psoriasis), diabetes, eating disorders (bulimia), juvenile rheumatoid arthritis, posttraumatic stress disorder, and psychiatric problems. Generally, the massage therapy has resulted in lower anxiety and stress hormones and improved clinical course. Having grandparent volunteers and parents give the therapy enhances their own wellness and provides a cost-effective treatment for the children. | |
8781716 | Immunoglobulin allotypes (GM and KM) and their interactions with HLA antigens in autoimmun | 1995 | GM and KM immunoglobulin (Ig) allotypes and their interactions with HLA antigens have been analyzed in various autoimmune diseases: multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus, coeliac disease, Crohn's disease, Graves' disease, atrophic thyroiditis, Hashimoto's thyroiditis, myasthenia gravis, chronic active hepatitis, alopecia areata, uveitis, vitiligo, Turner's syndrome, glomerular nephritis, Berger's disease and idiopathic dilated cardiomyopathy. This review reports published results about associations or linkages, as well as the origins of the populations, the numbers of patients and controls tested. The possible role of Ig polymorphisms in the physiopathology of autoimmune diseases is discussed. Ig allotypes and statistical methods used to analyse the HLA and Ig data are also described. | |
7980711 | Lp(a) lipoprotein in cardiovascular disease. | 1994 Aug | The article summarizes the increased knowledge about the enigmatic Lp(a) lipoprotein and its clinical importance over the past 20 years. The mode of inheritance, the unique features of Lp(a) composition and structure and the unusual distribution of the mainly genetically determined plasma Lp(a) levels are discussed. The main factors that can significantly change the inherited plasma Lp(a) levels are endocrine disorders and hormone treatment. It seems possible that sex hormones protect females to a large extent from the potentially deleterious effects of inherited high Lp(a) levels until menopause. The exceptionally strong independent association found in most studies between Lp(a) lipoprotein levels and atherosclerotic disorders indicates that Lp(a) is a factor of outstanding importance in the pathogenesis of atherosclerosis. Probable pathogenetic mechanisms are reviewed. The associations found between LP(a) and insulin release, rheumatoid arthritis and renal diseases suggest that Lp(a) may be involved in immunological mechanisms. In a new hypothesis it is suggested that an autoimmune process might especially occur in individuals with inherited high Lp(a) levels and certain HLA class II genotypes, triggered by a concurrent infection. | |
1481225 | Steroids, the steroid community, and Upjohn in perspective: a profile of innovation. | 1992 Dec | The announcement in 1949 at the Mayo Clinic of the dramatic effect of cortisone in alleviating the symptoms of rheumatoid arthritis triggered a competitive worldwide research and development effort directed toward a single goal, the practical synthesis of the rare corticosteroids. The confluence of an extraordinary coalescence of multiple events and circumstances in the growth of the Upjohn Company with the Mayo discovery, inclusive of a pioneering role in the steroid field, conspired to create an environment ripe for innovation. The breakthrough, which gave Upjohn an early competitive edge, followed with startling swiftness. A common mold of the genus Rhizopus was found to introduce enzymatically an 11 alpha-hydroxyl group directly into the female hormone progesterone, which had just been synthesized from the soybean sterol stigmasterol--a one-step solution to the known multistep alternatives for 11-oxygenation. Retrospective analysis of this event in perspective with other key developments before and after at Upjohn and in the steroid community reveals a striking profile of ongoing innovation. A parallel scenario in kind was repeated at Upjohn a quarter century later. The sister soybean sterol sitosterol was radically degraded microbiologically and concurrently oxygenated in ring C to produce 9 alpha-hydroxyandrostenedione, an alternative key intermediate for corticoid synthesis. New chemical processes, highly integrated with existing processes, assured the continuation of Upjohn's leading role in steroid hormone production. | |
1417124 | Repetitive strain disorder: towards diagnostic criteria. | 1992 Aug | Thirteen women (mean age 48.2 years; range 25-60 years) all of whom had developed musculoskeletal symptoms during employment in an industrial job with repetitive tasks were referred by their trade unions for adjudication on the cause of symptoms. One had rheumatoid arthritis. A study of the other 12 women provided an opportunity to document the natural history of repetitive strain disorder. Early symptoms of weakness were diffuse but were always relieved by rest. Several months later localisation of symptoms at a tendon, nerve, or enthesis could be predicted from the analysis of the action required in the particular repetitive task. Six of the 12 women required an operation several years later, thus providing histological confirmation of the presence of a lesion. Early loss of grip strength measured by a sphygmomanometer cuff compared with an unaffected control subject and improved by rest may be the most valuable sign in excluding compensation neurosis. The estimated prevalence of repetitive strain disorder defined by these strict criteria was at least 2% in conveyor belt workers. | |
1615302 | [Vasculitic skin lesions caused by nonsteroidal anti-inflammatory agents]. | 1992 Jun 13 | Today, non-steroidal anti-inflammatory drugs are very frequently prescribed agents. These drugs are responsible for side effects which are rarely recognized and poorly understood. One of these side effects is leukocytoclastic vasculitis with or without skin ulcerations. Rheumatoid arthritis and other mixed connective tissue diseases may also lead to vasculitis ulcerations, which explains the difficulty of correct diagnosis in each case. In addition, disease-modifying drugs such as methotrexate, frequently used in the above-mentioned syndromes, further complicate the situation because these agents may also produce vasculitis. In the present case study we analyze and discuss the diagnosis and follow-up in three of our patients with vasculitis skin ulcerations. In two of them, the vasculitis was attributed to the use of naproxen. Despite thorough examination and documentation of all three cases, etiologic evaluation was difficult and complex. | |
1555501 | [Extracorporeal shockwave lithotripsy in gallstone perforation]. | 1992 Apr 3 | A 78-year-old man with rheumatoid arthritis, arteriosclerosis and cardiac arrhythmias (Lown grade IVb) was admitted to hospital because of haematemesis. Gastroscopy revealed a narrow, deformed duodenal bulb with a bleeding ulcer crater on the posterior wall and a mucosal protrusion 1 cm in diameter. In the course of the illness the duodenal bulb obstruction increased further and there was recurrent vomiting. Repeat gastroscopy 7 days later showed a gallstone, about 4 cm in diameter, which had perforated into the duodenal bulb and could not be removed endoscopically. Because of the serious nature of the other diseases an operation was not undertaken, but an ultrasound-guided extracorporeal shockwave lithotripsy was performed. In three sessions this succeeded without complication to break up the stone, the larger fragments of which were then removed endoscopically while the small ones passed through the gut spontaneously. Subsequent ultrasonography demonstrated a shrunk, stone-free gallbladder with a cholecystoduodenal fistula. Afterwards the patient was again able to take food by mouth without any problems. | |
1562038 | Hyperprolactinemia in systemic lupus erythematosus: association with disease activity. | 1992 Apr | This study was designed to determine the prevalence and clinical significance of hyperprolactinemia in systemic lupus erythematosus (SLE) and other rheumatic diseases. Basal levels of prolactin were determined in 130 nonselected sera from patients with rheumatic diseases including 45 with SLE, 31 with rheumatoid arthritis, 23 with osteoarthritis, 18 with fibromyalgia, and 13 with polymyalgia rheumatica. Serum samples of 28 healthy subjects were used as normal controls. Serum prolactin was measured by radioimmunoassay. ANA, anti-DNA, RNP, Sm, Ro, La, and anticardiolipin antibodies were determined by standard techniques. Elevated serum levels of prolactin (PRL greater than 20 ng/ml) were found in a subset of SLE patients. In addition, a direct correlation with clinical disease and serological (ANA) activity was also found. These findings suggest a potential role for this immunoregulatory hormone in SLE pathogenesis. | |
1503633 | Malignancy in autoimmune diseases. | 1992 Apr | Rheumatoid arthritis (RA) represents the autoimmune disease that has been most studied in relation to malignancy. An examination of all published cohort studies has indicated a 9.7-fold increase of non-Hodgkin's lymphoma among RA patients after immunosuppressive therapy, and a 2.5-fold increase in the absence of such treatment. Corresponding data for Sjögren's syndrome point to a similar contrast. These findings are inseparable from the hypothesis of impaired immunosurveillance which implies that malignancy is promoted by defects in the immune system. Studies of individuals treated with immunosuppressive drugs, particularly to prevent graft rejection, have indicated that immunosurveillance operates only against a restricted range of neoplasms. These include non-Hodgkin's lymphoma (NHL), squamous cell skin cancer, Kaposi's sarcoma and cervical carcinoma. Other states of immune impairment including AIDS are also associated with marked increases of NHL. There is a striking correspondence between malignancies for which there is epidemiological or laboratory evidence for a virus aetiology and those that are increased by immune impairment. In this respect the epidemiological evidence accords with experimental work that immunosurveillance primarily operates against neoplasms of viral origin. It is therefore possible that a viral aetiology also underlies the excess of NHL in certain autoimmune disorders, particularly after immunosuppressive therapy. | |
8151573 | Class II alleles in juvenile arthritis in Czech children. | 1994 Jan | OBJECTIVE: Patients with pauciarticular and polyarticular onset rheumatoid factor (RF) negative juvenile arthritis (JA) have been reported to have a variety of HLA associations. The reason for the differences found in several recent studies is not known. We compare a new series of patients investigated in Prague, Czechoslovakia with those we reported from Dallas. METHODS: Czech patients with JA (N = 153) were classified clinically using the same criteria as in our studies in Dallas. The RF negative group included 56 patients that had persistent pauciarticular disease, 42 pauciarticular with polyarticular course and 39 with polyarticular onset. RF was present in 13 additional patients. HLA class II alleles were determined by oligotyping as previously described from our laboratory. RESULTS: DRB1*0801 was increased and DRB1*0701 was decreased in all the RF negative groups. The persistent pauciarticular group was associated with DRB1*11 and DPB1*0201 and lacked the association with DRB1*1301 seen in Dallas. Also found in Prague and not in Dallas were an increase in the frequency of DR2 in pauciarticular patients with early conversion and of DRB1*1201 in patients with iritis. Certain HLA associations (DRB1*0801, DPB1*0201) appear to be present in patients with JA in most studies; others (DRB1*1301, DPB1*0301) are more variable. CONCLUSION: The reason for differences in the HLA risk factors observed in our 2 populations is not known. Clinical heterogeneity not detected by our method seems the most likely explanation. Genetic and environmental factors may also play a role. | |
7837146 | Selective expression of V beta families by T cells in the blood and salivary gland infiltr | 1994 Oct | OBJECTIVE: The T cell infiltration of the salivary gland of patients with Sjögren's syndrome (SS) has been implicated in the pathogenic process of the disease. We examined the representation of V beta subsets in the blood and salivary tissue of patients with SS. METHODS: Circulating T cells from 12 patients and paired samples of blood and labial salivary glands obtained from 8 patients were studied. A panel of monoclonal antibodies directed against the variable region of the T cell receptor was used to enumerate the cells expressing V beta families in the peripheral blood by flow cytometry, and in tissue sections by immunofluorescence. RESULTS: We found an increase of cells bearing V beta 2 family gene products in the circulation, and an increase in both V beta 2 and V beta 8 in the salivary gland infiltrate of patients with SS. No significant difference was noted between the 5 DR3+ patients and 7 DR3- patients studied with regard to the V beta families seen. CONCLUSION: Our data are consistent with a role for specific T cell families in the pathogenesis of SS. |