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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7299766 | Lack of antibody in rheumatoid sera to autologous synovial macrophages and dendritic cells | 1981 Jul | We tested the hypothesis that antigens which stimulate the chronic immune reactivity in rheumatoid synovia might be associated with synovial macrophages and dendritic cells. ADCC assays were used to test sera from 15 RA patients and 8 non-RA controls for antibody to autologous primary and secondary cell cultures prepared by enzymatic digestion of synovial tissue. Such autoantibody was not detected in any of the 23 patients using assay conditions which minimized potential ADCC blocking effects of immune complexes and multinuclear giant cells. Collagenase producing dendritic and multinuclear giant cells. Collagenase activity and dendritic cells occurred with equal frequency in both RA and non-RA primary monolayers. | |
849643 | Serum effects of mitogenic reactivity in subjects with systemic lupus erythematosus, rheum | 1977 Jan | Methodological problems which affect the assessment of humoral effects on mitogenic reactivity include: (1) the source and concentration of serum used to support cell cultures; (2) the day to-day variability of inhibitory effects and (3) the specific activity of [3H]thymidine added to the culture. These problems were alleviated by addition of half concentration (7-5%) of pooled normal human serum to all cultures, the intoruction of anti-lymphocyte serum as a suitable internal control for monitoring the suppressability of lymphocytes and a reduction of specific activity of the [3H]thymidine to 1-3 C2/mM. Inhibitory factors were loosely bound to the lymphocyte surface and eluted off after incubation at 37 degrees C for 1 hr. Cells from twenty-five subjects and paired controls were cultured simultaneously in medium containing either 15% normal human serum (NHS) or 7-5% patient and 7-5% NHS. The cells were stimulated with various dilutions of phytohaemagglutinin, Con A or pokeweed mitogen. Lupus serums suppressed the reactivity of autologous lymphocytes to PHA and pokeweed mitogen. Serums from subjects with RA and scleroderma did not significantly inhibit blastogenesis of autologous lymphocytes. One-half of the lupus serums significantly inhibited the reactivity of homologous lymphocytes to two of three mitogens. Only one of eight scleroderma serums and none of twelve RA serums and none of twelve RA serums had this effect. All patients serums were examined for antilymphocyte antibodies by microcytotoxicity and immunofluorescent techniques. These antibodies were usually found in SLE, and were often observed in subjects with rheumatoid arthritis but not scleroderma. A firm relationship between serum suppressors of lymphocyte blastogenesis and anti-lymphocyte antibodies was not found. | |
3928684 | Anti-Fab antibodies in humans. Predominance of minor immunoglobulin G subclasses in rheuma | 1985 Aug | Isoelectric focusing analyses of sera from patients with rheumatoid arthritis (RA) demonstrate two populations of antibodies directed against the Fab portion of pooled human IgG. One population is composed of polyclonal alkaline anti-Fab antibodies (alpha FABA) and the other, acidic alpha FABA which are more clonally restricted. In this study we have identified the immunoglobulin classes and subclasses of these antibodies in RA sera. Enzyme-linked immunosorbent assays (ELISA) demonstrated alpha FABA in RA sera to be predominantly IgG. A large portion of IgG alpha FABA existed as immune complexes, inasmuch as dialysis of RA sera against 6 M urea before ELISA analysis was necessary for maximal detection of alpha FABA activity. Chromatofocusing of RA sera isolated alpha FABA of different charges and revealed the acidic clonally restricted alpha FABA to be IgG4 and IgG3, whereas the polyclonal alkaline group contained IgG1, IgG2, and IgG3. Overall, acidic IgG3 and IgG4 comprised 70% of IgG alpha FABA, and high levels of IgG4 were seen in most RA sera. When alpha FABA were elevated in normal sera, they were primarily of the IgG4 subclass, and also existed as immune complexes. Serum anti-Fab activity was removed by adsorption of sera with Fab fragments. Anti-Fab antibodies of both kappa and lambda light-chain types were present in RA sera, and F(ab')2 fragments of RA serum immunoglobulin were found to possess anti-Fab activity. These studies indicate that alpha FABA in RA sera are limited to the IgG class, and that most of these antibodies exist as immune complexes and display clonal and minor IgG subclass restriction. | |
7381068 | Behçet's disease and treatment with colchicine. | 1980 May | A case of Behçet's disease characterized by anterior uveitis, arthritis, oral, genital, and cutaneous lesions, as well as gastrointestinal involvement, all documented over a 10-month period, is presented. Less commonly appreciated complications, such as pyoderma gangrenosum, hidradenitis suppurativa, perianal fistula, and persisting leukocytosis, were among striking clinical features of the patient's history. Remission of cutaneous lesions and no recurrence of ocular or gastrointestinal manifestations occurred with 0.6 mg oral colchicine twice daily in a period of 5 weeks. | |
6658399 | Serum ferritin and the assessment of iron deficiency in rheumatoid arthritis. | 1983 | In order to evaluate the diagnostic and pathogenetic importance of s-ferritin and p-lactoferrin in the anemia of rheumatoid arthritis (RA), 38 patients were examined. Twenty-one out of 38 randomly selected anemic patients with classical or definite RA had iron deficiency, as estimated from the iron content in stained bone marrow aspiration. S-ferritin concentrations below 60 micrograms per litre had sensitivity and a specificity for iron deficiency of 86% and 88%, respectively, which was much better than such commonly used variables as s-iron, p-transferrin, MCV, and MCHC. Although this cut-off level is higher than in patients without inflammatory disease, s-ferritin was not correlated to disease activity. In 7 out of 8 patients, the s-ferritin level rose during iron therapy. P-lactoferrin values were within the normal range and did not vary with the anemia or with disease activity. Thus p-lactoferrin appears to be of no pathogenetic importance in the anemia of RA. | |
4067848 | Pharmacokinetics of tiaprofenic acid in healthy and arthritic subjects. | 1985 Sep | Disposition kinetics of nonsteroidal, anti-inflammatory tiaprofenic acid (1) and its metabolites were studied in healthy subjects and arthritic patients under treatment with 200 mg of the drug three times daily. The concentration of the drug and its metabolites were measured using a sensitive and specific HPLC method. The pharmacokinetics of tiaprofenic acid in arthritic patients seems to be similar to those in healthy subjects. The drug is rapidly absorbed, extensively bound to plasma proteins and, upon repeated administration, is accumulated in the body only to a limited extent. While only unchanged drug was found in plasma, a negligible amount of the unchanged drug was recovered from urine. The major pathway of drug elimination seems to be through conjugation. The reduced and oxidized metabolites of 1, 2 and 3, respectively also are found in urine as conjugates. The conjugates are, however, relatively unstable and are readily hydrolyzed to their parent compounds upon storage or addition of alkali. As elimination of the drug is dependent upon urinary excretion of the conjugates, it may be influenced by reduced renal function or the presence of other drugs. | |
6799579 | Measurement of the complement C3 breakdown product C3d by rocket immunoelectrophoresis. | 1982 | A method is described for quantitative measurement of C3d in plasma and synovial fluid by the use of rocket immunoelectrophoresis after fractionation of the samples with 22% polyethylene glycol. This method has the advantage over radial immunodiffusion of being more sensitive (detecting C3d down to 3 mg/l) whilst proving equally reproducible. Investigations indicate that the collection of blood samples in EDTA prevents in vitro activation of C3 even after storage for up to 6 h at room temperature and up to 12 weeks at -70 degrees C. Elevated levels of C3d were found in a proportion of SLE and RA plasma samples and in synovial fluids from patients with inflammatory synovitis. It is suggested that C3 conversion in vivo may be assessed by measurement of C3d by the technique described, and when used in conjunction with measurements of complement components and immune complexes, offers a means of investigating complement catabolism by the classical and alternative pathways. | |
6610510 | Analysis of in vitro polyclonal B cell differentiation responses to bacterial peptidoglyca | 1984 May | To gain insight into possible determinants of in vivo polyclonal B cell activation seen in rheumatoid arthritis (RA), we enumerated immunoglobulin secreting cells appearing in cultures of peripheral blood mononuclear cells that were stimulated with pokeweed mitogen (PWM) or a newly described polyclonal B cell activator, bacterial peptidoglycan. Peptidoglycan, the major constituent of the cell wall of gram positive bacteria, has properties which warrant its consideration in the pathogenesis of RA; including the ability to induce rheumatoid factor production as well as a RA like syndrome in experimental animals. RA patients as a group had similar immunoglobulin secreting cell responses in PWM stimulated cultures compared to arthritis controls and showed moderately depressed responses compared to healthy volunteers. However, their in vitro responses to peptidoglycan were markedly depressed when compared to those of both control groups. Of note, severely reduced peptidoglycan-induced responses were seen in 26 of 55 rheumatoid patients who demonstrated intact PWM-induced responses. These impaired responses to peptidoglycan were not due to (1) aberrant kinetic response; (2) shift in the dose-response pattern; (3) decreased cell survival in culture or (4) the inability of peptidoglycan to activate RA cells. Cell fractionation studies indicated that peptidoglycan reactive B cells were present in the blood of some patients but their reactivity was abrogated by suppressor T cells. These studies provide evidence of aberrant in vitro polyclonal B cell activation in patients with RA and provide a basis for further investigation of peptidoglycan as an immunopathogenetic agent in this disease. | |
699547 | The role of computed tomography in the evaluation of upper cervical spine pathology. | 1978 | A series of nine patients with symptoms referable to the upper cervical spine were recently studied by both conventional radiographic techniques and computed axial tomography (CT), in an attempt to ascertain the effectiveness of CT in evaluating upper cervical spine pathology. We found CT a useful tool in diagnosing a variety of pathological conditions in this region, particularly when they involve subtle neural arch fractures, rotational deformities, or compromise of the neural canal. | |
335682 | [Cortisonoids in the therapy of rheumatic diseases]. | 1977 Jul 15 | Taking into consideration the special therapeutic problems in rheumatology a short survey oriented to practice on the treatment with cortisonoids is given. The pharmacology of these compounds is dealt with in short. Emphases of the description are general principles of treatment, indications and dosage in systemic and local treatment, side effects, problems of long-term treatment, application of ACTH, the cortisonoid withdrawal syndrome, prophylaxis of therapy complications and references to the reduction of the dose or to the withdrawal of the treatment with cortisonoids. | |
7230162 | Plasma exchange therapy for severe penicillamine-induced myasthenia gravis. | 1981 Mar | Two rheumatoid patients with typical D-penicillamine-induced myasthenia gravis, both resistant to anticholinesterase therapy, were treated with intensive plasma exchange. With this therapy, both patients quickly regained normal muscle power. Plasma exchange therapy may benefit penicillamine-induced myasthenic patients who develop life-threatening weakness despite withdrawal of D-penicillamine and the use of anticholinesterase medication. | |
6213366 | Induction of cartilage degradation in experimental arthritis produced by allogeneic and xe | 1982 | A single intra-articular injection of proteoglycan (PG) antigens induced sterile inflammatory response and cartilage degradation in preimmunized rabbits and dogs. Both cell-mediated and humoral immune reactions could be detected against PG antigens in these animals, but there was no response against collagen Type II. The lymphocytes isolated from the inflamed synovial layer proved to be predominantly of T cell type. The cartilage degradation was indicated by the accumulation of IgG and complement in the superficial layer of the articular cartilage. By the diminished number of chondrocytes and by the increased binding of specific antibodies in the ground substance. The results suggest that PG antigens trigger local immune reactions which become self-sustaining by enzymatic exposure of antigenic sites. The anti-PG antibodies are cytotoxic to articular chondrocytes and thus can block the continuous neogenesis of matrix components which may lead ultimately to deterioration of the cartilage. This type of experimental arthritis appears to be a model closely related to rheumatoid arthritis. | |
776838 | Induction of adjuvant arthritis in the rat by various bacterial cell walls and their water | 1976 | A number of purified cell walls of various gram-positive bacteria had arthritogenic activity in the rat. The water-soluble adjuvant-active component(s), which were isolated from some of these cell walls by utilizing a peptidoglycan-degrading enzyme, did produce severe adjuvant arthritis. However, the components obtained by digestion with glycan-degrading enzymes failed to produce arthritis. Thus, the present finding indicates the importance of a peptidoglycan portion, especially its intact glycan chain, for induction of adjuvant arthritis. | |
2415656 | IgG rheumatoid factors and staphylococcal protein A bind to a common molecular site on IgG | 1985 Dec 1 | The antigenic determinant on the Fc region of human IgG for two IgG rheumatoid factors (IgG-RF) from patients with rheumatoid arthritis were investigated in detail. The RF did not interact with IgG fragments that contained the C gamma 2 or C gamma 3 region alone, but required the presence of both regions for binding. The RF binding to solid-phase IgG were poorly inhibited by the IgG3 subclass and strongly inhibited by staphylococcal protein A (SPA) (42 kD), and fragment D of SPA (7 kD), indicating that the binding site is most likely the same as the Ga antigenic determinant described for IgM-RF, and is in the same location as the site on IgG that binds SPA. pH titration studies of the RF binding to IgG indicated the involvement of histidine and lysine or tyrosine side chains. Chemical modification studies showed the histidines were involved on the Fc side of the interactions, and tyrosines were involved on both the antigenic and antibody sides of the interactions. Lysines were not involved. The above information, and the knowledge of the number and position in space of the amino acid residues involved in the C gamma 2-C gamma 3 interface region of IgG, the binding site for SPA, and the amino acid substitutions in IgG3 that account for its inability to bind protein A, allowed the identification of the site on IgG that bind IgG-RF. This binding site involves some of the same amino acid side chains, His 435, Tyr 436, and one or both His 433 and 310, and is in the same location as the site that binds SPA. The same site is likely to be a common antigenic determinant for other RF. Furthermore, the described molecular mimicry suggests a biological relationship between bacterial Fc-binding proteins and the production of RF in rheumatoid arthritis. | |
7229514 | IgG rheumatoid factor: analysis of various species of IgG for detection by radioimmunoassa | 1981 Jun | IgM RF is known to react with many species of IgG. This study examined nine species of IgG to determine which was the most sensitive and specific to detect IgG RF by radioimmunoassay. For 19 IgM RF-positive sera, horse IgG was significantly more sensitive than all IgG preparations tested except rabbit IgG. The IgG used include sheep, swine, goat, bovine, and chicken as well as human and baboon Fc. For 22 IgM RF-negative sera from patients with rheumatoid arthritis, only one was positive for IgG RF with rabbit IgG, whereas five were positive with horse IgG. Analysis after preparative ultracentrifugation of a variety of sera positive and negative for IgM RF indicated that horse IgG was more sensitive, whereas rabbit IgG was more specific for the detection of IgG RF by our radioimmunoassay. IgM RF, on the other hand, was more sensitively detected by human Fc than by any preparation other than whole human IgG. | |
10439 | Evaluation of analgesic action and efficacy of antirheumatic drugs. Study of 10 drugs in 6 | 1976 Sep | A single-blind non-crossover method for assessing the potential effectiveness of antirheumatic drugs has been described. The method employs entirely subjective indices and incorporates a daily pain chart for measuring the pain response over the duration of the trial. In addition, the mean number of days withdrawn and patients' satisfaction rating are measured. The statistical method can correct for initial imbalances between groups and allows for the valid comparison of drugs from separate trials. Ten antirheumatic medications were evaluated using this technique in 684 patients with rheumatoid arthritis, and the results are in agreement with those of previous studies using standard clinical methods. The new method is simple, rapid in performance, economical in terms of cost and time, and has been shown to be sensitive and reproducible. The results indicate that there are no significant differences in efficacy between the currently available non-steroidal, anti-inflammatory analgesic drugs, in the treatment of rheumatoid arthritis. | |
995608 | [Gastric mucosa in patients with rheumatoid polyarthritis treated by anti-inflammatory age | 1976 Dec 4 | One hundred patients (50 male, 50 female) suffering from rheumatoid arthritis, treated for more than 6 months with steroid and/or non-steroid anti-inflammatory agents were studied using barium X-rays and gastro-fibroscopy. In 69, one or more gastric biopsies were taken during the endoscopy. The study showed a marked preponderance of ulcerous lesions in males, 9 of the 13 iatrogenic ulcers being found in this sex. It also confirmed the frequency of gastritis and the absence of any correlation between clinical signs and radio-endoscopic findings as well as between the latter and histopathological data. An ultra structural study carried out in 20 cases revealed focal lesions of the clear cells of the neck of the fundus and antral glands and, in 4 cases, marked changes in the gastric endocrine cells. | |
6725347 | A technique for difficult arthrodesis of the knee. | 1984 May | Twenty knees, in which a total of 32 previous operations had been performed, were arthrodesed by the Charnley compression technique combined with intramedullary nailing. Patients with previous infection were excluded from the series, but three neuropathic knees were included. Bony union was evident after an average of six months in all but one patient who died three months after operation. One patient developed deep infection that resolved after removing the nail. The combined technique is simple and only limited bone resection is needed; it gives immediate stability and relief of pain with minimal morbidity. | |
117056 | Improved detection of immune complexes in human and mouse serum using a microassay adaptat | 1979 | A microassay adaptation of the [125I]C1q binding test for the detection of circulating immune complexes is described. This technique is more rapid to perform, requires smaller volumes of serum and reagents, and surprisingly, increases the sensitivity of the assay when compared to the previously reported C1q binding method. | |
8473 | Biological aspects of leukotactic factors. | 1976 Jul | Quantitation of leukotaxis involves direct visualization of migrated cells either as total cell numbers or according to depth of penetration of cells into filters. Newer approaches utilize radioactively labeled cells or movement in gel. Considerable controversy exists regarding the structural attributes of chemotactic activity, although synthetic peptides emphasize the importance of primary structure. Leukotactic factors, both complement-derived and lymphocyte-generated, have been found in many conditions both in vitro and in vivo. There is increasing evidence that the leukotactic system plays an important role in the pathogenesis of inflammation. |