Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 6981833 | Some ultrastructural aspect of T and B lymphocytes and their significance in chronic inter | 1982 Jan | Some peculiar aspects of T and B lymphocytes from patients with chronic internal diseases with immune component such as: chronic hepatitis (CH), rheumatoid arthritis (RA), diabetes mellitus (DM), systemic lupus erythematosus (SLE), chronic lymphocytic leukemia (CLL) and others, could be detected using transmission electron microscopy (TEM) or scanning electron microscopy (SEM) in association with cytomorphologic, cytoenzymochemical and/or cytoimmunologic methods. Among the more frequent aspects observed were the change of the T and B lymphocyte balance and the presence of giant nucleoli associated with RNA hyposynthesis. This latter aspect was proved to be a sign of unfavourable prognosis and of resistance to immunosuppressive treatments in diseases such as: RA, SLE and CLL. | |
| 7251195 | Levamisole-induced neutropenia and agranulocytosis: association with HLA B27 leukocyte agg | 1981 | Among 37 patients treated with levamisole for rheumatoid arthritis (n = 19), for Reiter's disease (n = 4) and for chronic articular brucellosis (n = 14) followed up during 6-12 months, 3 developed agranulocytosis and 3 severe neutropenia. Serum samples drawn before and during treatment were tested for leukocyte agglutinating and lymphocytotoxic antibodies. Leukocyte agglutinating antibodies were induced in 8 patients, in 5 of them in association with agranulocytosis or neutropenia. In 1 patient with agranulocytosis and in another one with neutropenia lymphocytotoxic antibodies were also induced. Two agranulocytotic and one neutropenic patient possessed HLA B27 antigen. In altogether 11 HLA B27 carriers the number of circulating neutrophils were significantly reduced during levamisole treatment when compared with those of patients lacking HLA B27 antigen. | |
| 7438779 | Histologic observations of pleomorphic corynebacterium-like microorganisms in diabetic scl | 1980 Dec | Diabetic scleredema adultorum is a rare connective tissue disorder characterized by scleroderma-like changes, usually affecting the skin of the neck, shoulders, and upper back in diabetics. Presented herein are two cases in which pleomorphic, but predominantly coccoid forms, were observed in acid-fast, Giemsa, and Gram-stained tissue, sections of the affected skin. Culture of the skin was positive for a microaerophilic, corynebacterium-like organism in one case and an anaerobic Propionibacterium (Corynebacterium) sp in the other case. The morphologic appearance of the bacterial isolates greatly resembled the morphologic forms observed in the tissue sections, suggesting that bacteria, possibly in a cell-wall-deficient phase, may play a role in the pathogenesis of this disorder. Findings of similar bacteria in previously reported cases of other connective tissue disorders such as sclerodermiformis, and rheumatoid arthritis, might support our idea that bacteria could supply the antigenic stimulus for the production of scleredema. | |
| 6777493 | Studies of the intestinal metabolism of oral gold. | 1980 Sep | In order to understand some of the unique toxic/therapeutic properties of the orally administered gold containing compound auranofin, the intestinal metabolism of gold was studied in 4 normal subjects. A triple lumen intestinal perfusion apparatus was used to measure intestinal flux using a non-absorbable radiolabelled marker dilution technique. Over a short (50 cm) segment of proximal small bowel, substantial disappearance of gold was observed; the findings, however, were most consistent with a loose, reversible adsorption onto the enteric cell surface rather than true trans-mucosal absorption. There was no evidence for an entero-hepatic recirculation of gold in these subjects or in 4 additional patients with rheumatoid arthritis studied in a similar manner. | |
| 7394058 | The effect of anti-inflammatory drugs on glycosaminoglycan sulphation in pig cartilage. | 1980 Mar | Indomethacin, aspirin and hydrocortisone have been shown to inhibit glycosaminoglycan sulphation in pig costal cartilage discs. The doses at which inhibition was observed varied from pig to pig from 0.1 - 50 microgram/ml for indomethacin, 40 - 150 microgram/ml for aspirin and 0.5 - 1 mg/ml for hydrocortisone, doses which are achieved clinically in the treatment of joint diseases. In a minority of experiments a significant stimulation of glycosaminoglycan sulphation was observed at lower doses of indomethacin and hydrocortisone but not aspirin. THe results suggest that in rheumatoid arthritis but more especially osteoarthritis, treatment with these drugs should aim at finding the lowest doses which have a therapeutic effect. As importantly the clinician should always consider using lower doses just as much as higher doses when the first dose regimen is unsatisfactory. | |
| 393057 | Anterior segment fluorescein angiography in inflammatory diseases of the cornea. | 1979 Oct | To study the vascular changes in inflammatory diseases of the cornea 22 patients with various corneal inflammations were examined by means of anterior segment fluorescein angiography. Simple avascular central and marginal corneal ulcers stained with fluorescein in the late phase of angiography. An inflamed limbus and an early microscopic pannus adjacent to the ulcer were seeen in simple corneal ulcers. Progressive pannus with pronounced fluorescein leakage was observed in chronic corneal ulcer, disciform keratitis, Mooren's ulcer, and complicated acute keratoconus. In sclerokeratouveitis and in gutter associated with rheumatoid arthritis the corneal vessels showed less leakage. The iris vessels showed fluorescein leakage as a sign of irritative iritis during the active stage of simple and chronic corneal ulcers, in disciform keratitis, Mooren's ulcer, and in graft rejection. It is concluded that anterior segment fluorescein angiography gives valuable information of the vascular architecture, flow and leakage in inflammatory diseases of the cornea. | |
| 418759 | Histocompatibility antigens (HLA): associations with immunopathic diseases and with respon | 1977 Dec | Described is the experience from a single histocompatibility typing laboratory sampling, firstly, Australian patients with various immunopathic diseases and, secondly, subjects previously classified as "responders" or "non-responders" to various microbial antigens. The diseases considered included chronic active hepatitis (CAH) and various cirrhoses, "thyrogastric" autoimmune diseases, systemic lupus erythematosus (SLE), rheumatoid arthritis, dermatitis herpetiformis (DH) with intestinal villous atrophy, and multiple sclerosis (MS). The immune responses considered included those to flagellin, candidin, mumps, trichophyton, tuberculin and streptococcal enzymes. The HLA specificities particularly associated with disease included B8 (CAH, thyrotoxicosis SLE, DH, and miscellaneous immunopathic diseases) and B7 (thyrotoxicosis, SLE, DH, and MS). The same specificities were present in excess, although not impressively so, among responders to certain of the microbial antigens, i.e. B7 with high responders to flagellin and B8 (and A1) with responders to trichophyton. | |
| 60503 | Antiglobulin factor in sera from patients with liver disease. | 1976 Feb | (1) An antiglobulin factor, non-neutralizable by human gamma-globulin, was demonstrated in sera of two patients with liver disease. (2) By absorption and elution techniques, two fractions were differentiated in a serum: one is reactive to rabbit antibody and the other seems cross-reactive to rabbit and human antibodies. (3) In double immunodiffusion test, the antiglobulin factor formed a precipitation band with heat-aggregated human IgG as did rheumatoid arthritis serum. (4) While the antiglobulin activity to rabbit antibody was demonstrated in both the IgM and IgG fractions, the reactivity to human antibody was localized in the IgM fraction. (5) From its selective reactivity to individual anti-D sera (sensitizers), at least a part of the specificity of the antiglobulin factor must be related to anti-Gm (1), and consequently can be regarded as auto-reactive. | |
| 797666 | Structure and biological functions of human IgD. VII. IgD antinuclear antibodies in sera o | 1976 | Indirect immunofluorescent tests were employed to study antinuclear antibodies (ANA) of the IgD class in sera from patients with autoimmune disease. In sera containing IgG-ANA, IgD-ANA was detected in 48% of patients with systemic lupus erythematosus, 37% with rheumatoid arthritis, 30% with Raynaud's disease, 23% with systemic scleroderma and 20% with discoid lupus erythematosus. Quantitative comparison of serum IgG, IgA, IgM and IgD between IgG-ANA-positive sera with and without IgD-ANA revealed that patients with IgD-ANA also had elevated serum IgA levels. The detection of IgD-ANA in over 36% of the patient population suggests that IgD may play a role in autoimmune disorders. | |
| 7213431 | Interaction between rheumatoid factor and antibody/DNA complexes: enhancement of complemen | 1981 Mar | The influence of rheumatoid factor (RF) on the complement mediated binding of antibody/double-stranded DNA immune complexes to red blood cells has been investigated. Our results indicate that RF enhances this binding reaction, apparently by fixing complement via its own Fc region. These findings suggest that under certain circumstances, RF may play an exacerbating role in the antibody/DNA induced glomerulonephritis of systemic lupus erythematosus. | |
| 6235249 | Gastrointestinal microbleeding associated with the use of etodolac, ibuprofen, indomethaci | 1984 May | Etodolac, a nonsteroidal antiinflammatory and analgesic drug, was used in a randomized, parallel group, open-label design study, with stool analysis conducted in a blind fashion, to compare its effect in normal men in doses of 400 mg (N = 11) and 600 mg (N = 12) b.i.d. on gastrointestinal microbleeding with that of 600 mg ibuprofen, q.i.d. (N = 12), 50 mg indomethacin in the morning, 50 mg at noon, and 100 mg h.s. (N = 9), and 375 mg naproxen b.i.d. (N = 9). Etodolac was given at about 2 1/2 and 3 1/2 times the mean effective dose used for treating patients with rheumatoid arthritis. The other drugs were given at their manufacturers' maximum recommended doses. Lead-in placebo was given for one week, active drug for one week, and washout placebo for one week. Fecal blood loss was measured by the 51Cr-tagged red cell method, and was averaged over days 4-7 (baseline), 11-14 (treatment period), and 17-20 (washout). The mean increase in blood loss for the treatment period for the 400 mg etodolac b.i.d. group (0.13 ml) and 600 mg etodolac b.i.d. group (0.10 ml) was significantly less (P = 0.001) than the corresponding values for ibuprofen (1.14 ml), indomethacin (1.20 ml), and naproxen (0.87 ml). There was no tendency for greater blood loss at higher doses of etodolac. Etodolac at doses in excess of the mean effective dose in osteoarthritis and rheumatoid arthritis caused significantly less microbleeding in normal male volunteers during the seven-day treatment period than the other drugs tested, and not clinically more than that occurring during baseline placebo. | |
| 6437309 | Primary Sjögren's syndrome and other autoimmune diseases in families. Prevalence and immu | 1984 Dec | The relationships of human leukocyte antigen (HLA) and heavy chain immunoglobulin (Gm) haplotypes to disease and autoantibody expression were examined in six large kindreds, each having one or more members with primary Sjögren's syndrome. Various other autoimmune diseases and autoantibodies occurred among the 117 relatives in these families. The HLA and Gm haplotypes did not necessarily segregate persons into those with Sjögren's syndrome, other autoimmune disorders, or serologic abnormalities, but HLA alleles DR3 and DR2 occurred in significant excess in relatives with Sjögren's syndrome, irrespective of HLA haplotype. Segregation analysis suggested a Mendelian dominant genetic defect common to the many autoimmune diseases and serologic reactions that was not linked to HLA or Gm. A significant effect of female sex was also documented. These studies suggest that Sjögren's syndrome results from the interaction of several HLA-linked and non-HLA-linked genes. | |
| 6238753 | Characterization of the phenotype and function of lymphocytes infiltrating the salivary gl | 1983 | Monoclonal antibodies directed against T-cell subsets, B-cell subsets, and monocytes were used to characterize the cells infiltrating the salivary glands of patients with primary Sjogren syndrome (1 degree SS). Analysis of stained frozen tissue sections and lymphocyte suspensions derived from salivary glands revealed the majority of infiltrating cells to be T cells (reactive with antibodies SC1 and Leu 4) of the Leu 3a+ subset (greater than 70% reactive). Of particular interest, a high frequency of Ia+ T cells (up to 50% of T cells) and B cells reactive with antibody B532 (5-15% of infiltrating cells) were found in salivary gland lymphocytes (SGL) but not in peripheral blood lymphocytes (PBL) of the same patients. Our finding that the phenotype of SGL was significantly different from PBL emphasizes the need to characterize lymphocytes at the site of tissue destruction. In vitro functional assays demonstrated that the OKT4+ SGL exhibited T-helper activity but not natural killer, antibody-dependent cellular cytotoxicity, or cytotoxic T-lymphocyte activity. Of note, rheumatoid factor (IgM anti-IgG) was produced by SGL but not by the corresponding PBL. Our studies on SG-lymphocyte function represent an early step in elucidating the cellular and subcellular events responsible for this autoimmune disease. | |
| 402475 | Sodium aurothiomalate, gold keratinate, and various tetracyclines in mycoplasma-induced ar | 1977 Feb | Sodium aurothiomalate (ATM), gold keratinate and five different tetracyclines were investigated for activity against M. arthritidis strain ATCC 14124 and M. pulmonis strain JB, both in vitro and in rodents with arthritis caused by these mycoplasmas. In vitro, ATM had only slight activity against M. arthritidis and M. pulmonis, while gold keratinate was virtually inactive against M. pulmonis. In contrast, the tetracyclines were highly active against both mycoplasmas. The tetracyclines and the gold salts were both predominantly mycoplasmastatic. In both rats and mice, parenteral administration of ATM, begun shortly before or after infection of rodents with mycoplasmas, prevented the development of arthritis. ATM or gold keratinate, given subcutaneously to mice already arthritic from infection with M. pulmonis, reduced the severity of the arthritis, even although gold keratinate was inactive aganist this mycoplasma in vitro. Moreover, direct testing of serum, collected from mice treated with gold keratinate, failed to demonstrate antimycoplasmal activity in vitro. These results suggest that the action of gold-containing drugs in mycoplasmal arthritis is due to biological properties of gold other than antimycoplasmal activity. Tetracyclines were also found to be effective in preventing arthritis in rats and mice when given subcutaneously. With high doses, subcutaneous, but not oral, therapy significantly reduced the severity of established arthritis in mice infected with M. pulmonis. The blood levels achieved with the different tetracyclines, when related to their therapeutic activity, indicated that good antimycoplasmal activity and adequate absorption from the gut were not the only properties needed for optimal effectiveness. The results are discussed in relation to treatment of rheumatoid patients with tetracycline HCl. | |
| 6315022 | Morphologic and mitogenic responses of rabbit synovial fibroblasts to transforming growth | 1983 Nov | We tested the hypothesis that normal synovial fibroblasts might proliferate in response to transforming growth factors (TGFs), peptides that are extracted with acid-ethanol from bovine kidney or salivary gland and that cause anchorage-independent growth of normal cells. A 72-hour exposure of confluent monolayers of rabbit synovial fibroblasts in 10% fetal calf serum to partially purified TGF-beta in the presence of TGF-alpha gave a 2- to 5-fold increase in incorporation of 3H-thymidine, protein content, and cell number. Similar results were obtained with high pressure liquid chromatography-purified TGF-beta in the presence of epidermal growth factor (EGF) (a type of TGF-alpha). By itself, purified TGF-beta was not mitogenic; it depended absolutely on EGF. However, only TGF-beta along with EGF, and not EGF alone, induced a marked morphologic change: a piling up of cells into foci resembling those commonly seen in primary cultures of rheumatoid synovial cells. Mitogenic responses induced by the TGF-beta-EGF combination were prevented by all-trans-retinoic acid but not by indomethacin or dexamethasone. The data indicate that TGF-beta, a peptide extracted from normal cells, can act in concert with EGF to cause proliferation and piling up of synovial cells and raise the possibility that these factors may play a role in rheumatoid arthritis and other proliferative but nonmalignant diseases as well. | |
| 30943591 | Enteric Microorganisms in Rheumatoid Diseases: Causative Agents and Possible Mechanisms. | 1985 Jun | The role of foodborne enteric pathogens in the development of three seronegative spondarthropathies (ankylosing spondylitis, Reiter's disease and reactive arthritis) is discussed. Although the prevalence of the HLA-B27 antigen in blood-related individuals suggests a genetic predisposition to these diseases, exogenous environmental factors are also indicated. A clinical profile is given to clarify certain relationships of the seronegative arthropathies. Evidence of the involvement of enteric pathogens in the onset of these conditions following gastrointestinal illness is considered along with the interactions of general and molecular mechanisms of the disease processes and the immune response. | |
| 3887095 | Weber-Christian disease. Analysis of 15 cases and review of the literature. | 1985 May | We report 15 patients encountered over 13 years who presented with inflammation of subcutaneous fat and were given clinical and pathologic diagnoses of Weber--Christian disease (WCD). Prominent clinical features included female predominance, lower extremity nodules, fevers, arthritis/arthralgias, and myalgias. Notable laboratory features were elevated erythrocyte sedimentation rate, anemia, leukopenia, and hypocomplementemia, frequently with circulating 7S IgM or immune complexes at times of active symptoms. Histologic findings were lobular--together with frequent septal--panniculitis, fat-laden macrophages, variable cellular infiltrates, necrosis, and occasional vasculitis. Follow-up revealed the death of 2 patients and disease stabilization or improvement in 13 patients. Six patients developed features of other diseases (factitial disease, erythema nodosum, acute myelogenous leukemia, rheumatoid arthritis, systemic lupus erythematosus, and sarcoid) and a seventh may have had erythema induratum. We suggest that classic WCD, as originally described, reflects an increasingly recognized spectrum of panniculitides. These are syndromes of diverse etiology that share many clinical, inflammatory, and immunologic features. | |
| 3002397 | Effects of gold sodium thiomalate on functional correlates of human monocyte maturation. | 1985 Dec | The mechanism of action of gold salts in the treatment of rheumatoid arthritis is unknown. Effects of gold on monocyte-macrophage function could be due to inhibition of maturation and differentiation. We found that 3 markers of monocyte differentiation, loss of peroxidase activity, spontaneous synthesis of C2, and spontaneous cytotoxicity for chicken erythrocytes, were all inhibited by gold treatment. This was not a general toxic effect since phorbol myristate acetate could still induce gold-treated monocytes to lyse chicken erythrocytes. Also, phorbol myristate acetate-stimulated superoxide production, a monocyte function not requiring further differentiation, was not inhibited by incubation with gold. Lymphokine-stimulated cytotoxicity for nucleated target cells, another function of monocytes, was inhibited only partially for certain target cells and not at all for others. These data suggest that gold has the capacity to selectively inhibit some monocyte functions which are associated with macrophage differentiation. | |
| 4040759 | Anticytoskeletal autoantibodies in the connective tissue diseases. | 1985 Aug | The sera of 103 patients with connective tissue diseases were studied for the presence of anticytoskeletal antibodies by using an indirect immunofluorescence method. PTK2 cells fixed with paraformaldehyde and digitonin were used as substrate. Antibodies to intermediate filaments were detected in sera of 85.7% of polymyositis/dermatomyositis (PM/DM), 62.8% of systemic sclerosis, 54.5% of rheumatoid arthritis, and 37.5% of systemic lupus erythematosus patients, and in 42.5% of normal sera. High titers of these antibodies, which were IgM, were present in 30% of patients' and 5% of normal sera. Antibodies to microfilaments were present in 11.6% of patients' sera and absent in all control sera. These antibodies were IgM or IgG. The switch from an IgM to an IgG antibody was observed in 1 patient. An IgG antibody to the spindle poles and midbody of mitotic cells was present in the serum of 1 patient with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Antibodies to intermediate filaments and to microfilaments occur commonly in the connective tissue diseases, particularly in PM/DM, and are not detected with substrates or fixation methods used in routine antinuclear antibody testing. | |
| 6654954 | Levels of fibrinogen/fibrin degradation fragment E and related substances in sera and effu | 1983 | A radioimmunoassay (RIA) was developed and used to determine the level of fragment E [a fibrinogen/fibrin degradation product (FDP)] and of fragment-E-containing substances (FES) in sera and effusion fluids of patients with malignant diseases. Sera of patients with other diseases and sera of healthy individuals served as controls. Results were expressed as units/ml (U/ml), one unit being equivalent to 40 ng pure fragment E. Effusion fluids of both malignant and nonmalignant origin contained relatively high levels of fragment-E-containing substances, up to 7,500 U/ml. Normal sera had less than 30 U/ml, while sera of patients with a variety of neoplastic or nonneoplastic conditions contained larger amounts, reaching to hundreds and, in rare cases (some patients with rheumatoid arthritis), even thousands of U/ml. Some of the highest levels in the malignant sera were found in samples from patients with Burkitt's lymphoma and stomach cancer. About 10%-20% of the reactive material in effusions and 20%-40% in the sera consisted of fragment E. These results confirm earlier findings of high FDP levels in neoplasia. Given the higher accuracy of the radioimmunoassay and its suitability for large scale testing, it would appear worthwhile to continue such studies to explore the clinical usefulness of the RIA for fragment E. |