Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2814381 | Results of subglandular breast augmentation using a new classification method--18-year fol | 1989 | The main problem after augmentation mammaplasty is the formation of capsular contractures. The frequency of this complication varies in different reports. In this study the results in 60 women 15-21 years after subglandular breast augmentation are presented. The patients completed a questionnaire and the breasts were judged according to a new Breast Augmentation Classification (BAC) scale. Of all breasts examined 79% had grade III or IV, but 77% of the patients were satisfied with the final result. However, 84% thought that their breasts were too hard. Breast cancer had not developed in any patient. Rheumatoid arthritis developed in one patient 4 years after the operation. Capsular contracture and unacceptable results after subglandular breast augmentation were found in the major portion of the patients in this study. | |
| 2461571 | A nonimmunoglobulin precipitin to tissue extracts in pathological human sera. | 1988 Nov | An alpha-globulin component was noted in pathological human sera, which produced gel precipitation reactions with extracts of human and animal liver. The highest incidence of the precipitin was found in malaria (95%), renal graft rejection (81%), and rheumatoid arthritis (57%). The precipitinogen was thermostable and ethanol soluble; of two precipitation lines formed by this component, one merged into identity reaction with a line produced by commercial lecithin of bovine origin. The possible diagnostic application of the reactions noted was considered. | |
| 3229029 | The effect of in vivo and in vitro methotrexate on lymphocyte proliferation as measured by | 1988 Oct | In several studies methotrexate therapy of patients with rheumatoid arthritis has not been found to depress the lymphocyte response to mitogens measured by the uptake of tritiated thymidine. We have postulated two effects of methotrexate on stimulated lymphocytes in vitro: a decrease in cell proliferation, but also a relative increase in thymidine uptake reflecting a specific decrease in the intracellular thymidine pool. The increased incorporation of tritiated guanosine by mitogen-stimulated lymphocytes was found to be markedly depressed by methotrexate (1 x 10(-7) M) in vitro whereas the incorporation of thymidine was often unchanged. Thymidine uptake of lymphocytes may not be an appropriate measure of stimulation in the presence of methotrexate. | |
| 2838005 | Diseases associated with exposure to silica and nonfibrous silicate minerals. Silicosis an | 1988 Jul | Silicosis, a disease of historical importance, continues to occur cryptically today. Its pathogenesis is under ongoing study as new concepts of pathobiology evolve. In this article, the gross and microscopic features of the disease in the lungs and the lesions in lymph nodes and other viscera are described. These tissue changes are then discussed in the context of clinical disease and other possible or established complications of silica exposure (ie, scleroderma and rheumatoid arthritis, glomerulonephritis, and bronchogenic carcinoma). Silicates are members of a large family of common minerals, some of which have commercial importance. Silicates are less fibrogenic than silica when inhaled into the lungs, but cause characteristic lesions after heavy prolonged exposure. The features of these disease conditions are described herein. Various aspects of the mineralogy and tissue diagnosis of silicosis and lung disease due to silicates are reviewed. An overview of contemporary regulatory considerations is provided. | |
| 2832212 | Oxygen radical induced alterations in polyclonal IgG. | 1988 Mar 28 | In the sera and synovial fluid of patients with rheumatoid arthritis, part of the IgG fraction is found in an aggregated and fluorescent form. Oxygen-free radicals have been implicated in this denaturation, although the precise radical species responsible is unknown. In this work, oxygen-free radicals generated radiolytically were allowed to attack polyclonal IgG in solution. OH radicals induced aggregation of the monomer and a new fluorescence appeared in the visible region (Ex 360 nm, Em 454 nm). The superoxide radical anion was found to be inert in both these respects, whilst peroxy radicals induced autofluorescence without concomitant aggregation. The results suggest that OH.and/or peroxy radical attack may be an in vivo mechanism for IgG denaturation. | |
| 3213273 | [Studies of the in vitro toxicity of D-penicillamine in the Chinese hamster ovary system]. | 1988 | The amino-thiol-containing compound D-penicillamine is used as a disease-modifying drug in the treatment of rheumatoid arthritis. In the present study the effects of D-penicillamine on Chinese hamster ovary cells (CHO) were evaluated. It could be shown that only high doses, i.e. doses exceeding the therapeutically occurring plasma concentration many times, were toxic to the cells, leading to an early death of the cells. High doses (1,500 micrograms/ml) of D-penicillamine caused an inhibition of the endogenous pyrimidine synthesis of the CHO and lead to a drastic reduction of the cellular protein biosynthesis. The observations made are discussed with respect to formerly published data about mutagenicity and carcinogenicity of D-penicillamine. | |
| 3598998 | An antigen in metaphase chromatin and the midbody of mammalian cells binds to scleroderma | 1987 Apr | Antibodies from 5 patients with systemic sclerosis reacted with an antigen localized to the metaphase chromatin, the cleavage furrow and the midbody of anaphase and telophase HEp-2 cells. The titer of antimidbody antibodies ranged from 1:160 to 1:1280. Four patients had systemic sclerosis and one had idiopathic Raynaud's phenomenon. In situ biochemical characterization of the antigen revealed that it was resistant to DNase I, micrococcal nuclease and RNase A, but was sensitive to trypsin treatment. The antigen remained insoluble in 400 mM acetic acid but was extracted from the cells with 400 mM hydrochloric acid. The antibody was not seen in sera from 2500 normal female blood donors, 120 patients with systemic lupus, 60 patients with rheumatoid arthritis, 15 patients with linear scleroderma or 25 patients with Raynaud's disease. | |
| 3033240 | Effect of low dose methotrexate on neutrophil chemotaxis induced by leukotriene B4 and com | 1987 Feb | When mediators of inflammation such as complement component C5a or leukotriene B4 are introduced into an air pouch created in mice, these mediators induce the migration of neutrophils into the air pouch. Pretreatment of mice with low doses of methotrexate inhibits leukotriene B4 or C5a induced neutrophil migration into the air pouch. Inhibition of neutrophil chemotaxis by methotrexate may, at least in part, account for the rapid onset of antiinflammatory activity that was observed in clinical trials with methotrexate in rheumatoid arthritis. | |
| 3093826 | Are some major in vivo effects of gold related to microenvironments of decreased selenium? | 1986 Aug | Gold interacts with selenium in vivo, and the normal distribution of selenium among tissues and subcellular compartments changes. Literature evidence shows that many of the effects of gold compounds on the polymorphonuclear neutrophil, macrophage, and lymphocyte cellular components of the immune system are similar to effects observed in these cellular components in selenium-deficient animals. Affected by these two metals are immune functions related to phagocytic cell migration, phagocytosis, microbial killing, lymphocyte mitogenesis/DNA synthesis, arachidonic acid metabolism/prostaglandin synthesis, and immunoglobulin production. The interaction of gold with selenium in vivo may be responsible for some of the multiparameter-based actions of gold compounds used in the treatment of inflammatory diseases such as rheumatoid arthritis. One mechanism by which gold exerts its clinical effects may be related to its interaction with selenium to produce, in specific microenvironments, decreased levels of this essential trace element. | |
| 2673426 | Extracorporeal immunoadsorption with IM-PH or IM-TR column. | 1989 | In order to selectively remove pathogenic macromolecular reactants, a biological affinity type adsorbent (a DNA colloidin charcoal column or protein A sepharose CL4B = Prosorba) has been developed and used for the treatment of immune disorders, alloimmunization and cancer. However, because physiologically active materials are required in this procedure, it is difficult to ensure an adequate supply of raw materials (and their handling, sterilization and preservation as an immunoadsorbent. To overcome the above-mentioned problems, we developed physicochemical type immunoadsorbents IM-TR and IM-PH, which consist of polyvinyl alcohol gel where tryptophan, in the former, and phenylalanine, in the latter, is used as a ligand. IM-PH has a better selectivity than IM-TR, however, IM-TR is a more efficient adsorbent of anti-acethylcholine receptor antibody than IM-PH. IM-PH plasma perfusion has been successfully used with patients with rheumatoid arthritis, systemic lupus erythematosus (SLE), and multiple sclerosis (MS). | |
| 2760173 | Presence of antibodies in the sera of patients with Graves' disease recognizing a 23 kilod | 1989 Sep | We examined whether antibodies (present in sera from patients with Graves' disease) might be directed against a connective tissue cellular component of the anatomical regions affected in the peripheral manifestations of that disease. Accordingly, we performed immunoblot analyses of cultured retroocular and pretibial fibroblasts. Retroocular connective tissue was obtained during orbital decompression surgery (n = 7) and at autopsy from normal individuals (n = 2). Pretibial skin biopsies were obtained from patients with pretibial dermopathy (n = 3) and at autopsy (n = 2). In addition, biopsies from other regions [extraocular muscle (n = 6), thyroid (n = 2), and abdominal skin (n = 3)] were also collected at surgery or autopsy. Serum samples were obtained from patients with severe Graves' ophthalmopathy (n = 31), hyperthyroid Graves' disease without overt ophthalmopathy (n = 13), nodular thyroid disease (n = 7), Hashimoto's thyroiditis (n = 7), rheumatoid arthritis (n = 5), and systemic lupus erythematosus (n = 3) and from normal individuals (n = 33). Electrophoresed fibroblast proteins were immunoblotted with 1:100 dilutions of sera using an antihuman immunoglobulin G-alkaline phosphatase conjugate. Antibodies against a 23kDa fibroblast protein were present in the sera from 24 of 44 (56%) of patients with Graves' disease with or without ophthalmopathy, 0 of 7 nodular thyroid disease, 0 of 7 Hashimoto's thyroiditis, 0 of 5 rheumatoid arthritis, 0 of 3 systemic lupus erythematosus, and 5 of 33 (15%) normal subjects. Significant differences in the observed frequency of antibodies existed between the Graves' disease group and the normal control group (P less than 0.01) or those patients with the other conditions (P less than 0.01). This 23kDa antigen was apparent in fibroblasts derived from individuals with Graves' disease as well as normal individuals and was present in fibroblasts from all anatomical sites studied. It was the sole protein uniquely recognized by sera from patients with Graves' disease. However, this serum reactivity did not appear to be related to the presence of clinically overt ophthalmopathy or pretibial dermopathy. Subcellular localization studies disclosed that the antigen was present in the supernatant but not the pellet resulting from a 100,000 x g centrifugation of whole cell sonicates. Antibodies against a 23kDa fibroblast protein are present in the majority of sera from patients with Graves' disease and rarely in sera from either normal individuals or those with other thyroid disorders or autoimmune diseases. Our results suggest the possibility that antibodies directed against this fibroblast antigen may be related to the developm | |
| 3049797 | T cell antigen receptors in autoimmunity. | 1988 Sep 15 | Three mAb to variable region determinants of the alpha/beta-chain TCR were used to detect discrete populations of peripheral blood T cells. T cells sharing a TCR determinant defined by such an antibody presumably use the same or similar TCR V or J genes for their alpha- or beta-chains. Thus analysis with these mAb provides a tool to investigate TCR gene usage and expression. Since autoantigen specific T cells may play an important role in initiating autoimmune diseases, TCR were analyzed in different autoimmune diseases and control groups including rheumatoid arthritis, Graves disease, idiopathic thrombocytopenic purpura, psoriasis, SLE, insulin-dependent diabetes mellitus, and in nonautoimmune control diseases and normals. Purified T cells were stained by indirect immunofluorescence with three mAb to TCR variable regions: mAb S511 stains 1.8 +/- 0.9% (mean +/- 2 SD), mAb C37 stains 3.4 +/- 1.5% and mAb OT145 stains from 0 to 6% of T cells from normal donors. Several individuals were identified with expanded subsets of positive T cells. One patient with adult ITP followed during a 12-mo period consistently had elevated percentages of T cells staining with the mAb OT145 (15.9 to 24.5%). These cells were found to be exclusively CD8+. By Southern blotting DNA prepared from these OT145+, CD8+ cells, but not DNA from the patient's OT145- T cells, revealed a clonal rearrangement using a beta-chain C region probe. Thus this patient had a monoclonal expansion of CD8+, OT145+ cells. Hyperexpression of a TCR variable region, as defined by the available mAb, could not be associated with any of the diseases studied. Examination of T cells at the site of autoimmunity, such as T cells from rheumatoid arthritis synovial fluid, revealed normal percentages of cells staining with these mAb. Immunoperoxidase staining of psoriatic lesional skin showed no striking enrichment of T cells bearing one or the other TCR type. | |
| 2226575 | Clinical implications of cartilage metabolism in arthritis. | 1990 | The ability of articular cartilage to withstand repeated mechanical loading with relatively little wear over a lifetime results from the properties of the extracellular matrix (ECM) and the optimal function of the chondrocytes which are responsible for the synthesis and presumably maintenance of this ECM. The properties of the ECM are accounted for by the relationship of the major aggregating, polyanionic, negatively charged proteoglycans with their potent viscoelastic properties to the network of collagens and several noncollagenous proteins. The major collagen (type II) interacts with type IX collagen in a highly specific manner. Type IX collagen has a chondroitin sulfate side chain and can also bind to the aggregating proteoglycans through a basic amino terminal domain. In inflammation, injury and probably repeated wear, function of the chondrocytes is disturbed, mediated by the action of potent cytokines, which results in release of degradative enzymes and alterations in the pattern of synthesis of the ECM. Identification of the critical cytokines and the sequence of events that result from their action should provide the basis for rational prophylaxis and therapy of disorders such as osteoarthritis and rheumatoid arthritis. Articular cartilage has unique mechanical properties which permit repeated mechanical loading with relatively little wear over a lifetime. These properties result from the special character of the extracellular matrix (ECM) and optimal functioning of the component cells (chondrocytes) which are responsible for the synthesis and presumably, maintenance of this matrix. Articular chondrocytes survive and perform these critical functions in an anaerobic environment remote from the vasculature and must derive their nutrition from the synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2080850 | Pharmacokinetics and dosage regimens of anti-inflammatory drugs. | 1990 | The term anti-inflammatory drug, in its broadest sense, encompasses a number of very diverse compounds, ranging from steroids to non-steroidal anti-inflammatory drugs (NSAIDs) and from disease modifying agents (used in the treatment of canine rheumatoid arthritis) to chondroprotective agents (used in the treatment of osteoarthrosis and traumatic arthritis in the horse). For many of these drugs (eg, chondroprotective and disease modifying agents) the mode of action is unknown and even with steroids and NSAIDs there is no universal agreement on mechanism of action. It is therefore in many cases impossible to link pharmacokinetic data to a drug's pharmacodynamics, for example to an effect on a specific biochemical marker. Some agents, including corticosteroids, may have indirect modes of action, so that the pharmacodynamic half-life can be much longer than (and not clearly related to) the pharmacokinetic half-life. In other cases, clinical benefits may only become apparent after several weeks or even months. It can therefore be difficult or impossible to use classical pharmacokinetic approaches to set dosing intervals and dose rates for clinical use. To some extent, the position is more straightforward with NSAIDs. However, even with these drugs simple approaches are not possible and this paper will review briefly some of the studies undertaken in our laboratory which have attempted to utilize NSAID kinetics to set dosage schedules for clinical use. | |
| 1930317 | Effect of an extract of the Chinese herbal remedy Tripterygium wilfordii Hook F on human i | 1991 Oct | Tripterygium wilfordii Hook F (TWH) is a vine-like plant that grows in a wide area of south China. An alcohol extract of this plant known as T2 has been suggested to be effective in the treatment of rheumatoid arthritis (RA). To examine the mechanism by which this herbal remedy might be effective in RA, the capacity of T2 to alter human immune responsiveness in vitro was investigated. Human peripheral blood mononuclear cells were obtained from normal adults and separated into purified populations of monocytes, T cells, and B cells. T2 at 0.1-1 micrograms/ml inhibited antigen- and mitogen-stimulated proliferation of T cells and B cells, interleukin-2 (IL-2) production by T cells, and immunoglobulin production by B cells. T2 did not affect IL-2 receptor expression by T cells, IL-1 production by monocytes, or the capacity of monocytes to present antigen. Inhibition could not be accounted for by nonspecific toxicity. These results support the conclusion that T2 exerts a powerful suppressive effect on human immune responses. This action might account for its therapeutic effectiveness in RA. | |
| 1751309 | Murine models for systemic lupus erythematosus and Sjögren's syndrome. | 1991 Oct | Of the types of defects that have been observed in autoimmune mice, two are common to most strains and appear to be of critical importance in the development of autoimmune disease. The first of these is a deficiency in the maintenance of self-tolerance by B or T lymphocytes. This is an intrinsic defect due to genetic abnormalities that presumably affect an early developmental signaling mechanism. The disruption of early B- and T-cell development leads to the appearance of lymphocytes that are predisposed to loss of tolerance. In certain strains of autoimmune mice, it also leads to overproduction of Ly1+ (CD5+) B cells or CD4-CD8-B220+ T cells, which apparently do not contribute to autoimmunity. The second type of defect is a strain-specific, antigen-driven autoimmune disease syndrome. This defect is limited by the affinities of the available T-cell receptor and immunoglobulin variable regions and the efficiency of antigen presentation. Current evidence suggests that the major histocompatibility complex molecules play the most important role in determining which autoantigens lead to a pathogenic antigen-driven immune response. For example, the type and magnitude of the autoimmune response may be directed by the production of specific cytokines. The type of antigen and the context of its presentation can bias the production of cytokines that favor the production of the Th2 subset of CD4+ T helper cells. These cells secrete predominantly interleukin-4, interleukin-5, and interleukin-10, and may contribute to a chronic response and autoimmune disease. | |
| 2165882 | Fibroblast markers in labial salivary gland biopsies in progressive systemic sclerosis. | 1990 May | Labial salivary gland (LSG) biopsies from 13 patients were studied. Three were normal glands, five showed fibrosis induced by progressive systemic sclerosis (PSS) and five more had PSS-induced fibrosis combined with and focal sialadenitis compatible with Sjögren's syndrome (SS). Monoclonal antibodies to proline-4-hydroxylase (alpha PH or 5B5-A) and the carboxyterminal domain of human type I procollagen (alpha pC or M-38) were used as fibroblast markers. Immunostaining was done with avidin-biotin-peroxidase complex (ABC). Using various sample controls (including cultured fibroblasts and specimens enriched for lymphocytes, plasma cells, granulocytes, monocytes and dendritic cells) as well as analysis of various LSG resident cells, the specificity of the alpha PH and alpha pC markers for fibroblasts was established. Cross reactions were only seen with plasma cells and acinar cells containing the beta subunit of PH or disulfide isomerase involved in SS-SH interchange reactions in these secretory cells. All fibroblasts in fibroblast monolayer cultures at their logarithmic phase of growth stained with the fibroblast markers studied, but false negative staining was seen with resting, mature fibroblasts in dense connective tissue in LSG sections. Therefore, it can be concluded that proline 4-hydroxylase and the COOH-terminal domain of type-I procollagen both indicate fibroblast involvement in collagen (type l) synthesis and thus identify active but not resting fibroblasts. PH+ fibroblast-like cells and pC+ fibroblasts were both more frequent in PSS LSGs than in normal glands, suggesting active local fibroblast involvement in PSS.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2033260 | Human extracellular recombinant phospholipase A2 induces an inflammatory response in rabbi | 1991 Jun 1 | Phospholipase A2 (PLA2) enzymes hydrolyze membrane phospholipids liberating fatty acid and lysophospholipid. This event is thought to be the rate-limiting step in the generation of the lipid proinflammatory mediators, the eicosanoids and possibly platelet-activating factor. For this reason, extracellular forms of PLA2 have been postulated to be a component of the inflammatory cascade in certain biologic settings. In the synovial fluid of patients with inflammatory arthritides, substantial amounts of PLA2 activity have been found, and subsequently, one enzyme was purified, cloned, and expressed. Here we show that the pure recombinant enzyme free of any proinflammatory contaminants elicits a dramatic inflammatory, arthritogenic response when injected into the joint space of healthy rabbits. Within 24 h, extensive leukocyte infiltration and hyperplasia of the synovial lining cells were observed, and prostaglandin production in the joint space increased. In comparison, pancreatic PLA2(2) had little activity in this system, whereas a very inflammatory cobra venom enzyme was intermediate in its effects. In view of the presence of the enzyme in inflamed joints, the fact that its synthesis and secretion can be induced by proinflammatory cytokines and its proinflammatory biologic activity, we suggest that synovial PLA2 plays an exacerbating role in acute episodes in chronic inflammatory conditions such as rheumatoid arthritis. | |
| 2506879 | A high incidence of rheumatoid factor idiotypes in monoclonal proteins in the serum and in | 1989 Aug | Patients with Sjögren's syndrome (SS) develop lymphoproliferative disorders such as monoclonal gammopathies and non-Hodgkin's lymphomas. Cross-reactive idiotypes (CRI) were studied in 22 serum monoclonal immunoglobulins (Igs) and in cytoplasmic Ig in four B-cell lymphoma cells in patients with SS. This was done by utilizing monoclonal anti-idiotypic antibodies which were produced against monoclonal rheumatoid factors (RF) derived from three patients with SS and one patient with Waldenström's macroglobulinemia. By the Western blotting or dot immunobinding technique, CRI was detected not only in monoclonal RFs but in monoclonal Igs which had different heavy- or light-chains from the original monoclonal RF used for immunization. A higher incidence of CRI was found in 22 monoclonal Igs associated with SS than in 27 monoclonal Igs in patients with Waldenström's macroglobulinemia, multiple myeloma or malignant lymphoma. In four patients with malignant lymphoma associated with SS, three showed one or three CRI in the lymphoma cells, whereas only two out of 20 patients with other malignant lymphoma showed CRI, demonstrating a significant difference between two groups. These data indicate that monoclonal proliferation of B-cell lineage in patients with SS, benign or malignant, takes place more often among RF-producing clones than other B-cell disorders. | |
| 1365482 | A rheumatologist's viewpoint. | 1991 | Attitudes to prescribing anti-inflammatory drugs have changed considerably over the last 25 years and there is now a recognition of the need to balance effectiveness with reduced risks of serious adverse reactions. Such serious side-effects often involve the upper gastrointestinal tract, and there are differences between anti-inflammatory drugs in the frequency with which they cause significant problems at this site. Anti-inflammatory drugs with a lesser propensity to cause gastrointestinal reactions may have an advantage. Several risk factors may be important for upper gastrointestinal side-effects including sex, age, history of dyspepsia, other diseases and the type of arthritis. Results from post-marketing surveillance studies of nabumetone in the United Kingdom and the Federal Republic of Germany showed that although patients with a previous history of dyspepsia were more likely to stop the drug due to an adverse reaction, the majority continued without any problem. Interestingly, patients with rheumatoid arthritis were more likely to stop therapy due to side-effects, though it was not clear if this was due to their disease or to multi-morbidity. Strategies are needed when prescribing anti-inflammatory drugs which take into account the type of patient, their disease, and the best drug. In many instances this could be nabumetone. |