Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2112209 | [Inflammatory reaction and laboratory tests: serum amyloid A (SAA) protein]. | 1990 Mar | Serum amyloid A protein (SAA) is a sensitive acute phase reactant. Here, the assay of SAA in serum and its clinical significance are reviewed. SAA was measured simply by radial immunodiffusion and enzyme immunoassay with rabbit anti-amyloid A antibodies, however further investigation is necessary because SAA is an insoluble apolipoprotein. The concentration of SAA was 1.5-3.0 folds higher at physiological states, and 3.0-10.0 folds higher at inflammatory states than that of C-reactive protein (CRP). Therefore, SAA might be a sensitive and useful method for full observation of diseases. At the acute phase such as myocardial infarction, SAA changed at the same time as CRP. Most inflammatory disorders, for example, rheumatoid arthritis and malignant tumors which show elevation of CRP, showed elevation of SAA. These two proteins were strongly correlated, but showed no disease specificity. Also at secondary amyloidosis which was caused by deposition of SAA fragments, the level of SAA did not indicate the presence of amyloid. Only at the time of kidney allograft rejection for a recipient, was SAA elevated markedly in comparison with CRP. Recently, we developed a method of quantitative analysis of SAA isotypes and applied it in a few cases. Although significant features for diseases have not been obtained yet, such analysis might become useful for the physiological and pathological understanding of SAA. | |
| 2601077 | [Fundamental examination and the reference values of anticardiolipin antibodies]. | 1989 Oct | We studied sera from 146 healthy individuals in a fundamental examination to obtain reference values for anticardiolipin antibodies by the enzyme-linked immunosorbent assay (ELISA). The good results were obtained in the evaluation of concentrations of pretreatment substances, cardiolipin antigen and serum samples, as well as in reproducibility and stability on the storage of the samples. However, there was interference by triglycerides, hemoglobin and birilubin. The O.D. values and positive values of IgG, IgA and IgM in healthy individuals were 0.105, 0.111, 0.173 and 4.1%, 2.7%, 2.7% respectively. Furthermore, the incidences of anticardiolipin antibodies in systemic lupus erythematosus, mixed connective tissue disease, progressive systemic sclerosis, Sjogren's syndrome, polymyositis/dermatomyositis, rheumatoid arthritis, unclassified connective tissue disease, polyartertis nodosa and idiopathic thrombocytopenic purpura were 48.0%, 40.0%, 50.0%, 21.4%, 26.3%, 29.4%, 40.0% and 25.0% respectively. Especially, the incidence of IgG antibody against cardiolipin was high. Detection of phospholipid cardiolipin antibodies using ELISA was considered to be a useful for clinical diagnosis and monitoring of patients with systemic lupus erythematosus and associated autoimmune disorders. | |
| 2484582 | Metallothionein induction by nonsteroidal antiinflammatory drugs. | 1989 Jul | In the present study we report on the effects of commonly used nonsteroidal antiinflammatory drugs on metallothionein (MT) and MT-I mRNA levels. A single dose of chloroquine (100 mg/kg), diclofenac (100 mg/kg), indomethacin (10 mg/kg), or piroxicam (100 mg/kg) was administered ip to C57B1 mice. After 18 h, MT levels were determined with a Cd-saturation radioassay. MT-I mRNA levels were measured by Northern Blot analyses using a probe containing the mouse MT-I gene. All drugs tested caused an increase in the MT content of the liver but not of the kidneys and lung. The lowest and highest effects were observed with chloroquine (8 times the control value) and diclofenac (18 times), respectively. In accordance with the stimulation of MT synthesis, increased accumulation of hepatic MT-I mRNA could be demonstrated. These results indicate that elevated MT levels may contribute to the effectiveness of nonsteroidal antiinflammatory drugs in the treatment of rheumatoid arthritis (RA). | |
| 2764472 | Theophylline assay on Kodak Ektachem DTSC--performance and interference by structurally-re | 1989 May | Theophylline was measured with a Kodak Ektachem DTSC using its property of uncompetitive inhibition of alkaline phosphatase. Within- and between-batch reproducibility was satisfactory. Agreement with consensus mean values on quality assessment samples was good as was agreement on patients' samples with a high performance liquid chromatography reference method and an automated fluorescence polarisation immunoassay. At therapeutic theophylline concentrations, no interference was seen with caffeine, theobromine, 1,7-dimethylxanthine, 1,3-dimethyluric acid or 3-propylxanthine. 3-methylxanthine (a theophylline metabolite) gave a positive bias but the concentrations of this metabolite found in serum are such that the clinical significance of this finding is questionable. Salicylate at concentrations which might be found during therapy for paediatric rheumatoid arthritis also gave a positive bias. | |
| 3327885 | Immunosuppressant therapy of inflammatory bowel disease. Pharmacologic and clinical aspect | 1987 Dec | The history of immunosuppressant drug use, both azathioprine (Aza) and 6-mercaptopurine (6-MP), in inflammatory bowel disease (IBD) over the past 20 years is briefly reviewed. The two drugs appear identical in their pharmacologic and biologic effects. Azathioprine is converted to 6-MP while in the body. Conflicting reports on the effectiveness of Aza have been published. The major National Cooperative Crohn's Disease Study (NCCDS) has found no advantage in Aza over placebo. In contrast, 6-MP was found to be effective in a large randomized trial. The shortcomings of the NCCDS reports are discussed with possible explanations for their negative findings. Our own studies, dating from 1968, are reviewed with 38 patients having been treated for up to 18 years, always in combination with small doses of steroids. Our results with Aza are similar to those of Present and Korelitz with 6-MP; about 70% of previously intractable patients improved substantially. Both Aza and 6-MP bring about healing and closure of most fistulas. Side effects can be serious but are usually manageable and, to some extent, preventable by appropriate dosage schedules. Since Aza has been approved for another benign, presumably autoimmune disease--rheumatoid arthritis--and because of its extensive use in other autoimmune diseases, we prefer to use Aza in selected patients with Crohn's disease who have failed to respond to more conventional modes of therapy. The use of immunosuppressants in ulcerative colitis is less clearly indicated. | |
| 3118442 | Vascular damage and factor-VIII-related antigen in the rheumatic diseases. | 1987 | Factor-VIII-Related antigen (VIII R:Ag) is known to be produced by the blood vessel wall. Noxious stimuli increase endothelial release of VIII R:Ag. It might be expected that the development of vasculitis would be associated with increased levels of VIII R:Ag. To investigate this, eight different groups of subjects were studied: 25 patients with systemic sclerosis, 19 with systemic lupus erythematosus, 15 with rheumatoid arthritis (RA) plus vasculitis, 19 with systemic vasculitis and 14 with atherosclerosis. These groups were compared to 29 patients with primary Raynaud's disease, 15 with RA without vasculitis and 50 controls. Results showed that where there was evidence of vascular disease, then VIII R:Ag was elevated. VIII R:Ag appeared to be a more specific marker for vascular damage than erythrocyte sedimentation rate or C-reactive protein. Longitudinal studies in 11 patients showed good correlation between progression of vascular disease and VIII R:Ag. | |
| 1772292 | Ankylosing spondylitis: an autoimmune disease? | 1991 Nov | Identification of several autoantibodies in serum samples from patients with ankylosing spondylitis or suspected ankylosing spondylitis is reported. Five antibodies associated with ankylosing spondylitis were identified by applying cytoimmunofluorescence and immunoblotting techniques to antigen pools from insect tissue. At least one of these antibodies was found in 82% of serum samples from patients with ankylosing spondylitis. A 36 kD drosophila antigen, which showed the most common and most dominant reaction, was further purified and isolated. Thirty two (34%) of the serum samples from 95 patients with definite ankylosing spondylitis and 12 (28%) of the serum samples from 43 patients with suspected ankylosing spondylitis reacted with this antigen. Antibodies purified from the 36 kD antigen reacted specifically with a 69 kD antigen present in separations of total protein preparations from human lymphocytes and HeLa cells. The 36 kD antibody was not found in 29 patients with rheumatoid arthritis nor in 38 apparently healthy controls. The prevalence of the 36 kD antibody was comparable in HLA-B27 positive and negative patients. In addition, the same immunoreaction was found in patients with so called 'seronegative' spondylarthropathies, particularly of the ankylosing spondylitis-type, suggesting that this antibody is specific for ankylosing spondylitis or other 'seronegative' spondylarthropathies with the typical clinical and radiological changes of ankylosing spondylitis. | |
| 1896520 | Analgesic, antipyretic and anti-inflammatory properties of Euphorbia hirta. | 1991 Jun | Lyophilised aqueous extract of Euphorbia hirta L. (Euphorbiaceae) has been evaluated for analgesic, antipyretic and anti-inflammatory properties in mice and rats, in order to complete its activity profile, after the confirmation of the existence of a central depressant activity particularly expressed by a strong sedative effect, associated with anxiolytic effects. This study leads us to the conclusion that this plant extract exerts central analgesic properties. Such a dose-dependent action was obtained against chemical (writhing test) and thermic (hot plate test) stimuli, respectively, from the doses of 20 and 25 mg/kg and it was inhibited by a naloxone pretreatment, a specific morphinic antagonist compound. An antipyretic activity was obtained at the sedative doses of 100 and 400 mg/kg, on the yeast-induced hyperthermia. Finally, significant and dose-dependent anti-inflammatory effects were observed on an acute inflammatory process (carrageenan-induced edema test in rats) from the dose of 100 mg/kg. On the other hand, plant extract remained inactive on chronic processes such as Freund's adjuvant-induced rheumatoid arthritis, after a chronic treatment during fourteen days at the daily dose of 200 or 400 mg/kg; however, if inefficacy was observed on rat backpaws edema and on loss of weight, the aqueous extract reduced the inflammatory hyperalgia. | |
| 1658616 | [Anti-idiotypic and natural catalytically active antibodies]. | 1991 May | The principal existence of natural catalytic antibodies in the autoimmune sera is discussed. In the course of the autoimmune process, the induction of antiidiotypic antibodies against topoisomerase I has been shown in the sera of patients with scleroderma, systemic lupus erythematosus, and rheumatoid arthritis. The above antibodies were obtained in preparative amounts. Proceeding from the concept of the idiotypic network, the antibodies were suggested to be natural enzymes and their properties were studied. They appeared to be anti-DNA antibodies, competing with the native topoisomerase I for binding to anti-topoisomerase monoclonal antibodies and possessing highly specific DNA-binding activity (Kd is about 0.1 nM). The antiidiotypic antibodies specifically inhibit the topoisomerase-catalysed relaxation reaction and affect the formation of covalent DNA-protein complex. Possible involvement of antiidiotypic antibodies against topoisomerase in the catalysis of reactions of DNA transformation is analysed. Catalytic antibodies that are natural enzymes possessing DNA-nicking activity have been isolated from the blood sera of patients with different autoimmune pathologies. | |
| 1649289 | Enhanced repair and regeneration of periodontal lesions in tetracycline-treated patients. | 1991 May | A group of cases is presented in which dramatic repair and regeneration of periodontal tissues lost as a result of periodontitis have occurred following systemic administration of tetracycline either alone or in combination with other forms of periodontal therapy. The nature and extent of regeneration demonstrated in these patients appears to be more dramatic than what has been shown previously when more conventional forms of periodontal therapy were utilized, even including bone grafting and guided tissue regeneration. The type of repair described has been shown in many instances to be long standing and is probably not totally related to the antibacterial characteristics of tetracycline. It is suggested that the ability of this drug to inhibit collagenolytic enzymes (collagenases) may have influenced the favorable clinical results achieved. The anti-collagenolytic properties of tetracycline are being considered with increasing frequency in the treatment of other systemic diseases characterized by collagen breakdown such as corneal ulcers, rheumatoid arthritis, diabetes, and dystrophic epidermolysis bullosa. Given the highly collagenous nature of the tissues of the periodontium, this report suggests that tetracycline could be of considerable value in the treatment of some types of periodontitis. | |
| 1899015 | T-gamma-lymphoproliferative disorder arising in a background of autoimmune disease and ter | 1991 Jan | T-gamma-lymphoproliferative disorder, a syndrome of T-cell lymphocytosis with neutropenia has been described in patients with various autoimmune disorders, especially rheumatoid arthritis. We report a case of T-gamma-lymphoproliferative disorder occurring in a 42-year-old white woman with a long history of dermatitis herpetiformis and subsequent development of Coomb's positive autoimmune hemolytic anemia and polymyositis. The peripheral blood lymphocytes showed the T-suppressor cell phenotype (CD2-, CD3-, CD8-, and CD4-). DNA analysis of the peripheral blood lymphocytes revealed a T-cell receptor beta-chain gene rearrangement and an immunoglobulin heavy-chain gene rearrangement. The patient's course was marked by numerous bouts of infection. The unique factor in this patient was the development of a plasma cell dyscrasia and amyloidosis prior to death. | |
| 2215698 | X-ray structure of phospholipase A2 complexed with a substrate-derived inhibitor. | 1990 Oct 18 | Phospholipases A2 play a part in a number of physiologically important cellular processes such as inflammation, blood platelet aggregation and acute hypersensitivity. These processes are all initiated by the release of arachidonic acid from cell membranes which is catalysed by intracellular phospholipases A2 and followed by conversion of arachidonic acid to prostaglandins, leukotrienes or thromboxanes. An imbalance in the production of these compounds can lead to chronic inflammatory diseases such as rheumatoid arthritis and asthma. Inhibitors of phospholipase A2 might therefore act to reduce the effects of inflammation, so structural information about the binding of phospholipase A2 to its substrates could be helpful in the design of therapeutic drugs. The three-dimensional structure is not known for any intracellular phospholipase A2, but these enzymes share significant sequence homology with secreted phospholipases, for which some of the structures have been determined. Here we report the structure of a complex between an extracellular phospholipase A2 and a competitively inhibiting substrate analogue, which reveals considerable detail about the interaction and suggests a mechanism for catalysis by this enzyme. | |
| 18415250 | [The therapy of pain in rheumatic joint-and spine diseases.]. | 1990 Sep | The therapy of pain caused by rheumatic diseases above all must take into consideration the cause of the pain. In rheumatoid arthritis, especially in the early stages, inflammation is the primary cause of the pain. The pain decreases the inflammation subsides following the administration of non-steroidal anti-inflammatory drugs (NSAIDs), or corticosteroids, if necessary. The so-called disease modifying anti-rheumatic drugs do not influence the inflammation or consequently, the pain directly, but rather through mechanisms before the local joint process some of which are not exactly known. In later stages of the progressive joint degeneration the NSAIDs only have a limited effect regarding the inhibition of inflammation. In osteoarthrosis, in which the pain is caused by a secondary inflammation and increasingly by capsular, muscular and tendon involvement, the pain is only treated by NSAIDs in active inflammatory stages; otherwise, the treatment is physical activity and medication. In degenerative and static disorders of the spine the pain is caused predominantly by muscular bracing. Therefore, physical and especially gymnastic therapy play a major role. Whether muscle relaxants have an effect on muscle bracing is doubtful. If there is pressure on the ligaments and, in cases of vertebral dislocation with overstraining of the vertebral joints, therapy with local injections is indicated. The pain in osteoporosis is also predominantly muscular and must be treated accordingly. Above all, high doses of calcium and calcitonin are effective analgesics. Moreover, fluoride also acts as an analgesic once the osteoporosis has stabilized. In most cases fibromyalgia, which is mostly of a psychosomatic nature, cannot be influenced by medical therapy. Instead repeated attempts at treatment help to make the affliction chronic with neurotic fixation. Also, as a rule, myotonolytic and tranquilizing substances are not effective. | |
| 2117509 | Autoantibodies to mitochondrial and centromere antigens in primary biliary cirrhosis and s | 1990 Aug | High levels of IgG antibodies to the multi-enzyme complex bovine pyruvate dehydrogenase (PDHC) were detected by a sensitive ELISA in all patients with histologically proven primary biliary cirrhosis (PBC), in a minority of patients with systemic sclerosis without overt PBC or with chronic liver diseases of another cause and in no rheumatoid arthritis or normal controls. Most (15/21) but not all of these positive patients recognized a 70-kD (E2) component of PDHC on immunoblotting. Additional recognition of a centromere-associated 140-kD polypeptide was associated with the presence of scleroderma-like features (Raynaud's phenomenon and sclerodactyly) in PBC, further emphasizing the serological and clinical overlap between these two conditions. | |
| 2669369 | Recombinant human erythropoietin. | 1989 Jul | Erythropoietin is produced mainly by the kidneys and stimulates erythropoiesis in the bone marrow. Chronic renal failure is characterized by anemia, which is principally caused by erythropoietin deficiency. Recombinant human erythropoietin (r-hEPO) corrects the anemia of chronic renal disease and improves patient well-being, exercise tolerance, and cognitive function. The clinical pharmacology, efficacy, safety, and tolerance of r-hEPO are presented. Four major studies attest to r-hEPO's efficacy in the treatment of anemia of chronic renal disease and document potential toxicities of hypertension, iron deficiency, thrombosis, and bone pain. Careful attention to the extent of correction of the hematocrit, increased heparinization during hemodialysis therapy, and compliance with dietary restrictions may minimize the incidence and severity of adverse reactions. Resistance to r-hEPO may be due to iron deficiency, aluminum toxicity, or inflammation, including infection. Potential future uses of r-hEPO include the treatment of various other anemias, such as those seen in sickle cell anemia, rheumatoid arthritis, and autologous blood donation. Controlled clinical studies in these areas have not been reported. | |
| 2511359 | [A fatal case of pemphigus vulgaris with interstitial pneumonia occurring during gold ther | 1989 May | We report a case of a 52-year-old female with therapy-resistant pemphigus vulgaris. She was treated with prednisone, azathioprine and gold sodium thiomalate. After administration of a total dose of 110 mg gold sodium thiomalate, she suddenly developed pityriasis rose-like drug eruptions and interstitial pneumonia and died despite intensive care including pulse therapy. In Japan, there have been 8 reported cases of pemphigus or bullous pemphigoid that developed interstitial pneumonia during gold therapy. In these 7 cases, interstitial pneumonia occurred after administration of 110 to 430 mg gold sodium thiomalate, and 4 cases died. This rate of death is higher than those with other diseases: i.e., 9 dead cases among 99 cases of interstitial pneumonia developing in patients with rheumatoid arthritis or asthma under treatment with gold sodium thiomalate. We think that it is necessary to reevaluate the combined treatment of sodium thiomalate and other immunosuppressive drugs such as azathioprine in pemphigus, because we also found 2 other fatal cases among the 4 reported ones with interstitial pneumonia. | |
| 2746564 | Evidence of a new antigen-antibody system (anti-Mic-1) in patients with systemic lupus ery | 1989 Feb | Autoimmune thyroid diseases may occur in association with systemic rheumatic disorders, and usually they show a high prevalence of antithyroglobulin and antimicrosomal antibodies. We report 6 patients with the clinical association of systemic lupus erythematosus (SLE) and hyperthyroidism. Of interest, in 5 of the 6 patients (83%), we found an antibody directed against a microsomal extract of human thyroid gland which was different than previous microsomal antibodies in that it was a precipitating antibody; we have called it anti-Mic-1 antibody. We investigated the prevalence of this specific autoimmune reaction in 58 patients with idiopathic SLE, 30 with hyperthyroidism, 15 with Hashimoto's thyroiditis, 25 with insulin dependent diabetes mellitus, 45 with rheumatoid arthritis, and 25 healthy controls. No control had anti-Mic-1 antibody. In addition, this antibody was shown to be organ specific. We suggest that patients with the combined association of SLE and hyperthyroidism may represent a different subset in the spectrum of SLE. The high prevalence of this antigen-antibody reaction in these cases may serve as a serological marker of this association. | |
| 3150970 | Stimulatory effects of anti-rheumatic drugs on human neutrophil functions. | 1988 Nov | Auranofin (AF), D-penicillamine (D-pen) and thiola are prescribed as disease-modifying drugs in the treatment of rheumatoid arthritis (RA). We have shown here that auranofin, 10(-8) to 10(-6) M, D-penicillamine, 10(-6) to 10(-3) M, thiola, 10(-7) to 10(-3) M, and the tripeptide thiol, glutathione, 10(-6) to 10(-3) M, enhanced f-met-leu-phe-induced lysosomal enzyme release and the phagocytic uptake of bacteria by up to 40%. The previously reported inhibitory effects of AF were only observed at concentrations in excess of those likely to be available to effector cells in vivo. The stimulatory effects of thiola and D-pen occurred at concentrations likely to be available to effector cells in vivo and, therefore, may be of greater clinical relevance. There is evidence that the drugs used in this study exert their effects via a thiol moiety and their therapeutic effect is preceded by an elevation of intracellular thiol levels. | |
| 3262853 | Office management of rheumatic disease. Pharmacology and laboratory evaluation. | 1988 Oct | Nonsteroidal anti-inflammatory drugs are the primary therapy in most of the rheumatic diseases. After an adequate trial of NSAIDs in a patient with rheumatoid arthritis, the physician would usually add either a slow-acting remittive drug or an antimalarial. If the response to these drugs is unsatisfactory, or they have lost their effectiveness, then a cytotoxic drug would be considered for RA. With major organ involvement in systemic lupus erythematosus or with vasculitis (polymyalgia rheumatica/temporal arteritis and polyarteritis nodosa), corticosteroids would play an important role. Cytotoxic drugs are being used with increased frequency in conditions that may be refractory to steroids, such as polyarteritis or Wegener's granulomatosis, and when the side effects of high dose steroids are becoming intolerable. Whichever drug is chosen, careful instruction to the patient and follow-up of that patient for side effects are essential. | |
| 3632003 | Membrane attack complex of complement in leukocytoclastic vasculitis of the skin. Presence | 1987 Sep | The presence of the membrane attack complex of complement (MAC) was studied by a two-step immunofluorescence method in 15 patients with leukocytoclastic vasculitis of the skin, using an antibody against MAC neoantigen. Perivascular deposits of MAC were present in 13 specimens of lesional skin and only two specimens of clinically uninvolved skin, suggesting a possible pathogenetic role for MAC in the development of a skin lesion. Control studies were performed on the clinically normal skin of 15 individuals (11 patients with various nonbullous skin diseases and four healthy volunteers) and on skin lesions of seven patients with inflammatory skin diseases. In the clinically normal skin of only one patient, perivascular deposits of MAC were detected. This patient had rheumatoid arthritis and a cutaneous eruption due to the administration of aurothioglucose. We conclude that the activation of the terminal components of the complement system may play an important role in the formation of lesions in leukocytoclastic vasculitis of the skin, but is not an indispensable condition. |