Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 677268 | Anchoring fibrils. A new connective tissue structure in fibrotic lung disease. | 1978 Aug | Electron microscopic studies of lung were made and compared in 17 patients with lung disease (10 with idiopathic pulmonary fibrosis, 3 with collagen--vascular diseases, 3 with sarcoidosis, and 1 with chronic eosinophilic pneumonia) and in 5 control patients. In control patients, the alveolar epithelial cells were normal, and no hemidesmosomes were present between the plasma membranes and the basal laminae. In comparison, cuboidal alveolar epithelial cells were present in 15 of the patients with fibrotic lung disease; in 9 of these the alveolar epithelial cells were multilayered. In 7 of the latter 9 patients (5 with idiopathic pulmonary fibrosis and 2 with collagen-vascular diseases), the basal laminae of the alveolar epithelial cells were attached to the plasma membranes by hemidesmosomes and to the underlying interstitial connective tissue by "anchoring fibrils." These fibrils measured from 4000 to 6000 A in length and from 200 to 600 A in width. One or both ends of the anchoring fibrils inserted into thebasal lamina, often forming arcs through which collagen fibrils and connective tissue microfibrils penetrated. Anchoring fibrils showed a complex pattern of transverse banding, which differed from that of collagen and appeared to be symmetric about the center of the fibril. These anchoring fibrils, which resemble those in normal skin and other tissues, were not found in lungs of control patients. In addition, there was a significant correlation between the severity of the pulmonary fibrosis and the presence of anchoring fibrils. These observations suggest that in severe fibrotic lung disease, anchoring fibrils reinforce the attachment of the basal lamina of multilayered alveolar epithelial cells to interstitial connective tissue. | |
| 1179858 | [Changes of various organs in joint diseases]. | 1975 Jul | In a review of organic changes of rheumatic diseases the more important changes of skeletal musculature, gastro-intestinal apparatus, kidneys, blood vessels and eyes are discussed. The paper is based upon investigations, publications and post-graduate activities of the Rheumatism Research Institute of Prague. | |
| 2579756 | Anti-phospholipid antibodies in syphilis and a thrombotic subset of SLE: distinct profiles | 1985 Feb | In a study of connective tissue and infectious disease sera, we have demonstrated IgM and IgG anti-cardiolipin activity, in a solid phase radioimmunoassay, in systemic lupus erythematosus (SLE), rheumatoid arthritis, syphilis and in acute malaria caused by four different species of Plasmodium. The highest values were noted in SLE (IgM anti-cardiolipin P less than 0.005, IgG anti-cardiolipin P less than 0.01), but there was no correlation with anti-dsDNA, rheumatoid factor or VDRL titres in any disease group. Anti-cardiolipin binding was significantly associated with the lupus anticoagulant, thrombocytopenia, spontaneous abortions and thromboses in the SLE patients. Ten SLE sera from this thrombotic subset and 10 syphilitic sera with similar anti-cardiolipin activity, were tested against four phospholipid antigens and showed significantly different anti-phosphatidyl ethanolamine/anti-phosphatidyl serine binding ratios (P less than 0.001). These differences in phospholipid epitope specificity could explain the specificity of the VDRL antigen in syphilis serology, and we discuss a putative role for anti-phosphatidyl serine in the thrombotic diathesis of SLE. | |
| 3927297 | Arthritis induced by a T-lymphocyte clone that responds to Mycobacterium tuberculosis and | 1985 Aug | Adjuvant arthritis characterized by chronic inflammation of the joints of rats is induced by immunization to Mycobacterium tuberculosis. To learn how autoimmune arthritis may be caused by a microbial antigen, we isolated a T-lymphocyte clone specific for M. tuberculosis antigens that was strongly arthritogenic. We now report that the clone recognized, in addition to M. tuberculosis antigens, antigens present in human synovial fluid, medium of chondrocyte cultures, and proteoglycans purified from cartilage. These observations indicate that the target antigen for the arthritogenic clone resides in the proteoglycan component of cartilage. As this arthritogenic clone shows specificity for both a M. tuberculosis antigen and a cartilage constituent we conclude that disease is probably caused by antigenic cross-reactivity. Thus, an autoimmune disease may be triggered by structural mimicry between antigens in the environment and self-antigens in the individual. | |
| 337458 | [Associated and secondary chondrocalcinosis]. | 1977 Oct | The authors consider the problems posed by secondary and associated chondrocalcinosis (CCA) on the basis of a study carried out at many French Rheumatology centres (Centres de Rhumatologie Française) and in the light of data in the literature. CCA is associated with gout in 4 percent of cases, with hyperparathyroidism in 3.9 percent of cases, with haemochromatosis in 1.7 percent of cases and with hypothyroidism in 0.8 percent of cases. The existence of secondary CCA in gout, hyperparathyroidism, haemochromatosis, Wilson's disease, ochronosis, hypophosphatasia and perhaps hypothyroidism seems proven. These secondary cases of CCA represent 10.7 percent of the total 1226 : here CCA seems to form one element of a much broader syndrome, namely the metabolic arthropathies. The other associations, with the exception of those which are not considered in this paper (rheumatoid polyarthritis, diabetes mellitus, Paget's disease, osteochrondromatosis, acromegalia), are probably coincidental. | |
| 4352576 | Measurement of inorganic pyrophosphate in biological fluids. Elevated levels in some patie | 1973 Aug | A rapid and relatively simple method for measurement of inorganic pyrophosphate (PPi) in biological samples has been described. The mean +/-SEM of plasma samples from 94 normal subjects was 1.8+/-0.06 muM, giving a normal range (99% confidence limits) of 0.16 - 3.40 mumol/liter. Analysis of 17 plasma samples in duplicate showed a standard deviation of 0.18, giving a 99% probability that a single determination of plasma PPi would be +/-0.68 muM of the true value. The mean PPi levels in plasma from subjects with osteoarthritis, pseudogout, acromegaly, and uremia were significantly greater than the normal mean (P < 0.01). Samples from rheumatoid arthritis showed PPi levels distributed about a mean identical to the normal mean. Plasma inorganic orthophosphate levels correlated positively with PPi levels in samples from normal subjects and in samples from patients with osteoarthritis, pseudogout, and uremia, but not with acromegaly. This correlation was statistically significant only in the normal samples and in those from patients with osteoarthritis. | |
| 781416 | Diagnosis and treatment of pure red cell aplasia. | 1976 Sep | Pure red cell aplasia is a selective aplasia of the marrow erythroid cells. Unlike aplastic anemia, the marrow has a normal cellularity and the patients generally have normal leukocyte and platelet blood counts. The congenital form of the disease occurs in the firlst 1 1/2 years of life and is often responsive to corticosteroids. The acquired form may be secondary to infections, drugs, chemicals, or hemolytic anemia (aplastic crisis). In these cases it is often acute and self-limited with cessation of the infection or drug ingestion. It may also be secondary to systemic lupus erythematosus, rheumatoid arthritis, acute severe renal failure, severe nutritional deficiency, or diverse neoplasms, and may remit with treatment of the primary condition. When a thymoma is present, it should be resected since a remission is produced in 29 per cent of these patients. The remaining patients have an acquired primary form of the disease that tends to be chronic and in some cases may have an immune pathogenesis. A cytotoxic immunoglobulin inhibitor of the marrow erythroid cells or erythropoietin has been described and these patients may respond to prednisone and/or to cytotoxic immunosuppressive drugs such as cyclophosphamide and 6-mercaptopurine. Pure red cell aplasia appears to be more common than the literature has revealed and has stimulated much investigation into an immune pathogenesis for marrow failure. | |
| 4166 | Adjuvant and immunostimulating activities of water-soluble substances extracted from Mycob | 1975 Sep | Water-soluble substances have been extracted from two strains of Mycobacterium tuberculosis var. hominis: the native hydrosoluble part (polysaccharide and peptidoglycan), a substance in which the polysaccharide moiety is less abundant than in the latter, the acetylated peptidoglycan and, finally a tetrasaccharide-heptapeptide. All four types of substances, when they were injected together with Freund's incomplete adjuvant, exerted an adjuvant effect on the production of delayed-type hypersensitivity to ovalbumin in the guinea pig and on the production of anti-influenza virus antibodies in the rabbit. Injected intravenously in the mouse, they increased the number of antibody-producing cells in the spleen and enhanced the graft versus host reaction; no effect was seen on the phagocytic activity of the reticulo-endothelial system. By contrast with wax D, the water-soluble substances were devoid of arthritis-inducing activity in the rat. Altogether, these water-soluble substances seem to be endowed with at least some of the adjuvant activities of Freund's complete adjuvant and some of the immunostimulant activities of a live Mycobacterium like BCG. | |
| 231404 | Prostaglandins and their regulation in rheumatoid inflammation. | 1979 | Prostaglandins, especially PGE2 and PGI2, appear to participate in the development of inflammatory reactions. While these PGs may act to promote inflammation, they may also inhibit immune reactions; this effect is largely related to stimulation of adenylate cyclase. Human rheumatoid synovial tissue explants and derived adherent synovial cells (ASC) in vitro produce large amounts of PG, primarily PGE2, which may participate in the pathogenesis of rheumatoid inflammation and promote the osteoclastic resorption of juxtaarticular bone. Rheumatoid synovial organ cultures are unusual in that they derive a significant proportion of archidonic acid substrate for the PGE2 synthesis from triglycerides, while ASC utilize primarily phospholipids. Aspirin-like, nonsteroidal anti-inflammatory drugs inhibit PGE2 synthesis by rheumatoid synovial organ cultures at concentrations similar to those achieved in plasma during therapy. Glucocorticoids are also potent inhibitors of PGE2 synthesis, and evidence from experiments with tissue labeled with 1-[14C]arachidonic acid indicates that glucocorticoids do not act to inhibit arachidonic acid release, as has been postulated for other tissues. Human peripheral blood mononuclear cells produce a factor (MCF) that regularly stimulates the production of PGE2 and collagenase from resting ASC often by over 100-fold. The MCF appears to be produced by monocytes, and its production by monocytes is enhanced by lectin-stimulated T-cells. The ability of ASC to respond to exogenous PGE2 stimulation of cAMP synthesis is inhibited or stimulated by factors that increase or decrease PGE2 levels, respectively, in the cultures. The MCF augments the responsiveness of cAMP response to PGE2 in indomethacin-treated cultures. These in vitro experiments suggest that the pathogenesis of rheumatoid inflammation involves interactions between monocyte-macrophages, lymphocytes, and synovial cells regulating the production of PGE2, cAMP, and other factors. | |
| 263731 | Thyroid-stimulating antibodies in patients with autoimmune disorders. | 1978 Aug | A radioreceptor assay was used to measure thyroid-stimulating antibody (TSAb) in 1) patients with Graves' disease with untreated hyperthyroidism, selected for absence of clinically significant eye disease; 2) patients with Graves' ophthalmopathy, with and without previously treated hyperthyroidism; 3) patients with other thyroid disorders; 4) patients with other autoimmune disorders; and 5) normal subjects. TSAb was detected in 14 of 15 (93%) patients with Graves' hyperthyroidism and in 10 of 16 (63%) patients with Graves' ophthalmopathy. Of the patients with Graves' ophthalmopathy, TSAb was detected in 9 of 10 patients who had once been hyperthyroid and in only 1 of 6 patients who had never been hyperthyroid (euthyroid Graves' disease). TSAb was detected in 1 patient with idiopathic Addison's disease (autoimmune adrenalitis) and in 1 patient with juvenile diabetes mellitus (both of whom were euthyroid), and borderline levels were found in 1 patient with Sjögren's syndrome and 1 patient with methyldopa-induced antired blood cell antibodies. TSAb was not detected in normal subjects or patients with other thyroid disorders. The conclusions are: 1) the test is very useful in the diagnosis of Graves' disease; 2) Graves' eye disease may be a frequently associated but separate disorder; and 3) because TSAb may be present in some euthyroid patients with other autoimmune disorders, TSAb production may occur primarily because of a disorder in the immune system. | |
| 3992038 | The adrenochrome pathway. A potential catabolic route for adrenaline metabolism in inflamm | 1985 | Polymorphonuclear leukocytes activated by latex (polystyrene) beads or the chemotactic peptide N-formyl Met Leu Phe stimulated the oxidation of adrenaline (0.3 microM-10 mM) to adrenochrome, detected spectrophotometrically at 480 nm or by a high-performance liquid chromatographic (HPLC) method. This oxidation was detectable within 5 min and continued for at least 4 hr. Over the concentration range 0.3-10 microM, more than 80% of the adrenaline oxidation occurred via the adrenochrome pathway rather than the amine oxidase-catechol methyltransferase pathway. Medium isolated after stimulation of the polymorphonuclear leukocytes retained the ability to oxidize adrenaline to adrenochrome. Serum from patients after myocardial infarction induced more oxidation of adrenaline to adrenochrome than control serum. Superoxide dismutase, catalase, and azide inhibited by 70-95% the oxidation of adrenaline to adrenochrome, either by cells or medium. Commercially available adrenochrome was biologically active, but some of the actions were due to contaminants of the preparation. HPLC of an extract of synovial fluid from a patient with rheumatoid arthritis, a fluid that contains polymorphonuclear leukocytes, showed a peak identical to that of the adrenochrome standard. The results provide a cellular mechanism for adrenochrome formation and preliminary evidence that adrenochrome can be produced in inflammatory conditions in which polymorphonuclear leukocyte infiltration occurs. | |
| 6967746 | Studies on levamisole--induced agranulocytosis. | 1980 Sep | Widespread clinical trials of leavo-tetramisole (levamisole) as an immunopotentiating agent in rheumatoid arthritis, metastatic carcinoma, and immunodeficiency states have been complicated by agranulocytosis (AGC) in 2.5%-13% of patients. Other than a relationship with prolonged high dosage, very little is known regarding the pathogenesis of levamisole-induced AGC. Whereas leukoagglutination was negative, fluorochromatic microgranulocytotoxicity (GCY) tests were positive with serum from 10 of 10 acutely neutropenic patients. The antibody was IgM, reacted with 100% of unrelated granulocytes, but not with T or B lymphocytes. Some sera also reacted with monocytes and the myeloid cell line, K-562. Tests for antigen-antibody complexes or cold autoantibodies were negative. Although clinical evidence strongly suggests a haptene (drug) mechanism, in vitro mixing experiments were also negative. An alternative choice parallels the model of aldomet-induced Coombs'-positive hemolytic anemia. Finally, GCY first became positive 2-3 mo prior to the onset of AGC on two patients, suggesting the possibility of identifying those at risk well before the onset of neutropenia. | |
| 50336 | Acute anaphylaxis associated with serum complement depletion. | 1975 Sep | A 45-year-old woman with rheumatoid arthritis developed anaphylaxis 6 min after receiving a subcutaneous injection of lidocaine, followed by an intra-articular injection of lidocaine mixed with methprednisolone acetate. One hour after the onset of anaphylaxis, serum complement component levels were markedly depressed and remained so far 18 hr. Circulating immune complexes and antibodies to lidocaine could not be demonstrated. Neither lidocaine nor methylprednisolone acetate activated the patient's complement system in vitro. Subsequently, total hemolytic activity (CH50) levels were variable, complement component protein concentrations of C1q, C1s, C4, C2, C3, C5, C6, C9, and Factor B were normal, but hemolytic activity of C4 and C2 was diminished. Serum C1 inhibitor concentrations were normal or slightly depressed. The patient has never had any symptoms suggestive of angiodema. It is postulated that the endogenous complement abnormality present in this patient may have contributed to the anaphylactic reaction. | |
| 6230705 | Differences in the kinetics of the autologous mixed lymphocyte reaction between the variou | 1983 | Kinetic studies of autologous mixed lymphocyte reaction (AMLR) over 7 days were made in 86 patients with various connective tissue diseases. None was receiving any treatment and each disease group was controlled with age-sex matched healthy controls. There were exceptions, but, as a rule, SLE patients (n = 22) had decreased responses on days 6-7. This was more apparent in patients with active disease than in those with inactive disease. Patients with scleroderma (n = 21) had early (day 4) proliferative responses. Half of the patients with RA (n = 14) had early (day 3) proliferation, but as a group they had normal increase in 3HtdR uptake on day 7. Patients with primary Sjögren's syndrome showed flat curves throughout and no significant proliferation on days 6-7 of culture. The pattern found in patients with mixed connective tissue disease (n = 11) was also peculiar in that they had peak proliferative responses on day 3 and normal 3HtdR uptake on days 6 and 7 of the AMLR. The number of patients with dermatomyositis or polymyositis was small (n = 6), but they showed a significant mean decrease in uptake on days 6-7. Studies using subpopulations of stimulatory cells further indicate that these patterns reflect immunoregulatory disturbances peculiar to each disease. | |
| 6113812 | Urinary enzyme measurements in the diagnosis of renal disorders. | 1981 May | In view of Mattenheimer's comprehensive review of enzymes in renal disease in this journal only four years ago, major emphasis has been placed at the recent Symposium on Diagnostic Significance of Enzymes and Proteins in Urine held at Kanderstag, Switzerland in March of 1978. The pathophysiology of enzyme release in renal disease is presented, the current status of enzyme measurement reviewed, and the laboratory findings in several main types of renal disease summarized. While the measurement of selected urinary enzymes has been found extremely useful in specific situations, most investigators agree that routine screening is not warranted at this time. Newer developments in the measurement of isoenzyme patterns hold promise of introducing increased diagnostic specificity and appear to be the wave of the future. | |
| 984019 | Acinar pancreatic tumor with metastatic fat necrosis: report of a case and review of rheum | 1976 Nov | This report deals with a pancreatic tumor associated with metastatic fat necrosis. Our patient displayed the full gamut of nodular panniculitis, polyarthritis, fever, eosinophilia, hyperlipasemia, lytic bones lesions, and marrow fat necrosis. The rheumatologic features are reviewed. Elevated serum lipase is a most helpful laboratory confirmation. The tumor in our patient presented a difficult problem in classification. Although the appearance under light microscopy was most compatible with islet cell carcinoma or islet cell carcinoid, the ultrastructural characteristics were those of acinar carcinoma. | |
| 95543 | [Clinical significance of the radioimmunological determination of beta-thromboglobulin and | 1979 | Recently new radioimmunoassay methods have been established to measure plasma concentrations of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4), platelet release products which are set free when platelets aggregate. Plasma concentrations of beta-TG and PF4 were investigated in disorders with increased thromboembolic risk. Extremely high concentrations of these platelet proteins were found in patients with venous thrombosis, pulmonary embolism, polycythemia vera, and chronic renal failure. Moderately increased beta-TG and PF4 levels were observed in patients with peripheral vascular disease, coronary artery disease, chronic rheumatoid arthritis, multiple myeloma, and diabetes mellitus. These data indicate, that plasma concentrations of beta-TG and PF4 are useful parameters for the evaluation of the "in vivo" platelet activity. By using these new methods for clinical applications special blood sampling conditions have been taken into account; moreover one has to consider that the plasma levels of the platelet "release products" are dependent from renal function. | |
| 140239 | [Index of fibrinolysis with new fibrin plate (author's transl)]. | 1977 | Plasminogen-free fibrin plate (fP) which was made from treated commerical bovine fibrinogen with Lysine-Sepharose was developed in our laboratory. This new fibrin plate showed the following specificities. a) This new fibrin plate did not show any lysis with high amount of streptokinase and Urokinase (10,000 u/ml and 500 u/ml). b) The concentrations of its substrate was the same as standard plate (SP) and its substrate was not denatured compared with heated plate (HP). c) The activity of plasmin can be measured quantitatively on fP and linear correlation between plasmin units and lysis area was showen. d) This procedure of new fibrin plate was easy and simple and could be applicable to the materials of other species, i.e., human, rabbit and porcine. With the use of two kinds of bovine fibrin plate (SP and fP), activation of fibrinolysis of human plasma, euglobulin and plasminogen induced by SK and UK was investigated and each correlation ship between sample and activator was studied statistically. From these results, "Index of fibrinolysis" meaning of fibrinolytic components such as plasmin, plasminogen, activator, proactivator, anti-activator and anti-plasmin were indicated. Indeed, these index of fibrinolysis were calculated from the lysis area of plasma+SK, Eug.+SK and Eug.+UK by each formula and index obtained from some physiological and pathological condition showed us many new information about fibrinolysis. | |
| 1172464 | [Severe side-effects of treatment with D-penicillamine (author's transl)]. | 1975 Aug 8 | In a 53-year-old woman an acute allergic thrombocytopenia (acute Werlhf's disease) occurred after treatment with D-penicillamine for one month which led to death. In two further patients transitory platelet deficiencies were observed after six and two months which regressed completely in six months and four weeks, respectively. One of the patients had nephrotic syndrome and a retrobulbar neuritis at the same time. Both symptoms were equally transitory and could not be demonstrated five weeks after cessation of therapy. In a further case a lethal Lyell syndrome developed three weeks after therapy was started. These observations show that during D-penicillamine treatment weekly, and later fornightly, blood counts should be performed. In the occurence of thrombocytopenia, leucopenia or anaemia treatments should be stopped; Signs of drug intolerance together with exanthemata should also led to a critical review of the indications and the dosage. D-Penicillamine should not be used when hypersensitivity to penicillin exists or when cell deficiencies have occurred after anti-reheumatic medication. The development of proteinuria should also result in withdrawal of the drug. Therapy with D-penicillamine requires conscientious follow-up urinalyses and blood counts as well as attention to allergic rashes. | |
| 1131284 | Efficacy of lithium in rheumatoid arthritis with granulocytopenia (felty's syndrome). A pr | 1975 Mar | Lithium carbonate was given orally for 6 weeks in varying doses to 10 patients with Felty's syndrome. All patients receiving 900 mg of lithium daily showed statistically significant elevations in granulocyte count during therapy. The effect was usually noted within a week and did not persist when the drug was withdrawn. The percentage increase in mean absolute granulocyte count varied between 138% and 617% of control value in different patients; the lower values were observed in those patients with basal serum lithium concentrations less than 0.5 mEq/liter. It is concluded that a consistent rise in peripheral blood granulocytes was achieved by lithium carbonate in a dosage of 900 mg daily in patients with Felty's syndrome. |