Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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1130072 | [Biosynthesis of collagen and mode of action of D-penicillamine (author's transl)]. | 1975 Jan 10 | The biosynthesis and metabolism of collagen are complex processes and are regulated by different enzyme systems. In theory these processes can be influenced at a number of different stages. The therapeutic prevention of excessive collagen and fibril synthesis is a desirable aim, although there is a lack of substances suitable for this purpose. One substance employed is D-penicillamine (D-PA), which blocks aldehyde condensation, inhibits the cross-linking of the peptide chains and the formation of collagen fibrils. Other characteristics of D-PA which are of therapeutic interest are chelate formation with heavy metals and the depolymerizing action on macroglobulins. D-PA may possibly by of some value in the chemotherapy of certain tumours and for sensitizing tumour cells to irradiation. It remains to be investigated whether D-PA or similar substances could be of therapeutic value in arteriosclerosis, in which an increased deposition of collagen in the basal membranes is the fundamental process. The successful therapeutic use of D-PA in rheumatoid arthritis and chronic active cirrhoses of the liver justifies the hope that this substance may favourably influence disorders of collagen metabolism. | |
27743077 | Clinical and radiographic evaluation of modular knee replacement : A review of 95 cases. | 1982 Jun | Ninety-five modular total knee replacements, 54 of them unicompartmental, have been reviewed. The average follow-up was three years.The major indication for operation was pain. A precise preoperative radiographic evaluation and a technique for a positioning the components are described. This had led to a significant improvement in the clinical and radiographic results in 67 out of 95 knees which were operated on. The modifications concern the orientation of the tibial cut, the placing of the femoral components and the correction of axial deviation.The main causes of the 13% of failures in our series were either errors in positioning the components or a preoperative diagnosis of rheumatoid arthritis.Unicompartmental replacement gave similar results in both valgus and varus knees, and the morbidity was lower than in the bicompartmental replacements. The best results were obtained in osteoarthristic knees in elderly patients and in posttraumatic osteoarthritis. | |
4022693 | Reye syndrome associated with aspirin therapy for systemic lupus erythematosus. | 1985 Aug | A 14-year-old girl in whom Reye syndrome developed during aspirin therapy for an inflammatory disorder proven to be systemic lupus erythematosus is reported. This case and similar cases of Reye syndrome in patients with juvenile rheumatoid arthritis suggest that an etiologic relationship exists between salicylate therapy and Reye syndrome in children with collagen vascular disorders. | |
6439870 | A single step radial immunodiffusion (RID) method for the quantitation of monomeric IgM. | 1984 Sep | Monomeric IgM (7S IgM) is present in the serum of patients with certain inflammatory and neoplastic conditions. In the past it has been necessary to separate 7S IgM from 19S IgM by chromatography or ultra-centrifugation prior to its quantification, however, 7% agarose gels allow migration of 7S molecules while retarding the migration of larger (19S) molecules. We describe the development of a RID method on 7% agarose and detail the optimum conditions for the preparation of gels and standards in order to quantify 7S IgM present in serum in a single step without prior separation from 19S IgM. The major difficulties encountered were in the preparation of the agarose gels and the conditions necessary to overcome the difficulties are described. A linear relationship was found between the ring diameter squared and the 7S IgM concentration. The assay could detect as little as 15 micrograms/ml of 7S IgM. Within assay variability was 15.4%. In the sera of 45 normal individuals monomeric IgM was not detected whereas 15 (43%) of an unselected group of patients with rheumatoid arthritis had measurable levels of 7S IgM. This method for quantifying 7S IgM is both simple and inexpensive, and because of the ease with which large numbers of sera can be processed in a single assay it is less time consuming than other methods used to quantify 7S IgM. | |
6467672 | Selection against genetic defects in semen donors. | 1984 Aug | Artificial insemination donor selection requires predicting which men are likely to beget the healthiest offspring. Methods are developed for calculating the "offspring excess recurrence risk", delta R, for an anomaly in the offspring of an afflicted father. Mainly from published family survey and population data delta R is computed for 38 disorders. From a small survey a value for the with-treatment "affliction burden", Bt, is assigned to each anomaly. For each disorder the "offspring excess burden expectation" is delta RBt. Defects such as cataract, hereditary Parkinson disease, psoriasis, seropositive rheumatoid arthritis, and schizophrenia have such a high delta RBt that they are individually sufficient cause for rejecting a donor candidate. A candidate may be rejected because of a combination of lesser defects with sigma delta RBt exceeding an acceptable limit. A limit should also be placed on Bt, because the affliction burden for Tay-Sachs disease or cystic fibrosis is intolerable, however infrequent. Most of the important hereditary defects are late onset, and for the older donor the opportunity to select more directly against late-onset disorders offsets the added risk of newly-arising gene mutations. The most careful donor selection cannot completely eliminate the risk of a child inheriting some disorder, but selection can reduce the average total burden by as much as 17%. | |
6225740 | Frambu Health Centre: promoting family focused care for disabled children. | 1983 Jun | During the last 30 years the Frambu Health Centre has evolved from a summer-camp site for children with poliomyelitis to a modern information and treatment Centre for families with disabled members. Since 1976, fortnightly courses have been held for an increasing number of patients with rare, often congenital and/or hereditary disorders (anorectal anomalies, bladder extrophy, congenital heart defects, cystic fibrosis, severe diabetes, hemophilia, hip joint defects, juvenile rheumatoid arthritis, minimal brain dysfunction, muscular dystrophy, phenylketonuria, psychosis/autism, spina bifida, Huntington's chorea, osteogenesis imperfecta, retitinitis pigmentosa, a. o.). This article describes the facilities, operation, financing and staff at Frambu. An outline of the course programme is given. The contents of two research projects carried out at Frambu are described. When families with rare disorders meet for the first time, new perspectives open up. Exchange of experience and feelings, establishing lay organizations, collating and distributing information to professionals and families are some of the important results of the Frambu courses. | |
7073977 | Acid lysosomal hydrolases in systemic sclerosis and other connective tissue diseases. | 1982 May | The activities of five lysosomal hydrolases were determined fluorometrically in the serum of patients with systemic sclerosis (PSS), systemic lupus erythematosus (SLE), dermatomyositis (DM), rheumatoid arthritis (RA), or Raynaud's disease (RD). In PSS the beta-galactosidase activity was significantly increased compared with controls and the other connective tissue diseases. The beta-N-acetyl-glucosaminidase was significantly increased in PSS, SLE and DM. In PSS both enzymes were more active in the early stage of the disease than later. These changes of enzyme pattern seem to be a relatively reliable marker for the differential diagnosis of PSS compared to other connective tissue diseases, especially for RD, in which the beta-galactosidase activity was significantly decreased. Further work is required to determine whether these polysaccharide-degrading acid hydrolases play a role in the pathogenesis of PSS. | |
7015004 | [Antinuclear antibodies in diagnosis of rheumatic diseases (author's transl)]. | 1981 Mar 16 | Hundred ana-positive sera--60 sera of SLE-patients and 40 sera of patients suffering from rheumatoid arthritis--were investigated for ana and DNA-antibodies. For these purposes nine different methods including several radioimmunological and immunofluorescence techniques with partially distinct antigen-specificities were tested. While the radioimmunoassays showed only slightly different results, significant differences in sensitivity as well as in antibody specificity existed mainly in the indirect immunofluorescence techniques using different substrates. For clinical use, a combination of various techniques seemed to be useful i.e. indirect immunofluorescence on hemolysed bird erythrocytes and on frozen native rat liver sections. For DNA-antibodies in diagnosis and control during the course of the diseases the radioimmunoassay with simultaneous detection of antibodies to single- and double stranded DNA is most suitable. Antibodies to distinct nuclear antigens are detectable in various amount in the rheumatic diseases. While ds-DNA-antibodies seemed to be most specific for SLE, ss-DNA-antibodies occurred in nearly all ana-positive sera and seemed to be less specific for one disease than all the other ana-fractions. | |
315314 | Pharmacokinetics of fenbufen in man. | 1979 Aug | The pharmacokinetics of fenbufen (3,4-biphenylcarbonyl proprionic acid) a new antiinflammatory agent, and its metabolites, gamma-hydroxy-4-biphenylbutyric acid and 4-biphenylacetic acid have been studied after oral administration to seven patients with rheumatoid arthritis. Fenbufen was administered as a single oral dose of 600 mg in hard gelatine capsules. A specific, sensitive gas chromatographic method was used to measure the concentration of the three compounds. A linear two-compartment open model appeared suitable to describe the course of the plasma level of fenbufen with time. This compound appeared in the blood after a lag time of 0.45 h and the peak plasma concentration of 5.97 micrograms/ml was observed after 1.19 h. The half-life of plasma disappearance was 10.26 h for fenbufen and 10.07 h and at 9.95 for metabolites II and III, respectively. | |
342086 | The clinical pharmacology of methotrexate: new applications of an old drug. | 1978 Jan | Methotrexate is now used widely for the treatment of acute leukemia, non-Hodgkin's lymphoma, osteogenic sarcoma, choriocarcinoma, breast carcinoma, pulmonary and epidermoid carcinoma, and intrathecal chemotherapy. It is also useful in bone marrow transplantation, severe psoriasis, rheumatoid arthritis, dermatomyositis, Wegener's granulomatosis and sarcoidosis. The recent dramatic intensification of methotrexate therapy can be attributed in part to advances in our understanding of the clinical pharmacology of the folate antagonists, as well as to the combination of positive results and their effective dissemination to medical oncologists. The review summarizes the pharmacologic findings and illustrates how they are currently being applied to the treatment of malignant disease. | |
781314 | Immunologic considerations in renovascular hypertension. | 1976 Aug | For decades certain diseases, such as glomerulonephritis, polyarteritis nodosa, scleroderma and serum sickness, have been linked with autoimmune pathogenesis. During recent years a host of additional diseases traditionally thought to have some genetic predisposition but with obscure etiology have been suspected of being autoimmune in nature. Rheumatoid arthritis, diabetes, myasthenia gravis and thyroiditis are diseases of widely divergent organ systems, yet may well have common pathways of pathology via immune complexing mechanisms. Herein we present evidence supporting the concept that renal artery stenosis (occurring primarily in association with the middle aortic syndrome or after renal transplantation) is of immune etiology. Although the specific antigenic agent is still to be defined there is growing acceptance of the theory that medium and large vessels are subject to autoimmune vasculitis in many aspects similar to the autoimmune affections of small vessels. Several cases are presented. Some of these suggest an immune reaction by the natural history but without evidence of immunochemical reactants in the involved vessels, presumably because active disease was arrested at the time of study. In other cases immunofluorescent preparations demonstrate reactants in the walls of the vessels to document the hypothesis more convincingly. | |
3876902 | T lymphocyte subsets of the infiltrating cells in the salivary gland and kidney of a patie | 1985 Jul | Lymphocyte subsets in the salivary gland and kidney were examined in a 38 years-old female patient with Sjögren's syndrome associated with interstitial nephritis by PAP immunoperoxidase method using monoclonal antibodies. Predominant cells of the infiltrating cells in both tissues were T lymphocytes and most of them were Ia+, OKT4+ cells (activated helper/inducer T lymphocytes). A small number of T lymphocytes were OKT8+ (suppressor/cytotoxic T lymphocytes). Moreover, we found the OKT8+ cells invading the salivary duct epithelial cells. There was no difference in the proportion of lymphocyte subsets of the infiltrating cells between the salivary gland and kidney. A similar pathologic mechanism of tissue damage, therefore, was suggested in both tissues. | |
7035032 | Autoantibody to a novel neuronal antigen in systemic lupus erythematosus and in normal hum | 1981 Jun | A non-Fc receptor-bearing mouse neuroblastoma cell line, Neuro-2a, was used in indirect immunofluorescence tests to characterize the pattern of anti-neuronal activity of human sera in 41 cases of systemic lupus erythematosus (SLE), including seven cases of cerebral lupus, 30 "disease controls" (rheumatoid arthritis and chronic active hepatitis) and 30 healthy subjects. The immunofluorescence reaction with Neuro-2a gave a uniform ring fluorescence of the cell surface of cultured cells at 4 and at 37 degrees C, clusters were seen at 5 to 10 min and surface globules at 20 to 120 min. Titres of antibody to Neuro-2a in SLE ranged from less than 5 (seven cases), 5 to 20 (23 cases) and greater than or equal to 40 (11 cases). Titres of 80 to 160 were given by five of seven cases of cerebral lupus and two of 34 cases without cerebral lupus. Antibody to Neuro-2a was demonstrable in subjects without SLE, but to lower titres (less than 5-20). Of 11 SLE sera with antibody titres greater than or equal to 1:40, the antibody class was IgM in eight, IgG in two and both IgM and IgG in one. Absorption studies indicated that serum reactivity against Neuro-2a cells could be removed from some SLE sera with the cultured human neuroblastoma cell line, SK-N-SH, but not with mouse fibroblasts, mouse 3T3 cells, rat C6 glioma cells, rat transformed mesenchymal cells, nor by homogenates of mouse brain, heart, liver of kidney. Detection of antibody to Neuro-2a cell may be helpful in identifying patients with cerebral disease due to SLE. | |
3933518 | Effects of 1-hydroxyethylidene-1,1 bisphosphonate and (chloro-4 phenyl) thiomethylene bisp | 1985 Nov 15 | Articular chondrocytes and synovial cells were stimulated to produce collagenase, neutral casein and proteoglycan-degrading proteinases by conditioned medium from human peripheral blood mononuclear cells. Collagenase, neutral casein and proteoglycan-degrading proteinase secretion was inhibited by SR 41319, a new bisphosphonate, in a concentration-dependent manner. Complete inhibition was achieved at about 0.3 mM. EHDP exhibited the same general profile but was about 10-fold less active and never completely inhibited the enzyme secretion. When added before MCF, SR 41319 had a protective effect against subsequent activation of the cells by MCF. SR 41319 also inhibited the increase of enzyme secretion by cells previously stimulated with MCF. The results suggest that the ability of SR 41319 to inhibit the MCF-mediated secretion of neutral enzymes involved in cartilage destruction could be valuable in the management of connective tissue damage in rheumatoid arthritis. | |
2991183 | Primary culture of ant venom gland cells. | 1985 Jun | Venom from the ant Pseudomyrmex triplarinus reduces the symptoms and swelling of rheumatoid arthritis. The cells that produce the venom were dissected from larval and pupal ants and culture conditions studied. Cell dissociation, with minimal amount of damage, was done with 0.25% trypsin at 4 degrees C with subsequent use of soybean trypsin inhibitor. A new medium was formulated and epidermal growth factor, fibroblast growth factor, insulin, cAMP, cGMP, and isoproterenol were beneficial. The optimum osmotic pressure was a relatively high 500 mOSM. Conditioning the medium with an established insect cell line was essential for long-term cell survival. Under these culture conditions the structural and metabolic integrity of the cells were maintained for up to 12 mo. | |
3836708 | Detection of IgG-bearing erythrocytes by a sensitive Staphylococcus aureus protein A-bindi | 1985 | We describe a sensitive radioassay for detecting erythrocyte-associated immunoglobulin employing the immunoglobulin-specific reagent Staphylococcus aureus protein A. The assay was used to determine the extent to which erythrocytes from patients with different connective tissue disease bind radiolabelled protein A. Increased amounts of protein A were bound by erythrocytes from patients with systemic lupus erythematosus or with progressive systemic sclerosis when compared to a control group, whereas there was no significant binding to erythrocytes from patients with rheumatoid arthritis or with polymyositis-dermatomyositis. The assay, because of its high sensitivity and of the availability of the reagent in pure form, should be useful for the investigation of cell-bound antibodies and for the differential diagnosis of connective tissue diseases. | |
6549416 | Protein C antigen is not an acute phase reactant and is often high in ischemic heart disea | 1984 Dec 29 | Protein C, an antithrombotic protein, was measured immunologically in 299 patients with clinical conditions associated with a high frequency of venous or arterial thromboembolism. The mean protein C antigen (PC:Ag) level was high for 48 patients with ischemic heart disease and, to a lesser extent, for 95 diabetics. In 28 patients with thrombotic strokes, 48 patients with proximal deep-vein thrombosis and in 80 patients with localized or metastatic tumors, mean PC:Ag was normal. Comparison of the pattern of changes of PC:Ag levels with those of fibrinogen, orosomucoid and prothrombin in 21 patients during the postoperative period and in 20 patients with active rheumatoid arthritis ruled out the possibility that high PC:Ag is non-specific, acute-phase reaction to inflammation, tissue injury or neoplastic growth. Therefore, high PC:Ag might be specifically related to the thrombotic tendency of these patients, but the mechanism of such a relationship remains to be clarified. | |
6210324 | Demonstration of anti-keratin antibodies by ELISA using keratin or thiol-containing compou | 1984 Dec 14 | During the development of an enzyme-linked immunosorbent assay (ELISA) for the demonstration of anti-keratin antibodies (AKA) it was observed that rabbit anti-keratin antisera also reacted with polystyrene surfaces treated with beta-mercaptoethanol in 8 M urea (ME-urea). Sera from non-immunized rabbits or rabbits immunized with antigens unrelated to keratin failed to react. The specificity of the reaction was further assessed by absorption experiments and by testing affinity-purified AKA. IgM activity against ME-urea could be demonstrated in 62.5% of sera from patients with infectious mononucleosis and in 37.5% of sera from patients with rheumatoid arthritis, and there was a good correlation to the presence of AKA. Coating of the solid phase with compounds containing free SH groups in 4-8 M urea generated the antigen of this ELISA. The exact molecular configuration of this presumptive synthetic antigen is obscure, but the ME-urea ELISA seems to provide a simple way to detect anti-keratin antibodies of a certain specificity. | |
6429015 | Correlation between changes induced by venous occlusion on factor VIII-von Willebrand fact | 1984 | The effects of standardized venous occlusion (VO) on factor VIII-von Willebrand factor (F VIII-VWF) components (F VIII:C, F VIIIR:AG, F VIIIR:RCof) and on fibrinolytic activity were investigated in 45 healthy subjects, in 28 women on oral contraceptives, and in 78 patients with various chronic diseases (28 with peripheral arterial disease, 19 with liver cirrhosis, 13 with rheumatoid arthritis, and 18 with diabetes). All the three F VIII-VWF components showed highly significant increases, although not of the same magnitude, with consequent variations in the ratios between them. A significant activation of fibrinolysis was also demonstrated with both euglobulin lysis time (ELT) and diluted blood clot lysis time (DBCLT). A strong linear correlation between pre- and post-stasis values was recorded for all the F VIII-VWF components and for the two fibrinolysis tests. No significant relationship was, on the contrary, found between F VIII-VWF and fibrinolytic parameters. | |
6400538 | [Iron and iron-binding proteins in inflammation and tumors]. | 1984 | Iron and iron binding proteins are involved in various regulatory mechanisms in infections and tumors. Chronic infections and tumors are the most common reasons of anemias in hospitalized patients in industrial countries. Although a lot of investigative work has been done to identify the underlying mechanisms many details are still poorly understood. This paper gives a review of our present knowledge from experimental work, reported in the literature together with own results. The main emphasis is laid on new findings about the importance of a possible regulatory role of iron and iron bindings proteins on the surface of cells of the immune system in the immune surveillance as well as in non immune functions. Using a cytotoxic assay with a monoclonal antiplacental ferritin antibody which was developed by C. Moroz, surface ferritin was not only detected on peripheral mononuclear cells of patients with early stages of breast cancer but also in patients with rheumatoid arthritis which has not been reported so far. Possible connections of inflammatory states with tumors are discussed regarding the results with ferritin bearing lymphocytes together with other findings about the role of cell bound iron binding proteins in conditions of tumor and inflammation. |