Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2802796 | Low avidity antibodies to dsDNA as a diagnostic tool. | 1989 Sep | An evaluation of the diagnostic value of low avidity antibodies to double stranded DNA (dsDNA) measured by the polyethylene glycol (PEG) assay was undertaken. By routine screening low avidity anti-dsDNA were detected in the serum samples of 106 hitherto unknown patients. Clinical data of these patients were collected and when only low avidity anti-dsDNA was present (n = 92) a varied disease spectrum was observed. A diagnosis of systemic lupus erythematosus (SLE) was established in 48/92 (52%), lupus-like disease in 21/92 (23%), autoimmune hepatitis in 9/92 (10%), rheumatoid arthritis in 8/92 (9%), and mixed connective tissue disease in 2/92 (2%) of all patients. Patients with definite SLE were all older than 45 years and predominantly female (46/48, 96%). They showed a remarkably low incidence of renal disease (2/69, 3%). When high avidity antibodies to dsDNA as measured by the Farr assay were present as well (n = 14) a diagnosis of SLE could be established in 12/14 (86%) of all patients, indicating the secondary importance of low avidity anti-dsDNA in these patients. | |
| 2467774 | Antibody binding of macromolecular DNA and RNA in the plasma of SLE patients. | 1989 Mar | Plasmapheresis fluids from 20 patients with clinically active SLE, from three patients with Waldenstrom's disease, from three patients with rheumatoid arthritis, two patients with myasthenia gravis and other diseases including active systemic disorders were precipitated using polyethylene glycol 6000 (PEG). By applying ethidium bromide staining, plasma nucleic acids (PNA) could be demonstrated in PEG-precipitates of SLE patients exclusively. Purified immunoglobulins of SLE plasma precipitates were shown to form antigen-antibody complexes with PNA as demonstrated by electronmicroscopy. Further characterization of PNA by agarose gel electrophoresis revealed a molecular weight up to 20 kbp. Cesium chloride buoyant density gradients showed non-homogeneous molecules, excluding pure microbial origin. In spite of RNase digestion, the PNA contained RNA with 30-70% riboguanosine as shown by nucleoside analysis. The high amount of guanosine-rich RNA was further supported by similarities between PNA and polyriboguanylic acid in hyperchrome shifting due to thermic denaturation. HPLC analysis showed a molecular weight of ribonucleic acids of more than 60 b thus excluding mere oligonucleotides. In contrast to B-type dsDNA, PNA from SLE patients were immunogenic. Antibodies against PNA could be induced in rabbits by subcutaneous injection. The antisera thus obtained showed crossreactivity with polyriboguanylic acid and dsDNA preparations. | |
| 2510275 | Endoscopic evaluation of rioprostil in the management of non-steroidal anti-inflammatory d | 1989 | The effects of the synthetic prostaglandin E1 analogue, rioprostil, on non-steroidal anti-inflammatory drug-induced (NSAID) gastritis are investigated. The study is of randomized, double-blind design. Patients are included who had classical or definite rheumatoid arthritis or osteoarthritis, had been taking a stable dose of NSAID or aspirin for at least one month and had endoscopically proven gastric lesion. Endoscopy is performed prior to, and at 4, 8 and 12 weeks of the treatment period. Patients receive either rioprostil, 300 micrograms or 100 micrograms q.d.s., or placebo q.d.s. The results of the endoscopies show greater healing of the mucosa in patients taking rioprostil compared with those taking placebo. It is therefore concluded that rioprostil is an effective compound for the management of patients with NSAID-induced gastritis. | |
| 2438072 | Heterogeneity of thyroid autoantigens identified by immunoblotting. | 1987 Jun | Autoimmune thyroid disease in man is commonly associated with autoantibodies against thyroglobulin, microsomes, and the TSH receptor, and the character and specificity of these antithyroid antibodies have been extensively utilized in investigating these conditions. In the present study we have asked whether other thyroid-related antigens exist, against which autoantibodies may be directed. A crude thyroid extract was separated by polyacrylamide gel electrophoresis followed by immunoblotting with serum obtained from patients with Graves' disease or Hashimoto's thyroiditis. Antibodies in sera from patients with Graves' disease and Hashimoto's thyroiditis reacted with many antigenic determinants in immunoblots of the thyroid membrane preparation (2000g supernatant). These determinants were disease specific in that sera from normals and patients with Addison's disease and rheumatoid arthritis did not react, but there was no difference between the patterns of reactivity with Graves' disease or Hashimoto's thyroiditis sera. Thyroglobulin produced two predominant bands of reactivity at 320 and 200 kDa, whereas purified microsomal antigen produced a triplet of bands around 105 kDa, when these preparations were reacted with appropriate autoimmune sera. Nonetheless, some sera produced additional bands with the microsomal antigen blots, indicating that some of the antigens which were detected using crude thyroid membrane remained in the microsome preparation to produce multiple antibody binding reactivities. We were unable to inhibit any of the antibody binding with TSH. Purification of individual thyroid antigens on the basis of their molecular weights should standardize current antibody assays and permit more detailed evaluation of the cellular immune responses in Graves' disease and Hashimoto's thyroiditis. | |
| 3030427 | The effect of D-penicillamine on myeloperoxidase: formation of compound III and inhibition | 1987 Mar 18 | The inhibitory effect of the anti-arthritic drug D-penicillamine on the formation of hypochlorite (HOCl) by myeloperoxidase from H2O2 and Cl- was investigated. When D-penicillamine was added to myeloperoxidase under turnover conditions, Compound III was formed, the superoxide derivative of the enzyme. Compound III was not formed when D-penicillamine was added in the presence of EDTA or in the absence of oxygen. However, when H2O2 was added to myeloperoxidase, D-penicillamine and EDTA, Compound III was formed. Therefore it is concluded that formation of Compound III is initiated by metal-catalysed oxidation of the thiol group of this anti-arthritic drug, resulting in formation of superoxide anions. Once Compound III is formed, a chain reaction is started via which the thiol groups of other D-penicillamine molecules are oxidized to disulphides. Concomitantly, Compound I of myeloperoxidase would be reduced to Compound II and superoxide anions would be generated from oxygen. This conclusion is supported by experiments which showed that formation of Compound III of myeloperoxidase by D-penicillamine depended on the chloride concentration. Thus, an enzyme intermediate which is active in chlorination (i.e. Compound I) participated in the generation of superoxide anions from the anti-arthritic drug. From the results described in this paper it is proposed that D-penicillamine may exert its therapeutic effect in the treatment of rheumatoid arthritis by scavenging HOCl and by converting myeloperoxidase to Compound III, which is inactive in the formation of HOCl. | |
| 3636599 | Cephalosporin antibiotics can be modified to inhibit human leukocyte elastase. | 1986 Jul 10 | Several laboratories, including our own have reported the synthesis and activity of certain low relative molecular mass inhibitors of mammalian serine proteases, especially human leukocyte elastase (HLE, EC 3.4.21.37), an enzyme whose degradative activity on lung elastin has been implicated as a major causative factor in the induction of pulmonary emphysema, and which is present in the azurophil granules of human polymorphonuclear leukocytes (PMN). Normally, these granules fuse with phagosomes containing engulfed foreign material (such as bacteria), and HLE, in combination with other lysosomal enzymes, catabolizes the particles. Under certain pathological conditions, however, PMN become attached to host protein (elastin fibres, basement membrane, connective tissue, immune complexes), and in response to this adherence, the granules may fuse with the PMN outer membrane and release their contents, including HLE, directly onto the tissue. Besides emphysema, HLE may also contribute to the pathogenesis of disease states such as adult respiratory distress syndrome, and its potential involvement in rheumatoid arthritis makes HLE inhibitors of considerable interest. It is known that cephalosporin antibiotics (for example, cephalothin (compound I, Table 2)) are acylating inhibitors of bacterial serine proteases which help synthesize the cell wall by performing a transpeptidation reaction on a peptidyl substrate bearing a D-Ala-D-Ala terminus. We now report that neutral cephalosporins (that is, compounds not bearing a free carboxyl at position C-4) can be modified to become potent time-dependent inhibitors of HLE. | |
| 3017245 | Defective Epstein-Barr virus specific suppressor T cell function in progressive systemic s | 1986 Jul | Several immunoregulatory defects of Epstein-Barr virus (EBV) induced B cell activation have been described in patients with rheumatoid arthritis (RA), suggesting that EBV may have a role in the pathogenesis of RA. We assessed EBV specific T cell regulation in 20 patients with progressive systemic sclerosis (PSS) and immune to EBV and in 10 control subjects also immune to EBV by comparing the secretion of IgM into supernatants of 16 day cultures of B cells alone and cocultures of B and autologous T cells. In control subjects autologous T cells mediated a significant decrease in the secretion of IgM by B cells at 12 and 16 days of culture. Analysis of individual responses showed the existence of two subgroups of patients with PSS: group I (10 patients) had a suppressor T cell function similar to that of controls; group II (10 patients) had a defective T cell function. Differences in the duration or severity of the disease, the slow acting therapeutic agents, and anti-inflammatory drugs could not account for these subdivisions. These results suggest that several immunoregulatory defects of EBV induced B cell activation exist in different connective tissue diseases. | |
| 1771651 | Trace analysis of methotrexate and 7-hydroxymethotrexate in human plasma and urine by a no | 1991 Nov | A new high-performance liquid chromatographic method for the quantitative determination of methotrexate (MTX) and its metabolite 7-hydroxymethotrexate (7-OHMTX) in blood plasma and urine was developed. The method utilized a solid-phase extraction procedure (Certify II cartridges) for the simultaneous isolation of MTX and 7-OHMTX. Chromatographic separation was achieved using a C18 reversed-phase column with isocratic elution. The eluent was irradiated with UV light of 254 nm, which converted MTX and 7-OHMTX by photolytic oxidation to fluorescent products. The limits of detection of MTX and 7-OHMTX in plasma were approximately 0.2 and 1 nmol/L, respectively. The intraday variability in the quantitation of MTX and 7-OHMTX was less than 8% down to 1 nmol/L and 4.6 nmol/L, respectively. Both MTX and 7-OHMTX could be detected in plasma from a patient being treated for rheumatoid arthritis 1 week after the last dose (10 mg orally). | |
| 1896808 | The effect of polyacrylic acid polymers on small-intestinal function and permeability chan | 1991 Jul | Non-steroidal anti-inflammatory drug (NSAID)-induced increased small-intestinal permeability appears to be a prerequisite for the development of NSAID enteropathy, which is a cause of much morbidity in patients with rheumatoid arthritis. We assessed, with a combined absorption-permeability test, the effects of Carbopol (a polyacrylic acid polymer capable of increasing mucus strength and viscosity) on intestinal function and whether it protected against indomethacin-induced increased intestinal permeability. Using a test solution of 3-0-methyl-D-glucose, D-xylose, L-rhamnose, and 51Cr-labelled ethylenediaminetetraacetic acid with 5-h urine collections for marker analyses, we tested 16 subjects, as base line, after 20 ml Carbopol 4 times daily for 4 days, after indomethacin alone (75 + 75 mg), and after coadministration of Carbopol and indomethacin. Carbopol had no significant effect on the permeation or absorption of the test substances. Indomethacin increased intestinal permeability significantly, and this was unaffected when Carbopol was coadministered with indomethacin, showing that Carbopol does not limit the immediate damage of NSAIDs on the small intestine. | |
| 2038014 | NSAID gastropathy: the second most deadly rheumatic disease? Epidemiology and risk apprais | 1991 Mar | Nonsteroidal antiinflammatory drug (NSAID) gastrointestinal (GI) pathology (gastropathy) accounts for over 70,000 hospitalizations and over 7,000 deaths annually in the United States. Not all patients, however, are at equal risk. Major risk factors for serious events (hospitalization or death) in patients with rheumatoid arthritis (RA) are age, level of disability, concurrent use of prednisone, prior NSAID side effects and NSAID dose. For the average patient with RA, the chance of hospitalization or death due to a GI event is about 1.3 to 1.6% over the course of 12 months and about 1 in 3 over the entire course of the disease. Subgroups of patients have risks ranging from nearly zero to as high as 4 or 5%/years. A simple scoring system based on multivariate analysis of risk factors permits the clinician to directly calculate the risk for the individual patient. | |
| 2197219 | Interleukin-6: historical background, genetics and biological significance. | 1990 Mar | Interleukin-6 (IL-6) is a pleiotropic cytokine previously known as B cell stimulatory factor (BSF-2), interferon-beta 2 (IFN-beta 2), 26-kDa protein, and hepatocyte stimulating factor (HSF). The name IL-6 was proposed when the nucleotide sequences of the cDNAs for these proteins had been determined and the molecules were found to be identical. IL-6 production can be induced by a wide variety of agents in a wide range of cells, although IL-6 gene expression seems to be regulated in a tissue and stimulus specific manner. At least 3 different signal pathways regulate IL-6 gene expression, emphasizing its multiply inducible nature. The currently known activities of IL-6 include regulatory functions in hematopoiesis, immune reactions and acute phase responses. IL-6 appears to be a key member of the IL family; however, it is still poorly understood how IL-6 interacts with other lymphokines within the network. The anti-viral activity of IL-6 seems to be negligible. Elevated IL-6 levels have been found in diseases like rheumatoid arthritis, multiple myeloma and systemic lupus erythematosus. The abnormal expression and dysregulation of IL-6 in certain disorders may be a typical feature of this cytokine, making it the first cytokine that may be directly related to pathogenesis. | |
| 2550484 | Tumor necrosis factor causes amplification of arachidonic acid metabolism in response to i | 1989 Oct | Tumor necrosis factor stimulated prostaglandin E2 synthesis in Swiss 3T3 fibroblasts. Interleukin 1 also stimulated prostaglandin synthesis. Simultaneous addition of tumor necrosis factor and interleukin 1 synergistically stimulated prostaglandin synthesis, even when both growth factors were added at what would be supramaximal concentrations by themselves. Several small peptides and nonpeptides rapidly stimulate prostaglandin synthesis in these cells. Pretreatment with tumor necrosis factor synergistically enhanced prostaglandin synthesis in response to bradykinin, bombesin, thrombin, norepinephrine, and platelet-activating factor. Thus, tumor necrosis factor stimulates prostaglandin synthesis and greatly amplifies prostaglandin synthesis in response to other agonists. This finding may have significance in chronic inflammatory diseases such as rheumatoid arthritis in which several hormones and growth factors may synergistically augment eicosanoid synthesis. | |
| 2682060 | [Evaluation of ceftazidime monotherapy in Pseudomonas aeruginosa bacteremias. Prospective | 1989 Sep 16 | Twenty-six episodes of Pseudomonas aeruginosa bacteremia treated with intravenous ceftazidime, 4-6 g/day were evaluated. Treatment was begun within the first 24 hours after the isolation of the microorganism and was maintained for 10-12 days. In two patients with neutropenia amikacin was added during the initial 48-72 hours until the susceptibility to ceftazidime was known. All isolates were sensitive to ceftazidime. The most common underlying diseases were neoplasia (12), diabetes with stroke (4), neurosurgical and vascular procedures (4), rheumatoid arthritis (2), burns (2), cor pulmonale (1), and hypertension (1). The origins of bacteremia were urinary (12), pulmonary (9), and unknown (5). The infection was hospital-acquired in 77% and community-acquired in 23%. A critical clinical status and the presence of complications were significantly (p less than 0.01) associated with an increased mortality rate. Clinical outcome was good in 18/26 (70%), with a 30% mortality rate. The microbiological evolution showed 14 eradications, 6 persistences, 3 relapses and 3 colonizations. Resistance did not develop during therapy. Ceftazidime may be a good alternative therapy for these severe infections, although wider comparative studies are required for a better evaluation. | |
| 2738687 | Radiopharmaceuticals for radiation synovectomy: evaluation of two yttrium-90 particulate a | 1989 Jun | Radiation synovectomy, a noninvasive therapeutic alternative to surgical synovectomy, has not gained widespread acceptance in the United States because of the lack of a suitable radiopharmaceutical. Two new radioactive particles, [90Y]Ca oxalate and [90Y]ferric hydroxide macroaggregates (FHMA), were developed in our laboratory and evaluated for size, stability, and joint leakage. More than 90% of the [90Y]Ca oxalate particles were in the optimal size range of 1-10 microns, and the unbound activity in serum and synovial fluid was 3.7% to 5.0%. Following injection in rabbit knees, leakage of [90Y]Ca oxalate was 5 +/- 2%, with localization primarily in the bone and virtually no uptake by the lymph nodes or liver. Yttrium-90 FHMA particles were larger (95% greater than 10 microns), and at least on a microscopic level, appeared to distribute homogeneously over the articular surface. Leakage of [90Y]FHMA was initially less but eventually slightly exceeded that of [90Y]Ca oxalate. Nevertheless, both radiopharmaceuticals can provide a satisfactory therapeutic dose to the knee with less than half the leakage and a marked reduction in absorbed dose to nontarget tissues compared to previously tested agents. Ease of preparation, physical characteristics of the 90Y beta ray, and apparent lack of substantial leakage from the joint make these agents extremely attractive for clinical evaluation in rheumatoid arthritis patients who are unresponsive to medical therapy. | |
| 2745573 | Antibodies to hnRNP core protein A1 in connective tissue diseases. | 1989 May | We investigated the specificity of circulating autoantibodies to a heterogeneous nuclear ribonuclear protein A1 (hnRNP A1), obtained by recombinant DNA technique, in different rheumatic diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), scleroderma, primary Sjogren's syndrome (SS), idiopathic Raynaud (IR), mixed connective tissue disease (MCTD), and healthy donors. All sera were tested by ELISA on hnRNP A1 protein. Positive values were obtained in 22% SLE, 19% scleroderma, 10% IR, 40% (2/5) MCTD, 5% SS, and 50% RA patients. The majority of patients reacted with the aminoterminal part (UP1) of hnRNP A1; however, some RA patients reacted also with the carboxy-terminal part that shows partial homology with keratin. Therefore, hnRNP A1 (UP1) can be considered a target of antinuclear autoimmunity in various rheumatic disorders. | |
| 2626678 | Potential influences of ketoprofen on human healthy and osteoarthritic cartilage in vitro. | 1989 | Ketoprofen (Orudis, Rhône-Poulenc) is an anti-inflammatory drug with analgesic properties that is used in diseases such as rheumatoid arthritis and osteoarthritis (OA). It is therefore of interest to know whether ketoprofen has a direct influence on cartilage metabolism. We studied the effects of ketoprofen in therapeutic concentrations, on proteoglycan (PG) turnover in explants of human cartilage. The cartilage specimens were divided into three groups: healthy young (less than or equal to 3 yrs) n = 8, healthy old (mean 56 yrs) n = 13 and OA cartilage (greater than or equal to 65 yrs) n = 15. The rate of PG synthesis at day 4 of the culture was measured by the uptake of 35S sulphate. Cartilage PG content and PG release into the medium were determined over 8 days of culture. Ketoprofen stimulated the rate of PG synthesis of young cartilage, but not of old cartilage. In OA cartilage both stimulation and suppression occurred. Ketoprofen had no influence on cartilage PG content and PG release of healthy or OA cartilage during the 8 days of culture. The cartilage was examined histologically, and graded for severity of OA. There was no relation between the severity of OA and the effect of ketoprofen. | |
| 3259125 | The synovial membrane in osteoarthritis: a histological study including the characterisati | 1988 Apr | Inflammatory infiltration of the synovial membrane has been described in a proportion of cases of osteoarthritis (OA). Using conventional histology, lymphoid follicles, diffuse fibrosis, and perivascular fibrosis were shown to be present to a significantly greater extent and in more synovial membranes in osteoarthritis than in those cases where there was a mechanical or traumatic background to the joint disease. Calcium pyrophosphate dihydrate crystals (five patients) and detritus fragments of bone and cartilage (seven patients) were present in small numbers of the total cases of OA (38) studied. Neither of these features was related to the presence of an inflammatory infiltrate. Examination of 20 osteoarthritic synovial membranes using monoclonal antibodies showed the presence of lymphoid follicles containing T helper and T suppressor lymphocytes, B lymphocytes, and macrophages expressing HLA-DR in five cases. The T helper:suppressor ratio varied between 1:1 and 2.5:1 in these follicles. In addition, half of the OA samples, including these five cases, showed the presence of a diffuse cellular infiltrate containing T and B lymphocytes and macrophages, which were HLA-DR positive. Granulocytes were present in this diffuse infiltrate in those cases containing lymphoid follicles. The results confirm the presence of an inflammatory form of osteoarthritis but also show that the proportions of lymphoid cells are not the same as those considered to be typical of rheumatoid arthritis. | |
| 3307298 | The prevalence of renal amyloidosis of the AA-type in a series of 1,158 consecutive autops | 1987 Sep | To determine the prevalence of renal amyloidosis of the AA-type in a defined population, formalin-fixed specimens from the kidneys of all the cases autopsied in 1983 at The General Hospital of Malmö, Sweden, were investigated using immunohistochemical techniques. Amyloid deposits of protein AA were found in 10 of 1,158 investigated cases and the calculated prevalence was 0.86 per cent. The mean age at death of the individuals with the AA-type of amyloidosis was 79 years. Six of the cases with amyloidosis had rheumatoid arthritis. The avidin-biotin-peroxidase complex technique was found to be superior to the immunofluorescence method and a high sensitivity and specificity was achieved when sequence-specific antibodies against a synthetized nonapeptide corresponding to a hydrophilic segment of the polypeptide chain of protein AA were used in the assay. Nine cases with other types of amyloid deposits in the kidneys were also detected. None of these cases showed any AA immunoreactivity but all of them demonstrated Congophilic deposits which were immunohistochemically stained by antibodies against the amyloid P-component. The prevalence of renal amyloidosis comprising all types of amyloid protein deposits was 1.64 per cent. | |
| 3725418 | The use of 125I labelled staphylococcal protein A in the diagnosis of autoimmune thrombocy | 1986 Jan | Platelet-associated immunoglobulin (IgG) has been measured directly on platelets from normal and thrombocytopenic subjects by a modified radioactive Coombs technique. Platelet-associated IgG was detected using 125I-staphylococcal protein A after which platelets were separated from unbound 125I-protein A by centrifugation through oil. Elevated values of platelet-associated IgG were observed in 17 of 19 patients with autoimmune thrombocytopenic purpura. All patients with thrombocytopenia associated with systemic lupus erythematosus or rheumatoid arthritis showed elevated platelet-associated IgG, while normal values were found in diverse thrombocytopenias which were non-immunological in origin. Measurement of anti-platelet antibody levels by an indirect test was less reliable in diagnosing autoimmune thrombocytopenic purpura, since only 7 of the 19 patients gave elevated values. However, the indirect test was reliable in the diagnosis of quinine-dependent immune thrombocytopenia; all 6 patients with suspected quinine purpura gave strongly positive indirect tests when 1 mM quinine was added to the patient's plasma. The use of 125I-protein A to detect platelet-associated IgG provides a rapid and simple technique for the reliable diagnosis of immune thrombocytopenia. | |
| 1802631 | Epidemiology of abnormal liver function tests in general practice in a defined population | 1991 Oct | It is common for general practitioners (GPs) to refer patients suspected of impaired liver function for laboratory tests (alkaline phosphatase, lactate dehydrogenase, bilirubin, prothrombin, aspartate aminotransferase). In a prospective multipractice study over a six-month period, including 30 GPs, 55 patients were recorded as having, for the first time, a high level of alkaline phosphatase (AP) as an isolated finding, 14 with an increase of aspartate aminotransferase (ASAT), eight with an increase of both AP and ASAT, three with an increase of ASAT, AP, and bilirubin, two with an isolated increase of lactate dehydrogenase (LDH), one with an increase of ASAT, AP, and bilirubin, combined with a low prothrombin (PP), and, finally, one patient with a low prothrombin in isolation. In most cases the tests were requested because of unspecific symptoms. The most common causes of abnormal test results were neoplasms, alcoholic liver disease, and heart failure. Thirty patients were referred to hospital for further investigations. During the same study period, 50 patients with known abnormal liver function tests were recorded, and the most common causes of these abnormalities were neoplasms, rheumatoid arthritis, and alcoholic liver disease. |