Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 6369943 | C-reactive protein in pediatrics. | 1983 | CRP levels have been found to be helpful in differential diagnosis and in following the clinical course and response to treatment of various disorders. Of particular interest is their value in the diagnosis of serious bacterial infections in neonates, such as meningitis, septicemia, and osteomyelitis. While no individual has been reported to be deficient in CRP, it is possible that abnormalities of CRP synthesis and function will be found. As increasing knowledge of the role of CRP accumulates, it is conceivable that CRP may acquire some therapeutic value. Increasing availability of rapid quantitative methods for CRP is likely to result in greater clinical usefulness. | |
| 1154031 | Clinical significance of gastrin radioimmunoassay. | 1975 Jul | Serum gastrin radioimmunoassay (RIA) is a sensitive and specific method suitable for measurement of circulating concentrations of this peptide hormone, which is a major regulator of gastric acid secretion. When performed under optimal conditions this RIA permits measurement of low and normal serum gastrin levels and changes that occur after physiologic stimulation. Hypergastrinemia may be secondary to atrophy of the acid-secreting gastric mucosa. This form of pypergastrinemia is appropriate and leads to no seriousequences. Hypergastrinemia associated with gastric acid hypersecretion is inappropriate. The major cause is a gastrinsecreting tumor (gastrinoma) that produces the clinical picture of the Aollinger-Ellison syndrome. The differential diagnosis of inappropraite hypergastrinemia includes antral G-cell hyperplasia and ISOLATED RETAINED ANTRUM. Accurate diagnosis of these conditions may be aided by ancillary studies including feeding, secretin, and calcium stimulation tests. Distinction among these conditions is important in planning appropriate surgical tratment. | |
| 432549 | The relationship between marrow iron stores, plasma ferritin concentrations and iron absor | 1979 Feb | The percentage absorption from a 3 mg dose of ferrous iron was measured in 50 subjects with iron stores that varied over a wide range. Iron status was assessed by a number of measurements, including the haemoglobin concentration, the plasma iron concentration, the total iron-binding capacity, the plasma ferritin concentration and the concentration of non-haem iron in the bone marrow. There were good inverse correlations between the log percentage iron absorption and both the log marrow non-haem iron concentration (r -0.94; P less than 0.001) and the log plasma ferritin concentration (r -0.78; P less than 0.001). In addition, there was a positive ferritin concentration (r +0.84; P less than 0.001). These results suggest that reticuloendothelial iron stores represent an important determinant of iron absorption and that their size can be guaged from the plasma ferritin concentration. | |
| 6328909 | Mechanisms of mediator release from neutrophils. | 1984 | The encounter of neutrophils with immune complexes and complement components - in the bulk phase or on a surface - leads to their secretion of lysosomal hydrolases, especially neutral proteases, which provoke tissue injury. Secretion of lysosomal enzymes and generation of reactive oxygen species (e.g., O2-. generation are stimulus-specific and can be dissected to establish cause and effect relationships by means of: a) kinetic analysis, b) variations in the stimulus, and c) use of impermeant reagents to block discrete responses. Neutrophils also generate products of 11-cyclooxygenase (e.g., PGE2, TxA2) and of the 5- and 15-lipoxygenases (mono-, di-, and tri-HETEs, LTB4, and their isomers). But the cyclooxygenase products (save TxA2) are not phlogistic by themselves: they inhibit the functions of neutrophils, platelets, macrophages, and mast cells. The most potent pro-inflammatory agent yet identified as a product of arachidonate is LTB4. LTB4 is a potent Ca ionophore, constricts airways, is a potent chemoattractant, and induces local inflammation. | |
| 6293513 | Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophil | 1982 Dec | The ability of sera from patients with systemic lupus erythematosus (SLE) and Felty's syndrome to induce increased adhesiveness of normal human neutrophils (PMN) was investigated. PMN from normal healthy donors were incubated in sera from 19 patients with active SLE, 12 with inactive SLE, 20 with Felty's, 24 with rheumatoid arthritis, and 34 normal persons. After incubation, the degree of adherence of the PMN to human endothelial cells in culture, their aggregation, and superoxide (O2-) generation were determined. Sera from patients with both active SLE and Felty's syndrome induced significantly increased PMN adherence to endothelial cells and PMN aggregation in vitro, compared with normal sera. This increased adherence to endothelial cells was maintained after heat treatment (56 degrees C for 30 minutes) of the sera. In O2- generation experiments, sera from patients with active SLE induced significantly increased O2- release from normal PMN using both fresh and heat-treated sera. Sera from Felty's patients demonstrated the same effect with heat-treated sera but not ith fresh sera. When sera from patients with active SLE and Felty's syndrome were used, all three parameters correlated significantly with each other in individual patients. In contrast, sera from the 12 patients with inactive SLE and 24 rheumatoid arthritis patients without Felty's failed to induce significant differences in the three parameters studied when compared with 34 normal controls. Fractionation of 3 SLE sera and 1 Felty's serum on Sephadex G-200 demonstrated that the adherence enhancing factor was present in both IgG and IgG-excluded fractions. The observed increased adhesiveness of PMN induced by SLE and Felty's sera may, at least in part, contribute to the neutropenia which is common in these diseases. Increased O2- release associated with PMN adherence may contribute to endothelial cell damage and vascular injury, which is also a common manifestation of these diseases. | |
| 6366034 | Problems of antiarthritic therapy in the elderly. | 1984 Mar | Rheumatic diseases are prevalent in the elderly population, resulting in high morbidity caused mainly by lack of mobility. Consequently, the use of antirheumatic drugs in older persons is extensive. This review outlines some of the hazards encountered in the use of antirheumatic drugs in the elderly. Analgesics such as propoxyphene and acetaminophen are useful adjuncts to the treatment of arthritic pain, but propoxyphene has been associated with respiratory depression, and renal clearance of acetaminophen is reduced in elderly subjects. Salicylates may cause deafness, and like the other nonsteroidal anti-inflammatory drugs, may cause salt and water retention resulting in congestive cardiac failure. Phenylbutazone should not be used because of the risk of blood dyscrasia, and indomethacin has been reported as interfering with the antihypertensive effect of beta-blockers. Chloroquine levels may be raised in patients with impaired renal function, and there is increased risk of retinal damage with the drug in elderly subjects. Injectable gold compounds and penicillamine are not contraindicated in the elderly, because they are just as efficacious as in younger persons for the treatment of rheumatoid arthritis. Toxicity due to gold compound is not increased in the elderly, but skin rashes and abnormalities of taste do occur more commonly in elderly patients treated with penicillamine. Corticosteroids do not affect disease progression and therefore should be used only in acute severe disease for short periods of time. As in the younger population, treatment of gout in the elderly is dependent on renal function.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2995229 | Polymorphonuclear leukocyte-mediated cell and tissue injury: oxygen metabolites and their | 1985 Oct | Reactive oxygen metabolic products derived from an activated NADPH oxidase present in the cell membrane of PMNs and mononuclear phagocytic cells play a critical role in the host's defense against bacterial infection. Recent studies have also demonstrated the ability of these toxic products to initiate eukaryotic cell injury and promote the development of the acute inflammatory responses. Experimental studies suggest that neutrophil-derived oxygen metabolites contribute to the development of the tissue injury associated with a variety of disease states, including emphysema, myocardial infarction, adult respiratory distress syndrome, immune complex-mediated vasculitis, and rheumatoid arthritis. Future studies to define further the mechanisms by which reactive oxygen-derived metabolic products mediate tissue injury will provide insight into the development of new therapeutic strategies for the modulation of disease states that are mediated by the recruitment and activation of PMNs. | |
| 1106038 | [Clinical study on a new acetylsalicylic acid/paracetamol preparation with gastric acid re | 1975 Sep | The authors describe a simple non-crossover-blind test for the evaluation of subjective indices. A table for recording pains during the 14 days' study is described. The patient's satisfaction with the treatment and the number of days until withdrawal from the trial are recorded. The statistical procedure takes into consideration differences between the treatment groups and makes possible a valuable comparison with drugs tested in other clinical trials. The three dose schedules of antirheumatic treatment were tested on 122 patients and the results compared with those of 342 patients treated with the 6 other antirheumatic drugs (enteric-coated aspirin, paracetamol, indomethacin, flurbiprofen, mefenamic acid, and prednisolone) and those of 41 patients who received placebos. The results show that Safapryn (3,6 g aspirin + 3.0 g paracetamol daily) compared with 3.9 g enteric coated aspirin does not offer any advantage in its analgesic effect, although it gives rise to fewer side effects. Phenylbutazone (3000 mg) was almost as effective as 15 mg prednisolone daily. Between the effects of this dosage of phenylbutazone and other non-steroidal antirheumatic drugs, however, no significant difference could be detected. 50 mg phenylbutazone daily and placebo treatment could not be distinguished. The authors thank the Arthritis and Rheumatism Council for Research in Great Britain for its financial support. One of the authors (PL) was a Merck, Sharp, and Dohme Research Fellow and another one (PMB) received a Robins research scholarship. | |
| 3913771 | Drug interactions with methotrexate. | 1985 Dec | General mechanisms of drug interactions are reviewed, as well as the effects of various drugs on the absorption, distribution, protein binding, eliminations and cellular transport of methotrexate. Published studies demonstrate that prior or concomitant administration of other drugs can alter the efficacy and toxicity of methotrexate. Nonabsorbable antibiotics can decrease methotrexate absorption. Nephrotoxic drugs can decrease methotrexate renal clearance. Salicylates and probenecid may decrease the plasma protein binding and renal tubular secretion of methotrexate. However, the clinical significance of many of these drug interactions is not known or has not been substantiated by extensive clinical observations. | |
| 6431807 | Use of ibuprofen in unusual circumstances. | 1984 Jul 13 | The clinical pharmacology of ibuprofen (Motrin, Upjohn) in relation to the pathophysiologic aspects of various diseases is explained. An understanding of prostaglandin's numerous effects can help the clinician to expand the use of ibuprofen (as in Barttern's syndrome) and to exercise caution as warranted, as when treating patients with renal disease. Knowledge of ibuprofen's clinical pharmacology may also enable practitioners to prescribe the drug rationally in situations not well represented in the literature, as in the elderly or in individuals with bleeding diatheses or severe liver disease. The use of ibuprofen in multiple-drug therapy with aspirin, warfarin, phenytoin, digoxin, or lithium is explored. Perusal of the literature enables the clinician to gain an awareness of patient subpopulations warranting careful use of medication, including the elderly or individuals with systemic lupus erythematosus, mixed connective tissue disease, or aspirin-induced asthma. | |
| 4020137 | Disease-associated loss of erythrocyte complement receptors (CR1, C3b receptors) in patien | 1985 Sep | Although surface membrane density of complement receptor type one (CR1) on erythrocytes (E) is probably an inherited trait among normal individuals, recent evidence from our laboratories suggests that the reduced number of CR1 per E observed in patients with systemic lupus erythematosus (SLE) results from acquired as well as genetic factors. In the present investigation, the number of CR1 per E was quantitated with 125I-monoclonal anti-CR1 and was found to vary inversely with disease activity in patients with SLE who were followed serially for as long as 14 mo. Although evidence for E surface-bound immune complexes or fixed C3b/iC3b was not obtained, periods of disease activity and low amounts of CR1 per E correlated with the presence of 100 to 800 molecules per E of fixed C3dg fragments (less than 100 C3dg per E in normal subjects). Reduced CR1 and excess fixed C3dg on E also were observed in patients with other disorders associated with complement activation, including chronic cold agglutinin disease, autoimmune hemolytic anemia, paroxysmal nocturnal hemoglobinuria (PNH), Sjögren's syndrome, and mycoplasma pneumonia. A significant negative correlation (r = -0.498) between CR1/E and fixed C3dg/E was demonstrable in 255 individual assays evaluated by regression analysis. CR1 decreased and fixed C3dg increased during active disease; the converse was obtained during remission. In patients with active SLE, both serum complement activity and E CR1 decreased, whereas fixed C3dg fragments increased. By piecewise linear regression analysis, the appearance of 100 to 400 C3dg molecules on patients' E corresponded to a 27 to 60%, reduction in the number of CR1 per E (p less than 0.0002), confirming that fixation of C3 to E was correlated with a loss of CR1. In patients with PNH, low values for CR1 were observed on moderately complement-sensitive PNH type II E in association with increased fixed C3 fragments; however, the markedly complement-sensitive PNH type III E had essentially normal amounts of CR1 and bore little fixed C3. The addition of soluble DNA/anti-DNA immune complexes to normal blood generated levels of fixed C3dg fragments on E comparable to those observed on E from patients with SLE. Kinetic experiments indicated that C3b was fixed to E during the process of immune complex binding and release from E CR1, and that this fixed C3b was subsequently degraded rapidly to fixed iC3b and more slowly to fixed C3dg without the loss of CR1 that occurs in vivo.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 6426043 | Comparison of the kinetics of parenteral and oral gold. | 1983 | The intramuscular (gold sodium thiomalate and aurothioglucose) and the orally (auranofin) administered gold compounds exhibit contrasting patterns of absorption, excretion and body tissue and fluid levels. The parenteral compounds are fully absorbed after injection but negligibly absorbed orally. Approximately 25% of the gold in auranofin is orally absorbed. Serum gold levels peak several hours after injection during conventional weekly treatment, attaining concentrations of 600-800 micrograms/dl, and then decline gradually, reaching 300-350 micrograms/dl before the next injection. Whole blood gold levels with auranofin vary from 10 to 90 micrograms/dl with doses of 1-9 mg/day. Blood gold levels plateau after 6-8 weeks with the injectable compounds and after 12 weeks with oral gold, reflecting the shorter blood half-life of gold sodium thiomalate (5.5 days) than of auranofin (17-26 days). A larger fraction of gold is within or attached to circulating blood cells, especially erythrocytes, with auranofin than with injectable gold. Fourty percent of the administered dose is excreted during injectable chrysotherapy, and 75-100% is recovered in excreta with auranofin. Parenteral gold is excreted primarily in urine (70%) while auranofin gold is recovered primarily in faeces (95%). Approximately 43% of intravenous radiolabelled gold sodium thiomalate is retained in the body at 60 days and 30% at 180 days; only 15% of radiolabelled auranofin remains at 10 days and less than 1% at 180 days. During injectable therapy, the total body burden of gold rises steadily; preliminary studies suggest minimal tissue accumulation with auranofin. | |
| 6978220 | Radioimmunoassay profile of antiglobulins in connective tissue diseases: elevated level of | 1981 Dec | A microplate radioimmunoassay for IgG, IgA and IgM antiglobulins reactive with rabbit IgG was performed on sera from 69 patients with various connective tissue diseases. IgM antiglobulins were detected in rheumatoid arthritis, systemic sicca syndrome and some patients with systemic vasculitis. IgA antiglobulins were found in seven of 10 patients with systemic sicca syndrome and only five of 59 patients with other connective tissue diseases. There was no correlation between the levels of IgM and IgA antiglobulins in the systemic sicca syndrome or rheumatoid arthritis (r = -0.21 and 0.2 respectively). IgG antiglobulins were not detected in any serum which lacked IgM or IgA antiglobulins. IgG isolated by DEAE columns showed antiglobulin activity in six of 15 rheumatoid arthritis and two of 10 systemic sicca syndrome sera tested. Antiglobulin analysis of sera fractionated by sucrose density ultracentrifugation at neutral and acid pH enabled the size of each class of antiglobulin to be determined. In certain sera, antiglobulin activity extended into the denser region of the gradient at pH 7.2 suggesting that the antiglobulins were complexed. | |
| 6105169 | Necrotizing vasculitis. | 1980 Jul | Necrotizing vasculitis is a term used to describe vessel wall necrosis due to neutrophil infiltration. Current evidence strongly suggests that these cells are responding to elaboration of chemotactic factors of the complement cascade released at the site of deposition of immune complexes in the vessel wall. The antibody is usually IgG or IgM (and rarely IgA), but the only antigens identified with even a minimum certainty are the streptococcal M protein, the hepatitis B surface antigen, and Mycobacterium tuberculosis. Vessels may be involved, leading to specific signs or symptoms, in a wide range of organs, but with those of the skin, kidney, joints, and gastrointestinal tract leading the list. Why vessels of different sizes or location become involved in individual patients is unknown. Therapy with nontoxic drugs, such as antihistamines or salicylates, is indicated when the disease is mild, but vital organ involvement may necessitate therapy with systemic corticosteroids and/or cyclophosphamide. | |
| 1081878 | Some biological properties of flurbiprofen, an anti-inflammatory, analgesic and antipyreti | 1975 Nov | 2-(2-Fluoro-4-biphenyl)propionic acid (flurbiprofen) possesses peripheral analgesic, anti-inflammatory and antipyretic properties. It does not possess glucocorticoid or adrenocortical-stimulating properties. It is a highly potent agent which in acute pharmacological test systems produced a significant pharmacological effect in single oral doses varying from 0.04 to 0.47 mg/kg. The peak plasma concentrations attained after these doses were generally of the order of 1 to 3 mug/ml. Doses of 0.33 mg/kg/day, which gave peak plasma concentrations of 0.6 mug/ml, produced a significant inhibition of rat adjuvant arthritis, both developing and established. The very shallow dose-response curves for flurbiprofen compared with acetylsalicylic acid, especially in the mouse and the rat test systems, are not due to an unreliable or abnormal absorption, which suggests that in these species the mode of action of flurbiprofen is not identical with that of acetylsalicylic acid. | |
| 1146663 | Platelet 5-hydroxy-tryptamine in thrombotic and non-thrombotic diseases. | 1975 May | It is generally accepted that platelets from the main constituent of a thrombus. Experimental work has shown that 5-hydroxy-tryptamine (5 HT) in a concentration of 0.06 mg/ml produces clumping of the platelets. In view of this it was decided to estimate platelet 5 HT in thrombotic and non-thrombotic diseases. Thirty-five patients were investigated. Estimations of 5 HT were made on washed platelets rather than platelet-rich plasma which has been used in previous studies. Three groups were recognized on the basis of platelet 5 HT values. The first group consisted of five subjects who were clinically asymptomatic at the time of investigation but died 24 to 48 hours later and were shown at autopsy to have deep-vein thrombosis and pulmonary embolism; they had the highest level of platelet 5 HT. The second group comprised eight patients with cerebral thrombosis whose platelet 5 HT ranged between 1529 and 2183 ng/10-9. There were 22 subjects in the third group (11 apparently normal and 11 with different pathologies). Their platelet 5 HT ranged from 611 to 877 ng/10-9 and did not vary in the different pathological conditions studied. Since the highest level of platelet 5 HT was observed in patients prior to the formation or embolization of a thrombus, it is suggested that this may have some role in initiating thrombus formation. | |
| 3875464 | Lymphocytotoxic antibodies in primary biliary cirrhosis. | 1985 Sep | Sera of 30 patients with primary biliary cirrhosis (PBC) and 72 normal subjects matched for age and sex were examined for the presence of lymphocytotoxic antibodies (LCAs) against B and T cells at 4 degrees C and 37 degrees C. Patients were prospectively screened for: Sjögren's syndrome, scleroderma, Hashimoto's thyroiditis, and rheumatoid arthritis, in which LCAs have been described. Seventeen patients with PBC (56.6%) had LCAs against B cells as compared with only 11 of the 72 normal subjects (P less than 0.001). Five PBC patients (16.6%) also reacted against T cells as compared with none in control group (P less than 0.01). Clinical and biochemical features and the histological stage of PBC were similar in patients with and without LCA. Sjögren's syndrome was present in 13 patients--two with scleroderma and another with Hashimoto's thyroiditis. No patient had rheumatoid arthritis. The prevalence of LCAs was similar in PBC patients with or without autoimmune associated disease (54% vs 59%). We conclude that in PBC a high incidence of LCA is unrelated to the presence of an associated disease. LCA in PBC might be a nonspecific marker of an immune disorder. | |
| 1092714 | Studies with human leukocyte lysosomes. Evidence for antilysosome antibodies in lupus eryt | 1975 Feb | Human lysosomes were isolated from normal peripheral blood leukoyctes and characterized by electron microscopy, enzyme analysis, and assays for DNA and RNA. Stored sera from 37 unselected patients with systemic lupus erythematosus (SLE), including active and inactive, treated and untreated cases, were tested in complement fixation (CF) reactions with these lysosome preparations. 23 SLE sera exhibited positive CR reactions, as did sera from two patients with "lupoid" hepatitis. The seven SLE sera with strongest CF reactivity also demonstrated gel precipitin reactions with lysosomes. Neither CF nor precipitin reactions with lysosomes were observed with normal sera or with sera of patients with drug-induced lupus syndrome, rheumatoid arthritis (RA), polymyositis, or autoimmune hemolytic anemia. By several criteria the antilysosome CF and precipitin reactions of SLE sera cound not be attributed to antibody to DNA, RNA, or other intracellular organelles. The lysosomal component reactive with SLE sera in CF assays was sedimentable at high speed and is presumably membrane associated. The CF activity of two representative SLE sera was associated with IgG globulins by Sephadex filtration. A search for lysosomal antigen in SLE and related disorders was also made. By employing rabbit antiserum to human lysosomes in immunodiffusion, a soluble lysosomal component, apparently distinct from the sedimentable (membrane-associated) antigen described above, was identified in serum, synovial fluid, or pleural fluid from patients with SLE, RA, ankylosing spondylitis, and leukemoid reaction. An antigenically identical soluble component reactive with the rabbit antiserum could be released in vitro from intact lysosomes by repeated freeze-thaw cycles.. | |
| 3921313 | The computed tomographic findings in benign diseases of the vertebral column. | 1985 | Computed tomography (CT) has revolutionized the diagnosis of diseases affecting the vertebral column. CT effectively demonstrates the bony vertebral column with its intervertebral articulations, its soft tissue contents, and the surrounding paravertebral soft tissues. The vertebral column may be the site of involvement of a wide variety of benign diseases. These diseases may be congenital or acquired and may arise from within the spinal canal, from the vertebrae themselves, or from the paravertebral soft tissues. These lesions may be unsuspected clinically and may be detected incidentally in patients undergoing CT of the spine for nonspecific complaints. The axial projection is extremely useful in displaying spinal anatomy and pathology and, combined with sagittal and coronal reformation, provides diagnostic information not possible from any other radiological modality. More invasive radiological procedures, such as myelography, may in many cases be obviated, especially if shorter segments of the vertebral column are to be surveyed. The CT findings in many cases are sufficiently characteristic to enable a specific diagnosis to be made. | |
| 6812344 | Influence of nandrolondecanoate on the pituitary-gonadal axis in males. | 1982 Sep | Different anabolic steroids can exercise different effects on the pituitary-gonadal axis in males. During a pilot study regarding the possible beneficial effect of the anabolic steroid nandrolondecanoate (ND) on bone metabolism in patients with rheumatoid arthritis additional endocrinological parameters were studies. A significant decrease was found in the serum levels of testosterone, androstenedione and FSH and the ratio of testosterone/oestradiol. There was a significant increase in the serum levels of oestrone. The levels of oestradiol, SHBG, LH and cortisol remained unchanged. An inhibitory effect of ND on testicular testosterone secretion is assumed. The decrease in androstenedione levels is explained by the diminished testosterone secretion. The rise in oestrone levels is explained by peripheral aromatizing of ND to oestrogens. The presented findings are in accordance with the hypothesis that sex steroids can act directly on the pituitary resulting in selective FSH and LH secretion. The possible role of the ratio testosterone/oestradiol in controlling gonadotrophin output is discussed. |