Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 950647 | Cycloalkanoindoles. 1. Syntheses and antiinflammatory actions of some acidic tetrahydrocar | 1976 Jun | A novel series of acidic cycloalkanoindoles comprising tetrahydrocarbazole-, cyclopentindole-, and cycloheptindole-1-acetic acids has been synthesized via the Fischer indolization between a phenylhydrazine and a 1-alkyl-2-oxocycloalkaneacetic acid ester. These compounds were evaluated, orally, for their capacities to decrease estabished adjuvant arthritis in rats. The most active compound of the series was 1-ethyl-8-n-propyl-1,2,3,4-tetrahydrocarbazole-1-acetic acid (AY-24 873),which had an ED50 of 1.1 +/- 0.2 mg/kg. AY-24 873 was also studied orally in rats for its effect on the acute inflammatory response in the carrageenin paw edema test. It was found that AY-24 873 was about ten times more active against the chromic than against the acute models of inflammation used. | |
| 7016719 | On the significance of C2, C4, and factor B polymorphisms in disease. | 1981 | In this review article, recent evidence is presented that some diseases like insulin-dependent diabetes mellitus, multiple sclerosis, and idiopathic membranous nephropathy, which are primarily associated with HLA-D,DR, are also related to the rare C2, C4, and Factor B alleles. Circumstantial evidence is available that at least some of these rare variants may be functionally deficient. Based on the concept of functionally interacting gene clusters, mutant complement genes may lead to impaired effector mechanisms in virus neutralization or lysis of virus-infected cells. Other mechanisms such as alteration of vascular permeability may be involved in the development of proliferative retinopathy and familial hypertension. In lepromatous lepra, an impaired cell-mediated lysis of M. leprae may be related to the hemolytically inactive C4F1 allelic product. | |
| 1096633 | The development and resolution of glomerular basement membrane changes associated with sub | 1975 May | The morphogenesis of glomerular basement membrane changes associated with subepithelial immune deposits was studied in kidney biopsies from patients with gold-induced membranous glomerulonephoritis. Serial biopsies showed focal accumulations of additional basement membrane material around the deposits, suggesting that the deposited material stimulated the epithelium to increased synthesis. Moreover, the deposits were gradually displaced towards the inner (endothelia) side of the basement membrane during the course of the disease, suggesting that this layer undergoes a slow continuous turnover, with removal at its endothelial aspect. The two processes--increased epithelial synthesis and turnover--are suggested to constitute the basis of a natural healing process resulting in elimination of the deposits and structural restoration of the basement membrane. The epithelial slit membranes were dislocated externally by the deposits or the excessive basement membrane material, indicating that their barrier function is preserved even in this pathologic condition. | |
| 6869408 | Ophthalmologic considerations and testing in patients receiving long-term antimalarial the | 1983 Jul 18 | We do not as yet understand all the mechanisms involved in retinal toxicity. Such risk is lower with hydroxychloroquine than with chloroquine. The risk of true retinopathy rises with duration of therapy. The benefit/risk ratio for hydroxychloroquine is at least equal to or better than that of chloroquine, and when the currently recommended dosages of 400 mg per day of hydroxychloroquine and 250 mg per day of chloroquine are not exceeded, this ratio is medically and ophthalmologically acceptable. The most useful tests to detect retinopathy are ophthalmoscopic and/or photographic observation of the macular area for changes in pigmentation, sensitive central visual field testing, and automated computerized perimeter. These tests can be conducted by the attending physician provided that (1) baseline ophthalmologic studies are done (to exclude pre-existing ocular abnormalities); (2) such studies are conducted every six months thereafter; and (3) the patient with ocular abnormalities is immediately referred to an ophthalmologist for further evaluation, even in the absence of symptoms. | |
| 373084 | A comparative, double-blind study on tolfenamic acid in the treatment of rheumatoid arthri | 1979 | Sixty patients with diagnosed rheumatoid arthritis were treated at random with tolfenamic acid, a new nonsteroid anti-inflammatory analgesic, in a daily dose of 600 mg, or with phenylbutazone 300 mg or acetylsalicylic acid 1,500 mg daily. Both the patients and the physician found that tolfenamic acid had a clearly better effect than phenylbutazone or the low-dose acetylsalicylic acid used as a control. Tolfenamic acid and acetylsalicylic acid were well tolerated. Serious side-effects (leukopenia and thrombocytopenia in one case, hematemesis and melena in another) only occurred in those patients who received phenylbutazone. | |
| 6606219 | An extended C1q-binding assay using lactoperoxidase- and chloramine-T-iodinated C1q. Immed | 1983 Oct | An extension of the C1q-binding assay for the detection of immune-aggregate-mediated and non-immune-aggregate-mediated C1q binding is reported. The assay involves the use of two different C1q preparations, one radioiodinated by means of lactoperoxidase (LPO-125I-C1q) and the other by means of chloramine-T (CT-125I-C1q). The treatment with CT for 20 min at room temperature before iodination for 1 min led to abolishment of the C1q-binding capacities to complexed IgG: approximately 50% of LPO-125I-C1q but only 2% of CT-125I-C1q bound to 80 micrograms/ml of IgG forming part of tetanus toxoid/anti-tetanus toxoid complexes or to 200 micrograms/ml of heat-aggregated human gamma globulin. Similar results were obtained with staphylococcal protein-A-aggregated IgG. CT-treated C1q was haemolytically inactive. In contrast to the results with complexed IgG, CT treatment did not markedly reduce binding capacities of C1q to heparin: approximately 55% of LPO- and CT-125I-C1q were bound by 127 U/ml of commercial heparin in normal human serum. Both C1q preparations bound to a comparable extent to fibronectin, fibrinogen, and various bacterial endotoxins. When the LPO- and CT-125I-C1q-binding patterns obtained on serum samples from patients with systemic lupus erythematosus, rheumatoid arthritis, or essential mixed cryoglobulinaemia were compared with binding patterns observed using laboratory reactants, an immediate detection of non-immune-aggregate-mediated C1q binding became possible. | |
| 6190598 | Immunomodulation by isoprinosine: effects on in vitro immune functions of lymphocytes from | 1983 Apr | Isoprinosine (IPS) is a new anti-viral agent which appears to have immunomodulatory activities which include its ability to enhance the in vitro blastogenic responses of normal lymphocytes to mitogens. The present study compares the effects of IPS on the in vitro immune functions of peripheral blood mononuclear cells (PBMC) from systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients with its effects on PBMC from normal controls. Each mitogen (Con A, PHA or PWM) was used at its optimal concentration with a range of IPS concentrations (0-25 micrograms/ml). PHA-induced blastogenesis by PBMC from all three groups was enhanced by IPS at or above 5 micrograms/ml. The Con A-induced responses of SLE lymphocytes were significantly enhanced over controls by IPS (P less than 0.02 at 5 micrograms/ml) while those of RA lymphocytes were not. IPS had little effect on PWM-induced blastogenesis by RA lymphocytes but did enhance the blastogenic responses of SLE lymphocytes (P less than 0.01 at 5 micrograms/ml). In contrast, the characteristically high immunoglobulin synthesis by SLE lymphocytes was decreased by IPS. The mechanism responsible for these effects is not known but IL-2 production by patient lymphocytes in vitro which was low for both RA (P less than 0.01) and SLE (P less than 0.02) increased significantly (P less than 0.05) when SLE lymphocytes were cultured with IPS. These data identify IPS as an agent for the study of aberrant immune regulation in autoimmune diseases and suggest that it may have potential therapeutic value in SLE. | |
| 377449 | Clinical comparative evaluation of choline magnesium trisalicylate and acetylsalicylic aci | 1979 May | A multicentre double-blind comparison of choline magnesium trisalicylate (CMT) and acetylsalicylic acid (ACSA) compared the two medications for seven weeks in rheumatoid arthritis patients. Investigators measured the number of painful and swollen joints and the duration of morning stiffness, and assessed the overall condition of each patient. Both medications were highly effective in significantly reducing the severity of symptoms flaring after interruption of prior therapy. CMT achieved a greater reduction in the number of swollen joints than did ACSA (P less than 0.05). The incidence of adverse side-effects per patient was significantly less with CMT (P less than 0.05) (ACSA 32.1%; CMT, 16.3%. A larger percentage of ACSA patients (50.8%) reported adverse side-effects than did CMT patients 28.4%) (P less than 0.02). | |
| 4017423 | Effects of age and disease on the pharmacokinetics and pharmacodynamics of sulindac. | 1985 Aug | The disposition and effect on hemostasis of a single 150 mg dose of sulindac was studied in young healthy subjects and in older patients with arthritis. Older patients were restudied after 2 weeks of sulindac, 150 mg b.i.d. The only difference in disposition of the first dose was a reduced plasma sulfone metabolite concentration in the elderly patients with arthritis. Chronic sulindac dosing resulted in accumulation of the drug and its sulfone and sulfide metabolites in plasma to a greater extent than previously reported for young subjects. No differences in renal clearance of sulindac and its sulfone metabolite related to age or chronic drug dosing were observed. No renal excretion of the active sulfide metabolite was detected. Bleeding time in the elderly patients was shorter than in the young healthy subjects before sulindac dosing, but was prolonged in the elderly patients after 2 weeks of dosing to values similar to control data from the young healthy subjects. This change correlated weakly with plasma sulfide metabolite concentrations. Differences in bleeding time were not reflected in changes in platelet aggregation induced by adenosine diphosphate either with respect to age or chronic drug dosing. Our data provide no justification for lowering the recommended dose of sulindac for patients older than 65 years of age. | |
| 7046457 | Antigen handling in antigen-induced arthritis in mice: an autoradiographic and immunofluor | 1982 Jul | Antigen localization after intraarticular antigen injection was studied in immune and nonimmune mice using autoradiographic and immunofluorescence techniques on whole joint sections. After intraarticular injection of radiolabeled methylated bovine serum albumin (125I-mBSA) in immune mice, labeling in the synovium and synovial exudate diminished rapidly, apart from some deposits in fibrinlike material present in the joint cavity. Long-term antigen retention was found in avascular and hypovascular structures lining the joint cavity, albeit not along the whole surface; eg, labeling remained present at the edges of the femoral condyle hyaline cartilage but not at the central weight-bearing region; long-term retention at ligaments was only found at the insertion sites. Immunofluorescence data in immune animals showed antigen retention together with the presence of immunoglobulins and complement, indicating that antigen is retained at least in part in the form of immune complexes. Nonimmune mice showed even higher long-term antigen retention than immune animals, probably related to physico-chemical properties of the antigen enabling nonimmune binding to articular structures, but also indicating that the presence of joint inflammation in the immune animals enhances antigen clearance. Histologic examination of the ligaments and patellar cartilage of immune mice did reveal that long-term antigen retention was not anatomically related to nearby inflammation or to local tissue damage. The importance of long-term antigen retention for the chronicity of arthritis may lie in the leakage of small amounts of this antigen to joint compartments where it does behave as an inflammatory stimulus; it may further be that it renders the joint a specifically hypersensitive area. | |
| 6114491 | Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients wi | 1981 May | The activity of phospholipase inhibitory protein, lipomodulin, partially purified from rabbit neutrophils, was markedly decreased after treatment with sera from patients with rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis. The decrease of the protein's inhibitory activity on phospholipase A2 paralleled the amount of [35S]methionine-labeled lipomodulin precipitated by the sera. Absorption of patients' sera with anti-human IgM (mu chain) or protein A-agarose, but not with anti-human IgG (gamma chain), decreased their ability to decrease the activity of lipomodulin on phospholipase A2 or to precipitate the radioactive lipomodulin. The IgM fraction of patients' sera could precipitate [35S]methionine-labeled lipomodulin (40,000 daltons) which comigrated with highly purified lipomodulin on gel electrophoresis with sodium dodecyl sulfate. All of these observations suggest that the sera of many patients with rheumatic diseases contain autoantibody against lipomodulin. A monoclonal antibody against lipomodulin was also obtained. Stimulating human fibroblasts with bradykinin in the presence of monoclonal antilipomodulin antibody markedly enhanced arachidonic acid release due to the activation of phospholipase(s) in the intact cells, and this stimulatory effect was blocked by adding purified lipomodulin. These findings suggest that lipomodulin regulates the activity of phospholipase(s) on the cell surface and that autoantibodies against lipomodulin may play a role in certain symptoms of rheumatic diseases, especially by the formation of prostaglandins and other metabolites of arachidonic acid. | |
| 392694 | Radioimmunoassays of human myoglobin in serum and urine. | 1979 Feb | Two solid-phase radioimmunoassays have been developed for the detection of myoglobin in serum and urine. The sensitivity of the methods is 0.1 and 0.5 microgram/l, respectively, with a coefficient of variation of the respective method of 7-8%. The mean serum concentration of myoglobin in ninety-nine healthy blood donors was 44.3 microgram/l +/- 18.0 microgram/l (SD) with a significant difference (P less than 0.001) between men (50.6 +/- 19.8) and women (35.7 +/- 10.4). Serum myoglobin was positively correlated to age (P less than 0.05), body weight (P less than 0.02), serum creatine kinase (P less than 0.001), and serum creatinine (P less than 0.001) to galactose elimination rate. Serum myoglobin levels were not influenced by exhaustive short time dynamic exercise. The mean urinary excretion of myoglobin in twenty-four healthy students was 1.2 microgram/24 h (range 0.1-4 microgram/24 h). Myoglobin excretion was correlated to excretion of beta 2-microglobulin (P less than 0.02) but not to serum levels of myoglobin. No indications of circulating antibodies to myoglobin were obtained when assaying sixty-seven rheumatoid arthritis and thirteen myastenia gravis sera. Presence of other myoglobin binding substances in serum, which would interfere with the assays also seemed unlikely. Determination of myoglobin in serum by sensitive and specific method might be of clinical value in the diagnosis of diseases involving muscle tissues. | |
| 6388973 | An enzyme-linked immunoassay for detection of IgG- and C3-containing circulating immune co | 1983 | We developed a simplified, relatively rapid, inexpensive, antigen-nonspecific, enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG)- and C3-containing circulating immune complexes (CICs), adapted from a solid-phase anti-C3 radioimmunoassay (RIA). Standards (containing purified, heat-aggregated IgG and fresh human serum) or samples were allowed to react with goat F(ab')2 antihuman C3 bound to the matrix of microtiter plates. Then alkaline phosphatase conjugated to goat IgG fraction antihuman IgG was added, followed by p-nitrophenylphosphate, optical densities determined, and concentrations of CICs calculated. We found excellent correlations between serum and plasma CIC levels by either ELISA (r = 0.95, p less than 0.01) or RIA (r = 0.89, p less than 0.01). Furthermore, ELISA quantitation of CICs correlated well with RIA (serum, n = 75, r = 0.64, p less than 0.01; plasma, n = 101, r = 0.56, p less than 0.01). By ELISA we found 32 normal subjects had 38 +/- 12 micrograms CIC/ml in serum and 34 +/- 10 micrograms CIC/ml in plasma. Patients with systemic lupus erythematosus (39% of 27 patients, p less than 0.05) had significantly elevated CIC levels compared with normal (serum, 157 +/- 50 micrograms/ml, p less than 0.01; plasma, 89 +/- 23 micrograms/ml, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 6439564 | Sex hormones in male patients with systemic lupus erythematosus: a comparison with other d | 1983 | There is substantial evidence for alteration of oestrogen metabolism in both males and females with systemic lupus erythematosus (SLE). Low testosterone levels have been described in men with SLE, and it has been suggested that this may be a further predisposing factor to the development of the disease. Serum testosterone, oestradiol, FSH and LH levels were measured on two or more occasions in nine male patients with SLE. Similar estimations were performed on four other groups for comparison: ten male patients with rheumatoid arthritis, six male patients on long-term steroid therapy, eleven male patients with renal failure on long-term haemodialysis and eleven healthy male volunteers. Mean testosterone levels were significantly reduced in all disease groups and there was no significant difference between patients with SLE and those with other chronic disorders. Oestradiol levels were normal in all groups, but there was a trend to elevated mean levels of FSH and LH (p 0.05 for the haemodialysis group). Our results confirm that testosterone levels are low in males with SLE, but suggest that this is an effect of chronic disease, and therefore unlikely to be a pre-existing risk factor for the development of SLE in men. | |
| 6318343 | [Drug concentrations in blood, synovial fluid, synovial membrane, periarticular bone, musc | 1983 Dec 12 | The therapeutic activity of antiinflammatory agents in rheumatic joint disease is related to their presence at the target site of action, i.e. the joints. Tissue concentrations of such agents have been previously determined in patients with rheumatic disorders under long-term treatment with acemetacin and indomethacin (Köhler et al., 1981). The purpose of the present study was to determine concentrations of ketoprofen and acetylsalicylic acid in blood as well as synovial fluid, synovial membrane and periarticular bone and adipose tissue, three hours after administration of a single dose. Drug concentrations found in each of these tissues following a single intramuscular injection were sufficient to ensure therapeutic efficiency. | |
| 539789 | Serum antioxidant activity in normal and abnormal subjects. | 1979 Nov | Serum oxidant activity (AOA) was correlated with the serum caeruloplasmin and serum copper concentration and with the total and available serum iron-binding capacity in 313 normal and abnormal subjects. In all groups except in patients with Wilson's disease (hepatolenticular degeneration) there was a highly significant direct correlation between serum AOA and serum caeruloplasmin concentration. A statistically significant direct correlation between serum AOA and the available iron-binding capacity of serum was found only in normal subjects and in children with thalassemia major and iron overload. There was no correlation between serum AOA and the serum tocopherol concentration in any of the groups studied. | |
| 6220955 | Cellular immune function in rheumatic disease. | 1983 May | Investigation of the cellular immune function in patients with rheumatic diseases is important in elucidating the pathogenesis of the disease processes and in determining the associated abnormalities of recognition and regulation exerted by the immune system. However, because of the lack of specificity and the variations noted from laboratory to laboratory, tests of cellular immune function are, at present, of little value in the laboratory diagnosis of these diseases. The abnormalities found in the rheumatic diseases occur with many autoimmune diseases and other inflammatory states. The common pathway of immune abnormalities appears to be influenced by several factors. They include several genetic loci, possible environmental factors, and immunologic mechanisms, which appear to interact in an intimate way to induce various autoimmune diseases. | |
| 4758660 | Serum carcinoembryonic antigen in clinical disorders. | 1973 Oct | Carcinoembryonic antigen (CEA) levels have been measured in the serum of 490 patients and 93 normal controls using the double antibody radioimmunoassay technique. Levels were elevated in 71 of patients with carcinomata of the gastrointestinal tract and in 42% with other types of malignancy. In patients with non-neoplastic disease of the gastrointestinal tract and liver, elevated levels were found in 14 and 66% respectively. In general the CEA level tends to be higher in cancer patients with haematogenous dissemination. Following complete surgical removal of a tumour, levels fall to normal within 14 days in the majority of patients. Of 33 patients studied during follow up, elevated levels were found in 12, 10 of whom had evidence of recurrence. The significance of these findings and the possible application of CEA assay in clinical practice are discussed. | |
| 418787 | Comparison of gold levels and distribution in guinea pig serum. | 1978 May | Serum levels after oral administration of 30 mg/kg of sodium aurothiomalate (Myocrisin), triethylphosphine gold chloride, or triphenylphosphine gold chloride to guinea pigs indicated that all were orally absorbed. However, the serum gold level of triethylphosphine gold chloride was three to four times that of Myocrisin or triphenylphosphine gold chloride and was comparable with the serum level produced when the same dose of Myocrisin was injected intramuscularly. A comparative time-course study between intramuscular administration of Myocrisin and oral administration of triethylphosphine gold chl;ride indicated that during the first 24 hours after intramuscular injection of Myocrisin, a large fraction of the gold was not protein-bound, whereas all detectable gold in serum after oral administration of triethylphosphine gold chloride was protein-bound. Gold levels in the separated protein fractions indicate that the gamma-globulin level after oral administration of triethylphosphine gold chloride is approximately three times higher after 24 hours than with intramuscular Myocrisin. | |
| 3911867 | Osteoarthritis of the hip. Radiologic findings and etiology. | 1985 | The purpose of the work was to investigate: Whether osteoarthritis of the hip can be divided into radiologic classes by examining the tendency of osteoarthritis of the hips to increase the growth and calcific content of the bone on the one hand and the associated loss of calcium and cartilage and the deformation and destruction of bone on the other. The prevalence of osteoarthritis of the hip in the internal medicinal and surgical outpatients of the University Central Hospital of Oulu, who were radiographed. Whether osteoarthritis of the hip or its different radiologic manifestations correlate with the patient's age, sex, occupation and strenuousity of work, rickets, cancerous diseases, diabetes, rheumatoid arthritis, family history, parity, smoking, obesity, physical activity, corticosteroid and anti-epileptic medication, and previous injuries to the lower extremities causing immobilization. Whether the radiologic findings of osteoarthritis of the hip are associated with typical symptoms. Whether there are correlations between the effects of medication and physiotherapy and the radiologic forms of osteoarthritis of the hip. The study population consisted of two series, of which the first included 401 patients: 167 males and 234 females. The second, or major part comprised 518 patients, of whom 249 were male and 269 female. For all these patients we had radiograms available which permitted reliable assessment of the hip condition. The second series, i.e. the latter group of 518 patients, also filled in a questionnaire which dealt with the etiology and symptoms of the osteoarthritis of the hip as well as the therapies they had received. Whenever possible, the changes of the pelvis and the lumbar spine were also assessed on the basis of the radiograms. On the basis of the radiologic findings, osteoarthritis of the hip was divided into two qualitative classes, hypertrophic and destructive, and a mixed type, and into three grades of severity. Hypertrophic osteoarthritis of the hips accounted for 51% of the cases, destructive for 20% and mixed type for 29%. The percentages for the different severities were 47% for the mild, 16% for the moderately severe and 37% for the severe. A total of 26% of the cases were right-sided, 22% left-sided and 52% bilateral. The mild, bilateral cases of osteoarthritis were mostly hypertrophic, whereas destructive osteoarthritis was clearly more common in the unilateral cases. Hypertrophic osteoarthritis was also more frequent in younger age-groups and destructive in older age-groups. The osteoarthritis of the older patients was more severe.(ABSTRACT TRUNCATED AT 400 WORDS) |