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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3780677 | Suppression of urokinase-type plasminogen activator mRNA levels in human fibrosarcoma cell | 1986 Sep | Suppression of plasminogen activator (PA) activity has been invoked as being part of the general anti-inflammatory action of glucocorticoids. Low concentrations of the synthetic glucocorticoid, dexamethasone (Dex), reduce urokinase-type PA mRNA levels in two cell types, namely a human fibrosarcoma line, HT1080, and synovial fibroblast-like cells isolated from human joints. Conversely, metallothionein IIa (MTIIa) mRNA levels in these cells are raised by Dex. These findings, by suggesting that it is possible to suppress urokinase-type PA activity at the level of gene expression, may have therapeutic implications for diseases such as rheumatoid arthritis where proteases may be contributing to the extensive tissue damage and inflammation. | |
3504709 | Stimulation of bone resorption in cultured mouse calvaria by Lys-bradykinin (kallidin), a | 1986 Sep | Lys-Bradykinin (kallidin) stimulated bone resorption in vitro as assessed by the release of 45Ca and 3H from mouse calvaria radiolabelled in vivo with [45Ca]CaCl2 and [3H]proline, respectively. The stimulatory effect of Lys-bradykinin was reduced by calcitonin, indicating that the bone resorptive effect of Lys-bradykinin was dependent on osteoclastic activity. Different inhibitors of arachidonic acid metabolism, including glucocorticoids, inhibited Lys-bradykinin stimulated mobilization of mineral, implicating the synthesis of prostaglandins as an intermediary step. Lys-Bradykinin enhanced the biosynthesis of PGE2 in osteoblast-like cells isolated from mouse calvaria. In view of these findings and the capacity of mast cells to generate kininogenase activity, resulting in formation of Lys-bradykinin and bradykinin, the role of these cells in the pathogenesis of bone loss in rheumatoid arthritis, mastocytosis and osteoporosis is discussed. | |
3021365 | The effect of N-(2-carboxyphenyl)-4-chloroantranilic acid disodium salt (CCA) on concanava | 1986 Jul | Superoxide anion (O2-), generated and released by mononuclear phagocytes (M phi), plays significant roles in tissue damage accompanying inflammatory and immunological reactions. N-(2-carboxyphenyl)-4-chloroantranilic acid disodium salt (CCA), is a newly synthesized immunomodulator for which therapeutic efficacy in the treatment of rheumatoid arthritis (RA) has been reported. In this investigation, we have examined the effect of CCA on concanavalin A (Con A)-induced O2- release in human M phi. Exposure of M phi to Con A induced a large increase of O2- release. Preincubation of M phi with CCA suppressed O2- release induced by Con A almost to a control level. On the contrary, CCA itself did not have a significant effect on basal O2- release from M phi. These results indicate that the inhibition of O2- release from activated M phi may be an important factor in the anti-inflammatory effects of this drug. | |
1751298 | Imaging of the skeleton and soft tissue in children. | 1991 Dec | Normal metaphyses in infants contain a step-off not to be confused with child abuse. Extension of physeal lucency into the metaphyses can be a sign of healing child-abuse fracture of experimental physeal fracture, as well as deferoxamine overdose. Sonography can reveal costochondral dislocation, the pattern of healing fracture callus, the patellar tendon in jumper's knee, synovium of rheumatoid arthritis, sequestrum in advanced osteomyelitis, the unossified dislocated patella, and, even after 2 years of age, the dislocated femoral head. Further developments concern bone scanning, MR imaging, CT, and plain films of specific trauma, tumor, and infectious, metabolic, and orthopaedic conditions. Ultrasound has been proven useful for radiologist removal of soft tissue foreign bodies, whereas CT can be helpful for osteoid osteoma nidus removal under imaging control. | |
1878841 | Mechanisms of action of intravenous immunoglobulin therapy and potential use in autoimmune | 1991 Sep 15 | It has been almost 10 years since the observations on the efficacy of intravenous immunoglobulin (IVIG) in patients with autoimmune thrombocytopenic purpura. Over the next decade, IVIG was used in other types of autoimmune diseases. Much work has also been done on gaining a better understanding of the mechanism(s) by which IVIG exerts its effects in these autoimmune diseases. This review examines the proposed mechanisms of action of IVIG and establishes a rationale for the use of this type of therapy in systemic lupus erythematosus (SLE) and other autoimmune connective tissue disorders. Currently, only anecdotal reports are available on the treatment of SLE with IVIG. Nevertheless, studies thus far suggest that IVIG may be useful in selected SLE patients with cytopenias and cutaneous vasculitis and may have a steroid-sparing effect in patients with SLE and juvenile rheumatoid arthritis. In SLE patients with renal disease, it should be used cautiously because some patients have worsening of their renal function with IVIG infusions. These preliminary experiences suggest that multicenter controlled trials on the therapeutic use of IVIG in SLE and other connective tissue disorders would be important. | |
2047367 | Recognition of recombinant Toxoplasma gondii antigens by human sera in an ELISA. | 1991 | We developed an enzyme-linked immunosorbent assay (ELISA) that uses one of two recombinant polypeptides, termed H4/GST and H11/GST, as diagnostic antigens for the detection of antibodies to Toxoplasma gondii in human sera. A total of 59 sera from humans with acute toxoplasmosis, 194 sera from patients with chronic toxoplasmosis, and 151 sera from subjects who were not infected with T. gondii were examined. In all, 68% of the sera from humans with acute toxoplasmosis reacted positively with one or both recombinant T. gondii antigens. By contrast, only 14% of those from patients with chronic toxoplasmosis recognized H4/GST or H11/GST. None of the sera from humans who were not infected with T. gondii, including patients with echinococcosis, entamoebosis, toxocarosis, trichinellosis, glandular fever, or rheumatoid arthritis, recognized H4/GST or H11/GST. | |
2698067 | [Symptomatic pericardial effusions in childhood]. | 1989 Dec | We present the clinical data and the management of twelve patients with symptomatic pericardial effusion (PE). The etiology of PE was: Chronic renal failure, viral infection, cardiac surgery, juvenile rheumatoid arthritis and chronic myelocytic leukemia. Four cases were diagnosed as idiophatic. PE in childhood is usually asymptomatic. When symptoms are present they are non-specific and don't help to know the size of the effusion; therefore, it's necessary to practice an echocardiography to demostrate the presence of PE. The hemodynamic findings permit to diferentiate patients with and without cardiac tamponade. The treatment of first choice is aspirin. In patients with cardiac tamponade the treatment should be pericardiocentesis. | |
2534451 | [Detection rate of antibodies against delta virus among HBsAg carriers in a region with mo | 1989 Nov | Radioimmunoassay and enzyme-immunoassay were used to study the detection rates of HBsAg and anti-Delta in blood donors and subjects at high risk of infection with hepatitis B (HB) in the Byelorussian SSR. The republic was found to belong to the region with a moderate prevalence of HB and low prevalence of delta-virus infection. The detection rate of anti-delta antibodies in individual population groups depends on the level of HBsAg carrier state and is closely associated with prolonged treatment in medical institutions. Patients with tuberculosis, rheumatoid arthritis, diabetes mellitus, and cirrhosis of the liver are important reservoirs of HB and delta-virus infection for a region with moderate prevalence of HB virus and low prevalence of delta-virus. Infection with delta-virus is very important in unfavourable outcomes of acute and chronic viral hepatitides in the region. | |
2482400 | Double-marker analysis of B lymphocyte subsets using a combination of immunofluorescence a | 1989 Oct | Double-marker assays were developed for enumerating CD5+ B-cells and CD25+ activated B-cells. To measure CD5+ B-cells, CD19+ (pan B-specific) cells were first isolated from peripheral blood mononuclear cells using anti-Leu12-coated immunomagnetic beads (Dynabeads). Positively selected cells were stained for surface immunoglobulin (sIg) and then incubated with anti-Leu1-coated Dynabeads. Fluorescent cells which also bound Dynabeads could be readily enumerated. The proportion of CD5+ B-cells was found to be significantly elevated in 9 of 20 patients with definite rheumatoid arthritis. B-cells bearing the interleukin-2 receptor (IL-2-R, CD25) were identified in pokeweed mitogen-stimulated PBM by sIg fluorescence and rosetting with anti-Tac-labelled Dynabeads. The kinetics of CD25 expression following activation were found to be different for B- and non-B-cells. | |
2787397 | Arthrographic findings in the temporomandibular joint in patients with rheumatic disease. | 1989 Aug | Hypocycloidal multisection tomography and lower-space arthrotomography with videofluoroscopy were performed on 20 symptomatic temporomandibular joints (TMJs) of 17 patients. All patients (16 women, one man, aged 17 to 38 years) had definite or suspected rheumatoid arthritis (adult or juvenile type), ankylosing spondylitis, or psoriatic arthropathy. Bone abnormalities were found in 14 TMJs, primarily cortical erosion (11 joints), but also condylar flattening (three joints). Irregularity in outline of the contrast material, bone contour-contrast material gaps, evidence of adherent discs and/or small joint compartments indicated synovial hyperplasia/pannus formation in 15 joints. Six of these (four with normal disc position) showed perforation between the joint compartments. In those with normal disc position the perforation seemed to occur in the central portion. Ten of the 15 joints had normal disc position; the remaining five had anterior disc displacement without reduction. One joint showed only disc displacement. Most joints with bone abnormalities (12 of 14) showed arthrographic signs of rheumatic involvement. Such signs were also observed in two of the six joints with no bone abnormalities, indicating the value of arthrography in the early diagnosis of patients with rheumatic disease and TMJ problems. | |
2565212 | The pharmacokinetics of albumin conjugates of D-penicillamine in rats. | 1989 Mar | A protein conjugate that forms during the metabolism of D-penicillamine (D-PEN) in rats is electrophoretically indistinguishable from the (D-PEN-albumin) mixed disulfide that forms during the oxidation of D-PEN in plasma in vitro. Both the conjugate formed in vivo and the mixed disulfide synthesized in vitro are eliminated slowly in rats, with half-lives of 5.33 +/- 0.25 days and 3.48 +/- 0.42 days, respectively. These half-lives approximate or exceed the half-lives of radioiodinated plasma protein in the animals. The stability of the D-PEN-albumin conjugate contrasts with the rapid elimination of D-PEN itself and probably explains delayed elimination of D-PEN-containing disulfides in humans. Stable modification of tissue proteins by D-PEN may also be involved in the mode of action of D-PEN in rheumatoid arthritis. | |
2640480 | [Isolation and characterization of immune complexes associated with malignant tumors and l | 1989 | We are dedicated to the study of circulating immune complexes (CIC) associated with different diseases: malignant tumors, leprosy and rheumatoid arthritis. Immune complexes were evaluated by various methods: 125I-Clq binding assay, 125I-IgG binding test, 125I-bovine conglutinin binding assay and polyethylene glycol precipitation test (3.5% and 2.5%). Techniques for the isolation and splitting of CIC in their components were performed in sera from patients with tumors and with leprosy. These methods consisted in the combination of CIC with protein A followed by elution with different buffers. CIC splitting techniques were first applied on immune complexes formed in vitro (BSA-aBSA, OVA-aOVA). The analysis of CIC fractions was done by SDS-PAGE, immunoelectrophoresis and immunoblotting techniques. Results were as follows: CIC levels correlated with active stages of disease, decreasing during remission so that CIC detection can be useful to evaluate response to treatment. The isolation and splitting of immune complexes into their components resulted in the obtention of immunologically active fractions, especially in sera from patients with gastrointestinal and breast cancer and with leprosy. | |
3240973 | Determination of gold in animal tissue by graphite furnace atomic absorption spectrophotom | 1988 Nov | Historically, compounds that contain gold have been used to treat conditions such as rheumatoid arthritis in humans. However, understanding of the metabolic fate of gold in biological tissues has been limited by lack of sensitive quantitative methods of analysis. We addressed this problem by developing a graphite furnace atomic absorption (GFAA) spectrophotometric method to measure trace amounts of gold. This method was validated on small samples of beef liver, kidney, and bone. The samples were digested in micro-Kjeldahl flasks with a mixture of sulfuric, perchloric, and nitric acids; the residue was treated with aqua regia and extracted into methylisobutyl ketone (MIBK); levels of gold were then measured by GFAA. All the reagents were of an ultra-pure grade and were monitored for gold content. We established that the linear range of quantitation was from 1 to 2500 ppb. Multiple extractions with MIBK were not necessary to recover all the gold, and, in most cases, use of ultra-pure acids was not necessary. A scan of the extracts by inductively coupled argon plasma atomic emission spectrophotometry revealed no appreciable concentration of elements that would be most likely to interfere with the determination of gold. Average recoveries of gold ranged from 102 to 111%, and the overall coefficient of variation was 5.5%. | |
3361575 | (Acyloxy)benzophenones and (acyloxy)-4-pyrones. A new class of inhibitors of human neutrop | 1988 May | A series of 4-(acyloxy)- and 4,4'-bis(acyloxy)benzophenones were synthesized. Some of them, pivalates (trimethylacetates) and isobutyrates in particular, were found to be potent and selective inhibitors of human neutrophil (leukocyte) elastase. A series of 2-[(acyloxy)methyl]-5-(acyloxy)-4-pyrones were synthesized regioselectively from kojic acid. The 4-pyrones bearing a long chain acyl group at the 2-position and either pivaloyloxy or isobutyryloxy at the 5-position were potent and selective inhibitors of the human elastase. A number of analogues and derivatives in both series were synthesized in order to study the structure-activity relationship as summarized in Tables I-VI and in Tables IX and X. The inhibition was selective to human neutrophil elastase. No inhibition of porcine pancreatic elastase or bovine pancreatic chymotrypsin (Tables VII and XI) was observed. The most likely mechanism of inhibition is discussed. The implication of these findings for the treatment of rheumatoid arthritis and emphysema is outlined. | |
3372096 | Computed tomography with multiplanar reformation and three-dimensional image reconstructio | 1988 | Computed tomography (CT) with multiplanar reformation and three-dimensional (3D) image reconstruction was used pre-operatively to outline the bony morphological changes and femoral-acetabular relationships in 25 adult patients suffering from hip disease. Diagnoses included ischaemic necrosis of the femoral head, osteoarthritis, rheumatoid arthritis, calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, previous trauma and chronic dislocation. Polyethylene models of the femora and acetabula were constructed from three-dimensional contouring of CT data and compared with resected specimens in patients subjected to subsequent total hip arthroplasty. Information provided by this imaging technique was useful in both selecting and guiding the most appropriate surgical procedure and it was found that models depicted the actual bony contours with reasonable accuracy. CT combined with multiplanar reformation and 3D analysis may be the optimal pre-operative means of assessment of the diseased adult hip. | |
2820173 | Thymopoietin and thymopentin enhance the levels of ACTH, beta-endorphin and beta-lipotropi | 1987 Aug | Thymopoietin and thymopentin are well characterized polypeptides influencing immunoregulation by several mechanisms. Proposed as a therapy in diseases with major immune abnormalities such as rheumatoid arthritis, thymopentin improved within 2 weeks some clinical parameters as pain and joint swelling. The hypothesis that this spectacular effect could be mediated through interactions with anti-inflammatory (ACTH) and pain relieving (beta-endorphin) hormones producing cells was tested on the rat isolated pituitary cell model. Thymopentin and thymopoietin can enhance in vitro the levels of ACTH, beta-endorphin and beta-lipotropin in a time- and dose-dependent fashion for physiological concentrations ranging from 10(-12) to 10(-8) mol/l. The action on pituitary cells was restricted to those molecules as no changes occurred in LH, FSH, GH, TSH and PRL levels, after otherwise identical experimental conditions. | |
3040994 | Regulation of collagenase gene expression in synovial cells. | 1987 May | The metalloproteinase collagenase that is synthesized and secreted by synovial cells is responsible for the large amount of connective tissue destruction seen in rheumatoid arthritis. We have used a model system of cultured rabbit synovial fibroblasts to better understand mechanisms controlling both the induction and suppression of collagenase synthesis. Induction of collagenase requires an increase in collagenase mRNA and concomitantly, suppression of collagenase synthesis by retinoids and glucocorticoids is accompanied by a decrease in collagenase mRNA. Another metalloproteinase, activator, which is responsible for the activation of latent procollagenase and which has gelatinolytic ability, is coordinately regulated with collagenase. We conclude that there may exist a family of metalloproteinases that is important in the modulation of connective tissues and that is coordinately regulated at the level of mRNA. | |
3326434 | Comparing HEp-2 cell line with rat liver in routine screening test for antinuclear and ant | 1987 | The comparative study of the human tumor cell line HEp-2 and rat liver for the detection of antinuclear and antinucleolar autoantibodies by the indirect immunofluorescence technic in routine screening test demonstrate that, taking titer and staining pattern into account, both substrates are able to separate autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, scleroderma and primary biliary cirrhosis) patients from healthy subjects. The minimal screening test must include sera diluted 1:20 and 1:80. The capability of the HEp-2 substrate to reveal and to discriminate different speckled nuclear and nucleolar patterns explain its greater performance, notably in detecting anticentromere antibodies highly specific for the CREST syndrome and a speckled nuclear antibody frequently associated with primary biliary cirrhosis, allowing an earlier diagnosis of autoimmune diseases presenting these patterns. | |
2944700 | The catabolic fate of hyaluronic acid. | 1986 | Part of the hyaluronic acid (HA) synthesized in peripheral tissues enters the blood circulation through the lymph. It is rapidly taken up by the endothelial cells in the liver (half-life in blood is 2.5-5.5 minutes) and degraded. Pure primary cultures of liver endothelial cells were obtained by a newly developed technique and used to follow the metabolism of the polysaccharide on the cell surface. At 37 degrees C the HA is effectively endocytosed and degraded to acetate and lactate. A radioassay specific for HA and sensitive in the nanogram range has been developed to follow the concentration of HA in serum. The normal level in man is 10 to 100 micrograms/l. Elevated serum levels of HA are seen in liver cirrhosis, rheumatoid arthritis and scleroderma indicating that both an impaired catabolism in the liver and an increased synthesis in the peripheral tissues can modify the HA level. | |
1813195 | [A case of progressive systemic sclerosis and Sjögren's syndrome complicated by parkinson | 1991 Nov | A 79-year-old woman was consulted by us because of 2 years' history of difficulty in neck flexion and frozen gait. On admission, the neurological examination disclosed findings compatible with parkinsonism such as bradykinesia and muscle rigidity. In addition, she felt thirsty and hard skin, cyanosis and Raynaud phenomenon in the limbs. These were consistent with diagnosis of progressive systemic sclerosis and Sjögren's syndrome, which was then confirmed by high titers of anti-nuclear antibody and anti-ENA antibody and abnormal sialogram; marked decrease of saliva and tear secretion was demonstrated. Brain CT and angiography showed no evidence of ischemic stroke. Parkinson symptoms were not relieved by a month's treatment with L-dopa, but was improved by 3 weeks' administration of corticosteroids; the latter also provided a benefit to the poor circulation in her finger tips. Parkinsonism in the present case is likely related to Sjögren's syndrome. Our report proposes a possibility of autoimmune disease as one of underlying causes for drug-resistant parkinsonism. |