Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2295163 | Reconstruction of the deficient acetabulum using the bipolar socket. | 1990 Feb | Although originally conceived as part of a two-stage procedure for the reconstruction of the deficient acetabulum, the use of a bipolar/grafting technique in selected patients can provide acceptable results as a definitive procedure. Critical technical considerations include proper preparation and grafting of the acetabular bed and careful sizing of the outer bipolar shell. Acceptable levels of pain relief and functional gain were obtained in 47 cases, with a follow-up mean Harris hip score of 86. Despite some initial socket migration in all hips, roentgenographic stability was gained after the first year. One acetabular failure was related to graft placement in the superolateral position. Bipolar reconstruction is indicated for contained acetabular defects only. In addition, the surgeon must have access to a complete inventory of socket sizes to ensure a proper fit and a bone bank to obtain adequate amounts of allogeneic bone. | |
| 1759148 | [Determination of alcohol dehydrogenase genotype: no correlation between isoenzyme pattern | 1991 Dec 14 | Mounting evidence from various fields of research links the oxidation product of alcohol, acetaldehyde, with the development of alcohol abuse-related pathology. One factor governing the production of acetaldehyde is the genetically determined pattern of class I alcohol dehydrogenase isoenzymes, consisting of "fast" beta 2 and gamma 1 and "slow" beta 1 and gamma 2 subunits. Alcoholics carrying the beta 2 and gamma 1 genes might, therefore, be more susceptible to alcohol-related liver disease. To verify this hypothesis we developed a method based on the polymerase chain reaction and restriction enzyme digestion in order to genotype individuals with respect to their alcohol dehydrogenase isoenzyme pattern. In a total of 100 caucasian individuals the following genotypes were determined: beta 1 beta 1, 92; beta 1 beta 2, 8; beta 2 beta 2 0; gamma 1 gamma 1, 38; gamma 1 gamma 2, 51; gamma 2 gamma 2, 11. No statistically significant differences in the distribution of isoenzymes were detectable between alcoholics with liver disease, patients with non-alcohol abuse-related liver disease, patients with rheumatoid arthritis and healthy controls. | |
| 2500315 | [Measurement of anticardiolipin antibodies and its significance in systemic lupus erythema | 1989 Feb | A method for detection of anticardiolipin (ACL) antibodies with enzyme-linked immunosorbent assay was developed. Microtitre plates were coated with cardiolipin at a concentration of 20 micrograms/ml by evaporation under 4 degree centigrade overnight. Non-specific binding of diluted sera was eliminated by blocking of plates with 10% fetal calf serum in phosphate buffered saline (FCS/PBS) for 2 hours at room temperature. Sera (50 microliters/well) at a dilution of 1:100 were incubated for 2 hours at room temperature. Horseradish peroxidase conjugated rabbit anti-human IgG, IgM, IgA at a dilution of 1:2000, 1:1000, 1:500 respectively was added to the wells, and incubated for one and half hours at room temperature. The results were read at 490nm after incubation with substrates at 37 degree centigrade. 85 patients with systemic lupus erythematosus (SLE), 45 with rheumatoid arthritis (RA), 25 with progressive systemic scleroderma (PSS), and 18 primary Sjogren's syndrome were tested. The frequency of ACL antibody in SLE (48%) was much higher than that in RA (11%), PSS (12), SS (5.5). Three isotypes of ACL (IgG, IgM, IgA) were detected in the study with predominance of IgG isotype. ACL antibody was significantly associated with thrombosis, cutaneous vasculopathy, thrombocytopenia, and spontaneous abortion in patients with SLE. Strong relationship between ACL antibody and lupus anticoagulant was found. There was no correlation between ACL and anti-DNA antibodies, nor was ACL and VDRL test. The level of ACL antibody could be reduced by use of corticosteroids. | |
| 2186003 | Penicillamine-induced pemphigus erythematosus. | 1990 Apr | Pemphigus erythematosus occurred in a patient with rheumatoid arthritis who was treated with D-penicillamine. The skin lesions appeared 4 months after the onset of D-penicillamine treatment and persisted 14 years after cessation of this drug. Topical betamethasone dipropionate applications resulted in complete regression of the cutaneous lesions. | |
| 3521618 | Piroxicam capsules versus suppositories: a pharmacokinetic and clinical trial. | 1986 Apr | 15 patients with rheumatoid arthritis or osteoarthritis received a single dose (20 mg) piroxicam (Felden) as suppository. Serum piroxicam concentrations were assayed by fluorometry 1, 2, 4, and 8 h after the installation of the suppository, the mean values being 1.3, 1.9, 1.8, and 1.8 mg/l, respectively. Then the patients continued on oral piroxicam 20 mg daily for maximum 3 weeks, and serum piroxicam levels (mean 6.3 mg/l) were checked at the end of this period. Nine patients then continued on piroxicam suppositories 20 mg daily for one week, and serum piroxicam levels (mean 4.5 mg/l) were again assayed at the end of this maintenance. Pain at rest, pain on motion, and joint movement restriction were scored on day 1, after oral maintenance, and after rectal maintenance. Reduced scores were found with time, but the only statistically significant effect was in the overall subjective pain relief measured after oral maintenance. Rectal irritation was recorded in one patient. It is concluded that a) absorption of piroxicam from suppository was adequate, b) it was possible to maintain adequate serum piroxicam levels by repeated administration of suppository for one week, and c) the gastrointestinal toleration was acceptable in these patients selected for showing poor tolerance towards other nonsteroidal antiinflammatories. | |
| 2132565 | Administration of folinic acid after low dose methotrexate in patients with rheumatoid art | 1990 Sep | Folinic acid (leucovorin) supplementation has been suggested as a possible means of treating the short term side effects that occur with low dose methotrexate (MTX). However, it has not been established whether leucovorin will abrogate the antiarthritic effect of MTX. We entered 20 patients with rheumatoid arthritis treated with MTX into a 48 week randomized, double blind, crossover trial of folinic acid vs placebo. The dose of folinic acid was equal to the dose of MTX and it was given orally 4 h following the single, weekly MTX administration. Under these conditions, leucovorin did not decrease the therapeutic effect of MTX. While the incidence of stomatitis and gastrointestinal toxicity were lower during leucovorin treatment, our study lacked sufficient power to establish a statistically significant difference. | |
| 1977186 | The source and significance of raised serum enzymes in rheumatoid arthritis. | 1990 Aug | Hepatobiliary dysfunction in rheumatoid arthritis has been suggested on the basis of raised serum activity of alkaline phosphatase, 5-nucleotidase, lactic dehydrogenase and gamma-glutamyl transferase, but a specific pathological lesion has not been demonstrated and serum transaminases and bilirubin are almost invariably normal. This paper reports a series of studies designed to determine the tissues of origin of the enzymes and offers an alternative interpretation of the enzymological findings. The results suggest that only alkaline phosphatase originates from the liver, while lactic dehydrogenase and 5-nucleotidase originate from synovial fluid polymorphs and synovial lining cells, respectively. Serum alkaline phosphatase may be induced by inflammatory mediators such as interleukin-1 because it correlates with the acute phase response. Serum lactic dehydrogenase is an integrated measure of polymorph lysis in all joints and offers a marker of joint inflammation more specific than measures such as the ESR. Levels of serum 5-nucleotidase provide information about the activity of the synovium. Finally, because hepatic necrosis does not normally occur, the transaminases may be used to monitor drug toxicity. | |
| 3624864 | The subclass distribution of human IgG rheumatoid factor. | 1987 Sep 1 | The subclass distribution of IgG rheumatoid factor (RF) was determined by a sensitive ELISA assay in sera from patients with rheumatoid arthritis and from normal controls. In both instances, the most important subclasses were IgG1 and IgG4. The IgG4 RF was directed against the Fc region of IgG, and recognized human as well as rabbit IgG. Although human IgG4 myeloma proteins bound to rabbit IgG better than did myelomas of other IgG subclasses, the IgG4 RF activity in rheumatoid sera showed an additional specificity, because the fraction of IgG4 RF/total IgG4 for rheumatoid arthritis sera was far greater than for myelomas. This inference was supported by the observation that there was persistent, albeit diminished, IgG RF activity in pepsin-digested, RF-containing sera (but not myeloma proteins), indicating that a critical component of IgG4 RF activity was contained within the Fab region of the IgG4 molecule. The finding of large quantities of IgG4 RF was not due to a bias of the assay, because the preponderance of IgG4 did not extend to the subclass distribution of antibodies directed against other antigens. The demonstration of an important role for IgG4 as a RF is of special interest because of the relative inability of this subclass to fix complement or to bind to Fc receptors, and because of its potential role as a mediator of increased vascular permeability. | |
| 3623827 | Serum oxidation activities and rheumatoid arthritis. | 1987 | The serum oxidation activity (SOA) of patients with rheumatoid arthritis (RA) and other connective-tissue diseases (OCTD) was measured by a new colorimetric procedure the authors have devised, using o-phenylene diamine (OPD) as the indicator. A comparison was made between SOA and other clinical data, such as patient age, the particular stages of the disease and its total duration, number of joints with active synovitis, arthritic score, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), RA test results, rheumatoid arthritis haemagglutination titre (RAHA), ceruloplasmine (CP) and transferrin. Fifty-three out of 73 patients with RA (72.6%) and thirteen out of 34 patients with OCTD (38.2%) showed high levels of SOA (mean + 2SD of the control value). A significant correlation was noted between SOA and the number of joints with active synovitis, serum CP, CRP and ESR in RA patients. SOA and lipid peroxide (LP) were inversely correlated to a very significant extent. In OCTD, SOA showed a significant correlation with CP, but not with CRP or ESR. The number of active synovitis in RA patients indicated their high correlation with SOA. Drugs generally used for RA therapy, such as D-penicillamine and tiobutarit (SA96), were found to have anti-oxidant activity in the presence of RA sera. On the basis of these data, it is apparent that SOA is a reliable indicator of RA activity, and that the oxidation of various body constituents and fluids may be essential to the inflammatory processes of RA. | |
| 1776368 | [Rheumatologic and radiologic symptoms of secondary hyperparathyroidism: retrospective lon | 1991 Sep | Despite recent improvements of hemodialysis (HD) techniques, symptoms due to secondary hyperparathyroidism (HPT) contribute to longtime complications of HD patients. The aim of the present retrospective study was to determine the incidence and localization of radiological joint and bone lesions in 175 patients on chronic HD. In 108 patients the diagnosis of HPT was made by radiologic criteria. 56% had radiomorphologic lesions of the hands, 45% of the acromio-clavicular (AC) joint, 31% of the shoulder, and 27% of the pelvis. No sex difference was found for prevalence of HPT in these patients, nor was one found for any of the underlying renal diseases. There was a negative correlation between elevated serum parathyroid hormone and serum aluminum concentrations. In 111 patients the history of bone and joint pain was evaluated. 54% of these patients suffered from bone pain, arthralgia, and morning stiffness. Radiological lesions of AC-joint correlated with shoulder pain in 38%. Our data show that even in the predialytic phase of renal insufficiency x-rays of the shoulder are helpful in early diagnosis of HPT. Skeletal manifestations specific for one of the underlying renal diseases do not exist. Elevated PTH levels are a good indicator of HPT in these patients, whereas low levels of PTH do not exclude radiological manifestations. In contrast to beta 2-microglobulin amyloidosis, pain does not occur during rest and is not worsened during HD. Treatment with non-steroidal antiinflammatory drugs led to pain relief in the majority of patients. Pain history in patients on chronic HD provides important information concerning the differential diagnosis of HPT/beta 2-microglobulin amyloidosis. | |
| 3954470 | 2',5'-oligoadenylate synthetase induction in lymphocytes of patients with connective tissu | 1986 Mar | Spontaneous production of the interferon induced enzyme 2',5'-oligoadenylate synthetase (2',5'-A synthetase) was significantly greater in blood lymphocytes of patients with systemic lupus erythematosus (SLE), Behçet's syndrome, and rheumatoid arthritis than in control lymphocytes. Alpha interferon (IFN-alpha) induced comparable production of enzyme in normal, rheumatoid, and Behçet's lymphocytes, and reduced, but still appreciable amounts in SLE lymphocytes. Phytohaemagglutinin (PHA) did not induce enzyme. Thus spontaneous production of 2',5'-A synthetase is encountered in several connective tissue diseases and seems likely to be induced by in-vivo exposure to interferons. | |
| 1902981 | Branhamella catarrhalis as a cause of multiple subpleural abscesses. | 1991 | A pure growth of Branhamella catarrhalis was obtained from subpleural abscesses in a 65-year-old fisherman with a persistent pneumothorax; underlying disorders included lung fibrosis, rheumatoid arthritis, and diabetes mellitus. A thoracotomy revealed extensive thickening of the visceral pleura covering multiple subpleural abscesses. There was a protracted postoperative course despite surgical debridement and antibiotic treatment with a cephalosporin and erythromycin. | |
| 1645488 | [Proteolytic enzymes and the destruction of articular cartilage in arthritis and chronic p | 1991 | The extracellular matrix (ECM) of articular cartilage is subject to a steady remodelling process. The collagenous components of the ECM are characterized by a very low rate of metabolism, whereas the proteoglycans exhibit an active turnover. The main proteolytic enzymes degrading the ECM components are collagenase, gelatinase and stromelysin. These enzymes undergo under pathological circumstances a remarkable enhancement of synthesis and activity. Although each of these enzymes appears to degrade one ECM component specifically, there is evidence for synergistic effects of most of them. Gelatinase acts synergistically with collagenase in degrading insoluble interstitial collagens and stromelysin activates collagenase. Thus a cascade mechanism may exist in which the cartilage-ECM is completely degraded. Yet, it is not crucial which part of the ECM (collagens or proteoglycans) is primarily degraded. The integrity of the ECM rather depends on the balance between anabolic and catabolic processes, the upset of which results in damage of the articular cartilage. Cartilage destruction in rheumatoid arthritis and osteoarthritis is considered to be a result of this imbalance in favour of the catabolic processes. This would lead to a decrease in proteoglycans which causes fibronectin deposition in the cartilage ECM. Due to chemotaxic effects of fibronectin on fibroblasts, the enrichment of this glycoprotein in the ECM gives rise to cartilage fibrosis and early degeneration. | |
| 2716010 | In vitro effect of select nonsteroidal antiinflammatory drugs on the synthesis and activit | 1989 Jan | Nutriment replenished conditioned media derived from cultures of osteoarthritic and rheumatoid synovial tissue contain factors of variable molecular weight, independent of prostaglandin activity, which are capable of reversibly down-regulating cartilage matrix proteoglycan synthesis. Piroxicam significantly reduced anabolic suppressant factor production on an apparent selective basis. It could be shown to partially modify the chromatographic profile of newly synthesized osteoarthritic synovial tissue protein fractions containing suppressant activity. Dependent on experimental design, piroxicam also partially blocked inhibitory activity at a chondrocyte level. Indomethacin and sodium salicylate were essentially without effect. | |
| 3110942 | Pharmacology of auranofin: overview and update. | 1986 | Auranofin, the only approved oral gold complex of value in suppressing rheumatoid arthritis, differs from injectable gold compounds molecularly and pharmacologically. Although comparably efficacious, the side-effect profiles of oral and intramuscular gold differ, and the withdrawal rate for adverse reactions is several-fold lower with auranofin. Considerably less elemental gold is available to the internal milieu with auranofin than with gold sodium thiomalate (3 mg/week vs. 25 mg/week), a difference reflected in lower blood, synovial fluid and tissue gold levels. Approximately 25% of the administered auranofin dose is absorbed orally, and 85% is recovered in feces. Serum gold levels are 300-400 micrograms/dl one week after injectable gold and 60-70 micrograms/dl daily with auranofin (6 mg/d). But, surprisingly, the fraction of gold associated with the red blood cell fraction is higher with auranofin. Blood gold levels do not correlate with clinical response to treatment or frequency or type of adverse reaction, regardless of the gold preparation used. Similar results obtain with penicillamine. Methotrexate blood levels are not related to the development of hepatic fibrosis. The mechanisms of gold action in rheumatoid arthritis are unknown, despite the laboratory definition of multiple antiinflammatory, immunologic and other effects. Sulfhydryl binding activity, an established property of injectable gold compounds and penicillamine of potential importance pharmacodynamically, is limited with auranofin. | |
| 2148942 | Gold sodium thiomalate (GTM) induces hypersensitivity to thiomalate, the thiol carrier of | 1990 Sep | A case of the gold sodium thiomalate (GTM)-induced eruptions with thiomalate (TM) hypersensitivity was reported. A 61-year-old Japanese woman developed lichenoid and seborrheic dermatitis (SD)-like eruptions with alopetia, when the total dosage of GTM administered for rheumatoid arthritis became 110 mg. The eruptions slowly disappeared with pigmentation after discontinuance of the GTM therapy, and the resumption resulted in the development of similar eruptions. She showed a positive reaction to GTM in an intradermal test. She also showed a positive response to TM, which is the thiol carrier of GTM, in the patch test, but a negative one to metallic gold. After administration of auranofin (AF), she also developed the SD-like eruptions with hypersensitivity to metallic gold as well as AF on patch testing, but did not develop the lichenoid ones. Our animal experiments revealed an almost complete cross reaction between GTM and TM, but only a partial one between GTM and aurothioglucose, which have dissmilar structures in the carrier part for gold. Probable roles of hypersensitivity to TM and metallic gold, which are metabolites of GTM, were discussed, respectively, in the genesis of the GTM-induced lichenoid eruptions and the AF-induced SD-like eruptions. | |
| 2937582 | Decreased C3b receptors (CR1) on erythrocytes from patients with systemic lupus erythemato | 1986 Jan | Using 125I-F(ab')2 anti-CR1 we have measured C3b receptors (CR1) on the erythrocytes of 56 normal individuals 26 patients with systemic lupus erythematosus (SLE) and 24 with rheumatoid arthritis (RA). The mean number of CR1 sites in SLE (1150/cell) but not RA (1460/cell) was significantly lower (P less than 0.01) than normal (2200/cell). Although the cumulative frequency curve for normals showed minor inflections at frequencies of 18% and 64%, these were not sufficiently marked to permit us to conclude that they distinguished subpopulations of different CR1 phenotypes. Measurement of CR1 numbers of two normal families and four families of SLE patients indicated that low CR1 numbers aggregated in families as did high CR1 numbers, a finding which suggests that CR1 numbers are under genetic control. However, certain observations in SLE patients indicated that low CR1 numbers could be an acquired abnormality. These included, (a) absent CR1 phenotype in a patient whose family had moderate and high CR1 numbers, (b) increasing CR1 numbers as SLE patients went into remission, (c) CR1 numbers were lower in patients with active compared with inactive disease and (d) CR1 numbers were different in each of two sets of identical twins (Fig. 4A). Our conclusions are that, (a) genetic factors probably influence CR1 numbers in normal individuals, (b) that our findings were not inconsistent with the two codominant allele models (Wilson et al., 1982), and (c) the low CR1 phenotype of SLE patients may be secondary to the disease process. | |
| 3086002 | Mechanisms of macrophage activation in rheumatoid arthritis: the role of gamma-interferon. | 1986 Mar | Gamma-interferon (gamma-IFN) is a potent inducer of surface expression of class II MHC molecules in vitro. Enhanced HLA-DR expression is a characteristic immuno-histological feature of rheumatoid joints. To assess the possible relevance of gamma-IFN to macrophage (M phi) activation in rheumatoid arthritis (RA) we investigated the spontaneous and mitogen-induced production of gamma-IFN by RA lymphocytes using a sensitive radioimmunoassay. Synovial fluids (SF) from a variety of inflammatory and non-inflammatory rheumatic diseases did not contain measurable amounts of IFN. RA lymphocytes from peripheral blood (PBL) and joints failed to show spontaneous gamma-IFN production. RA and control PBL were equally responsive to both mitogen stimulation and to the addition of exogenous interleukin 2 (IL-2) as control PBL. SF lymphocytes from RA patients showed a significantly decreased PHA-stimulated gamma-IFN production and this was in contrast to the SF lymphocytes from patients with other inflammatory joint diseases who showed significantly increased gamma-IFN production compared with matched PB lymphocytes. These results show that gamma-IFN production by peripheral blood and joint cells from patients with RA is normal and it remains to be established whether gamma-IFN is the factor responsible for the macrophage activation seen in the disease. | |
| 3492852 | [Myasthenia induced by D-penicillamine. Apropos of 2 case reports]. | 1986 Nov | Two cases of penicillamine-induced myasthenia gravis in rheumatoid polyarthritis are reported. A complete recovery was obtained in both cases. The authors discuss the clinical presentation and the pathogenetic mechanisms of that drug-induced myasthenia gravis. The presence in both cases of both the HLA antigens DR1 and BW35 is emphasized. | |
| 2310227 | A novel assay for neutrophil clustering activity of human sera: relation to disease activi | 1990 Jan | A simple and reproducible method for the measurement of serum neutrophil clustering activity was developed. High clustering activity was found in 19/30 patients with active systemic lupus erythematosus (SLE), and 14/20 of those with severe disease flares. In contrast, 0/10 patients with quiescent SLE and 2/20 patients with rheumatoid arthritis had high neutrophil clustering activity. Particularly high clustering activity was found in patients with SLE with lupus glomerulonephritis and in certain patients with central nervous system disease. An inverse correlation was found between neutrophil clustering activity and peripheral blood neutrophil count in patients with SLE not treated with glucocorticoids, and clustering activity was high in all patients with low neutrophil counts in this group. A moderate correlation was found between neutrophil clustering activity and C1q binding circulating immune complexes. Non-steroidal anti-inflammatory drugs and glucocorticoids had little direct effect on neutrophil clustering activity. |