Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2562891 | Patients' preference in indomethacin trials: an overview. | 1989 Jan 14 | Meta-analysis was used to study patients' preference in 37 crossover trials that compared indomethacin with newer non-steroidal, antiinflammatory drugs (NSAIDs). 3 reports did not present numerical data. Patients who withdrew from the trial were included in the analysis. The difference between the proportion of patients who preferred the new drug and the proportion who preferred indomethacin (the therapeutic gain) was 14%. After exclusion of 2 unreliable studies the therapeutic gain was only 7%, and when 4 preliminary reports were also ignored, the gain was 5% (95% confidence interval 0 to 10%). In two additional analyses in which the 2 outlying results were excluded, the gain was also 5%. The findings do not support the trend to replace indomethacin with newer NSAIDs. | |
| 3321756 | [Endoscopic studies of the stomach tolerance of ibuprofen: comparison of 2 galenically dif | 1987 Sep | In randomised crossover fashion, the gastric and duodenal tolerability of two different ibuprofen galenic formulations were directly compared in ten healthy volunteers. An endoscopic evaluation was performed after 7 and 14 days treatment. 300 mg Ibuprofen q.i.d. as pellets, as well as 600 mg Ibuprofen b.i.d. as dragees, evoked a lesion score of 1.6 +/- 0.3 and 1.7 +/- 0.4 after 7 days of treatment (n.s.). After 14 days, the lesion score under ibuprofen dragees was slightly higher (1.9 +/- 0.3) when compared with the pellet formulation (1.6 +/- 0.3). This difference did not reach statistical significance. Both ibuprofen preparations were well tolerated. | |
| 2735964 | Central nervous system toxicity associated with weekly low-dose methotrexate treatment. | 1989 Jun | Central nervous system (CNS) toxicity from low-dose methotrexate (MTX) has been reported rarely, and reported symptoms consist primarily of dizziness and headache. We reviewed the records of 25 consecutive patients treated with low-dose MTX, and found 5 who had spontaneously reported unpleasant cranial sensations, mood alteration, or memory impairment. Rechallenge with MTX on 5 occasions in 3 patients led to recurrent CNS symptoms in all cases. CNS toxicity was the sole reason for discontinuation of MTX in 2 patients. These 5 patients differed from the 20 without CNS toxicity in age (mean 68 versus 50) and baseline serum creatinine level (1.3 mg/dl versus 0.9 mg/dl), but not in weekly dosage of MTX (12 mg versus 16 mg). These results suggest that CNS toxicity is more common than previously reported, particularly in older patients with mild renal insufficiency. | |
| 2154997 | Ligand-dependent release of active neutrophil collagenase. | 1990 Feb | The amount of active neutrophil (PMN) collagenase released extracellularly is dependent on the PMN-activating ligand. Neutrophils stimulated with soluble ligands, including FMLP, platelet-activating factor, or heat-aggregated IgG, released very little active collagenase, in contrast to cells stimulated with opsonized zymosan or surface-bound IgG. However, opsonized zymosan and surface-bound IgG did not differ appreciably from soluble ligands in effecting PMN production of superoxide, release of the specific granule component lactoferrin, or total (latent plus active) collagenase release, which suggests that there is more efficient collagenase activation during PMN stimulation with surface-bound ligands. These results suggest a role for surface (cartilage)-bound IgG in the release and activation of human neutrophil collagenase in the joints of patients with rheumatoid arthritis. | |
| 3084781 | Chrysiasis: the role of sun exposure in dermal hyperpigmentation secondary to gold therapy | 1986 Feb | To investigate the role of sun exposure in the pathophysiology of chrysiasis, we studied 10 Caucasian female patients with rheumatoid arthritis: 4 with clinically apparent chrysiasis and 6 without apparent pigmentation. Three patients without chrysiasis had received over 4 g of gold and 3 less than one g. The mean melanin score, determined by histological examination of sun exposed and nonsun exposed skin, was significantly higher in the sun exposed skin of the chrysiasis and high dose controls than low dose controls (p less than .05). Concentration of gold measured semiquantitatively by transmission electron microscopy and quantitatively by atomic absorption showed increased gold concentration in sun exposed when compared to nonsun exposed skin of chrysiasis and high dose controls (p = .26). Low dose controls had no gold demonstrated by either method. Our results suggest that gold deposition in the dermis stimulates melain production and that melanin is important in hyperpigmentation of chrysiasis. Furthermore ultraviolet light may induce preferential uptake of gold by the skin. | |
| 1744001 | Contribution of T-cell receptor-contacting and peptide-binding residues of the class II mo | 1991 Oct | The relative contributions of putative T-cell receptor (TCR)-contacting and peptide-binding residues of a major histocompatibility complex (MHC) class II restriction element to serologic and antigen-specific T-cell recognition were investigated by site-specific mutagenesis. Amino acids 70 and 71 in the DR beta 1 domain of DR4 Dw10 are uniquely differnet from the other Dw subtypes of DR4. Residue 70 is predicted to be located at the membrane-distal surface of the class II molecule, where it may influence T-cell recognition by a direct interaction with a TCR. Residue 71 is predicted to form part of the antigen-binding groove where its influence on T-cell recognition may be mediated indirectly via an effect on peptide binding. Transfected murine L cells were produced expressing the products of DR4 Dw10B genes in which the codons for residues 70 and 71 had been mutated towards DR4 Dw14. Support for the predicted orientations of beta-chain residues 70 and 71 was lent by the observation that only residue 70 plays an important role in the formation of a serologic determinant. Mutation of this residue was sufficient to produce recovery of recognition by a human monoclonal antibody, NI, which has specificity for all the DR4 subtypes with the exception of DR4 Dw10. The human T-cell clone HA1.7, specific for influenza virus hemagglutinin (HA) peptide 307-319 and restricted by DR1 Dw1, exhibits degeneracy of MHC restriction on the DR4 Dw subtypes with the exception of DR4 Dw10.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1770259 | [The distribution of S-100 protein positive chondrocytes in the human articular cartilages | 1991 Oct | There have been few reports on the localization of S-100 protein positive chondrocytes in the human articular cartilages. We studied 59 articular cartilages of the aged subjects, 65 osteoarthritic (OA) and 39 rheumatoid arthritic (RA) articular cartilages, to detect the histological localization of S-100 protein using immunoperoxidase method (ABC). The results obtained from normal cartilages demonstrated strongly positive cells representing hypertrophic chondrocytes in the perivascular areas of the neonatal articular cartilage and in the deep zone of the infant articular cartilage. The moderately positive cells were found in the intermediate zone of infant and adult articular cartilages. In mild OA, there were many positive chondrocytes in the intermediate zone with erosion of the surface layer, while in moderate or severe OA many strongly positive cells were found in clusters. The hypertrophic cells in the metaplastic cartilage arising from bone marrow in subjects with severe OA, or from pannus after RA were also positive. It is therefore, suggested that S-100 protein may be correlated with the metabolic activity of the cartilage matrix such as collagen and proteoglycan, as reported in the literature. S-100 protein further, appears to be useful for evaluating histologically the activity of cartilage repair in the pathologic human articular cartilages. | |
| 2199577 | Analysis of glycosylation changes in IgG using lectins. | 1990 Jul 20 | A simple rapid assay based on the ability of lectins to bind carbohydrates has been developed to analyse changes in the oligosaccharide chains of IgG. Bandeiraea simplicifolia lectin and Ricinus communis agglutinin have been used to detect terminal N-acetylglucosamine and galactose moieties respectively in IgG using immunodot-blotting. IgG samples (approximately 1 micrograms) were dot-blotted onto nitrocellulose followed by boiling of the blots to expose the carbohydrate moieties. The blots were then treated with biotinylated lectins followed by either streptavidin-biotin-hydrogen peroxidase conjugate or 125I-labelled streptavidin. The colour was developed using chloronaphthol and the blots read on a densitometer. The labelled blots were cut and read on a gamma counter. The use of a monoclonal antibody to N-acetylglucosamine is also discussed. The results obtained using this method are comparable to those obtained by structural analysis. | |
| 2909442 | Toward an epidemiology of gastropathy associated with nonsteroidal antiinflammatory drug u | 1989 Feb | The thesis of this paper is that gastropathy associated with nonsteroidal antiinflammatory drugs (NSAIDs) is the most frequent and, in aggregate, the most severe drug side effect in the United States. This work is based on a consecutive series of 2400 patients with rheumatoid arthritis followed prospectively for an average of 3.5 yr by ARAMIS, the American Rheumatism Association Medical Information System. We present a preliminary exploration of the magnitude of the problem, the population at risk, and the patients within that population who are at particularly high risk. Patients on NSAIDs had a hazard ratio for gastrointestinal (GI) hospitalization that was 6.45 times that of patients not on NSAIDs. Characteristically, high-risk patients for GI hospitalization and GI death are older, have had previous upper abdominal pain, have previously stopped NSAIDs for GI side effects, and have previously used antacids or H2-receptor antagonists for GI side effects. They also are frequently on corticosteroids. In contrast, patients attributing relatively minor symptoms to the drug tend to be younger and more frequently female. Our preliminary analysis is univariate and, as these variables are interdependent, firm conclusions regarding the relative importance of these risk factors will require reevaluating our data base as it is expanded using multivariate analysis. The syndrome of NSAID-associated gastropathy can be estimated to account for at least 2600 deaths and 20,000 hospitalizations each year in patients with rheumatoid arthritis alone. | |
| 2269468 | Human rheumatoid synovial cell stimulation by the membrane attack complex and other pore-f | 1990 Nov | The effects of non-lethal amounts of a variety of pore-forming agents on cultured human rheumatoid synovial cells (HRSC) have been investigated. Non-lethal complement membrane attack and non-lethal amounts of melittin, perforin and ionomycin all caused a biphasic release of prostaglandin E2 (PGE2) from HRSC, an early phase of release occurring within 1 hr and a second larger phase commencing after 4 hr and continuing over the 24-hr time-course. Removal of extracellular calcium abolished the release of PGE2 under all conditions of non-lethal attack. Modulation of G-protein activity reduced the second phase of release caused by non-lethal doses of the membrane-attack complex (MAC) from 800 ng/10(6) cells PGE2 to around 300 ng/10(6) cells. Non-lethal levels of the MAC also caused release of interleukin-6 (IL-6) from HRSC over the 24-hr time-course, with levels reaching 550 ng/10(6) cells at 24 hr compared to background levels of 200 ng/10(6) cells. No detectable release of IL-1 alpha could be measured at any time following non-lethal complement membrane attack. These results suggest a role for the MAC as an initiating mediator inducing the inflammation associated with rheumatoid arthritis. | |
| 1701992 | Role of cytokines in inflammatory synovitis. The coordinate regulation of intercellular ad | 1990 Dec | This study was undertaken in an effort to understand the role of cytokines in T lymphocyte trafficking into inflamed synovium and in the potential enhancement of antigen presentation by human synovial fibroblasts. We found that interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interferon-gamma (IFN gamma) each increased the cell surface expression of intercellular adhesion molecule 1 (ICAM-1) on human synovial fibroblasts in a dose- and time-dependent manner. Maximal ICAM-1 expression occurred within 8 hours of induction, with the following order of efficacy: IFN gamma greater than TNF alpha greater than IL-1 beta. The number of cells bearing the ICAM-1 antigen also increased, from a basal level of approximately 30% to more than 83% after cytokine induction (for all 3 cytokines). ICAM-1 expression rapidly decreased following cytokine removal. The expression of lymphocyte function-associated antigen 3 was also examined, but it was not changed by any of the 3 cytokines. Class I major histocompatibility complex antigen expression was increased modestly by all 3 cytokines, and expression was maximal by 24 hours after treatment. Only IFN gamma induced HLA class II antigen expression, and this expression persisted for up to 6 days following removal of the lymphokine. IL-6 and granulocyte-macrophage colony-stimulating factor had no effect on any of the parameters examined. Our data support an interactive role for inflammatory cytokines and the expression of adhesion ligands and HLA antigens by human synovial fibroblasts in the pathogenesis of synovial inflammation in rheumatoid arthritis. | |
| 1828664 | Do gamma delta T cells play an important role in autoimmune disease? | 1991 Feb | A T cell subpopulation using an alternative receptor heterodimer (gamma delta T cells) contributes 0.5-10% to the T cell population in the normal peripheral blood. One subset of gamma delta T cells (V gamma 9+/V delta 2+/ C gamma 1) preferentially recognizes mycobacterial antigens, which are the triggering antigens in the rat adjuvant arthritis (AA), an animal model with some similarities with rheumatoid arthritis (RA). Here we summarize data on the prevalence of gamma delta T cells in peripheral blood, synovial fluid and synovial membranes of RA patients which show that gamma delta T cells, in particular the subset reactive with mycobacterial antigens in normal individuals, are rare in all studied compartments. Furthermore, there was no enrichment of gamma delta T cells in the peripheral blood of patients with ankylosing spondylitis or systemic lupus erythematosus, autoimmune diseases with involvement of the joints. In the AA model depletion of the "conventional" alpha beta T cells completely prevented the induction of the disease and very effectively improved ongoing arthritis even though substantial numbers of gamma delta T cells were present in these animals. Taken together, our data do not support the notion of a significant contribution of gamma delta T cells to chronic joint inflammation in the autoimmune diseases studied or in adjuvant arthritis. | |
| 3488273 | IgG anti-IgA1 and anti-IgA2 antibodies: their measurement by an enzyme-linked immunosorben | 1986 | IgG anti-IgA antibodies were measured by an enzyme-linked immunosorbent assay using one IgA1 and one IgA2 (m1) myeloma and a pooled IgA protein preparation as antigens. Class-specific anti-IgA antibodies occurred in 0.8% of non-IgA-deficient sera and 24.3% of IgA-deficient sera. Antibodies reacting with IgA1 only occurred in 2.6% of non-IgA-deficient sera and 6.7% of IgA-deficient sera. Antibodies reacting with IgA2 only occurred in 0.6% of non-IgA-deficient sera and 2.7% of IgA-deficient sera. The prevalence of anti-IgA in IgA deficients with inflammatory disease was higher (81.8%) than in IgA deficients without disease (24.1%) and was accounted for by class-specific antibodies. | |
| 1722125 | Specific high performance liquid chromatographic determination of the molecular weight and | 1991 Nov | A simple High performance liquid chromatographic (HPLC) method for the specific determination of the molecular weight and concentration of hyaluronic acid (HA) in complex mixtures has been developed. Hyaluronate-binding proteins isolated from bovine cartilage labelled by 125I or fluoresceinisothiocyanate were used as specific markers. The specific binding affinities of the markers were compared and were found to have association constants of 1.6 x 10(7) M-1 and 1.2 x 10(7) M-1 respectively. The HA levels and molecular weight distributions can be easily determined in the range 10-500 ng/mL in complex mixtures by the use of markers, molecular sieving HPLC columns and appropriate detectors. It has been demonstrated clearly that the method is useful for the highly specific determination of the parameters in complex biological samples such as serum and synovial fluids and is recommended for clinical applications. | |
| 3780056 | Antibody to intermediate filaments of the cytoskeleton in patients with Behçet's disease. | 1986 Dec | Antibodies to 10-nm intermediate filaments (anti-IF) were determined in the sera of 30 patients with Behçet's disease (BD), in addition to C-reactive protein and C9, and an attempt has been made to determine whether the presence of anti-IF indicate disease activity. The vimentin type of anti-IF was found to be positive in 14 out of 30 patients with BD (47%), whereas it was positive in 35% of the patients with rheumatoid arthritis (20 cases), 16% of the patients with systemic lupus erythematosus (19 cases) and in only 9% of the normal controls. The anti-IF were predominantly IgG class and the titers in BD were significantly higher than those in normal controls. Out of the 14 patients with anti-IF, 10 showed significantly increased levels of serum C9 and 8 showed increased levels of CRP activity. Only one patient showed increased C9, but was negative for anti-IF and CRP. The presence of anti-IF in the patients' sera was found to be a more sensitive indicator, though not specific, for the clinical assessment of disease activity. | |
| 1825323 | A double-blind gastroscopic evaluation of the effects of etodolac and naproxen on the gast | 1991 Jan | The aim of this clinical, endoscopical study was to evaluate the therapeutic efficacy and the gastric tolerability of etodolac, a new anti-inflammatory, non-steroidal drug, compared with naproxen. The study was conducted on 48 patients suffering from rheumatoid arthritis. 44 of whom completed the trial. After an initial oesophagogastroduodenoscopy to exclude the presence of gastric mucosal lesions, patients were randomly allocated to double-blind treatment with either etodolac 200 mg b.i.d. or naproxen 500 mg b.i.d. for a period of 4 weeks. Endoscopic control followed this treatment period. Both drugs proved effective in relieving clinical symptoms, without a statistically significant difference. Gastric mucosal lesions were observed in 15% of etodolac-treated patients and in 46% of patients treated with naproxen (P less than 0.05) (95% CI 0.01-0.60). Painful dyspepsia was observed in 15% of patients treated with etodolac vs. 38% of patients on naproxen therapy. This study demonstrates that etodolac is at least as active as naproxen in relieving rheumatic symptoms, and its administration results in a significantly lower degree of gastric damage. | |
| 2585886 | Ischemic heart disease in systemic lupus erythematosus. A retrospective study of 65 patien | 1989 Sep | We studied the frequency of ST-T changes and ischemic heart disease (IHD) in prednisolone (PSL)-treated systemic lupus erythematosus (SLE) patients and compared them with the age-matched control of rheumatoid arthritis patients not receiving PSL. Twenty-five (38%) of the 65 SLE patients revealed ST-T changes as ST elevation (4%), ST depression (36%) and T wave flattening or inversion (60%). Among the control patients 4 (10%) had T wave flattening or inversion. The frequencies of ST-T changes in patients receiving total PSL dose of up to 5g and greater than 5g were 23% and 48%, respectively. Four patients developed IHD at an unusually young age during remission of SLE while receiving low dose of PSL and 2 of them later died of myocardial infarction (MI). The latter 2 patients had received PSL pulse therapy prior to MI. Regular ECG check up for SLE patients while they are on low dose PSL or pulse therapy may help reveal early ECG abnormalities and thus detect and treat one of the major risks of long-term effects of corticosteroid therapy. | |
| 3261186 | HLA-DR4 and other genetic markers in rheumatoid arthritis. | 1988 | In a new series of RA patients the association with HLA-DR4 was again found to be highly significant. Also increased were the DR4 associated antigens DRw53 and DQw3. Hybridization of a DQ-beta probe to Bg1 II-digested DNA showed that a variant of DQw3, characterized by a 4.3 kb fragment and related to the serological specificity TA10, was markedly increased among DR4 positive RA patients. HLA-DR1 was also increased in RA and appeared to be independent of the increase of DR4. Although the DR1 association was weaker, it was observed in both patients with and without RF. In contrast, DR4 was found to be increased significantly only in the RF positive group of patients, as previously observed. Development of RA in multiple-case families was found to be linked to the inheritance of DR4 positive haplotypes. The possible role of risk factors associated with polymorphic markers of the T-cell receptor genes was investigated. An allelic marker associated with one of the variable gene subfamilies of the beta-chain was found to be associated with RA. The results suggest that susceptibility for development of RA is influenced by alleles of the T-cell receptor in conjunction with the class II HLA factors with which the T-cell receptor interacts in the course of the immune response. | |
| 3257581 | Efficient propagation and cloning of human T cells in the absence of antigen by means of O | 1988 Jan | The analysis of T lymphocytes infiltrating tissues afflicted by autoimmune diseases may provide major clues towards understanding the pathogenesis of such diseases. Currently the best approach to studying heterogeneous populations such as T lymphocytes involves long-term culture and cloning. In order to grow and clone T lymphocytes, regular restimulation with the specific antigen is essential, otherwise growth will stop and/or specificity may be lost. In autoimmune diseases the antigens involved in triggering the immunological reaction of T cells are usually unknown. Therefore an alternative way of stimulating T lymphocytes without loss of specificity is clearly needed. Here we describe the cloning and expansion of antigen-specific T cell clones from the blood of a healthy donor to sizeable numbers of cells (greater than 10(8)) by means of anti-CD3 monoclonal antibody and recombinant IL-2. The results obtained showed that this approach can be used to clone and 'expand' T lymphocytes that retain antigen specificity over a prolonged period, in this case over 10 weeks. This technique has been used to clone and expand T lymphocytes infiltrating the affected tissues in a variety of autoimmune disorders such as Hashimoto's thyroiditis, Graves' disease, and rheumatoid arthritis, and is an efficient method of propagating T cells, by mimicking the antigenic stimulus. | |
| 1907059 | Arachidonic acid metabolism: role in inflammation. | 1991 | Arachidonic acid is oxygenated and further transformed into a variety of products which mediate or modulate inflammatory reactions. The cyclo-oxygenase pathway, which is inhibited by nonsteroidal anti-inflammatory drugs, produces vasodilator prostaglandins such as PGE2 and prostacyclin (PGI2) and also thromboxane A4, a potent platelet aggregating agent. Recent work has demonstrated the importance of products formed via various lipoxygenase-catalyzed reactions. Leukotrienes are formed by initial oxygenation at C-5 followed by further transformation to an unstable epoxide intermediate, leukotriene A4 (LTA4). The intermediate can be converted into LTB4 by hydrolysis and into LTC4 by conjugation with glutathione. The formation of the leukotriene, LTA4, is catalyzed by a 5-lipoxygenase possessing both lipoxygenase and LTA4-synthase activities. Unlike other lipoxygenases, this enzyme requires multiple stimulatory factors for maximal activity. These include Ca2+, ATP, and three non-dialyzable cellular components. The cDNAs for human 5-lipoxygenase and LTA4-hydrolase have recently been cloned and the amino acid sequences for the enzymes have been deduced. LTC4 and its metabolites, LTD4 and LTE4, increase vascular permeability and contract airway smooth muscle. Leukotriene B4 causes adherence of neutrophils to endothelial cells and is a potent chemotactic agent. It also stimulates release of lysosomal enzymes and generation of superoxide anion in neutrophils. Oxygenation of arachidonic acid at C-12 and C-15 generates products (5S, 12S-DHETE and 14,15-DHETE) which can modulate various neutrophil functions. A new group of arachidonic acid-derived products was recently discovered. These compounds (lipoxins), formed by oxygenation at C-5 and C-15 and additional reactions, contain a conjugated tetraene structure and three alcohol groups.(ABSTRACT TRUNCATED AT 250 WORDS) |