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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2063729 | [Determination of circulating immune complexes and of their component immunoglobulin class | 1991 | In 353 sera (from healthy donors as well as patients suffering from rheumatoid arthritis, systemic lupus erythematosus, hepatitis, malignant melanoma) circulating immune complexes were determined by C1q-binding test and a C1q solid-phase ELISA. Using peroxidase-labelled antibodies (from rabbit) against human mu-, gamma-, and alpha-heavy chains, the immunoglobulin classes in the complexes were determined. In rheumatoid arthritis, immune complexes contain IgM more frequently (41.5%) than in systemic lupus erythematosus (10%). Immune complexes containing only IgA as immunoglobulin were found in 24 cases. Our results including binding experiments with chemically aggregated IgA suggest, that the binding of C1q to IgA is not necessarily followed by classical complement activation. | |
2173500 | Oxidative response of polymorphonuclear leucocytes to synovial fluids from patients with r | 1990 Sep | Only a minority (7/35, 20%) of synovial fluids from patients with rheumatoid arthritis (RA) and none from patients with other arthritides stimulated the oxidative response of polymorphonuclear leucocytes (PMNs). Superoxide anion generation was measured by superoxide dismutase inhibitable reduction of cytochrome c. The same synovial fluids stimulated superoxide release by PMNs regardless of their source, though they elicited a greater response from RA synovial fluid PMNs than from either RA blood PMNs or blood PMNs from normal subjects. The remaining synovial fluids failed to stimulate any of the PMNs, though some (2/10) stimulated PMNs pretreated with cytochalasin B. The stimulatory activity was removed from RA synovial fluids by protein A-Sepharose and eluted with the void volume on gel chromatography. It is considered that immunoglobulin aggregates in some RA synovial fluids may stimulate the oxidative response of PMNs in the joint space but that most do not because these fluids contain either a specific inhibitor or immunoglobulin aggregates of an inappropriate type, or both. | |
2113447 | Interferon-gamma mRNA expression upon in vitro T lymphocyte activation is decreased in rhe | 1990 Jul | A decreased production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) upon in vitro stimulation by phytohemagglutinin (PHA) peripheral blood leucocyte in active rheumatoid arthritis (RA) patients has been described as an important immunological abnormality in this disease. However, the molecular level at which this defect might occur has not been fully documented. We have investigated the kinetics of IFN-gamma, interleukin-2 receptor (IL-2 R), and interleukin-1 beta (IL-1 beta) messenger RNA (mRNA) expression in RA patients (n = 9) and normal controls (n = 5) after PHA leucocyte activation. We demonstrate here a significantly decreased expression of IFN-gamma mRNA in RA patients without modification of its kinetics associated with a similar IL-1 beta mRNA expression. | |
3197362 | Bradykinin is increased during acute and chronic inflammation: therapeutic implications. | 1988 Dec | Bradykinin is a potent pain-producing substance, yet little is known about its role in inflammation. The present study measured circulating levels of immunoreactive bradykinin in a clinical model of acute inflammation (oral surgery) and chronic inflammation (rheumatoid arthritis) and in the rat carrageenan model of inflammation. The effects of a kallikrein inhibitor (soybean trypsin inhibitor) on blocking bradykinin synthesis in vitro and its analgesic actions in the rat model were also evaluated. Levels of immunoreactive bradykinin increased threefold to fourfold during oral surgery. Levels were twofold to threefold greater in patients with rheumatoid arthritis compared with control subjects. Levels of immunoreactive bradykinin increased twofold in rats during carrageenan inflammation. Soybean trypsin inhibitor blocked synthesis of bradykinin in vitro and possessed analgesic activity in rats. The results indicate that the bradykinin system is activated during inflammation. Kallikrein inhibitors may represent a new class of analgesic/antiinflammatory drugs. | |
2833185 | Relation between synovial fluid C3 degradation products and local joint inflammation in rh | 1988 Mar | C3 degradation products (C3dg/d) were estimated in 288 synovial fluid (SF) samples (rheumatoid arthritis (RA) 93, osteoarthritis (OA) 68, chronic pyrophosphate arthropathy 80, acute pseudogout 20, others 27) from knees of 138 patients (bilateral 67, serial sampling on two to six occasions 40). At each aspiration knees were defined as 'active' or 'inactive' by single observer global assessment using six clinical parameters of inflammation. Lack of correlation between paired SF and plasma C3dg/d implied local C3 activation within joints. Raised SF C3d levels were found in active compared with inactive RA joints (mean (range) 51 (15-105) and 6 (0-15) units/ml respectively). Low SF C3dg/d levels were found in OA (mean (range) 0.8 (0-7) units/ml) and chronic pyrophosphate arthropathy (mean (range) 4 (0-16) units/ml), irrespective of clinical activity. In contrast, very high levels (mean (range) 61 (16-126) units/ml) were present in all cases of pseudogout. These differences remained after correction for SF C3 or albumin. This study is the first to show a positive correlation between SF C3dg/d and local inflammation in RA joints. It further suggests that C3 activation is a constant feature of pseudogout but not an accompaniment of inflammation associated with chronic crystal associated synovitis or OA. | |
2814208 | Occurrence of interleukin-1 in human synovial fluid: detection by RIA, bioassay and presen | 1989 | Synovial fluid (SF) from patients with osteoarthritis (OA), rheumatoid arthritis (RA), and various other arthridites was analyzed to assess the prevalence of interleukin-1 (IL-1) using both radioimmunoassay competitive inhibition specific for the beta form of IL-1 and the D10.G4.1 cell line bioassay which measures both alpha and beta forms of IL-1. Using radioimmunoassay competitive inhibition, IL-1 beta was found in 45% and 60% of individual samples from patients with OA and RA respectively. When RA and OA SF were examined in sequentially obtained samples, IL-1 beta occurred in one or more samples from 8 of 10 patients studied, suggesting the probability that it can be produced at some time in SF by all patients with these conditions. No correlation between SF leukocyte counts and the occurrence of IL-1 beta was noted and no effect of antiinflammatory drug treatment on the prevalence of IL-1 beta was found. When tested for the presence of IL-1 by the D10.G4-1 cell line, 66% and 50% of RA and OA patients respectively were found to contain IL-1. These were not in total concordance with results obtained by RIA. Of all SF tested, seven were negative by RIA but positive by D10.G4.1 and these are considered to contain IL-1 alpha. Seven samples which were RIA positive and D10.G4.1 negative were tested for their ability to inhibit IL-1 responses in the bioassay. Five of these contained inhibitor and one markedly enhanced the proliferative response of D10.G4.1 to a known amount of IL-1.(ABSTRACT TRUNCATED AT 250 WORDS) | |
3589998 | [Circadian rhythm of uric acid levels of the serum in gout]. | 1987 | Uric acid concentration in the serum was investigated 3 times a day using the uricase method in 15 gout inpatients on a hypopurine diet with age- and sex-adjusted caloric content. The highest uric acid concentration was noted at 7 a. m., the lowest concentration value at 11 p. m. The highest renal clearance values were noted from 7 a. m. till 3 p. m., the lowest ones from 11 p. m. till 7 a. m. Similar regularities were noted in 15 rheumatoid arthritic patients, however uric acid concentration in the serum was lower and its renal excretion was 1.7 times more effective. | |
1716899 | Natural IgG to epidermal cytokeratins vs IgG to the stratum corneum of the rat oesophagus | 1991 Jun | In order to study the relationships between the circulating IgG autoantibodies to epidermal cytokeratins (AECK), which were described in normal human sera as well as in sera from patients with various diseases, and the so-called 'antikeratin' IgG antibodies ('AKA'), which are highly specific for rheumatoid arthritis (RA), we simultaneously investigated AECK by a specific ELISA using cytokeratins from human stratum corneum (SC) and 'AKA' by semiquantitative indirect immunofluorescence assay on rat oesophagus epithelium, in a large series of 595 rheumatic sera including 229 RA. AECK were found to be present in all the 595 sera, with large inter-individual variations in titre. Whatever the titre chosen as threshold, the autoantibodies (auto-Ab) were never found to be specific for any rheumatic disease. Moreover, in RA, they were found to vary independently of IgM rheumatoid factor (IgM-RF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), while they were found to vary in parallel with the total serum IgG concentration. In contrast, although 568 of the 595 rheumatic sera contained antibodies that labelled the rat oesophagus SC, the highest titre-like values were obtained with RA sera. At a convenient threshold, 95 (41.5%) of the 229 RA were detected while only three false positives (0.08%) remained among the 366 non-RA sera. Moreover, in RA, 'AKA' were found to be related to IgM-RF, ESR and CRP, while their titre was found to be independent of the total serum IgG concentration. Lastly, no statistical correlation was found between the antibodies, either in the whole sample of 595 sera or in any diagnostic group. In conclusion, the simultaneous investigation of AECK and 'AKA' showed that they differ from each other in all the aspects explored. AECK belong to the widely explored family of natural auto-Ab against cytoskeleton components and do not constitute a diagnostic marker while, on the other hand, 'AKA' confirmed their high diagnostic specificity for RA. It can also be asserted that, in spite of their name, 'AKA' do not recognize human epidermal cytokeratins, at least in the denatured form they present in ELISA. Therefore, they recognize either conformational epitope(s) appearing on cytokeratins during the late stages of the cornification process, or epitope(s) borne by rat cytokeratins but absent on human cytokeratins, or lastly a non-cytokeratin SC antigen. | |
3312603 | Nicardipine for the treatment of Raynaud's phenomena: a double blind crossover trial of a | 1987 Aug | Fifteen patients with Raynaud's phenomenon [systemic lupus erythematosus (6), progressive systemic sclerosis (8) and rheumatoid arthritis (1)] and 12 patients with Raynaud's disease participated in a parallel, 4-week/arm, double blind, crossover study of nicardipine, an experimental calcium channel blocker. Nicardipine significantly improved pain (p = 0.03), decreased number of Raynaud's attacks (p less than 0.03), and was preferred over placebo (p less than 0.05) in the patients with Raynaud's disease, but showed an effect only in the number of attacks (p = 0.049) among the group with Raynaud's phenomenon. Plethysmography showed no drug effects. One patient discontinued the trial after developing headaches while taking placebo. Nonlimiting toxicity occurred more commonly with drug than placebo (15 vs 9 times, p less than 0.05). Our study demonstrated that nicardipine improves symptoms in Raynaud's disease, but is not effective in Raynaud's phenomenon. | |
2789325 | Interleukin 1 in rheumatoid arthritis: potentiation of immune responses within the joint. | 1989 Fall | Specific immunoassays were used to measure IL-1 peptides in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and in the serum of age-matched healthy controls. Patients with RA had raised levels of both IL-1 beta and IL-1 alpha in their sera compared to controls. Synovial fluid levels of IL-1 beta significantly correlated with immunoreactive IL-2 and soluble IL-2 receptor (sIL-2R). In addition, incubation of synovial fluid MNC with human recombinant (hr) IL-1 caused a dose-dependent increase in the level of sIL-2R in the cell supernatant. Finally, production of IL-1 beta and IL-6 from RA peripheral blood (PB) and synovial fluid (SF) MNC was examined. PBMNC spontaneously produced low levels of IL-1 beta and IL-6 that were augmented by the addition of hr IL-1 alpha. In contrast, SFMNC spontaneously produced high levels of IL-1 beta but only low levels of IL-6, again this production was augmented by the addition of hr IL-1 alpha. Taken together, the data suggests that IL-1 potentiates immune responses within the joint. | |
3950143 | Cervical myelopathy: a comparison of magnetic resonance and myelography. | 1986 Mar | Fifty-seven patients with a strong clinical suspicion of cervical myelopathy were studied with body coil magnetic resonance (MR) and conventional myelography or CT myelography. Eight patients were believed to have normal studies with both modalities. There were six patients with syringomyelia; four with an intramedullary tumor; one with an arteriovenous malformation; 19 with cervical spondylosis at multiple levels; eight with cervical spondylosis at a single level; four with extensive rheumatoid arthritis; four with extradural neoplasm; two with trauma; and one patient with an epidural abscess. In this study, body coil MR was the superior examination for the evaluation of an intramedullary process. It was as diagnostic as myelography in one case of an extramedullary intradural lesion. In patients with extradural disease, body coil MR was the superior study in 45%, equivalent to myelography in 37%, and, although still diagnostic, inferior to myelography in 17%. In 8% of the cases, body coil MR was at best equivocal, whereas myelography was diagnostic. It appears that in technically adequate studies, MR is at least equivalent to myelography in its ability to delineate disease. A superior MR study provides a better appraisal of the size and character of the spinal cord as well as the degree of both anterior and posterior defects on the subarachnoid space and neural structures. In addition, MR is as good as conventional myelography for the identification of extrinsic cervical cord lesions producing cervical myelopathy. Finally, an additional small group of 30 patients were studied with a prototype surface coil to determine its advantages relative to body coil imaging. Each patient had correlative myelography. As with body coil MR, imaging with the surface coil was believed to be more informative than conventional myelography in four patients with intramedullary lesions. The remaining 26 patients suffered from cervical spondylosis. Surface coil MR was believed to be more informative than myelography in six cases (23%), equivalent to myelography in 19 (73%), and less diagnostic than myelography in one (4%). The improved spatial resolution with the use of the surface coil was believed to increase the accuracy of MR. | |
3075109 | [Gastroduodenal lesions in rheumatoid arthritis. Evaluation and treatment]. | 1988 | In a group of 70 patients of both sexes been treated with antiinflammatory drugs, affected by Rheumatoid Arthritis in activity, we have found the presence of lesions, erosions and gastroduodenal ulcers in 40% by endoscopic examination (26% erosions and 14% ulcers), without any relation with clinical symptoms. Those patients who received larger doses than 30mgr./kg./day of AAS suffered most frequently lesions (43.8%). These 28 patients with lesions have been studied prospectively in a double blind method, and treated twice a day with 150 mgs. doses of Ranitidine or Placebo, throughout a period of 5 weeks without discontinuing the treatment with anti-inflammatories (AAS, Indomethacin, steroids). At the end of the trial those patients who failed in healing their lesions were treated with Ranitidine in the same doses for another period of 5 weeks. The treatment with Ranitidine in doses of 300 mgr/day has resulted curative of the gastroduodenal lesions, although maintaining the aggressive drugs, in the 87% of the patients. We have observed that the treatment with Placebo is less effective and that difference has high statistical significance (p 0.005). | |
1801259 | Fusion of the occiput to the upper cervical spine. A review of 37 cases. | 1991 Oct | This is the first report of a large series of patients undergoing preoperative traction to reduce spinomedullary compression from cranial settling. In all cases, an attempt was made to reduce the malalignment with Gardner-Wells or halo traction before posterior fusion. One patient required an anterior retropharyngeal decompression of the odontoid performed as a one-stage procedure at the time of the posterior operation, and two required subsequent anterior transoral-transpharyngeal resection of the odontoid. From 1974 to 1989, 37 patients underwent posterior occipital cervical arthrodesis. All cases presented with neurologic deficit, and most had signs of brain stem compression, such as L'hermitte's sign or Ondine's curse. The most common cause of basilar impression was rheumatoid arthritis, neoplastic destruction, previously failed C1-C2 fusion, or Down's syndrome. Mean postoperative follow-up was 2 years and 10 months; the patients with less than 2 years' follow-up were followed until successful fusion. Eight of 9 patients with L'hermitte's sign or Ondine's curse and 10 of 12 patients with intractable occipital pain were relieved of their symptoms after reduction and triple-wire stabilization-fusion. Eighteen of 25 patients with long tract signs improved after surgery. Interestingly, 14 (93.3%) of 15 patients with myelopathy improved when successful preoperative reduction of their deformity occurred, whereas only 4 (40%) of 10 patients with fixed basilar impression improved (chi 2 = 8.57, P = .014). Symptoms such as Ondine's curse, L'hermitte's sign, intractable occipital headache, and myelopathy are usually relieved by skeletal traction and posterior fusion without need of an additional transmucosal anterior procedure.(ABSTRACT TRUNCATED AT 250 WORDS) | |
2498190 | The chronic proliferative disease of large granular lymphocytes. | 1989 Jan | This review deals with the chronic lymphoproliferative disease of large granular lymphocytes endowed with T and natural killer cell characteristics. The disease is sufficiently characterized to allow its distinction from other lymphoproliferative disorders of the T cell type. The heterogeneous clinical course and laboratory findings illustrate the complexity of the interaction between proliferating large granular lymphocytes and other haematopoietic cells. | |
3140823 | Sex hormone status of male patients with rheumatoid arthritis: evidence of low serum conce | 1988 Oct | Serum concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, 17 beta-estradiol, testosterone, androstenedione, dehydrotestosterone, dehydroepiandrosterone sulfate, and cortisol were examined in 14 men with rheumatoid arthritis (RA) and in age-matched osteoarthritis controls. Hypophyseal, adrenal, and testicular responses to stimulation with luteinizing hormone-releasing hormone, adrenocorticotropin, and human chorionic gonadotropin, respectively, were evaluated in 8 RA patients and in 8 age-matched healthy volunteers. Basal serum testosterone concentrations were significantly lower in male RA patients than in the osteoarthritis control subjects (P less than 0.01). After human chorionic gonadotropin stimulation, serum concentrations of testosterone were also lower in the RA patients than in normal healthy controls (P less than 0.05). These findings suggest that diminished testicular steroid biosynthesis might contribute to the serum testosterone deficiency observed in male RA patients. | |
3526298 | Ketoprofen: a review of its pharmacologic and clinical properties. | 1986 May | Ketoprofen (Orudis), a highly potent and safe nonsteroidal antiinflammatory drug of the propionic acid derivative group, was synthesized in France by Rhône-Poulenc chemists in 1967, 3 years after the prototype ibuprofen. Ketoprofen was introduced in 1973 in France and the United Kingdom for antiinflammatory use. Today the drug is available in about 80 countries and has recently been approved in the United States for treatment of rheumatoid arthritis and osteoarthritis. The therapeutic experience with ketoprofen is estimated to have exceeded 3 million patient-years. Double-blind trials have established its therapeutic equivalence with aspirin, indomethacin, and ibuprofen in rheumatoid arthritis and with aspirin in osteoarthritis. Ketoprofen has a short half-life, a simple metabolism, and a broad therapeutic window, and does not accumulate with multiple doses. These features contribute to a rapid onset of action, flexible dosing, and a reliable tolerance profile. | |
2869760 | Histamine stimulates prostaglandin E production by rheumatoid synovial cells and human art | 1986 Feb | Histamine stimulates prostaglandin E (PGE) production by cultures of adherent rheumatoid synovial cells and human articular chondrocytes. When subcultured synovial fibroblasts or human articular chondrocytes were "primed" by preincubation with conditioned media from primary adherent rheumatoid synovial cell cultures (synovial factor), each produced even higher PGE levels upon histamine exposure. This histamine stimulation was prevented by histamine H1, but not H2, antagonists and was more marked if serum was absent from the culture media. Thus, histamine-induced PGE production by these cells is mediated via H1 receptor activation and subsequent arachidonic acid liberation. | |
2370425 | T cell receptor phenotypes in autoimmune thyroid disease. | 1990 Apr | We have examined T cell receptor expression by peripheral blood and thyroidal lymphocytes in Graves' disease and Hashimoto's thyroiditis, using monoclonal antibodies directed against three beta chain variable region families and against the gamma chain. There was no abnormal distribution of positive staining with the beta chain reagents (compared to normal peripheral blood) in either the thyroid or the blood. However, thyroidal lymphocytes contained an excess of gamma-chain-bearing T cells, compared to peripheral blood, in five of the seven patients in whom simultaneous samples were available. The gamma-chain-positive T cells were not altered in the blood lymphocyte population of untreated Graves' patients. These results suggest that the T cell response in autoimmune thyroid disease is polyclonal and that there may be a role (such as cytotoxicity) for T cells expressing the gamma delta type of T cell receptor in thyroiditis. | |
2556230 | Alterations in arachidonic acid metabolism and chemotactic response in polymorphonuclear l | 1989 Sep | This study examines the interrelationship between arachidonic acid (AA) metabolism and chemotactic potential of human peripheral blood neutrophils from both normal donors and patients with rheumatoid arthritis (RA). We demonstrate that there is a significant inverse relationship between the neutrophil's metabolic capability to produce [3H]LTB4 in response to ionophore A23187 stimulation versus the cell's chemotactic potential to optimal concentrations (i.e., 20 nM) of the chemotactic peptide f-Met-Leu-Phe as determined by leading front (r = 0.567, p = 0.009), mean depth (r = 0.458, p = 0.042), and population ratio (r = 0.471, p = 0.036) analyses. Subsequent Percoll density gradient studies revealed several RA neutrophil subpopulations exhibiting significantly enhanced (p less than 0.05) [3H] AA metabolism over corresponding density normal cells. Based on these results, we speculate that RA peripheral blood neutrophils have been "processed" to become less chemotactically-responsive yet more metabolically-active cells, and that the increased ability to produce LTB4 through both increased phospholipase A2 and lipoxygenase activities are part of the increased metabolic capabilities of the cell. | |
2943425 | PHA-T cells in systemic lupus erythematosus and in rheumatoid arthritis: abnormalities in | 1986 Jan | Analysis of T cells from patients with systemic lupus erythematosus (SLE) and with rheumatoid arthritis (RA) identified a deficit in the induction of HLA Class II antigens by PHA although the proliferative response was normal and in the [3H]thymidine incorporation in autologous mixed lymphocyte reactions (MLR) with PHA-T cells as stimulators. In RA these abnormalities were more marked in patients with active disease than in those in clinical remission. The deficit of autologous MLR with PHA-T cells was more marked than that of autologous MLR with non-T cells and of allogeneic MLR. Serum from patients with SLE and with RA did not display any detectable inhibitory activity on the induction of HLA Class II antigens by PHA, on the proliferative response of lymphocytes to PHA, on autologous MLR with PHA-T cells and with non-T cells as stimulators and on allogeneic MLR. These results suggest that the abnormalities we have identified reflect an intrinsic defect of T cells. |