Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3123673 | Immunosuppression as initial treatment for gold induced aplastic anemia. | 1987 Oct | Three patients who received antithymocyte globulin therapy for severe aplastic anemia due to gold therapy are described. In 2 patients the hemoglobin, white blood cell count and neutrophils were normal and platelet counts exceeded 100 X 10(9)/1 more than 2 years after treatment. The 3rd patient did not respond to antithymocyte globulin or to cyclosporine therapy; subsequent allogeneic bone marrow transplantation resulted in satisfactory engraftment at 12 months. In all 3 patients the arthritis was improved after the episode of marrow aplasia and its treatment. Including these 3 patients, 12 reported patients with severe aplastic anemia due to gold have now been treated with antithymocyte globulin; 8 have shown significant improvement. These results are better than those reported for any other treatment. Antithymocyte globulin may be optimal initial treatment for this serious disorder. | |
| 2491600 | Antinuclear antibodies detected by indirect immunofluorescence on HEp2 cells and by immuno | 1989 | The HEp2 cell cultures appeared highly sensitive in detecting the antinuclear antibodies (ANAb) in systemic sclerosis, principally anticentromere antibodies of the CREST syndrome. The immunoblotting used with either complex cellular extracts from HeLa and rabbit thymus or purified nuclear components (high mobility group (HMG) proteins and histones) is able to identify precisely the ANAb targets and to contribute to diagnosis. With nuclear extracts of HeLa cells, the sera from 75.8% of CREST syndrome subjects stained 18 and 22 kD proteins. Corresponding antibodies were also detected in 72.7% of these patients, on HEp2 centromers by indirect immunofluorescence. With the same extracts, 33.3% of sera from diffuse sclerosis/acrosclerosis patients contain antibodies staining 86, 73, 32 and 30kD. These sera also stain 77, 66 and 63kD from thymus extracts. Corresponding antibodies will be the anti-SCL-70 antibodies defined by double immunodiffusion. The anti-HMG antibodies were infrequent in systemic sclerosis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and consequently without interest for diagnosis. The anti-whole histones antibodies which are less frequent in diffuse sclerosis/acrosclerosis (35.7%) than in SLE (41.3%) recognize especially H1 and H2A in the first diseases, H1 and H2B in SLE and H1 and H3 in RA. | |
| 1855751 | [Therapy of degenerative rheumatic diseases. Need for additional analgesic medication with | 1991 Apr 10 | In 40 inpatients with painful degenerative diseases, the additional requirement for nonsteroidal anti-inflammatory drugs (NAIDs) to obtain results identical with a given daily dose of either 3 x 30 drops of Phytodolor N or placebo administered over 3 weeks was investigated. Under Phytodolor N, a total of 100 mg of diclofenac and 1 tablet (500 mg) of paracetamol were additionally administered in 18 patients; under placebo, 2,400 mg of diclofenac and 3 tablets of paracetamol. In terms of days, additional medication was required on 3 days in the Phytodolor group, and on 47 days in the placebo group. Under Phytodolor N, the improvements obtained were identical to those in the group receiving in part considerably higher doses of NSAIDs and placebo. Clinical improvements are marked and major improvements (p less than 0.05) occur after only 1 week, with improvement being progressive. No side effects were observed. | |
| 2115417 | Soluble CD8 in patients with rheumatic diseases. | 1990 Jun | An ELISA was used to measure soluble CD8 (sCD8) in the sera and synovial fluids (SF) of patients with rheumatic diseases. Patients with rheumatoid arthritis (RA) had raised levels of sCD8 both in their sera and in their SF compared with patients with osteoarthritis and age-matched healthy controls. In individual RA patients, serial serum sCD8 levels initially fell and then rose preceding clinical improvement. In four patients where serum sCD8 levels rose and clinical improvement occurred, subsequent spontaneous decreases of serum sCD8 level preceded increased clinical disease activity by up to 2 weeks. In general, RA SF mononuclear cells (SFMNC) spontaneously produced high levels of sCD8. In contrast, autologous peripheral blood MNC only produced comparable levels after mitogenic stimulation. Incubation of SFMNC with increasing concentrations of human recombinant tumour necrosis factor alpha resulted in a dose-dependent potentiation of sCD8 release into the supernatant. There was an inverse relationship between the ability of SFMNC to release sCD8 and soluble interleukin-2 receptor, indicating that the CD8+ T cell population may play an important immunoregulatory role in RA. | |
| 2802793 | Synthesis of the active metabolite of vitamin D, 1,25(OH)2D3, by synovial fluid macrophage | 1989 Sep | Synthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been shown in cells from knee joint synovial fluid of 20 patients with inflammatory rheumatoid disease, reactive or psoriatic arthritis, or gout, all of which had high synovial fluid cell counts, and by cells from a patient with aseptic necrosis of a femoral condyle after short term (less than 24 hours) or long term (seven days) primary culture. Cells from 18 patients with inflammatory arthritis, five of which had low synovial fluid cell counts and cells from six patients with osteoarthritis were unable to synthesise this metabolite from 25-hydroxyvitamin D3 (25(OH)D3). Macrophages are believed to be the cells responsible for synthesising 1,25(OH)2D3 because these were significantly more numerous in samples that formed 1,25(OH)2D3; they were also the predominant cell type present in the aseptic necrosis sample and the only cell type present in preparations maintained for one week in monolayer culture. | |
| 3500239 | Determination of C4b.C4-bp complex formed by the activation of classical complement pathwa | 1987 Dec 4 | We developed a quantitative enzyme-linked immunosorbent assay (ELISA) for the detection of C4b.C4-bp complex by incubating the sample on anti-C4-bp-coated plate and then developing with HRP-labeled anti-C4. The amount of C4b.C4-bp complex, generated in vivo by the interaction of purified C4b with C4-bp or normal human serum with aggregated human IgG, was measured by the ELISA. The complex, however, rapidly decreased in serum by the action of factor I. Six out of the 100 plasma samples from patients with various diseases were found positive in the ELISA. One plasma sample from a patient with SLE showed high level of C4b.C4-bp complex with decreased levels of factor I, C4, C4-bp and CH50. These results suggest that the detection of C4b.C4-bp complex is useful for monitoring the diseases in which the classical pathway activation is expected. | |
| 3511088 | Human-human hybridoma autoantibodies with both anti-DNA and rheumatoid factor activities. | 1986 Jan | Human hybridomas have been produced by fusing peripheral blood lymphocytes from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) with the GM 4672 human cell line. 262 hybridoma clones from the fusions of four RA and five SLE patients were screened for binding to denatured DNA (dDNA), native DNA, and the Fc fragment of human IgG (HIgG). Of the 17 hybridoma antibodies (nine RA, eight SLE) selected for strong binding to denatured DNA, Fc, or both, five reacted with dDNA only, one with Fc only, and eight with both dDNA and Fc. Hybridoma supernatants exhibiting dual reactivity were absorbed over HIgG and bovine serum albumin (BSA)-Sepharose immunoabsorbent columns. The reactivities to both DNA and HIgG were completely removed by the HIgG column but unaffected by passage over the BSA column, and both DNA binding and rheumatoid factor activities were recovered in the acid eluates from the Sepharose-IgG column. The binding of dual reactive hybridoma autoantibodies to the Fc fragment of HIgG was specifically competed by dDNA and HIgG, providing additional evidence that one antibody may be capable of reacting both as a rheumatoid factor and as an anti-DNA antibody. | |
| 2946224 | Gastrointestinal blood loss in arthritic patients receiving chronic dosing with etodolac a | 1986 Nov | Etodolac, a new anti-inflammatory analgesic drug found to be effective in treating arthritis in a dose range of 100 to 300 mg bid, has been shown to induce significantly less gastrointestinal microbleeding in normal men than several other NSAIDs. In this study, the effect on gastrointestinal blood loss of high-dose etodolac, 300 and 500 mg bid, versus piroxicam at its normal therapeutic dose of 20 mg qd, was investigated by the 51Cr method in 23 men with osteo- or rheumatoid arthritis. Placebo periods preceded and followed 28 days of active drug treatment. Blood and stool analyses were performed by an analyst not aware of drug assignment or study design. Patients receiving piroxicam, but not those receiving either dose of etodolac, had a significantly higher mean level of fecal blood loss in the active treatment phase compared with the pretreatment placebo level (p less than 0.01). Further, microbleeding was significantly greater for the piroxicam group during treatment than for either of the etodolac groups (p less than 0.01). There were no significant differences in fecal blood loss between the two groups receiving etodolac compared with pretreatment. Even at doses two to three times those found effective in the treatment of arthritis, etodolac produces no increase in fecal blood loss, in contrast to blood loss seen with the recommended dose of piroxicam. Fecal blood loss in osteoarthritic patients, not receiving an NSAID, was similar to normal subjects in previous studies. | |
| 2923503 | Measurement of sulphated glycosaminoglycans and proteoglycan fragments in arthritic synovi | 1989 Jan | Immunoreactive proteoglycans (iPGs) and sulphated glycosaminoglycans (GAGs) were assayed in synovial fluid obtained from 22 patients with osteoarthritis (OA), 21 with rheumatoid arthritis (RA), 13 with gout, and five with Reiter's syndrome. A strong positive linear correlation was observed between concentrations of sulphated GAGs and iPGs in RA (r = 0.95) and gout (r = 0.94). A linear correlation was also observed in OA (r = 0.65). Patients with gout and Reiter's syndrome had significantly higher concentrations of sulphated GAGs and iPGs than patients with OA or RA. Patients with gout also had significantly higher total quantities of sulphated GAGs and iPGs in the knee joint cavity than patients with OA or RA. In all four diseases similar profiles were observed when comparisons were made between the total quantities and concentrations of sulphated GAGs and iPGs in synovial fluid. These results indicate that the observed differences in concentrations are not simply a function of dilution. The concentrations of sulphated GAGs and iPGs did not correlate closely with the type or number of inflammatory cells in the synovial fluid. Considerable variation was noted in the sulphated GAG/iPG ratios, suggesting that different mechanisms may be contributing to the release of proteoglycans in the diseases studied. | |
| 2170450 | The complete nucleotide sequences of the heavy chain variable regions of six monospecific | 1990 Oct | Structural studies of human monoclonal rheumatoid factors (RF) derived from patients with monoclonal gammapathies have revealed a restriction in the usage of heavy and light chain variable regions. These studies have suggested that germline genes with little if any somatic mutation can generate RF specificity. However, there is no information presently available regarding the primary structure and genetic origin of RF in rheumatoid arthritis. In this study, we have isolated and sequenced the VH regions of six monoclonal RF derived from the synovial membranes of two patients with rheumatoid arthritis and one with the juvenile polyarticular form of the disease. We found the same VH families as previously reported among monoclonal paraproteins with RF activity. However, our sample was diverse regarding the VH, DH, and JH gene segments used. Among VHI RF there was conservation in the length of CDRIII as well as restriction in the amino acid generated at the V-D junction, as opposed to VHIII RF and non-RF VHI molecules that are highly heterogeneous in these two aspects. We also found that different JH gene segments may contribute to RF specificity. The VH, DH, and JH elements of one RF in our study all had clearly identifiable germline counterparts. This RF displays a nearly germline configuration throughout its entire heavy chain and represents another example of an autoantibody encoded by one of the VH gene segments from the preimmune fetal repertoire. | |
| 2464451 | Fine antigenic specificities of antibodies in sera from patients with D-penicillamine-indu | 1988 Oct | A small fraction of patients with rheumatoid arthritis and other diseases on D-penicillamine treatment may develop antibodies against the acetylcholine receptor (AChR) and symptoms of myasthenia gravis (MG). The mechanism leading to this phenomenon is not known. We have studied the fine antigenic specificities of the anti-AChR antibodies in 19 D-penicillamine-induced MG (pen-MG) patients and compared them with those of antibodies from 204 idiopathic MG patients (the data for 122 obtained from earlier experiments). Antigenic specificities of the circulating antibodies were determined by the capacity of monoclonal antibodies (MoAbs), against certain determinants on the AChR, to inhibit binding of the serum antibodies to the AChR. Monoclonal antibodies against alpha, beta and gamma subunits were used. The anti-AChR antibody patterns of pen-MG patients were very similar to those of idiopathic MG patients. Antibodies to the main immunogenic region, which is located on the extracellular surface of the alpha-subunit, were the predominant group. The variations of antibody specificities in serial sera collected from individual patients at different times were usually small, as were those of idiopathic MG. These results strongly suggest that the antibody repertoire in the sera of idiopathic and pen-MG patients is very similar. | |
| 3661053 | Antibodies to membrane antigens in autoimmune thyroid disease. | 1987 Sep | The possibility that sera from patients with autoimmune thyroid diseases contain autoantibodies to thyroid membrane proteins distinct from microsomal antigen and the TSH receptor has been investigated using (a) solid phase assay system based on human thyroid membranes and 125I-labelled protein A and (b) immunoprecipitation of detergent solubilized 125I-labelled thyroid membranes followed by gel electrophoresis and autoradiography. In the solid phase assay binding to membranes showed a highly significant correlation with binding to microsomes (r = 0.82; P less than 0.001; N = 82) indicating that the interaction between the serum and the membranes was due principally to microsomal antibody binding to microsomal antigen contaminating the membrane preparations. However, there were some discrepancies suggesting that an additional antigen-antibody system was involved. This possibility was then investigated using immunoprecipitation of 125I-labelled thyroid membranes. A labelled protein with mol wt 54 K was specifically immunoprecipitated (relative to normal pool serum) by 3 out of 4 sera from patients with Graves' disease who showed high binding to thyroid membranes. A further 4 sera from such patients with low membrane binding affinity failed to immunoprecipitate the 54 K protein. Sera from some patients with Hashimoto's disease and some patients with rheumatoid arthritis and one patient with Addison's disease also immunoprecipitated the 54 K protein from solubilized thyroid membranes. These studies suggested that antibodies interacting with the 54 K protein contributed to the discrepancies between thyroid membrane and microsome binding. However, the 54 K protein was also immunoprecipitated from detergent solubilized membranes prepared from human placenta, skeletal muscle and adrenal tissue.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2111124 | Genes associated with rheumatoid arthritis and mild inflammatory arthritis. II. Associatio | 1990 Apr | Associations were sought between major histocompatibility complex (MHC) genes on chromosome 6 and the complement component C3 and immunoglobulin genes located on other chromosomes which might contribute to susceptibility to mild inflammatory arthritis (IA) or definite rheumatoid arthritis (RA). Frequencies of the complement C3F allele were raised in patients with IA but were normal in patients with RA and controls. When associations between C3F and MHC genes were sought frequencies of some MHC genes were greater in patients with C3F than in those without--for example, HLA-B8 and DR3 in patients with RA and DR2 in patients with IA. Conversely, DR4 frequency was lower in patients with IA with C3F than in those without. Thus the C3F allele may act independently or exert an epistatic effect on MHC genes to increase susceptibility or protect against disease. The frequency of the immunoglobulin heavy chain allotype Glm(2) on chromosome 14 was increased in patients with RA but only in those with the phenotype Gm1,2,3,17;21,5; no significant associations were found between MHC genes and Gm phenotypes. Further, no associations of MHC, C3F, and immunoglobulin genes were shared by patients with RA and those with IA, indicating a different genetic basis for the two clinical entities. | |
| 3716887 | Transclival transcervical approach to the upper cervical spine and clivus. | 1986 | The transclival-transcervical approach to lesions of the craniocervical junction is described. It gives reasonable access to the lower part of the clivus and to C1 and C2 for removal to tumours and stabilization of fractures and otherwise caused dislocations of this region. Because an opening of the pharynx can be avoided, reconstruction work can be done using bone graft or reinforced methyl-methacrylate without risk of infectious contamination. The results obtained in 6 cases are presented. | |
| 2772260 | Measurement of the chronic pain experience: development of an instrument. | 1989 Aug | Development and testing of the Chronic Pain Experience Instrument (CPEI) were initiated to address the need for a valid and reliable instrument for the accurate clinical assessment of, as well as for the empirical investigation of, the chronic pain experience, that is, the personal response to living with nonmalignant persistent pain. When tested with persons with rheumatic disease (N = 160), the 16-item CPEI demonstrated high internal consistency, adequate stability, and moderate construct validity. Analysis included coefficient alpha, interitem correlations, item-scale correlations, Pearson r, factor analysis, and predictive modeling. Additional testing of the CPEI is suggested prior to its clinical application. | |
| 2760657 | Diagnosis deferred--the clinical spectrum of diagnostic uncertainty. | 1989 | This study attempts to define the term "Diagnosis Deferred" (DD) and determine its natural history and outcome. It is suggested that such a "non-diagnosis" should be used when the clinical and laboratory picture cannot be explained by any known disease entity after a minimum of 5 days hospitalization. During a 9 year period (1972-1980) 250 patients (1.8%) were identified as warranting the term DD from a total of 14,098 admissions to a department of Internal Medicine. Their average stay in hospital was 11.5 days. There was no sex difference between the patients, whose average age was 42.8 +/- 17.6 years (mean +/- SD; range 14-93). Three complaints predominated: joint pains (21.6%), abdominal pain (20.4%) and chest pain (16.8%). In 103 of the patients, there was follow-up information until the diagnosis was made or for at least 24 months (average 53.0 +/- 40.0 months, range 2-186). These patients were representative of the original cohort in both age, sex and classification of symptoms. Forty-three patients (42%) were subsequently diagnosed. 58% of these patients were diagnosed as a result of a change in or appearance of a clinical symptom during the follow-up period. "The survival of diagnostic uncertainty" in 50% of the patients was 84.5 months (7 years) with a range of 2-13 years. This time was significantly shorter for chest pain than for abdominal pain (33 months vs 87 months) (p = 0.003). In patients with "Diagnosis Deferred", a diagnosis was reached in 42%; in 22% the symptoms disappeared leaving 36% undiagnosed, and a continuing clinical challenge. | |
| 2834287 | [Expression of interleukin 2 receptors in in vivo Epstein-Barr virus transformed B lymphoc | 1988 Feb | Interleukin-2 (IL-2) enhances the proliferation of in vivo Epstein-Barr virus-(EBV)-transformed B-cells from patients with a present or past history of infectious mononucleosis. In contrast, there is less expression of functional IL-2 receptors on EBV-transformed B-cells from patients with rheumatoid arthritis. These results suggest differences in the involvement of B-cells in EBV-associated diseases. | |
| 2148285 | Cytolytic activity in T cell clones derived from human synovial rheumatoid membrane: inhib | 1990 Dec | A panel of T cell clones was derived from the synovial membrane of a patient with rheumatoid arthritis (RA). We investigated whether T cell clones with cytolytic properties were present and whether T cell cytotoxicity was influenced by the presence of synovial fluid. These issues were studied using anti-CD3 and lectin-induced cytotoxicity assays. The majority of the T cell clones derived from the synovial membrane showed cytotoxic properties although non-cytotoxic clones were also found. Three clones (N11, N6 and N15) showed strong cytotoxicity (more than 40% lysis at an effector-to-target cell ratio of 10:1) whereas three clones (N16, N4 and N14) were non-cytotoxic (less than 20% lysis at an effector-to-target cell ratio of 10:1). The induction of cytotoxicity in the anti-CD3-driven system was shown to be dependent on the dose of anti-CD3 present. When synovial fluid was added to these assays a strong inhibition of cytotoxicity was found. This inhibition of cytotoxicity was found with synovial fluid samples of RA patients, as well as with non-RA synovial fluids. Both anti-CD3 and lectin-dependent cytotoxicity assays were strongly inhibited. In conclusion, T cell clones with cytotoxic activity can be isolated from rheumatoid synovial membrane. In the presence of synovial fluid these cytotoxic cells are inhibited to exert their cytotoxic function. | |
| 3021211 | Purification of human collagenases with a hydroxamic acid affinity column. | 1986 Sep 9 | Human collagenase has been isolated from skin fibroblasts and rheumatoid synovium by using an affinity matrix, prepared by coupling Pro-Leu-Gly-NHOH to agarose. Following the methodology described herein, the skin enzyme was isolated in two steps in 76% yield and the synovial enzyme was purified in three steps in 71% yield. Importantly, each enzyme hydrolyzed collagen into 3/4-1/4 cleavage fragments, indicating that a true collagenase had been isolated. The column was specific for the human enzyme since the collagenase from Clostridium histolyticum did not bind. The affinity ligand was designed according to the formalism proposed by Holmquist and Vallee [Holmquist, B., & Vallee, B. L. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 6216] that effective metalloenzyme inhibitors can be synthesized by coupling a suitable metal-coordinating group to a substrate analogue. In this case, the hydroxamic acid probably coordinates to the active-site metal and the Pro-Leu-Gly moiety is similar to the carboxyl side of the cleavage site of collagen, the enzyme's substrate. The IC50 for N-(benzyloxycarbonyl)-Pro-Leu-Gly-NHOH is 4 X 10(-5) M for both enzymes. The affinity chromatographic procedures described here should aid in future studies on vertebrate collagenases. | |
| 1844738 | [Secondary bladder amyloidosis: a case of salvage cystectomy for massive hematuria]. | 1991 Dec | Amyloidosis of the bladder associated with systemic amyloidosis secondary to rheumatoid arthritis is a rare disease. Due to the absence of routine screening, its incidence appears to be understimated and only 11 cases, all symptomatic, have been reported in the literature. The symptoms of this disease are dominated by macroscopic haematuria, always massive, which may be life-threatening. We report a case in which the severity of this haematuria required emergency cystectomy to ensure haemostatis, which revealed amyloidosis on histological examination. |