Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1722512 | Gold treatment of rheumatoid arthritis decreases synovial expression of the endothelial le | 1991 Oct | Leukocyte adhesion receptors on endothelial cells play an important role in the evolution of synovitis. We studied sequential synovial biopsies at Weeks 0, 2 and 12 in 11 patients with rheumatoid arthritis beginning parenteral gold therapy either alone or combined with 120 mg intramuscular methylprednisolone acetate at Weeks 0, 4 and 8 of treatment. Expression of endothelial leukocyte adhesion molecule 1 (ELAM-1) decreased on synovial blood vessels after both 2 and 12 weeks treatment (p less than 0.05), while the overall vascularity of the synovium did not change. Neutrophil numbers within the synovial membrane also decreased although this did not reach statistical significance. In contrast, there was no significant change in numbers or subset distribution of T cells or in Class II MHC expression by synovial lining cells, mononuclear cells or endothelial cells. Our results suggest that one of the early effects of intramuscular gold and glucocorticoid therapy may be a downregulation of the acute inflammatory process associated with the endothelial expression of a neutrophil adhesion receptor and the subsequent recruitment of neutrophils into the joint. | |
| 2326477 | Rheumatic disease of the temporomandibular joint: MR imaging and tomographic manifestation | 1990 May | Thirty-six temporomandibular joints (TMJs) in 28 symptomatic patients (aged 14-40 years) with rheumatic disease (mostly rheumatoid arthritis) were studied with magnetic resonance (MR) imaging and hypocycloidal tomography. MR images of four TMJs were normal. Another four TMJs showed internal derangement. Of the 28 TMJs presumed to show rheumatic disease involvement (26 with condylar destruction or deformation), 23 showed abnormal disk structure--five showing severe disk destruction and 18 showing less severe abnormalities (inhomogeneous structure, fragmentation, poor delineation, and severe flattening). MR images showed bone abnormalities in 27 of the 36 TMJs, and tomography showed abnormalities in 25 of the 36 TMJs. Good agreement between the two imaging modalities regarding surface irregularities was found. However, MR imaging demonstrated more extensive bone abnormalities than did tomography in 11 TMJs. The potential of MR imaging for depicting bone and soft-tissue abnormalities associated with rheumatic TMJ involvement was clearly demonstrated. | |
| 3690982 | The present and future of comprehensive outcome measures for rheumatic diseases. | 1987 Sep | In recent years, outcome, or health status, measurement has received wide attention in rheumatology. These measures are based on the concept of maintaining or improving health as the goal of medical care, the World Health Organization (WHO) definition of health, and measurement of those factors that directly impact the patient rather than the traditional measures of disease process. Within this framework, outcomes important to the patient with rheumatic diseases have been identified. They have been conceptualized in general terms of physical, psychological and social functioning or specifically by dimensions of death, disability, discomfort, side effects and economic costs. Two widely used outcome measures, the health assessment questionnaire (HAQ) and the arthritis impact measurement scales (AIMS), are described. Outcomes are measured by patient self-reported questionnaires which have been rigorously tested to establish the measurement properties of reliability and validity. Results show that patient self-report is valid, outcomes are accurately measured, correlate with traditional endpoints, and are sensitive to change over time. These measures are particularly suited for use in follow-up studies because of their simplicity, ease of administration, and cost. Future directions include additional study to define clinically meaningful change, extension of validations to many of the rheumatic diseases, the design of special purpose questionnaires and the development of the cumulative outcome concept. | |
| 3787173 | Clinical significance of surface and internal pools of platelet-associated immunoglobulins | 1986 Sep | We have investigated serum platelet bindable IgG(SPBIgG) and platelet-associated IgG(PAIgG) in patients with immune thrombocytopenia (IT) to ascertain the significance of the larger amounts of PAIgG reported both in normals and in patients using homogenized (Total:T-PAIgG) instead of intact platelets (Surface:S-PAIgG). 12 patients, during active immune thrombocytopenia (A-IT), and 18 patients in steroid-induced remission (S-IT), were studied. As control we considered 20 patients with non-immune thrombocytopenia (N-IT) and 29 subjects with normal platelet count. The average positivity of SPBIgG was 41% with a higher percentage in A-IT (66%) than in S-IT (16%). The results of PAIgG also indicate a different behaviour in A-IT and S-IT of surface and cytoplasmatic pools. During A-IT both pools are enhanced with prevalence towards the surface one (S-PAIgG). On the contrary, during steroid-induced remission, despite the normal amount of the S-PAIgG present the internal pool still increases, indicating a steady-state of IT and the possible existence of a platelet phagocytic activity. | |
| 3708231 | Haematological reassessment of rheumatoid arthritis using an automated method. | 1986 May | Thirteen haematological parameters were measured in 44 patients with rheumatoid arthritis (RA) and 39 disease control patients with ankylosing spondylitis (AS). Using a 10 000 cells per sample automated differential counter the most frequent abnormalities found were monocytopenia, low numbers of large unstained cells, basophilia and increased numbers of cells with high peroxidase activity (HPX). The total white cell count, lymphocyte and monocyte counts, the HPX count, platelet distribution width and erythrocyte sedimentation rate were able to distinguish RA from AS at a statistically significant level. Discriminant function analysis showed that a maximum of 55% of RA patients could be correctly classified into disease state when combinations of six out of seven laboratory tests were used. | |
| 3512683 | Physical and mechanical properties of joints (the pathomechanics of articular cartilage de | 1986 Jan | A review of the literature was performed to determine current theories regarding the physiology of human articular cartilage. The process of chondrodegeneration in rheumatoid arthritis and osteoarthritis was then discussed. Clinical pedal pathology was used to emphasize important but abstract concepts. | |
| 1666693 | [Rheumatoid arthritis: cyclic nucleotides in the blood plasma]. | 1991 | The content of cyclic nucleotides in blood plasma was measured in 151 patients suffering from rheumatoid arthritis. As compared to the control, the patients demonstrated a significant decrease of the cAMP content and a rise of the cGMP content. The disease standing was found to produce an appreciable effect on the cAMP content. RA patients untreated with glucocorticoids manifested significant correlations between the content of cyclic nucleotides and some characteristics of inflammation and of the immune status. At the same time the majority of such correlations may be lost under conditions of hormonal dependence, which is likely to attest to dysregulation of inflammatory process. In the course of the treatment, the content of cAMP in the plasma increase is attended by a reduction increases in 63.8% of the patients. In the majority of them, that of the level of circulating immune complexes, thereby supporting the relationship between immunopathological and metabolic disorders at the cellular level. | |
| 2081495 | Penetration of the active metabolite of nabumetone into synovial fluid and adherent tissue | 1990 | The concentration of 6-methoxy-2-naphthylacetic acid (6-MNA) in plasma, synovial fluid, synovial tissue and fibrous capsule tissue was determined in an open study with 20 patients scheduled for knee joint surgery after oral treatment with nabumetone under steady-state conditions. 6-MNA is the principle metabolite of the prodrug nabumetone arising from an extensive first-pass metabolism in the liver. Patients suffering from rheumatoid arthritis (n = 12) or osteoarthritis stage III or IV (n = 8) received a daily dose of nabumetone 1 g in the evening starting 4 days prior to surgery. On day 1 an additional loading dose of nabumetone 1 g was given in the morning. At the time of surgery (day 5), blood, synovial tissue and fibrous capsule tissue were taken simultaneously. The samples were analysed by high performance liquid chromatography. After 4 days of treatment mean 6-MNA concentration in plasma was 40.76 mg/L, in synovial fluid 34.79 mg/L, in synovial tissue 19.33 mg/g and in fibrous capsule tissue 11.43 mg/g. Under steady-state conditions mean synovial fluid levels of 6-MNA were higher than after administration of a single dose and, in common with levels in synovial tissue, persist in a range sufficient for in vitro cyclo-oxygenase inhibition. | |
| 3213265 | [Trans-synovial kinetics of tiaprofenic acid]. | 1988 May | The transsynovial distribution and tissue accumulation of tiaprofenic acid (Surgam)--a nonsteroidal anti-inflammatory agent--was studied in 55 patients scheduled for knee joint surgery. The patients suffering from rheumatoid arthritis (53), ankylosing spondylitis (1) or a chronicly irritated knee joint (1), received 300 mg of tiaprofenic acid b.i.d. starting 4 days prior to surgery. Samples of plasma, synovial fluid, fat, muscle, bone and synovial tissue were obtained simultaneously at defined times following the last dose. The samples were analyzed for tiaprofenic acid employing HPLC. Peak plasma concentrations of 28.6 micrograms/ml were achieved after 1 h, whereas synovial levels rose up to 2.8 micrograms/ml after 8 h. The time course of the concentration ratios indicates equilibration of both compartments 6 h following the last dose. Elimination occurs with half-lives of 1.9 h from plasma and 3.1 h from synovial fluid. During this period, synovial levels persist in a range sufficient for in vitro cyclooxygenase inhibition. In contrast, tiaprofenic acid does not exert marked tissue affinity, probably due to its hydrophilic properties. | |
| 2213755 | Pulsed suppressive treatment in rheumatoid arthritis: intravenous methylprednisolone and n | 1990 Jul | Persistent polyarticular rheumatoid arthritis (RA) and aggressive disease flares resistant to conventional therapy can effectively be controlled by intravenous pulse methylprednisolone (IVMP) or nitrogen mustard (HN2). The efficacy, toxicity and immunologic effects of each agent are reviewed. Clinical response is evident within days of the start of therapy for both; persisting up to 6 weeks for IVMP and at least 59 days for HN2. Morbidity from both agents is minimal when appropriate precautions are taken. No mortalities directly related to either modality have been reported in RA. | |
| 2328582 | Long-term follow-up study of scleroplasty using autogenous periosteum. | 1990 Apr | Autogenous periosteum was used to reinforce scleral thinning, perforation, or corneoscleral wound dehiscence in four eyes of three patients with necrotizing scleritis or peripheral ulcerative keratitis associated with advanced rheumatoid arthritis. All grafts have remained intact during an average follow-up interval of 36 months (range, 19-52 months). The postoperative visual acuity ranged between 20/30-20/60. Two eyes exhibited age-related macular degeneration, and one eye had an epiretinal membrane postoperatively. No systemic complications occurred following surgery. | |
| 2656078 | Mechanisms of tissue damage by the membrane attack complex of complement. | 1989 | This article explores the role of the cytolytic membrane attack complex of complement in the pathogenesis of inflammatory diseases. Evidence of nucleated cell resistance to lysis by the membrane attack complex and the stimulation of secretion of pro-inflammatory factors in the absence of cell death in a variety of cell types in vitro are documented, and the possible significance of these non-lethal effects to the pathogenesis of inflammatory diseases highlighted. | |
| 3075072 | Evidence for activation of rheumatoid synovial T lymphocytes--development of rheumatoid T | 1988 | Rheumatoid arthritis joints are infiltrated by numerous T cells. These T cells coexist in close proximity to HLA class I and class II bearing accessory cells. A great proportion of the rheumatoid T cells are activated in vivo as shown by their microscopic appearance, expression of surface activation antigens, spontaneous proliferation and their spontaneous production and consumption of interleukin-2 (IL-2). T cells from the rheumatoid lesions also express high levels of mRNA for IL-2, for IL-2-receptor and for other mediators. The expression of IL-2-receptors by activated synovial T cells make it easy to propagate them in IL-2 containing media which is the basis for the subsequent development of T cell clones. The rheumatoid T cells are hypo-responsive after stimulation with antigens and anti-CD3 antibodies which indicate that the CD3-TCR complex has been modulated in vivo. | |
| 2786461 | Alpha-1-antitrypsin (PI) and vitamin-D binding globulin (GC) phenotypes in rheumatoid arth | 1989 Apr | The distribution of alpha-1-antitrypsin (PI) and vitamin D-binding globulin (GC) phenotypes and gene frequencies has been examined in a homogenous group of clinically well-defined patients (N = 81) with rheumatoid arthritis. The distribution pattern of the two markers was then compared with two control groups consisting of 40 individuals with osteoarthritis and 192 randomly selected normal individuals, drawn from the same geographical area as the rheumatoid arthritis patients. No association was observed between alpha-1-antitrypsin subtypes or deficient alleles and any of clinical variables observed in rheumatoid arthritis cases. Although a slightly high frequency of the GC*2 allele and a low frequency of the GC*1S allele were observed in rheumatoid arthritis and osteoarthritis compared to controls, the differences were not statistically significant. However, within the patients two clinical variables were found to be significantly associated with a particular GC phenotype. Periarticular bony erosions and antinuclear antibody were positively and negatively associated with GC 1S-2 phenotype, respectively. | |
| 3495500 | The effect of low doses of prednisolone on T-cell subsets in rheumatoid arthritis. | 1987 | Prednisolone intake causes a drop in the absolute numbers of circulating T-cell populations. OKT4+ (helper-inducer) cells are more susceptible to this. Higher doses are needed to depress OKT8+ (suppressor-cytotoxic) cell numbers. Administration of up to 10 mg prednisolone affects the suppressor-cytotoxic (OKT8+) absolute cell numbers only in patients with initially low OKT4+/OKT8+ ratios and not the values of OKT8+ cells in patients with high OKT4+/OKT8+ ratios, since these patients already have low OKT8+ cell counts. | |
| 3266993 | Serum interleukin-2-receptor in rheumatoid arthritis: a prognostic indicator of disease ac | 1988 Aug | Interleukin-2 (IL-2) is an important growth factor for T lymphocytes. Its effects are mediated by cell surface receptors (IL-2 R) expressed on activated T cells. Receptor protein can be shed from cell membranes and the soluble form (sIL-2 R) is detectable by enzyme linked immunosorbent assay (ELISA). We have studied serial levels of sIL-2 R in the sera of patients with rheumatoid arthritis (RA). In 13 patients with active disease, the mean serum level of sIL-2 R was raised compared to age-matched healthy controls. In 48 samples taken at different times from 13 patients, serum sIL-2 R correlated significantly with Ritchie joint index, duration of early morning stiffness, patient pain score, physician's assessment, erythrocyte sedimentation rate (ESR) and platelet count. In individual patients, serial sIL-2 R serum levels fell with treatment preceding clinical improvement. In four patients where serum sIL-2 R levels fell and clinical improvement occurred, subsequent spontaneous increases of serum sIL-2 R level preceded increased clinical disease activity by up to 2 weeks. Serum sIL-2 R level in RA probably reflects activation of underlying immunopathogenic mechanisms and appears to be an excellent monitor of clinical disease activity. More importantly, a rising level may also predict exacerbation of disease activity. | |
| 1718404 | Complete sequence of the genes encoding the VH and VL regions of low- and high-affinity mo | 1991 Sep | We have characterized the VH and VL genes of three low-affinity polyreactive and two high-affinity monoreactive IgM and IgA1 rheumatoid factor (RF) mAb generated using circulating CD5+ B cells from a single rheumatoid arthritis patient. We found that four and one RF mAb utilized genes of the VHIV and VHIII families, respectively. The VHIV gene usage by these RF mAb differs from the preferential VHIII, VHI, and, to a lesser extent, VHII gene usage by the IgM with RF activity found in patients with mixed cryoglobulinemia, Waldenstrom's macroglobulinemia, and other monoclonal gammopathies. In addition, in contrast to the preponderant kappa L chain usage by the RF in these patients, a lambda L chain was utilized by all RF mAb from our rheumatoid arthritis patient. Two RF mAbs utilized V lambda I, two V lambda IV, and one V lambda III L chains. The VH genes of the two low-affinity polyreactive IgM RF mAb were in germline configuration. When compared with the deduced amino acid sequence of the putatively corresponding genomic segment, the VH gene of the high-affinity monoreactive IgM RF mAb displayed five amino acid differences, all of which are in the complementarity determining regions (CDR), possibly the result of a process of somatic point mutation and clonal selection driven by Ag. The unavailability of the corresponding genomic VH segment sequences made it impossible to infer whether the VH genes utilized by the two IgA1 RF were in a germline or somatically mutated configuration. Sequencing of the genes encoding the H chain CDR3 (D segments) revealed that all three low-affinity polyreactive RF mAb displayed a much longer D segment (36-45 bases) than their high-affinity monoreactive counterparts (15-24 bases), raising the possibility that a long D segment may be one of the factors involved in antibody polyreactivity. | |
| 1692420 | The prevalence and distribution of macrophages bearing Fc gamma R I, Fc gamma R II, and Fc | 1990 | Fc-receptors for IgG (Fc gamma R) are important triggers of effector function in macrophages. We have investigated the distribution of cells bearing Fc gamma R I, Fc gamma R II, and Fc gamma R III in 14 synovia and 3 nodules from rheumatoid arthritis (RA) patients, using monoclonal antibodies on serial cryostat sections. 8 osteoarthritis (OA), 2 ankylosing spondylitis (AS) patients and one sarcoid patient were also studied. Significant numbers of macrophages bearing Fc gamma R were present in inflamed synovial tissue with no significant difference in relative frequency between RA and OA. There was no correlation with the degree of lymphocytic infiltration. Distinctive staining patterns for the three Fc-receptors suggest differential regulation of these molecules on macrophages in synovium. | |
| 2386107 | Decreased cell proliferation and PGE2 production by fibroblasts treated with a modified he | 1990 Jun | Amiprilose hydrochloride, a modified hexose sugar effectively decreases proliferation of human skin and synovial fibroblasts and of rabbit synovial fibroblasts. It also decreases production of the inflammatory mediator prostaglandin E2 (PGE2) by these cells. Cell proliferation, measured by incorporation of 3H-thymidine and by cell number, is decreased by concentrations of amiprilose hydrochloride of 1 mg/ml, while PGE2 synthesis is decreased by concentrations as low as 10 micrograms/ml. Concentrations of 1 mg/ml are not cytotoxic, as measured by protein synthesis. The anti-proliferate and anti-inflammatory effects of amiprilose hydrochloride, combined with its lack of cytotoxicity, suggest that this compound may be useful in the treatment of rheumatoid arthritis, a chronic autoimmune proliferate and inflammatory disease of connective tissue. | |
| 1941818 | Complications of immunosuppression associated with weekly low dose methotrexate. | 1991 Aug | Complications of immunosuppression are thought to be rare with the use of low dose pulse methotrexate (MTX) for nonneoplastic conditions. We describe 4 complications of immunosuppression observed in a group of 41 patients who had received MTX for at least 6 months, during a 2-year period. We report the first case of a reversible lymphoproliferative disorder similar to that reported with immunosuppressive therapy associated with organ transplantation. Two cases of disseminated herpes zoster and 1 case with Pneumocystis carinii pneumonia are described. As the indications for the use of low dose MTX broaden and older patients with other comorbid diseases are included, our experience suggests that complications of immunosuppression with prolonged use of MTX may be seen more commonly. |