Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3587472 | Goodpasture's syndrome in a patient receiving penicillamine and carbimazole. | 1987 | A 51-year-old woman with advanced rheumatoid arthritis developed a Goodpasture's syndrome during treatment with penicillamine and carbimazole. Circulating antiglomerular basement membrane antibodies (anti-GBM) were present. Renal biopsy showed focal necrotizing glomerulonephritis with crescents, and HLA typing showed the presence of DR3 and DR4. The patient responded dramatically to pulse methylprednisolone and cyclophosphamide, with both clinical remission and disappearance of anti-GBM antibodies. | |
| 1719988 | Measurement of an adhesion molecule as an indicator of inflammatory disease activity. Up-r | 1991 Nov | The hyaluronate receptor (CD44) molecule is a multifunctional cell surface protein involved in T cell activation, monocyte cytokine release, fibroblast locomotion, and lymphocyte binding to high endothelial venules. To study the roles CD44 molecules play in inflammatory synovitis, we measured expression of CD44 in inflamed and noninflamed synovial fluid and tissue, using indirect immunofluorescence assays on tissue sections and quantitative Western blot analysis. The ability of purified CD44 protein to modulate T cell responses was tested in T cell activation assays in which CD44-containing liposomes were added in vitro. CD44 was widely expressed on many synovial cell types, and synovial tissue from rheumatoid arthritis (RA) patients contained 3.5 times more CD44 than tissue from osteoarthritis patients and 10.7 times more than tissue from patients with joint trauma. The level of soluble CD44 in RA synovial fluid was elevated only in fluids with low cell counts (less than or equal to 7,000/mm3), and not in RA synovial fluid with higher cell counts. Soluble purified CD44 protein in liposomes partially suppressed T cell activation in vitro. These data demonstrate that CD44 is up-regulated on many synovial cell types in patients with RA, and that the level of CD44 present in synovial tissue is related to the degree of synovial inflammation. Determination of ways to inhibit the proinflammatory functions of immune cell membrane CD44 molecules may provide new therapeutic modalities for RA. | |
| 2197030 | Biochemical and biological aspects of the plasminogen activation system. | 1990 Jun | Plasminogen activators (PAs) are specific proteolytic enzymes which convert the inactive proenzyme plasminogen to plasmin. The plasmin formed is a potent and nonspecific protease which cleaves blood fibrin clots and several other extracellular proteins. In addition to their primary role in the initiation of fibrinolysis, PAs are implicated in a variety of basic biological processes, such as, degradation of the extracellular matrix, tumor invasiveness, tissue remodelling, and cellular differentiation. This review describes recent observations on the biochemical and biophysical characteristics of the different components of the plasminogen activation system. This complex system includes: the proenzymes of tissue type PA (tPA) and urokinase type PA (uPA); the active enzymes tPA, uPA and plasmin; the substrate plasminogen; several natural inhibitors of PA and plasmin activity; and the cellular receptors that bind the proenzymes, enzymes, and inhibitor-enzyme complexes. Through the coordinated interactions of these components, the location, timing, and extent of potent proteolytic activity is controlled. Recent findings on the structure, properties, biological functions, and regulation of the different components of the plasminogen activation cascade are reviewed. Current methods for assay of the amount and activity of the enzymes, inhibitors, and receptors are described. Observations implying specific functions of the system in health and disease, and its potential utilization for diagnosis are examined. Specifically, the potential application of PAs as laboratory markers of neoplasia, as diagnostic tools in diseases of the blood clotting system, their use for monitoring of thrombolytic therapy, and their possible relevance in certain disease states are described. | |
| 1828327 | Methotrexate and histologic hepatic abnormalities: a meta-analysis. | 1991 Jun | STUDY OBJECTIVE: To determine the risk of liver toxicity from the long-term administration of methotrexate in patients with rheumatoid arthritis or psoriatic arthritis. DESIGN: A meta-analysis of 15 studies examining the relationship between long-term, low-dose methotrexate administration and biopsy evidence of liver fibrosis. PATIENTS: A total of 636 patients from 15 studies. RESULTS: The incidence of progression of liver disease (defined as worsening of at least one grade on the histologic classification of Roenigk) among 636 patients was 27.9% (95% confidence intervals 24.3 to 31.6). The rate of progression of liver disease in the 15 studies was associated with the cumulative dose of methotrexate (p = 0.01). Patients on average had a 6.7% (95% confidence intervals 2.1 to 11.4) chance of progressing at least one histologic grade on liver biopsy for each gram of methotrexate taken. The overall incidence of advanced pathologic changes on liver biopsy (grades IIIB or IV) among 636 patients was 5.0% (95% confidence intervals 3.5 to 7.0). The development of advanced histologic changes was not associated with the cumulative dose of methotrexate (p = 0.08). Patients who according to their history were heavy drinkers (at least 100 g of alcohol per week) were more likely to have advanced changes on liver biopsy (17.8% versus 4.5%, p = 0.0003) and to show histologic progression (73.3% versus 25.9%, p = 0.0002). Patients with psoriasis were more likely than patients with rheumatoid arthritis to have advanced changes (7.7% versus 2.7%, p = 0.003) and histologic progression (33.1% versus 24.3%, p = 0.02). CONCLUSIONS: The risk of liver toxicity in patients undergoing long-term, low-dose methotrexate therapy is substantial, and that risk increases with the total cumulative dose and with heavy consumption of alcohol. Heavy users of alcohol should not receive long-term methotrexate therapy. For most patients who are not heavy users of alcohol, liver biopsies should be done periodically to monitor for the occurrence of liver toxicity. | |
| 2500703 | A functional study of purified CD4+ and CD8+ cells isolated from synovial fluid of patient | 1989 Jun | The purpose of this investigation was to study purified synovial fluid (SF) CD4+ and CD8+ cells from patients with rheumatoid arthritis (RA) and other inflammatory joint diseases (non-RA) with respect to the proliferative response to mitogens and recombinant interleukin 2 (rIL-2). Highly purified cell subsets were isolated by an immunomagnetic technique, and spontaneous proliferation as well as proliferative reSponses to rIL-2 and a combination of phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) (to substitute for accessory cells) were measured. Some patients had SF CD4+ and/or CD8+ cells with moderately increased spontaneous proliferation, but only the CD4+ cells of the two patient groups differed significantly from the peripheral blood (PB) T-cell subsets of healthy individuals who served as controls. The response to rIL-2 was variable but generally low, although about 50% of the CD4+ and 20% of the SF CD8+ cells of both patient groups expressed the Tac antigen. The response to PHA/PMA was significantly lower for RA SF CD4+ cells than for non-RA SF CD4+ cells, which again was lower than for normal PB CD4+ cells. SF CD8+ response to PMA/PHA by both groups of patients was somewhat decreased, but not significantly lower than in the controls. Thus, the CD4+ cells seemed functionally more deviant than the CD8+ cells in both patient groups, but the abnormality was most pronounced in the RA group. The results demonstrate that the previously reported diminished response to mitogens by SF mononuclear cells is present even when SF CD4+ cells are cultured alone. This indicates that these T cells have a reduced response, probably because of prior activation. | |
| 2367097 | Appendicular arthropathy. | 1990 Jul | The radiographic examination plays an extremely important role in the diagnosis of appendicular arthropathies. Accurate diagnosis can be made by observing the radiographic abnormalities in the bones surrounding the joint involved and the distribution of the abnormalities within the joint or the body. | |
| 2338498 | Trimer and tetramer complexes containing C1 esterase inhibitor, C1r and C1s, in serum and | 1990 May 8 | During activation, the first component of complement C1q (C1r-C1s)2 is dissociated in conjunction with the formation of complexes containing C1 esterase inhibitor (C1-INH). Trimer complexes, with zymogen C1s associated with a firm C1-INH-C1r complex (C1-INH-C1r-C1s) can be distinguished from tetramer complexes C1-INH-C1r-C1s-C1-INH) in which C1-INH is firmly bound to both proteases. In the present study a two-stage electroimmunoassay was developed for the specific measurement of C1-INH-C1r-C1s. In the first step, C1-INH and its complexes were immunoprecipitated with anti-C1-INH during electrophoresis in the presence of Ca2+. In the second step, C1s contained in C1-INH-C1r-C1s was dissociated in the presence of EDTA and was measured by immunoprecipitation with anti-C1s. C1-INH-C1r-C1s were consistently found in normal sera. Normal sera did not contain C1-INH-C1r-C1s-C1-INH as assessed with a previously described ELISA procedure. Sera and synovial fluids from two groups of patients with inflammatory arthritis were investigated. In rheumatoid arthritis patients (n = 15) C1-INH-C1r-C1s complexes were usually found at high concentration both in serum and synovial fluid. C1-INH-C1r-C1s-C1-INH complexes were also present with values that were higher in synovial fluid than in serum, in accord with previous findings of classical pathway activation in the inflamed joints of the patients. Patients with spondylarthritic syndromes (n = 7) had serum and synovial fluid C1-INH-C1r-C1s concentrations that were comparable to those of the rheumatoid arthritis patients. If at all present, C1-INH-C1r-C1s-C1-INH were detected in trace amounts. Thus, C1 activation in patients with spondylarthritic syndromes appeared to be efficiently controlled at the C1r level. Distinguishing between C1-INH-C1r-C1s and C1-INH-C1r-C1s-C1-INH may prove of value in further studies of the activation and control of C1 in disease. | |
| 1650070 | [Central analgesic effects of non-steroidal anti-rheumatic agents]. | 1991 | NSAIDs, including acetylsalicylic acid, are frequently classified as peripherally-acting analgesics. This is based on the fact that these substances, among other effects, inhibit the biosynthesis of prostaglandines. A few solid arguments, however, stand against an exclusively peripheral mode of the analgesic action of NSAIDs in the sense of an inhibition of prostaglandin synthesis. It should be noted here that the analgesically-effective doses do not suffice to block prostaglandin synthesis. Furthermore, the inhibiting effects of paracetamol and metamizol are far weaker or are not at all present, although both substances are reliably-effective analgesics. The NSAIDs indometacin, ibuprofen, and diclofenac are capable of suppressing the sensory response of the nociceptive system via a central effect. In experimental studies with rats under urethane anesthesia, the nociceptive activity of individual neurons of the thalamus (the dorsomedial part of the ventral nucleus) was measured. The activity was triggered via an electric stimulation of afferent C-fibres in the ipsilateral or contralateral sural nerve. The NSAIDs named suppressed the evoked nociceptive activity in a dose-dependent manner. At the highest doses, the suppression resulted in a difference of approx. 60% of the control activity. The ED50 values were 5 mg/kg for indometacin, 10.9 mg/kg for diclofenac, and 15.6 mg/kg for ibuprofen. These results support the theory that the central effects of NSAIDs contribute to their analgesic efficacy. The possible mechanisms of these effects will be discussed. A practical significance of the central analgesic effects of NSAIDs could be that their therapeutic applicability is not limited only to the treatment of pain, which results from an activation of nociceptors. | |
| 2016122 | An investigation of T-cell subset phenotype and function in the rheumatoid synovium using | 1991 Feb | Cryostat sections of synovial biopsy tissue from patients with active rheumatoid arthritis (RA), spondyloarthritis (SpA) and osteoarthritis (OA) have been investigated for interleukin-2 (IL-2) mRNA and protein production. In situ hybridization using 32P-labelled oligonucleotide probes based on IL-2 gene sequences coded by exon 1 and exon 3 of the IL-2 gene revealed IL-2 mRNA over lymphoid aggregates in RA and SpA tissue. No IL-2 mRNA was detected in OA tissue and reflected the absence of lymphoid infiltrates in these tissues. Total mRNA, as detected by a 32P oligo dT probe, was found in all tissue examined. IL-2 protein product was detected by monoclonal antibody staining in SpA but not in RA or OA tissue. This is the first report of in situ studies of lymphoid function in the microenvironment of the RA synovium. Whether these data reflect the function of normal CD3+ CD4+ CD45RO+ T-cell subsets in the diseased joint remains to be resolved. | |
| 1700467 | Monoreactive and polyreactive rheumatoid factors produced by in vitro Epstein-Barr virus-t | 1990 Oct | The CD5 membrane molecule, initially identified as an exclusive T-cell marker, also defines a phenotypically and functionally distinct B-lymphocyte population. In normal individuals, CD5+ B cells are committed to secrete 'natural' polyreactive (auto)antibodies, that is antibodies, mainly IgM, endowed with multiple antigen-binding capabilities, including rheumatoid factor (RF) activity. At variance with this, in rheumatoid arthritis (RA) as well as in other autoimmune conditions, monoreactive autoantibodies binding with high affinity and specificity to a given self antigen have been isolated and the cells from which they originate differently related to the CD5+ B-lymphocyte subset. Here, we studied the proportions of CD5+ B cells and the characteristics, in terms of polyreactivity and monoreactivity, of RF produced by B lymphocytes in RA patients with classified disease activity. Our results suggest that patients with a more severe disease activity have higher proportions of CD5+ B cells and higher frequencies of B lymphocytes committed to secrete RF, with the characteristics of polyreactive antibodies. On the other hand, we did not find a significant difference between the proportions of peripheral B cells producing monoreactive RF in patients with high- versus patients with low-activity RA. However, in two highly active RA patients, we found that synovial fluid, compared with peripheral blood, was significantly enriched for (IgG and IgA) monoreactive RF-producing B cells. | |
| 1650220 | Synovial fluid 5'-nucleotidase activity. Relationship to other purine catabolic enzymes an | 1991 Aug | We measured 5'-nucleotidase (5NT) activity in synovial fluid from 159 patients with various diagnoses. The activity of 5NT was compared with activities of nucleotide pyrophosphohydrolase, alkaline and neutral phosphatases, and adenosine deaminase, in the same samples. Higher levels of 5NT activity occurred in synovial fluid from osteoarthritic joints than from joints of patients with gout, pseudogout, or rheumatoid arthritis. The highest levels of 5NT activity were found in synovial fluid from patients with Milwaukee shoulder syndrome and from osteoarthritis patients in whom deposition of calcium-containing crystals was also present. | |
| 3235506 | Assay for D-penicillamine-protein conjugate in human plasma utilising chemical reduction f | 1988 Sep 9 | D-Penicillamine (D-pen), a thiol with antirheumatic activity, forms a mixed disulphide with albumin in vivo. This conjugate is important in the pharmacokinetics and possibly the mode of action of D-pen. An assay was devised for D-pen-albumin disulphide, based on separation from plasma by acid precipitation followed by quantitative reduction with sodium borohydride in an anoxic environment. The liberated D-pen was then assayed by high-performance liquid chromatography with gold/mercury electrochemical detection. The assay was sensitive to 1.2-microM D-pen-albumin disulphide (signal-to-noise ratio greater than 2), absolute recovery was 92.7% and intra-assay coefficient of variation was 4.6% in human plasma. This technique also may be useful for quantitating protein conjugates of other thiols. | |
| 3066650 | [Auto-immune hypoglycemic syndrome induced by pyritinol]. | 1988 Jul | The auto-immune hypoglycemic syndrome is characterized by the association of hypoglycemia (clinical and/or biological) and anti-insulin antibodies in patients who have never received exogenous insulin. Initially this syndrome was most often described in Japanese patients some of whom were treated with drugs containing a sulfydril group. We now recall the case of a female caucasian patient treated with Pyritinol for rhumatoid polyarthritis and who presented severe spontaneous hypoglycemia linked with the presence of anti-insulin antibodies in her serum. The level of her antibodies decreased abruptly on suspension of the drug. The recent and more developed characterization techniques of the different forms of circulating insulin and of their antibodies may help to differenciate an auto-immune hypoglycemia from hypoglycemia due to the secret auto-administration of bovine and porcine insuline, and permit us to suggest that an abnormality in the structure of the molecule of insulin might be a cause of this syndrome. However, the exact mechanism of hypoglycemia linked with the presence of anti-insulin auto-antibodies is not yet clear as is the predisposition of a drug with a sulfydril group to induce such an auto-immune phenomenon. | |
| 2677142 | In vitro responses to a 65-kilodalton mycobacterial protein by synovial T cells from infla | 1989 Oct 15 | Bacterial Ag, especially those of mycobacteria, have been implicated in the pathogenesis of experimental inflammatory arthritis in rodents, while in man, reactive arthritis has a clear temporal relationship to infection with particular bacteria. To investigate the role of immune responses to bacterial Ag in inflammatory arthritis, we have examined the proliferative responses of paired synovial fluid and PBMC when stimulated with 1) suspensions of irradiated or heat-killed bacteria associated with reactive arthritis (ReA), 2) purified protein derivative, 3) a recombinant 65-kDa heat shock protein of Mycobacterium leprae. The 65-kDa Ag was stimulatory to synovial fluid mononuclear cells, but not PBMC, from patients with different arthropathies, including most of those with ReA, but also some with rheumatoid arthritis. Furthermore, the magnitude of these responses correlated more closely with responses to ReA-associated bacteria (such as Salmonella), than with responses to the mycobacterial Ag represented in purified protein derivative. These results suggest that the 65-kDa molecule, which is common to a wide range of bacteria, may be an important immunogen for the T cell-mediated immune responses within the joint in different clinically defined inflammatory arthropathies. | |
| 2297544 | Modulation of plasminogen activator production by interleukin 1: differential responses of | 1990 Jan 23 | Rheumatoid synovial fibroblasts were treated with purified porcine interleukin 1 alpha and recombinant human interleukin 1B, and the production of secreted and cell-associated plasminogen activator activity was measured. No stimulation of plasminogen activator activity was seen in response to either preparation of interleukin 1, and in more than half of the cell cultures interleukin 1 caused a significant decrease in the secreted levels of PA activity. Increased levels of prostaglandin E were produced in the same experiments, indicating that the cells were responsive to the interleukin 1 preparations. Both retinoic acid and unfractionated monocyte conditioned medium were able to stimulate the production of PA activity by the rheumatoid synovial fibroblast cultures. The rheumatoid synovial fibroblasts produced two species of plasminogen activator as indicated by SDS polyacrylamide gel electrophoresis, with apparent Mr of approx. 50,000 and 100,000. The Mr = 50,000 species co-migrates with urokinase-type plasminogen activator. No species is produced which co-migrates with tissue type plasminogen activator. Studies with antibodies also indicate that the activity produced is urokinase-type plasminogen activator. The Mr = 100,000 species may be an enzyme-inhibitor complex. Two non-rheumatoid synovial fibroblast cultures and two out of six human skin fibroblast cultures did produce elevated levels of plasminogen activator activity in response to recombinant human interleukin 1B. The results suggest that fibroblast populations may differ in their response to interleukin 1, in terms of production of plasminogen activator activity. | |
| 1722907 | [Reliability and validity of the Zurich Questionnaire of Coping with Illness]. | 1991 | The coping behavior of three groups of patients (N = 585) was assessed by a 45-item-questionnaire, a revised version of the Zurich Coping Questionnaire (ZKV) published earlier. The following three coping patterns resulted, established by factor analysis: ZKV-1: Depressive coping (Cronbach-alpha = .86), ZKV-2: Self-encouragement/distraction (.81) and ZKV-3: Problem tackling (.60). Retest-stability for the two scales 1 and 3 was high (r greater than .74, 12-month-interval). Concurrent and prognostic validity was assessed. The results indicate that the ZKV is a useful instrument for coping research, especially for the prognostic rating of the subsequent coping behavior. | |
| 3497900 | Lymphocyte migration in the rheumatoid synovial membrane. | 1987 | There are impressive similarities between the lymphocyte populations in lymph node and synovial membrane: similar amounts and classes of immunoglobulins are synthesized; lymphoid aggregates, when present in the rheumatoid synovial membrane, resemble those of the lymph node paracortex in being composed predominantly of helper-inducer T4 cells; B cells which leave tall endothelial PCV together with the T cells, tend to segregate themselves from the T cell aggregates and migrate to areas rich in macrophages where they proliferate and differentiate. In the lymph node, the B cells migrate to the primary follicles of the outer cortex and to the medullary region, while in the synovial membrane the corresponding region is the transitional area, which contains lymphocytes (predominantly T8 cells), macrophages and plasma cells. | |
| 2453101 | [Hemorheologic changes in chronic polyarthritis]. | 1988 Jan | The haemorheological status of plasma-(P eta) and blood-viscosity (B eta), erythrocyte aggregation (EA) and erythrocyte filterability (EF), blood sedimentation rate (BSG), haematocrit (HCT), plasma fibrinogen and alpha-2-macroglobulin was investigated on 46 patients suffering from chronic polyarthritis (c.P.). The results were compared with those from a control group of 20 healthy subjects with a similar distribution of age and sex. All the haemorheological data from the c.P. patients showed a significantly decreased blood fluidity (p less than or equal to 0.001 or p less than or equal to 0.01). These differences were highly significant for the female patients (n = 29), but for the men (n = 17) only at slight shift was seen. The comparison of clinically acute and non-acute disease in the patients showed a significant worsening of P eta, B eta and EF during the acute state, while the EA remained unaffected. The limited blood fluidity is seen as a result of the basic illness. At present, the pathophysiological meaning of these findings is still hypothetical: further investigations are required. | |
| 2174073 | IL-1 regulation of transin/stromelysin transcription in rheumatoid synovial fibroblasts ap | 1990 Dec 1 | IL-1, like other agents that have been shown a capacity to induce protein kinase C, is a potent transcriptional activator of the metalloproteinase, stromelysin, in synovial and other fibroblasts. cAMP has been shown to inhibit stromelysin transcription in fibroblasts of nonsynovial origin, and is regarded as an important second messenger for IL-1. In addition to stimulating metalloproteinase transcription, IL-1 also induces PGE2 production in synoviocytes. We determined that rIL-1 alpha led to the time-dependent accumulation of intracellular cAMP in serum-starved rheumatoid synovial fibroblasts, and that the effect was blocked by indomethacin. The cAMP agonists forskolin, 3-isobutyl-1-methylxanthine, and PGE2 suppressed the IL-1 induction of stromelysin; conversely, indomethacin superinduced IL-1-elicited stromelysin mRNA. These results were recapitulated on the transcriptional level in cells transfected with the rat transin/stromelysin promoter in a reporter (CAT) construct. 2',5'-Dideoxyadenosine, an inhibitor of adenylate cyclase, also augmented the IL-1 induction of stromeylsin mRNA, as did H-8, a specific inhibitor of the cAMP-dependent protein kinase A. Staurosporine and H-7, inhibitors of protein kinase C, blocked the IL-1 induction of stromelysin mRNA. We conclude that IL-1 appears to stimulate at least two transduction pathways in synovial fibroblasts from patients with rheumatoid arthritis, and that these have antagonistic effects on the regulation of stromelysin transcription. | |
| 1988587 | The interspinous method of posterior atlantoaxial arthrodesis. | 1991 Feb | Thirty-six patients underwent C1-2 posterior wiring and fusion procedures over a 5-year period for unstable C-2 fractures (eight cases), unstable atlas-axis combination fractures (six cases), rheumatoid C1-2 instability (14 cases), os odontoideum (four cases), traumatic C1-2 ligamentous instability (three cases), or instability secondary to a C-2 tumor (one case). In each case, the atlantoaxial arthrodesis utilized sublaminar wire at C-1 and incorporated an iliac-crest strut-graft positioned between the posterior arches of C-1 and C-2, held in place by securing wire around the base of the spinous process of the axis. Follow-up examination was performed in all patients after a mean postoperative duration of 33.7 months. The technical aspects and clinical merits of this fusion procedure, which led to a 97% union rate (one nonunion) and minimal morbidity and mortality rates, are presented. |