Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rabbit articular chondrocytes synthesize type II collagen [3alpha(1)(II)] in vivo and type I collagen [2alpha(1)(I).alpha(2)] in monolayer cultures. In suspension culture the nature of phenotype depends on extracellular Ca(2+). The relationship of Ca(2+) and 3':5'-cyclic AMP (cAMP) in regulation of collagen synthesis has been investigated. In suspension culture, cAMP levels of chondrocytes increase by 2- to 3-fold and then reach basal values regardless of the presence or absence of extracellular Ca(2+). The cells, however, synthesize primarily type II collagen in the absence of CaCl(2) in the medium and type I collagen in medium containing 1.8 mM CaCl(2). If CaCl(2) is added when intracellular cAMP levels are low, the phenotype is type I collagen. These observations minimize the role of cAMP as a second messenger in the chondrocyte culture system. Increasing endogenous cAMP with a phosphodiesterase inhibitor or adding exogenous dibutyryl-cAMP leads the cells to synthesize type I collagen, although this effect is significantly less pronounced if the medium contains ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA). Increased concentrations of cAMP may mobilize the intracellular calcium pools and activate the cells to switch their phenotypic expression. Prostaglandins E(2) and F(2)alpha, thought to be involved in rheumatoid arthritis and bone resorption, have no significant effect on cAMP content of chondrocytes and alter their collagen phenotype to a small extent.
 ...
PMID:Synthesis of collagen by chondrocytes in suspension culture: modulation by calcium, 3':5'-cyclic AMP, and prostaglandins. 19 10

Twenty-seven synovial fluids from rheumatoid arthritis (RA) patients and 17 synovial fluids from controls were investigated in a new radioimmunoassay for anticollagen antibodies. In vitro labeled human 14C-collagen of type I in native or denatured state was used as antigen. Passive hemagglutination was used in comparison. Parameters for defining positive results in radioimmunoassay were evaluated on the basis of control synovial fluids. Synovial fluids from 20 RA patients (74%) showed antibodies to denatured collagen; synovial fluids from 8 RA patients (30%) also demonstrated antibodies to native collagen. Control fluids of posttraumatic effusions were negative; among the other controls synovial fluid from 1 psoriatic arthritis patient reacted positively. Inhibition experiments showed that antibodies to denatured collagen cross-reacted with native collagen. Inhibition with human denatured type III collagen displayed strong cross-reactivity of anti-type I collagen antibodies with type III collagen.
 ...
PMID:Demonstration of anticollagen antibodies in rheumatoid arthritis synovial fluids by 14C-radioimmunoassay. 63 91

Using an assay to measure antigen-induction of a lymphocyte mediator, LIF, we detected cellular sensitivities to native human types II and III collagens in three-quarters of a group of 50 patients with rheumatoid arthritis. There was no cellular response to type I collagen. Cellular reactivities to collagen were absent in a group of 41 patients who had other kinds of arthritis, such as osteoarthritis, crystalline-induced synovitis, or arthropathies associated with a high prevalence of the HLA-B27 antigen. Lymphocytes, responding to an unknown persistent antigenic stimulus, are thought to play a major role in the pathogenesis of rheumatoid arthritis. It has previously been hypothesized that collagen might function as an autoantigen in this disease. Based on the disease specificity of our findings and the tissue distribution of types II and III collagens, we propose that cellular sensitivities to these structural proteins may be involved in the pathogenesis of rheumatoid arthritis.
 ...
PMID:Cellular sensitivity to collagen in rheumatoid arthritis. 75 87

Degradation of cartilage in rheumatoid arthritis (RA) may be in part due to release of collagenase from specific granules of polymorphonuclear neutrophil leukocytes (PMNs) during degranulation. We decided to study, not synovial fluid (SF) collagenase, but PMN collagenase reserves. PMN were isolated from parallel SF and peripheral blood (PB) samples obtained from 7-arthritis patients. PMNs were stimulated in vitro by tetradecanoyl-phorbol-13-acetate (TPA). Collagenase activity in the supernatant without and with phenylmercuric chloride activation was studied. Compared to PB PMNs, there was no consistent decrease in the total collagenase reserves in the inflammatory SF PMNs. This suggests that the release of collagenase in the inflammatory synovial fluid does not deplete SF PMNs of the collagenase synthesized at the myelocyte stage. The role of PMN collagenase in pathogenesis of cartilage destruction would then seem to be more dependent on local release and autoactivation at cartilage surface by adherent PMNs and not excessive collagenase release from free floating SF PMNs at single cell level. Furthermore, under the experimental conditions used the proportion of collagenase released in active form was higher in SF PMN specimens than in PB PMN specimens (p less than 0.01). The predominant collagenous component of adult cartilage, native type II collagen, was degraded by PMN collagenase as fast as native type I collagen. These findings suggest an important role for this enzyme in destruction of the free cartilage surface in RA.
 ...
PMID:Collagenase reserves in polymorphonuclear neutrophil leukocytes from synovial fluid and peripheral blood of patients with rheumatoid arthritis. 165 76

Peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (SSc) produced increased amounts of interleukin-2 (IL-2), in a dose-dependent manner, in response to stimulation with human type I collagen, whereas PBMC from normal subjects did not. At a dose of 50 micrograms human type I collagen/10(6) PBMC, PBMC from SSc patients (n = 17) produced 8 times as much IL-2 as did PBMC from 16 normal subjects (P less than 0.005) and 3 times as much as did PBMC from a group of 13 rheumatoid arthritis patients (P less than 0.05). In contrast, IL-2 production by PBMC after nonspecific stimulation with the mitogen, phytohemagglutinin, did not differ among the SSc, rheumatoid arthritis, and normal control groups. Cell depletion experiments indicated that the IL-2-producing cells in SSc patients are CD4+. Thus, SSc patients have CD4 cells that are specifically sensitized to human type I collagen and can produce increased levels of IL-2. Measurement of IL-2 production stimulated by human type I collagen may be useful in evaluating disease activity, and further investigation of this process may contribute to the delineation of the pathogenesis of SSc.
 ...
PMID:Increased interleukin-2 production in response to human type I collagen stimulation in patients with systemic sclerosis. 202 11

The distribution of frequencies of HLA-DR alloantigens in HLA-DR4 negative subjects was determined in patients with Rheumatoid arthritis (RA) and normal individuals. An increased incidence of HLA-DR1 alloantigen in DR4 negative RA patients (45.9%) compared with DR4 negative healthy controls (23.6%) was found. The difference became significant when the incidence of DR1 was compared between patients with severe disease stages (III-IV) (75%) in contrast to 32% of incidence in patients of the milder stages (I-II) (p less than 0.05). Using Enzyme Linked Immunosorbent Assay we have determined the incidence of serum antibodies to native bovine type I and type II collagens and proteoglycans in patients with RA. Presence of serum antibodies to native type I collagen was detected in 59% of patients with RA, 60% of sera exhibited reactivity to type II collagen and 12% had antibodies to proteoglycans. There was no correlation between the presence of antibodies to type I and II collagens and disease stages, however, the incidence of serum antibodies to proteoglycans was increased in severe disease stages. On the other hand, the presence of high levels of antibodies to type I collagen was associated to HLA-DR1 antigen, (p less than 0.05).
 ...
PMID:Rheumatoid arthritis and its association with HLA-DR antigens. II. Antibodies to native connective tissue antigens detected by enzyme linked immunosorbent assay. 249 46

Collagenases are known to be associated with tissue destruction in chronic inflammatory diseases such as periodontal diseases and rheumatoid arthritis. Collagenases are secreted by circulating inflammatory cells (polymorphonuclear leukocytes and monocytes), resident mesenchymal cells and epithelial cells in latent forms, which can be activated by proteases and compounds reacting with protein thiol groups. We have studied here the effects of oxygen-derived free radicals (ODFR) on latent human neutrophil collagenase. Also, in order to elucidate the cellular sources of collagenases, the ability of human gingival crevicular fluid (GCF) collagenases both from adult periodontitis (AP) and localized juvenile periodontitis (LJP) patients to degrade soluble interstitial collagen types I and II was studied. ODFR generated by the xanthine oxidase/hypoxanthine system in the presence of trace amounts of iron and EDTA activated latent neutrophil collagenase to an equal extent as the known activators phenylmercuric chloride and gold thioglucose. ODFR activation was inhibited by desferoxamine and mannitol as well as by superoxide dismutase and catalase. Clear differences in the susceptibility of collagen types I and II to AP and LJP GCF collagenases were observed. AP GCF collagenase degraded type I and II collagens at equal rates, resembling the substrate-specificity of human neutrophil collagenase. LJP GCF collagenase degraded type I collagen considerably faster than type II collagen, which was only negligibly degraded. This corresponds to the substrate specificity of fibroblast collagenase. Zymographic evaluation of gelatinolytic proteases showed the presence of 90 and 68 kD gelatinases in both AP and LJP GCF. Non-proteolytic means apparently provide a potent activation pathway of neutrophil collagenase in vivo and the hydroxyl radical was identified to be one of the potent activating oxidants.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Non-proteolytic activation of latent human neutrophil collagenase and its role in matrix destruction in periodontal diseases. 256 61

Long-term synovial fibroblast cultures were exposed to interleukin 1 (IL-1) or prostaglandin E2 (PGE2). The normally spindle-shaped fibroblasts changed to stellate-shaped cells, resembling the HLA-DR-positive, collagenase-producing cells which are normally seen only in primary cultures from enzyme-digested rheumatoid synovial tissue. However, the IL-1- or PGE2-induced fibroblasts were not HLA-DR-positive. This suggests that these cell populations represent originally different cell lines or that the expression of HLA-DR antigens is not induced by the agents used. For further characterization of these stellate cells, the location of fibronectin and type I collagen was studied by specific antibodies and the pericellular coat around fibroblasts was visualized by the erythrocyte exclusion method. Both IL-1 and PGE2 treatments destroyed the intercellular fibronectin network. Type I collagen was detected as intracellular granules. The stellate fibroblasts were usually full of these granules in contrast to intact fibroblasts in which the number of collagen fluorescence granules varied greatly. The pericellular coat known to be formed mainly by hyaluronic acid was similar around spindle and stellate-shaped fibroblasts. Rheumatoid arthritis-derived fibroblasts did not differ from their non-rheumatoid counterparts in any of the experiments. The effect of IL-1 and PGE2 on fibroblasts simulates the interaction between mononuclear cells and fibroblasts in synovial stroma and also potentially the interactions between different cell types in synovial lining.
 ...
PMID:Connective tissue components in synovial fibroblast cultures exposed to interleukin 1 and prostaglandin E2. 287 May 82

Rheumatic disease sera were examined by a sensitive and specific enzyme linked immunosorbent assay (ELISA) for antibodies to native and to denatured type IV collagen from basement membranes of bovine anterior lens capsules or human placenta. The frequency of antitype IV collagen antibodies depended on the antigen and the disease studied. No controls had human type IV collagen antibodies and only 5.6% had antibody to bovine type IV collagen. Antibody to one or more of our 4 antigens was seen in 20% of children with juvenile rheumatoid arthritis (JRA), 35% of patients with mixed connective tissue disease (MCTD), 40% of those with juvenile dermatomyositis (DM), 52% of adults with rheumatoid arthritis (RA), 56% of patients with scleroderma and 60% of patients with systemic lupus erythematosus (SLE). Antibodies to native human type IV collagen were rare (0-10%) except in SLE (45%). Antibodies to denatured human type IV collagen were commoner in RA, scleroderma and SLE. Antibodies to native bovine type IV collagen occurred in 8-20% of patient sera, and to denatured antigen in 25-26% of scleroderma, MCTD and DM patients. Antibovine type IV collagen activity measured by ELISA could be absorbed from positive sera by preincubation of the sera with bovine type IV collagen but not bovine type I collagen or native human placental type IV collagen, indicating that the antibodies were specific for bovine type IV collagen.
 ...
PMID:Antibodies to type IV collagen in rheumatic diseases. 301 40

Gold sodium thiomalate, a drug used widely in the therapy of rheumatoid arthritis, was found to be an activator of latent human polymorphonuclear leukocyte collagenase. The activation was demonstrated by two distinct and independent collagenase assays: by recording with a spectrophotometer at 227 nm the enzyme-induced increase in ultraviolet difference absorbance of native type I collagen connected to the cleavage of collagen at 37 degrees C [(1986) Eur. J. Biochem. 156, 1-4] and by SDS-polyacrylamide gel electrophoresis analysis of formation of specific products of collagen resulting from collagenase cleavage at 25 degrees C. Activation of latent collagenase by gold sodium thiomalate appeared to be of the same magnitude as by the known activator phenylmercuric chloride.
 ...
PMID:Gold sodium thiomalate activates latent human leukocyte collagenase. 302 35


1 2 3 4 5 6 7 8 9 10 Next >>