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

For examination of glycosaminoglycane (GAG) in the normal synovial membrane and in the synovial membrane of patients with rheumatoid arthritis (RA) fat free dry tissue was digested with papain. The GAG was fractonated with cetylpyridiniumchloride according to Svejcar's and Robertson's techniques and afterwards it was characterised in detail. The total amount of GAG per gramme of fat free dry tissue was the same in RA and in controls. The GAG distribution pattern was significantly changed: 1. A large fraction of hyaluronic acid was found in acutely inflamed tissue with only few scars. 2. In tissue with much cicatrization, however, acute processes accompanied by large amounts of hyaluronic acid appeared unimportant. There the L-iduronic acid content of the Ch-4-S and the Ch-6-S fractions (increased hybridization) and its total amount was increased. The tendency to increased epimerization of D-glycuronic acid to L-iduronic acid in the GAG-chains was clearly shown by an increase of the GAG-fraction, which contains relatively pure dermatane sulphate.
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PMID:[The synovial membrane in rheumatoid arthritis: change in the glycosaminoglycan pattern]. 13 64

IgM rheumatoid factors (RF) were isolated from the sera of patients with rheumatoid arthritis and a serologically active Fabmicron RF fragment prepared by papain digestion. A radioimmunoassay was developed for the determination of interaction of 19S IgM RF and Fabmicron RF with human 7S IgG, heat-aggregated IgG, rabbit 7S IgG, and human pFc'. RF isolated under neutral conditions had a very low binding constant for human 7S IgG (of the order of 10(2) to 10(3) 1 mole-1) and a considerably higher value (ca. 10(5)) for the aggregated protein and monomeric rabbit IgG. RF obtained under acid conditions which dissociate the complexes with endogenous Ig, had a higher avidity for human IgG monomer as expected and also a comparable reactivity with rabbit IgG. Monovalent Fabmicron fragments of 'acid' RF had closely similar affinities for 7S and aggregated IgG suggesting that the enhanced binding with the aggregated protein is essentially dependent on its multivalency rather than the exposure of a new determinant lacking in the native molecule.
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PMID:The binding constants of IgM rheumatoid factors and their univalent fragments for native and aggregated human IgG;. 84 79

The glycosaminoglycans (GAG) directly adsorbable from undiluted plasma on DE-52 anion-exchange cellulose (free GAG) and the GAG adsorbable on AG 1 X 2 anion exchange resin after papain proteolysis (bound GAG) were determined in 35 patients suffering from active erosive rheumatoid arthritis (RA) and in 50 control subjects. Free GAG levels were significantly elevated in both female (p less than 0.001) and male (p less than 0.05) RA patients. Bound GAG levels were significantly depressed in female (p less than 0.02) but not in male RA patients. Total GAG concentrations in RA patients and in controls were fairly similar. No consistent differences in the electrophoretic patterns of the plasma GAG from RA patients and controls were discernible. The free GAG concentrations in RA plasma samples did not correlate with seropositivity or ESR.
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PMID:Acid glycosaminoglycans in plasma. II. Findings in rheumatoid arthritis. 92 24

Whole body elimination studies of human serum IgG have showm that C57Bl miceare tolerant to this protein at low concentrations. The present study demonstrates that tolerance to this protein may be broken by presensitization of the mouse with the pepsin-derived fragments of human IgG (F(ab)2 and pFc), in marked contrast to the papain-derived fragments (Fab and Fc). Sensitization with F(ab)2 fragments induced a distinctive elimination pattern of the intact protein which was analogousto that observed in non-sensitized mice injected with serum IgG isolated from patients with rheumatoid arthritis. Since, by circular dichroism studies, we have previouslyimplicated a structural anomaly at or near the hinge region of the 'rheumatoid' IgGmolecule, our observations are discussed in relationship to a possible immune aetiologyfor rheumatoid arthritis.
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PMID:Catabolism of human IgG in mice sensitized to various IgG fragments. Similarities to the catabolism of rheumatoid IgG in mice. 115 Mar 12

A new model employing latex of papaya as an inflammagen has been developed for testing anti-inflammatory activity. The latex (exudate) was harvested from the unripe papaya fruit, which had been dried under vacuum. The latex was then suspended in 0.05 M sodium acetate buffer. This suspension when injected in rat hind paw produced concentration-dependent inflammation. Of the 0.25% of this suspension, 0.1 ml was found ideal for evaluating anti-inflammatory activity of test drugs. This concentration produced 70%-100% inflammation lasting for about 5 hr with a maximum effect at h 3. The test drugs employed were prednisolone, aspirin, indomethacin, phenylbutazone, ibuprofen, piroxicam, chloroquine, levamisole, and a mixture of boswellic acids. For comparison, these drugs were also tested against carrageenan-induced inflammation. All the test drugs--steroidal, aspirin, and non-aspirin-like--showed anti-inflammatory activity against latex-induced inflammation. The activity of chloroquine, levamisole, and boswellic acids was significantly more against latex as compared with that of the carrageenan model. The inflammation caused by latex may be attributed to both its hydrolytic enzymes--papain and chymopapain--and glutathione, the activator of these enzymes. These enzymes seem to act like lysosomal enzymes that are released in inflammatory disease processes which mediate inflammation by stimulating the synthesis of prostaglandins. The papaya latex-induced inflammation model appears to be a sensitive, broad-based, and relevant one likely to prove useful for discovering new and effective drugs against inflammation and rheumatoid arthritis.
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PMID:A sensitive and relevant model for evaluating anti-inflammatory activity-papaya latex-induced rat paw inflammation. 139 54

Human leucocyte elastase (HLE) cleaves IgG into Fab and Fc fragments. The Fc fragment bears an elastase-specific antigen and has previously been reported to be found in synovial fluid during rheumatoid arthritis. In addition, biological activity of elastase-specific Fc fragments has been described in modulating granulocyte oxidative metabolism. To investigate further regulatory effects of the elastase-induced IgG cleavage products, we tested the elastase and myeloperoxidase release of granulocytes. IgG fragments induce no enzyme release of unstimulated neutrophils. But elastase and myeloperoxidase release of cytochalasin b/FMLP-treated neutrophils is stimulated in a dose-dependent manner by the Fab fragments. The extent of stimulation depends on stimulus concentration and is at its maximum for low (e.g. 2.5 x 10(-8) M) FMLP concentration. Ten nanomoles Fab/4 x 10(6) PMN augment elastase release to 206% and myeloperoxidase release to 155% after pre-stimulation with 2.5 x 10(-8) M FMLP. Fc fragments stimulate elastase release to 162% but no MPO release. Untreated IgG1 and analog Fab and Fc fragments produced by papain cleavage react similarly. Elastase-generated IgG fragments may therefore up-regulate their concentration by simulating elastase release. The concomitantly stimulated release of myeloperoxidase may influence bactericidal activity and termination of oxidative burst.
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PMID:Stimulation of neutrophil elastase and myeloperoxidase release by IgG fragments. 216 86

We have recently reported the presence of IgG which has a potent inhibitory activity against IL-1 alpha in some sera from patients with rheumatoid arthritis. The mechanism of this inhibition by IgG against IL-1 alpha is now elucidated. IgG with IL-1 alpha-inhibitory activity inhibited the binding of 125I-IL-1 alpha to receptors on rheumatoid synovial cells. In addition, preincubation of synovial cells with the inhibitory IgG did not block the binding of 125I-IL-1 alpha to receptors, suggesting a direct interaction between IgG and IL-1 alpha. To examine which region of the IgG, namely Fab or Fc region, has the inhibitory activity, the IgG was digested with papain, and Fab and Fc fragments were purified. Fab fragments, but not Fc fragments, inhibited both IL-1 alpha-induced thymocyte-proliferation and the binding of 125I-IL-1 alpha to receptors. We further demonstrated that the inhibitory IgG which was bound to protein A Sepharose could bind a significant amount of 125I-IL-1 alpha, whereas only a negligible binding of the radiolabeled ligand was detected when IgG without the inhibitory activity was used as control. Moreover, the binding of 125I-IL-1 alpha to IgG with the inhibitory activity was clearly blocked by Fab fragments of IgG having the inhibitory activity. Finally, affinity-purified IgG over an IL-alpha affinity column showed approximately 100-fold more potent inhibitory activity on IL-1 alpha-induced thymocyte proliferation compared with untreated IgG. From these results, we conclude that IgG molecules with IL-1-alpha-inhibitory activity are neutralizing autoantibodies against IL-1 alpha.
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PMID:Demonstration of neutralizing autoantibodies against IL-1 alpha in sera from patients with rheumatoid arthritis. 239 74

Several complexes of enzymes and immunoglobulins were detected at the same time in the serum of a patient with seropositive rheumatoid arthritis. The enzymes which were found to complex with immunoglobulins were lactate dehydrogenase, alkaline phosphatase (liver, bone, placental, and intestinal isoenzymes), amylase, cytosol leucine aminopeptidase, and microsomal leucine aminopeptidase. Reconstitution studies after papain or pepsin digestion showed that the association site of the enzymes was in the Fab portion of the immunoglobulin component. We found these complexes to be the result of an antibody-antigen reaction. The binding capacity of each enzyme was variable over the entire time course. The patient's immunoglobulins, complexed with lactate dehydrogenase or amylase, could not be reconstituted using alkaline phosphatase, cytosol leucine aminopeptidase, or microsomal leucine aminopeptidase in vitro. Therefore, this suggests that the immunoglobulins which bind to each enzyme are independent of each other.
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PMID:A case of rheumatoid arthritis with various enzyme-immunoglobulin complexes. 242 42

Synovial fluid samples (139) from 121 patients with rheumatoid arthritis, osteoarthritis, pseudogout, chronic pyrophosphate arthritis, gout, and reactive arthritis were analysed for cartilage proteoglycan components. Keratan sulphate (KS) epitope was determined by a competitive radioimmunoassay, and total sulphated glycosaminoglycans (S-GAG) were determined after papain digestion by a specific dye binding assay. Increased concentration of both KS epitope and S-GAG were found in synovial fluid from joints with acute inflammatory arthropathy (gout, pseudogout, and reactive arthritis). Analysis of consecutive samples from the same joint at different stages showed that the concentration of KS epitope or total S-GAG varied with acute inflammatory activity. In samples from patients with chronic conditions during active and inactive inflammatory phases concentrations were much lower and not distinguishable among these disease groups. The detection of raised concentration of proteoglycan components may reflect the rapid depletion or greatly increased turnover of proteoglycan in the articular cartilage during acute inflammation in the joint. This did not appear to be sustained in most patients with chronic joint diseases.
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PMID:Increased concentrations of proteoglycan components in the synovial fluids of patients with acute but not chronic joint disease. 246 86

An enzyme-linked immuno-sorbent assay (ELISA) for quantitation of rheumatoid factors (RF) of IgM, IgA and IgG isotypes has been established. A complex of human serum albumin (HSA) and rabbit IgG anti-HSA antibodies is used as antigen for RF. The binding of RF is detected by stepwise additions of biotinylated monoclonal antibodies specific for human IgM, IgG or IgA, alkaline phosphatase-conjugated streptavidin, and substrate. The assay is simple and applicable to routine testing of large numbers of sera. It discriminates between false and true IgG-RF by papain digestion of sera that turn out positive by the screening for IgG-RF. Of 241 randomly selected patients with rheumatoid arthritis (RA) as well as other rheumatoid and infectious diseases, 110 were Waaler-Rose-positive while 127 were IgM-RF-positive in ELISA. The correlation between the Waaler-Rose test and IgM-RF ELISA was highly significant (r = 0.82). By testing 65 of these sera (all IgM-RF positive), 25 (39%) were also true IgG-RF positive (42 (64%) in the screening). When 40 Waaler-Rose-positive RA patients were tested, 20 and 21 were also positive for IgG- and IgA-RF, respectively. Eight IgM-, one IgA- and no IgG-RF positive tests were recovered when 48 Waaler-Rose negative RA patients were studied.
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PMID:Quantitation of rheumatoid factors (RF) of IgM, IgA and IgG isotypes by a simple and sensitive ELISA. Discrimination between false and true IgG-RF. 307 Jul 22


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