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)

Hyaluronic acid (4 mg/ml) augmented elevenfold the copper-catalyzed (7 muM) thermal (63 degrees C, 2 hours) aggregation of human gamma globulin (2 mg/ml) in 0.075 M phosphate buffer, pH 7.4. Almost no augmentation of aggregation occurred with hyaluronidase-treated hyaluronate. Hyaluronate-augmented copper-catalyzed thermal aggregation was inhibited by L-histidine, gold thiomalate, N-ethylmaleimide, p-chloromercuribenzoic acid, and ethylenediaminetetraacetic acid. Together with previous reports of a decreased blood histidine concentration in rheumatoid arthritis, these studies provide a possible explanation for the affinity of this disease for joints.
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PMID:Sulfhydryl-dependent thermal aggregation of human gamma globulin: augmentation by hyaluronic acid. 4 54

Serum glycosaminoglycans were studied in patients with rheumatoid arthritis by means of electrophoresis. Dismucopolysaccharidemia, which was observed in these patients, was manifested in alteration in the ratio of hyaluronic acid and chondroitin-4-sulphate and also in occurrence of heparin associated with protein and chondroitin-6-sulphate in blood serum. The latter fractions of glycosaminoglycans are not usually found in blood of healthy persons. The alteration in the ratio of fractions of glycosaminoglycans was accompanied by a decrease in content of hyaluronic acid in synovial tissue of the joints impaired, by an increased excretion of the substance with urine and also by the increased activity of hyaluronidase in blood serum, articular fluid and in synovial tissue. The alterations in the composition of blood glycosaminoglycans, which correlated with the clinical manifestations of the disease, suggest that impairments of metabolism of the carbohydrate-containing biopolymers are involved in the genesis of rheumatoid arthritis.
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PMID:[Glycosaminoglycans in blood serum of patients with rheumatoid arthritis]. 14 May 27

Synovial cell lines were established from patients with rheumatoid arthritis (RA) and from normal human embryos. High levels of hyaluronic acid (HA) were produced by some RA cell lines, some of which were partially or completely resistant to infection with Newcastle disease virus (NDV), vesicular stomatitis virus (VSV), and rubella virus (RV). Normal fetal synovial cells lines were susceptible to NDV, VSV, and RV. Infection with virus became possible after treatment of RA cells with hyaluronidase to depolymerize HA, and HA prevented infection of normal synovial cells with VSV. These results provide evidence that HA and not chronic or latent viral infection is responsible for the lack of susceptibility of RA synovial cells to certain viruses.
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PMID:Rubella and rheumatoid arthritis: hyaluronic acid and susceptibility of cultured rheumatoid synovial cells to viruses. 16 79

A potential enzymic mechanism for the degradation of glycosaminogly cans was characterised using enzymes found in rheumatoid synovial fluid from the knee joint. This mechanism involves a true hyluronidase together with the concerted action of beta-glucuronidase and beta-N-acetylhexosaminidase. The contribution of the exopolysaccharidases to hyaluronate degradation was demonstrated by the use of specific inhibitors, while the distinct identity of a true hyaluronidase was shown by ammonium sulphate and agarose gel column fractionations. Only the hyluronidase fraction was capable of degrading high molecular weight hyaluronate. The exopolysaccharidase activities were shown to be markedly elevated in rheumatoid as compared to osteoarthritic synovial fluid and also normal serum. On the other hand, hyluronidase was similarly active in rheumatoid and osteoarthritic synovial fluids; both these levels were lower than that of normal human serum. Hyaluronidase in synovial fluid may thus be derived by diffusion from serum, since it is of relatively low molecular weight (60 000). The pH requirements of this enzyme system and the strong inhibition of hyaluronidase by synovial fluid make it unlikely that the mechanism operates extracellularly. It is proposed that as a lysosomal mechanism, however, it is an important contributing factor in the chronic erosion process characteristic of rheumatoid arthritis.
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PMID:The characterisation and function of the polysaccharidases of human synovial fluid in rheumatoid and osteoarthritis. 23 48

In the present study we investigated the antiinflammatory effect of pentosanpolysulfate (SP 54) in combination with metamizol using different forms of rat paw edema (induced by dextrane, hyaluronidase, trypsin, formaldehyde, carragenine or kaolin). After s. c. application Probaphen, a new drug containing pentosanpolysulfate, metamizol, and lidocaine, proved in our experiments to exert an antiphlogistic effect about 40% stronger than the equivalent amount of SP 54 alone. Since pentosanpolysulfate by itself has no analgetic activity, its combination with metamizol results in a formulation which is not only a more potent antiinflammatory drug but will aslo counteract pains which accompany most edematous reactions. Probaphen may therefore be suggested for the treatment of rheumatoid arthritis and similar inflammatory and edematous processes. First clinical studies and reports on Probaphen fully support our pharmacological results.
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PMID:[Pharmacological studies on the antiphlogistic effect of pentosanpolysulfate in combination with metamizol]. 57 70

Fourteen antirheumatoid drugs were tested for their effects on the in vitro hyaluronidase activity of normal human serum. Four drugs produced significant changes in enzyme activity. Different results were obtained with ovine testicular hyaluronidase when diluted with either saline or inactivated human serum. No increase in serum hyaluronidase activity was found in patients with rheumatoid arthritis. There was no evidence for the existence of tissue specific isoenzymes of hyaluronidase in the serum of either normal subjects or patients with rheumatoid arthritis.
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PMID:The effects of anti-rheumatoid drugs on the in vitro activity of human serum hyaluronidase. 95 80

Hyaluronan (hyaluronic acid) is a high-molecular-mass polysaccharide found in the extracellular matrix, especially of soft connective tissues. It is synthesized in the plasma membrane of fibroblasts and other cells by addition of sugars to the reducing end of the polymer, whereas the nonreducing end protrudes into the pericellular space. The polysaccharide is catabolized locally or carried by lymph to lymph nodes or the general circulation, from where it is cleared by the endothelial cells of the liver sinusoids. The overall turnover rate is surprisingly rapid for a connective tissue matrix component (t1/2 0.5 to a few days). Hyaluronan has been assigned various physiological functions in the intercellular matrix, e.g., in water and plasma protein homeostasis. Hyaluronan production increases in proliferating cells and the polymer may play a role in mitosis. Extensive hyaluronidase-sensitive coats have been identified around mesenchymal cells. They are either anchored firmly in the plasma membrane or bound via hyaluronan-specific binding proteins (receptors). Such receptors have now been identified on many different cells, e.g., the lymphocyte homing receptor CD 44. Interaction between a hyaluronan receptor and extracellular polysaccharide has been connected with locomotion and cell migration. Hyaluronan seems to play an important role during development and differentiation and has other cell regulatory activities. Hyaluronan has also been recognized in clinical medicine. A concentrated solution of hyaluronan (10 mg/ml) has, through its tissue protective and rheological properties, become a device in ophthalmic surgery. Analysis of serum hyaluronan is promising in the diagnosis of liver disease and various inflammatory conditions, e.g., rheumatoid arthritis. Interstitial edema caused by accumulation of hyaluronan may cause dysfunction in various organs.
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PMID:Hyaluronan. 156 92

To identify the local factors in cartilage that are responsible for the induction of pannus invasion, a 14 day organ culture study in which rheumatoid synovium was grown in contact with cartilage pieces was carried out. Rheumatoid synovium preferentially extended over hyaluronidase treated cartilage pieces, but detached from untreated pieces. Rheumatoid synovium extended over hyaluronidase treated cartilage surfaces containing fibronectin more extensively than over surfaces treated with hyaluronidase only. Extension over hyaluronidase treated cartilage surfaces containing immune complexes was small. The adherence of synovial cells to hyaluronidase treated cartilage slices in vitro was specifically inhibited by the synthetic peptide, Gly-Arg-Gly-Asp-Ser-Pro, which is the adhesive portion of the fibronectin molecule. Furthermore, synovial fibroblast-like cellular extension, morphologically similar to rheumatoid pannus, was observed in the organ culture experiments in which rheumatoid synovium grew over hyaluronidase treated cartilage surfaces containing fibronectin. Synovial tissue extension over fibronectin coated surfaces was inhibited when hyaluronic acid and chondroitin-4-sulphate, major components of cartilage proteoglycans, were present on the cartilage surface. These findings suggest that fibronectin present in the superficial region of cartilage potentiates rheumatoid synovial extension and proteoglycans and immune complexes inhibit rheumatoid synovial extension. It is likely that fibronectin deposited on the eroded surface of articular cartilage induces pannus formation in rheumatoid arthritis.
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PMID:Pathogenic importance of fibronectin in the superficial region of articular cartilage as a local factor for the induction of pannus extension on rheumatoid articular cartilage. 163 60

A cofactor that selectively opsonizes particulate activators of the human alternative complement pathway and enhances their phagocytosis by human monocytes was identified in synovial fluids of patients with rheumatoid arthritis. The active material was present in fluids treated with protease inhibitors, was heat stable, and was unaffected by incubation with hyaluronidase. Chromatographic isolation of synovial fluid fibronectin by gelatin affinity and by immunoaffinity on antifibronectin monoclonal antibody BD4 yielded similar quantities of protein for each of 3 fluids. Synovial fluid proteins with the BD4 fibronectin epitope accounted for essentially all of the phagocytosis-enhancing activity and expressed this activity by opsonizing target activators. Additional chromatographic analyses of synovial fluid fibronectin with the BD4 epitope were carried out using Sepharose-bearing gelatin and 4 additional antifibronectin monoclonal antibodies. The opsonic materials were characterized as having 2 distinct fibronectin epitopes, which always mapped from the cell adhesive domain to the carboxyl-terminus of plasma fibronectin, but only rarely contained the gelatin binding domain.
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PMID:Identification and characterization of opsonic fibronectin in synovial fluids of patients with active rheumatoid arthritis. 171 22

A sandwich-binding protein assay to determine the concentration of hyaluronic acid (HA) in body fluids has been developed. In this method, a hyaluronic acid binding protein (HABP) was adsorbed to the surface of a solid phase, and HA bound to HABP on the solid phase was detected by biotin-conjugated HABP. The method could assay HA levels within 6 hours using precoated microwells with HABP. HA could be determined in the range of 2-500 micrograms/l by this method using 50 microliters of serum. Within-run precision (CV) was 5.2-10.2%. The specificity of HABP to HA was confirmed by the elimination of the reaction with treatment by hyaluronidase digestion. Serum HA levels (median; range) of patients with rheumatoid arthritis (34; 2-187 micrograms/l) were shown to be higher than those with osteoarthritis (1; 1-21 micrograms/ml) and healthy controls (2; 1-8 micrograms/ml). No correlation between levels of HA and rheumatoid factor was found. HA was demonstrated to be a potential diagnostic marker for rheumatoid arthritis, and this HABP assay could be useful for determination of HA in clinical laboratory tests.
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PMID:Assay of serum hyaluronic acid in clinical application. 247 93


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