Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence and titer of cathepsin D agglutinators (CDA) were significantly higher in seropositive rheumatoid arthritis (RA) sera than in the sera of healthy blood donors or of patients with other rheumatic diseases, including seronegative RA. A significant elevation was also found in synovial fluid (SF) samples from seropositive RA patients. CDA in the SF tended to be increased when compared with the corresponding serum. The levels of CDA correlated positively with those of rheumatoid factors (RF) when the latter were determined with IgG anti-CD Ripley-coated erythrocytes, but not when they were determined by the Waaler-Rose or latex tests. The increased CDA titers do not seem to be the result of significant amounts of IgM agglutinators or of the presence of IgM-RF. These findings suggest the existence of a link between the formation of RF and CDA, but the nature of this link cannot be fully explained.
Arthritis Rheum 1977 Jun
PMID:Cathepsin D agglutinators in rheumatoid arthritis. I. Increased CDA titers in serum and synovial fluid of patients with seropositive RA. 6 78

Tissue culture methods demonstrated the production of agglutinators against the cathepsin D site in IgG (CDA) and a neutral protease site in IgG (NPA) by rheumatoid synovial tissue. Seven of 11 specimens from seropositive and 2 of 7 specimens from seronegative RA patients were positive for CDA, whereas 2 of 11 specimens from seropositive and 1 of 7 specimens from seronegative patients were positive for NPA. None of the 6 control specimens was positive for both types of agglutinators. Chromatography of two synovial tissue incubates showed that the CDA were of the IgG type. By the immunofluorescence technique, plasma cells containing CDA were demonstrated in rheumatoid synovial tissue and draining lymph nodes of rheumatoid joints. The staining for CDA in the synovium was different from the staining for pepsin agglutinators in adjacent sections. Phagolysosomes containing CDA were found in synovial exudate cells from rheumatoid patients as well as in phagocytosing lining cells and macrophages of the sublining layer of rheumatoid synovial tissue. These findings suggest that antibodies directed at hidden antigenic sites in IgG revealed by endogenous proteolysis take part in the immune reaction and in the inflammation of rheumatoid joints.
Arthritis Rheum
PMID:Cathepsin D agglutinators and neutral protease agglutinators in rheumatoid arthritis. II. Production of CDA and NPA by rheumatoid synovium and phagocytosis of CDA by synovial phagocytic cells. 7 Nov 53

Connective tissue cells are capable of both synthesizing and degrading the macromolecular components of the extracellular matrix. The degradation of proteoglycan and collagen has been shown to be associated with the extracellular release of proteolytic enzymes, some of which are of lysosomal origin. The identity in carilage of two previously unrecognized proteases, capable of proteoglycan breakdown (CPGases), has recently been achieved by the use of a new assay for proteoglycan degradation. These enzymes have been shown to be synthesized and released in response to vitamin A. The third proteoglycan degrading enzyme of connective tissue cells, cathepsin D, has been located in the pericellular environment by trapping with specific antibody and the pattern of release studied in organ culture, experimental arthritis and in human rheumatoid tissues. The secretion of this enzyme and possibly also of the other CPGases is thought to be of importance in the local (pericellular) turnover of matrix macromolecules and, in association with collagenase, to be the cause of the excessive degradation in the pannus erosion of articular cartilage in rheumatoid arthritis.
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PMID:The secretion of enzymes into the pericellular environment. 23 25

Over 20 successive intra-articular injections of autologous or homologous cathepsin D-Fab2 produce chronic destructive arthritis marked by dense round-cell infiltration, epitheloid hyperplasia of the lining layer, lymph nodules and a few germinal centres. 75% of the animals become Rf-positive and develop high titers of homoreactants to cathepsin D-Fab. Both these antibodies are synthesized in the synovial membrane and phagocytosed. Careful study of control animals makes it possible to exclude the possibility that the effects observed are due to the repeated joint traumata, to endo- or exotoxin-like substances, to chromatographed lysosomal material or to traces of cathepsin D. Autologous and homologous Fab2 have largely identical effects, while those of homologous or autologous IgG are much less marked. These comparisons suggest that the cathepsin D site of IgG acts as a strong antigen when exposed in the joint. The synovitis thereby induced has a pronounced tendency to spread to the left knee joint which was injected with physiological saline.
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PMID:Experimental arthritis of rabbits caused by intra-articular injection of autologous Fab2 produced by digestion of IgG with cathepsin D. II. Microscopical and immunohistochemical findings in long-term experiments. 79 20

A single intraarticular injection of carrageenin into the rabbit knee joint initiates an inflammatory reaction in the synovial tissues. the exudate from the joint was able to degrade proteoglycan at pH 5.2 and pH 7.2. Further characterization of proteolytic enzymes in the inflamed synovial tissues showed the presence of cathepsin D, a neutral protease, and cathepsin B1. Maximum activities of two lysosomal enzymes, acid phosphatase and cathepsin D, were observed within 7 days of injection. Most of this activity was found to be associated with cells in the synovial fluid.
Arthritis Rheum
PMID:Carrageenin-induced arthritis. III. Proteolytic enzymes present in rabbit knee joints after a single intraarticular injection of carrageenin. 99 38

The proteinase cathepsin D which degrades proteoglycan was never demonstrated in extracellular sites in tissues from patients with traumatized meniscoid cartilage, either before or after culture with an antiserum to human cathepsin D. In contrast, in synovia (but not usually cartilage) from the knees of 6 of 11 rheumatoid patients, extracellular cathepsin D was commonly detected by culturing tissues with an antiserum to this enzyme.
Arthritis Rheum
PMID:Secretion and localization of cathepsin D in synovial tissues removed from rheumatoid and traumatized joints. An immunohistochemical study. 103 89

Fragments of bovine plasma fibronectin produced by cathepsin D digestion are reportedly mitogenic for hamster fibroblasts. Rheumatoid arthritis synovial fluid contains many fibronectin fragments, which may contribute to the proliferation of synovial cells. We have therefore investigated the potential of fibronectin fragments to stimulate proliferation of synovial fibroblast-like cells using human material. Affinity-purified human plasma and synovial fluid fibronectin was digested with cathepsin D at pH 3.5 for 0-18 h and proteolysis stopped with pepstatin. A variety of fragments were produced ranging from 50 to 200 kDa when analysed by SDS-PAGE. The proliferative activity of various test preparations was studied using quiescent human skin and synovial fibroblasts. Tests were applied for 24 h to 10(4) cells and DNA synthesis measured by tritiated thymidine incorporation. Both undigested and peptides of fibronectin consistently failed to stimulate DNA synthesis in fibroblasts at all concentrations tested, compared with a phosphate-buffered saline control. This was in marked contrast to human synovial fluid from either rheumatoid arthritis or osteoarthritis patients, which stimulated DNA synthesis in the same system (P less than 0.01). Therefore, our data do not confirm the findings of previous studies in which animal materials were used. We can find no evidence that fibronectin fragments play a role in stimulating synovial proliferation in inflammatory arthritis.
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PMID:Synovial fluid fibronectin fragments: no evidence for a mitogenic effect on fibroblasts. 207 72

Activity of cathepsin D in synovial fluid of the knee joint and blood of 113 patients with injuries of this joint was studied. A conclusion is made about pathogenetic role of cathepsin D in the development of reactive arthritis.
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PMID:[Role of cathepsin D of synovial fluid of the knee joint in the pathogenesis of traumatic arthritis]. 404 47

The activity of collagenase, cathepsin B1, cathepsin D and Hyaluronidase was determined in skin, bone, liver, kidney, spleen and serum of adjuvant induced arthritic rats during the acute and chronic phase of the disease. Collagenase was assayed directly in tissue extract by a solution method using radioactive labelled substrate. The activity of collagenase, cathepsin B1 and D was found to increase significantly at both phases of the disease. The activity of hyaluronidase decreased significantly in liver, kidney and spleen of arthritic rats, while in skin, bone and serum no significant change was observed. The results are discussed with respect to catabolism of collagen in adjuvant induced arthritis. Prednisolone and L-thyroxine were administered to arthritic rats and the activity of collagenase, cathepsin B1, cathepsin D and hyaluronidase was determined in the treated groups during the acute and chronic phase of the disease. Prednisolone was found to suppress the development of arthritis which, in turn, decreased the increased activity of collagenase and lysosomal enzymes cathepsin B1 and D in tissues and serum of arthritic rats. L-Thyroxine was found to slowly diminish the development of inflammation and its beneficial action was found in mesenchymal tissues and skin of arthritic rats but not in bone.
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PMID:Effect of adjuvant arthritis on collagenase and certain lysosomal enzymes in relation to the catabolism of collagen. 624 97

Cultured tissue slices from normal immature rabbit articular cartilage released latent neutral metalloproteinases into serum-free medium. On activation with 4-aminophenylmercuric acetate, these metalloproteinases could degrade collagen, proteoglycan, and gelatin. Also produced were an acid proteinase with the properties of cathepsin D and an inhibitor of the neutral metalloproteinases. The appearance of both the proteinases and the inhibitor in the culture medium could be prevented by incubation of cultures with cycloheximide. The active and latent forms of the proteinases were characterized using Ultrogel AcA 54 chromatography.
Arthritis Rheum 1983 Aug
PMID:Characterization of latent and active forms of cartilage proteinases produced by normal immature rabbit articular cartilage in tissue culture. 634 45


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