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)

Synovial fluid samples were collected from 45 patients with rheumatoid arthritis, spondylarthropathy, or osteoarthritis, to study their content of elastase (EC 3.4.21.37) and of cysteine proteinases (EC 3.4.22.1, 3.4.22.15). We measured both elastase complexed with alpha 1-proteinase inhibitor and elastase activity toward the substrate L-pyroglutamyl-L-prolyl-L-valine-p-nitroanilide. Cysteine proteinase activities were measured with the substrates N-benzyloxycarbonyl-L-phenylalanyl-L-arginine-7-amido-4-methylcoumarin (Z-Phe-Arg-AMC) and Z-Arg-Arg-AMC and the inhibitor E-64 [L-trans-epoxysuccinyl-leucyl-amido-(4-guanidino)-butane]. In all these enzyme assays, higher median values were obtained in inflammatory arthropathies than in osteoarthritis. The concentration of the elastase-alpha 1-proteinase inhibitor complex and of elastase and cysteine proteinase activities were statistically higher in patients with rheumatoid arthritis than in patients with osteoarthritis. The difference in results between patients with spondylarthropathy and patients with osteoarthritis was statistically significant only for the elastase-alpha 1-proteinase inhibitor complex. The median values of the complex and of both enzyme activities were higher in patients with rheumatoid arthritis than in patients with spondylarthropathy; however, the difference was statistically significant only for the cysteine proteinase activity measured with Z-Arg-Arg-AMC substrate. These results suggest that both elastase and cysteine proteinases, which are increased in patients with inflammatory arthritis, are involved in cartilage degradation in these arthropathies.
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PMID:Measurement of elastase and cysteine proteinases in synovial fluid of patients with rheumatoid arthritis, sero-negative spondylarthropathies, and osteoarthritis. 152

Based on the concept that proteolytic enzymes, like cathepsins, are associated with tissue destruction, we investigated the expression of the matrix-degrading cysteine proteinase cathepsin B in synovial tissues from the joints of patients with rheumatoid arthritis. The data indicate an enhanced transcription of cathepsin B in synovial cells when compared with normal fibroblasts, cathepsin B-producing epithelial tumor cells (SW1116), or fibroblasts derived from inflamed tonsils. Immunolocalization of cathepsin B appeared to be restricted mainly to the synovial cells attached to cartilage and bone at sites of rheumatoid joint erosion.
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PMID:Cathepsin B in synovial cells at the site of joint destruction in rheumatoid arthritis. 195 21

Joint and bone damage in rheumatoid arthritis is thought to be caused primarily by an imbalance between proteolytic proteinases and their specific inhibitors. Matrix destruction can in part result from the activity of lysosomal cystein proteinases such as cathepsin B and L. Cathepsins usually are determined by enzyme immuno-assay. The aim of this study was the direct determination of synovial thiol-proteolytic activity by spectrofluorimetry using a synthetic substrate (Z-Phe-Arg-NMec) and a cystein proteinase specific inhibitor (E64 = L-trans-epoxy-succinyl-leucylamino-(4 guanidino)-butane). 18 rheumatoid synovial fluids were tested compared to 10 osteoarthritic synovial fluids. Thiol-proteolytic activity appeared higher in rheumatoid arthritis compared to osteo-arthrosis (mean value = 1,311 mU/l vs 156 mU/l, p less than 0.01). Synovial thiol-proteolytic activity is well correlated with synovial elastase-alpha1-proteinase-inhibitor complex. The authors found no correlation with synovial polymorphonuclear count (p = 0.38) nor with clinical and biological parameters of disease evolution. The highest values were observed in patient with radiological signs of joint destruction. Synovial thiol-proteolytic activity might represent the potential destructive evolution of rheumatoid arthritis.
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PMID:[Thiol-proteolytic activity in rheumatoid polyarthritis. Assay by spectrofluorimetry]. 204 9

Synovial fluids and sera of patients with inflammatory and metabolic joint diseases contain different cysteine proteinases. The quantities of cathepsins B and H were determined by newly developed specific enzyme-linked immunoassay tests (ELISA), with detection limits of 0.5 microgram/l for cathepsin B and 3 micrograms/l for cathepsin H. The values of cathepsin B in normal sera ranged from 0.6 microgram/l to 2 micrograms/l, whereas in sera of patients with joint diseases they ranged from 1.7 micrograms/l to 18 micrograms/l. Cathepsin H was not found in sera (values below 3 micrograms/l), but was measurable in patients' synovial fluids. Patients with rheumatoid arthritis have on average the highest values of cathepsin B in synovial fluids, whereas patients with undifferentiated arthritis have the highest values of cathepsin H. The results show that cathepsins B and H are present in arthritic synovial fluids, where they may be implicated in destructive processes. There is yet no clear correlation between the quantity of each cathepsin released in synovia and the clinical diagnosis or the stage of the disease.
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PMID:Determination of cathepsins B and H in sera and synovial fluids of patients with different joint diseases. 232 22

Blood monocytes isolated from healthy human donors were cultivated for 3 days in the presence of recombinant human interferons (rHuIFN) alpha, beta, gamma. Intracellular activity of cathepsin B was recorded. All rHuIFNs suppressed the cathepsin B activity in the monocytes, rHuIFNs alpha and beta suppressed in a dose-dependent manner, whereas rHuIFN-gamma was suppressive only at low concentrations (1-10 U/ml). In parallel experiments, monocytes were stimulated with carrageenan, which caused increased cathepsin B activity in the cells. This increase was reduced to the level of activity in nonstimulated cells by all rHuIFNs. We have previously reported that cathepsin B may be involved in the pathogenesis of rheumatoid arthritis, and the present results may have a bearing on the effects of HuIFNs on the immune system.
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PMID:The effect of recombinant interferons on cathepsin B activity in human monocytes. 247 2

Cathepsin B was cytochemically investigated in the cells of synovial membranes and in the cell pellet of synovial fluids obtained from 50 patients with rheumatoid arthritis and eight patients with various nonrheumatoid arthropathies. The activity of Cathepsin B was estimated by using the substrate N-alpha-benzoyl-DL-arginine-naphthylamide HCl and diazoic dye Fast Corinth V in phosphate buffer pH 6.0 in the presence of EDTA and cysteine. A significant activity of cathepsin B was shown in lining mesothelial cells, in macrophages of the submesothelial infiltrations, as well as in fibroblasts prominent in the deep areas of rheumatoid synovial membranes. In the cell pellets of synovial fluids the highest activity of cathepsin B was found in the macrophages and polymorphonuclear leukocytes, accompanied by a variable activity in lymphocytes. The considerable activity of cathepsin B, an enzyme with degradative action upon collagen and proteoglycans, in the main cellular populations of rheumatoid synovial membranes and fluids, suggests its involvement in the genesis and maintenance of rheumatoid lesions.
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PMID:Cytochemical investigation of cathepsin B in rheumatoid synovial membrane and fluid. 293 23

Synovial fluid of patients with different inflammatory and metabolic joint diseases contains low-molecular CPIs (stefins and cystatins) and high-molecular CPIs (kininogens). An additional inhibitory fragment with a molecular mass of about 20 kDa, which is a part of the kininogen molecule, has been detected. Cathepsin B and cystatin C were determined by ELISA test in 47 patients with rheumatoid arthritis, seronegative spondylarthritis, osteoarthritis, undifferentiated arthritis and gout. A significantly higher amount of cathepsin B was found in patients with rheumatoid arthritis. The elevation of cathepsin B was accompanied by an increased amount of cystatin C.
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PMID:Human cathepsin B and cysteine proteinase inhibitors (CPIs) in inflammatory and metabolic joint diseases. 326 7

Cathepsin B is a lysosomal enzyme of importance in many physiological and pathological processes. Its distribution in human tissues was studied by an indirect immunoperoxidase method. Cathepsin B was demonstrated in macrophages, hepatocytes, renal tubules, gastrointestinal epithelium and fibroblasts, confirming previous studies. It was demonstrated for the first time by immunohistology in several other tissues, especially stratified squamous epithelium, transitional epithelium, salivary glands, pancreas, central and peripheral neuronal cell bodies, trophoblast and all endocrine organs. Widespread distribution of cathepsin B has been postulated several times but this is the fullest evidence that the enzyme indeed occurs in many organs. In pathology cathepsin B has so far been thought to be involved in demyelination, emphysema, rheumatoid arthritis and neoplastic infiltration.
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PMID:The distribution of cathepsin B in human tissues. 388 45

Mouse peritoneal macrophages were stimulated by sera from patients with active rheumatoid arthritis (RA) to increased intracellular cathepsin B activity. By gel filtration of three RA sera, the stimulatory activity was found in the IgG and to a lesser extent in the IgM containing fraction. The DEAE-cellulose purified IgG preparations of five additional RA patients stimulated intracellular cathepsin B activity significantly above IgG from healthy controls. IgG and IgM antibodies to macrophages were detected in sera from RA patients but not from controls by indirect immunofluorescence (IIF) technique. Pepsin F (ab')2 fragments of IgG from the RA patients also gave clearcut membrane fluorescent staining of the macrophages which demonstrated the antibody nature of the binding. A good correlation between the cathepsin B assay and the IIF was found when serial dilutions of serum were compared.
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PMID:A serum antibody in patients with rheumatoid arthritis stimulates cathepsin B activity in peritoneal mouse macrophages. 636 Apr 38

Cultures of non-elicited mouse peritoneal macrophages were used as a test system to study the effect of sera from patients with rheumatoid arthritis (RA) on intra-cellular cathepsin B activity of macrophages. Sequential sera obtained during and after pregnancy from six RA patients, and sera from six actively ill, non-pregnant RA patients were compared to six healthy female controls and 3rd trimester healthy women. Sera from actively ill RA patients (both pregnant and non-pregnant) caused macrophage cathepsin B levels significantly above normal controls, while intra-cellular activities of beta-glucuronidase and N-acetyl-glucosaminidase did not differ from the controls. A significant correlation between activity of RA and intracellular cathepsin B was found in pregnant patients. It is suggested that a factor (or factors) present in serum from patients with active RA causes a rise of intracellular cathepsin B in macrophages.
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PMID:Stimulation of murine macrophage cathepsin B by serum from patients with rheumatoid arthritis: an indicator of disease activity. 683 68


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