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)

A one-step sandwich enzyme immunoassay (EIA) for matrix metalloproteinase 3 (MMP-3; stromelysin-1) was developed. The assay system used two simultaneous immunoreactions using a solid phase monoclonal antibody and a horseradish peroxidase-labeled monoclonal antibody (Fab'). The sensitivity of the assay system was 20 micrograms/l and linearity was obtained between 31 and 500 micrograms/l. The EIA system was capable of measuring both precursor and active forms of MMP-3 as well as the forms of MMP-3 complexed with tissue inhibitors of metalloproteinases. MMP-3 levels as measured by this assay are significantly higher in the sera of patients with rheumatoid arthritis as compared to those of healthy subjects and patients with osteoarthritis. Immunoblot analyses showed that in the sera and synovial fluids of patients with rheumatoid arthritis, MMP-3 is present in the 59- and 57-kDa precursor forms.
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PMID:A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 3 (stromelysin-1) using monoclonal antibodies. 128 63

Rheumatoid arthritis is known to afflict the temporomandibular joint (TMJ) with common symptoms including pain during function, tenderness on palpation, stiffness, and crepitus. New evidence suggests that metalloproteinases may be responsible for tissue changes that occur in rheumatoid arthritis. These enzymes are collagenase, gelatinase, and proteoglycanase. Antiinflammatory drugs are the first line of management for pain and inflammation in rheumatoid arthritis. This paper, however, suggests that because increased joint load is believed to cause a greater expression of destructive metalloproteinase, it is appropriate to assess even the asymptomatic temporomandibular joint and the muscles of mastication for early objective signs of dysfunction or discomfort. Interceptive management, by the use of load-reducing appliance therapy, may enable reduction of the expression of destructive metalloproteinase within the joint, thereby reducing joint destruction.
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PMID:Rheumatoid arthritis and its implications in temporomandibular disorders. 130 53

Concentrations of prostaglandin E2, interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha, phospholipase A2, collagenase and proteoglycanase activity were determined in synovial fluid from 26 patients with osteoarthrosis of the knee and 10 with rheumatoid arthritis. Osteoarthrosis synovial fluid was characterised by the absence of interleukin 1 beta while tumour necrosis factor alpha and interleukin 6 were present in relatively large amounts, by a very high phospholipase A2 activity contrasting with a very low concentration of prostaglandin E2, and by a collagenase/proteoglycanase activity only slightly less constant and high as in rheumatoid arthritis. In osteoarthrosis patients, the interleukin 6 concentration, but not that of tumor necrosis factor alpha, was correlated with the collagenase and proteoglycanase activity of synovial fluid.
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PMID:[Cytokines, prostaglandin E2, phospholipase A and metalloproteases in synovial fluid in osteoarthritis]. 205 24

Tissue inhibitor of metalloproteinases (TIMP) is the major inhibitor of collagenase, gelatinase, proteoglycanase, stromelysin, and metalloelastases. An imbalance between proteases and inhibitors has been implicated in numerous disease processes including tumor invasion, rheumatoid arthritis, emphysema, and aortic aneurysm disease. The purpose of this investigation was to develop a polyclonal antibody to recombinant TIMP and establish an immunoassay to measure immunoreactive protein in normal and diseased tissues. A polyclonal antibody was produced in rabbit against recombinant human TIMP which was characterized and used to establish a radioimmunoassay. The assay was used to measure immunoreactive protein in fibroblast conditioned medium, human serum, and aortic extracts. There was more immunoreactive TIMP in matrix associated urea extracts than soluble salt extracts from human aorta, suggesting that TIMP is matrix associated. The sensitivity of the assay enables the specific measurement of this inhibitor in serum, fibroblast culture medium, and tissue extracts.
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PMID:Tissue inhibitor of metalloproteases (TIMP) is matrix associated in aortic tissue: report of a radioimmunoassay. 232 85

In order to clarify the role of CD5 antigen on B cell in autoimmunity, we examined B cells from patients with rheumatoid arthritis (RA). The percentages of CD5 positive B cells were increased in peripheral blood from RA compared with normal. Normal and RA B cells were stimulated with two kinds of monoclonal antibodies to CD5 (Leu-1, SL-1) which recognize different epitopes. RA B cells proliferated and secreted IgM by CD5 antibody stimulation in combination with IL-1. Our observations imply that CD5 positive B cells in RA are in their differentiation stage and that CD5 antigen might be one of the triggers to activate CD5 positive B cells in vivo to produce autoantibody.
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PMID:Stimulatory effect of CD5 antibody on B cells from patients with rheumatoid arthritis. 245 73

Metalloproteinases produced by connective tissue cells may play a key part in the destruction of joints in rheumatoid arthritis. Matrix metalloproteinase 3 (MMP-3; stromelysin) capable of degrading cartilage proteoglycans and type IX collagen and of activating procollagenase was immunolocalised in hyperplastic synovial lining cells in rheumatoid synovium, but not in the cells of normal synovium. Cells responsible for synthesis of MMP-3 have the phenotype of synovioblasts (B cells) by immunoelectron microscopy, but not of phagocytic synovial macrophages (A cells). Cultured monolayer of rheumatoid synovial cells synthesises MMP-3 only under treatment with macrophage conditioned medium. Immunolocalisation of MMP-3 in rheumatoid synovium and cultured synovial cells was possible when the specimens were treated with a monovalent ionophore, monensin. These results suggest that MMP-3 is synthesised and secreted continuously without storage from hyperplastic synovioblasts stimulated by factor(s) derived from activated macrophages present in the synovium.
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PMID:Immunolocalization of matrix metalloproteinase 3 (stromelysin) in rheumatoid synovioblasts (B cells): correlation with rheumatoid arthritis. 267 82

We have investigated the relationship between the monokine interleukin 1 (IL-1) and the connective tissue-stimulating activities produced by monocytes such as mononuclear cell factor (MCF). Using almost exclusively human tissue we have monitored a wide range of MCF-like activities through the partial purification of IL-1 by gel filtration and isoelectric focusing. Activities measured include stimulation of chondrocytes to produce prostaglandins, plasminogen activator and proteoglycanase, enhancement of synovial cell proliferation, and stimulation of cartilage resorption, in addition to IL-1 (lymphocyte activating factor) activity. The activities described show the same molecular heterogeneity; the active material has similar potencies in the different systems, and removal of IL-1 activity by pretreatment with phenylglyoxal also results in loss of the connective tissue-stimulating activities. These results show that the factors responsible for this wide range of activities are very closely related to IL-1 and give further evidence in support of the possible involvement of IL-1 in the processes of joint destruction occurring in chronic inflammatory conditions such as rheumatoid arthritis.
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PMID:Modulation of connective tissue metabolism by partially purified human interleukin 1. 387 64

Stromelysin-1 (MMP-3) is a metalloproteinase that degrades articular cartilage matrix in patients with rheumatoid arthritis (RA). We measured MMP-3 in the sera from patients with RA and other connective tissue diseases using specific sandwich EIA and studied its clinical significance in early onset RA. MMP-3 level in healthy control (n = 170) was significantly higher in male than in female. The level of MMP-3 in RA was significantly and dramatically higher than in healthy control, osteoarthritis, systemic lupus erythematosus, progressive systemic sclerosis, primary sjogren's syndrome, mixed connective tissue disease, gouty arthritis and traumatic arthritis. Serum MMP-3 significantly correlated with serum BUN or serum creatinine levels in SLE patients but not in RA patients. In early onset RA, serum MMP-3 level was significantly elevated. Furthermore, when the relationship between the serum MMP-3 level and X-ray findings of the joints in RA was studied, it was found that MMP-3 level was elevated even in stage I or II and that there was no statistical differences between stage I or II and stage III or IV, suggesting that serum MMP-3 level is elevated in the early stage of initial inflammatory process when only mild cartilage degradation is seen. These results suggest that measurements of serum MMP-3 is an important tool for establishing diagnosis of early onset RA, and that serum MMP-3 level may be a marker of cartilage destruction and of estimating therapeutic efficacy in early onset RA.
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PMID:[Stromelysin-1 (MMP-3) level in the sera from patients with rheumatoid arthritis and other connective tissue diseases--clinical significances in early onset rheumatoid arthritis]. 773 85

Death from cancer results from the development of metastases or local progression of tumour. Metastasis and local progression may result from the inappropriate activity of metalloproteinases released by tumour cells or of their regulatory peptides. We have developed quantitative assays for interstitial collagenase, stromelysin 1 and tissue inhibitors of metalloproteinase (TIMP) 1 and 2, which have allowed the study of serum levels of these proteins. Sera from 40 patients with prostatic cancer, stored prior to and after 6 and 12 months' treatment with a gonadotrophin-releasing hormone agonist and an anti-androgen were analysed. Levels were compared with two control groups, comprising 21 patients with active rheumatoid arthritis and 56 age-matched hospital attenders without arthritis or cancer. Contrasting levels have been found in patients with prostatic cancer as compared with hospital controls without cancer and patients with rheumatoid arthritis. Patients with prostatic cancer had higher levels of TIMP-1 and collagenase (P = 0.0001) and lower levels of TIMP-2 (P = 0.003) than controls. Patients with metastatic cancer had significantly higher levels of collagenase than those without metastases (P = 0.02). Patients with rheumatoid arthritis had significantly higher levels of stromelysin than either controls (P = 0.002) or patients with cancer (P = 0.008). Serum tissue inhibitor of metalloproteinase 1 in combination with collagenase levels was as sensitive as prostate-specific antigen as a marker of metastatic disease. These findings provide a basis for the investigation of the role of metalloproteinases and their inhibitors in other malignancies.
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PMID:Serum metalloproteinases and their inhibitors: markers for malignant potential. 808 Jul 38

In this study, we evaluated the in vitro and in vivo potency of human leukocyte elastase (HLE) and human cathepsin G (HCG) as proteoglycanases. In vitro evaluation was done using bovine nasal septum aggrecan and aggrecan/hyaluronan aggregate as substrates. Enzyme activity was assessed by the ability of the proteinases to abrogate the ability of aggrecan to aggregate with hyaluronan. In vivo activity of the proteinases was tested by injecting purified HLE and HCG intra-articularly into rabbit stifle joints and quantifying the levels of proteoglycan released into synovial fluids. On a molar basis, HCG was at least tenfold more potent than HLE as a proteoglycanase in vitro. Moreover, HCG was twofold more potent as a proteoglycanase in vivo. In contrast, HLE hydrolyzed elastin approximately 22-fold faster than HCG, but was only slightly more rapid than HCG when [3H]-transferrin was used as substrate. These data indicate that HCG is more potent than HLE as a proteoglycanase both in vitro and in vivo. Thus, HCG could be more important in the pathogenesis of rheumatoid arthritis than previously suspected.
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PMID:Comparison of the proteoglycanolytic activities of human leukocyte elastase and human cathepsin G in vitro and in vivo. 814 41


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