Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A fibrin glue preparation has been obtained from pooled human plasma using a procedure which includes a solvent-detergent (SD) treatment to inactivate lipid-enveloped viruses. The SD treatment inactivated greater than or equal to 5.5 log10 of HIV in less than 45 min, and greater than or equal to 5 log10 and greater than or equal to 6.5 log10 of VSV and Sindbis virus, respectively, in less than 2 h. The product was found to contain high quantities of fibrinogen (116 +/- 2.49 g/l; n = 12), factor XIII (35 +/- 2.88 U/ml) and von Willebrand factor (23 +/- 1.9 U/ml ristocetin cofactor activity), and relatively low levels of fibronectin (5.9 +/- 0.51 g/l). Plasminogen, the precursor of plasmin, which may play a negative role by decreasing the resistance of the fibrin clot, was at only 0.03 g/l. Cellulose acetate electrophoresis showed 95% gamma-proteins and 5% alpha-2-beta proteins. Sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions detected three main protein bands with apparent molecular weights of 65, 56 and 47 kilodaltons, probably corresponding to the alpha, beta, and gamma fibrinogen subunits. Other characteristics of the product included (1) high clottability of fibrinogen (over 85%); (2) absence of low molecular weight fibrin degradation products; (3) rapid solubilization at room temperature (less than 10 min); (4) high tensile strength (202 +/- 27 g/cm2 after 2 h of application), and (5) high elasticity of the fibrin clot. In addition, scanning electron microscopy revealed a highly organized structure showing tridimensional arrangement of the fibrin fibers. SD treated fibrin glue should efficiently replace autologous fibrinogen or cryoprecipitate preparations for surgical application.
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PMID:Biochemical and physical properties of a solvent-detergent-treated fibrin glue. 216 Jan 46

The ability of differentiating sensory neurons to remodel a fibronectin substratum was examined. During the early stages of neurite outgrowth, fibronectin was cleared from areas beneath the neuronal soma and processes. The removal of fibronectin occurred in the presence and absence of plasminogen and was associated with the release of fibronectin fragments into the culture medium. The degradation of fibronectin was dependent upon neuronal contact with the substratum. Extraction of cells with the nonionic detergent Triton X-114 identified plasminogen activator and plasmin associated with the cell surface. These findings suggest that the plasminogen activator/plasmin system may play an important role in the interaction of differentiating sensory neurons with the extracellular matrix during axonal outgrowth.
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PMID:Degradation of underlying extracellular matrix by sensory neurons during neurite outgrowth. 218 79

Human rheumatoid synovial cells in culture secrete at least three related metalloproteinases that digest extracellular matrix macromolecules. One of them, termed matrix metalloproteinase 2 (MMP-2), has been purified as an inactive zymogen (proMMP-2). The final product is homogeneous on SDS/PAGE with Mr = 72,000 under reducing conditions. The NH2-terminal sequence of proMMP-2 is Ala-Pro-Ser-Pro-Ile-Ile-Lys-Phe-Pro-Gly-Asp-Val-Ala-Pro-Lys-Thr, which is identical to that of the so-called '72-kDa type IV collagenase/gelatinase'. The zymogen can be rapidly activated by 4-aminophenylmercuric acetate to an active form of MMP-2 with Mr = 67,000, and the new NH2-terminal generated is Tyr-Asn-Phe-Phe-Pro-Arg-Lys-Pro-Lys-Trp-Asp-Lys-Asn-Gln-Ile. However, following 4-aminophenylmercuric acetate activation, MMP-2 is gradually inactivated by autolysis. Nine endopeptidases (trypsin, chymotrypsin, plasmin, plasma kallikrein, thrombin, neutrophil elastase, cathepsin G, matrix metalloproteinase 3, and thermolysin) were tested for their abilities to activate proMMP-2, but none had this ability. This contrasts with the proteolytic activation of proMMP-1 (procollagenase) and proMMP-3 (prostromelysin). The optimal activity of MMP-2 against azocoll is around pH 8.5, but about 50% of activity is retained at pH 6.5. Enzymic activity is inhibited by EDTA, 1,10-phenanthroline or tissue inhibitor of metalloproteinases, but not by inhibitors of serine, cysteine or aspartic proteinases. MMP-2 digests gelatin, fibronectin, laminin, and collagen type V, and to a lesser extent type IV collagen, cartilage proteoglycan and elastin. Comparative studies on digestion of collagen types IV and V by MMP-2 and MMP-3 (stromelysin) indicate that MMP-3 degrades type IV collagen more readily than MMP-2, while MMP-2 digests type V collagen effectively. Biosynthetic studies of MMPs using cultured human rheumatoid synovial fibroblasts indicated that the production of both proMMP-1 and proMMP-3 is negligible but it is greatly enhanced by the treatment with rabbit-macrophage-conditioned medium, whereas the synthesis of proMMP-2 is constitutively expressed by these cells and is not significantly affected by the treatment. This suggests that the physiological and/or pathological role of MMP-2 and its site of action may be different from those of MMP-1 and MMP-3.
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PMID:Matrix metalloproteinase 2 from human rheumatoid synovial fibroblasts. Purification and activation of the precursor and enzymic properties. 226 96

Abundant deposition of bronchoalveolar fibrin and fibronectin occurs during the exudative phase of the adult respiratory distress syndrome (ARDS), promoting hyaline-membrane formation and subsequent alveolar fibrosis. To explore the mechanisms that account for the persistence of bronchoalveolar fibrin and fibronectin, we compared the activity of urokinase, which is necessary for plasminogen activation and fibrin degradation, in cell-free bronchoalveolar-lavage fluid from 8 patients with ARDS, 9 patients with acute pulmonary diseases other than ARDS, and 10 normal subjects. The mean level of urokinase activity in the lavage fluid from the patients with ARDS was 0.003 IU per milliliter of fluid (range, 0 to 0.008), which was significantly lower (P = 0.001) than the level in the fluid from either the patients with pulmonary diseases other than ARDS (0.118 IU per milliliter [range, 0.032 to 0.295]) or the normal subjects (0.129 IU per milliliter [range, 0.045 to 0.198]). The lavage fluid from all the patients with ARDS also had antiplasmin activity, which would promote the persistence of fibrin. A true decrease in urokinase activity was confirmed by the failure of the lavage fluid from the patients with ARDS to convert [125I]plasminogen to plasmin. Despite the low urokinase activity, immunochemical assays revealed normal levels of urokinase antigen in the fluid from the patients with ARDS, suggesting the presence of urokinase inhibitors. Inhibitors were demonstrated directly by a fibrin gel-underlay assay that detects complexes of urokinase with inhibitors. Plasminogen-activator inhibitor type 1 was the principal inhibitor identified. We conclude that increased antifibrinolytic activity due to both urokinase inhibitors and antiplasmins in the bronchoalveolar compartment of patients with ARDS contributes to the formation and persistence of hyaline membranes, a key component of alveolar histopathology in ARDS.
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PMID:Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome. 231 27

Fibronectin (Fn), a high molecular weight glycoprotein, was found to constitute 0.43% of the normal adult beagle dog lung. The tissue Fn (TFn) was solubilized by sequential chemical extractions and quantified by ELISA (enzyme-linked immunoabsorbent assay). Subsequent plasmin digestion did not appear to solubilize significantly more Fn. Since 70% of the lung tissue was solubilized by the extractions and plasmin digestions, the TFn quantified represented the bulk of lung Fn. The TFn was identical to plasma fibronectin in the ELISA and one can infer that the Fn molecule is not significantly altered as it is incorporated into the lung connective tissue matrix. Lungs from beagles in which fibrosis had been induced with bleomycin contained 0.99% Fn, more than a twofold increase over normal. In the ELISA TFn from fibrotic lungs gave an inhibition curve of the same shape as did TFn from normal lungs. Thus, Fn from fibrotic lungs is not different qualitatively from Fn from normal lungs in any way detectable with this antiserum. The TFn content of plasmin digests of intact lung was less than that of extracts, which was the converse of results obtained on placenta (B. A. Bray (1985) Biochem. J. 226, 811-815). This difference between lung TFn and placental TFn may be due to differences in degree of glycosylation, which determines susceptibility to proteases.
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PMID:The fibronectin content of canine lungs is increased in bleomycin-induced fibrosis. 242 83

Human blood plasma fibronectin decreased slightly the incorporation of precursors into nucleic acids of granulation tissue culture cells. A slight fragmentation of fibronectin, where the fragments with 180-200 kD molecular mass were developed, led to occurrence of the activity 2-fold stimulating the DNA synthesis. After more effective proteolysis using plasmin and trypsin the stimulating effect of fibronectin fragments on synthesis of nucleic acids maintained and constituted 165 +/- 12% and 127 +/- 7% for DNA and RNA, respectively.
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PMID:[Fibronectin fragmentation unmasks the activity stimulating DNA and RNA biosynthesis in granulation tissue cells in vitro]. 243 1

In a patient with chronic corneal ulcer, resistant to conventional therapy, analysis of tear fluid revealed a high plasmin activity which could be inhibited by aprotinin, an inhibitor of serine proteinases. Therapy with topical aprotinin resulted in rapid epithelialization. After this initial patient, within a period of four months tear fluid specimens of altogether 48 patients with corneal lesions were analyzed, and 32 were found to be positive for proteolytic activity. Of these 18 were treated with topical aprotinin which rapidly promoted corneal epithelial healing. Six of these patients had been treated with conventional therapy for 3-10 weeks but proved to be completely therapy-resistant. Our observations on three successfully treated patients with chemical burns of the cornea indicated appearance of plasmin in tear fluid after a few days correlating with cessation of epithelialization. In all patients, in which tear fluid plasmin activity was followed, the activity disappeared during aprotinin therapy correlating with corneal re-epithelialization. In some patients with low proteolytic activity aprotinin was combined with fibronectin with a beneficial therapeutic effect. No proteolytic activity was found in the tear fluid of control individuals. These preliminary data indicate that in patients with treatment-resistant corneal lesions inhibition of proteolytic activity can assist in epithelial healing. Such an inhibition is likely to be a prerequisite for the proteinase-sensitive cell adhesion proteins such as fibronectin to promote epithelialization.
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PMID:Plasmin in tear fluid of patients with corneal ulcers: basis for new therapy. 243 58

Guanidinobenzoatase is a proteolytic enzyme capable of degrading fibronectin and is a tumour associated enzyme. Guanidinobenzoatase has been shown to be an arginine selective protease and is distinct from trypsin, plasmin and thrombin, the latter enzymes can be assayed with bis(carbobenzyloxycarbonyl-L-argininamido)-Rhodamine or BZAR. Guanidinobenzoatase is inhibited by BZAR when the enzyme is assayed in free solution and when the enzyme is cell-bound in frozen sections of tumour containing tissues. It is proposed that BZAR and its analogues may be of value in inhibiting tumour cell invasion in vivo and also that the selectivity of BZAR may be used to direct cytotoxic drugs to tumour cells possessing active guanidinobenzoatase.
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PMID:Inhibition of guanidinobenzoatase by a substrate for trypsin-like enzymes. 246 71

Primary adherence and attachment area of seeded human endothelial cells (EC) were determined on differently coated polytetrafluoroethylene (PTFE) grafts. Cell counts and morphometric analyses were done immediately after 60 minutes of electronically controlled seeding of 3 x 10(4) EC/cm2, as well as after 3 hours of subsequent incubation. Cell adherence and cell spreading were distinctly superior on two surface-covering substrates: fibronectin-treated type I/III collagen and fibrinolytically inhibited fibrin glue. Uncovered, purely fibronectin- or laminin-coated PTFE or type IV collagen treated with the specifically binding glycoprotein laminin showed a far lower EC attachment rate and less pronounced cell spreading. It appears that not only a high surface content of fibronectin but also a smooth PTFE-covering matrix are prerequisites for optimal primary adherence and cell spreading. Because fibrin glue might be fibrinolytically degraded despite its plasmin-inhibiting epsilon-amino-caproic acid compound, type I/III collagen plus fibronectin could provide an optimal precoating substrate for EC lining of PTFE grafts.
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PMID:Precoating substrate and surface configuration determine adherence and spreading of seeded endothelial cells on polytetrafluoroethylene grafts. 246 98

Previous studies have implicated proteases, acting extracellularly, in the mechanism of polyneuronal synapse elimination. Most studies have focused on mammalian, especially rodent, skeletal muscle, where retraction of subordinate nerve terminals occurs during a narrow time window 2-3 weeks after birth. To date no specific protease(s) has been detected that (i) coincides in time with maximal synapse elimination and (ii) is known to act extracellularly on specific extracellular matrix proteins. In previous studies of denervation in adult mouse muscle, rapid activation of urokinase-type plasminogen activator, a neutral serine protease, was detected. This enzyme, by activation of plasminogen to plasmin, specifically degrades matrix components such as fibronectin, type IV collagen, and laminin in muscle. We now present evidence for an initial increase and subsequent decrease in soluble urokinase-type PA--and, to a lesser extent, tissue PA--in developing muscle, suggesting postnatal developmental regulation of these enzymes during the period of maximal synapse elimination. Although considerably higher in specific activity, membrane-bound PA activity followed the wave of synapse elimination, possibly indicating a longer half-life of membrane-bound enzyme(s).
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PMID:Decrease in plasminogen activator correlates with synapse elimination during neonatal development of mouse skeletal muscle. 249 3


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