Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To analyze relating factors to early repairment of the surgical margin of the remnant liver we measured plasma fibronectin (FN), coagulation factor XIII (XIII), polymorphonuclear leukocyte elastase (PMNE), platelet counts (Plt), prothrombin time (PT%) before and at the first, third, 7th and 14th days after liver resection in 25 patients. Changes in these factors (1) were compared with their clinical status, such as liver cirrhosis, high fever, abscess formation, duration of drainage and use of microwave tissue coagulator (MTC) (2). The multivariate analysis about the factors influencing the duration of hospital stay (3) were carried out. (1) In the all cases FN, XIII (14th), PT%, Plt decreased and PMNE increased significantly versus pre-operative data. There were significant correlations between FN and XIII, FN and PMNE. (2) In the cirrhotic group FN, XIII, PT% and Plt were significantly lower than those of non cirrhotic group. In the abscess formation group PT% was significantly lower than the no abscess formation group. In the MTC group XIII, PT% and Plt were significantly lower than those of the no-MTC group. In conclusion, FN, XIII, Plt and PT% in the cirrhotic, high fever, abscess formation or longer drainage group were in lower levels compared with the each control group. (3) By the multivariate analyses, abscess formation, high fever and liver cirrhosis were the most influencing factors for the duration of hospital stay.
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PMID:[Analysis of factors relating to early repairment of the surgical margin following liver resection--factors relating to duration of hospital stay]. 187 92

Isocoumarins are potent mechanism-based heterocyclic irreversible inhibitors for a variety of serine proteases. Most serine proteases are inhibited by the general serine protease inhibitor 3,4-dichloroisocoumarin, whereas isocoumarins containing hydrophobic 7-acylamino groups are potent inhibitors for human leukocyte elastase and those containing 7-alkylureidogroups are inhibitors for procine pancreatic elastase. Isocoumarins containing basic side chains that resemble arginine are potent inhibitors for trypsin-like enzymes. A number of 3-alkoxy-4-chloro-7-guanidinoisocoumarins are potent inhibitors of bovine thrombin, human factor Xa, human factor XIa, human factor XIIa, human plasma kallikrein, porcine pancreatic kallikrein, and bovine trypsin. Another cathionic derivative, 4-chloro-3-(2-isothiureidoethoxy) isocoumarin, is less reactive toward many of these enzymes but is an extremely potent inhibitor of human plasma kallikrein. Several guanidinoisocoumarins have been tested as anticoagulants in human plasma and are effective at prolonging the prothrombin time. The mechanism of inhibition by this class of heterocyclic inactivators involves formation of an acyl enzyme by reaction of the active site serine with the isocoumarin carbonyl group. Isocoumarins with 7-amino or 7-guanidino groups will then decompose further to quinone imine methide intermediates, which react further with an active site residue (probably His-57) to form stable inhibited enzyme derivatives. Isocoumarins should be useful in further investigations of the physiological function of serine proteases and may have future therapeutic utility for the treatment of emphysema and coagulation disorders.
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PMID:Mechanism-based isocoumarin inhibitors for serine proteases: use of active site structure and substrate specificity in inhibitor design. 265 46

In 42 patients with septic shock, 29 of whom underwent substitution with antithrombin III concentrate and fresh frozen plasma for coagulation disorders, the proteinase-inhibitor complexes thrombin-antithrombin III and neutrophil elastase-alpha 1 proteinase inhibitor, were elevated on admission. On admission, the elastase complex was significantly higher in the patients receiving substitution (p = 0.0039), but at the endpoint it was higher in the non-survivors (p = 0.0040). The elastase decrease was confined to the substitution group with the thrombin complex decreasing in both groups. Initially the thrombin complex correlated with prothrombin times and factor XIII, while the elastase complex correlated with creatinine, thrombocyte count and prothrombin times in the late stages. Hemostatic disturbance, thrombin generation and neutrophil elastase release were favorably influenced by substitution. Furthermore, in this uncontrolled pilot study, the survival rate was higher in the treated (16 of 29) than in the untreated (1 of 13) patients, although the treated patients initially had pronounced hemostatic disturbances.
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PMID:The disturbance of hemostasis in septic shock: role of neutrophil elastase and thrombin, effects of antithrombin III and plasma substitution. 278 82

Protein S (PS) is a vitamin K-dependent anticoagulant that acts as a cofactor to activated protein C (APC). To date PS has not been shown to possess anticoagulant activity in the absence of APC. In this study, we have developed monoclonal antibody to protein S and used to purify the protein to homogeneity from plasma. Affinity purified protein S (PSM), although identical to the conventionally purified protein as judged by SDS-PAGE, had significant anticoagulant activity in the absence of APC when measured in a factor Xa recalcification time. Using SDS-PAGE we have demonstrated that prothrombin cleavage by factor Xa was inhibited in the presence of PSM. Kinetic analysis of the reaction revealed that PSM competitively inhibited factor Xa mediated cleavage of prothrombin. PS preincubated with the monoclonal antibody, acquired similar anticoagulant properties. These results suggest that the interaction of the monoclonal antibody with PS results in an alteration in the protein exposing sites that mediate the observed anticoagulant effect. Support that the protein was altered was derived from the observation that PSM was eight fold more sensitive to cleavage by thrombin and human neutrophil elastase than conventionally purified protein S. These observations suggest that PS can be modified in vitro to a protein with APC-independent anticoagulant activity and raise the possibility that a similar alteration could occur in vivo through the binding protein S to a cellular or plasma protein.
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PMID:The anticoagulant properties of a modified form of protein S. 297 8

125I-labeled heparin cofactor II (HCII) was mixed with plasma and coagulation was initiated by addition of CaCl2, phospholipids, and kaolin or tissue factor. In the presence of 67 micrograms/ml of dermatan sulfate, radioactivity was detected in a band which corresponded to the thrombin-HCII complex (Mr = 96,000) upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. No other complexes were observed. The thrombin-HCII complex was undetectable when 5 units/ml of heparin was present or when prothrombin-deficient plasma was used. In experiments with purified proteases, HCII did not significantly inhibit coagulation factors VIIa, IXa, Xa, XIa, XIIa, kallikrein, activated protein C, plasmin, urokinase, tissue plasminogen activator, leukocyte elastase, the gamma-subunit of nerve growth factor, and the epidermal growth factor-binding protein. HCII inhibited leukocyte cathepsin G slowly, with a rate constant of 8 X 10(4) M-1 min-1 in the presence of dermatan sulfate. These results indicate that the protease specificity of HCII is more restricted than that of other plasma protease inhibitors and suggest that the anticoagulant effect of dermatan sulfate is due solely to inhibition of thrombin by HCII.
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PMID:The protease specificity of heparin cofactor II. Inhibition of thrombin generated during coagulation. 383 15

Proteases have a wide range of functions: digestion (pancreatic proteases), protein catabolism (lysosomal proteases), blood coagulation, immune defences (complement), cellular division and proliferation, generation of biologically active oligopeptides (kinins, hormones) from inactive polypeptide precursors, inactivation of these oligopeptides, etc. The body protects itself against its own proteases, either by confining them to a given compartment (lysosome), by synthesising them in the form of inactive precursors (trypsinogen, prothrombin, etc.), or by synthesising proteins with an antiprotease activity. Any disturbance in one of the elements of this protective system may lead to severe pathological consequences: acute hemorrhagic pancreatitis with shock, coagulation disturbances (deficient hepatic synthesis of coagulation factors, congenital antithrombin III deficiency), angioneurotic oedema (congenital deficiency of C'l esterase inhibitor) pulmonary emphysema (local secretion of leukocyte elastase, congenital deficiency of alpha a-antitrypsin).
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PMID:[Problems in intensive care posed by imbalance in the protease--protease inhibitor system]. 611 Dec 72

The ability of intact peripheral blood monocytes to modulate factor V procoagulant activity was studied using electrophoretic and autoradiographic techniques coupled to functional assessment of cofactor activity. Incubation of plasma concentrations of factor V with monocytes (5 x 10(6)/ml) resulted in the time-dependent cleavage of the 330-kDa protein. Activation occurred via several high molecular mass intermediates (> or = 200 kDa) to yield peptides of 150, 140, 120, 94, 91, 82, and 80 kDa, which paralleled the expression of cofactor activity. The cleavage pattern observed differed from that obtained with either thrombin or factor Xa as an activator. The incubation time required to achieve full cofactor activity was dependent on the monocyte donor and ranged from 10 min to 1 h and was consistently slightly lower than that obtained with thrombin-activated factor Va. Cofactor activity was not diminished by additional incubation. The cofactor activity generated bound to the monocyte such that a competent prothrombinase complex was formed at the monocyte membrane surface. Furthermore, within 5 min of factor V addition to monocytes, near maximal cofactor activity (approximately 70%) was bound and expressed on the monocyte membrane. The proteolytic activity toward factor V was associated primarily with the monocyte membrane, as little proteolytic activity was released into the cell-free supernatant. Proteolytic activity was inhibited by diisopropyl fluorophosphate and phenylmethanesulfonyl fluoride. However, the inhibitor profile obtained with alpha 1-antiproteinase inhibitor, alpha 1-antichymotrypsin, and alpha 2-macroglobulin suggested membrane-bound forms of elastase and cathepsin G were mediating, in large part, the proteolysis observed. These data were confirmed using purified preparations of both proteases and a specific anti-human leukocyte elastase antibody. Thus, expression of these proteases at the monocyte surface may contribute to thrombin generation at extravascular tissue sites by catalyzing the activation of the essential cofactor, factor Va, which binds to the monocyte surface and supports the factor Xa-catalyzed activation of prothrombin.
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PMID:Human coagulation factor V is activated to the functional cofactor by elastase and cathepsin G expressed at the monocyte surface. 783 8

Ecotin, a serine protease inhibitor found in the periplasm of Escherichia coli, has been characterized as an extremely potent anticoagulant and reversible tight-binding inhibitor of human factor Xa (FXa). The ecotin gene was cloned by PCR, highly expressed in E. coli, and purified from the E. coli periplasm. The binding of ecotin to FXa was stoichiometric with an equilibrium dissociation constant Ki of 54 pM. The association rate constant was 1.35 x 10(6) M-1 s-1, and the dissociation rate constant, measured in the presence of human leukocyte elastase (HLE) to prevent reassociation of ecotin with FXa, was 6.5 x 10(-5) s-1. Ecotin prolonged clotting time ca. 10-fold at 0.3 microM and at 2 microM in activated partial thromboplastin time and prothrombin time assays, respectively. Ecotin did not effectively inhibit the human plasma proteases thrombin, tissue factor.factor VIIa, factor XIa, activated protein C, plasmin, or tissue plasminogen activator (t-PA); however, it did potently inhibit factor XIIa, plasma kallikrein, HLE, and bovine trypsin and chymotrypsin. Coincubation of ecotin and FXa at 10 microM each resulted in a (ecotin)2.(FXa)2 complex as determined by gel filtration. Dimerization of ecotin alone was measured by fluorescence titration which yielded a Kd of ca. 390 nM. FXa cleaved ecotin slowly at pH 4.0 between M84 and M85. Replacement of the P1 Met84 residue with Arg and Lys led to FXa inhibitors with Ki values of 11 and 21 pM, respectively. The P1 Arg and Lys mutants also significantly inhibited thrombin, factor XIa, activated protein C, plasmin, factor XIIa, kallikrein, and bovine trypsin and chymotrypsin but did not inhibit tissue factor.factor VIIa, t-PA, or HLE.
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PMID:Ecotin is a potent anticoagulant and reversible tight-binding inhibitor of factor Xa. 814 99

The mechanism of tissue damage by extracorporeal shock wave lithotripsy has not been clarified, but proteolytic enzymes are known to play an important role in tissue breakdown in response to other types of injury. Screening tests for activation of the proteolytic enzymes kallikrein, plasmin, trypsins 1 and 2, and granulocyte elastase therefore were performed for 4 to 5 hours in 14 dogs after unilateral treatment with 1500 or 2000 extracorporeal shock waves under anesthesia and vigorous hydration. We also studied the activity of the proenzymes prekallikrein, plasminogen, and prothrombin and three plasma protease inhibitors (kallikrein inhibitor, antiplasmin, and antithrombin III). Blood from both renal veins (treated and control kidneys) and the aorta and tissue samples of the injured renal parenchyma and corresponding areas of the control kidneys revealed no proteolytic enzyme activation by the shock waves and no decline in the activities of proenzymes and enzymes inhibitors. Significant proteolysis does not seem to play a part in the tissue injury induced by extracorporeal shock wave lithotripsy.
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PMID:Absence of activation of proteolytic enzymes by extracorporeal shock waves. 835 13

A brief explanation of the molecular markers of coagulation, fibrinolysis and endothelial cell activation was done. The clinical significance of markers, such as, soluble fibrin monomer complex, FDP D-dimer, prothrombin fragment 1 + 2, thrombin-antithrombin III complex, plasmin-alpha 2 plasmin inhibitor complex and plasma thrombomodulin in our patients with disseminated intravascular coagulation (DIC) due to abdominal sepsis and malignancy is discussed. The coagulopathy in the DIC patients due to abdominal sepsis had a different aspect from that in the DIC patients due to malignancy. Activation of the coagulation and fibrinolytic systems in sepsis was milder than that in malignancy, despite the decrease of antithrombin III activity in the patients with sepsis. In the patients with sepsis, granulocyte elastase was increased. It was proposed that the coagulopathy was caused not only thrombin formation but also by granulocyte proteinase. It could be expected that the pathophysiology of disseminated intravascular coagulation should be clarified, because of the high sensitivity.
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PMID:[Advancement in the diagnosis of disseminated intravascular coagulation for the surgeon]. 838 85


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