Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 new quantitative model for the examination of potential thrombolytic agents is described. A thrombus was formed in the inferior vena cava of the rabbit, using 125 I-labelled fibrinogen mixed with a standard amount of thromboplastin. The thrombus was anchored securely by means of a woollen thread inserted longitudinally into the lumen of the vein. Thrombotic extension of the radioactive clot and rethrombosis during the experimental period (5 h) were prevented by the administration of intravenous heparin. In control animals, the thrombus remained stable and there was no rise in te radioactivity of the circulating blood during 5 h. In animals given thrombolytic agents, lysis could be followed continuously by measuring the rise in blood radioactivity. Total lysis was determined by counting the radio-label in the residual clot after treatment. The model has been used to study the thrombolytic activity of streptokinase-human plasminogen complexes, activator-free plasmins of human and porcine origin, and human plasmin produced by streptokinase (SK) activation of human plasminogen. The role of activator complexes in the thrombolytic activity of SK-activated plasmin is discussed.
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PMID:The evaluation of plasmin and streptokinase activator complexes in a new rabbit model of venous thrombosis. 645 12

By means of the method of ROLA & PUDLES modified by the authors the effect of trypsin and chymotrypsin inhibitors isolated from body walls of Ascaris lumbricoides on coagulation and fibrinolysis of human plasma in vitro was studied. The effect of both Ascaris inhibitors on coagulation phases I and II, the inhibition of thromboplastin and thrombin generations (thromboelastography, prothrombin and thrombin times) and the fibrinogenesis retardation of human plasma (time of lysis of euglobulin clot, time of clot fibrinolysis activated by streptokinase) were found. "The stairs phenomenon" was observed on thromboelastographic curves. The plasmin activity in an active form as well as its formation from plasminogen by streptokinase activation were reduced by chymotrypsin and trypsin Ascaris inhibitors alike.
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PMID:[Effect of proteolysis inhibitors from Ascaris lumbricoides on the coagulation and fibrinolysis of human plasma]. 712 86

The tick Boophilus microplus contains a protein that inhibits a range of proteolytic enzymes. Variations in the concentration of this protein throughtout the life cycle were followed by measuring simultaneously the inhibition of trypsin and chymotrypsin and reaction with an antiserum to the purified inhibitor. The protein is present in large amounts in eggs and in unfed larvae, but its concentration falls very rapidly after the start of the parasitic stage of the life cycle. This, together with previous evidence, suggests that the inhibitor is important both in eggs and in the initial establishment of the parasite on its host. The activity of the protein towards several enzymes has been measured as an indication of its possible function. Bovine trypsin, chymotrypsin and plasmin and pig pancreatic kallikrein are all inhibited. The protein also affects the blood-coagulation system at several points, since it prolongs both activated-partial-thromboplastin time and prothrombin time. It inhibits the complement-dependent lysis of erythrocytes, but is without significant effect on mitogen-induced lymphocyte stimulation. Thus the inhibitor could have several effects on the host that would be beneficial to the parasite.
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PMID:On the biological role of a proteolytic-enzyme inhibitor from the ectoparasitic tick Boophilus microplus. 745 13

We had rare opportunities to examine changes in fibrin degradation products (FDP)-D-dimer (DD), thrombin-antithrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC) and other coagulation parameters during the clinical courses of living-related partial liver transplantation (LRPLT). In seven out of eight recipients without severe rejection and/or disseminated intravascular coagulation (DIC), FDP-DD values reached their maximum at 5 to 10 days after transplantation, then gradually decreased. On the other hand, TAT values rose to the maximum at anhepatic or reperfusion phase of liver transplantation. These data represent hypercoagulation in consequence of tissue thromboplastin activation after extensive operation. Changes in PIC, tissue-type plasminogen activator, and plasminogen activator inhibitor-1 (PAI-1) in the clinical course of case 1 suggested that fibrinolysis was suppressed by relatively elevated level of PAI-1 around the operation, but thereafter was adversely accelerated by relatively lower levels of PAI-1. In comparison with patients with DIC, TAT was much higher but PIC was significantly lower in recipients of LRPLT. These findings indicated that marked hypercoagulation and mild to moderate hyperfibrinolysis occurred in recipients of LRPLT.
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PMID:[Changes in coagulation parameters during the clinical courses of recipients of living-related partial liver transplantation]. 747 43

Thrombin and plasmin generation were assessed in patients with endemic hepatosplenic schistomiasis (15 hepatosplenomegalic, 15 splenomegalic, 15 with advanced hepatic fibrosis and ascites and 15 hepatosplenic patients with hematemesis). Prolongation of prothrombin time, partial thromboplastin time and thrombin time, thrombocytopenia, hypofibrinogenemia, a decrease in antithrombin III and protein C and S levels and elevation in fibrinopeptide A, D-dimer and thrombin-antithrombin complex levels were detected in all groups. The deficit in hemostatic parameters was more pronounced with the advancement of the disease and was maximal in the hematemesis group. Our data demonstrate an increase in both thrombin and plasmin generation and indicate that low grade disseminated intravascular coagulation may occur in association with endemic Egyptian hepatosplenic schistosomiasis even in the steady state without overt bleeding.
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PMID:Disseminated intravascular coagulation in endemic hepatosplenic schistosomiasis. 748 60

Rheumatoid arthritis is a chronic inflammatory disease caused essentially by an immune-mediated mechanism. However, abnormalities of the clotting system have also been incriminated as having an important role in the pathogenesis of this disease. This study aims at assessing the clotting system and collagen metabolism alterations and the relationship between perturbances of the hemostatic pathway and the destructive and fibroproliferative processes in patients with rheumatoid arthritis. The coagulation system was evaluated by measuring thrombin-antithrombin III complex (TAT), prothrombin time (PT), activated partial thromboplastin time (APTT), and antithrombin III (AT-III). The fibrinolysis system was assessed by measuring fibrin degradation products (FDP), fibrinogen (FBG), alpha 2-antiplasmin (alpha 2-PI), D-dimer (DD) and plasmin-alpha 2-antiplasmin complex (PAP). As markers of collagen metabolism, the type III procollagen peptide (PIIIP) and the 7S domain of type IV collagen (7S-collagen) were determined. Blood concentrations of DD, PAP, TAT, PIIIP, and 7S-collagen were significantly higher in rheumatoid arthritis patients compared to controls. Serum levels of PIIIP were significantly correlated with PT, APTT, AT-III, FDP, and DD. 7S-collagen levels were inversely related to AT-III and FBG values. This study demonstrated the occurrence of a subclinical intravascular coagulation in rheumatoid arthritis and suggested the important role of blood coagulation in the alteration of the extracellular matrix metabolism in this disease.
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PMID:Correlation between clotting and collagen metabolism markers in rheumatoid arthritis. 751 17

The Alzheimer's disease related protein, amyloid beta-protein precursor (A beta PP), contains a domain homologous to Kunitz-type serine protease inhibitors (KPI). The recombinant KPI domain of A beta PP is a potent inhibitor of coagulation factors XIa and IXa and functions as an anticoagulant in vitro. Here we report the expression, purification, and characterization of a reactive center lysine mutant of the KPI domain of A beta PP (KPI-Lys17). An expression plasmid for the KPI-Lys17 domain of A beta PP encoded amino acids 285-345 of the A beta PP cDNA containing a lysine substitution at arginine 17 in the KPI domain. The secreted 61-amino acid product was purified to homogeneity and functionally characterized. The protease inhibitory properties of the KPI-Lys17 domain were compared to those of the native KPI domain of A beta PP. Both KPI domains equally inhibited trypsin, chymotrypsin, and coagulation factors IXa and Xa. However, the KPI-Lys17 domain was an approximately 25-fold less effective inhibitor of coagulation factor XIa resulting in markedly less prolongation of the activated partial thromboplastin time compared to the native KPI domain of A beta PP. On the other hand, the KPI-Lys17 domain was an approximately 10- and 5-fold better inhibitor of plasmin in a chromogenic substrate assay and in a fibrinolytic assay, respectively, than the native KPI domain of A beta PP. Together, these studies suggest that the KPI-Lys17 domain has enhanced anti-fibrinolytic and diminished factor XIa inhibitory properties compared to the native KPI domain of A beta PP.
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PMID:Enhanced plasmin inhibition by a reactive center lysine mutant of the Kunitz-type protease inhibitor domain of the amyloid beta-protein precursor. 755 14

Phage displaying APPI Kunitz domain libraries have been used to design potent and selective active site inhibitors of human plasma kallikrein, a serine protease that plays an important role in both inflammation and coagulation. Selected clones from two Kunitz domain libraries randomized at or near the binding loop (positions 11-13, 15-19, and 34) were sequenced following five rounds of selection on immobilized plasma kallikrein. Invariant preferences for Arg at position 15 and His at position 18 were found, whereas His, Ala, Ala, and Pro were highly preferred residues at positions 13, 16, 17, and 19, respectively. At position 11 Pro, Asp, and Glu were favored, while hydrophobic residues were preferred at position 34. Selected variants, purified by trypsin affinity chromatography and reverse phase high performance liquid chromatography, potently inhibited plasma kallikrein, with apparent equilibrium dissociation constants (Ki*) ranging from approximately 75 to 300 pM. From sequence and activity data, consensus mutants were constructed by site directed mutagenesis. One such mutant, KALI-DY, which differed from APPI at 6 key residues (T11D, P13H, M17A, I18H, S19P, and F34Y), inhibited plasma kallikrein with a Ki* = 15 +/- 14 pM, representing an increase in binding affinity of more than 10,000-fold compared to APPI. Similar to APPI, the variants also inhibited Factor XIa with high affinity, with Ki* values ranging from approximately 0.3 to 15 nM; KALI-DY inhibited Factor XIa with a Ki* = 8.2 +/- 3.5 nM. KALI-DY did not inhibit plasmin, thrombin, Factor Xa, Factor XIIa, activated protein C, or tissue factor. Factor VIIa. Consistent with the protease specificity profile, KALI-DY did not prolong the clotting time in a prothrombin time assay, but did prolong the clotting time in an activated partial thromboplastin time assay > 3.5-fold at 1 microM.
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PMID:Potent and selective Kunitz domain inhibitors of plasma kallikrein designed by phage display. 759 8

To assess the blood coagulative and fibrinolytic responses during cemented femoral neck replacement, we measured these parameters in 9 patients, including anti-thrombin III (AT-III), prothrombin time (PT) and activated partial thromboplastin time (APTT) before surgery, just before packing bone cement and after the insertion of the prosthesis. We also measured thrombin-anti-thrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC), and D-dimer. A significant increase in APTT, and decrease in AT-III and PT were observed before the insertion of bone cement and prosthesis. The value of TAT and D-dimer increased significantly after the insertion of the prosthesis, but there were no significant changes in PIC. The data suggest that blood coagulation is activated after the insertion of bone cement and prosthesis into the femoral shaft, and in addition, the fibrinolysis is also accelerated secondary to the activation of the coagulation. Further investigations are needed to establish whether the activation of the coagulation induced by the cemented replacement exerts a great influence on the appearance of pulmonary thrombosis or circulatory depression.
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PMID:Blood coagulation and fibrinolytic activity during femoral neck prosthetic replacement using bone cement. 760 97

Aprotinin is a nonspecific serine protease inhibitor extracted from bovine lung. It was first used during cardiopulmonary bypass to inhibit plasmin-induced complement activation. By chance significant reductions of blood loss and blood requirements were noted in treated patients. Subsequent investigation showed improved hemostasis to result from protection of platelet adhesive receptors (Gp Ib) at the onset of cardiopulmonary bypass. Without aprotinin the contact system of plasma is massively activated on first passage through the cardiopulmonary bypass circuit. Activation of the intrinsic coagulation pathway causes thrombin formation, which impairs platelet adhesive function. Aprotinin blocks contact activation of the kallikrein system during cardiopulmonary bypass and in synergy with heparin prevents thrombin formation through inhibition of the intrinsic clotting cascade. It is likely that neither thrombin nor platelets become involved in the blood-foreign surface contact activation process in aprotinin-treated patients. The fact that the hemostatic process is affected from the very beginning of cardiopulmonary bypass is substantiated by the fact that low-dose aprotinin therapy (2 x 10(6) KIU aprotinin added to the pump prime) leads to the same preservative effect on Gp Ib receptors and blood loss as continuous high-dose infusion (6 x 10(6) KIU) throughout the whole surgical procedure. In the presence of heparin aprotinin prolongs the activated clotting time and the in vitro activated partial thromboplastin time. This has important implications for heparin dosage. An inhibitory effect on the endothelial cell anticoagulant function may also have consequences during hypothermic low flow and circulatory arrest states.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aprotinin in perspective. 768 54


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