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:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coagulation disorders have been noted during orthotopic liver transplantation (OLT) especially just after reperfusion of the grafted liver. This study was undertaken to clarify the coagulation disorders following reperfusion of the liver graft. OLT was carried out in adult mongrel dogs using a cuff technique. Fresh and 24-hour preserved livers were grafted. Platelet count (P1), activated partial thromboplastin time (A-PTT), prothrombin time (PT) and plasma fibrinogen levels (Fng) were measured before and after OLT. Next perfusate obtained from fresh livers or preserved livers for 24-hours or 48-hours was determined for their ability of inducing coagulation disorders when infused in untreated dogs, and was also tested for their activity of platelet aggregation, tissue thromboplastin (F-III), and plasminogen activator (PA). All dogs which received preserved livers showed a marked coagulation disorders including a decrease in P1 and Fng, and prolongation of A-PTT and PT, but the dogs with fresh liver grafts did not. Infusion of the perfusate collected from a perfusion of the preserved liver induced similar coagulation disorders in untreated dogs. The perfusate obtained from the preserved liver showed significant increased F-III activity as compared with that from fresh liver. On the other hand, neither direct platelet aggregation activity nor PA activity was seen or very low if any. These results indicate that F-III liberated from a damaged liver is responsible for the coagulation disorders after reperfusion of the graft in liver transplantation.
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PMID:[Coagulation disorders during orthotopic liver transplantation]. 279 56

The effects on the fibrinolytic system after a single s.c. bolus injection (at 9 a.m.) of either 5000 IU conventional heparin or 5000 anti-Xa U of a fractionated low molecular weight heparin (Fragmin, KabiVitrum, Sweden) were investigated in 9 healthy volunteers. The effects were compared to those of an injection of normal saline in 6 volunteers. Samples for biochemical analyses were taken regularily during 6 hours after drug or placebo administration. In the coagulation system the following parameters were measured: Activated partial thromboplastin time (APTT), anti-Xa activity, thrombin time and fibrinogen. The fibrinolytic system was monitored by analysing: plasminogen, alpha 2-antiplasmin, fibrin(ogen) degradation products (FDP), euglobulin clot lysis time (ECLT), tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor (PAI) activity. Injection of the 2 drugs was followed by elevations in APTT and anti-Xa activity, and were more pronounced for Fragmin than heparin. The fibrinolytic system exhibited a diurnal variation with decreasing PAI activity and increasing t-PA activity during the day. Volunteers receiving normal saline (placebo) showed a similar pattern. The results were unrelated to heparin. It is concluded from this study that neither heparin nor Fragmin had any significant effect on the fibrinolytic parameters when measured after a single s.c. bolus injection since the observed variations were within the diurnal range.
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PMID:Heparin and fibrinolysis--comparison of subcutaneous administration of unfractionated and low molecular weight heparin. 283 26

Incubation of HTC rat hepatoma cells with the synthetic glucocorticoid dexamethasone rapidly inhibits plasminogen activator (PA) activity secondary to the induction of a specific acid-stable inhibitor of plasminogen activation (Cwikel, B. J., Barouski-Miller, P.A., Coleman, P.L., and Gelehrter, T.D. (1984) J. Biol. Chem. 259, 6847-6851). We have further characterized this inhibitor with respect to its interaction with both urokinase and tissue plasminogen activator, and its protease specificity. The HTC PA inhibitor rapidly inhibits urokinase and tissue plasminogen activator with an apparent second-order rate constant of 3-5 x 10(7) M-1 X s-1. The inhibitor forms stable covalent complexes with both urokinase and tissue plasminogen activator, with which plasmin, trypsin, and factor Xa apparently do not compete. Complex formation is saturable and requires the active site of the PA. The mass of the inhibitor-PA complex is 50,000 daltons greater than that of PA alone, consistent with an Mr for the PA inhibitor of 50,000 as demonstrated directly by reverse fibrin autography. The HTC PA inhibitor does not inhibit thrombin and differs in its kinetic and biochemical properties from protease nexin.
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PMID:Characterization of the dexamethasone-induced inhibitor of plasminogen activator in HTC hepatoma cells. 293 42

As the cells forming the luminal vascular surface, endothelial cells are strategically positioned to play an important role in the regulation of coagulation. They cannot be regarded as an inert surface lining the vessel wall since they possess multiple activities. Anticoagulant properties include provision of a cell surface with heparin-like molecules (which can serve as binding sites for antithrombin III), synthesis of thrombomodulin (which alters the substrate specificity of thrombin), maintenance of a low level of tissue factor and generation of prostacyclin. In addition to these anticoagulant properties, endothelial cells can play a role in procoagulant reactions. Studies which have examined mechanisms underlying the localization of thrombotic processes have suggested the possible involvement of endothelial cells in procoagulant events. Endothelial cells have been found to propagate factor X and prothrombin activation once factor IXa and factor Xa have been formed. Factors regulating the balance of plasminogen activator and inhibitor synthesis are also under study. Perturbation of endothelial cells with induction of tissue factor and production of platelet-activating factor and thromboxane provides a model of the thrombotic state in which endothelium can promote coagulation. The multiple properties of endothelial cells indicate that a continuous blood flow in an unperturbed region of the vessel wall results from a complex interplay of anticoagulant and procoagulant activities. In a perturbed region, endothelial cells might initiate coagulation and the thrombin formed on the surface of endothelial cells might then lead to recruitment of platelets.
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PMID:The role of endothelium in the homeostatic balance of haemostasis. 299 30

A complex series of reactions are involved in the assembly, function, and regulation of the prothrombinase complex. Since the enzyme is multicomponent in nature and each component is required for catalytic function, modulation of enzymatic activity can be achieved in a variety of ways. In addition, since complex assembly so profoundly affects reaction rates, mechanisms that perturb complex formation either positively or negatively have a profound effect on thrombin generation and its local physiologic effects. All of the cells that support prothrombinase assembly and hence thrombin generation respond to thrombin in a variety of ways. Thrombin selectively binds to thrombomodulin and heparin-like molecules expressed on the endothelial cell surface. Thrombin induces the release (and possible synthesis of) prostacyclin, plasminogen activator inhibitor, platelet-derived growth factor, and interleukin-1 and inhibits the release of plasminogen activator from vascular endothelium. Interleukin-1 is a potent mediator of inflammatory phenomena as well as an inducer of tissue factor synthesis in vascular endothelium. With respect to platelets, thrombin selectively binds and stimulates the platelet release reaction and subsequent aggregation. The thrombin-induced release of platelet-derived growth factor from both platelets and vascular endothelium may play a role in inflammation, wound healing, and atherogenesis. Thrombin itself is a potent mitogen of mesenchymal cells, and more recently has been shown to be not only a chemoattractant, but also a mitogen for monocytes. Thrombin also appears to bind selectively to monocytes and in so doing induces release of interleukin-1. Thrombin affects a myriad of cellular responses related to hemostasis, thrombosis, inflammation, would repair, and atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of thrombin generation at cell surfaces. 305 86

It has been demonstrated that the surface of large VLDL Sf 100-400 can bind both prothrombin and Factor X(Xa) and that on VLDL Factor Xa can convert prothrombin to thrombin, which degrades apo B and apo E. It has been reported also that the VLDL kinetically supports the conversion of prothrombin to thrombin. The binding of vitamin K-dependent proteins to phospholipid is partially Ca2+-dependent and probably involves their Gla residues. The complex of VLDL, prothrombin, Factor Xa, and Ca2+ lacks only Factor Va, a lipid associating, non-Gla residue containing 330 kd protein, to complete the "prothrombinase complex." Factor V (Va) is found at very low concentrations in the circulation, but is localized on platelets, monocytes, and the endothelium. VLDL can bind both to monocytes and to the endothelium, for example, through both receptor and non-receptor pathways. When carrying this complement of the prothrombinase complex, this subpopulation of VLDL, in the presence of Factor Va on cell surfaces, could conceivably upset the local balance of pro- and anticoagulant activities. Thus, directly or indirectly the increased triglyceride levels, reflected in increased VLDL in patients, may alter this balance, and thereby produce a "hypercoagulable state." This is a simplistic view of the potential role of VLDL in the interplay of cells, coagulation proteins, and the regulatory systems involved in vivo. To realize the degree of complexity that we may need to address, we need only look at the work of Booyse et al in this issue of Seminars, in which they demonstrate that hypertriglyceridemic VLDL, in contrast to normal VLDL, do not support the early release of t-PA from endothelial cells, an antifibrinolytic event.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vitamin K-dependent proteins bind to very low-density lipoproteins. 305 90

Recombinant tissue-type plasminogen activator (t-PA) is a DNA-synthesized thrombolytic agent recently approved for clinical trials. We present the results of t-PA infusions in 18 patients with thrombosed peripheral arteries (12 patients) and peripheral bypass grafts (six patients). The duration of occlusion ranged from 1 to 21 days (mean, 6.8 days). Infusions of t-PA were done by way of an intra-arterial approach at a dose of 0.1 mg/kg/hr. All patients demonstrated thrombus lysis angiographically. Fifteen of 18 (83%) had clinical as well as angiographic improvement. Secondary procedures to maintain patency of the arterial segment were required in seven patients. No complications occurred that were related to the t-PA infusion. No significant prolongation of the prothrombin, thrombin, or activated partial thromboplastin times occurred. At the end of t-PA infusion, the mean circulating fibrinogen level was 59% of the starting value. The therapeutic use of t-PA is still in its preliminary stages and the efficacy and safety of this promising agent need to be further established. From our early experience with t-PA, it appears to be safe as well as effective.
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PMID:Peripheral artery and bypass graft thrombolysis with recombinant human tissue-type plasminogen activator. 307 38

Vasopressin infusions in normal volunteers that produce concentrations in plasma comparable to those seen during stress, cause an increase in plasma factor VIII and shortening of the euglobulin clot lysis time (ECLT). We have investigated the relationship between endogenous vasopressin (aVP) release and haemostatic function in 7 patients undergoing major abdominal surgery. Blood samples were taken at nine intervals during the operative procedure. Plasma aVP levels peaked at median values of 51 pg/ml during bowel manipulation and remained elevated on the first post-operative day. Following, and in close temporal relationship with the rise in aVP there were increases in factor VIII coagulant activity, the ristocetin co-factor, von Willebrand antigen, plasminogen activator activity (10(6)/ECLT2) and fibrinopeptide A concentrations with shortening of the activated partial thromboplastin time. The relationship was similar to that seen following infusion of aVP in human volunteers. The results are consistent with the hypothesis that aVP is an important mediator of changes in haemostatic function which accompany stress and might contribute to the thrombotic risk associated with surgical operations.
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PMID:Intra-operative activation of coagulation--a stimulus to thrombosis mediated by vasopressin? 308 60

The effect of Norplant subdermal implants on 22 different hemostatic variables was determined in 100 women attending the Fertility Control Clinic of the Singapore National University Hospital before and after 6 and 12 months of use. The factors analyzed were: hematocrit, hemoglobin (Hb), prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, fibrinogen, coagulation factor II, Factor V,Factor VII, Factor VIII, Factor VIIIR:Ag, Factor X, plasminogen activator, FDP, plasminogen (imm), antithrombin III (functional), antithrombin (antigen), protein C, alpha2-antiplasmin, alpha2-macroglobulin, alpha2-antitrypsin, platelet count, platelet aggregation (ADP), and platelet aggregation (collagen). The factors that differed significantly after 12 months were: Hb,PT,APTT, Factors II,V,VII, and VIIIR:Ag, Plasminogen (imm), antithrombin III(antigen), alpha2-antiplasmin, platelet count, and platelet aggregation. Most of these differences, while significant, were still within the normal range, except for PT,APTT, and platelet count. The subjects were considered to be in an enhanced risk for hypercoagulation and thrombosis.
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PMID:The effects of Norplant-2 rods on clinical chemistry in Singaporean acceptors after 1 year of use: haemostatic changes. 314 69

Tissue fibrin deposition may be an important component of inflammatory reactions. Current evidence suggests that intraalveolar procoagulant (PC) and plasminogen activator (PA) activities may be important determinants of local fibrin turnover in lung injury. In this study, we measured the PC and PA activities in cell-free bronchoalveolar lavage fluid (BALF) obtained from 17 patients with pulmonary sarcoidosis and 12 normal volunteers. Procoagulant activity was assayed by timing clot formation in a one-stage coagulation assay, and plasminogen activator activity was determined by measuring plasminogen-dependent lysis of [125I]fibrin. Mean PC activity in the sarcoidosis group was significantly elevated (102 +/- 25 versus 31.5 +/- 8.1 tissue thromboplastin units/ml; p less than 0.002), with 6 of 17 patient values beyond the 95% confidence limits of normals. These differences were not seen when PC activity was corrected for total protein in BAL. In contrast, PA activity tended to be lower in the sarcoidosis group (0.54 +/- 0.094 versus 0.643 +/- 0.106 Plough units/ml, p less than 0.3), and this difference became significant when PA was normalized to total protein (p less than 0.001). The ratio of procoagulant activity compared to plasminogen activator (PC/PA) was greater in the patients with sarcoidosis than normals (258 +/- 54 versus 40.3 +/- 6.4; p less than 0.001). The PC/PA ratios in 14 of 17 patients exceeded the 95% confidence limits of normals. In the sarcoidosis group, the PC/PA ratio correlated weakly with the number and percentage of lymphocytes retrieved by BAL. The plasminogen activator was a urokinase by molecular weight (53 kDa) and by comparing neutralization of PA activity by antibodies against urokinase and tissue plasminogen activator. The procoagulant was particulate and functioned as a factor X activator comprised of tissue thromboplastin and factor VII. We conclude that in pulmonary sarcoidosis, abnormal expression of procoagulant and plasminogen activator activities in alveolar fluid may favor accumulation of fibrin matrix at inflammatory foci.
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PMID:Procoagulant and plasminogen activator activities of bronchoalveolar fluid in patients with pulmonary sarcoidosis. 337 Dec 78


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