Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The profile of blood coagulation and fibrinolysis was studied in detail in eight patients with acute thrombotic thrombocytopenic purpura (TTP). In the majority of the patients, fibrinogen, factor XIII, antithrombin III, alpha 2-plasmin inhibitor, plasminogen, and alpha 2-macroglobulin were normal, whereas FDP, plasmin-alpha 2-plasmin inhibitor complex, and tissue-type plasminogen activator antigen were marginally or moderately elevated. Low fibronectin values were observed in four patients. Protein C and C4b-binding protein were nearly normal, whereas total protein S and free protein S were reduced in five and six patients, respectively. A positive correlation was found between total protein S and C4 and between free protein S and C3. von Willebrand factor antigen (vWf:Ag) and ristocetin cofactor (RCof) were either normal or elevated, but RCof/vWf:Ag ratio was decreased in seven patients. Crossed immunoelectrophoresis and sodium dodecyl sulfate (SDS)-agarose gel electrophoresis revealed that the large vWf multimers were either absent from or relatively decreased in all patients except one. In addition, one patient had unusually large vWf multimers, and a low-molecular-weight vWf fragment was apparently observed in three patients. These findings indicate that the intravascular generation of thrombin and plasmin was minimal in TTP and suggest that the alterations of the vWf molecule were caused not only by consumption through its participation in platelet thrombus formation but also by accelerated proteolysis. Low protein S values would be related to the immunological abnormalities underlying TTP.
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PMID:Coagulation studies in thrombotic thrombocytopenic purpura, with special reference to von Willebrand factor and protein S. 252 Dec 76

Changes in the protein C-thrombomodulin (PC-TM) system in relation to other coagulofibrinolytic parameters were examined in 25 patients undergoing open heart surgery. Although all patients were given heparin, a decrease in antithrombin III (ATIII) and progressive increase in thrombin-ATIII complex (TAT) and fibrinopeptide A (FPA) levels were noted during cardiopulmonary bypass, which indicated that heparinization did not completely inhibit the formation of thrombin and its function. C1-inactivator (INA) resistant fibrinolytic activity increased markedly during CPB, in parallel with the change of tissue plasminogen activator antigen (t-PA;Ag), which indicates that fibrinolytic activity during CPB is mainly of extrinsic origin caused by t-PA. Protein C antigen (PC;Ag), protein S antigen (PS;Ag), and thrombomodulin antigen (TM;Ag) were all decreased significantly during CPB. This is considered to reflect the activation and consumption of the PC-TM system in response to generated thrombin. Furthermore, enhancement of the extrinsic fibrinolytic system is easily explained by the action of activated PC, which counteracts plasminogen activator inhibitor (PAI-1), to cause enhancement of t-PA activity.
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PMID:The role of the protein C-thrombomodulin system in physiologic anticoagulation during cardiopulmonary bypass. 255 68

Systemic activation of the coagulation mechanism is known to exist in patients with colon cancer. The mechanism of such activation was investigated using immunohistochemical techniques applied to fresh frozen sections of resected primary colon cancer specimens. Tumor cells stained for tissue factor, factor V, and urokinase-type plasminogen activator. Perivascular and intercellular areas stained for fibrinogen and the "a" subunit of factor XIII. Staining was minimal or absent for protein C, protein S, plasminogen activator inhibitors 1-3, factor VII, factor X, and fibrin (the antigenic site on the amino-terminal portion of B beta chain that is exposed following thrombin cleavage of fibrinopeptide B was not detected). The lack of an intact thrombin-generating pathway in situ associated with viable colon cancer cells is consistent with the findings of others that coagulation activation in colon cancer may be triggered by a soluble tumor product that exerts its effect at sites distant from the tumor. These results may explain the absence of clinical responsiveness of colon cancer to antithrombotic drug therapy and may clarify therapeutic strategies for this common tumor.
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PMID:Indirect activation of blood coagulation in colon cancer. 269 22

Hemostatic changes were evaluated in ten patients with acute lymphoblastic leukemia and lymphoma who received chemotherapy with L-asparaginase, vincristine, and prednisolone for 1 week. Following treatment, prothrombin time and activated partial thromboplastin time were significantly prolonged, while a marked decrease in fibrinogen levels was observed. The values for cross-linked fibrin degradation products, however, remained within normal limits during treatment, which excluded the possibility of disseminated intravascular coagulation. The concentrations of coagulation inhibitors (antithrombin III, protein C, and protein S), plasminogen, and alpha 2 antiplasmin also significantly decreased; however, levels of both tissue-type plasminogen activator and plasminogen activator inhibitor, which are synthesized in endothelial cells, increased during the treatment. Although a decrease was observed in concentrations of many coagulation factors, including subunits A and B of factor XIII, the activity and antigenicity of factor VII significantly increased following the treatment. From this study, we concluded that these hemostatic abnormalities caused by the administration of L-asparaginase produced a labile condition that easily inclines to bleeding or thrombosis.
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PMID:Changes in hemostatic and fibrinolytic proteins in patients receiving L-asparaginase therapy. 275

The effect of purified human activated protein C (APC) and protein S on fibrinolysis was studied by using an in vitro blood clot lysis technique. Blood clots were formed from citrated blood (supplemented with 125I-fibrinogen) by adding thrombin and Ca2+-ions; lysis of the clots was achieved by adding tissue-type plasminogen activator. The release of labeled fibrin degradation products from the clots into the supernatant was followed in time. We clearly demonstrated that APC accelerates whole blood clot lysis in vitro. The effect of APC was completely quenched by antiprotein C IgG, pretreatment of APC with diisopropylfluorophosphate, and preincubation of the blood with antiprotein S IgG. This demonstrates that both the active site of APC and the presence of the cofactor, protein S, are essential for the expression of the profibrinolytic properties. At present, the substrate of APC involved in the regulation of fibrinolysis is not yet known. Analysis of the radiolabeled fibrin degradation products demonstrated that APC had no effect on the fibrin cross-linking capacity of factor XIII.
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PMID:The cofactor role of protein S in the acceleration of whole blood clot lysis by activated protein C in vitro. 293 72

Platelets stimulated with thrombin release an inhibitor of plasminogen activator (PAI), which has been shown previously to be neutralized by activated protein C (APC). The requirements for optimal neutralization of PAI activity were investigated. The releasate of gel-filtered human platelets stimulated with thrombin served as a source of PAI. When 6 X 10(8) platelets/mL were incubated with thrombin (1 IU/mL), the releasate contained 18 to 26 ng/mL PAI as determined by incubation of the releasate with urokinase and measurement of residual urokinase activity on plasminogen (S2251). Preincubation of PAI with up to 4 micrograms/mL APC for two hours yielded less than 20% neutralization of PAI activity. In the presence of protein S, phospholipid, and Ca2+, neutralization of PAI activity was time-dependent with 50% neutralization occurring in two hours with 1 microgram/mL APC. The cofactor effects of protein S and phospholipid were concentration-dependent with half-maximal acceleration at approximately 3 micrograms/mL protein S and 10 micrograms/mL phospholipid when the experiments were performed at 1 microgram/mL APC. Diisopropylfluorophosphate-inactivated APC, gla-domainless APC, and thrombin-cleaved protein S had no effect on PAI activity, indicating requirement for preservation of the APC active site and of the Ca2+ binding ability of both APC and protein S. These results suggest coordinate binding of APC and protein S onto phospholipid membrane as a prerequisite for optimal expression of PAI neutralized by APC.
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PMID:Protein S is a cofactor for activated protein C neutralization of an inhibitor of plasminogen activation released from platelets. 294 43

The effect of purified human activated protein C (APC) on fibrinolysis was studied using a clot lysis system consisting of purified glu-plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor (released from endothelial cells or blood platelets), fibrinogen, 125I-fibrinogen and thrombin. All proteins were of human origin. In this system APC could increase fibrinolysis in a dose dependent way, without affecting fibrin formation or fibrin crosslinking. However, this profibrinolytic effect of APC could only be observed when plasminogen activator inhibitor (PAI-1) was present. The effect of APC was completely quenched by pretreatment of APC with anti-protein C IgG or di-isopropyl-fluorophosphate. Addition of the cofactors of APC-protein S, Ca2+-ions and phospholipid-alone or in combination did not enhance the profibrinolytic effect of APC. These observations indicate that human APC can accelerate in vitro clot lysis by the inactivation of PAI-1 activity. However, the neutralization of PAI-1 by APC is independent of the presence or absence of protein S, phospholipid and Ca2+-ions.
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PMID:Activated protein C increases fibrin clot lysis by neutralization of plasminogen activator inhibitor--no evidence for a cofactor role of protein S. 297 9

Three patients with karyotype XYY who had presented with deep vein thrombosis and leg ulcers (plus pulmonary embolism in two of them) were investigated for: (1) androgens (plasma testosterone measurement, testosterone oestradiol binding globulin (TeBG) assay, GnRH 50 micrograms test), and (2) haemostasis by fibrinolysis tests (euglobulin lysis time and area, antigenic plasminogen activator assay before and after 10 min venostasis). Full evaluation of haemostasis failed to demonstrate the presence of circulating anticoagulant or of antithrombin III, protein C and protein S deficiencies. One patient had neither hormonal nor fibrinolytic abnormality. The other two patients shared some clinical features with male hypogonadism (gynoid morphotype in both, hypotrophy of the testes in one, gynaecomastia in the other). They also had hormonal disorders ("over-response" to the GnRH test in one case, elevated TeGB in the other case) and abnormalities of fibrinolysis (poor response to venostasis, high baseline level of plasminogen activator). Response to venostasis became normal after 3 months of treatment with percutaneous dihydrosterone 125 mg per day in the two patients with initially poor response. The mechanism of venous pathology in XYY subjects is discussed. A genetic defect not involving the fibrinolysis system is possible since fibrinolysis was normal in one patient; however, abnormal fibrinolysis may have been responsible for the venous pathology in the other 2 patients. The role played by abnormalities of fibrinolysis in the pathogenesis of deep vein thrombosis and leg ulcers is recalled, and the possible implication of these abnormalities in patients with XYY karyotype is emphasized.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Post-phlebitic leg ulcers and XYY karyotype: fibrinolysis and androgenic function tests. Apropos of 3 cases]. 343 47

Some molecular defects of components of the coagulation or fibrinolytic system are associated with thromboembolism. One possibility is that physiologic inhibitors of the coagulation system have an abnormal function e.g. protein C, protein S, antithrombin III and cofactor II of heparin. Also a hindered activation of the fibrinolytic system may predispose to thrombosis; the impaired activation may be due to deficient synthesis and/or release of tissue-plasminogen activator, an increased level of its inhibitor or a functional defect of the plasminogen molecule. A few cases of congenital dysfibrinogenemia have been described in which the functional defects of the molecule are held responsible for recurrent thrombosis. An acquired thrombotic disorder is due to the presence of immunoglobulins which prolongs phospholipid-dependent coagulation by binding to epitopes of some phospholipids. This so-called lupus anticoagulant was originally described in patients with systemic lupus erythematosus but is a misnomer as it is more frequently encountered in patients without lupus.
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PMID:[Molecular defects of coagulation factors and of the fibrinolytic system associated with thromboembolism]. 354 55

In this study the influence of low-dose oral contraceptives (OC) on the different components of the fibrinolytic system before and immediately after maximal exercise was examined in a group of 18 moderately active women. Nine women using OC and nine control women performed a maximal effort treadmill protocol. Comparison of the resting parameters revealed higher plasma FbDP, plasminogen, alpha 2-antiplasmin and protein C concentrations, and lower PAI activity in the OC group. No differences were observed in plasma concentrations of t-PA antigen, t-PA activity, PAI antigen, antithrombin III, and protein S. Acute maximal exercise resulted in significant increases in t-PA antigen, t-PA activity, t-PA/PAI complexes, and FbDP in both groups of subjects, while PAI activity was reduced. No significant differences were found for the change in those parameters between control and OC users. Exercise induced no variation in any of the groups for PAI antigen, alpha 2-antiplasmin, plasminogen, protein C, or protein S. Our data suggest that changes in the fibrinolytic system induced by physical exercise are not affected by oral contraceptives.
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PMID:Effects of oral contraceptives on fibrinolytic response to exercise. 756 82


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