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)

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

We have isolated three cDNA clones for human alpha 2-plasmin inhibitor (alpha 2-PI). Two clones are from human hepatoma cell line, Hep G2, and cover the entire protein coding region plus the 3'-flanking region up to the poly(A) sequence, and the other clone is from human liver and contains the carboxyl-terminal half. The total length of the cDNAs is 2.29 kb, corresponding to more than 95% of the full-length mRNA. alpha 2-PI seems to consist of 452 amino acid residues plus 39 amino acid residues for the signal peptide. The amino acid sequence shows 23 to 28% homology to those of five other protease inhibitors, plasminogen activator inhibitor (PAI), protein C inhibitor (PCI), alpha 1-antitrypsin (alpha 1-AT), antithrombin III (AT III), and alpha 1-antichymotrypsin (alpha 1-AC). alpha 2-PI seems to be the most distantly related among these inhibitors. Comparison of the phylogenetic trees of proteases and their inhibitors indicates that four proteases, namely elastase (or trypsin), chymotrypsin, plasminogen activator, and thrombin, may have evolved concurrently with the corresponding inhibitors. However, alpha 2-PI and PCI seem to have evolved asynchronously from their substrates. The data suggest that alpha 2-PI may originally have inhibited some protease other than plasmin, and protein C may have had an inhibitor different from the present one early in its evolutionary history.
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PMID:Structure of human alpha 2-plasmin inhibitor deduced from the cDNA sequence. 283 Feb 48

Fetal and neonatal lamb hemostasis were studied from the 60th day of pregnancy to birth. Platelet counts and blood coagulation, as assessed by tests such as recalcification time and thromboelastography, were similar in fetuses, neonates, and adult sheep. The values of coagulation factors were low, ie, vitamin K-dependent Factors II, VII, IX, and X remained unchanged (30 and 40% of adult reference values) until the last 10 days of gestation, and then increased until birth (40 to 60%). Values of fibrinogen and Factor V followed a similar pattern, although their activities became identical to adult values at birth. Also, we measured values of protein C and antithrombin III, which are synthesized by the liver. The importance of hepatic failure and fetal vitamin K deficiency were discussed. Factors VIII and XII activities increased gradually during pregnancy to reach adult values at birth. Fetal fibrinolytic activity increased. This could not be explained by the values of tissue-type plasminogen activator (it was not detectable) or by the presence of its fast-acting inhibitor, whose concentration did not decrease.
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PMID:Hemostasis development in the lamb fetus and neonate. 291 28

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

We report the production, purification, characterization, and partial amino acid sequence of a plasminogen inhibitor (PA-I). The starting material is culture fluid from phorbol myristate 13-acetate-treated U-937 cells and the isolation steps consist of preparative isoelectric focusing followed by affinity chromatography on Cibacron Blue-Sepharose. PA-I migrates as a closely spaced doublet of 47-kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and forms covalent complexes with urokinase and two-chain tissue-type plasminogen activator, displaying second order rate constants of 0.9 X 10(6) M-1 s-1 and 0.2 X 10(6) M-1 s-1, respectively. Upon treatment with 1 M NH4OH, the covalent complexes were hydrolyzed, yielding a 35-kDa inhibitor fragment. A partial amino acid sequence of PA-I showed that it belongs to the antithrombin III family of inhibitors. PA-I is immunologically related to a PA-inhibitor from human placenta. mRNA from phorbol myristate 13-acetate-treated U-937 cells directed, in a rabbit reticulocyte derived cell-free system, the biosynthesis of only one 47-kDa protein that could be immunoprecipitated with anti-PA-I IgG, indicating that the two molecular forms of PA-I are the products of post-translational processing.
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PMID:Purification and characterization of a plasminogen activator inhibitor from the histiocytic lymphoma cell line U-937. 309 45

The fibrinolytic system was investigated in 120 patients with spontaneous or recurrent deep vein thrombosis (DVT) without any known organic disease able to explain by itself the occurrence of a thrombosis and without any known defect of antithrombin III, Heparin Cofactor II, Protein C, or Protein S. The assays included: Euglobulin fibrinolytic activity (EFA), tissue-type plasminogen activator related antigen (t-PA-Ag) and plasminogen activator inhibitor activity (PA inhibitor), which were measured before and after 10 min of venous occlusion (V.O.). On the basis of the results, the patients could be classified in 3 groups: good responders with an at least two-fold increase of EFA after venous occlusion (n = 76), poor responders with a lesser increase of EFA due to deficient release of t-PA (n = 12), and poor responders with a normal t-PA release but an increased level of PA-Inhibitor (n = 32). The poor responders due to deficient t-PA release (10% of total) had a higher incidence of recurrence of deep vein thrombosis, than the other groups (p less than 0.01). An overall correlation was found between the level of PA-Inhibitor activity and the triglyceride level (r = 0.40, p less than 0.01), suggesting that these elevations may be due to a common cause, at least in some of the patients. It is concluded that a poor fibrinolytic response to venous occlusion occurs in 35 percent of DVT patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep venous thrombosis. 310 59

Various human malignant tumors, including malignant melanoma, showed an absence of fibrinolytic activity by the histochemical fibrin slide method. In contrast, a tissue plasminogen activator has been isolated both from extracts of melanoma tissues and melanoma cell lines in culture, and has been characterized to be a potent plasminogen activator. In an attempt to resolve this apparent discrepancy, we studied biopsied specimens of melanoma and several melanoma cell lines by the immunoperoxidase method. Tissue plasminogen activator was observed in melanoma tissues and cell lines while the various inhibitors of fibrinolysis, including alpha 2-anti-plasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, and antithrombin III were found intracellularly only in the melanoma tumor cells, but not in melanoma cell lines. We believe that these inhibitors are derived from the blood and are bound to the tissue plasminogen activator within the melanoma cells. This hypothesis is supported by in vivo studies showing binding of tissue plasminogen activator in cultured cell lines to several inhibitors. Since these are potent inhibitors of fibrinolysis, their presence in tumor cells would explain the lack of fibrinolytic activity in melanoma tissues.
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PMID:Tumor growth and metastases in malignant disease. A review. 314 46

In eight male patients with normal liver and kidney function fibrinolytic components were measured in arterial blood and in renal and hepatic vein blood, obtained during catheterization for analysis of hypertension. Blood samples were collected simultaneously from veins und corresponding arteries before and 5 minutes after the completion of intravenous injection of desmopressin (DDAVP), 0.4 micrograms/kg body weight over a 10 minute period. DDAVP induced a rise in t-PA antigen and activity, and in von Willebrand factor, accompanied by a decrease in free PA-inhibitor level. We failed to detect a significant rise in plasma urokinase activity. The concentrations of fibrinogen, plasminogen, alpha 2-antiplasmin, antithrombin III and coeruloplasmin did not change either. Renal production of t-PA under basal conditions was inferred from a negative arterio-venous (A-V) difference in t-PA-activity and in t-PA-antigen levels but this could not be confirmed by orthogonal regression analysis of the same data. A-V differences of other fibrinolytic factors were negligible. In the hepatic vessels a significant positive A-V difference of t-PA-activity and of t-PA-antigen levels was a uniform finding. After DDAVP, when plasma levels were elevated, the mean A-V difference was proportionally higher, consistent with a constant fractional elimination rate. Free PA-inhibitor was virtually absent from arterial blood after DDAVP, but appeared in hepatic vein blood, indicating either production of the inhibitor by the liver or dissociation of a circulating complex of t-PA and its inhibitor in the liver. The blood levels of the other investigated components did not show any change upon passage through the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal and hepatic handling of endogenous tissue-type plasminogen activator (t-PA) and its inhibitor in man. 314 78

Various human malignant tumors including malignant melanoma showed an absence of fibrinolytic activity in previous histochemical fibrin studies. In contrast, a tissue plasminogen activator has been isolated both from extracts of melanoma tissues and melanoma cell lines in culture and has been characterized to be a potent plasminogen activator. In an attempt to resolve this apparent discrepancy, we studied biopsies specimens of melanoma, several melanoma cell lines and melanoma xenografts by the immunoperoxidase method. Tissue plasminogen activator was observed in melanoma tissues, cell lines and xenografts, while various inhibitors of fibrinolysis, including alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin and antithrombin III, were found intracellularly only in the melanoma tumor cells but not in melanoma cell lines nor in xenografts. We believe that these inhibitors are derived from the blood and are bound to the tissue plasminogen activator within the melanoma cells. Their presence in tumor cells would explain the lack of fibrinolytic activity in melanoma tissues.
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PMID:Tissue plasminogen activator and inhibitors of fibrinolysis in malignant melanoma. 314 30

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


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