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)

Plasma levels of tissue-plasminogen activator.plasminogen activator inhibitor (t-PA.PAI) complex and active PAI were assayed in 58 cases of disseminated intravascular coagulation (DIC). A significant elevation of both parameters was observed in most cases of DIC, especially in patients with non-Hodgkin lymphoma, sepsis, or some patients with acute leukemia, but no such elevation was observed in patients with acute promyelocytic leukemia (APL). The levels of both parameters were higher in cases of DIC with multiple organ failure (MOF) than in those without MOF. Since no elevation of t-PA.PAI complex was observed in most cases of APL, t-PA did not seem to play an important role in the activation of fibrinolytic system in APL. Active PAI, which reflects the inhibitory regulation in fibrinolytic system, was considered to play a role in the progression of MOF. Plasma levels of active PAI were low in the cases of APL, which had no complication of MOF.
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PMID:Changes in plasma levels of tissue-plasminogen activator/inhibitor complex and active plasminogen activator inhibitor in patients with disseminated intravascular coagulation. 130 60

Two short-lived vitamin K-dependent factors, factor VII and protein C, were measured by both functional and antigenic techniques in 3 hematological conditions known for their risk of hepatotoxicity: Following use of asparaginase and bisantrene, and patients at high risk of hepatic veno-occlusive disease after allogenic bone marrow transplantation for relapse of acute leukemia of accelerated phase of evoluted chronic myelogenic leukemia. In these 3 conditions functionally measured levels of protein C and factor VII, and antigenically measured levels of both these factors proved to be early markers of incipient hepatic involvement. These tests were easy to use routinely were reproducible, and proved to be predictive of veno-occlusive disease in grafted patients at the preconditioning stage. In the follow-up of bone marrow grafted patients plasma markers of endothelial function (von Willebrand's factor, tissue type plasminogen activator, and plasma activity of angiotensin converting enzyme) were significantly altered at the time of overdose with cyclosporin A, probably due to a drug-induced in vivo lesion of the endothelium. In the search for cytoprotective drugs for the prevention of veno-occlusive disease in bone marrow grafted patients prostaglandin E1 (PGE1) was given prior to and for at least 4 weeks after transplantation and proved to be effective by biological criteria (the level of protein C mainly). This deserves further study in a prospective clinical trial of the potential usefulness of PGE1 in preventing liver veno-occlusive disease in bone marrow grafted patients.
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PMID:[Hemostasis tests as markers of hepatic and endothelial toxicity in chemotherapy]. 329 Aug 34

In recent years, it is known that endothelial cells play an important role in the genesis of some diseases, but there are only few papers dealing with the role of endothelial cells in leukemia. In this study some of the active factors released by the endothelial cells in patients with acute leukemia such as von Willebrand factor, prostaglandin, fibronectin, tissue-type plasminogen activator and its inhibitor were determined. It was found that the levels of these factors changed significantly in patients with acute leukemia, as compared with those in normal controls, especially in cases with bleeding tendency and infection. The possible mechanism and the clinical significance were discussed.
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PMID:[Active factors released by endothelial cells in acute leukemia]. 804 83

We have examined the mononuclear cell fraction from 35 individuals, 18 with hematologic malignancies and 17 healthy controls for the presence of cell surface-associated plasminogen activator (PA) activity. PA activity was found on the cell surface of 10 out of 12 samples from patients with acute leukemia. In addition to active urokinase (uPA) found on the cell surface in four out of five acute myeloid leukemia patients, tissue-type PA activity was detected in the same samples (3 of 5). Two out of four samples from acute lymphoid leukemia displayed only uPA activity and three out of three samples from biphenotypic leukemia were also clearly uPA-positive. Plasmin activity was not detected in any of the samples. PA activity was not found on the surface of mononuclear cells from either patients with chronic lymphoid leukemia or healthy controls and, in this respect, the cell surface-bound uPA activity behaved as a marker for acute leukemia. The finding of PA activity on the cell surface in acute leukemia suggests that there may be continuous generation of plasmin with consequent consumption of plasma plasmin inhibitors.
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PMID:Abundant urokinase activity on the surface of mononuclear cells from blood and bone marrow of acute leukemia patients. 833 54

Disturbances in the regulation of the balance between the fibrinolytic and procoagulant properties of leukemic cells may contribute to the coagulopathy of acute leukemia. The coagulant response to a number of stimuli is regulated by the expression of tissue factor, but the role of the plasminogen activator inhibitors, PAI-1 and PAI-2, in contributing to the net coagulant response is not known. In this study, we have examined the production of these proteins by cultured myeloid leukemic cells arrested at different stages of differentiation. Northern blot analysis showed time-dependent and differential production of mRNA for PAI-2 and tissue factor, and to a much lesser extent, PAI-1, in response to the differentiating agent, 12-phorbol-13-myristate acetate. The capacity to synthesize PAI-2 appeared to be related to the stage of myeloid cell differentiation. Examination of the gene products by immunoblot analysis demonstrated multiple forms of PAI-2 in all myeloid cells examined. In addition, a common characteristic of all the myeloid cells was the production of a high molecular weight species of tissue factor which may be a secreted form unique to leukemic cells. Taken together, the findings demonstrate that myeloid leukemic cells are capable of generating a multicomponent coagulant response.
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PMID:Tissue factor and plasminogen activator inhibitor expression in the differentiation of myeloid leukemic cells. 830 77

Human promyelocytic HL-60 cells have been used as a model of acute leukemia to investigate the expression and the regulation of matrix metalloproteases (MMPs), known to contribute to the degradation of extracellular matrix components. As shown by gelatin zymography, HL-60 cells constitutively released significant amounts of proMMP-9 (92 kDa) and moderate amounts of proMMP-2 (72 kDa). Furthermore, casein zymography confirmed the presence of serine proteases in the form of pro-urokinase. Activation of proMMP-9 was dependent on the plasminogen activator/plasmin (PA/plasmin) system and was inhibited by aprotinin. MMP-9 was only detected in cellular extracts or conditioned media incubated with HL-60 cells, indicating that cells are essential to the activation process. Addition of plasminogen increased by 3-fold the basal invasive rate of these cells across a matrigel layer (2.1% versus 0.7% in control cells after 4 h of incubation). Taken together, these results indicate that HL-60 cells exhibit an autocrine activation mechanism of proMMP-9 via the PA/plasmin system and that activation of proMMP-9 increases their invasive potential.
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PMID:Production and activation of matrix metalloprotease-9 (MMP-9) by HL-60 promyelocytic leukemia cells. 932 78

In this study, we examined changes in the plasma levels of total plasminogen activator inhibitor-I (PAI-I) and tissue-type plasminogen activator (tPA)/PAI-I complex in patients with disseminated intravascular coagulation (DIC) and in those with thrombotic thrombocytopenic purpura (TTP) to investigate the fibrinolytic function and its relation to organ failure. The plasma levels of total PAI-1 and tPA/PAI-I complex were significantly higher in patients with DIC, pre-DIC, and TTP than in those with non-DIC. The plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, thrombomodulin (TM), total PAI-I, and tPA/PAI-I complex were significantly higher in patients with organ failure than in those without organ failure. The plasma levels of total PAI-I and tPA/PAI-I complex were markedly increased in patients with acute leukemia. The plasma levels of total PAI-I, but not those of tPA/PAI-I complex, were significantly increased in patients with sepsis or with solid cancer. In all cases, total PAI-I or tPA/PAI-I complex was not significantly correlated with any hemostatic marker. Measurement of total PAI-I and tPA/PAI-I complex may be useful in the diagnosis of DIC.
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PMID:Plasma levels of total plasminogen activator inhibitor-I (PAI-I) and tPA/PAI-1 complex in patients with disseminated intravascular coagulation and thrombotic thrombocytopenic purpura. 1144 85

Sudden chest pain, dyspnea, and tachypnea occurred in a 21-year-old female who was undergoing induction chemotherapy under a diagnosis of minimally differentiated acute leukemia (M0). The arterial blood gas (ABG) tensions were decreased (PO2 71.6 mm Hg, PCO2 23.7 mm Hg), and an electrocardiogram showed a right-bundle branch block. Coagulation abnormalities (PT 73.1%, APTT 39.4 s, FDP 235mg/dl) were observed 72 h before onset. Echocardiography revealed a large thrombus in a right ventricle. A diagnosis of pulmonary thromboembolism (PTE) was made, and a tissue-type plasminogen activator (monteplase) was administered under percutaneous cardiopulmonary support (PCPS). The complete lysis of thrombus was confirmed by an echocardiogram 8 h later. Symptoms and ABG data were also improved. PTE in adult AML cases is rare, but should be considered as one of the life-threatening complications in AML patients under chemotherapy who develop respiratory difficulties. We suggest a careful monitoring of coagulation abnormalities for the prediction of PTE during chemotherapy for AML, and the use of tissue-type plasminogen activator (t-PA), monteplase, for the treatment of PTE in these cases.
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PMID:A Case of Minimally Differentiated Acute Leukemia (AML-M0) Complicated by Ventricle Thrombosis During Remission-induction. 2740 95