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)

Inflammatory cells, e.g., neutrophils, monocytes, and macrophages are presumed to be a source of circulating phospholipase A in nonpancreatic diseases. Therefore, we investigated in a preliminary study whether serum phospholipase A activity is related to leukocyte counts in 43 patients with hematological diseases. Serum PLA activity was significantly increased in patients with Hodgkin's disease, acute monocytic leukemia, myelofibrosis with myeloid metaplasia, and polycythemia vera when compared with patients with chronic myelogenous leukemia, chronic lymphocytic leukemia, and acute myelogenous leukemia, but did not correlate with total leukocyte counts.
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PMID:Serum phospholipase A in hematological diseases. 292 59

Previous studies have shown that the response of patients with acute myeloid leukemia to induction chemotherapy can be predicted by the species of plasminogen activator that their cells secrete. Patients whose cells secreted tissue plasminogen activator (tPA) only failed to respond to combination chemotherapy. Individuals whose leukemic cells display features of the early progenitor phenotype also respond poorly to therapy. This suggested that the two species of plasminogen activator secreted by leukemic cells might be produced by normal cells at distinct stages of differentiation. These results indicate that the secretion of the two enzyme types is a differentiation-linked property of normal cells with tPA being produced by granulocyte/macrophage progenitors and urokinase by more differentiated cells and by mature neutrophils and macrophages.
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PMID:Differentiation-linked secretion of urokinase and tissue plasminogen activator by normal human hemopoietic cells. 310 48

This investigation was undertaken to examine the extent to which leukemic cell functions are susceptible to regulation in vitro and to investigate their heterogeneity in this regard. Since plasminogen activator release is known to be a modulatable cellular function that can be influenced by antiinflammatory steroids and tetradecanoyl phorbol acetate (TPA), the effect of these two compounds on the secretion of urokinase- or tissue-type enzymes by leukemic cells was studied. The release of both enzyme species could be stimulated or suppressed by these substances by mechanisms that were inhibitable by actinomycin-D and hence required transcription of new mRNA. Plasminogen activator release by cells from 41/45 patients with AML was either stimulated or inhibited by 10(-7) M dexamethasone, implying that most AML cells possess glucocorticoid receptors. In 26/45 cases, the enzyme was inhibited by this steroid to less than 25% of control values. Pronounced inhibition of this degree was not encountered with normal polymorphonuclear leukocytes. Plasminogen activator secretion by AML cells was profoundly inhibited in 20/41 cases by 1 ng/ml TPA and stimulated in 8/41 cases. Leukemic blasts varied considerably in their response to dexamethasone and TPA. Plasminogen activator release should prove a sensitive means of monitoring the responses of AML cells to biologically active compounds.
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PMID:The effects of dexamethasone and tetradecanoyl phorbol acetate on plasminogen activator release by human acute myeloid leukemia cells. 657 77

Peripheral blood cell preparation from 23 normal subjects and 72 patients with acute and 32 patients with chronic myeloid leukemia were cultured in vitro and released plasminogen activators were analyzed. The quantity of plasminogen activator secreted by leukemic cells varied widely and could not be correlated with the clinical severity of the disease. Immunochemical and electrophoretic techniques have been used to show that normal peripheral blood granulocytes released exclusively urokinase-like plasminogen activator, whereas leukemic cells secreted either urokinase or a tissue activator-like enzyme. The molecular species of enzyme released by acute myeloid leukemic cells may serve as a diagnostic marker of relevance to the management of this disease, since patients with acute myeloid leukemia whose cells released only tissue plasminogen activator did not respond to combination chemotherapy. Tissue plasminogen activators released by leukemic cells may display an unusual electrophoretic pattern that resembles that shown by urokinase. Immunochemical procedures are therefore essential for the correct identification of these enzymes.
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PMID:The secretion of plasminogen activators by human myeloid leukemic cells in vitro. 657 78

Haemostatic parameters were studied in 12 adult patients with acute myeloid leukaemia and acute lymphoblastic leukaemia in complete remission using high-dose cytosine arabinoside regiments together with with other drugs. Increased tissue plasminogen activator (t-PA:Ag) antigen 4 hours after AraC application (p < 0.05) as well as increased levels of plasminogen activator inhibitor activity (PAI) (p < 0.05) and fibrinopeptide A (FPA) antigen (p < 0.05) were observed on day 2. All patients during bone marrow aplasia suffered from infectious complications (7 from sepsis and 5 from fever of undetermined origin). During that period of infection the increased levels of FPA on day 21 (p < 0.05), PAI on days 15 and 21 (p < 0.05) and fibrinogen on day 21 (p < 0.05) as well as decreased values of antithrombin III (p < 0.05) on day 21 and protein C on day 15 (p < 0.05) were measured. t-PA:Ag, plasminogen, alpha 2 antiplasmin and fibrin(ogen) degradation products were within normal throughout infectious complications. None of the patients experienced clinically manifest thrombotic complication. Though the results demonstrate that changes found were not clinically important (even if they were statistically significant), and that haemostasis was compensated as well as that thrombosis was not serious problem, authors recommend routine haemostasis monitoring in acute leukaemia patients, especially at diagnosis, in association with chemotherapy and during infectious complications.
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PMID:[Hemostasis in patients with acute leukemia treated with high doses of cytosine-arabinoside: the effect of chemotherapy and infectious complications on hemostasis]. 781 98

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

The aim of this study was to investigate by flow cytometry the expression of the UPA-R (Urokinase type plasminogen activator receptor-CD87) on the blastic population of AML and ALL patients in order to evaluate whether the presence of this molecule could be associated with peculiar clinical and biologic features of leukemic cells. Five different monoclonal antibodies (MoAbs) (clones: 3B10#; VIM5*; 109#; 68#; 100#) were used in order to detect the distinct forms of this cellular receptor. Cell reactivity varied significantly from case to case, also depending on the MoAb used for the flow cytometry analysis. In brief, 3B10# and VIM5* MoAbs were found to be positive in more than 90% of monocytes and neutrophils from healthy subjects, while the number of positive cells was decreased (60%) using the 109# MoAb. However, either 68# and 100# MoAbs recognised only a low number of blood monocytes and neutrophils (8-20%), while lymphocytes were unreactive with all the five UPA-R MoAbs. ALL cells were found to be CD87 negative in all cases. Blasts from AML showed a heterogeneous pattern of expression for the UPA-R MoAbs, being the reactivity strictly dependent on the MoAb used, and, to a higher extent, on the degree and type of maturation of the blastic cells. The number of blasts recognising 3B10# and VIM5* MoAbs was significantly higher than that reacting with the remaining MoAbs irrespective of the FAB subtype. Since proteolytic enzymes, like UPA, play a key role in the dissolution of the extracellular matrix, and in facilitating the cell egress from the bone marrow, it is conceivable that the expression of the UPA-R could contribute to the invasive properties and, possibly, metastatic potential of leukemic cells.
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PMID:Flow cytometry evaluation of urokinase-type plasminogen activator receptor (UPA-R) in acute myeloid leukemia cells. 851 88

Veno-occlusive disease (VOD) is a serious complication of myeloablative therapy and stem cell transplantation. We here describe a case of VOD in a patient with acute myeloid leukemia (AML), who received an autologous peripheral blood stem cell graft after busulphan/cyclophosphamide conditioning in first complete remission and who developed severe VOD at day 17. Color-flow sonography of the portal and hepatic veins revealed hepatofugal blood flow in the portal vein and an absence of flow in the hepatic vein. Treatment with recombinant tissue plasminogen activator (t-PA) was started at a dose of 10 mg/day and increased to 20 mg/day because color-flow sonography indicated no change of blood flow. Daily sonography was continued to monitor the portal and hepatic blood flow in order to assess the need for continuation of t-PA. Once an objective sonographic improvement was observed, t-PA treatment was tapered and stopped. This case demonstrates that color-flow sonography can be used to confirm the clinical diagnosis of VOD. Furthermore this technique provides a way for easily and reliably evaluating the effect in relation to dose of thrombolytic therapy needed. It improves the quality of clinical monitoring which is needed for effective treatment of VOD while minimizing the risk of serious bleeding complications.
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PMID:Color-flow imaging sonography of portal and hepatic vein flow to monitor fibrinolytic therapy with r-TPA for veno-occlusive disease following myeloablative treatment. 957 16

Since the initial description of the disease, the life-threatening coagulopathy associated with acute promyelocytic leukaemia (APL) has been the defining clinical characteristic. Historically, this uncommon subtype of acute myeloid leukaemia has been associated with a high mortality rate during induction therapy, most frequently attributable to haemorrhage. Since the introduction of all-trans retinoic acid (ATRA) into the therapy of all patients with APL, disease-free survival and overall survival have improved dramatically, such that the disease is now highly curable. However, induction mortality remains a major problem and haemorrhage still accounts for the majority of such early deaths. Pathogenesis of the coagulopathy is complex and includes disseminated intravascular coagulation (DIC), fibrinolysis and proteolysis. As a result, while the predominant clinical manifestation of the coagulopathy is haemorrhage, thromboembolic events may occur both at presentation and during therapy. A major recent finding is the high expression of annexin II in the leukaemic cells from patients with APL. Annexin II is a protein with high affinity for plasminogen and tissue-type plasminogen activator (tPA), and also acts as a cofactor for plasminogen activation by tPA. As a result, both plasminogen and tPA are increased on the cell surface of the leukaemic cell, increasing plasmin activity. Annexin II is expressed in high amounts in cerebral microvascular endothelial cells, perhaps accounting for the relatively high incidence of intracranial haemorrhage in APL compared with other sites. Microparticles are cell-derived membrane fragments originating from normal cells or released from malignant cells involved in activating coagulation. Recent studies have found that microparticles containing tissue factor, tPA, plasminogen activator inhibitor-1 and annexin II have been found in the plasma of APL patients, suggesting a role in pathogenesis of the coagulopathy. Treatment of the coagulopathy remains primarily supportive. Aggressive transfusions of platelets and cryoprecipitate appear to be important. There is no clear role for the routine use of heparin or antifibrinolytic therapy. The most important factor may be the early introduction of ATRA at the first suspicion of a diagnosis of APL, before it is confirmed genetically.
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PMID:The coagulopathy of acute promyelocytic leukaemia revisited. 1928 82

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


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