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)

In pre-eclampsia (PE), reduced levels of plasma urokinase-like plasminogen activator (u-PA) and plasminogen activator inhibitor-2 (PAI-2), and increased levels of plasma tissue-type plasminogen activator (t-PA) antigen were seen. The majority of moderate and severe pre-eclamptic women (7 out of 10) ended up with pre-term delivery as compared with 2 out of 11 who went on to term. Patients with moderate and severe PE had significantly lower levels (mean +/- SD, ng/ml) of PAI-2 (58.4 +/- 34.9) and u-PA antigen (1.61 +/- 0.62) as compared to those with mild PE (95.6 +/- 39.3 and 1.61 +/- 0.62 and 2.12 +/- 0.61, respectively). Significantly raised t-PA antigen (14.6 +/- 5.7 ng/ml) was seen in moderate and severe PE as compared with mild PE (9.9 +/- 3.4 ng/ml). PAI-1 activity was significantly raised only in moderate and severe PE as compared with normal pregnancy. There were no significant differences in thrombin-antithrombin-III complexes, D-dimer and beta-thromboglobulin levels between the PE group and normal pregnancy, although these parameters were above the non-pregnant levels. Platelets in PE were within the range found in normal pregnancy. It appears that measurements of plasma u-PA and PAI-2 levels in patients with PE may have prognostic value in determining the outcome of pregnancy in this pregnancy disorder.
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PMID:Plasminogen activators, plasminogen activator inhibitors and markers of intravascular coagulation in pre-eclampsia. 833 Jul 65

Timely initiation of thrombolytic therapy can achieve coronary reperfusion, a reduction in infarct size, a preservation of left ventricular function and a reduction in mortality. It is therefore an established procedure in acute myocardial infarction. The major drawback is an increased rate of bleeding. As a consequence thrombolytic therapy is at present withheld from many patients with contraindications. Other problems include relative inefficacy of presently available thrombolytic agents and early reocclusion of primarily successfully reperfused vessels. New approaches to optimize the risk/benefit ratio for the patient and to make thrombolytic therapy available to more patients include new antithrombin and antiplatelet agents as adjunctive therapy, synergistic combinations of plasminogen activators, mutants of t-PA and prourokinase, chimeric molecules and antibody-targeted thrombolysis.
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PMID:[Thrombolytic therapy of acute myocardial infarct--current status and new developments]. 833 27

A recent report described a thrombin inhibitory activity in the soluble fraction of human placenta and the cytosolic fraction of K562 cells. Isolation and characterization of the functionally inactive 35-38-kDa placental form of this protein revealed that it was a novel serine proteinase inhibitor (Coughlin, P. B., Tetaz, T., and Salem, H. H. (1993) J. Biol. Chem. 268, 9541-9547). In the present study, we observed a 67-kDa sodium dodecyl sulfate (SDS)-stable complex when 125I-thrombin was incubated with the cytosolic fraction of a monkey kidney epithelial cell line, BSC-1. This complex was not observed in either the particulate cell fraction extracted with 0.2% Triton X-100 or medium conditioned by cells, suggesting that the thrombin-complexing factor is confined to the cytoplasm. The cytoplasmic antithrombin activity was purified to apparent homogeneity from the cytosol of BSC-1 cells previously pulsed with [35S]methionine by a combination of heparin-agarose chromatography, Mono Q fast protein liquid chromatography, and anhydrotrypsin-Affi-Gel 10 affinity chromatography. Analysis of the affinity-purified preparation by SDS-polyacrylamide gel electrophoresis and fluorography revealed a single protein with an apparent molecular mass of 38 kDa. The purified 38-kDa protein inhibited the amidolytic activities of thrombin, trypsin, urokinase, and factor Xa but not that of elastase. Incubation of the 38-kDa protein with excess thrombin identified approximately 60% of the labeled 38-kDa protein in an SDS-stable 67-kDa complex. The purified 38-kDa inhibitor was cleaved with cyanogen bromide and the isolated peptides subjected to microsequencing. Amino acid sequence obtained for a region within this protein exhibited significant homology with human antithrombin III and plasminogen activator inhibitors 1 and 2. This homologous peptide contained the full complement of residues designated as highly conserved in helix F of the greater serine proteinase inhibitor superfamily. In addition, an internal sequence of GGGGDIHQGF was found in the monkey cytoplasmic inhibitor, which is identical to that reported for an internal sequence of the human placental inhibitor. These findings confirm the existence of a novel cytoplasmic serine proteinase inhibitor in mammalian cells and provide additional details of its molecular properties. The physiological function of this novel serine proteinase inhibitor in cytoplasm is unknown.
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PMID:Isolation and characterization of an intracellular serine proteinase inhibitor from a monkey kidney epithelial cell line. 840 7

In order to predict a hypercoagulable state in patients with advanced breast cancer receiving medical treatment, the effects of chemoendocrine therapy on the coagulation-fibrinolytic systems were investigated prospectively. The patients were randomly divided into two groups. The ACT group had 38 patients, who received 20 mg/m2 adriamycin (ADM) i.v. on days 1 and 8, 100 mg cyclophosphamide (CPA) p.o. on days 1-14, and 20 mg tamoxifen (TAM) p.o. daily. The ACM group had 44 patients, who received 20 mg/m2 ADM i.v. on days 1 and 8, 100 mg CPA p.o. on days 1-14 and 1200 mg medroxyprogesterone acetate (MPA) p.o. daily. The treatment was repeated every 28 days until there was evidence of progressive disease or until the full ADM dose (550 mg/m2) had been given. The following 9 hematologic parameters were measured every 4 weeks: alpha 2-plasmin inhibitor plasmin complex (PIC), anti-thrombin-III (AT-III), D-dimer (Dd), fibrinogen (Fg), plasminogen (Pg), protein C (PC), thrombin-antithrombin-III complex (TAT-III), tissue plasminogen activator (t-PA), and factor X (FX). Compared to the ACT group, patients in the ACM group showed significantly higher values of AT-III and PC, which exceeded the normal ranges. The levels of Pg, t-PA and FX were significantly higher in the ACM group than in the ACT group, but were still within the normal ranges. The levels of TAT-III, Dd and PIC decreased in the ACT group and were unchanged in the ACM group after the start of treatment. Fg remained unchanged in both groups after the start of treatment. One patient in the ACM group had thrombophlebitis of the lower extremities with high levels of TAT-III, Dd and PIC and a decrease of Fg, but her condition returned to normal after reduction of the MPA dose. Although these data are not directly indicative of a hypercoagulable state in patients receiving chemoendocrine therapy, changes in AT-III, TAT-III, Dd and PIC should be monitored carefully when this type of treatment is given.
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PMID:Effects of chemoendocrine therapy on the coagulation-fibrinolytic systems in patients with advanced breast cancer. Japan Advanced Breast Cancer Study Group and Japan Clinical Oncology Group. 851 13

Deep vein thrombosis may begin during surgery with the tourniquet inflated. Arterial levels of fibrinopeptide A, thrombin-antithrombin complexes, D-dimer, tissue plasminogen activator (t-PA) activity, and t-PA antigen were measured before surgery, during surgery with the tourniquet inflated, and following deflation of the tourniquet in 12 patients undergoing total knee arthroplasty. Minimal increases in fibrinopeptide A, thrombin-antithrombin complexes, and D-dimer were noted during surgery with the tourniquet inflated, but significant increases occurred immediately following deflation of the tourniquet. In 10 patients, intravenous heparin administration significantly suppressed the rise in fibrinopeptide A, but did not significantly alter the increases in either thrombin-antithrombin complexes, D-dimer, t-PA antigen, or t-PA activity. This study provides further evidence that deep vein thrombosis begins during surgery.
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PMID:Changes in circulatory indices of thrombosis and fibrinolysis during total knee arthroplasty performed under tourniquet. 852 13

The aim of the study was to determine the haemostatic components activity of organs in declamping shock. The abdominal aorta was cross-clamped below or above renal arteries. No significant changes in tromboplastic and antithrombin activities were found in the kidney, liver, lung, heart and skeletal muscle. Renal cortex and medulla as well as the lungs show higher plasminogen activator activity and considerably higher antiplasmin activity. Diminished fibrinolysis in the kidney and the lung may promote thrombotic complications.
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PMID:Hemostatic activity of organs in declamping shock. 852 87

We investigated hemostatic abnormalities in 37 patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) (PE patients) and in 40 patients with DVT without PE (DVT patients). Plasma fibrinogen, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex, fibrin-D-dimer, activated protein C (APC)-protein C inhibitor (PCI) complex, von Willebrand factor (vWf), tissue plasminogen activator (t-PA), PA inhibitor-I (PAI-1), and thrombomodulin levels in both PE and DVT patients were significantly increased compared with normal volunteers. Plasma APC-PCI complex, PAI-1, and vWf levels in PE patients were significantly higher than those in DVT patients without PE. These findings indicate that PE patients are more hypercoagulable and hypofibrinolytic than DVT patients. Plasma TAT, APC-PCI complex, PAI-1, and vWf levels were the most sensitive indicators for PE. In these patients, increases in TAT and APC-PCI complex suggest DVT and increased PAI-1 and vWf suggest the risk of onset of PE.
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PMID:Hemostatic abnormalities in patients with pulmonary embolism compared with that in deep vein thrombosis. 856 33

Beside the direct inhibition of thrombin and its regulatory functions, many of the newer antithrombin agents produce several additional effects, unrelated to their anticoagulant actions. Synthetic peptide inhibitors are capable of producing fibrinolytic compromise by virtue of their actions on fibrinolytic enzymes such as t-PA, plasmin, urokinase and protein Ca. In addition, the low molecular weight arginine-containing peptides are also known to produce hemodynamic and hemostatic deficits. The designs of the ongoing clinical trials are largely empirical because of the non-availability of valid pharmacologic and toxicologic data on thrombin inhibitors. In contrast to heparin, none of the thrombin inhibitors produce endogenous release of tissue factor pathway inhibitor (TFPI) in the experimental and clinical settings. These observations suggest that beside the direct inhibition of thrombin, these agents also produce multiple additional effects that can significantly contribute to their pharmacologic and toxicologic profile.
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PMID:Comparative pharmacology of site directed antithrombin agents. Implication in drug development. 857 9

Abnormal cytokine levels have been described in patients with chronic liver disease, but studies correlating cytokine homeostasis with abnormalities in coagulation and fibrinolysis are lacking. In order to establish a link between cytokines and the hemostatic changes the following parameters were determined in 44 patients with cirrhosis (alcoholic = 15, postnecrotic = 22, others = 7): TNF-alpha, IL-6, thrombin-antithrombin (TAT) complexes, prothrombin fragment 1 + 2 (F1 + 2) and t-PA by using enzyme-linked immunosorbent assays, and PAI-1, plasminogen and alpha 2-antiplasmin (alpha 2-AP) by using chromogenic substrates. All patients were at stages B and C of Child's classification when entering the study. Mean cytokine concentrations were significantly higher in cirrhotic patients as compared to age- and sex-matched controls (p < 0.009). There was a significant increase of TAT (p < 0.02) and F1 + 2 (p < 0.001) in the patients groups, suggesting a grade of intravascular coagulation. A hyperfibrinolytic state as demonstrated by an increase of t-PA and decrease of plasminogen and alpha 2-AP was also observed (p < 0.001). We could define a subgroup of patients with cytokine values higher than 20 pg/ml. Interestingly, in this group there was a significant increase of TAT (p < 0.04) and t-PA (p < 0.02) levels and a decrease of plasminogen and alpha 2-AP (p < 0.02) as compared to values observed in patients with cytokines lower than 20 pg/ml. We conclude that high levels of TNF-alpha and IL-6 may contribute to hyperfibrinolysis and intravascular coagulation in patients with liver cirrhosis, as assessed by the increase of TAT and t-PA levels and the reduction of plasminogen and alpha 2-AP.
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PMID:Increased concentrations of tumor necrosis factor and interleukin-6 contribute to the hemostatic abnormalities in advanced liver disease. 858 22

To examine whether exercise-induced thrombin formation is accompanied by increased in vivo plasmin formation, we measured molecular markers and neoantigens of the hemostatic system in 10 male subjects (mean 29 yr. range 19-38) before, immediately after, and 2, 8, and 21 h after a triathlon lasting 128-163 min. Thrombin-antithrombin (TAT) complexes, fibrinopeptide A (FPA), and tissue plasminogen activator (t-PA) antigen were maximally increased immediately after exercise and decreased thereafter rapidly. Prothrombin fragment 1 + 2 (PTF1 + 2), fibrin degradation products (FbDP) and plasmin-antiplasmin (PAP) complexes rose to a similar extent 0 and 2 h after exercise decreased thereafter. The maximal levels of PTF1 + 2, TAT, FPA, and FbDP were 1.5-, 2.1-, 1.8-, and 1.9-fold above baseline, respectively. This investigation shows that strenuous prolonged exercise leads to a moderate activation of blood coagulation resulting in thrombin and fibrin formation which is accompanied by a greatly enhanced plasmin generation. It is concluded that the hemostatic of healthy individuals is well kept in balance when stimulated by prolonged strenuous exercise.
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PMID:Balanced activation of coagulation and fibrinolysis after a 2-h triathlon. 858 81


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