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)

HTC cell variants chosen for their lack of tyrosine aminotransferase (EC 2.6.1.5) (TAT) induction by glucocorticoids were tested for interrelated effects on other glucocorticoid responses: TAT induction by dibutyryl cyclic AMP (dBcAMP) +/- dexamethasone, glutamine synthetase (GS) induction, cyclic nucleotide phosphodieterase (PDE) suppression, inhibition of alpha-aminoisobutyric acid (AIB) uptake, inhibition of plasminogen activator (PA), and induction of mouse mammary tumor virus (MTV). Loss of TAT induction by steroid was accompanied by loss of TAT induction by dBcAMP and of PDE suppression by steroid. In addition, subclones of MTV-infected cells were examined for the effect of the virus on glutamine synthetase (GS) and TAT induction. The virus had no effect on their induction in wild-type cells and no effect on GS induction in the variants. One MTV-infected subclone from a TAT variant, however, showed significant return of TAT induction.
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PMID:Unlinked control of multiple glucocorticoid-induced processes in HTC cells. 3 58

Medroxyprogesterone acetate (MPA), which is widely used clinically as an anticancer steroid preparation, is a very useful drug that seldom causes severe side effects such as bone marrow suppression, and can be dispensed at the outpatient clinic for an oral administration at home to the advantage of QOL. Recently however, there have been several reports suggesting its relationship with thrombosis. We measured t-PA, protein C, factor X, AT III, TAT, plasminogen, PIC, fibrinogen, and D-dimer in 11 patients with gynecologic malignancies who are treated with MPA (600 mg/day) and 11 controls. Then we examined the effects of the drug on blood coagulation and fibrinolytic activities. No changes in these parameters clearly suggested thrombogenesis in either group at this measurement or during the observation period (17 months at the maximum). The present study found no remarkable abnormalities in the blood coagulation and fibrinolytic activities. Thus, to avoid the use of MPA to patients at risk is considered to be the most important precaution for prevention of thrombosis.
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PMID:[Effect of high-dose medroxyprogesterone acetate on coagulative and fibrinolytic factors in patients with gynecological cancers]. 153 83

We examined the hemostatic abnormality of liver disease using hemostatic molecular markers, i.e. TAT, FPA and SFMC for coagulation, B beta 15-42, FDP, D dimer and PIC for fibrinolysis, t-PA and TM for vessel wall. The molecular markers for coagulation were generally increased in cases of liver disease, which was most sensitively reflected by FPA. On the other hand, it was postulated that SFMC was a marker reflecting the complication of DIC in these cases. Hyperfibrinolysis of liver disease was sensitively reflected by the increase of B beta 15-42, and an occasional increase of SFMC or FDP was thought to indicate the complication of DIC in these cases. A high correlation was found between t-PA and TM. It was postulated that the increase of the both markers in liver disease was due to deteriorated clearance by liver dysfunction, although TM is regarded as a marker reflecting endothelial injury. It was expected that visualization of hemostatic disorder of liver disease was made practical with the use of radar chart of these molecular markers.
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PMID:[Analysis of hemostatic abnormality in various disease using molecular-I. Liver disease]. 182 41

Patients received 2,000 ml of dialysate intraperitoneally with five exchanges per day during continuous peritoneal dialysis (CAPD) for the treatment of terminal renal insufficiency. During a dwell time of 4 h the dialysate reached a total protein concentration up to 100 mg/dl by mass transfer of intravascular proteins. The composition is dependent on the molecular weight of the proteins. This results in an intraperitoneal hemostatic system of low concentration and different composition. We found an intraperitoneal fibrinogen cleavage and thrombin-antithrombin III-complex formation leading to increased levels of fibrinopeptide A (FPA: 33.3 +/- 7.0 ng/ml) and thrombin-antithrombin III-complex (TAT: 4.7 +/- 0.4 ng/ml) in plasma by mass transfer from dialysate to plasma. t-PA (tissue plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) concentrations in plasma were within the normal range. The dialysate concentrations indicated a low local secretion. The fibrinolytic fibrin fragment D-dimer and the fibrinogen degradation product concentrations in plasma were greater than in dialysate. But the relations of the proteins between plasma and dialysate refer to a local intraperitoneal production as well. The results show that intraperitoneal coagulation predominates over fibrinolysis which is accompanied by an intravascular fibrinolysis in patients undergoing CAPD. Neoantigens produced in dialysate and diffused to plasma are comparable to changes seen in disseminated intravascular coagulation.
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PMID:Relation of intraperitoneal and intravascular coagulation and fibrinolysis related antigens in peritoneal dialysis. 220 48

Indicating activation of coagulation fibrinopeptide A (FPA) was elevated in 80.1% (mean = 10.5 ng/ml; P less than 0.01) and thrombin-antithrombin III complexes in 58.3% (TAT; mean = 5.3 ng/ml; p less than 0.05) in patients with adenocarcinomas (n = 57). In patients with non-Hodgkin's lymphomas (n = 30), however, elevation was observed only in 66.6% (FPA) and in 42.8% (TAT). Incidence of thrombosis is high only in the first group Local fibrinolysis explains elevated D-dimer in adenocarcinomas (1,818 ng/ml; p less than 0.01) and in non-Hodgkin's lymphomas (576 ng/ml; p less than 0.05). Significantly increased t-PA antigen was not committed by adequately increased t-PA activity in adenocarcinomas, because of high levels of the acute-phase protein, plasminogen activator inhibitor (mean = 25.3; p less than 0.01), indicating systemic hypofibrinolysis. Hemostatic disorder in patients with malignancy can be attributed to a combination of acute-phase reaction and an activation of coagulation.
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PMID:Investigations of coagulation system and fibrinolysis in patients with disseminated adenocarcinomas and non-Hodgkin's lymphomas. 221 92

The dramatic changes in morphology induced by nanomolar doses of tumor-promoting agents, especially in epithelial cells, have been noted previously (Driedger and Blumberg, 1980; Rifkin et al., 1979; Croop et al., 1980; Phaire-Washington et al., 1980; Ohuchi and Levine, 1980; Ojakian, 1981; Fey and Penman, 1984). This chapter shows the effect of the tumor promoter TPA on the underlying skeletal framework, which is involved in the maintenance of both cell and epithelial tissue morphology. It should be emphasized, however, that similar results are obtained for all the tumor promoters as well as for the complete, ultimate carcinogens examined so far. The organization of the cytoskeletal elements involved in these morphological changes is faithfully retained during the fractionation procedure employed here, as is evident from SEM and TEM analysis of Triton-extracted cells. A number of promoting agents have been compared, and the degree of disorganization viewed in these whole mounts appears to parallel the potency of the promoting agents as measured by other assays (Fey and Penman, 1984). Also, the inactive analogues of phorbol ester have no effect on cell structure (Rifkin et al., 1979; Ojakian, 1981; Fey and Penman, 1984). We suggest that the effect of TPA on the cytoskeleton occurs early as compared with many of the commonly studied biochemical responses and may indeed underlie many of the previously described cellular response to promoting agents, such as mitogenic stimulation. TPA-induced alterations in NM-IF scaffold occur in the absence of both protein and RNA synthesis (Fey and Penman, 1984). By contrast, plasminogen activator, stimulated by TPA (Wigler and Weinstein, 1976), is completely blocked by pretreatment with both cycloheximide and actinomycin D (Weinstein et al., 1977; Ojakian, 1981). Ornithine decarboxylase, another enzyme that is rapidly induced by tumor promoters, is inhibited by both cycloheximide and actinomycin D in the presence of TPA (O'Brien, 1976). Thus two of the early biochemical markers for tumor-promoter activity are separable from the induction of cytoskeletal alterations by TPA. One of the most striking features of the response to promoting agents is the adoption of the transformed phenotype, in which cells lose growth control and cease being organized into meaningful tissue structure. The alteration of desmosomal and junctional associations and the concomitant change in cytokeratin organization are clearly related to the breakdown of epithelial organization. The phenotype is completely reversible although it takes about 3 days for the mode line to reestablish normal morphology (data not shown).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The morphological oncogenic signature. Reorganization of epithelial cytoarchitecture and metabolic regulation by tumor promoters and by transformation. 307 72

A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo-controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans.
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PMID:Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23). 778 Jan 31

Human hepatocyte growth factor (hHGF) has considerable sequence homology with plasminogen and both proteins can be activated by plasminogen activators. The aim of this study was to investigate the relationship between plasma hHGF and fibrinolysis in patients with fulminant hepatic failure (FHF), in whom proteases of coagulation are known to be activated and hHGF levels have been shown to be raised as a consequence of hepatic regeneration. Serum hHGF measured by ELISA was increased in FHF (median 6.67 ng/ml, range 1.2-62 ng/ml), but the values did not correlate with the decreased plasminogen level (median 9%., range 0.7-35.5%) or the level of t-PA which was normal. There was a significant correlation between serum hHGF and increased plasma D-dimer (median 2,163 microgram/l, range 39-7 311 microgram/l), produced by the action of plasmin on fibrin and increased plasma thrombin-antithrombin III complexes (TAT, median 31.7 microgram/l, range 3.7-105 microgram/l). These relationship could be indicative of an involvement of blood coagulation, possibly a specific serine protease, in hHGF activity. After liver transplantation, plasma hHGF was rapidly cleared to almost normal levels, whereas D-dimer and TAT continued to be at elevated levels.
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PMID:Hepatocyte growth factor and plasminogen activation in fulminant hepatic failure. 784 6

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

The effects of moderate 30 min cycle ergometer exercise (aerobic metabolism; 0.85-3.71 mmol.1(-1) lactate) followed by short-term exercise at maximal capacity (anaerobic metabolism; 5.09 to 17.75 mmol.1(-1) lactate) on endothelin (ET) and hemostatic variables (tissue plasminogen activator [t-PA] antigen, prothrombin fragments [F1,2], thrombin-antithrombin III complex [TAT], prothrombin time and partial thromboplastin time) were investigated in 15 male healthy subjects of varying fitness levels. Endothelin was measured twice before and immediately after maximal cycle exercise. The results show an increase in endothelin concentration [10.0 pg.ml-1 (baseline) + 6.1 pg.ml-1 (increase post exercise)]. ET did not increase under control conditions. Moderate 30 min exercise caused an increase in t-PA antigen concentration (3.66 + 3.15 ng.ml-1) and short-term maximal exercise produced a markedly higher elevation in this variable (+10.6 ng.ml-1). F1,2 increased (810 + 40 pmol.l-1) under moderate and by 150 pmol.l-1 under anaerobic exercise. TAT increased only at maximal exercise levels (1.01 + 0.32 ng.l-1). No changes were found in any of these variables under control conditions. No correlation of endothelin and the hemostatic variables was found. It is concluded that endothelin and hemostatic markers increase independently during moderate and maximal exercise.
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PMID:Influence of maximal ergometric exercise on endothelin concentrations in relation to molecular markers of the hemostatic system. 874 88


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