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)

Although it has been previously considered that blood fibrinolytic capacity is reduced during pregnancy, this has been disputed. Also the mechanisms underlying any change in fibrinolysis in pregnancy require clarification. We have therefore measured the plasma activity of tissue plasminogen activator (t-PA) and inhibitors (t-PAi) and the concentration of the pregnancy specific inhibitor (PA12) antigen, as well as the euglobulin clot lysis time (ECLT) during normal pregnancy. Plasma concentrations of fibrinogen, plasminogen, fibrin(ogen) degradation products (FDP) and cross-linked products (D-dimer) were also monitored. We confirm a marked reduction of the fibrinolytic activity of the plasma euglobulin fraction from the second trimester, and a parallel reduction in t-PA and increase in t-PAi activities, with rapid return to non-pregnant levels post-partum. In contrast, PAI2, whilst undetectable in non-pregnant control plasma, was already measurable in the first trimester, increased through pregnancy, and remained at a high concentration up to at least 48 h post-partum. Fibrinogen and plasminogen concentrations rose progressively through pregnancy and FDP and D-dimer were frequently detectable in late pregnancy plasma. Changes in the ECLT and plasma t-PA and t-PAi activities in pregnancy cannot therefore be directly related to the concentration of PAI2 antigen. Also, despite the apparent marked reduction in fibrinolytic capacity fibrin(ogen) breakdown products are frequently present in increased plasma concentrations in late pregnancy.
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PMID:Fibrinolysis during normal human pregnancy: complex inter-relationships between plasma levels of tissue plasminogen activator and inhibitors and the euglobulin clot lysis time. 313 43

Development of appropriate clinical dose regimens of individual plasminogen activators such as tissue-type plasminogen activator (t-PA) has generally relied primarily on nonpharmacological endpoints such as angiographically documented clot lysis. The recent availability of monoclonal antibodies that differentiate products of plasmin lysis of fibrin from those of lysis of fibrinogen should permit delineation of the relative fibrin specificity of different plasminogen activators or of different doses of the same activator in vivo. Thus, their use should accelerate and facilitate development of implementation of optimal dose regimens for diverse activators and combinations of activators. The present study was designed to determine whether assay of such markers effectively differentiates effects of two doses of t-PA, each of which are comparably effective in opening infarct-related arteries, in patients studied at the Washington University Clinical Unit of the National Institutes of Health-sponsored Thrombolysis in Myocardial Infarction Trial. The extent of lysis of fibrin and of lysis of fibrinogen by plasmin resulting from administration of t-PA was evaluated in 19 patients given 150 mg t-PA over 6 hours and 17 given 100 mg over the same interval by assay of serially obtained plasma samples for crosslinked fibrin degradation products (XL-FDP) and B beta 1-42, a peptide released when fibrinogen is degraded to fragment X by plasmin. XL-FDP were markedly elevated after 6-hour infusions of both doses of t-PA. However, elevations were not more with the higher dose [peak value, 4,321 +/- 986 ng/ml (+/- SEM)] compared with the lower dose (3,397 +/- 1,096 ng/ml) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization in vivo of the fibrin specificity of activators of the fibrinolytic system. 313 54

Levels of alpha 2PI-plasmin complex and tissue-type plasminogen activator (t-PA) in plasma were determined in 10 cases of acute promyelocytic leukemia (APL) with marked coagulopathy and in 10 cases of hematological malignancies with DIC to investigate relevance to fibrinolysis. In the both groups, levels of alpha 2PI-plasmin complex increased and were inversely proportional to levels of fibrinogen and alpha 2PI. Levels of t-PA in plasma increased moderately in the majority of the both groups. Serial observation of the concentrations of t-PA with corresponding changes in the levels of fibrinogen, alpha 2PI, alpha 2PI-plasmin complex and FDP could not demonstrate any significant relationship between levels of t-PA and the other parameters. From these results, it is unlikely that levels of t-PA in plasma directly influence on the degree of consumption of alpha 2PI or of formation of alpha 2PI-plasmin complex in most cases of DIC.
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PMID:Changes in levels of t-PA and alpha 2PI-plasmin complex in plasma in patients with DIC. 314 64

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

Plasminogen is said to be synthesized in many organs, but the major source of its production is considered to be the liver. The production of plasminogen is observed in fetal life, but its plasma level is low in new born infants, rising rapidly to attain adult levels in about 13 weeks. The plasma levels do not change much with age. Although the fibrinolytic enzyme system is influenced by many factors such as hormones, exercise, emotion, age, sex, nutritional states etc., the plasma levels of plasminogen are relatively stable. In this presentation we would like to discuss three important subjects related to the physiology of plasminogen. The first subject is the activation pathway of the native form of plasminogen (Glu-plg) by various activators in the plasma or clotted plasma. Glu-plg was not easily activated by activators such as urokinase (UK) or tissue plasminogen activator (t-PA), but activated very easily in the presence of fibrin clot. In the presence of purified clot, Glu-plg was partly activated by activators to Glu-plasmin, but also converted to Lys-plg by preformed plasmin, subsequently being activated to plasmin. Glu-plg I (containing two carbohydrate chains) changed conformation more easily upon interaction with fibrin than Glu-plg II (containing one carbohydrate chain) and Glu-plg I was also more easily activated by activators than Glu-plg II. Although Glu-plg was hardly activated by activators in the plasma, Glu-plg was activated easily in the presence of plasma clot. Results of immunoblotting experiments indicated that Glu-plg was mainly activated by activators directly to plasmin, not via Lys-plg in contrast to purified systems. The second subject is the degradation of plasminogen by elastase. Plasminogen may be degraded by proteolytic enzymes such as cathepsin or elastase. The degradation of plasminogen by elastase is shown to give rise to K1 to K3, K4, and mini-plg (containing K5). We have shown that the degradation rate to Glu-plg by elastase increased in the presence of tranexamic acid, indicating that the conformational change of Glu-plg in the presence of tranexamic acid resulted in the exposure of the hydrophobic regions connecting K3, K4 and K5, thus making them accessible to elastase. Consequently, Lys-plg or conformationally altered Glu-plg (possibly bound to fibrin or FDP) is more easily degraded in vivo. The last subject is relationship between plasma plasminogen levels and fibrinolytic activity in various ages. Although plasma plasminogen levels do not change with age, the fibrinolytic activity lowers.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Physiology of plasminogen: with special reference to activation and degradation. 328 Apr 23

Balb/c mice were immunized with a mixture of fibrin degradation products (XDPs) prepared by complete lysis of a human blood clot by tissue-type plasminogen activator and purified by immunoaffinity chromatography. Spleen cells of the mice were fused with P3 X 63 Ag 8653 myeloma cells. A clone (FDP 14) was selected that produces monoclonal antibodies (MoAbs) of the IgG1 kappa type that react with a neoantigenic determinant exposed in these XDPs, but not in intact fibrinogen or in fibrin monomers. Furthermore, the MoAb is reactive with some pure, individual degradation products of fibrinogen (fragments X, Y, E, and the N-terminal disulphide knot) and with the fibrinogen B beta-chain but not with A alpha- and gamma-chains or with fragments D, FCB-2 and FCB-3. Comparison of the known primary structures of these fibrinogen fragments indicates that the stretch B beta 54-118 comprises at least an important part of the epitope recognized by FDP-14. Apparently, this stretch contributes importantly to a neoantigenic determinant that is not functional in intact fibrinogen and fibrin monomer and that can be made functional by reduction of fibrinogen, or by digestion with plasmin or CNBr.
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PMID:Production and characterization of a monoclonal antibody reactive with a specific neoantigenic determinant (comprising B beta 54-118) in degradation products of fibrin and of fibrinogen. 373 Jun 8

We have studied the involvement of fibrinolysis in acute rejection after kidney transplantation by analyzing changes in urinary levels of substances such as FDP, D-dimer, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI). Fibrinolytic activity was found to be low (that is, PAI is dominant) during acute rejection, and it was elevated (that is, PA became dominant) as acute rejection subsided. It appears that the dominance of PA leads to an increase in the products of fibrinolysis and an elevation in the D-dimer/FDP ratio, resulting in disappearance of the acute rejection. Based on these findings, we thought it necessary to administer t-PA to kidney recipients so that PA becomes dominant earlier and the acute rejection can be reduced. It is necessary for us to directly study the phenomena within the kidneys. Therefore, we recently conducted a histochemical study of the distribution of t-PA, Urokinase type PA (u-PA) and PAI in transplanted kidneys. Transplanted kidney, which functioned well or showed signs of acute or chronic rejection, were biopsied. These renal samples as well as control samples (biopsied from normal nongrafted kidney) were examined as to distribution of t-PA, u-PA and PAI by the indirect enzyme complement method. In conclusion, t-PA, u-PA and PAI were detected in the glomeruli, arterioles, tubule and interstices of the control kidneys, well functioning grafts, acutely rejected grafts chronically rejected grafts. All samples showed intense chromatic responses in the arterioles and part of the tubules. On the whole, the chromatic response tended to be more intense in the acute rejection group than in the other group.
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PMID:[Tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in transplanted kidneys]. 759 85

The changes in local lesion after high-voltage electric burns ares dependent on many factors. One of the important factors is the change in coagulation. In this paper, a high-voltage electrical burn model was reproduced in rabbits for the purpose of investigating the coagulation mechanism. It was found that AT-III and PC showed elevation and declination, respectively, at 6h and 12h postburn. PAI:A and t-PA:A also showed obvious changes, while FDP showed continuous elevation at 6h up to 5d postburn. The findings probable provided the explanation of the occurrence of thrombosis at 6h to 12h postburn, and the second episode of thrombosis on the 5th day.
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PMID:[Mechanism of changes in coagulation after electric burns in rabbits]. 772 8

Plasma thrombin-antithrombin III complex (TAT), FDP-D-dimer, activated protein C (APC)-protein C inhibitor (PCI) complex, and tissue type plasminogen activator (t-PA), PA inhibitor-1 (PAI-I) were significantly increased in patients with acute myocardial infarction (AMI) at onset. These patients exhibited a hypercoagulable state and protein C activation at onset. The plasma PCI level at onset of AMI was within the normal range, but was significantly decreased after percutaneous transluminal coronary angioplasty (PTCA). After PTCA, plasma t-PA, FDP-D-dimer, and plasmin-alpha 2-plasmin inhibitor were increased but APC-PCI complex and TAT were not. The decrease in PCI after PTCA may have been caused by the activation of fibrinolysis. PCI may play an important role in the inhibition of fibrinolysis in stimulated or damaged endothelial cells. These findings suggest that the protein C pathway plays an important role in the onset of AMI and after PTCA.
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PMID:Decreased protein C inhibitor after percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction. 774 Nov 29

Haemostatic measurements were undertaken in 132 patients diagnosed with heat stroke during the pilgrimage to Makkah, in two successive summers of 1989-90. The control group comprised 49 patients, all pilgrims, with a wide range of clinical conditions, but without hyperpyrexia or deranged haemostasis. Heat stroke patients showed (i) significant prolongation of the prothrombin (PT), activated partial thromboplastin (aPTT) and thrombin times (TT) but normal reptilase time (RT); (ii) significant reduction in plasma levels of antithrombin III (AT-III), factor V, proteins C and S, plasminogen activator inhibitor (PAI) and platelet count; (iii) increase in plasma factor VIII, tissue plasminogen activator (t-PA) and serum FDP; (iv) no significant changes in plasma fibrinogen, plasminogen, alpha 2-antiplasmin and factors VII and X. Heat stroke patients were then grouped into those with and those without bleeding symptoms. Bleeders showed greater prolongation of the PT, aPTT and TT and significant reductions in fibrinogen, AT-III, factors V, VIII and X, plasminogen, alpha 2-antiplasmin and platelet count. Logistic regression and discriminant analysis showed that AT-III was the parameter associated most with heat stroke and reliable enough to predict its occurrence, whether or not bleeding occurred. The results indicate that activation of the haemostatic mechanism, consumptive in nature, regularly accompanies heat stroke and highlights the physiological role of AT-III in checking this activation process.
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PMID:The coagulopathy of heat stroke: alterations in coagulation and fibrinolysis in heat stroke patients during the pilgrimage (Haj) to Makkah. 786 79


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