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)

Tumor plasminogen activator (PA) has been alleged to play a role in the growth and metastasis of tumors. Before such a role can be realized, PA first must be released from tumor cells. Having determined intra- and extracellular PA and PA-inhibitor activities in an experimental pancreatic ascites tumor grown in hamsters, the release of PA from these cells was investigated. No PA activity was detected in the suspension medium of freshly isolated tumor cells; inclusion of plasminogen, fibrinogen, or collagen in the medium yielded similar negative results. On the other hand, PA activity was demonstrated to be released in a time-dependent manner from these tumor cells embedded in fibrin clots. Plasminogen activator activity also was not found in the suspension medium of frozen-thawed tumor cells, despite the fact that most of them had breaks on their cell membrane. Unlike freshly isolated tumor cells, PA was not released from frozen-thawed cells embedded in fibrin clots. Full PA activity was demonstrated in frozen-thawed cells treated with Triton X-100, however. Frozen-thawed cells exhibited signs of severe damage, and more than 80% of them failed to exclude trypan blue. Obviously PA is released from viable tumor cells embedded in fibrin clots but not suspended in artificial medium. The PA-release mechanism, not PA itself, is destroyed in cells rendered nonviable by freeze thawing.
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PMID:Importance of viability and attachment to an ascites tumor in the release of plasminogen activator. 190 26

We studied the effects of urokinase (UK), pro-urokinase (pro-UK), and recombinant tissue-type plasminogen activator (rt-PA) on platelet aggregation and the production of thromboxane A2 (TXA2) in vitro. Both UK and pro-UK inhibited the platelet aggregation induced by adenosine 5'-diphosphate (ADP), collagen, or thrombin in a concentration-dependent manner. In contrast, although a low dose of rt-PA (5 to 10 x 10(4) U/ml) blunted platelet aggregability, a high dose (40 to 60 x 10(4) U/ml) led to platelet hyperaggregation. UK and pro-UK markedly inhibited TXA2 synthesis during ADP-induced platelet aggregation. Despite the significant reduction of TXA2 synthesis by 10 x 10(4) U/ml rt-PA, a concentration of 60 x 10(4) U/ml rt-PA had no effect on synthesis. These results indicate that UK and pro-UK each inhibit platelet function, but a high concentration of rt-PA enhances platelet aggregability. This finding may at least in part contribute to the high incidence of reocclusion after initially successful thrombolysis with rt-PA.
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PMID:Possible mechanism of vascular reocclusion after initially successful thrombolysis with recombinant tissue-type plasminogen activator. 190 79

Recently it has been reported that cell-mediated immune (CMI) reaction is related to the blister formation as well as the reaction of autoantibody against the basement membrane zone (BMZ-Ab) in bullous pemphigoid (BP). Previously we reported that T-cells infiltrated were producing gamma-interferon (IFN-gamma) and that high levels of IFN-gamma were detected in the blister fluids of BP. In the present study, in order to find the effect of IFN-gamma on the skin, we have done the organ culture of normal skin explants with IFN-gamma. The dermal-epidermal separation (DES) was histologically observed in skin explants which were incubated with high level of IFN-gamma after 24 hours. The DES was found to be located between the basal layer and the site of laminin and type IV collagen. It is considered that IFN-gamma alters the antigenicity and mediates to release some other cytokines in CMI reaction. In addition to these, IFN-gamma seems to directly work on the DES in normal skin. Around the DES of the skin explants, plasminogen activator was accelerated immunohistologically. The results suggest that IFN-gamma mediated by CMI response also plays an important role as well as the autoantibody in the blister formation of BP.
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PMID:[The role of gamma-interferon in blister formation of bullous pemphigoid]. 190 56

The aim of this study was to evaluate the effects of a preparation of low molecular weight heparan sulphate (LMW-HS) on the fibrinolytic system. Twenty-five healthy volunteers received LMW-HS by mouth in three separate experiments. In the first experiment, 10 volunteers received either 80 mg LMW-HS or placebo in a single-blind cross-over study; blood samples were taken before and 1, 2, 3 and 6 h after treatment. LMW-HS caused an increase in global fibrinolysis, the effect being greatest after 2-3 h and disappearing by 6 h. However, neither plasminogen activator activity nor tissue-type plasminogen activator (tPA) antigen levels were changed. In the second experiment, daily doses of 80 mg LMW-HS were administered to 10 volunteers for 7 days; this regimen did not produce a statistically significant increase in fibrinolytic activity for the whole group although some individuals did respond markedly. In the third experiment, 160 mg LMW-HS administered to five volunteers did not affect ADP- and collagen-induced platelet aggregation. In vitro, LMW-HS added to plasma at concentrations of 20 and 30 micrograms/ml, brought about a significant increase in apparent plasminogen activator activity. These results suggest that the increased fibrinolytic activity seen after LMW-HS is due to the recruitment of additional amounts of tPA in the ex vivo test system. LMW-HS had no effect on plasminogen activator inhibitor.
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PMID:In vivo and in vitro effects of low molecular weight heparan sulphate on the human fibrinolytic enzyme system. 193 31

Because platelets and muscle cells share the same contractile proteins--actin and myosin--platelets may serve as a model for muscle research. To study the functional abnormalities and ultrastructural changes of platelets and to determine whether or not abnormalities in muscle contractile proteins and collagen play an important role in the pathogenesis of idiopathic scoliosis, the bleeding time, the platelet aggregation test, and the titers of platelet plasminogen activator inhibitors were measured and the electron microscopic findings were examined in 52 idiopathic scoliosis patients aged 7 to 28 years and in 49 normal individuals aged 8 to 38 years as a control group. We found no statistically significant difference between the two groups in the bleeding time, the platelet aggregation test, and the titers of platelet plasminogen activator inhibitors. In the electron microscopic findings, no specific abnormalities were found in platelets of idiopathic scoliosis patients. We concluded that idiopathic scoliotic patients have normal morphology and function of platelets, and there is no important role of contractile proteins in the pathogenesis of idiopathic scoliosis. In addition, since the bleeding time was in the normal range, no evidence of subendothelial collagen dysfunction was found in the idiopathic scoliosis patients.
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PMID:A study on platelet function in idiopathic scoliosis. 194 44

We evaluated the effect of the RGD-containing peptide, echistatin, on thrombolysis time and acute reocclusion in a canine model of coronary thrombosis/thrombolysis. Occlusive thrombus formation was induced by electrical injury, via a stimulating electrode, to the endothelial surface of the circumflex coronary artery in the open-chest, anesthetized dog in the presence of a critical stenosis. Fifteen minutes after occlusive thrombus formation, dogs received either an intravenous infusion of vehicle (saline at 0.1 ml/min) or echistatin (15 micrograms/kg/min i.v.). Heparin was given as an initial bolus (100 U/kg i.v.) 15 min after thrombus formation and repeated at hourly intervals (50 U/kg). This dose of heparin increased activated partial thromboplastin time to 1.5- to 2.5- fold over control. Thrombolysis was induced with recombinant tissue-type plasminogen activator (tPA) at a total dose of 1 mg/kg, intravenously administered over 90 min with 10% given as an initial bolus. The vehicle-treated animals reperfused at 48 +/- 9 min with a reperfusion incidence of 60% (3/5). The echistatin-treated animals reperfused at 46 +/- 5 min with a reperfusion incidence of 100% (5/5). After stopping the tPA infusion, acute reocclusion occurred in 100% (3/3) of the vehicle-treated dogs and in only 20% (1/5) of the echistatin-treated dogs. Echistatin caused a greater than 5-fold increase in buccal mucosa bleeding time and almost completely inhibited ex vivo platelet aggregation to ADP, collagen, and U-46619. Residual thrombus wet weight, determined at the end of the experiment, was significantly lower for the echistatin group (2.1 +/- 0.2 mg) compared to the vehicle group (5.8 +/- 0.7 mg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of reocclusion following tissue type plasminogen activator-induced thrombolysis by the RGD-containing peptide, echistatin, in a canine model of coronary thrombosis. 194 98

The kinetics of activation of Glu-plasminogen (Glu-Pg) and Lys77-Pg by two-chain recombinant tissue plasminogen activator (t-PA) were determined in the presence of isolated protein components of the extracellular matrix (ECM) and compared to activation in the presence of fibrinogen and fibrinogen fragments and in the absence of added protein. Several ECM protein components were as effective as fibrinogen fragments at stimulating Pg activation. Stimulation of Glu-Pg activation resulted from both a decrease in Km and an increase in Vmax, whereas stimulation of Lys77-Pg was due primarily to increases in Vmax. The most effective stimulators of activation were basement membrane type IV collagen and gelatin which resulted in a 21- and 55-fold increase, respectively, in the kcat/Km of Glu-Pg (relative to a 10-fold increase observed with fibrinogen fragments). Amidolytic activity of t-PA was also enhanced up to 12-fold by ECM proteins. However, plasmin amidolytic activity was unaffected by the presence of added proteins. These data suggest that several ECM-associated proteins can enhanced the activation of Pg in the absence of fibrin.
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PMID:Regulation of plasminogen activation by components of the extracellular matrix. 211 70

The sequelae of thrombus formation, both by shear forces and by collagen fiber, the subsequent coagulation, and the dislodgement of thrombi (thrombolysis) were measured from a small volume of nonanticoagulated blood sample, by a new instrument. Addition of streptokinase (SK) or tissue-type plasminogen activator (rt-PA) to the blood sample eliminated the need for anticoagulation for thrombolysis measurement: clot lysis preceded and allowed thrombolysis to occur. The test revealed activation of platelets and coagulation by SK and rt-PA. Apart from this general trend, platelet reactivity in response to plasminogen activator showed great individual variation. Whether the greatly enhanced (42%) or prolonged hemostasis (13%), observed in different blood samples with rt-PA, could be used as a predictor of reocclusion or bleeding complications remains to be established. Thrombolysis did not occur in 12% of the samples tested. These thrombolysis models may be useful for developing new agents for the dissolution of platelet-rich thrombi. It is suggested that this technique be used for monitoring thrombolytic therapy.
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PMID:Simultaneous measurement of all thrombosis parameters from native human blood: usefulness in monitoring efficacy and complications of thrombolytic therapy. 212 Oct 73

Plasma levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) and the in vitro ability of platelets to aggregate and of monocytes to express procoagulant (tissue factor) activity (PCA) were evaluated in five patients who are homozygous for familial hypercholesterolemia (FH) before and after a single and a regular 5-month cholesterol removal by low density lipoprotein (LDL) apheresis. The biweekly procedure resulted in a 25% to 30% reduction (approximately 150 mg/dl) in total and LDL cholesterol (both were greater than 550 mg/dl at the beginning of the study). The basal levels of t-PA antigen and fibrinolytic activity before and after 10 minutes of venous stasis, basal PAI activity, and PAI-1 antigen were comparable to controls and were not affected by LDL apheresis. Likewise, regardless of the cholesterol removal, the PCA of freshly isolated monocytes and that of monocytes incubated with lipopolysaccharide did not differ from control values. Finally, the pre-apheresis sensitivity of platelets to adenosine diphosphate, arachidonic acid, and collagen was 1.5 to 2 times the normal value. This ratio was unchanged throughout the 5-month procedure. We conclude that fibrinolysis and monocyte PCA are normal in FH patients, whereas platelet aggregation is abnormally high, and none of these parameters is significantly affected by a 25% to 30% reduction in total and LDL cholesterol by LDL apheresis. Furthermore, our data suggest that removal of cholesterol from plasma by LDL apheresis is important for gaining insight into the mechanisms involved in the ischemic complications of arteriosclerosis in FH patients.
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PMID:Hemostatic variables in homozygous familial hypercholesterolemia. Effect of regular plasma cholesterol removal by low density lipoprotein apheresis. 212 91

SK, t-PA or APSAC were incubated in human plasma (adjusted to 300,000 platelets/mm3), in vitro, for up to 90 minutes using concentrations which were equivalent to those achieved in the treatment of AMI patients. Aggregation was measured in response to ADP and collagen. SK inhibited platelet aggregation after a 60 minute incubation. t-PA was less inhibitory and significant effects were only achieved on extended incubation with a higher concentration of activator. APSAC markedly inhibited platelet aggregation in response to both ADP and collagen and the inhibition was achieved earlier than with SK. The difference in temporal response between APSAC and SK was not attributed to differences in systemic plasminogen activation. There was no influence of anti-SK antibody (IgG) on the platelet function response to APSAC or SK. Aspirin inhibited second phase aggregation induced by ADP but even in the presence of aspirin, the net inhibition of platelet aggregation was greater for APSAC than for SK. This marked effect of APSAC on platelet aggregation helps to explain the high initial patency and low re-occlusion rates seen when APSAC is administered to AMI patients.
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PMID:Comparison of the effects of streptokinase, t-PA and APSAC on human platelet aggregation in vitro in the absence and presence of aspirin. 212 20


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