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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship of plasminogen activator (PA) production to cell stage, cell number and changes in overall diameter and zona pellucida thickness for bovine embryos developing in vitro was determined. Late morulae to blastocysts (n = 80) were collected nonsurgically from naturally mated, estrous-synchronized, superovulated crossbred beef cows. Embryos were cultured, one embryo per 25-microliters microdrop, for 6 d. At 24-h intervals, embryos were evaluated for stage of development and transferred to fresh microdrops; media were recovered for PA analysis. In addition, embryo diameter and zona pellucida thickness were measured with an ocular micrometer. Plasminogen activator production was determined using a caseinolytic assay with urokinase as the standard. Changes in diameter, zona pellucida thickness and PA production per 24-h interval for each embryo were plotted, and the graphs were cut out and weighed. Sixty-one embryos (76%) completed the hatching process. Total PA production was correlated positively (P less than .005) to embryonic size (r = .40), developmental stage (r = .35) and cell number (r = .35) and negatively, but weakly, correlated to zona pellucida thickness (r = -.13; P = .267). Hatched embryos produced more total PA than embryos that did not hatch (.140 +/- .011 vs .070 +/- .019 g; P less than .01). These results suggest that as embryonic size and cell number increase and development progresses, bovine embryos liberate more PA.
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PMID:Relationship between plasminogen activator production and bovine embryo development in vitro. 238 91

Although the mechanisms involved in the pathophysiology of primary pulmonary hypertension have not yet been delineated, thrombosis has been implicated. This study was designed to determine whether thrombin activity as reflected by plasma concentrations of fibrinopeptide A (FPA), a marker of the action of thrombin on fibrinogen, is increased in patients with primary pulmonary hypertension. To evaluate fibrinolytic activity, we measured plasma concentrations of tissue-type plasminogen activator, plasminogen activator inhibitor-1, and cross-linked fibrin degradation products. We studied 31 patients with primary pulmonary hypertension. Plasma FPA concentrations measured by radioimmunoassay, were elevated to 87.4 +/- 36.9 ng/ml (mean +/- SEM). Fifteen minutes after administration of heparin (5,000 U), FPA concentrations decreased to 6.8 +/- 1.4 ng/ml (p less than 0.001 compared with preheparin levels). In 21 of 30 patients (70%), FPA concentrations after heparin administration were less than half the preheparin levels, a response consistent with inhibition of thrombin by heparin and the short half-life of FPA. Despite evidence for marked thrombin activity, plasma concentrations of cross-linked fibrin degradation products were normal in all but four patients. Plasminogen activator inhibitor-1 activity was elevated in 19 of the 27 patients in whom it was measured, potentially limiting the fibrinolytic response. The elevations of FPA indicate that thrombin activity is increased in vivo in patients with primary pulmonary hypertension. Thus, sequential assays of plasma markers of thrombosis and fibrinolysis in vivo may help identify those patients who may benefit from treatment with anticoagulants.
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PMID:Fibrinopeptide A levels indicative of pulmonary vascular thrombosis in patients with primary pulmonary hypertension. 239 5

Parameters of the fibrinolytic system were studied in a primate model where the generation of thrombin was promoted in vivo. The procoagulant stimulus used was a combination of human factor Xa in combination with phosphatidylcholine/phosphatidylserine lipid vesicles (PCPS) as the source of coagulant active phospholipid. The dosage of each component was formulated to provide a gradation of thrombin generating potential assessed prior to in vivo study in an in vitro clotting assay. These ranged from 25.25-36.60 pMole/kg (factor Xa) and 18.85-56.30 nMole/kg (PCPS). In each case, the ratio of the dose of factor Xa/PCPS was maintained at 0.65 (pMole factor Xa/nMole PCPS). Individual dosage combinations producing recalcification clotting times in vitro of 15, 20, 25 and 30 s were used in detailed in vivo studies. Previous studies in dogs had confirmed the thrombin generating potential of factor Xa/PCPS infusions and demonstrated an associated activation of protein C and increased fibrinolytic activity. This has now been extensively characterized in the chimpanzee as follows: 10 min after the infusion of the highest dose (36.6 pMole factor Xa/56.3 nMole PCPS kg bodyweight), the level of circulating t-PA had risen to 900 ng/ml (antigen), 885 IU/ml (functional). Dosage was observed with the lowest dose of 12.25 pMole factor Xa and 18.85 nMole PCPS being associated with relatively minor increases in circulating t-PA activity. There were no changes in u-PA at any dosage during the full time course of the experimental period (90 min). Plasminogen activation was also apparent with alpha-2 antiplasmin levels falling to 30-40% of pre-infusion levels at the highest dosages.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The fibrinolytic potential of the normal primate following the generation of thrombin in vivo. 240 50

Plasminogen activators (PA) in the euglobulin fraction of dextran sulfate activated plasma (DS-EF) were assayed on fibrin plates. Activity related to tissue plasminogen activator (t-PA) or urokinase (u-PA) was quantified by antiserum inhibition. The DS-EF contained 30% t-PA, 30% u-PA and 40-50% activity unrelated to t-PA or u-PA. The latter was completely inhibited by 1.7 mumol/1 C1-inhibitor (C1INH), the two former were less sensitive. Addition of flufenamate to the DS-EF (DS-EF/Fluf) from normal and two factor XII (F XII)-deficient plasmas increased their activities to the same high level. More than 50% of the activity was unrelated to t-PA or u-PA, 30-40% was u-PA and 5-10% t-PA related. After addition of fibrinogen to DS-EF/Fluf and clotting with thrombin, the remaining solution contained only about 30% of the total activity, including less than 10% u-PA. The epsilon-aminocaproic acid inhibition pattern obtained with the DS-EF was uniform, and thus different from the biphasic pattern obtained with the low fibrin affinity PA, two-chain urokinase. Thus, both the plasma u-PA and the major unidentified PA in plasma have affinity for fibrin.
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PMID:Assay characteristics and fibrin affinity of plasminogen activators of the intrinsic fibrinolytic system. 242 31

The effect of plasminogen on the ability of highly metastatic ESb mouse lymphoma cells to degrade heparan sulfate (HS) in the subendothelial extracellular matrix (ECM) was studied. A metabolically sulfate-labeled ECM was incubated with the lymphoma cells, and labeled degradation products were analyzed by gel filtration on Sepharose 6B. Heparanase-mediated release of low-Mr (0.5 less than Kav less than 0.85) HS cleavage products was stimulated fourfold in the presence of plasminogen. Incubation of plasminogen alone with the ECM resulted in its conversion into plasmin, which released high-Mr (Kav less than 0.33) labeled proteoglycans from the ECM. Heating the ECM (80 degrees C, 1 hr) abolished its ability to convert plasminogen into plasmin, yet plasminogen stimulated, through its activation by the ESb plasminogen activator, heparanase-mediated release of low-Mr HS fragments. Heparin inhibited both the basal and plasminogen-stimulated degradation of HS side chains but not the total amount of labeled material released from the ECM. In contrast, aprotinin inhibited the plasminogen-stimulated release of high- as well as low-Mr material. In the absence of plasminogen, degradation of heated ECM by ESb cells was completely inhibited by aprotinin, but there was only a partial inhibition of the degradation of native ECM and no effect on the degradation of soluble HS proteoglycan. These results demonstrate that proteolytic activity and heparanase participate synergistically in the sequential degradation of ECM HS and that the ESb proteolytic activity is crucial for this degradation when the ECM-associated protease is inactivated. Plasminogen may serve as a source for the proteolytic activity that produces a more accessible substrate to the heparanase.
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PMID:Involvement of both heparanase and plasminogen activator in lymphoma cell-mediated degradation of heparan sulfate in the subendothelial extracellular matrix. 242 87

Plasminogen preparation from donor blood and fibrinolytically active blood plasma from humans after sudden death were obtained using affinity chromatography on Lysin-sepharose 4B. The plasminogen preparation from donor blood was shown to be highly purified native plasminogen (Glu-plasminogen). The preparation containing activated plasminogen (Lys-plasminogen), plasmin, plasminogen activator, alpha 2-macroglobulin, alpha 1-antitrypsin, fibrin/fibrinogen was obtained from the blood plasma of humans after sudden death. The appearance of proteins lacking biological specificity to lysin-sepharose in the plasminogen preparation shows the ability of activated plasminogen and plasmin to form complexes with these proteins and demonstrates the retention of the functional activity in lysin-binding regions on their molecules. Monospecific sera to the isolated preparations were obtained, demonstrating the presence of the same immunochemical determinants in native and activated plasminogen.
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PMID:[Effect of endogenous fibrinolysis activation on human plasminogen]. 243 67

Activity of peritoneal plasminogen activator and its regulation by dextran and other macromolecules that clinically suppress postoperative adhesions was studied. Plasminogen activator activity was assayed by a two-stage globinolytic assay that monitors formation of plasmin, as well as by cleavage of a chromogenic peptide substrate (S-2444) in the presence of aprotinin (Trasylol). Plasminogen activator activity was located on the outer surface of human peritoneum. Incubation of peritoneal tissue with buffer in vitro (conditioning) prompted release of plasminogen activator into the conditioning medium. The released plasminogen activator formed a single band on sodium dodecyl sulfate-gel electrophoresis at an apparent molecular weight of 174,000 and was markedly suppressed by antiserum raised against human melanoma tissue-type plasminogen activator. Nonspecific proteolytic activity did not accumulate in the medium during conditioning. The presence of dextran 80 during conditioning of peritoneum reversibly suppressed tissue-bound plasminogen activator activity and reduced plasminogen activator activity in the spent medium. A similar inhibition of peritoneal plasminogen activator was induced by dextran 500, methyl cellulose, and polyvinylpyrrolidone. Dextran, when added to the medium after conditioning, had no direct inhibitory effect on plasminogen activator activity. Dextran did not induce peritoneal production of inhibitor(s) of trypsin, chymotrypsin, or urokinase. On the basis of these findings, two possible mechanisms for the effect of viscous polymers in the reduction of adhesion formation are proposed. These mechanisms consider the importance of peritoneal tissue-type plasminogen activator for removal of fibrin clots and suggest that polymer coating either prevents the shedding of plasminogen activator into the abdominal cavity or reduces the access of fibrin clots to the serosal surfaces.
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PMID:Effect of viscous macromolecules on peritoneal plasminogen activator activity: a potential mechanism for their ability to reduce postoperative adhesion formation. 245 68

Plasminogen activators were studied in blood urine in 207 patients with nephrotic syndrome of different etiological forms. The blood plasminogen activator activity was decreased in chronic glomerulonephritis, SLE, systemic vasculities as result of great level of inhibitors (L2M), penetration of enzymes to abdominal and pleural transudates, excretion to urine. The blood plasminogen activator activity and urokinase level in chronic glomerulonephritis was dependent on the degree of nephrotic syndrome. The plasminogen activator in amyloidosis was sharply elevated because of permanent irritability of endothelial wall by amyloid mass. Venous occlusion caused the release of plasminogen activator to blood only in more favourable clinical course of nephrotic syndrome.
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PMID:Plasminogen activator in nephrotic syndrome. 246 29

Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of fibrinolysis. It circulates in blood both in free active form and in inactive form complexed with tissue type plasminogen activator (t-PA). Control mechanisms for its synthesis and release from hepatocytes and endothelial cells are important in the pathogenesis of thrombosis. Possible risk factors for myocardial infarction include high insulin and PAI-1 levels, which correlate with one another in healthy subjects, and fibrinogen, which together with PAI-1, is an acute-phase reactant. We therefore studied the interrelationships between PAI-1, plasma insulin, and acute-phase proteins in 67 patients with angina pectoris. Plasma insulin correlated strongly (r = 0.59, p less than 0.001) with PAI activity, free PAI-1 antigen (r = 0.60, p less than 0.001), and total PAI-1 antigen (r = 0.58, p less than 0.001). The acute-phase proteins, fibrinogen and C-reactive protein, correlated significantly with t-PA antigen, total PAI-1 antigen, and PAI-1/t-PA complexes but not with PAI activity or free PAI-1. The results suggest that insulin stimulates synthesis and release of free PAI-1 (probably via hepatocytes as previously shown with cell culture) and that endothelial cell synthesis and release of t-PA, together with PAI-1, reflects a nonspecific acute-phase response to chronic vascular disease. Hyperinsulinemia found in patients with angina pectoris could play a role in the development of myocardial infarction via the induction of high plasma PAI-1 activity.
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PMID:Plasma plasminogen activator inhibitor-1 in angina pectoris. Influence of plasma insulin and acute-phase response. 247 Mar 43

The fibrinolytic system was investigated in 30 patients under oral anticoagulant therapy, and in 23 control patients not receiving oral anticoagulants. Patients under oral anticoagulant therapy had significantly higher tissue-plasminogen activator (t-PA) antigen levels than patients in the control group. Mean t-PA levels before venous occlusion were 18.4 ng/ml in the anticoagulated patients vs. 7.9 ng/ml in the control patients (p less than 0.001). After venous occlusion for 10 minutes, t-PA levels were 45.0 ng/ml in the anticoagulated patients and 24.2 ng/ml in the control patients (p less than 0.01). Plasminogen activator inhibitor (PAI) capacity was not significantly different in the two groups before venous occlusion (VO) but differed slightly (p less than 0.05) after VO. The net decrease in euglobulin lysis time (ELT) after venous occlusion (= ELT before VO - ELT after VO), indicating the relative potency of the fibrinolytic activity in blood, was also significantly higher in the anticoagulated patients (median 240 min vs. 125 min, p less than 0.001). These data indicate that oral anticoagulant therapy increases the fibrinolytic activity in blood, and thus may have an additional therapeutic effect in addition to anticoagulation.
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PMID:Increased tissue-plasminogen activator (t-PA) levels in patients under oral anticoagulant therapy. 249 37


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