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

Rabbit alveolar macrophages can directly stimulate either coagulation or fibrinolysis by producing tissue thromboplastin and plasminogen activator activities, respectively. However, it is not known whether these 2 opposed physiologic activities are expressed by the same or different cells within a population of alveolar macrophages. This study was undertaken to determine the distribution of procoagulant and plasminogen activator activities among density-defined populations of rabbit alveolar macrophages. Normal rabbit alveolar macrophages were separated into 4 density fractions on continuous gradients of Percoll, and the distribution of procoagulant and plasminogen activator activities among these fractions was determined. The procoagulant activity of the least dense cells (Fraction 1) was as much as 6 times greater than the activity displayed by denser cells (Fractions 2 to 4). By contrast, both cell-associated and secreted plasminogen activator activities were equally and uniformly distributed among all density fractions. These distributions of activities among density fractions persisted after the cells were incubated in culture medium for 24 h. After culture in vitro with lymphokine, procoagulant activity increased in the denser cells so that the activity became equal among all density fractions. We conclude that procoagulant activity distributes differently from plasminogen activator activity among fractions of normal rabbit alveolar macrophages separated according to cell density. By using density gradient fractionation, alveolar macrophages with predominantly procoagulant or plasminogen activator activities can be enriched from the lavage cell population; the dissimilar distribution of these 2 activities within the alveolar macrophage cell population does not reflect the presence of cells with fixed differences in their functional capacities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The distribution of procoagulant and plasminogen activator activities among density fractions of normal rabbit alveolar macrophages. 395 54

This study was performed to characterize selected pharmacologic properties and effects on the fibrinolytic system of tissue-type plasminogen activator synthesized by recombinant DNA technology (rt-PA) in 12 patients treated for coronary thrombosis. rt-PA was infused parenterally (by the intracoronary route in four patients and intravenously in eight) in doses of 8.3, 12.5, or 16.7 micrograms/kg/min for 30 to 60 min, yielding a total dosage of 20 to 40 mg/patient. The drug induced coronary thrombolysis in 10 of the 12 patients treated (83%), including six of the eight given rt-PA intravenously. No bleeding complications were encountered. Serial blood samples were obtained before, during, and after infusion of rt-PA and analyzed for t-PA antigen (i.e., immunoassayable rt-PA protein), functional fibrinolytic activity attributable to rt-PA, fibrinogen, plasminogen, alpha 2-antiplasmin, fibrinogen degradation products, prothrombin time, activated partial thromboplastin time, and protamine-corrected thrombin time. Pretreatment plasma t-PA antigen levels averaged 16.5 +/- 5(SD) ng/ml. Peak plasma values were generally proportional to dose, averaging 3330 +/- 1201 ng/ml. Approximately 90% of peak level was reached in 30 min, with a plateau at peak reached within 40 min. Functional t-PA activity increased monotonically in a comparable fashion. Curves for disappearance of both t-PA antigen and functional activity from plasma were monoexponential for at least two half-lives (r = .99 for both) and were concordant. The observed half-lives were similar, averaging 8.3 and 9.1 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacology in patients with evolving myocardial infarction of tissue-type plasminogen activator produced by recombinant DNA technology. 403 68

Monocyte infiltration and activation of the coagulation system have been implicated in the pathophysiology of glomerulonephritis. In this study, spontaneous procoagulant activity (PCA) was measured in circulating mononuclear cells to determine whether elevated PCA correlated with the presence of proliferative glomerulonephritis in patients with systemic lupus erythematosus (SLE). No increase in PCA was found in 20 patients with end-stage renal failure, 8 patients with glomerulonephritis without SLE, and 10 patients undergoing abdominal surgical or orthopedic procedures as compared with 20 normal controls. In eight patients with SLE but with no apparent active renal disease, PCA was not elevated above normal basal levels. Seven additional patients with SLE who had only mesangial proliferation on biopsy also had no increase in PCA. In contrast, eight patients with focal or diffuse proliferative lupus nephritis, and one patient with membranous nephritis who ultimately developed a proliferative lesion, had a marked increase in PCA with greater than 100 times the base-line levels. The activity was shown to originate in the monocyte fraction of the mononuclear cells and was shown to be capable of cleaving prothrombin directly. The prothrombinase activity was not Factor Xa, because it was not neutralized by anti-Factor X serum and was not inhibited by an established panel of Factor Xa inhibitors. Monocyte plasminogen activator determinations did not correlate with renal disease activity. We conclude that monocyte procoagulant activity, a direct prothrombinase, seems to correlate with endocapillary proliferation in lupus nephritis and could be a mediator of tissue injury.
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PMID:Monocyte procoagulant activity in glomerulonephritis associated with systemic lupus erythematosus. 403 82

Fibrinolysis may be impaired in coronary heart disease patients. 20 coronary heart disease patients and 10 control subjects were examined for tissue-plasminogen activator activity, tissue-plasminogen activator antigen, fast tissue-plasminogen activator inhibitor and other fibrinolytic and haemostatic parameters including antigenic and functional protein C. Both patient and control groups were similar in age and smoking habits. All of these patients had a myocardial infarction between 1-3 months before this study. Assays were evaluated before and after an exercise test. Prothrombin time, activated partial thromboplastin time, protein C, plasminogen, alpha 2-antiplasmin, fibrinogen/fibrin degradation products and contact-activated fibrinolysis were similar before and after exercise in both groups. Fibrinolytic activity assayed by the euglobulin lysis time and fibrin-plate lysis methods was decreased in the patient group as compared with the control group but the difference was not significant. In basal conditions, tissue-plasminogen activator activity was defective in 50% of the coronary heart disease patients (p less than 0.01) and after exercise this percentage rose to 77% (p less than 0.01). However, tissue-plasminogen activator antigen in the coronary heart disease group was similar to that of the control group, both before and after exercise. The activity of the tissue-plasminogen activator inhibitor was persistently increased in coronary heart disease though this increase was not statistically significant. It is concluded that in coronary heart disease patients there is a defective fibrinolytic activity probably due to an increase in tissue-plasminogen activator inhibitor.
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PMID:Reduced fibrinolytic activity in coronary heart disease in basal conditions and after exercise. 408 14

An endothelial cell-associated cofactor that greatly enhances the rate of protein C activation by thrombin has recently been described. The observation that the cofactor binds thrombin with unusually high affinity (K(d) = 0.5 nM) suggested that low level thrombin infusion into dogs might lead to the selective activation of protein C. Infusion of thrombin (1 U/min per kg body wt) into the jugular vein of dogs leads to the formation of a systemic anticoagulant activity within 5 min of starting the infusion. The plasma has a prolonged partial thromboplastin time and Factor X(a) clotting time, but there is no change in the thrombin clotting time. The systemic anticoagulant activity is identified as activated protein C for the following reasons: (a) anti-canine activated protein C IgG antibodies inhibit the anticoagulant activity; (b) the anticoagulant activity can be partially purified from the plasma of dogs infused with thrombin by barium citrate adsorption; (c) the anticoagulant has chromatographic properties on QAE Sephadex indistinguishable from those of activated protein C, and (d) the rate at which this anticoagulant is inhibited in citrated canine plasma is identical to that of canine activated protein C. The in vivo activation of protein C appears to be receptor mediated since it occurs at low thrombin concentration and since it can be progressively inhibited by simultaneous infusion of diisopropylphospho-thrombin with thrombin. The activation of protein C at low levels of thrombin is selective, since neither the platelet count nor the Factor V levels are altered. Thrombin infusion leads to an elevation in circulating plasminogen activator levels. This appears to be mediated through the activation of protein C since coinfusion of diisopropylphospho-thrombin with thrombin inhibits the increase in plasminogen activator levels. Pretreatment of dogs with dicumarol blocks both the formation of anticoagulant activity and the rise in plasminogen activator. When the dicumarol-treated dogs are supplemented with isolated protein C and thrombin is infused, the anticoagulant activity again appears and the circulating levels of plasminogen activator are again elevated. These studies illustrate that low levels of thrombin in vivo can activate protein C, which in turn can inhibit blood coagulation and initiate fibrinolysis by elevating circulating plasminogen activator levels.
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PMID:Activation of protein C in vivo. 617 16

Plasma coagulation factors were measured in twelve male insulin-dependent diabetics with no retinopathy, ten with background and ten with proliferative retinopathy and ten non-diabetics. Factor VIII pro-coagulant activities (VIII:C), ristocetin cofactor activities and factor VIII-related antigen concentrations (VIIIR:ag) were significantly related to the severity of diabetic retinopathy (P less than 0.025, trend test). The mean ratio of VIII:C/VIIIR:ag was lower in the diabetics with proliferative retinopathy than in the other groups of diabetics (P less than 0.05) or the controls (P less than 0.02). Concentrations of alpha 2 macroglobulin and alpha 1 antitrypsin were highest in diabetics with proliferative retinopathy (0.1 greater than P greater than 0.05, trend test) but mean prothrombin and activated partial thromboplastin times and mean concentrations of alpha 2 antiplasmin, plasminogen activator and antithrombin III were similar in all groups. Concentrations of the platelet-specific protein beta thromboglobulin, though higher in diabetics than controls (P less than 0.005), were not related to retinopathy. The plasma concentrations of coagulation factors did not correlate with creatinine clearance and there were no significant differences between groups in concentrations C-reactive protein; this suggests that the raised concentrations of coagulation factors in diabetics with retinopathy were not a result of associated nephropathy or an 'acute phase protein' response to diabetic tissue damage. Increased coagulation activity in diabetics may contribute to the development of retinopathy.
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PMID:Plasma haemostatic factors and diabetic retinopathy. 619 95

The effect of strenuous exercise on the fibrinolytic and coagulation mechanisms was examined in six healthy male subjects. Five min bicycle exercise at a work-rate of 800 to 1200 kpm. min-1 produced an abrupt increase in plasma plasminogen activator levels which disappeared after 90 min. However, there was no change in early or late fibrin degradation products nor was there a change in fibrinopeptide A levels or beta-thromboglobulin levels after exercise although activated partial thromboplastin times were significantly shortened. It is concluded that strenuous exercise does not produce any real increase in fibrinogen-fibrin conversion nor any real increase in the breakdown of these proteins. The role of exercise-induced release of plasminogen activator remains unclear, but probably helps to maintain plasma levels in a discontinuous manner concurrently with the continuous low-level secretion from the vascular wall. The shortening of partial thromboplastin time may be due to the raised levels of plasminogen activator changing the activation state of other coagulation factors.
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PMID:Exercise-induced fibrinolysis--fact or fiction? 621 83

Any diffuse lesion of the liver induces permanent hypercoagulation with subsequent permanent lysis and possible consumption or DIVC/Hemostasis depends on two distinct mechanisms: the platelets, whose functional activity is more important than numbers, and the coagulolytic equilibrium of the plasma. Apart from the activating and inhibiting enzymes of coagulation and lysis, the lungs and liver play an important role. The lungs filter and then determine lysis of the corpuscular agglomerates. The liver produces epuration of the activated factors and prothrombinase, as well as the plasminogen activator. Except in extremely severe cases, however, these functions are rarely involved. Investigations must be complete and include a test of platelet aggregation, a TEG on total blood to analyze whole coagulation, and tests for consumption and lysis. Coagulation and bleeding time tests are of great value during severe hemorrhagic attacks. Pathological examination should evaluate the condition of the vascular state and, more particularly, the presence of fibrin thrombi with the appropriate methods.
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PMID:[Introduction to the study of hemostasis in cirrhotic patients (author's transl)]. 625 23

We measured products of thrombin and plasmin action and of the platelet release reaction during exercise to determine if the well-known effect of exercise on in vitro coagulation and fibrinolytic tests reflects activity of these systems in vivo. Plasma fibrinopeptide A, produced by thrombin-mediated proteolysis of fibrinogen, increased with graded treadmill and cycle exercise to postexercise levels of 20--30 times resting values. Fibrin/fibrinogen-related D antigen increased in a similar fashion with peak levels at maximal O2 uptake. Plasma-activated partial thromboplastin times fell as fibrinopeptide A levels increased. Unheated fibrin plate lysis areas increased as D antigen concentrations rose, indicating increased release of plasminogen activator. In contrast to activation of the soluble coagulation and fibrinolytic systems, platelet counts and plasma levels of beta-thromboglobulin, a platelet release protein, did not change significantly with exercise. The effect of exercise on thrombin and plasmin was not influenced by prior physical training, but appeared to be less with cycle exercise than with treadmill exercise.
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PMID:Enhanced thrombin and plasmin activity with exercise in man. 645 Jan 95

The placenta contains such thrombotic factors as tissue thromboplastin, placental factor XIII, and placental urokinase inhibitor. On the other hand, there are some antithrombotic factors, for example, placental plasminogen activator and platelet aggregation inhibitor. This paper deals with another antithrombotic factor isolated from the human placenta. The results obtained are as follows: The placental coagulation inhibitor (PCI) was isolated from the human placental extract, by delipidation and chromatographic procedures with Con-A Sepharose, DEAE-Sephacel and gel filtration with Sephacryl S-300 and Sephadex G-100. The PCI was a protein, having a molecular weight of approximately 45,000 daltons. Immunological examination revealed that the PCI was different from such well-known anticoagulants as AT-III, alpha 1-AT, alpha 2-M, C1-INA, and the PCI had no heparin like characteristics. The PCI had neither fibrinolytic nor antifibrinolytic activity. Platelet aggregation was not inhibited by the PCI. The PCI had anticoagulant activity which prolongs both intrinsic and extrinsic coagulation systems.
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PMID:[Isolation and purification of placental coagulation inhibitor]. 652 Apr 78


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