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)

The aim of these studies was to investigate different regimens of thrombolytic therapy and oral anticoagulation, and to evaluate the effects of streptokinase (SK), heparin and warfarin in the treatment of deep vein thrombosis (DVT). Low-dose SK, although controlled according to the fibrinogen levels, did not provide improved thrombolysis compared to conventional high-dose SK, and more postthrombotic changes were registered after an average of 3 years. Furthermore, serious hemorrhagic side-effects occurred, which makes this regimen inexpedient. Various regimens of local venous infusion of SK were tried, and with a dose of 4,000 IU/h for 72 h in combination with heparin a thrombolytic effect was achieved, albeit not greater than usually observed with conventional SK. Systemic hypofibrinogenemia and hemorrhage were not avoided. A hitherto not described side-effect with bullous dermatitis was reported. Venographic severity of calf vein thrombosis displayed a statistically significant correlation to long-term hemodynamic changes, as assessed with foot volumetry, after an average of 5 years. This correlation was stronger for the size of the thrombus after initial treatment than for the size at diagnosis. Thus it seems important to treat calf vein thrombosis with heparin in order to limit the extent of the thrombus, thereby reducing long-term sequelae. During heparin treatment, an average reduction of the thrombi of 17% was observed. This reduction was significantly correlated to a short duration of symptoms but not to parameters of heparin therapy or fibrinolytic components. However, patients with substantial thrombolysis had high plasmin-alpha 2-antiplasmin (PAP) levels, and those with high tissue plasminogen activator (t-PA) inhibitor levels and remarkably also those with high t-PA antigen levels had no lysis. The concentration of t-PA antigen showed a significant increase during heparin infusion, whereas that of PAP and t-PA inhibitor was not influenced. By applying more intensive initial oral anticoagulation, stable therapeutic prothrombin time (PT)-levels were achieved one day earlier and the duration of heparin infusion could be equally reduced compared to the conventional regimen (4.4-5 days vs 5.4-6 days). The activity of coagulation factors II, VII, IX and X had dropped to the same level with both regimens the day heparin was discontinued, observed. The effectiveness of oral anticoagulation after DVT was studied in 596 patients treated for a total of 4450 months.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Studies on the medical treatment of deep vein thrombosis. 391 82

Twelve amino acid sequences of kringle-forming polypeptides were compiled from the known sequences of urokinase A-chain (human), a tissue-type plasminogen activator (human), prothrombin (human and bovine), and plasminogen (human). Their sequence homologies with maximum match were examined by a computer program. A homology alignment and graphic matrix analyses did show that they had a great degree of homology. All the cysteine residues responsible for the kringle structures of urokinase and the tissue-type plasminogen activator were confidently preserved as well as other proteins. A phylogenetic tree was then reconstructed, and the A- and S-chain of bovine and human prothrombins were accounted for the measurement of the evolutionary time span. It was found that urokinase had a larger time span, as much as 60 million years (MY), than the tissue-type plasminogen activator. A common ancestral element of the kringle-related serine proteases was placed at around 500 MY ago, as old as the diversion of the alpha- and beta-chains of hemoglobin. Thus, the kringle-families have undergone a substantial evolutionary divergence. Moreover, they can be subgrouped into three subfamilies: plasminogen activators, plasminogen, and prothrombin A-chains, the last being the most distantly diverged prothrombin S-chains.
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PMID:Homology of kringle structures in urokinase and tissue-type plasminogen activator: the phylogeny with the related serine proteases. 393 78

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

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

A family is described in which venous thrombosis developed in five members as early as 14 years of age. Routine coagulation studies, plasma antithrombin III, factor V, plasminogen, beta-thromboglobulin, fibrinopeptide A, prothrombin fragment F1+2, and thrombin-antithrombin III complex were all within normal limits. However, defective release of vascular plasminogen activator was observed on several occasions in all five subjects as compared with a control population of 125 persons (0.04 Committee on Thrombolytic Agents [CTA] units/ml plasma as compared with 0.21 CTS units/ml). In addition, levels of factor VII/von Willebrand's factor were significantly elevated above the normal range in this pedigree.
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PMID:Venous thrombosis in a family with defective release of vascular plasminogen activator and elevated plasma factor VIII/von Willebrand's factor. 640 91

The fibrinolytic response to trauma was investigated in 23 patients. Patients were triaged upon arrival in the emergency center into three groups; group I-patients with significant trauma who maintained normal vital signs, had a good prognosis, and tolerated the trauma well (mean injury severity score 8, range 4 to 12); group II--patients with significant trauma and transient episodes of hypotension, hypoxia, or acidosis who recovered (mean injury severity score 22, range 9 to 38); and group III--patients with profound or continued hypoxia and hypotension who eventually died of the trauma (mean injury severity score 41, range 30 to 50). Serial measurements of prothrombin time, activated partial thromboplastin time, and platelet count; concentrations of fibrinogen, plasminogen, and fibrin degradation products; and assays of euglobulin fraction fibrinolytic activity on plasminogen-free and plasminogen-rich fibrin plates were obtained on all patients. Coagulation studies documented a trauma-related coagulopathy that correlated with the degree of trauma. Plasminogen concentrations were initially depressed in all three groups; however by 24 hours group III patients were noted to have significantly elevated plasminogen concentrations while group I and group II patients had normal plasminogen concentrations. Fibrinolytic activity measured on plasminogen-free and plasminogen-rich fibrin plates was initially increased in all three groups with group III patients demonstrating the greatest increase. Over the succeeding 14 hours fibrinolytic activity returned to baseline values in group I and group II patients while group III patients demonstrated no detectable fibrinolytic activity for the remainder of the study period. This absence of fibrinolytic activity and increase in plasminogen concentrations in group III patients is thought to be caused by depletion of the intravascular plasminogen activator with the subsequent development of a hypofibrinolytic state.
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PMID:Fibrinolytic response to trauma. 671 Mar 42

Peritoneal fluid does not clot spontaneously on collection, due to a lack of prothrombin activation, consequent upon a virtual absence of factors V and VIII. Factor VIII related antigen is present in peritoneal fluid in only very small amounts, suggesting that this factor is excluded from the peritoneal cavity, probably by virtue of its size. Slight thrombin activity is demonstrated by the presence of fibrin monomers in the fluid. That peritoneal fluid also contains fibrinolytic activity is shown by high levels of plasminogen and plasmin-antiplasmin complexes, though no plasminogen activator could be detected. No differences were found in clotting and fibrinolytic activities, between fluid taken from these patients with, and those without, laparoscopic evidence of pelvic endometriosis.
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PMID:Clotting and fibrinolytic activities in peritoneal fluid. 677 52

Bovine-activated protein C, administered intravenously to dogs, increases the rate of lysis of whole blood clots. Protein C, bovine prothrombin, and diisopropylfluorophosphate-inactivated protein Ca do not increase the rate of lysis. Repeated infusions of protein Ca sustain rapid blood clot lysis, but neither elevate circulating fibrin-split products nor decrease circulating plasminogen levels. The administration of protein Ca results in the elevation of the levels of lysine-adsorbable plasminogen activator activity in the plasma. When partially purified concentrates of this activator are added to normal dog blood at the levels seen following protein Ca injection, the rate of clot lysis is similar to that seen after protein Ca injection. The addition of protein Ca to citrated whole blood in vitro, with the subsequent neutralization of protein Ca with antibodies, results in increased rates of lysis when plasma made from the treated blood is reinjected into the animal. The generation of fibrinolytic activity is dependent on both cellular and plasma components of blood. A model of protein Ca fibrinolytic activity has a minimum of two components: a secondary messenger formed by protein Ca action on blood cells and plasma, and the subsequent appearance of plasminogen activator in the animal in response to that messenger.
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PMID:Generation of fibrinolytic activity by infusion of activated protein C into dogs. 689 78

The aim of the studies was to determine the content of certain components of the haemostatic system in the neointima of a polyester graft implanted in the dog abdominal aorta over a 7-day period of observation. The neointima of an aortic polyester graft in the early postoperative period possesses a high thromboplastic activity, greater than that of the artery or vein, and containing prothrombin, active thrombin, platelet aggregating substances and heparin neutralizing substances. The plasminogen activator activity in the neointima of the polyester graft is also considerably higher than in the intima of arteries and veins.
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PMID:The haemostatic system components of neointima forming in polyester aortic grafts in the early postoperative period. 720 42


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