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)

Thrombin promotes the formation of arterial thrombi by converting fibrinogen to fibrin and by causing platelets to aggregate. We have examined the combined effects of plasminogen activators and inhibitors of platelet aggregation on the lysis of platelet-rich fibrin clots formed by alpha-thrombin in citrated platelet-rich plasma. The extent of platelet aggregation and clot formation were measured by recording light transmission in an aggregometer. Immediately after the formation of platelet-rich fibrin clots, addition of 2,000 U/ml streptokinase or 50 micrograms/ml recombinant tissue-type plasminogen activator alone resulted in the degradation of polymerized fibrin and the release of trapped platelet aggregates without causing significant platelet deaggregation. Preincubation of the platelet-rich plasma with 20 microM indomethacin for 1 min before thrombin stimulation or simultaneous addition of prostaglandin E1 (10 microM) with the plasminogen activators after thrombin stimulation resulted in spontaneous platelet deaggregation. Because platelet aggregation is, in part, mediated by the binding of Arg-Gly-Asp-containing adhesive proteins to activated platelets, the effect of Arg-Gly-Asp peptides on platelet deaggregation was examined. By itself, Gly-Arg-Gly-Asp-Ser-Pro specifically caused dose- and time-dependent deaggregation of platelet aggregates formed by ADP or by thrombin in the presence of 1 mM Gly-Pro-Arg-Pro, but had no effect on the dissociation of thrombin-induced platelet-rich fibrin clots. In combination with streptokinase or recombinant tissue-type plasminogen activator, Gly-Arg-Gly-Asp-Ser-Pro enhanced the rate of lysis of platelet-rich fibrin clots. The control Gly-Arg-Gly-Glu-Ser-Pro peptide was completely ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)
J Pharmacol Exp Ther 1991 Dec
PMID:Rapid dissociation of platelet-rich fibrin clots in vitro by a combination of plasminogen activators and antiplatelet agents. 176 85

The solution structure of a recombinant tissue-type plasminogen activator kringle 2 domain, complexed with the antifibrinolytic drug 6-aminohexanoic acid (6-AHA) was determined via 1H nuclear magnetic resonance spectroscopy and dynamical simulated annealing calculations. The structure determination is based on 610 intramolecular kringle 2 and 14 intermolecular kringle 2-6-AHA interproton distance restraints, as well as on 82 torsion angle restraints. Three sets of simulated annealing structures were computed from three different classes of starting structures: (1) random conformations devoid of disulfide bridges; (2) random conformations that contain correct disulfide bonds; and (3) a folded conformation modeled after the homologous prothrombin kringle 1 X-ray crystallographic structure. All three sets of structures are well defined, with averaged atomic root-mean-square deviations between individual structures and mean set structures of 0.77, 0.99 and 0.70 A for backbone atoms, and 1.36, 1.55 and 1.41 A for all atoms, respectively. Kringle 2 is an oblate ellipsoid with overall dimensions of approximately 34 A x 30 A x 17 A. It exhibits a compact globular conformation characterized by a number of turns and loop elements as well as by one right-handed alpha-helix and five (1 extended and 4 rudimentary) antiparallel beta-sheets. The extended beta-sheet exhibits a right-handed twist. Close van der Waals' contacts between the Cys22-Cys63 and Cys51-Cys75 disulfide bridges and the central hydrophobic core composed of the Trp25, Leu46, His48a and Trp62 side-chains are among the distinguishing features of the kringle 2 fold. The binding site for 6-AHA appears as a rather exposed cleft with a negatively charged locus defined by the Asp55 and Asp57 side-chains, and with an aromatic pocket structured by the Tyr36, Trp62, His64 and Trp72 side-chains. The Trp62 and His64 rings line the back surface of the pocket, while the Tyr36 and Trp72 rings confine it from two sides. The Trp62 and Trp72 indole rings conform a V-shaped groove. The methyl groups of Val35 also contribute lipophilic character to the ligand-interacting surface. It is suggested that the positively charged side-chains of Lys34 and, potentially, Arg69 may favor interactions with the carboxylate group of the ligand. The Trp25 and Tyr74 aromatic rings, although conserved elements of the binding site structure, seem not to undergo direct contacts with the ligand.
J Mol Biol 1991 Dec 20
PMID:Solution structure of the tissue-type plasminogen activator kringle 2 domain complexed to 6-aminohexanoic acid an antifibrinolytic drug. 176 44

The effects of endurance training on the skeletal muscle of rats have been studied at sea level and simulated high altitude (4,000 m). Male Wistar rats were randomly assigned to one of four groups: exercise at sea level, exercise at simulated high altitude, sedentary at sea level, and sedentary at high altitude (n = 8 in each group). Training consisted of swimming for 1 h/day in water at 36 degrees C for 14 wk. Training and exposure to a high-altitude environment produced a decrease in body weight (P less than 0.001). There was a significant linear correlation between muscle mass and body weight in the animals of all groups (r = 0.89, P less than 0.001). High-altitude training enhanced the percentage of type IIa fibers in the extensor digitorum longus muscle (EDL, P less than 0.05) and deep portions of the plantaris muscle (dPLA, P less than 0.01). High-altitude training also increased the percentage of type IIab fibers in fast-twitch muscles. These muscles showed marked metabolic adaptations: training increased the activity levels of enzymes involved in the citric acid cycle (citrate synthase, CS) and the beta-oxidation of fatty acids (3 hydroxyacyl CoA dehydrogenase, HAD). This increase occurred mainly at high altitude (36 and 31% for HAD in EDL and PLA muscles; 24 and 31% for CS in EDL and PLA muscles). Training increased the activity of enzymes involved in glucose phosphorylation (hexokinase). High-altitude training decreased lactate dehydrogenase activity. Endurance training performed at high altitude and sea level increased the isozyme 1-to-total lactate dehydrogenase activity ratio to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)
J Appl Physiol (1985) 1991 Dec
PMID:Skeletal muscle changes after endurance training at high altitude. 177

In order to evaluate precisely the fibrinolytic states in clinical disorders, plasma levels of D dimer (cross-linked fibrin degradation products) were measured by a newly developed, rapid quantitative method based on the latex photometric immunoassay in patients with hematological malignancies, diabetes mellitus, collagen disease, liver disease, thrombotic disease and disseminated intravascular coagulation (DIC). Plasma levels of D dimer were elevated in a variety of diseases, especially in DIC. Patients with hematological malignancies, liver disease and thrombotic disease also had relatively high levels of D dimer. On the whole, D dimer values were positively correlated with plasmin-alpha 2-plasmin inhibitor complex and thrombin-antithrombin III complex. In addition, plasma D dimer was measured during fibrinolytic therapy with urokinase or tissue-type plasminogen activator; its elevation was detected in some patients. These findings indicate that accelerated fibrinolysis is frequently observed in a variety of diseases, and that a rapid quantitative measurement of D dimer would be valuable for the precise assessment of fibrinolysis in these disease states.
Rinsho Ketsueki 1991 Dec
PMID:[Evaluation of clinical usefulness of a rapid quantitative measurement of D dimer (cross-linked fibrin degradation products)]. 177 52

Pseudomonas fluorescens strain M3/6 was inoculated into reconstituted NDM and incubated at 7 degrees C for 46 d. A significant amount of extracellular protease was produced, mainly during the latter part of the culture's life cycle. The protease was purified using ammonium sulfate fractionation, ion-exchange chromatography, and gel filtration. The isolated protease had activity on azocasein, alpha-, beta-, and kappa-caseins and a plasmin substrate but did not have plasminogen activator activity. The protease had a molecular weight of 45 kDa, an isoelectric point of pH 8.25, a broad temperature and pH range for activity, and was less heat stable in the isolated form than in the cell-free extract.
J Dairy Sci 1991 Dec
PMID:Purification and characterization of an extracellular protease produced by Pseudomonas fluorescens M3/6. 178 84

The study of immune and fibrinolytic systems in 216 atherosclerosis patients with associated chronic obstructions of the lungs revealed a discrete pattern of activity of plasminogen activator which is low in atherosclerosis in contrast to its elevation in combination of atherosclerosis with pulmonary obstructions. The latter cases manifest E-RFC relative number to be reduced in increased number of EAC-RFC. Growing amount of EA-RFM, elevated blood antithrombin III, activation of plasminogen activator in atherosclerosis coexistence with obstructive pulmonary lesions arrest the development of latent DIC syndrome and progression of atherosclerosis.
Klin Med (Mosk) 1991 Dec
PMID:[Changes in immune and fibrinolytic systems of patients with atherosclerosis and chronic nonspecific pulmonary diseases]. 178 74

The comparison of activator activity of blood, urine and pleural fluid in 55 patients suffering from chronic circulatory insufficiency, tuberculosis, pneumonia and lung cancer helped to determine pathognomonic signs for each of the exudates examined. Cardiac decompensation is associated with high activity of plasminogen activator in the transudate against low activator activity of the blood and urine. In tuberculous pleuritis there is low activator activity of the exudate in normal blood and urine parameters. Reduced activator activity of the blood, urine and pleural fluid is characteristic of parapneumonic pleuritis, while high activity of plasminogen activator in the blood and pleural exudate in its normal activity in the urine is seen in cancer pleuritis. The findings obtained can be used in clinical medicine for verification of pleural fluid nature.
Klin Med (Mosk) 1991 Dec
PMID:[Assessment of the activity of plasminogen activators in the differential diagnosis of pleural effusion]. 178 78

This study was aimed at examining the effect of chronic cigarette smoking on a venous occlusion test. Two groups of young healthy men, a control group of 20 non-smoking subjects and a group of 21 smoking subjects having an average consumption of 17.6 packages.day-1.years (SD 8.6) were studied. Venous occlusion performed in smokers did not induce a significant measurable release of von Willebrand factor (vWF). The release of tissue-type plasminogen activator (t-PA) was significantly weaker for the smokers than for the control group (P less than 0.02). An inverse correlation was found between the cumulative parameter of tobacco consumption and the measurable amount of t-PA Ag or vWF Ag released during venous occlusion (r' = -0.994 and r' = -0.889). Cigarette smoking is thus associated with disturbances of the biological response to this venous occlusion test.
Atherosclerosis 1991 Dec
PMID:Venous occlusion and chronic cigarette smoking: dose-dependent decrease in the measurable release of tissue-type plasminogen activator and von Willebrand factor. 178 7

When the rate of lysis of artificial thrombi (prepared from plasma or whole blood) was expressed according to the concentration of tissue type plasminogen activator (t-PA) or single chain urokinase type plasminogen activator (sc-uPA) then bell-shaped dose response curves were obtained, low rates being observed at concentrations of activator greater than 500 units/ml. Bell-shaped dose response curves were not observed for rate of lysis of artificial thrombi over the concentrations of streptokinase tested (SK) or for the lysis of plasma gel clots by any of the activators tested. Further investigation indicated that the preponderant mechanism for dissolution of thrombi at 500 units/ml of t-PA was by activation of the plasminogen within the thrombus (intrinsic) since the plasminogen present in the plasma perfusing the thrombus (extrinsic) rapidly became depleted. On the other hand, at 50 units/ml t-PA the lysis was observed to be due preponderantly to the action of plasmin arising from extrinsic rather than intrinsic plasminogen. If "plasminogen enriched" thrombi were prepared in the presence of Lys plasminogen (Lys-Plg) faster rates of lysis occurred and bell-shaped biometric curves were not observed.
Thromb Haemost 1991 Dec 02
PMID:Influence of intrinsic and extrinsic plasminogen upon the lysis of thrombi in vitro. 179 13

A hybrid hybridoma (FU1-74), secreting a bispecific monoclonal antibody (bs mAb), was obtained by fusion of a murine hybridoma secreting a monoclonal antibody (mAb) specific for human fibrin with a murine hybridoma secreting a mAb against urokinase-type plasminogen activator (u-PA). The bs mAb (MA-FU1-74), purified to homogeneity from mouse ascitic fluid, migrated as a single band with apparent Mr 150,000 on nonreduced SDS-PAGE and had an affinity for both human fibrin (Ka = 2 x 10(7) M-1) and for u-PA (Ka = 10(8) M-1) comparable to that of the mAbs obtained from the respective parental hybridomas. MA-FU1-74 did not influence the enzymatic activity of two-chain u-PA (tcu-PA) towards plasminogen or towards a chromogenic substrate. The complex of MA-FU1-74 with recombinant single chain u-PA (rscu-PA) or with tcu-PA (urokinase) enhanced the fibrinolytic potency of the plasminogen activator towards clotted human plasma 20-fold and 5-fold, respectively. In a hamster pulmonary embolism model, the rscu-PA/MA-FU1-74 complex had a 13- to 17-fold increased thrombolytic potency (percent lysis per mg/kg u-PA administered) relative to that of rscu-PA. The specific thrombolytic activity (percent lysis per microgram/ml steady state plasma level of u-PA antigen) of the complex was, however, not significantly different from that of rscu-PA. The complex of rscu-PA with the parental anti-u-PA mAb (MA-UK1-3) had only a 2-fold enhanced thrombolytic potency relative to that of rscu-PA and had a 5-fold decreased specific thrombolytic activity. The plasma clearance rates of the complexes of rscu-PA with both MA-FU1-74 and MA-UK1-3 were about 10-fold lower than that of rscu-PA. In a rabbit jugular vein thrombosis model, the rscu-PA/MA-FU1-74 complex had a 4-fold enhanced thrombolytic potency, an unchanged specific thrombolytic activity and 20-fold reduced plasma clearance. In both animal models, the rscu-PA/MA-FU1-74 complex did not cause more extensive systemic activation of the fibrinolytic system than rscu-PA. It is concluded that the bispecific anti-fibrin/anti-u-PA mAb MA-FU1-74 targets u-PA to the fibrin clot, resulting in a significantly enhanced thrombolytic potency of the plasminogen activator.
Thromb Haemost 1991 Dec 02
PMID:Enhancement of clot lysis in vitro and in vivo with a bispecific monoclonal antibody directed against human fibrin and against urokinase-type plasminogen activator. 179 14


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