bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Plasminogen Activator From Heart And Vascular Endothelium
Authors: Booth N A , Bennett B 
Published: July 2018

Plasminogen activators play a central role in fibrinolysis. At present little is known about the interrelationships and molecular properties of these protein(s). There have been conflicting reports on the number of polypeptide chains present in the active molecules; plasminogen activators, purified from human uterus and human plasma after venous occlusion, are reported to consist of two chains, each of approximately 30,000 MW, linked by disulphide bonds. In contrast, the protein purified from human vascular endothelium consists of a single chain of 67,000 MW. Evidence for proteolytic activation of a single chain precursor to a two-chain form has been obtained by Wallen, in that the protein could be isolated in the single chain form only if inhibitors of proteolysis were present throughout purification. The two-chain form was found to possess significantly greater activity. By analogy with other plasma systems, generation of an active two-chain form from a single-chain precursor may serve a regulatory function, but the role of limited proteolysis of plasminogen activator remains to be elucidated.Using modifications of reported methods, we have obtained improved purification of plasminogen activator from human heart and vascular endothelium by similar procedures. This has allowed detailed comparison of the enzyme from these two sources, in terms of chain structure, active site labelling and carbohydrate content. In particular, the effect of variation of conditions during purification on the chain structure of the isolated molecule has been studied.
Kinetic Characterization Of The Fast Acting Plasmin Inhibitor From Human Platelets
Authors: Hansen M Sandbjerg , Petersen Lars Chr 
Published: July 2018

An inhibitor of the plasma proteinase plasmin (EC 3.4.21.7) was partially purified from washed and lysed human blood platelets. The presence of the known plasma proteinase inhibitors in the preparations investigated was excluded by crossed immunoelectrophoresis and electroimmuno assay. The kinetics of the reaction between the inhibitor preparation and plasmin has been investigated using the synthetic chromogenic substrate S-2251 (D-Val-Leu-Lys-pNA).Residual plasmin activity was measured varying the amounts of inhibitor at various fixed concentrations of substrate (S-2251). The inhibitor is of the noncompetitive type as indicated by a Dixon-plot. The reaction between inhibitor and plasmin is fast with an estimated dissociation constant of approximately. 0.1. nM. The reaction is reversible as evidenced by the following findings: 1. inhibition in the presence of high concentrations of substrate is a fast reaction, but total inhibition of plasmin is not obtained, 2. inactivation of plasmin as a function of inhibitor concentration does not follow a simple titration curve, 3. addition of tranexamic acid increases the apparent Ki, 4. the complex beetween the inhibitor and plasmin is demonstrable in crossed immunoelectrophoresis but not in SDS-polyacrylamide gel electrophoresis. The results suggest that the platelet plasmin inhibitor is a reversible inhibitor with a high affinity for plasmin.
Action Of Foy, A Polyvalent Synthetic Inhibitor On Coagulation And Fibrinolysis
Authors: Stemberger A , Haas S , Stöhr R , Blümel G 
Published: July 2018

Foy(S 983), a low molecular synthetic protease inhibitor is discussed as a potential drug in acute pancreatitis and in traumatic haemorrhagic shock. Action on coagulation was tested using global clotting tests like aPTT and prothrombin time. In addition, the inhibitory effect was elucidated with chromogenic substrates on the X a- and thrombin level after exogenous or endogenous activation. This study was performed in comparison with aprotinin (TrasylolR) based on the assumption that 50 KIE aprotinin ≅ 0.1 mg Foy.Effect on fibrinolysis was tested after streptokinase (Sk) or urokinase activation. Due to the kallikrein, Xa and thrombin inhibition Foy showed a dose dependent strong effect on the endogenous and exogenous pathway in contrast to the weak effect of aprotinin on the endogenous system via kallikrein only. Plasmin inhibition of the two drugs were similar. However Foy interfered with the Sk-plasminogen activation and is an inhibitor of urokinase. Both drugs showed a strong inhibition on proteases harvested from the secretion of fistulas of the intestinal tract which are often responsible for disturbances in wound healing.
Disseminated Intravascular Coagulation In Patients With Fatty Liver Of Pregnancy. Onset Of Dic Prior To Labor
Authors: Liebman H , Sandler R , Patch M J , McGehee W G 
Published: July 2018

Fatty liver of pregnancy (FLP) is a rare syndrome with a high maternal mortality. Bleeding complications are frequent and are associated with disseminated intravascular coagulation (DIC). We have previously demonstrated that DIC in this syndrome can be persistent, lasting 2 to 6 days, and is associated with severe depressions of functional and antigenic antithrombin III (AT III). The severe depression of AT III in this syndrome is believed to secondary to decreased hepatic synthesis and increased consumption from DIC. We have hypothesized that DIC is initiated by active labor, persists because of the low levels of AT III and may be controlled by transfusion of fresh frozen plasma or AT III concentrate. Recently we saw a patient with FLP proven by biopsy who presented with jaundice, nausea, and emesis. The patient was not in active labor. In preparation for surgical delivery, coagulation studies were done which revealed DIC (abnormal screening tests, fibrinogen of 70mg/dl, fibrin split products of 320-640 ng/dl, depressed factors V ᶓ VIII and a positive protamine sulfate test). The patient was given 1500 cc of fresh frozen plasma and viable twins were surgically delivered on the second hospital day. Following delivery DIC subsided, but infusions of plasma were continued until the fourth hospital day.Subsequently we measured AT III using a fluorometric synthetic substrate (Protopath-see table above). From our observations on this patient we conclude (1) active labor is not necessary for the initiation of DIC in FLP (2) DIC in FLP can be associated with non-detectable functional AT III (3) transfusions of fresh frozen plasma can significantly increase functional AT III and may control DIC.
Comparison between a Direct and an Indirect Method for Determining Plasminogen
Authors: Hedner Ulla , Nilsson Inga Marie 
Published: July 2018

SummaryA caseinolytic method for plasminogen determination using 30% ammonium sulphate to remove the inhibitors was compared with an immunochemical method in 44 apparently healthy individuals, 25 pregnant women in the third trimester, 24 patients with different liver diseases, 20 patients receiving thrombolytic therapy, 7 patients with septicemia and 9 foetuses obtained by induced legal abortion. The correlation found was strong and the regression line was found to pass near origo, indicating that the two methods measured, the same substance.Both methods gave high plasminogen values in pregnant women and low values in patients receiving thrombolytic therapy and in foetuses.
An Accelerated Red-Cell Hemagglutination Inhibition Immunoassay for Measuring Fibrinogen Degradation Products in Human Serum
Authors: Fischer R , Furlan M , Beck E. A 
Published: July 2018

SummaryA further modification of Merskey’s hemagglutination inhibition assay for measurement of fibrinogen degradation products (FDP) in human serum was developed. Blood is clotted in the presence of protamine chloride (25 u/ml), in addition to thrombin and s-aminocaproic acid, and at room temperature. Defibrination is complete within 5 min even in blood obtained from patients on heparin treatment. The hemagglutination immunoassay was also considerably accelerated by immediate addition of sensitized red cells to the mixtures of antiserum and antigen dilutions at 37° C. Accurate readings of FDP titers may thus be obtained within 20 min following venipuncture.
Removal of Thrombokinase from Commercial Thrombin
Authors: Kerwin D. M , Milstone J. H 
Published: July 2018

SummaryCommercial thrombin was shown to contain appreciable amounts of thrombokinase. Passage through a DEAE-cellulose column substantially reduced the thrombokinase titer, although significant contamination could still be detected. Similarly, repeated barium sulfate adsorptions failed to remove the thrombokinase completely.However, barium sulfate adsorptions followed by passage through a column of DEAE-cellulose resulted in an essentially complete removal of the contaminant. Thrombin, so obtained, did not accelerate activation of prothrombin in the presence of calcium, phosphatide and barium carbonate adsorbed serum.Thrombokinase, separated by chromatography, was able to activate prothrombin very slowly in the presence of oxalate. Comparably dilute thrombin fractions and the unfractionated commercial preparation either did not possess this capability, or else this capability was obscured by a concomitant loss of thrombin.
Effect of Anticoagulating and Non-Anticoagulating Concentrations of Heparin on the Generalized Shwartzman Reaction
Authors: Corrigan J. J 
Published: July 2018

SummaryRabbits given 2 properly spaced intravenous injections of bacterial endotoxin develop bilateral renal cortical necrosis (generalized Shwartzman reaction - gSr). This renal lesion is the result of fibrin deposition secondary to diffuse intravascular clotting (DIC). Using this experimental model, the effect of anticoagulating (large) and non- anticoagulating (small) concentrations of heparin on the changes in blood platelets, plasma coagulation factors II, V, VIII and fibrinogen during the production of renal cortical necrosis was studied. The data demonstrate that all amounts of heparin given during, but not after, the period of intravascular clotting reduced the frequency of renal cortical necrosis. Anticoagulating concentrations completely prevented the renal lesion. Non-anticoagulating amounts could reduce the frequency of the renal lesions, but this effect was not predictable or consistent. Coagulation studies in the large dose group revealed thrombocytopenia reduced factors II, V, and VIII but no fibrinogen consumption. These findings suggest that heparin inhibits the formation of fibrin in vivo, thereby preventing the formation of renal cortical necrosis. The coagulation data in the small dose group differed in that fibrinogen consumption did occur. The possible explanations for the phenomenon were discussed.
Comparison of the Effects of Various Blood Plasma Expanders on Platelet Adhesiveness
Authors: Schneider J. A , Sanbar S. S , Zweifler A. J 
Published: July 2018

SummaryIn 30 non-anesthetized rabbits, platelet adhesiveness of arterial blood was determined before and 2, 6, and 24 h after 10 min intravenous infusions of either 20 ml isotonic saline solution (5 control rabbits), or 2.4 g each of dextran 40,000 (4 rabbits), dextran 70,000 (4 rabbits), polyvinylpyrrolidone (P. V. P.) 40,000 (8 rabbits), hydroxyethyl starch (H. E. S.) 60,000 (4 rabbits), or H. E. S. 450,000 (5 rabbits) in saline solution.Platelet adhesiveness did not change significantly after infusions of saline, dextran 40,000, or H. E. S. 450,000. In contrast, dextran 70,000 and H. E. S. 60,000 promptly produced about one-third decrease in platelet adhesiveness which returned toward control levels 24 h after the infusions. Finally, P.V.P. also promptly diminished percent platelet adhesiveness by about one-third of control values and this effect persisted 24 h after infusion. Changes in platelet adhesiveness did not correlate with alterations in hematocrit or platelet count.On a weight basis, P. V. P. elicits the most persistent decrease in platelet adhesiveness.
Preparation, Stabilization and Some Properties of Purified Human Plasmin*
Authors: Kline Daniel L , Fishman Jacob B ,   With the technical assistance of B. A. Lage
Published: July 2018

Summary1. Lysine increased the solubility, decreased the SK requirement and increased the stability of plasmin prepared from purified plasminogen by SK activation.2. A procedure is presented for the rapid and quantitative conversion of plasminogen to plasmin and storage of the plasmin in stable form at neutral pH as a lyophilized powder.3. Approximately 10% for the plasminogen molecule was split off during its activation. No carbohydrate was lost.4. The plasmin isolated was homogeneous in the ultracentrifuge at pH 2.5 and was quantitatively convertible to plasminogen activator by the addition of SK.
Streptokinase - Induced Proteolytic Activity with Respect to Age in Two Ethnic Groups in Israel
Authors: Rimon A , Segal S 
Published: July 2018

SummaryStreptokinase-induced proteolytic (caseinolytic) activity was determined in the plasma and in the euglobulin fraction of Yemenite and Ashkenazi Jews, with respect to age.In the plasma it was found, that in both groups the activity increased with age. In Ashkenasim, however, the activity levelled off at about 30 years of age, whereas, in Yemenites, it continued to increase with age. This was true for both sexes.In the euglobulin fraction, the activity was also found to increase with age, but to a lesser extent, than in the plasma. This increase was more pronounced in Yemenite than in Ashkenazi Jews, and in both groups levelled off at about 30 years of age. The possible significance of these observations apropos regulation of the fibrinolytic activity in the blood, is dicussed. It is suggested that Yemenite Jews have a more effective mechanism for handling clots with advancing years.
The Fibrinotic Index and Evidence for a Balanced Regulation of Coagulation Activities*
Authors: Grannis G. F , Kazal L. A 
Published: July 2018

SummaryThe fibrinogen, plasma antithrombin, and thrombin activity curves of twenty-four normal individuals were determined under carefully controlled conditions of analysis. From these determinations plasma prothrombin and thromboplastic activities were calculated. These activities were defined in kinetic terminology and a theoretical rate of fibrination in plasma was calculated and used as a basis for comparing plasmas. Compensatory relationships were found among the various activities. Thus, low values of thromboplastic activity were associated with increased concentrations of prothrombin and fibrinogen; the effect of the latter activities in increasing the potential of plasma for fibrination was moderated by an increase in antithrombin activity.The fibrin-forming potential of each plasma was calculated relative to the mean value for all plasmas, to furnish a fibrinotic index. The latter was relatively constant in spite of wide variations in discrete activities, indicating that a physiological balance is maintained among those coagulation factors responsible for fibrination.
Determination of Plasminogen in Human Plasma by a Casein Method*
Authors: Hedner Ulla , Nilsson Inga Marie 
Published: July 2018

SummaryA modification of the casein method for determination of plasminogen in plasma has been devised.1. Urokinase instead of streptokinase was used for activation of plasminogen in order to eliminate the effect of any antistreptokinase antibodies in the plasma.2. A purified and stable plasmin preparation according to Wallén was used for preparing reference curves.3. The plasminogen activity of plasma was converted into arbitrary casein - olytic units (ACU) defined in such a way that 10 caseinolytic units gave an extinction of 0.300.4. Removal of the plasmin inhibitors by acidification of plasma to pH 2.0 was found to be better than using euglobulin precipitation.5. The plasma should be tested immediately after thawing and not allowed to stand after acidification for obtaining optimal conditions.6. The method can be used for determination of plasminogen in plasma in patients treated with ssss-ACA and AMCA.7. The error of the method was found to be small ssss0.4.The mean plasminogen level in a normal group of 72 was found to be 9.5 ssss 1.7 ACU/ml plasma. No variation with sex and age was found.The method proved clinically useful. During the latter half of pregnancy the plasminogen level was found to be clearly elevated. In patients with liver cirrhosis the plasminogen level was low. It was a sensitive method for following the plasminogen content during streptokinase treatment.
The Mechanism of Activation of Cat Plasma by Streptokinase*
Authors: Mootse G , Fleming L.B , Cliffton E.E 
Published: July 2018

Summary1. The mechanism involved in the inactivation of cat plasma, serum, and plasma euglobulin by different concentrations of SK has been demonstrated.2. Two different caseinolytic entities were graphically differentiated. They were characterized by their time of formation and stability studies.3. With suboptimal SK concentration the development of the caseinolytic activity consisted of an initial rapid phase, followed by a slowly rising activity ; beta plasmin. With optimal SK concentration only the initial rapid caseinolytic activity was obtained (alpha plasmin).4. It is suggested that beta plasmin was formed by a reversible reaction and was inactivated when substrate was not present. With increasing SK concentration alpha plasmin formation competed with the beta plasmin formation.5. A comparison of potential caseinolytic activity of cat plasma, serum, and plasma euglobulin to beta and alpha plasmin is present.
The Effect of the Alkyl Tins on Platelet Aggregation
Authors: O’Brien Dr. J. R 
Published: July 2018

SummaryThe addition of the tri alkyl tins to stirred platelet rich plasma produces after a delay, gross platelet aggregation. The delay is decreased by Adenosine triphosphate and increased by Adenosine monophosphate. The tri alkyl tins may liberate Adenosine diphosphate from the platelets, possibly by stimulating an ATP-ase. Plasma as well as platelets can inactivate Adenosine diphosphate.
Disposable Plastic Cuvettes for Thrombelastography
Authors: Loeliger E. A , Veltkamp J. J , Mattern Mieke J , Hooij Henriëtte J 
Published: July 2018

SummaryThrombelastography can be performed by means of disposable plastic cuvettes instead of metallic cuvettes. There is no important difference between the curves obtained in cuvettes of the two different materials. Reproducibility plastic cuvettes appears to be as good as in metallic cuvettes; reproducibility seems to be even better. The use of plastic disposable cuvettes has important practical advantages.
Lauric Acid-Induced Thrombocytopenia and Thrombosis in Rabbits
Authors: Zbinden G 
Published: July 2018

SummaryIntravenous injection of 0.5% lauric acid solution into rabbits caused moderate to marked thrombocytopenia. With small doses (2.5 mg/kg) this thrombocyte decrease was reversible and microscopically demonstrable thrombosis in the lungs was only seen or suspected in a small number of rabbits 10 to 30 min after lauric acid injection. High doses were followed by partly reversible thrombocytopenia and by moderate to marked, sometimes lethal, thrombosis in the lungs still demonstrable 24 hrs after injection. Repeated administration of small doses of lauric acid did not lead to a depletion of the circulating thrombocytes. Thrombocytopenic response, however, appeared to be less pronounced after the second and subsequent injections. Studies with Cr51-labeled platelets indicate that during the reversible thrombocytopenia following a small intravenous dose of lauric acid platelets are retained in various organs, particularly the lungs.
Coagulation Studies after Administration of a Fat Emulsion, Intralipid®
Authors: Cronberg S , Nilsson Inga Marie 
Published: July 2018

SummaryA single infusion of a fat emulsion, Intralipid®, used for parenteral nutrition was given to 11 healthy normals, 3 patients with von Willebrand’s disease and 3 with mild or moderately severe thrombasthenia. The infusion had no effect on coagulation or the fibrinolytic system. Platelet adhesiveness, as determined with Hellem’s whole blood method, was markedly increased but not with his plasma-ADP method or with Salzman’s method. No shortening of the bleeding time was observed in the normals or in the patients with prolonged bleeding time. The change observed in platelet adhesiveness is therefore believed to be an in vitro artefact with no clinical relevance.
Comparative Studies of Fibrinolytic Inhibitors in Vitro
Authors: Maki M , Beller F. K 
Published: July 2018

SummaryEACA, AMCHA, Trasylol and Soya bean trypsin inhibitor were compared in regard to their inhibition potency as enzyme and activator inhibitors in vitro, in different test systems. The ratio in all systems for Trasylol and STI was 1:4/6 depending on the test system used. Both substances are only slightly less active as activator inhibitors than as plasmin inhibitors. The difference however, is so small that Trasylol as well as STI can be regarded as good activator inhibitors in vitro. Both substances inhibit plasmin as well as activator competitively and differ therefore with EACA and AMCHA.EACA and AMCHA are activator inhibitors and considerably less inactive in regard to plasmin inhibition. The already known fact that EACA inhibits the activator competitively was confirmed for AMCHA. The latter substance is 6-8 times more potent, than EACA.EACA, AMCHA, Trasylol and STI given in combination resulted in an additive or synergistic action, rather than a potentiating one as has been described in vivo.
Influence of Certain Drugs on the Adhesiveness of Human, Rat, and Rabbit Blood Platelets in Vitro
Authors: Reber K , Studer A 
Published: July 2018

SummaryThis is a comparative study of the methods described by H. P. Wright and O’Brien for determining the adhesiveness of thrombocytes. An attempt is made to characterize and statistically correlate both techniques. With the aid of a Coulter Counter for thrombocyte counts, a normal range is presented for human, rat, and rabbit blood. Anticoagulants used are sodium citrate and Heparin.The influence of Cocaine and the Serotonin antagonist Ro 3-0837 was studied on these same substrates, to determine a pharmacological interference with results of either Wright’s test or O’Brien’s. Both drugs are found to induce a statistically significant increase in the “thrombocyte count” as compared to the corresponding controls. These effects are not real but to be attributed to an increase in particle count due to thrombocyte fragmentation as a consequence of drug application. There is no evidence for the claim that these drugs decrease the adhesiveness of thrombocytes.Numerical results of both tests often show a high and statistically significant correlation, especially following the addition of Ro 3-0837. Such is not true of individual blood samples to which no drug has been added. Evidentally, both tests are not specific for the same characteristic of normal blood platelets. But, when Ro 3-0837 is added, the breakdown of unstable platelets is induced; and the corresponding increase in count of thrombocyte fragments is expressed by both tests in the same fashion.