bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activated Protein C Increases Fibrin Clot Lysis by Neutralization of Plasminogen Activator Inhibitor No Evidence for a Cofactor Role of Protein S
Authors: de Fouw N J , de Jong Y F , Haverkate F , Bertina R M 
Published: June 2018

summaryThe effect of purified human activated protein G (APC) on fibrinolysis was studied using a clot iysis system consisting of purified glu-plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor (released from endothelial cells or blood platelets), fibrinogen, 125T-fibrinogen and thrombin. All proteins were of human origin.In this system APC could increase fibrinolysis in a dose dependent way, without affecting fibrin formation or fibrin crosslinking. However, this profibrinolytic effect of APC could only be observed when plasminogen activator inhibitor (PAI-l) was present. The effect of APC was completely quenched by pretreatment of APC with anti-protein C IgG or di-isopropylfluorophosphate. Addition of the cofactors of APC:protein S, Ca2+-ions and phospholipid-alone or in combination did not enhance the profibrinolytic effect of APC. These observations indicate that human APC can accelerate in vitro clot lysis by the inactivation of PAI-1 activity. However, the neutralization of PAI-1 by APC is independent of the presence or absence of protein S, phospholipid and Ca2+-ions.
Effect of Thrombin on the Production of Plasminogen Activators and PA Inhibitor-1 by Human Foreskin Microvascular Endothelial Cells
Authors: Van Hinsbergh Victor W M , Sprengers Erik D , Kooistra Teake 
Published: June 2018

SummaryHuman foreskin microvascular endothelial cells synthesize and release tissue-type plasminogen activator (t-PA) in similar amounts as do endothelial cells from umbilical cord artery and vein. Human thrombin increases the production of t-PA by these cells, which could be visualized from 8 h after addition of 0.1-5 units/ml thrombin by fibrin autography after SDS polyacrylamide gel electrophoresis of the endothelial cell conditioned media. Thrombin also increased the secretion of t-PA antigen. Together with t-PA, human microvascular cells release urokinasetype plasminogen activator (u-PA) antigen and endothelial cell-type PA inhibitor, PA inhibitor-1, which were both demonstrated by specific immunoprécipitation from radiolabeled endothelial cell conditioned medium. Thrombin increases the release of u-PA antigen, but no u-PA activity could be demonstrated. Thrombin induced a two-fold stimulation of the synthesis and secretion of PA inhibitor-1 antigen. At 0.1 unit/ml thrombin also an increase in PA inhibitor activity was found. At high concentrations of thrombin a decrease of PA inhibitor activity was found, due to the conversion of the active 46 kD PA inhibitor-1 into a 42 kD product without PA inhibitor activity. Our data indicate that interaction of thrombin with microvascular endothelial cells will shift the balance between t-PA, u-PA and PA inhibitor-1, and thus affects the regulation of fibrinolysis.
Influence of Factor Xllla Activity on Human Whole Blood Clot Lysis In Vitro
Authors: Jansen J W C M , Haverkate F , Koopman J , Nieuwenhuis H K , Kluft C , Boschman Th A C 
Published: June 2018

SummaryWe studied the influence of Factor XIII a (F XIII a) activity on the lysis rate of fresh whole human blood clots, without using anticoagulants. Clotting was induced by exogenous thrombin, lysis by tissue-type Plasminogen Activator (t-PA) added before clotting. After various periods of time, lysis rates were determined by measuring the radioactivity in the supernatant of the clot originating from 125I-Fibrinogen added before clotting.Lysis rates were determined in the presence of endogenous F XHIa and compared with those obtained after specific inhibition of F XIII a activity. We used an IgG fraction of an antiserum quenching the F XIII a activity. Addition of increasing amounts of the antibodies to normal blood resulted in a dramatic increase in clot lysis rate, concomitant with loss of F XIII activity. Lysis of blood clots from a patient with a congenital, homozygous, functional α2-Antiplasmin (α2-AP) deficiency (α2-AP-Enschede) was not or slightly increased by the anti F XIII antibodies indicating that fibrin-fibrin crosslinking per se does not contribute essentially to resistance of the blood clot against fibrinolysis. Both active α2-AP and F XIII a are required for the major part of the F XIII-dependent resistance of whole blood clots against lysis.
In Vitro and In Vivo Pharmacological Profiles of the PAF Receptor Antagonist SRI 63-675
Authors: Handley Dean A , Van Valen Ronald G , Winslow Christine M , Tomesch John C , Saunders Robert N 
Published: June 2018

SummaryWe have examined a recently developed PAF antagonist SRI 63-675 (dimethyl-tetrahydrofuran-methoxyphosphinyloxy-ethylquinolinium) for its ability to inhibit several major PAF-induced physiological responses. The compound was a potent inhibitor of PAF-induced platelet aggregation in platelet rich plasma obtained from humans, guinea pigs, and rabbits, with IC50 values of 3.43, 0.25, and 0.97 μM, respectively. SRI 63-675 did not inhibit ADP, collagen nor epinephrine-induced human platelet aggregation. The IC50 for inhibition of PAF receptor binding to human platelets was 0.37 μM. In the rat SRI 63-675 inhibited 0.1 μg kg-1 i.v. PAF-induced hypotension, with an ED50 of 32 μg kg-1 i.v. Using the same PAF challenge in the guinea pig, SRI 63-675 inhibited the hemoconcentration (ED50 = 17 μg kg-1 i.v.) and bronchoconstriction (ED50 = 24 μg kg-1 i.v.) responses. In the primate, the ED50 was 28 μg kg-1 i.v. against 3.5 μg kg-1 PAF-induced hemoconcentration. The ratio (1:6) in the primate of PAF used (6.3 nmol kg-1) to antagonist at the ED50 (40.7 nmol kg-1) indicates exceptional potency of SRI 63675 in this species. The inhibition by SRI 63-675 of the major PAF-induced effects in the rat, guinea pig and primate suggests a common receptor may be involved in the expression of these PAF responses.
Reliability of a Single β-Thromboglobulin Measurement in a Diabetic Population : Importance of PGE1 in Anticoagulant Mixture
Authors: Scarabin P Y , Strain L , Ludlam C A , Jones J , Kohner E M 
Published: June 2018

SummaryDuring the collection of samples for plasma β-thromboglobulin (β-TG) determination, it is well established that artificially high values can be observed due to in-vitro release. To estimate the reliability of a single β-TG measurement, blood samples were collected simultaneously from both arms on two separate occasions in 56 diabetic patients selected for a clinical trial. From each arm, blood was taken into two tubes containing an anticoagulant mixture with (tube A) and without (tube B) PGE!. The overall mean value of B-TG in tube B was 1.14 times higher than in tube A (p <0.01). The markedly large between-arms variation accounted for the most part of within-subject variation in both tubes and was significantly greater in tube B than in tube A. Based on the difference between B-TG values from both arms, the number of subjects with artifically high B-TG values was significantly higher in tube B than in tube A on each occasion (overall rate: 28% and 14% respectively). Estimate of between-occasions variation showed that B-TG levels were relatively stable for each subject between two occasions in each tube. It is concluded that the use of PGEi decreases falsely high B-TG levels, but a single measurement of B-TG does not provide a reliable estimate of the true B-TG value in vivo.
Identification of Platelet Antigens by Monoclonal Antibodies Using Crossed Immunoelectrophoresis with Immunoblotting of the Monoclonal Antibody
Authors: Thorsen L I , Gaudernack G , Brosstad F , Pedersen T M , Solum N O 
Published: June 2018

SummaryA method is described for the identification of antigens by monoclonal antibodies. This is applicable whenever precipitating antibodies to the same antigens from a different species are available. The method is based upon: 1) Separation and immunoprécipitation of cellular proteins with a polyspecific antiserum in crossed immunoelectrophoresis in the presence of the non-denaturing detergent Triton X-100 and the monoclonal antibody. 2) Coprecipitation of the monoclonal antibody with its antigen. 3) Subsequent passive transfer of the monoclonal antibody in the antibody-antigen complex onto a nitrocellulose membrane. 4) Visualization of the blotted antibody using an enzyme-linked secondary antibody and a chromogenic substrate. 5) Identification of the corresponding antigen by comparisons to the immunoprecipitate pattern of the original immunoplate. To test this method we have analyzed the detection of the antigens recognized by six previously described monoclonal antibodies against platelet membrane proteins and von Willebrand factor. Specific immunoblots were obtained in each case using small amounts of monoclonal antibodies. Thus, the technique provides an alternative when epitopes are denatured by SDS, and avoids the use of radioactively labelled monoclonal antibodies.
Hageman Factor Activity in Liquoid-Induced Consumption Coagulopathy
Authors: Müller-Berghaus G , Lasch H. G 
Published: June 2018

Summary1. Consumption coagulopathy was induced by intravenous injection of Liquoid (sodium polyanetholsulfonate) into rabbits. Thirteen out of 21 animals injected with Liquoid showed fibrin formation in the renal glomerular capillaries characteristic of the generalized Shwartzman reaction. In these 13 animals, a pronounced drop in Hageman factor activity was observed in addition to a decrease in platelet counts and fibrinogen levels.2. The consumption coagulopathy induced by Liquoid could be prevented by pretreatment of the rabbits with phenprocoumon, a coumarin derivative. None of 21 rabbits pretreated by this anticoagulant and injected with Liquoid showed fibrin in the renal glomerular capillaries. Phenprocoumon pretreatment did not influence the decrease in platelet counts, but it did significantly diminish the drop in fibrinogen levels. Although disseminated intra vascular coagulation and the generalized Shwartzman reaction could be inhibited by phenprocoumon pretreatment, this anticoagulant could not prevent the initial drop in Hageman factor activity after Liquoid injection.3. Phenprocoumon did not influence the activity or synthesis of Hageman factor. As phenprocoumon pretreatment could not prevent the drop in Hageman factor activity after intravenous injection of Liquoid, it might be concluded that the Hageman factor is either consumed, directly inactivated or destroyed in the animals independent of the presence of the prothrombin complex. These findings support earlier studies which have shown that inhibition of Hageman factor activation in vivo can prevent the generalized Shwartzman reaction induced by Liquoid.
Fibrinolysis Induced by Factor XII Contained in Prothrombin Preparations
Authors: Landaburu R. H , Pernici C , Castellanos D. E 
Published: June 2018

SummaryProthrombin products prepared by Seegers procedure induce fibrinolysis when injected intravenously. This property is due to a contaminant denominated Prothrombin Activating Derivative-B, identified as factor XII. The fibrinolytic fraction accompanies prothrombin throughout the purification procedure and may be separated by chromatography on DEAE cellulose.
A Simplified Method for Preparation of Fibrinogen
Authors: Walker Louise , Catlin Avery 
Published: June 2018

SummaryA method for preparation of fibrinogen from human plasma is presented. The method, a modification of the glycine precipitation procedure of Kazal (6), is simple and rapid, requiring 8 hours or less. The fibrinogen solution is stable on storage in the refrigerator for at least 7 months, represents an average yield of 30-40% of that in the starting material, and is around 95% clottable. Clottability is good even on storage at 37° C for several days; it is generally around 80% clottable after this storage period. The solution is free of plasminogen and plasmin but contains trace amounts of FSF (fibrin stabilizing factor) and factor VIII (factor VIII activity tends to disappear with storage). Ultracentrifugal analysis shows a main peak comprising approximately 95% of the total area (apparent sedimentation coefficient 5.8 × 10-13) and a smaller peak comprising approximately 5% or less of the total area (apparent sedimentation coefficient 3-3.5 × 10−13).
Partial Purification and Characterization of Urinary Procoagulant
Authors: Aoki N , von Kaulla K. N 
Published: June 2018

SummaryPartial purification of the human urinary procoagulant was achieved and some of its properties characterized. Purification was accomplished by adsorption of urine with BaSO4, citrate elution, isoelectric precipitation followed by (NH4)2SO4 precipitation and chromatography on hydroxylapatite and Sephadex G-200. Sucrose gradient ultracentrifugation yielded two active components with different sedimentation rates. On electrophoresis the heavier component did not enter the polyacrylamide gel, and the smaller one gave no precipitin band with antihuman serum on immunodiffusion, indicating that the procoagulant does not originate from blood. The purified procoagulant required phospholipids or platelets to activate prothrombin in the presence of coagulation factors V, VII, X and Ca++, while the crude procoagulant preparations activated prothrombin to some extent without an addition of phospholipids or platelets. Thus, the purified urinary procoagulant does not act as a typical tissue thromboplastin whereas the crude preparation may contain it as a component or contaminant. Phosphorus-containing material which may be part of a moiety endowing crude procoagulant with tissue thromboplastin-like activity is largely removed by the purification procedure resulting in low levels in the purified procoagulant.The possible identity (relationship ? ) of urinary procoagulant with the protein component of tissue thromboplastin is discussed.
Methodische Untersuchungen zur Plättchenaggregation bei der Ratte
Authors: Hohage R , Hiemeyer V 
Published: June 2018

ZusammenfassungAn plättchenreichen Plasmen mit verschiedenem Antikoagulantienzusatz wurde die Aggregation von Rattenthrombozyten turbidimetrisch untersucht. Es zeigte sich, daß die Aussagekraft von Aggregationskurven bei Verwendung von Heparin als Antikoagulans wegen der Neigung zu Spontanaggregationen während der Präparation eingeschränkt ist. Ebenso ergab sich bei Zitratzusatz eine deutliche Beeinflussung des Kurvenverlaufes infolge leichter Schwankungen des Kalziumsgehaltes. Plasmen, die durch Zusatz von Zitrat + Heparin gewonnen warden, ließen eine nur geringe Neigung zu Spontanaggregationen erkennen, wobei der Kurvenverlauf nach Rekalzifizierung weitgehend unabhängig vom ursprünglichen Kalziumgehalt ist. Demnach erlaubt nur die Verwendung von Zitrat-Heparin-Plasma, das vor Versuchssbeginn rekalzifiziert wird, eine exakte Beurteilung der Plättchenfunktion einzelner Ratten.
Platelet Adhesiveness in Symptomatic Women Taking Oral Contraceptives
Authors: Zuck T. F , Bergin J. J , Raymond Jane M. , Dwyre W. R , Corby D. G 
Published: June 2018

SummaryPlatelet adhesiveness to glass was determined in several groups of women. Increases were found in women developing thrombovascular symptoms while taking combined oral contraceptives, compared to both normal women and asymptomatic users of oral contraceptives. Despite this increase, overlap of the groups did not permit discrimination between symptomatic and asymptomatic women. However, it is possible, that in concert with other coagulation changes, platelet adhesiveness to glass may prove adjunctive in defining women at increased risk of developing thrombovascular symptoms while taking oral contraceptives, and further define the mechanism of the increased risk.
Inhibition of Clot Retraction by Previous In Vitro Platelet Aggregation
Authors: de Gaetano G , Donati M. B , Vermylen J , Verstraete M 
Published: June 2018

SummaryClot retraction was not observed in plasma when coagulation was preceded by in vitro platelet aggregation; this inhibition was proportional to the degree of platelet aggregation.In the absence of continuous stirring, the coagulation of citrated-platelet rich plasma by CaCl2 was not preceded by measurable aggregation of platelets and was followed by normal retraction of the clot. In presence of a continuous stirring of platelet-rich plasma, the addition of CaCl2 led to platelet clumping and coagulation but not to clot retraction.Platelet-rich plasma containing ADP-unresponsive platelets, retracted normally.Using different inhibitors of platelet aggregation, clot retraction was shown to be inhibited by antimycin A and by 2-deoxy-D-glucose together, but was normal in presence of adenosine or acetylsalieylic acid.Which pool of ATP provides energy for clot retraction has been discussed.Suggestions were presented that the appearance of platelet factor 3 activity during clotting is not invariably linked to platelet aggregation.
Effects of N-(2-Diethylaminoethyl)-N-(2-hydroxy- 2-phenylethyl)-2,5-dichloroaniline (AN 162) on Platelet Function and Blood Coagulation
Authors: Kenzie R. D Mac , Blohm T. R 
Published: June 2018

SummaryWhen AN 162 was added to human citrated platelet-rich plasma at 30-300 µg/ml, it inhibited platelet aggregation induced by adenosine diphosphate, collagen, and thrombin. When AN 162 was given orally to guinea pigs at 30 to 100 mg/kg, an in vivo inhibitory effect on platelet aggregability was found. Though it activated platelet factor 3, the concentration of AN 162 required for substantial activation was greater than that for inhibition of platelet aggregation. No effect on plasma clotting factors was found at or below 300 µg/ml. Slight prolongation of whole blood clotting time was found in the rat and monkey.
Studies on the Participation of Hageman Factor in Fibrinolysis
Authors: McDonagh R.P , Ferguson J.H 
Published: June 2018

SummaryThe specific inhibition of the kaolin-mediated Hageman factor activation by the polycations : lysozyme, spermine tetrahydrochloride, and cytochrome c was confirmed. These polycations were without any antiplasmin or antiplasminogen-activator activity when tested in a one-stage lysis system. However, marked inhibition of plasminogen-activator generation in normal plasma by these polycations was noted in the activator-generation test. The proposed role of Hageman factor as that of a lysokinase or indirect activator of plasminogen is supported by these experiments.
The Kidney and Fibrinolysis
Authors: Marsh N. A 
Published: June 2018

SummaryMolecular exclusion chromatography was performed on samples of urine from normal and aminonucleoside nephrotic rats. Normal urine contained 2 peaks of urokinase activity, one having a molecular weight of 22,000 and the other around 200,000. Nephrotic urine contained three peaks of activity with MW’s 126,000, 60,000 and 30,000. Plasma activator determined from euglobulin precipitate had a MW. in excess of 200,000. The results indicate that in the normal animal, plasma plasminogen activator does not escape into the urine in substantial quantities but under the conditions of extreme proteinuria there may be some loss through the kidney. The alteration in urokinase output in nephrotic animals indicates a greatly disordered renal fibrinolytic enzyme system.The findings of this study largely support the hypothesis that plasma plasminogen activator of renal origin and urinary plasminogen activator (urokinase) are different molecular species.
Fibrinolytic Activation of Plasma by Means of Urokinase in Vitro and in Vivo
Authors: Nanninga L. B , Guest M. M 
Published: June 2018

SummaryThe activation of plasma by urokinase was studied in vitro by measuring the levels of fibrinogen, the anticoagulant split product of fibrinogen and the level of profibrinolysin. It is concluded that normal plasma contains about one CTA unit of plasmakinase, expressed in urokinase equivalents. The level of free fibrinolysin after complete activation of profibrinolysin was estimated to be approximately one-tenth of the initial profibrinolysin concentration. The split product of fibrinogen is present as an intermediate in a consecutive reaction in amounts dependent on the concentration of the activator present.
Persistence of Fibrinolytic Activity in Fragments of Human Veins Cultured in Vitro
Authors: Pandolfi M 
Published: June 2018

SummaryExplants from 5 adult human veins were cultured in a fibrinolytically inactive medium for 3 weeks and assayed for the presence of plasminogen activator by the fibrin slide technique. The explants from 3 veins showed fibrinolytic activity confined to their vasa vasorum for the whole duration of the culture; no decrease of activity was seen. The finding suggests that small blood vessels are able to synthesize plasminogen activator.
Acidosis Induced Disseminated Intravascular Microthrombosis and its Dissolution by Streptokinase
Authors: Broersma R. J , Bullemer G. D , Mammen E. F 
Published: June 2018

SummaryTo elucidate the mechanisms triggering disseminated intravascular coagulation (DIC) in shock, acidosis was produced in dogs by intravenous infusions of lactic acid over a period of 4 h. As the pH of the blood dropped, the blood pressure increased and the heart rate fell. The platelet counts dropped and whole blood clotting times shortened. The partial thromboplastin times and prothrombin times decreased as did the r-times and maximal amplitudes of the thrombelastograms. Simultaneously, the levels of prothrombin, fibrinogen, factors V and VIII decreased with time in acidosis. There was no evidence of a systemic activation of the fibrinolytic system. The euglobulin lysis times increased as did the thrombin times and there was no lysis observed in the thrombelastograms.Thrombi in the lungs, liver, spleen and kidneys, together with the coagulation changes indicated that the infusion of acid produced DIC, with the changes being similar to those produced in shock. The glomeruli were especially affected and the pictures were identical to those described in kidneys of animals having experienced a generalized Sanarelli-Shwartzman phenomenon.A pH value of 7.20 or lower appeared to be a potent trigger of intravascular coagulation. The lower the pH, the more thrombi were found in the tissues. The consumption of clotting factors and thrombus formation thus corresponded to the degree of acidosis.A generalized fibrinolytic state was induced using Streptokinase, after a 4 h period of acidosis and 1 h of compensation with sodium bicarbonate. Streptokinase was infused along with human euglobulin fractions on the basis of the streptokinase tolerance test of each dog’s blood and plasma. Thrombolysis was maintained for 3-4 h and this was reflected in the reduction of fibrin deposits in the tissues. Of 100 glomeruli counted/dog’s kidney, the average containing fibrin was 44 ± 11% after acidosis and 0.4 ± 0.3% after thrombolysis.
Some Properties of an Antiplasmin Substance from Rabbit Platelets
Authors: Wakabayashi K , Fujikawa K , Abe T 
Published: June 2018

SummaryRabbit platelets contained a proteinase inhibitor which inhibited plasmin, trypsin and chymotrypsin activities, and serum kallikrein to some extent. It did not inhibit pancreatic kallikrein and thrombin. It reacted stoechiometrically with these enzymes in a prompt fashion and was found to have a molecular weight of about 40,000.