bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Significant Enhancement of Fibrinolysis by Calcium Ion in a Cell Free System: The Shortening of Euglobulin Clot Lysis Time by Calcium Ion
Authors: Kojima Yumi , Urano Tetsumei , Kojima Kazuhisa , Serizawa Kiyohito , Takada Yumiko , Takada Akikazu 
Published: July 2018

SummaryWe investigated the roles of calcium ion (Ca2+) on euglobulin clot lysis time (ECLT) and found that the physiological concentration of Ca2+ significantly (4-5 times) shortened ECLT. The shortening was observed at the concentration of Ca2+ higher than 1.5-2.0 mM. Other divalent cations such as Mg2+, Zn2+ or Mn2+ didn’t change ECLT. Anti-tPA antibody or plasminogen activator inhibitor-1 prolonged ECLT in the absence of Ca2+, whereas they had no effect on ECLT shortened by Ca2+. Cl inactivator also had no effect. When barium absorbed plasma was employed, the shortening of ECLT by Ca2+ wasn’t observed, whereas it was recovered by the readdition of barium absorbed fraction. When factor X deficient plasma was employed, the shortening of ECLT by Ca2+ was also not observed. Thus, Ca2+ enhances fibrinolysis in a cell free system by a novel pathway in which the presence of factor X is prerequisite.
Neutrophil Derived Cathepsin G Induces Potentially Thrombogenic Changes in Human Endothelial Cells: a Scanning Electron Microscopy Study in Static and Dynamic Conditions
Authors: Kolpakov Valeri , D'Adamo Maria Cristina , Salvatore Lorena , Amore Concetta , Mironov Alexander , lacoviello Licia , Donati Maria Benedetta 
Published: July 2018

SummaryActivated neutrophils may promote thrombus formation by releasing proteases which may activate platelets, impair the fibrinolytic balance and injure the endothelial monolayer.We have investigated the morphological correlates of damage induced by activated neutrophils on the vascular wall, in particular the vascular injury induced by released cathepsin G in both static and dynamic conditions.Human umbilical vein endothelial cells were studied both in a cell culture system and in a model of perfused umbilical veins. At scanning electron microscopy, progressive alterations of the cell monolayer resulted in cell contraction, disruption of the intercellular contacts, formation of gaps and cell detachment.Contraction was associated with shape change of the endothelial cells, that appeared star-like, while the underlying extracellular matrix, a potentially thrombogenic surface, was exposed. Comparable cellular response was observed in an “in vivo” model of perfused rat arterial segment. Interestingly, cathepsin G was active at lower concentrations in perfused vessels than in culture systems. Restoration of blood flow in the arterial segment previously damaged by cathepsin G caused adhesion and spreading of platelets on the surface of the exposed extracellular matrix. The subsequent deposition of a fibrin network among adherent platelets, could be at least partially ascribed to the inhibition by cathepsin G of the vascular fibrinolytic potential.This study supports the suggestion that the release of cathepsin G by activated neutrophils, f.i. during inflammation, may contribute to thrombus formation by inducing extensive vascular damage.
Bridge Anticoagulant, a New Entity?
Authors: Mulder E 
Published: July 2018

SummaryAfter a critical analysis of the work of Nour Eldin and Wilkinson on the so-called Bridge anticoagulant, the author presents his own experimental work on this subject. It is concluded that one part of the evidence for a new inhibitor is not reproduceable, and that the other part depends on the presence of an inhibitor, anticephalin. This inhibitor has been known to exist for many years.
Über die Kontrolle der Wirkung fibrinolytischer Präparate
Authors: Fonio A 
Published: July 2018

Zusammenfassung1. Wird ein fibrinolytisch wirkendes Präparat dem Zitratplasma vor der Rekalzifizierung zugesetzt, dann befindet sich das Präparat bei Eintritt der Gerinnung und Beginn der Retraktion (in statu nascendi) bereits in den lockeren Fibrinmaschen und es wird ihm beim weiteren Eindringen kein Widerstand entgegengesetzt, so daß die fibrinolytische Auflösung des Gerinnsels unbehindert erfolgen kann (Prüfung 1).Wird im Gegensatz dazu das Präparat erst nach erfolgter Gerinnung und Retraktion zugeführt, dann setzen die fest retrahierten und einander eng anschließenden Fibrillenstränge seinem weiteren Eindringen Widerstand entgegen, so daß die totale fibrinolytische Auflösung des reträhierten Gerinnsels ausbleibt (Prüfung 2).2. Es werden sechs als fibrinolytisch-wirkend angegebene Präparate — drei Aktivatoren, zwei Plasminpräparate und ein weiteres in vitro nicht fibrinolytisch wirkendes Präparat — nach besonderen Testmethoden am Zitratplasma als Untersuchungssubstrat geprüft. Prüfung 1 : Zusatz des Präparates vor der Rekalzi-fizierung, und Prüfung 2: Zusatz nach Eintritt der Gerinnung und Retraktion.3. Eintragung der Befunde beider Methoden in je zwei Tabellen pro Präparat nach Prüfung 1 und 2 am Zitratplasma (Tabellen 1—14). Resultate: Prüfung 1: Drei Aktivatoren erwiesen sich als fibrinolytisch wirksam, ein Plasminpräparat desgleichen, zwei weitere Präparate wiesen keine Wirkung auf. Prüfung 2: Alle Präparate vermochten ausnahmslos keine totale Fibrinolysis des retrahierten Gerinnsels zu erzielen.4. Die gleichen Prüfungen mit gleicher Methodik und Dosierung wurden am Vollblutzitrat bei drei Aktivatoren durchgeführt (Tabellen 15—17). Die Resultate entsprechen den am Zitratplasma erhaltenen. Vorteile der Methode: Geringere Blutmenge, Wegfall der Zentrifugierung. Nachteil: Leicht erschwerte Beurteilung der Befunde durch den Gehalt an Erythrozyten.5. Übertragung der Befunde der Prüfung 1 und 2 auf die klinische Verwendung fibrinolytischer Präparate: Prüfung 1: Eine beginnende Thrombosierung mit einer Retraktion in statu nascendi, spontan erstmalig oder sekundär im Anschluß an bereits bestehenden Thrombus entstehend, wird durch ein wirksames fibrinolytisches Präparat günstig beeinflußt werden können. Prüfung 2: Ein bereits bestehender fest retrahierter Thrombus wird durch ein fibrinolytisches Präparat nicht zur Auflösung gebracht werden können. Bei wandständiger Haftung des Thrombus wird zudem nur eine frontale Angriffsfläche der fibrinolytischen Einwirkung ausgesetzt sein.
Substitution Therapy in Haemophilia B
Authors: Loeliger E. A , Hensen A , Mattern M. J , Alsbach E. E. J 
Published: July 2018

Conclusions1. Substitution therapy in haemophilia B without daily control of the Factor IX level in vivo by means of a reliable Factor IX assay cannot be adequate.2. The level of the Factor IX activity which, in cases of haemophilia B, ensures safe haemostasis after major trauma or in major surgery is at least 25% of normal.3. Assuming a normal t½ for Factor IX of 30 hours and a distribution pool of 7 l (normal adult), in cases of severe haemophilia the minimum amount of Factor IX to be rapidly transfused at the beginning of substitution (loading up of the pool up to 25%) is the amount present in 1.75 l of freshly drawn normal net plasma. The minimum daily dose necessary to maintain the 25% level is contained in 1 l. Due to the influence of body temperature, the required daily maintenance dose increases probably up to 2.4 l.4. Since rapid infusion of more than 1 l net plasma is not tolerated and since a daily dose of 2.4 l net plasma can hardly be achieved by means of exchange transfusion, partially purified and concentrated human Factor IX must be available. The plasma product PPSB, prepared by the “Centre National de Transfusion Sanguine” in Paris, contains, according to in vivo assays, about 10 times the activity of normal plasma for comparable volumes. The t½ of the Factor IX from PPSB appeared to be the same as from fresh plasma. The disappearance rate of the concentrated Factor IX from serum (CSB), prepared by the same institute, has not been estimated experimentally. According to clinical experience, however, the activity of CSB seems to be of a similar magnitude as that of PPSB. Adequate substitution with PPSB alone would require as initial loading-up dose 175 ml and as daily maintenance dose 100—240 ml of a 10-fold concentrated product, to be given in a continuous drip-infusion.5. In a case of mild haemophilia B (Factor IX ≅ 20%), transfusion of 0.8 l freshly drawn net plasma daily resulted in Factor IX levels of between 23 and 28% instead of the expected 35% of normal. This observation suggests that, for substitution therapy, mild cases of haemophilia B must be considered as rather severely affected.
Peptides Associated with Bovine Thrombin Preparations
Authors: Landaburu Ricardo H. , Harmison Charles R. , Seegers Walter H. 
Published: July 2018

SummaryWhen bovine thrombin was prepared by one method the N-terminal amino acid was glutamic acid while with another method it was threonine. In urea solution these N-terminal amino acids were removed in association with peptides and the N-terminal amino acid of the main protein was leucine. Urea treated thrombin had the same specific activity as the original from which it was prepared, and also had the same carbohydrate content. It was, however, less soluble in water and had a higher viscosity. The sedimentation constant was concentration dependent. Before treatment with urea the rate of change of the sedimentation constant with concentration was positive. After urea treatment it was negative. Extrapolation to zero concentration gave the same value for thrombin as for urea treated thrombin. The peptides removed from thrombin function to alter the properties of the protein. They are attached by bonds that are broken in urea solution. Very likely the original prothrombin molecule is, in part at least, composed of sub-units consisting of polypeptide chains held together by bonds broken by reagents such as sodium citrate. In addition to alanine, bovine prothrombin has arginine as N-terminal amino acid, but the latter was uncovered only in urea solution.
Methods for the Concentration of Bovine Ac-Globulin (Factor V)
Authors: Landaburu Ricardo H. , Seegers Walter H. 
Published: July 2018

SummaryAn attempt was made to obtain Ac-globulin from bovine plasma. The concentrates contain mostly protein, and phosphorus is also present. The stability characteristics vary from one preparation to another, but in general there was no loss before 1 month in a deep freeze or before 1 week in an icebox, or before 5 hours at room temperature. Reducing agents destroy the activity rapidly. S-acetylmercaptosuccinic anhydride is an effective stabilizing agent. Greatest stability was at pH 6.0.In the purification bovine plasma is adsorbed with barium carbonate and diluted 6-fold with water. Protein is removed at pH 6.0 and the Ac-globulin is precipitated at pH 5.0. Rivanol and alcohol fractionation is followed by chromatography on Amberlite IRC-50 or DEAE-cellulose. The final product is obtained by isoelectric precipitation.
Platelet Distribution and Survival in Plasma Clots and Thrombi
Authors: Wolf Peter 
Published: July 2018

SummaryViscous metamorphosis of platelets in native and sequestrene plasma, before and after thrombin and plasmin action, has been studied. A method for the examination of platelet distribution in plasma clots and tissue paraffin sections is described.It was found that not all platelets undergo viscous metamorphosis in plasma clots or in intravascular thrombi. Platelets before and after viscous metamorphosis are not digested by plasmin. After plasmin action intact platelets can still undergo viscous metamorphosis and the fibrils which are then produced are not made of fibrin.Thrombin in the absence of calcium ions will not cause platelets to undergo viscous metamorphosis.Total blockage of cardiac blood vessels by platelet masses in cases of cardiac infarction is demonstrated. The significance of these findings in relation to blood sludging, and future lines of treatment are discussed.
Beitrag zur fibrinolytischen Therapie mit Streptokinase und Fibrinolysin®
Authors: Fischbacher Walter 
Published: July 2018

ZusammenfassungNach einem Vergleich der direkt wirkenden Fibrinolytika (Streptokinase, Fibrinolysin, Urokinase) mit den indirekt wirkenden (Nikotinsäure und -derivate, Pyrexal u. a.) wird die Wirksamkeit verschiedener Streptokinase- und Fibrinolysinpräparate miteinander verglichen. Es werden Methoden im Thromb-elastographen beschrieben, welche sich gut eignen für die Vorkontrolle (und Dosierung) sowie für die Therapiekontrolle (SK-Toleranz; Plasmintoleranz; ε-ACS-Toleranz; Mischversuche zum Nachweis der SK-Aktivität). Die Resultate nach innerem Fibrinolysetyp und nach äußerem (therapeutischem) werden einander gegenübergestellt. Nach Angaben für die Dosierung und Applikationsart folgen vier ausgewählte klinisch-therapeutische Beispiele mit zum Teil sehr schönen Erfolgen. Die Indikationen, Kontraindikationen sowie die von uns gesehenen Komplikationen werden erläutert. Die Kombination mit Antikoagulantien ist obligat. Auf Grund von In-vitro-Versuchen nach äußerem Fibrinolysetyp scheint es, daß das „Fibrinolysin”, welches als Mischung von Streptokinase und Profibrinolysin aufzufassen ist, der Streptokinase alleine etwas überlegen ist.
A Critical Review of the Evidence for a Continuous Hemostasis in vivo
Authors: Hjort Peter F , Hasselback Richard 
Published: July 2018

I. ConclusionsInjury to vessels leads to the formation of platelet plugs and fibrin clots. For nearly a century it has been known that these mechanisms stop bleeding and may produce thrombi. They may be triggered by trivial trauma (180), and hemostasis possibly occurs in one or more vessels at all times in the normal body. The blood is capable of removing at least the fibrin part of such deposits; however, some of them may progress into arteriosclerotic lesions (59). The accumulated evidence, therefore, supports the concept of a hemostatic balance on the local level, triggered by an abnormal local factor.In this review, however, we are concerned with a general and continuous hemostasis which takes place on the normal, uninjured endothelium. Direct examinations have suggested that hemostatic products are present on normal endothelium, but these investigations cannot be accepted as conclusive. Much of the indirect evidence is weak or controversial. However, the purpura and increased capillary fragility in platelet disorders strongly suggest that platelets are important for vascular integrity, and animal experiments suggest that both platelets and coagulation influence vascular permeability. At present, therefore, the theory of continuous hemostasis can neither be accepted nor rejected; further evidence must be collected.
Die Anwendung von Gelfiltration zur weiteren Reinigung von Rinderprothrombin
Authors: Mammen E , Ramien A 
Published: July 2018

ZusammenfassungProthrombin wurde aus Rinderplasma nach der von Seegers beschriebenen Methode (13, 19) isoliert. Durch Gelfiltration an Sephadex G-75 konnte die spezifische Aktivität (Einheiten pro Milligramm Tyrosin) um 27 bis 45% gesteigert werden. Die Ausbeute an Prothrombin nach der Filtration betrug 87 bis 97%. Als Elutionsmittel wurde 0,9% Kochsalzlösung mit verschiedenem pH verwandt, wobei pH 7,0 und pH 8,0 die besten Ergebnisse brachten. Das durch Sephadex filtrierte Prothrombin hat seine Aktivierungseigenschaften nicht geändert, in 25%iger Natriumzitratlösung entsteht Thrombin, und mit Thrombin entsteht Autoprothrombin II. Die mit Sephadex erhaltenen Ergebnisse werden mit den bislang angewandten Verfahren der weiteren Reinigung von Prothrombin verglichen.
On the Inhibiting Effect of ε-Amino Caproic Acid upon the Fibrinolytic System During „Spontaneous Activation”
Authors: Doleschel W , Auerswald W , von Lützow A 
Published: July 2018

SummaryThe effect of ε-ACA (ε-amino caproic acid) upon the factors of the fibrinolytic system contained in a human euglobulin preparation was studied during “spontaneous activation“. The results obtained with the bovine fibrin plate method, the clot lysis, and the casein tests demonstrated a strong inhibitory effect of ε-ACA on the formation of a serum plasminogen activator and on the conversion of plasminogen into plasmin by this activator resulting in a “potentiated inhibition“. On the other hand, no inhibition of plasmin could be found with ε-ACA in concentrations below 0.1 molar. In tests on human fibrin plates finally it became obvious that the human serum plasminogen activator contained in purified human plasmin preparations, having a much higher specificity towards the human plasminogen than the bovine one becomes inhibited by relatively low ε-ACA concentrations. The significance of these results for the inhibitory effect of ε ACA on the fibrinolytic system in vivo was discussed.
The Effects of Leguminous Seed Extracts on Blood Coagulation
Authors: Speer R. J , Porter J. L 
Published: July 2018

SummaryThe saline extracts of one hundred leguminous seed were screened for their effect on blood coagulation by the following tests: thrombin clot time, recalcification time, Quick prothrombin time, clot lysis and clot retraction. Nineteen of these extracts, when reacted with normal plasma, gave a prolonged clot time in at least one of two tests: recalcification time and Quick prothrombin time. The eight which gave a prolonged Quick prothrombin time were tested for inhibition in the following assay systems: Factor V, factor VII-complex, and prothrombin. All nineteen, including the seventeen which prolonged the re-calcification time and the two which did not, were tested for their inhibitory action in the following assay systems: Factor VIII, factor IX, and plasma thromboplastin antecedent.The inhibition of prothrombin, factor V, and factor VII-complex was mild and not specific for any of these factors. Factor V activity was depressed more than the other two. By contrast, the inhibition of factor VIII, factor IX, and plasma thromboplastin antecedent was very strong and demonstrated a relatively high degree of specificity.
Three Dimensional Structure of Human Fibrinogen under Aqueous Conditions Visualized by Atomic Force Microscopy
Authors: Marchant Roger E , Barb Matthew D , Shainoff John R , Eppell Steven J , Wilson David L , Siedlecki Christopher A 
Published: July 2018

SummaryFibrinogen plays a central role in surface-induced thrombosis. However, the interactions of fibrinogen with different substrata remain poorly understood because of the difficulties involved in imaging globular proteins under aqueous conditions. We present detailed three dimensional molecular scale images of fibrinogen molecules on a hydrophobic surface under aqueous conditions obtained by atomic force microscopy. Hydrated fibrinogen monomers are visualized as overlapping ellipsoids; dimers and trimers have linear conformations predominantly, and increased affinity for the hydrophobic surface compared with monomeric fibrinogen. The results demonstrate the importance of hydration on protein structure and properties that affect surface-dependent interactions.
Soluble P-selectin in Atherosclerosis: A Comparison with Endothelial Cell and Platelet Markers
Authors: Blann Andrew D , Lip Gregory Y H , Beevers D Gareth , McCollum Charles N 
Published: July 2018

Summaryvon Willebrand factor and soluble thrombomodulin are established plasma markers of endothelial cell dysfunction, whilst beta thromboglobulin is an established plasma marker of platelet activity. Soluble P-selectin may be the product of either or both types of cell and levels of all four molecules have been previously found to be increased in atherosclerosis. To determine the relationship of soluble P-selectin to the endothelial cell and platelet products, we measured the four indices in a case control study of 55 patients with peripheral vascular disease and 55 age and sex matched controls, von Willebrand factor (p <0.0001), beta thromboglobulin (p = 0.0006), soluble P-selectin (p = 0.0021) and soluble thrombomodulin (p = 0.021) were all raised in the patients. Soluble P-selectin correlated with beta thromboglobulin (r = 0.34, p = 0.019) but failed to correlate with either endothelial cell marker. Co-culture of endothelial cells in vitro with bovine thrombin resulted in increased levels of von Willebrand factor in the supernatants but levels of soluble thrombomodulin and soluble P-selectin were not enhanced. Exposure of endothelial cell monolayers to elastase resulted in different patterns of release of von Willebrand factor, soluble thrombomodulin and soluble P-selectin. We suggest that soluble P-selectin is unlikely to arise from the endothelium and may be a new marker of platelet activation in atherosclerosis.
Positive Association of the β Fibrinogen H1/H2 Gene Variation to Basal Fibrinogen Levels and to the Increase in Fibrinogen Concentration during Acute Phase Reaction but not to Coronary Artery Disease and Myocardial Infarction
Authors: Gardemann Andreas , Schwartz Oliver , Haberbosch Werner , Katz Norbert , Weiß Tanja , Tillmanns Harald , Hehrlein Friedrich Wilhelm , Waas Wolfgang , Eberbach Andreas 
Published: July 2018

Summary
Background: Fibrinogen has been demonstrated to be an independent risk factor of cardiovascular disease. The absence of the Haelll cutting site (H2 allele) of an H1/H2 gene variation in the promoter region of the (β fibrinogen gene was associated with increased levels of fibrinogen. Methods and Results: In the present study, the effects of the H1/H2 gene variation not only on plasma fibrinogen concentrations but also on coronary artery disease (CAD) and myocardial infarction (MI) were investigated in 923 individuals who underwent coronary angiography for diagnostic purposes. Relation of the H1/H2 genotype to fibrinogen plasma levels: A strong association was observed between the H1/H2 gene variation and fibrinogen levels. The differences in fibrinogen plasma levels between H2H2 and H1H1 homozygotes were almost threefold more pronounced within subjects with clinical chemical signs of an acute phase reaction (CRP ≥ 7.5 mg/1) than within a subgroup of subjects without these signs (CRP < 7.5 mg/1) (median of CRP distribution: 7.5 mg/1). In 207 patients who underwent aortocoronary bypass surgery plasma fibrinogen levels were almost identical directly after surgery. Two days after operation fibrinogen increased to clearly higher levels in H2H2 homozygotes than in H1H2 and H1H1 genotypes, whereas almost the same maximal increases in fibrinogen concentrations were reached 3-4 days after surgery in all individuals. Relation of the H1/H2 genotype to CAD and MI. Whereas in the total population the plasma fibrinogen concentrations were strongly associated with smoking, CAD and MI, an association of the H1/H2 gene variation to CAD and MI was not detected. However, mean age at first MI of H2H2 individuals (62.9 years) was clearly higher than of H1H2 genotypes (56.9 years) and of H1H1 subjects (56.4 years). In addition, in a subgroup of individuals with a higher risk of MI by either high apoB and/or low apoAl plasma levels the portion of MI patients was clearly smaller within H2H2 homozygotes than within H1H2 or H1H1 genotypes, although – also in these high risk groups – mean age at first MI of H2H2 individuals were higher than of the other two genotypes.
Conclusions: Obviously, the H2 allele of the fibrinogen H1/H2 genotype does not only influence basal fibrinogen concentrations, but particularly also the extent of fibrinogen level increase during acute phase reaction. Whereas the fibrinogen plasma level is positively associated with coronary artery disease and myocardial infarction, the H2 allele - although exhibiting an association with elevated fibrinogen levels - was not positively associated with CAD and MI.