bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive Chronotropic Effect of Dialysable Peptides Derived from Plasmin Digestion of Bovine Fibrinogen Preparations. Role of Cyclic AMP
Authors: Buczko W. , Franco R. , Bianchetti G. , Donati M. B. , Gaetano G. de 
Published: June 2019

Dialysable peptides (< 5,000 M. W.) derived from plasmin digestion of bovine fibrinogen preparations (Kabi) exerted a marked positive chronotropic effect on isolated rat atria. This effect reached a peak within two to four minutes, lasted as a plateau during four to six minutes and then slowly disappeared. It was abolished by glycolytic inhibitors such as NaF and 2-deoxy-D-glucose, not by inhibitors of oxidative phosphorylation such as 2,4-dinitrophenol. Ouabain, histamine and propranolol had no effect on the digests-induced chronotropic effect. Theophylline, an inhibitor of phosphodiesterases, showed an additive effect, whereas imidazole, an activator of phosphodiesterases, was inhibitory. Both cyclic AMP levels and phosphorylase activity of isolated rat atria were increased by the digests. The maximum increase was observed 30 and 90 seconds respectively, after the addition of the digests to the isolated atria. Theophylline exerted an additive effect and imidazole an inhibitory effect on digests-induced increase of cyclic AMP levels and phosphorylase activity. In our test system, digests behaved similarly to glucagon. It is concluded that cyclic AMP plays an important role in mediating the described positive chronotropic effect of fibrinogen-derived peptides. Such a role of cyclic AMP could also be relevant for other biological activities exerted by these peptides (e.g. the inhibition of ADP-induced platelet aggregation and the increase of vascular permeability and of the chemotactic activity of leucocytes).(Supported by Grant N. 73.00400.04 of the Italian Research Council (C. N. R.).)
Flaujeac Trait: Deficiency of Human HMW Kininogen
Authors: Lacombe M. J. , Miller D. R. , Wuepper K. D. 
Published: June 2019

The propositus, a 50 year-old woman of French Caucasian extraction, was the product of a consanguineous marriage. Her plasma, obtained at the time of a surgical procedure, exhibited prolonged whole blood clotting time and prolonged activated PTT (618 sec); the one-stage prothrombin time was normal. Her plasma contained normal amounts of coagulation factors XII, XI, IX, VIII, VII, X, V, II, I and Fletcher factor. Full correction was obtained upon mixing with normal plasma, excluding a circulating anticoagulant. The defect of the propositus, surname Flaujeac, was designated Flaujeac Trait. Three of the patient’s children had reduced amounts of the factor (23%, 27%, 30%) while a fourth child was at the lower limit of normal (55%).Flaujeac trait plasma was also found to have prolonged euglobulin lysis (194 min), failure of kaolin-activated kinin formation or generation of the permeability globulin PF/dil. Each of these deficits was corrected by addition of a factor separable from Hageman factor or Fletcher factor (prekallikrein). The Flaujeac factor was identified as a heat stable, α-globulin which eluted from Sephadex G-200 corresponding to a MW of 170,000. The factor corresponded exactly with fractions containing HMW kininogen. The half-life in plasma following transfusion was 6.5 days. Kininogen antigen was markedly reduced in Flaujeac plasma, only some partially cross-reacting material remained. Antibody to kininogen depleted the factor from normal plasma.The intrinsic coagulation, fibrinolytic and kinin-forming pathways and the formation of PF/dil are dependent upon plasma HMW kininogen.
Interactions between Factors XII and XI and Activating Agents in Purified Systems
Authors: Binder B. , Krug G. , Vukovich Th. 
Published: June 2019

To obtain a better understanding of the activating mechanism of F XI we studied the interaction of highly purified F XII and F XI with activating agents (kaolin, cephalin) F XII as well as F XI were purified from ACD-plasma (ionic exchange procedures, gel fractionation). Both coagulation factors were obtained with a specific activity per mg protein of approximately 4000 times the value of the original plasma, showing a single band in polyacrylamide gel electrophoresis. The preparations contained less than 1 per cent of their activated forms.F XII and F XI as well as the mixture of both were exposed to kaolin, cephalin, or a kaolin-cephalin mixture, respectively. F XII was adsorbed to about 90 per cent by kaolin alone and the adsorbed fraction was activated completely within minutes; F XI on the other hand was neither adsorbed nor activated by kaolin. The kaolin-activated F XII effected practically no activation of F XI. By cephalin F XII was activated only within hours, but the so activated F XII produced activation of F XI corresponding to F XIIa available in a ratio F XIIa/F XI a of 10/1. A mixture of kaolin and cephalin activated F XII within minutes; ca 20 to 30 per cent of the resulting F XIIa activity became not adsorbed to kaolin and this F XII a activates F XI in the same ratio as in the case of cephalin-activated F XII. Gel fractionation of F XII and F XI together with cephalin revealed that only F XIIa is bound to the phospholipid; no solid complex formation was found between F XI and cephalin or between F XI and F XII.(Supp. by a Grant from the Eisner-Foundation.)
Heparin Neutralizing Activity in the Diagnosis of Acute Myocardial Infarction
Authors: O’Brien J. R. , Etherington M. D. , Jamieson S. , Sussex J. 
Published: June 2019

We have previously demonstrated that, relative to controls, patients long after myocardial infarction and patients with atherosclerosis have highly significantly shorter heparin thrombin clotting times (HTCT) using platelet poor plasma; but there was considerable overlap between the two groups.We have now studied 89 patients admitted with acute chest pain. In 54 of these a firm diagnosis of acute myocardial infarction (ac-MI) was made and the HTCT was very short (mean 12.8 sees) and in 48 it was less than 16 sees. In 34 patients, ac-MI was excluded and the diagnosis was usually “angina”; the HTCT was much longer (mean 25.1 sees) and in 32 it was over 16 sees. Thus there was almost no overlap between these two groups. It is suggested that this test should be adopted as a quick and reliable further test to establish a diagnosis of ac-MI (providing other reasons for very short HTCTs can be excluded, e.g. D. I. C., and provinding the patient’s thrombin clotting time is normal).This HTCT measures non-specific heparin neutralizing activity; nevertheless the evidence suggests that it is measuring platelet factor 4 liberated from damaged or “activated” platelets into the plasma. These findings underline the probable important contribution of platelets in ac-MI.
Study of Albinism in Relation to Hermanský-Pudlák Syndrome
Authors: Hermanský F. , Cieslar P. , Matousová O. , Smetana K. 
Published: June 2019

Up to now 24 patients with oculocutaneous albinism have been investigated in this study to find out the frequency of characteristic signs of HPS. Seven of them suffered from mild bleeding tendency. Platelet defects of storage pool disorder type have been revealed at a varying degree in all these cases. (Aggregation abnormalities, decrease of total platelet ADP contents and of its release, lower serotonin uptake with the lack of very dense bodies in ultrathin sections). This thrombocytophathy has been regularly associated with the storage of pigment typical for HPS in their bone marrow. In 7 of 17 remaining albinos with normal platelet functions some increase in the accumulation of non-specific cytochemically different lipopigments was noted.Our results demonstrate a rather frequent occurence of HPS in albinos and suggest a mutation of one common gene or of closely linked genes as a cause of complete HPS.
Amine Inhibition of Fibrin Cross-Linking
Authors: Dubiel M. K. , Scully M. F. , Lane D. A. , Kakkar V. V. 
Published: June 2019

Various amines have been shown to possess an inhibitory effect on the enzymatic cross-linking of fibrin in vitro, as measured by fibrin isolubility in monochloroacetic acid (Lorand, L. et al., Biochemistry, 7, 1214, 1968). The amines were found to act as pseudo-donor substrates for the enzyme Factor XIIIa.We have measured γ dimer and α polymer formation in vitro, using 125I-fibrinogen as a tracer. A solution of 0.4% fibrinogen clotted with thrombin at pH 7.5 produced 50% of the γ dimers within 2 seconds and 65% of the oc polymers in approximately 15 minutes. In the presence of 5 mM isoniazid, glycine methyl ester, histamine and putrescine, 60-70% inhibition of α polymer formation was observed at 15 minutes, as compared with the control incubation mixture. There was minimal inhibition of γ dimer formation. Tyramine and histidine dihydrochloride had no inhibitory effect upon either γ dimer or α polymer formation.These results provide further evidence that a carboxylate anion in the vicinity of the amino group reduces inhibition of Factor XIII a and suggests that inhibition as measured by acid insolubility is also influenced by α polymer formation.
Fibrin-Blood Platelet Interaction in a Contracting Clot
Authors: Cohen I. , Gabbay J. , Glaser T. , Oplatka A. 
Published: June 2019

The interaction of the fibrous protein fibrin and blood platelets was studied by measuring tension development in clots containing different ratios of these two components. Maximal isometric tension (MT) attained a saturating value when plotted as a function of the concentration of either component at a constant concentration of the other. The value of MT increases linearly with the minimal platelet concentration (Ps) required in order to reach saturation at various different fibrin concentrations. A linear relationship also holds in a plot of Ps versus the logarithm of the corresponding fibrin concentration. An attempt was made to calculate the isometric tension developed by a platelet.When the cylindrical clots contracted isotonically, the velocity normalized with respect to the momentary length was found to be constant. This velocity decreased in an hyperbolic manner with increasing fibrin concentration at a constant concentration of blood platelets. The results are interpreted in terms of a three-dimensional network in which the blood platelets serve as contractile cross-bridges connecting fibrin fibers.
Effects of pH on Arachidonic Acid Induced Platelet Aggregation
Authors: Gerrard J. M. , White J. G. , Krivit W. 
Published: June 2019

Arachidonic Acid (AA) produces platelet aggregation through conversion to Prostaglandin (PG) G a and PGH2. The present study evaluated the effect of pH on AA induced aggregation and production of PGG2 and PGH2. AA was added to 1 ml containing 2 × 108 washed platelets. The pH of the reaction was adjusted from pH 6.5 to pH 9.0 using C02 or NaHC03. Aggregation was monitored by recording nephelometry.Production of PGG2 and PGH2 was evaluated at 30 seconds after addition of AA by SnCl2 conversion of the endoperoxides to PGF2Ct and subsequent radioimmunoassay. Production of 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), 12L-hyd,roxy-5,8,10-heptadecatrienoic acid (HHT), and 8-(l-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (PHD), three metabolites of AA, was monitored using 1-14C AA and thin layer radiochromatography. The optimum pH for AA induced platelet aggregation and for production of PGG2 and PGH2 was 8.0. Maximal production of PHD similarly occurred at pH 8.0. However, production of HHT was maximal at pH 9.0 and production of HETE was maximal at pH 6.5. The results show that the platelet prostaglandin synthetase has a pH optimum of 8.0 similar to the sheep vesicular gland synthetase and suggests an enzymatic basis for the finding that the pH optimum for collagen induced aggregation of washed platelets is 8.0. The results also suggest that production of PHD, but not HHT or HETE, is closely linked both to platelet production of PGG2 and PGH2 and the degree of platelet aggregation.
The Isolation of Prothrombin Fragments from Plasma Clotted with Russell Viper Venom (RVV)
Authors: Aronson D. L. , Stevan L. , Ball A. P. , Franza R. B. , Young A. M. 
Published: June 2019

Plasma clotted with RVV (1 mg/L) for 90 minutes loses 60% of the measurable prothrombin. Batch adsorption of the serum with DEAE-cellulose followed by hydroxyapatite chromatography and gel filtration on Sephadex G-200 yields 4 mg/L of Fragment F1.2, the prothrombin NH2-terminal activation peptide of mass = 35,000 daltons. Identification is based on migration on SDS acrylamide electrophoresis and the ability of small amounts of thrombin to cleave F1.2 into F1 and F2.The presence of Fragment F1.2 after clotting plasma in this manner demonstrates that the average amount of thrombin present during clotting was less than 1 u/ml. This fact in combination with 60% prothrombin consumption indicates that the thrombin formed is inactivated in less than one minute.F1.2 is soluble in 0.9 M perchloric acid, as are F1 and F2. This property may simplify the purification process and allow quantitation of F1.2 release during clotting.
Prothrombin Activation
Authors: Greenberg J. , Goldstein R. 
Published: June 2019

Prothrombin DFP treated (II) when activated by Xa in the presence of 10-2 M DFP, generated 0.1 Iowa unit of active Thrombin (IIa) per one mg of II (IIa is 10-3 of the weight of Xa present); 26% of the original II was converted to inactive IIa- Reduction of the activation mixture produced chains of 42-57,000 daltons. During the first 90 sec of the lag phase of that reaction, peptides and/or amino acids were released. During the first hour of II activation by Xa in the presence of 10-5 M DFP (weights of active IIa ÷ f Xa = 0.9) transient intermediates of M. W. of 65-74,000 were observed. These findings indicate the following Xa activation of II pathway : II (one chain) → intermediate (s) (two chains) + peptides or amino acids → fragment(s) + thrombin(s) (two chains). The proposed pathway is consistent with earlier reports of production of fragments of 37,000 and 45,000 daltons, the multiple forms of II-, the rate and the yield of II conversion to IIa via its physiological phospholipoprotein complex and also of the kinetic rate requirement that II be attached to that complex, through its N-terminal portion, until the last step of IIa production. During the first ten min of II activation by Xa, in absence of DFP (IIa ÷ Xa = 2), the production of IIa was found to proceed partially via above Xa activation pathway. As the amounts of IIa increased, the IIa pathway (via Int. 1, 60,000 daltons) exceeded that of Xa pathway.(Supported by N. I. H. Grant # HL-14657.)
A Screening Method for Deep Venous Thrombosis
Authors: Jaffrin M. Y. , Michaux B. , Quarante J. J. 
Published: June 2019

This paper presents some preliminary results on a non invasive technique for the detection of deep venous thrombosis. This method is simple, completely atraumatic and capable of detecting silent thrombosis which eludes clinical examination. It also integrates the contribution of all veins in the limb in a single measurement. The principle of the method consists in interrupting the venous return in the thigh by a cuff inflated to pressures ranging from 30 to 50 mmHg. The subsequent increase in distal venous volume is monitored on the calf by a four-electrode impedance plethysmograph or by a mercury-in-silastic straingage plethysmograph (Parks) IPG 100 of Codman or Diacardyne of Ieram). The trace representing the limb volume or perimeter reaches a plateau after a period of about a minute when the rising venous pressure reaches the pressure in the thigh cuff, and the venous return is restored. Then the thigh cuff is rapidly deflated and the rate at which the limb volume returns to the preocclusion level is recorded. The signal decays approximately exponentially with time with a time constant equal to RC where C is the venous compliance and R the venous flow resistance downstream of the cuff. The time constant ranges from. 7 to 2 sec for healthy veins. If a large vein is thrombosed the flow resistance is higher and the time constant exceeds 2.5 sec. The method has being tested on about 50 patients of the Centre Hospitalier of Compiégne and compares favorably with clinical methods or with Doppler ultrasound if the leg and cuff are properly positioned. The average time constant was found to be equal to 1.75 sec for patients known to be free of thrombosis and to 4.0 sec for patients with confirmed venous thrombosis. Present work is directed towards improving the instrumentation. The determination of the time constant is made easier by filtering out arterial pulsations superposed on the signal. By using an automatic inflation with preset inflation pressure and duration accurate and reproducible inflation sequences of tho cuff are possible.This may lead to additional diagnostic criteria based on the rate of signal rise.
Ultrastructural Changes in Human Platelet During Fatty Acid Salt Aggregation
Authors: Prost-Dvojakovic R. J. , Men R. Le , Soria J. , Boisseau M. 
Published: June 2019

We studied ultrastructural changes in platelet aggregation induced by fatty acid (FFA) salts. The platelets were used either directly in their original plasma or separated from plasma proteins by washing or filtration on 2 B Sepharose gel and suspended in a buffer solution with or without albumin.After fixation for electron microscopy the aggregating FF A salts appear as micellar structures or spherules of large size ressembling liposomes.During the first seconds of contact between the platelets and the FFA salts we observed the spreading of platelets on the surface of the structures formed, and the particles smaller than 1 μ were phagocytized. After a few minutes platelet release occurred followed by total degranulation of platelets during the formation of aggregates. After eight minutes the aggregates still contain FFA salts structures.These results confirm our earlier views that the mechanism of FFA salt induced aggregation differs from that of aggregation by other agents, and could be due to the micellar structure.
Experimental Modification of the Platelet Release Reaction Induced by Collagen
Authors: Gordon J. L. , Maclntyre D. E. , Drummond A. H. 
Published: June 2019

Collagen-induced release of platelet constituents can be divided into two kinetically-distinct phases, only one of which is associated with platelet aggregation, and the aggregation-independent release is less susceptible to inhibition by pharmacological agents (Drummond and Gordon, 1974). Minor variations in experimental conditions alter the release reaction profile. Collagen was incubated with platelet rich plasma (PRP) for one minute at 37°, under conditions in which no aggregation occurred ( + 3nM EDTA or in absence of stirring). The reaction was ‘terminated’ by addition of ice-cold EDTA-saline and samples were then centrifuged (14,800 g) under the conditions described in the table.No significant release was detected under any of the above conditions if saline were substituted for collagen suspension.These results indicate that the storage temperature and time after centrifugation are as important as the centrifugation conditions themselves, and suggest reasons for discrepancies reported in previous studies of collagen induced release kinetics.Drummond, A. H. and Gordon, J. L. (1974). Brit. J. Pharmacol. 52, 130 P.
Leucocytes and Platelets in Isolated Lung Perfusion
Authors: Zandwijk N. van , Lenssen Th. F. J. , Prakke Elisabeth M. , Meer J. van der , Groen A. S. , Wagenvoort G. A. 
Published: June 2019

Removal of leucocytes and platelets from homologous blood prevents early functional and morphologic deterioration of an isolated rabbit lung preparation. Lungs perfused with whole blood have a marked ability for granulocyte sequestration. Control experiments in which the perfusion system was not connected with the lung revealed an increase of plasma serotonin and histamine levels due to platelet injury and/or aggregation generated by the perfusion circuit. When an isolated lung was connected with the circuit, plasma serotonin was largely metabolized. However, the metabolic uptake of serotonin by lungs perfused with whole blood decreased after 30 min while pulmonary vascular resistence (PVR) increased. In contrast, perfusion experiments with blood from which almost all leucocytes had been removed, were characterized by a less pronounced rise of plasma serotonin level and no or little change in PVR.It is concluded that leucocytes particularly granulocytes most likely traumatized by the extracorporeal procedure, have a detrimental effect on the integrity of perfused isolated lungs. Damage of endothelium, which has been recognized as a site of serotonin metabolism, could then be an early symptom. The results of our experiments in which the perfused isolated lung preparation has been used as a model for pulmonary dysfunction after extracorporeal circulation and massive transfusion warrants more attention to be paid to the role granulocytes and platelets play in the genesis of respiratory distress after such procedures.
Platelet Aggregation in whole Blood
Authors: Sivertsen Ulla 
Published: June 2019

A semi-micromethod for testing the aggregability of platelets in whole blood is described. Aggregation is induced with ADP at 37° C in 0,1 ml samples of citrated blood. At 30 seconds intervals aggregation is stopped and the number of nonaggregated platelets are determined.The main results as found in “normal” human donors (having received no drugs) are:1) Platelet aggregation in whole blood is less dependent on the pH, the platelet number, the time elapse from blood sampling to aggregation test as compared with platelet aggregation in plasma (a.m. Born).2) Disaggregation is only observed to a minor degree (after 180 seconds the maximal disaggregation amounts to 30% of the aggregated platelets).3) Secondary aggregation is negligible.The technique is simple and can be used in the clinic without special equipments. The results are discussed.
Light Scattering and Platelet Aggregation
Authors: Stoltz J. F. , Larcan A. , Batoz J. F. , Streif F. 
Published: June 2019

After a short recall of the theories concerning nephelometry and light scattering, the authors develop their experimental study, which is divided into three parts :- platelets absorption i.e. wave lengths- light variation curves transmitted or scattered according to platelet concentration- aggregation by nephelometric method and by light scattering.These experiments allow the authors to conclude that platelets do not present a specific absorption; that the variations of the light transmitted or scattered is exponential in function of the platelet concentration and that the aggregation test affords essentially a measurement of the decrease of the number of free platelets in the medium.Besides, they observe that the measures of aggregation kinetics, or the problem of platelet shape change are not specific and should be investigated with the help of other methods.This work was supported by D. R. M. E. grant (Biological Section).