bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Studies on Thrombolysis with Plasminogen and Streptokinase
Authors: Rice Lory R. , Sogar S. , Kakkar V. V. 
Published: June 2019

It has been suggested that in vivo thrombi and emboli become deficient in intrinsic plasminogen (Pig) though plasma proteins are still able to percolate through the fibrin mesh which forms the basic structure of the clot. Thus it is reasonable to expect that such Pig-deficient thrombi will be degraded at a faster rate, if perfusion with a plasminogen activator is preceded by a preliminary perfusion of plasminogen itself. Such a hypothesis has important implications for clinical therapy.Our studies were undertaken in vitro, using human thrombo-emboli removed at postmortem. An initial perfusion wit 125I-labelled Pig showed an uptake of Pig into the thrombus about 3 times higher than the perfusion fluid, as shown previously (Strachan et al., 1974). Subsequent perfusion with buffer containing streptokinase (Sk) showed increased lysis under certain conditions, compared to that when either Pig was omitted from the preliminary perfusion or Sk from the main perfusion. This enhanced lysis was shown to depend upon the Pig concentration of the perfusion fluid.Strachan, C. J. L. et al. (1974), Thrombosis Res., 4, 303.
Purification of Human Urokinase and its Topographical Localisation in Renal Parenchyma
Authors: Andrassy K. , Ritz E. , Bleyl U. , Egbring R. 
Published: June 2019

Urokinase Leo was separated by agar zone electrophoresis into an anodic and cathodic fraction. The cathodic fraction, isolated from agar gel by ultracentrifugation, showed two precipitation bands with rabbit Urokinase antibodies. Band I displayed main Urokinase activity, in band II Urokinase was present in a high molecular weight complex with human serum proteins (albumin, a2-macroglobulin, a2HS glycoprotein); with affinity chromatography further separation of Urokinase isoenzymes from serum proteins was possible. The isoelectric point of these two Urokinase isoenzymes were pH 6.8 and pH 8.7 respectively in preliminary results with isoelectric focusing. Purification steps were controlled by disc gel electrophoresis and immunological techniques (Ouchterlony technique, Immunoelectrophoresis, clot lysis test with Urokinase antibodies).Topographic localisation of Urokinase in renal tissue, investigated with antibodies against Urokinase isoenzymes, revealed Urokinase activity both in the iuxtamedullary region (V. arcuatae, V. interlobulares, less V. recta) and in calyceal epithelia of the renal pelvis.
Fibrinogen/Fibrin Degradation Products in Defibrination Syndrome Analysed on the Basis of Molecular Weight on Gel Exclusion Chromatography
Authors: Kazama M. , Abe T. 
Published: June 2019

1) Fresh citrated plasmas of cases of defibrination syndrome were chromatographed on Biogel A-5 m column, which revealed a two-peaked elution profile of fibrinogen-related antigen with reproducibility. The first peak was eluted at the Vo of the column and the second one at Ve of the early FDP. It was found in the preliminary experiments in vitro, that the big molecular FDP was formed exclusively in the process of fibrin clot lysis, irrespective if it was non-stabilized or stabilized.2) FDP in thesen patients’ serums, after thorough digestion with plasmin, were chromatographed on Sephadex G200 column. A reproducible elution profile of FDP-D antigen revealed single peak, of which Ve was corresponded with that of FDP-D monomer derived from fibrinogen or non-stabilized fibrin.It was postulated that the FDP in plasmas of defibrination syndrome were mainly originated from the fibrinogen or non-stabilized fibrin formed in the process of the diseases.
Inhibitory Effects of Estrogens on Antithrombin III.
Authors: Nagasawa H. , Hotta Y. , Takara N. , Fujimaki M. , Fukutake K. 
Published: June 2019

After the addition of purified estrogen preparation to the plasma, the anticoagulant activity of antithrombin III measured by Bigg’s method decreases in proportion to the amount of estrogen added. And the biological activity of antithrombin III in the plasma mixed with estrogen decreases proportionally in single immunodiffusion assay with anti-antithrombin III serum. The same findings mentioned above are also observed in the experiences with estron, equilin, equilenin and estradiol.Furthermore, the rocket formation of antithrombin III fraction prepared by Abild-gaard’s method in crossimmunoelectrophresis also disappeares by the addition of estrogen into the reaction mixture, and the electric mobility of antithrombin III fraction with estrogen increases the migration to the anode in polyacrylamide gel electrophoresis.
Fibrinolysis and Microthrombosis in Unselected Autopsies
Authors: Lindeman J. , Haverkate F. 
Published: June 2019

Blood samples taken from the right heart were analysed for euglobulin finbrinolytic activity and plasminogen. Tissue fibrinolytic activity of normally appearing parts of nine different organs from each case was investigated with the Todd slide technique. The same tissues were also studied for the presence of microthrombi.The main results and conclusions are:1. High blood activity was found in 17 of 60; no blood activity in 20 of 60.2. High blood activity was associated with the mode (sudden death) rather than with the cause of death or basis illness.3. In cases with blood activity, enzymatically determined plasminogen was zero, whereas antiplasminogen-related antigen was high, suggesting postmortem breakdown of plasminogen and no clearing.4. High blood activity was related with average or high tissue activity.5. In cases with high activity, almost no fibrin microthrombi were present outside local pathologic processes.6. Autopsies with low or no tissue activity generally showed no blood activity.7. In cases with low or no tissue activity, more fibrin microthrombi were found and gram negative endotoxic shock was frequently the cause of death.8. Hyalin microthrombi or globular clots were commonly found in autopsies with low and high activity.
Essential Fatty Acid Deficiency, a New Model for Basis Research in Thrombogenesis
Authors: Hornstra G. , Haddeman E. 
Published: June 2019

Platelet membranes are of primary importance in platelet thrombotic phenomena, whereas in the regulation of platelet function prostaglandins are thought to play a major role. Since esential fatty acids (EFA’s) are of great physiological importance, both as membrane components and as precursors of prostaglandins, EFA-deficiency may present an interesting model for basic research into thrombotic mechanisms.In rats EFA-deficiency caused impaired formation of arterial thrombi but aggregation of blood platelets in response to ADP, both in vivo and in vitro is normal. In contrast, platelet aggregation induced by collagen and Thrombofax® is definitely depressed, as is the release of newly absorbed 5-HT. Thrombin-induced release is enhanced. Platelet factor 3 content and -availability is significantly reduced. Platelet morphology, platelet count and recalcification plasma clotting times are normal.It is concluded that decreased arterial thrombosis tendency in EFA-deficiency is caused by decreased thrombotic properties of the blood platelets. Disturbed platelet membrane integrity and — prostaglandin production will be discussed as possible mechanisms of action.
The Effect of Reserpine on Aggregation of Avian Thrombocytes
Authors: Belamarich F. A. 
Published: June 2019

Avian nucleated thrombocytes are aggregated by acid-soluble collagen, and serotonin (5-hydroxytryptamine) is released from the thrombocytes during the process of aggregation. The action of collagen is inhibited by aspirin and methysergide, a serotonin antagonist. Exogenous serotonin can also induce aggregation. These observations suggest that serotonin, which has been shown to be stored in avian thrombocytes, acts similar to released ADP in mammalian platelets.Measurement of serotonin content in the blood of Peking ducks (Anas platyrhynchos) which had been given reserpine (3 mg/kg, blood withdrawn 20 hours after injection) showed that the serotonin content of whole blood and thrombocyte-rich-plasma fell to approximately 90 percent of the control level. Analysis of aggregation of thrombocytes from control and reserpinized ducks showed that reserpinization markedly decreased aggregation induced by collagen, while it enhanced aggregation induced by serotonin. These results are consistent with the concept of released serotonin playing a role in thrombocyte aggregation.(Supported by a grant from National Heart and Lung Institute HE 10002.)
Oral Anticoagulant Therapy and its Control: An International Survey
Authors: Lam-Po-Tang P. R. L. C. 
Published: June 2019

This is a survey made for the International Study Group for Anticoagulant Control. A questionnaire was sent to 37 countries and there were 31 replies. The information obtained indicated that the most widely used test in oral anticoagulant therapy is the one stage prothrombin estimation. There was a great diversity in the method of reporting prothrombin time results ; percentage activity of normal on the basis of saline dilution curve was marginally the most popular. Only 3 countries had any national or regional systems for anticoagulant control.Recommendations for the therapeutic range of dosage varied widely. The upper limit in one country may be the lower limit in another. The variation of therapeutic range was was still considerable in different countries even when a standard thromboplastin was used.The survey provided valuable data indicating the need for urgent measures to provide a uniform basis for clinical dosage of anticoagulant drugs, and its laboratory control. Given these wide variations, it would be impossible to compare the efficacy of oral anticoagulant therapy from country to country or to conduct meaningful multicentre trials.
Adverse Effect of Heparin on Thrombin Inactivation
Authors: Marciniak E. 
Published: June 2019

In the presence of heparin thrombin, although fast inactivated, impairs the inhibitory capacity of antithrombin III, in result of which the final amount of neutralized enzyme markedly decreases. This adverse effect of heparin was found during the reaction of purified thrombin with both purified human antithrombin III and native plasma hepariniz purified thrombin with both purified human antithrombin III and native plasma heparinized in vitro or in vivo. In the absence of heparin, at concentration equal to that in normal plasma antithrombin III binds 450 Iowa units of thrombin; in the presence of heparin (at 1 unit concentration) this binding is reduced to 145 thrombin units. A fast depletion of inhibitory capacity is also evident after a stepwise addition of thrombin in small installments into a medium containing antithrombin III and heparin. Portions of enzyme initially added disappear with great velocity; subsequent additions, however, accumulate building up a high thrombin level not seen in the absence of heparin. The escalation of thrombin is reversely proportional to the reacting antithrombin III level, thus especially noticeable in antithrombin III deficient plasma. Residual thrombin left in the presence of heparin disappears at a fast rate upon a new addition of antithrombin III. No decrease in anticoagulant properties of heparin is observed during these interactions. Binding of factor Xa to antithrombin III which reacted with thrombin and heparin is also decreased or abolished.These results indicate that in the presence of heparin thrombin not only exposes rapidly a binding site on the inhibitor, but also causes a further change leading to the deletion of antithrombin III binding properties. This may explain adverse, thrombotic effect of heparin sporadically seen in vivo, and suggests that heparin should be applied with caution in patients with antithrombin III deficiency.
The Significance of the Chronic Anticoagulant Treatment in Recurrent Thromboembolic Caused by Hereditary Antithrombin III Deficiency
Authors: Nagy I. , Losonczy H. 
Published: June 2019

It has been known since the publication of Egeberg (1965, 1970) and Marciniak (1974) that herditary antithrombin III deficiency could be the cause of recurrent venous thromboembolism.The authors observed in 5 cases of severe repeated venous thrombosis in young patients an antithrombin III decrease, which proved to be a hereditary abnormality. In the case of a 15 years old girl the late introduced anticoagulant treatment could not save the life of the patient, she died after repeated deep vein thrombosis. In the other cases the long-lasting anticoagulant treatment resulted in a perfect clinical improve, while the behaviour of antithrombin III was different; in some cases its quantity (determined by radial -immunodiffusion) and functional activity (examined by modified method of Gerendás and Rák) remained decreased, while in the other cases its functional activity increased during the anticoagulant treatment as it was found by Marciniak, too.It is most likely, that there are two types of hereditary antithrombin III decrease; in one of them the quantitative and functional decrease goes parallel, in the other there is mainly a functional decrease, which improves during the chronic anticoagulant treatment. The authors demonstrated the significance of the prolonged anticoagulant treatment in the patients with hereditary antithrombin III decrease.
Characteristics of Platelet Protransglutaminase (Factor XIII)-Binding Activity in Human Plasma
Authors: Bannerjee D. , Mosesson M. W. 
Published: June 2019

Human plasma Factor XIII (F. XIII) complex is composed of two types of noncovalently linked polypeptide chains termed a and b; only the a chain possesses catalytic potential. Platelet Factor XIII is comprised solely of a chains which are identical to those found in plasma. In this study platelets were utilized as a source of unbound a chains to characterize F. XIII (a chain)-binding activity in plasma and its subfractions. Upon exclusion chromatography of unheated plasma or of an unheated ammonium sulfate (20% sat.) subfraction, F. XIII activity emerged in a peak corresponding to a mol. wt. of < 500,000 (region 1). If these samples had first been heated at 60° to precipitate fibrinogen, F. XIII was eluted in a peak corresponding to a mol wt. of about 300,000 (region 2). Chromatography of the platelet zymogen alone resulted in a F. XIII peak corresponding in position to that of monomeric a chain (mol. wt. 80,000, region 3).Exclusion chromatography of the unheated ammonium sulfate fraction yielded, in addition to the F. XIII peak in region 1, a protein peak (peak II) in region 2 which contained no F. XIII. When peak II was mixed with platelet F. XIII, and again subjected to exclusion chromatography, the platelet F. XIII peak shifted from its expected position in region 3 and emerged instead in region 2 ; this behavior demonstrated F. XIII (a chain)-binding activity within peak II. The same chromatographic shift was observed in mixtures of platelet F. XIII and normal plasma or that from a patient with congenital F. XIII (a chain) deficiency. Immunochemical analyses of chromatographic fractions indicated that a chain-binding was due to complexing of a chains with freely circulating b chains. Since a chains and b chains have different biosynthetic sites we conclude that b chains serve as an extracellular F. XIII (a chain)-binding protein.Supported by NHLI grant HL-11409.
Interactions of Factor XIII Subunits as Studied by Affinity Chromatography
Authors: McDonagh Jan , McDonagh Richard P. 
Published: June 2019

A new method for studying the interactions of plasma factor XIII subunits, as well as purifying both plasma and platelet factor XIII, has been developed using an organomer-curial linked to agarose. Native plasma factor XIII a subunit binds to the ligand accompanied by b subunit, which can be dissociated from the ligated a subunit by treatment with thrombin and calcium. With various combinations of thrombin, calcium, and alteration of ionic strength it has been shown that: (a) both unactivated a subunit and thrombin activated a’ subunit bind to the ligand; (b) “excess” b subunit present in highly purified preparations of plasma factor XIII dissociates and can be eluted at low ionic strength in the absence of calcium or thrombin; (c) in our preparations of highly purified plasma factor XIII approximately 40% of b subunit is in “excess”; (d) the remaining b subunit can be eluted with thrombin and calcium; (e) both a and a’ subunits can be eluted with dithiothreitol ; (f ) when plasma factor XIII zymogen is applied to the column approximately equal amounts of a and b subunits co-elute with dithiothreitol. These observations offer further evidence for the roles of thrombin and calcium in the activation of plasma factor XIII and provide a new tool for studying the structure-function relationships of factor XIII.Supported by Grants HL 14228 and HL 06350 from the National Institutes of Health, U.S.A.
Action of Factor XIII on Transamidation Bounds between the Collagen Molecule Constituents
Authors: Soria J. , Soria G. , Boulard G. 
Published: June 2019

By polyacrylamide gel electrophoresis in the presence of SDS we observed that collagen polymerized in the presence of factor XIII a, is dissociated by urea into sub-units with a higher molecular weight than that polymerized in the absence of factor XIII.In the other hand, by phase contrast microscopy we have found that the structure of collagen is quite different when the polymerization process takes place in the presence or in the absence of activated factor XIII.This modification of collagen polymerization in the presence of factor XIII a possibly acts in wound healing.
Blood Platelets and Decompression Accidents in the Rat. Therapeutic Trials
Authors: Broussolle B. , Stoltz J. F. , Verry M. , Hyacinthe R. 
Published: June 2019

The pathogenesis of decompression accidents involves particularly disseminated vascular microthrombi composed of platelets clumps, lipids and red blood cells grouped around air microbubbles. In rat, the role of platelets, after rapid decompression (1 bar/20 sec. after being kept at 8 ATA for one hour), is investigated by means of filtration pressure measurements and PRP platelet counts. With decompression accidents, a rise in filtration pressure is observed but there is, above all, a 51% decrease in platelet counts due to disseminated platelet aggregates formed. After slow decompression, there is also a moderate depression (15%) of platelet levels, these not rising until the third day. In order to inhibit platelet aggregation, we used injectable anti-aggregating agents: Aspirin (20 mg/kg) Diamicron (50 mg/kg), S 2574 (100 mg/kg) before and after decompression and for the following three days. The best results were had with S 2574 which prevented fall in platelet levels. Parallely, mortality is reduced if the injection is given before rapid decompression.These results confirm the importance of platelets in decompression accidents. These therapeutic trials allow to consider the use of these products in human therapy.
Critical Analysis of Platelet Factor 4 (Antiheparin Activity) Assays
Authors: Hurlet A. , Beys G. De , Moriau M. , Monsieur A. , Schulzen E. , Masure R. 
Published: June 2019

Antiheparin activity is usually achieved by a heparin-thrombin time assay. Platelet free substrate plasma is adsorbed or not, calcium chloride used or not. Those technical conditions are analysed.Results are expressed by the amount of heparin units neutralized in the assay. With non adsorbed plasma substrate, calcium chloride generates thrombin, increasing antiheparin like activity. Lower antiheparin like activity is also observed with BaSO4 plasma substrate and with thrombin free of factor Xa. The amount of heparin units neutralized varies from 2.9 to 1.2 according to the system used.Tested without calcium, with Xa free thrombin and BaSO4 adsorbed substrate plasma, there exists a good relationship between the amount of heparin neutralized and various dilutions of serum, platelet rich plasma and platelet extract.An assay based on anti-Xa effect of heparin, set up according to the heparin assay of Yin, is compared to the method described above.
Fibrinogen Degradation in Normal and Fibrinolytic Plasma
Authors: Scully M. F. , Kakkar V. V. 
Published: June 2019

It has recently been shown that an α2-macroglobulin-plasmin complex isolated from normal plasma is capable of substantially degrading purified fibrinogen in solution in a manner similar to free plasmin (Harpel, P. C. and Mosesson, M. W., J. Clin. Invest., 52, 2175, 1973).To detect the presence of such fibrinogenolytic activity in normal plasma, 125I-fibrinogen was added to plasma which was then incubated at 37° C for 72 hours. No apparent degradation of the chains of clottable fibrinogen occurred under these conditions. There was, however, a 16% loss in clottability over this period, as measured by radioactivity. 5 units of urokinase/ml of plasma produced an 18% loss in clottability but no degradation of clottable fibrinogen chains occurred. The addition of 50 and 500 units of urokinase/ml of plasma produced, respectively, a 20% and 65% loss of clottability and a 25% and 80% degradation of α chains.If heterogeneity of fibrinogen in normal plasma is due to degradation of native fibrinogen by α2-macroglobulin-plasmin complex then our observations suggest that further degradation of fibrinogen only occurs in the presence of high levels of plasminogen activator.
Lysis of Crosslinked and Non-Crosslinked Purified Fibrin
Authors: Haverkate F. 
Published: June 2019

Several authors have reported that cross-linking by Factor XIII makes fibrin less susceptible to lysis by fibrinolytic enzymes, especially to plasminogen activators. However, the conclusions of most of these studies have been based on circumstantial evidence.To unambiguously establish a possible effect of cross-linking of fibrin on its resistance to lysis, the following experimental conditions are necessary (a) the use of preformed fibrin substrate, (b) the use of purified protein components, and (c) measurement of the extent of cross-linking. With due observance of these conditions, we determined lysis of both cross-linked and non cross-linked fibrin by plasmin, urokinase, and a human tissue activator by means of the fibrin plate assay. Purified preparations of fibrin, F XIII, and plasminogen were used. Cross-linking was determined by means of SDS polyacrylamide gel electrophoresis.The results revealed no differences in resistance to lysis of highly cross-linked and non-cross-linked fibrin.They suggest that the mechanism underlying the effect of F XIII on haemostasis is not directly related to a change in the resistance of the fibrin in the blood clot to lysis by fibrinolytic enzymes. For a better understanding of the role of F XIII in haemostasis, attention should be focused on processes which occur in the whole blood clot and not in purified fibrin.
Arterial Thromboembolism and Prosthetic Heart Valves. Effects of Acetylsalicylic Acid
Authors: Dale J. , Myhre E. , Storstein O. , Stormorken H. 
Published: June 2019

Prevention of arterial thromboembolism with acetylsalicylic acid (ASA) was studied double-blind in patients with aortic ball valve prostheses. Such patients have a high incidence of arterial emboli originating from thrombi formed on the valves, and the clinical effects of antithrombotic drugs can better be studied in this condition than in myocardial infarction, where the role of thrombosis is not definitely settled.A total of 156 patients with single Starr-Edwards aortic ball valves received either one gm. of ASA daily or placebo in combination with warfarin, and were observed for two years. Only two emboli were diagnosed in patients taking ASA, none of them severe. In the placebo group 12 thromboembolic episodes occurred in 10 patients, and three with cerebral emboli died. Gastrointestinal complications were seen more frequently in patients receiving ASA, while two persons in each group suffered from intracranial bleeding. It was concluded that ASA combined with anticoagulants offered a significantly better protection against arterial thromboembolic complications than did anticoagulant therapy alone.