bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Functional FVIII Measured in a Group of Haemophilia a Patients with a Homologous and Heterologous Anti VIII:C Serum
Authors: Muller H. P. , van Tilburg N.H. , Bertina R.M. , Veltkamp J.J.
Published: May 2019

After dissociation of the FVIII complex in the presence of high salt concentration a rabbit antiserum was developed against the low molecular weight fragment (LMW FVIII). The anti LMW FVIII had anti VIII. C activity (450 Eethesda units), but also precipitated’ against a FVIII concentrate. Adsorption of the antiserum with cryoprecipitate of a haemophilia A patient removed the precipitating properties (anti HMW FVIII), without affecting the anti VIII:C activity. The rabbit antibody and a human inhibitor were used in a fluid phase inhibitor neutralisation assay. The mean value of VIII.C. Ag in 23 normal persons was 83.5% (SD 25.9) when tested with the human antiserum; 90.1% (SD 27.1) when tested with the rabbit antiserum. The mean VIII. C was 86% (SD 23.3). (100% is the amount of VIII. C or VIII:C:Ag in 1 ml of pooled normal plasma.) 59 Patients with haemophilia A (severe, moderate, and mild) were tested. 6 Patients were A+ when tested with the human antibody, 12 patients were A+ when tested with the rabbit antibody. It is concluded that 1) heterogeneity among haemopni-lio patients exists, and 2) the rabbit antibody recognises more antigenic determinants on the VIII :C molecule than the human antibody used in this study.
Factor VIII Coagulant Antigen (VIII. CAg) in Fetal Blood Samples
Authors: Reisner H.M. , Buchanan P.D. , Strand E.A. , Barrow E.S. , Graham J.B.
Published: May 2019

Quantitative immunoradiometric assays (IRMAS) for the coagulant portion of the FVIII complex [VIII: CAg) have recently been described several laborateries (Reisner et al. Thrombosis Research, in press). The antigen detected by these assays is absent or decreased in the plasma of most individuals with severe hemophilia A, Levels of VIII:CAg and FVIII related antigen (VIIIR.Ag) were measured in ten presumably non-hemophiiic samples obtained either by fetoscopy or after abortion. Ratios of VIII:CAg to VIIIR:Ag ranged from .07 to .52 in four samples where both values could be determined. VI11 :CAg could not be detected in four other samples. Three of these also lacked detectable V111R:Ag and were probably diluted with amniotic fluid which has neither VIII:CAg nor VIIIR:Ag. One Sample had 80% VIIIR. Ag in the absence of detectable VIII:CAg. VIII:CAg was detected in six samples with a range of 4 to 50% of an adult normal pool. An aborted male fetus from a potential carrier of severe hemophilia A had an VIII:CAg to VIIIR:Ag ratio of .42 and was probably not affected, The low values of VIII. CAg seen in this preliminary study may be explained by the decrease in antigenicity seen in serum versus plastra samples in our assay. Hence, extreme care in sample preparation and storage must be exercised should this IRMA for VIII:CAg be used in fetal diagnosis of hemophilia A.
Prostaglandins and Platelet Function in Diabetes
Authors: García-Conde J. , Amado J.A. , Merino J. , Benet I.
Published: May 2019

We have studied platelet aggregation induced by 0,5 mM. Araquidonic acid (AA) addition to platelet-rich-plasma (PRP) from 21 insulin treated diabetic patients and in 21 non-diabetic controls. The velocity of aggregation was significantly higher in the diabetic group. There was no differences in the velocity of aggregation in patients with or without retinopathy.

The incubation of PRP of normal subjects at 37- during 5 minutes with 5,8 10-4 M. Imidazole changed the pattern of aggregation: The velocity of aggregation was slower and appeared a wave of disaggregation. Imida zole had not effect on aggregation in the diabetic group. This data add support to the findings published by COLWLLL showing that platelets from diabetics have hyperactive AA metabolism. Prostaglandin I2 (PGI2) obtained from rat aorta shows an inhibitory effect on ADP or AA induced aggregation. This effect is less marked in diabetic PRP than in PRP of normal controls. PGI2 release in platelet-poor-plasma from diabetics is normal. This can represent a resistance ot diabetic platelet to the anti aggregating effect of PGI 2. A similar finding was also appreciated with the PGE1 in three out of six patients so tar stu
Antiproteases, Fibrinogen-Split Products, Granulocytic Elastase, and Immunocomplexes in the Serum of Patients with Bronchogenic Carcinoma
Authors: Gropp C. , Egbring R. , Havemann K.
Published: May 2019

The antiproteases α1g-antitrypsin (α1AT), α2-macroglobulin (α2M) and antithrombin III (AT III) were determined in the serum of plasma of patients with lung cancer and in normal controls. Whereas there was no difference of α2-M and AT III levels in patients and controls, elevated levels of α1 AT could be found in lung cancer patients with extended disease. In the serum of these patients fibrinogen split-products (FDP) could also be demonstrated. To explain these results we looked for the protease plasminogen in the serum of these patients, but no abnormal plasminogen levels could be determined. But remarkably we could demonstrate a granulocytic elastase (ELP) in the sera of patients with metastases. This elastase, which was bound to α1AT is able to split fibrinogen. So the elevated levels of α1AT and FDP are probably explained by the release of ELP by granulocytes. As it is known that ELP is released by immuno-complexes, we determined circulating immunocomplexes in the sera of patients with lung cancer. Immunocomplexes could often be demonstrated in patients with metastases. Because fibrinogen split products {FDP) can suppress immune reactions, our results may contribute to the knowledge of the mechanism of tumor spread.
Antithrombin III and Venous Thrombosis
Authors: Thomas Duncan P.
Published: May 2019

Increasing interest in the physiological role of inhibitors of coagulation has highlighting the role of antithrombin III (AT III) as the most important naturally occurring inhibitor of venous thrombosis. Since Egeberg’s original description in 1965, it has been recognized that inherited deficiency of AT III is associated with an increased incidence of venous thromboembolism. The role of acquired deficiency of AT III in the pathogenesis of thromboembolism remainsless clear-cut, partly due to methodological differences. While low values have been reported in groups of patients with thromboembolism, estimations of AT III in individual patients are not allways abnormal. In general, studies which have measured protein concentration rather than functional activity, or cl otting assays which measure total antithrombin activity and not specific anti-Factor Xa activity have failed to demonstrate a clear relationship between AT III and thromboembolism. However, in two groups of patients, namely women on oral contraceptives and patients undergoing total hipreplacement, an acquired deficiency of AT III, particularly when measured by anti-Xa clotting assays, correlates highly with postoperative venous thrombosis. Although venous thrombosis may develop in patients despite normal AT III values, an activity below approximately 80% in an anti-Xa clotting assay has been found to be of predictive value in patients subjected to the stress of trauma or surgery.
Development of Screeningtests for Arterial Thrombosis
Authors: van Oost B. , van Hien-Hagg I. , Sixma J.J.
Published: May 2019

Circulation of released platelets may occur in arterial thrombosis or severe atherosclerosis. Treatment of human blood platelets in vitro with thrombin was utilized for the composition of artificial platelet populations with various amounts of released platelets Thrombin treatment (0.05-0.5 U/ml) caused a dose dependent decrease in platelet density that could be assayed by iso-osmolar Stractan density gradient centrifugation. Density distributions in platelet rich plasma of healthy young males were taken as normal values. An increased proportion of lighter platelets was detected in several patients with signs of arterial thrombosis. Platelet density fractions may be utilized in the search for other properties that are induced by thrombin treatment in vitro. The following new properties are indicative of such a treatment; -decrease in β-thromboglobulin content at 0,05 U thrombin/ml. - increase in adenine uptake at 0.5 U thrombin/ml. - decrease in serotonin-uptake at 5 U thrombin/ml.
Hyperviscosity and Coagulation Activation in Peripheral Vascular Disease
Authors: Stuart J. , George A.J. , Blunt R. J. , Strachan C.J.L. , Hurlow R.A.
Published: May 2019

Forty-two patients with Raynaud’s disease (21 idiopathic, 8 scleroderma, and 13 industrial) and 18 patients with lower limb vascular disease were matched for age, sex and smoking habit with 50 healthy controls. Whole-blood viscos ity was measured at 37, 27 and 220 and at 128, 23 and 0.2 s-1. Tests of platelet activation, coagulation, and fibrinolysis were also performed. All blood was taken understandardised, fasting, out-patient conditions.

Patients with extensive lower limb atherosclerosis showed an acute phase protein reaction (raised fibrinogen, factor VIII and haptoglobins), decreased fibrinolysis, and hyperviscosity. Patients with the milder forms of Raynaud’s disease showed hyperiscosity only, with normal or increased fibrinolysis, whereas patients with vibration induced disease showed more extensive changes. A minor degree of platelet activation occurred in all groups.

The differences in platelet function, coagulation, fibrinolysis, and vis cosity between these vascular disorders probably reflect the extent of endothelial cell damage irrespective of its aetiology.
The Relationship of Blood Viscosity to Coronary Artery Disease
Authors: Lowe G.D.O. , Drummond M.M. , Lorimer A.R. , Hutton I. , Forbes C.D. , Prentice C.R.M. , Barbenel J.C.
Published: May 2019

Increases in blood viscosity and its determinants (haematocrit and plasma fibrinogen) have been described in groups of subjects with clinical manifestations of arterial disease (myocardial infarction, angina, claudication). Viscosity factors may also be risk associations in prospective studies. We have studied the relationship of blood viscosity (shear rate 100s-0), haematocrit and fibrinogen to the extent of coronary artery occlusion in 50 males, aged 30-55, prior to coronary arteriography for chest pain. 26 subjects had significant occlusion (>50 per cent stenosis) of 2 or 3 major coronary arteries: 24 had single vessel disease or normal coronary arteries. 25 healthy controls were also studied. There were no significant differences in age or smoking habits between the three groups: use of beta-adrenergic blockers and plasma lipid levels were comparable in the two arteriography groups. Patients with extensive coronary artery disease had increased levels of viscosity and haematocrit (p<0.005), fibrinogen (p<0. 02) and viscosity corrected for haematocrit (p<0. 05), compared to angiographic or asymptomatic controls.
In Vitro Mechanism of Platelet Aggregation (PA) by Purified Plasma Membrane Vesicles (PMV) Shed by Mouse 15091A Tumor Cells
Authors: Gasic G.J. , Catalfamo J. L. , Gasic T. B. , Avdalovic N.
Published: May 2019

Cell transformation leads to increased blebbing of the plasma membrane and release of PMV with capacity for PA in the presence of heparin or hirudin (G.J. Stewart et al.). This PA is preceded by a lag of 2or more min. To investigate whether vesicle binding is a prerequisite for PA, 125I-lebelled vesicles were added to rat or mouse platelet rich plasma in the aggregometer, and radioactivity was measured in pellet and supernate fractions of samples taken at different time intervals. Most of the radioactivity was found with pelleted platelets, this association reached a maximal plateau at the mid point of the lag period. After 125I-label led vesicles interacted with platelets, characteristic polypeptide bands present in autoradiograms of SDS-PAGE of 125I-labelled vesicles alone were also present in SDS solubiliicd pellet fractions. Binding of radioactivity by platelets depended on a plasma cofactor(s) other than fibronogen since gel filtered platelets failed to bind 125I-labelled vesicles when fibronogen was added but did so in the presence of plasma; plasma was also required for aggregation. Isolation of the active fraction by step ammonium sulfate (AS) fractionation of plasma or its adsorption by barium citrate followed by AS elution, suggests that it may be a clotting factor(s) or a unique protein(s) that cofractionates with the prothrombin complex. In addition to its role in binding, this protein(s), when activated by vesicles or the platelet-vesicle complex, might also participate in PA.
A Clinical Trial of Warfarin in Cancer (Ca)
Authors: Zacharski L.R.
Published: May 2019

A 5-year study of the effect of warfarin on the natural history of human ca is in progress. The basis for this study is: the occurrence of clots at ca sites, uptake of tagged fibrinogen or anti-fibrinogen antibody into ca, occurrence of localized and disseminated intravascular coaqulation with ca, evidence from experimental ca systems of involvement of the clotting mechanism in the growth and spread of ca, and preliminary evidence of such involvement in man. Patients with either limited or extensive ca of the lung or large bowel, advanced prostatic ca or recurrent head and neck ca are randomized by hospital and performance status within 1 of 9 different strata to receive standard therapy with or without warfarin. Study design includes : 11 definition of exclusion criteria, 2) comparison of included vs. excluded patients, 3) classification and recording of bleeding complications, 4) serial tests for intravascular coagulation, 5) blinded reading of x-rays and scans used to follow tumor responses and, 6) use of physician extenders for patient screening and data collection. Patients are evaluable only if on-study at least 2 weeks. Response criteria include survival, tumor resDonse, changes in laboratory tests, causes of death and autopsy findings. Supported by the VA Cooperative Studies Program (CSPS75) of the VA Medical Research Service.
Platelet Release Reaction - A Predictor of Death Following Myocardial Infarction?
Authors: Heptinstall S. , Mulley G.P. , Taylor Patricia M. , Mitchell J.R.A.
Published: May 2019

A comparison has been rrade of the extent to which ADP can induoe the release reaction in platelets from 26 patients who, within 5 days, had sustained a myocardial infarction and fran 54 age-rratched arrbulant control subjects. Platelet rich plasma was prepared from blood collected into heparin (10 u/ml), samples were incubated with 3H-serotonin., aggregation was then induced by adding ADP (10 μM, final concentration) and the extent to which ADP irrluced the release reaction was detennined by rreasuring the arrount of the accumulated 3H-serotonin that was released.

The results ootained for the group of patients who had experienced a myocardial infarction were rot significantly different from those obtained for the ccntrols. However, a significant difference (P = 0.02) was observed between the results obtained for those patients who died within 12 months of the infarction (mean 29.4%± 5.6 of accumulated 3H-serotonin released by ADP) and those who survived (mean 12.0%±3.3). Of the 8 patients who died, 7 had platelets that released ≥ 20% of the 3H-serotonin that had platelets of the 18 patients who survived only 4 had platelels that released ≥ 20% 3H rotonin.
Exposure of a Human Platelet Fibrinogen Receptor by ADP
Authors: Bennett J. S. , Vilatre G.
Published: May 2019

Fibrinosen is a cofactor for the aggregation of human platelets by ADP but its precise role is not known. In order to clarify the function of fibrinogen in platelet aggregation, we measured the binding of 125I-labeled human fibrinogen to gel-filtered human platelets before and after platelet emulation by ADP. Incubations were performed without stirring to prevent platelet aggregation and secretion. Platelet-bound and free 125I-fibrinogen were separated by centrifugaron of the platelets through silicone oil. Specific fibrinogen binding was that ibrinogen which could be displaced from the platelets by a 10-fold excess unlabeled fibrinogen. Specific fibrinogen binding required platelet stimulation by ADP and either Ca+2 or Mg+2. Specific ending reached equilibrium within 60 sec. Demonstrated saturation kinetics, and did not occur with thrombasthenic platelets. Scatchard analysis demonstrated a single class of ending sites with a Kd of 25 ± 3.9 ug/ml and 39,000 ± 5,000 binding sites per platlet the extent of ADP-induced fibrinogen binding to unstirred platelets was compared to the extent of aggregation of stirred platelets induced by the same concentrations of ADP, correlation 0.96 was seen. This study demonstrates. that a uniform population of fibrinogen receptors is exposed on the platelet surface by ADP. Furthermore, we suggest that the fibrinogen molecules bound to the platelet as a result of ADP stimulation are directly involved in the platelet aggregation response.
Mobilization of Fibrinogen Receptor Sites on Human Platelets Stimulated with ADP is Prevented by Prostacyclin
Authors: Hawiger J. , Parkinson S. , Timmons S.
Published: May 2019

Fibrinogen is a plasma factor required for aggregation of human platelets by ADP. The mechanism of platelet-ADP-fibrinogen interaction was studied by measuring the equilibrium binding of 125I-fibrinogen to human platelets separated from plasma proteins. Binding of 125I-fibrinogen to platelets not stimulated with ADP was low and unaffected by an excess of unlabel led fibrinogen. However, when platelets were stimulated with 4μM of ADP, there was an eightfold increase In the number of available binding sites for human fibrinogen, with affinity constant of 1.9 x 109M-1. This striking increase in fibrinogen receptor sites on human platelets was specific for ADP as contrasted to ATP, AMP, and adenosine. Prostacyclin (Prostaglandin I2, PGI2), a novel prostaglandin produced by the blood vessel wall, completely blocked this ADP-induced increase in fibrinogen receptor sites on human platelets. The effect of PGI2 was prompt and concentration dependent, reaching maximum at 10-9M. 6-keto PGF2 a stable derivative ot PGI2, did not have such an effect. Thus movement of fibrinogen receptor sites on human platelet membrane stimulated with ADP is prevented by PGI2. This represents a new biologic property of this vascular hormone and contributes to better understanding of its potent inhibitory effect in vitro and in vivo on ADP-induced platelet aggregation requiring mobilization of fibrinogen receptor.
Isolation of a New Enzyme from Human Plasma Fractions and its Effects on Coagulation
Authors: Coan Michael H. , Schroeder Duane D. , Mozen Milton M.
Published: May 2019

A new hydrolase enzyme has been isolated from human plasma fractions. This enzyme has been purified to homogeneity by adsorption to and elution from DEAE-5ephadex, Benzamidine- EACA-Sepharose, and Heparin-5epharose. The molecular weight, as judged by SDSpolyacrylamide gel electrophoresis, is 70,000 daltons; and there are 2 peptide chains (45,000 and 25,000) after reduction. This enzyme, isolated in an active form, hydrolyzes 5-2238 (H-D-Phe-Pip-Arg-PNA), a chromogenic substrate (AB Kabi) , at a rapid rate, S-225l to a slishtly lesser extent, and S-2222, S-2302, and 5-2160 about equally and much more slowly. CaCl2 greatly enhances its activity. The enzyme is inhibited by antithrombin III especially in the presence of heparin, but poorly by soybean trypsin inhibitor or by diisopropyl fluorophosphate. The enzyme binds to and can be eluted from insoluble barium salts. In vitro, the protein will activate and degrade human Factor VIII, will activate human Factor V, and will inhibit epinephrine-induced platelet aggregation; however, the in vivo function is unknown . Comparison with known properties of protein C and other coagulation-related proteins indicates. that this enzyme has not been previously described.
The Prothrombin Activator of Echis Carinatus Venom:Characterization and Mode of Action
Authors: Morris S. , Kosow D.P.
Published: May 2019

The venom of the saw scaled viper, Echis carinatus, contains a protein capable of convertis prothrombin to thrombin. This prothrombin activator (ECA) has been purified 45-fold by affinity chromatography on wheat germ agglutinin followed by ion exchange chromatography on DEAE-Sephacil. ECA was homogeneous as assessed by dodecyl sulfate poly acrylamide gel electrophoresis (SDS-PACE). Sialic acid, neutral sugars, and hexosamines were present at 4.2, 7.2 and 5.8 w/wX respectively. Amino acid analysis of reduced and carboxymethylated ECA revealed an unusually high cysteine content of 9 moles %. ECA is inhibited by chelators such as EDTA and o-phenthroline, but is active after treatment with chelex. However, atomic absorption studies revealed that neither Ca, Co, Cr, Cu, FeMηnor घη is present at more than 0.01 moles/mole of active protein after chelex treatment. Arrhenlus plots of the temperature dependence of thrombin formation give a similar activation energy and T½ as Arrhenlus plots of data obtained for a temperature induced conformational change in prothrombin. These data suggest that the activation of prothrombin by ECA requires a particular conformational Isomer of prothrombin as well as a group on ECA which can interact with metal chelators.(Supported, in part, by NIH Grant HL 19282)
Proteolytic Degradation of the Aα Chain of Human Fibrinogen
Authors: Conkie J.A. , Walker Isobel D. , Davidson J.F.
Published: May 2019

On plasmin degradation of human fibrinogen, a number of polypeptides are released from the COOH-terminal part of the Aα chain. One of these fragments has been previously named by us as Aα-RA(26,000). By comparison of its molecular weight and amino acid composition analysis, this fragment is similar to the fragments A,H and Hi2-Met. Aα-RA(26,00O) appears to be derived from a precursor polypeptide of Mw 44,000, while in vitro and in vivo activation of the plasma fibrinolytic system also gives rise to an Aα-related antigen which is immunologically similar to the 44,000 MW polypeptide. On immunodiffusion with antiserum to the carboxymethylated Aα chain, Aα-RA(26 000) revealed a reaction of identity with the high solubility fibrinogen fraction 1-9 (major NH2-terminal Aα remnant, MW 34,000) and a reaction of non-identity with the ancrod-proauced COOH-terminal Aα polypeptides (MW 27,000-31,000). These immunodiffusion results provide evidence that the sequence of bond cleavages in the Aα chain leading to the formaron of fibrinogen 1-9 is different from that leading to the formation of Aα-Ra (126,000).
Role of Thrombolytic Therapy in Thrombotic Disease
Authors: Verstraete M.
Published: May 2019

Commercially available thrombolytic agents have been tried in many clinical conditions with convincing evidence of benefit in few. The clearest indications are in the venous circulation. Controlled clinical trials have shown that streptokinase dissolves extensive recent deep venous thrombi more often and much more completely than other drugs; there is emerging evidence that early lysis of a venous thrombus prevents destruction of the valves, the main cause of the postphlebitic syndrome. Massive and recent deep venous thrombosis extending above the knee in younger patients appears to be the best indication for streptokinase or urokinase. Urokinase (UK) or streptokinase (SK) are useful in the few patients who have acute massive pulmonary embolism with obstructed right-heart outflow but who do not appear to require surgical embolectomy to prevent immediate death. Other clinical conditions can be marginally improved by thrombolytic treatment as central vein occlusion, medium-risk myocardial infarction and acute obstruction of peripheral arteries in whom vascular surgery is contraindicated or failed. The search still continues for a more effective dose regimen given either continuously or intermittently with or without plasminogen or plasmin or after defibrination.
Acquired Inhibitors of Blood Coagulation in non Haemophiliac Patients
Authors: Roussi J.H. , Houbouyan L.L. , Delemme J. , Goguel A.F.
Published: May 2019

We report here a study concerning 25 cases of acquired inhibitors of blood coagulation observed in our hospital over the last 3 years. According to their mode of action, these anticoagulants could be divided into 2 groups: only 2 patients’plasmas had an elective effect on anti-haemophilic A factor (AHF), the 23 other inhibitors “luous-like” were directed against the “Prothrombinactivator complex” of factors Xa, V, and phospholipid and mainly against the phosohelipid. These antibodies generally occurred in elderly patients (older than 60 years) but 8 patients were between 15 and 30. Most were yomen; 13 inhibitors were associated with underlying diseases, well known to induce such abnormality (SLE, neoplasmic disease, poly-arthritis, auto-immune haemolysis). If the 2 AHF antibodies induced severe bleeding manifestations, on the other hand, the “lupus-like” inhibitors were generally clinically asymptomatic. These inhibitors have been particularly studied according to their immunological properties by several technics: immuno-neutralization, isolation of immiuno-globulins, gel filtration, and for one anti-AHF antibody 125-Iodin radio-labelling step followed by complex dissociation. Their specificity was IgG and/or IgM for the “lunus-like” anticoagulants, IgG k for one anti-AHF. The great majority of these inhibitors was still present all over the 3 years follow-up despite of Prednisone treatment for those associated with an underlying disease; the anti-AHF (70 Oxford U.) was successfully treated by Prednisone and Azathioprine. The knowledge of such acquired inhibitors might lead to a further approach in the concept of immune response in man.
Crotalase and Thrombin: Cohomology of Amino Acid Sequences as Evidence for a Common Ancestral Gene
Authors: Pirkle Hubert , Markland Francis S. , Theodor Ida , Baumgartner Richard
Published: May 2019

Crotalase is a coagulant eniyme from the venom of C. adamanteus which releases specifically fibrinopeptide A from fibrinogen and cleaves the single thrombin-vulnerable bond of prothrombin. Edman degradation of crotalase yielded a six-step N-terminal sequence which contained only one residue in common with the N-terminal sequence of the B-chain of thrombin (Magnussen; Thompson et al.). When the two sequences were compared with the N-terminal sequences of the heavy chains of factor IXa (Enfield) and factor Xa (Titani), extensive identity was noted in five of the six positions, indicating evolutionary relationship among the four proteins and the suitability of the crotalase molecule for structure-function studies of thrombin-like actions. Our method for demonstrating that crotalase and thrombin are evolutionarily related is novel and is termed cohomology. We regard two amino acid sequences to be cohomologous when they each exhibit appreciable similarity to one or more di’ferent sequences but not to each other. We have found that this approach to the determination of evolutionary relationship, while employed intuitively here, is amenable to rigorous mathematical formulation (to be published).
Three Sources of Purified Factor III for Monitoring Vitamin K Dependent Coagulant Factors Using a Synthetic Chromogenic Substrate
Authors: Oostryck R.
Published: May 2019

Methods used for monitoring coumarol treatment should be sensitive to the loss of calcium binding γ-carboxyl glutamic acids in the vitamin K dependent clotting factors. A two stage method sensitive to factors II-VII-X using the chromogenic substrate H-D-Phe-Pip-Arg-pNA has been evaluated using 75μl of reconstituted factor III containing 0.012μg of apoprotein III per ml for each assay. The reconstituted factor III used as the activator was prepared according to the method of Bjorklid et al. (1973) from human brain, human placental material and bovine brain, and from a phospholipid fraction - Gierksky et al. (1976).

This method was sensitive to the coumarol induced defect with all three sources of apoprotein III and correlated well with a standard saline thrombo plastin extract (r=0.85, 0.89 and 0.88 respectively) in a group of 80 dicouroarol treated patients and 20 normal subjects and appears to overcome the insensitivity usually associated with crude bovine thromboplastins. Bjorklid E, Storm E and Prydz H (1973)Biochemical and Biophysical Research Communication, 55, 969

Gierksky K E, Bjorklid E and Prydz H (1976) Scandinavian Journal of Haematology,16, 300.
Prothrombin: Receptors
Authors: Dejanov I.I.
Published: May 2019

The presence of prothrombin receptors on plasma membrane of red cells, granulocytes, lymphocytes and platelets with agglutination, itumunofluo- rescent microscopy and quantitative immunofluorescent methods was die-closed. The prothrombin-reactive structures on plasma membranes have different affinity and density in dependence of the cell species and the time of conservation. The prothrombin bound to cell receptoras has higher velocity of activation and activation products are wore resistant to inactivators. The existance of cell receptors for prothrombin adds a new dimension in the integral system of cellular and humoral cooperation in haemoetasis and thrombogenesis. A monospecific antiserum to human prothrombin was used.
Vertebrates Coagulation: the Intrinsic and Gxtrinsic Pathways; Extraphysiological Activators
Authors: Dange M. , Leroy J. , Degenne M. , Leclerc M.H , Theron J.F , Delahousse B.
Published: May 2019

A systematic coagulation study of forty different species of vertebrates using autoreagents (i.e: prepared from their own tissues), revealed biological activity of factors thought till now to be absent so early in the phylogenetic evolution because of their unreactivity with respect to standard reagents used currently in man.

Hybrid plasma fractions from man and other animal species demonstrated that the best extrinsic pathway kinetics were obtained by associating specific thromboplastins and specific factors VII-X.

The comparison of extraphysiological coagulation activators (such as Russell viper venom, Echis carinatus viper venom, staphylocoagulase, thrombin coagulase, Bothrops atrox viper venom, Agkistrodon contortrix snake venom) permits a chronological approximation of the coagulation factors evolutionary variations.

It should be noted that the Russell viper venom pathway is found in all vertebrates.
Effect of Age and Site on Transfusion Requirements of Adolescents With Severe Haemophilia A.
Authors: Aronstam A. , McLellan D.S. , Turk P.
Published: May 2019

4935 bleeding episodes in 75 adolescents with severe haemophilia A and without inhibitors to Factor VIII were studied during 5 years 1973-1977 6726 Factor VIII transfusions were given. 1.22 transfusions per bleed given in 1973 rose to 1.39 transfusions per bleed in 1977. 1.20 transfusions per bleed were given to 10 year olds which rose to 1.47 at 15 years. 745 bleeding episodes needed retransfusion within 24 hours. Iliopsoas (61% of bleeds) and retroperitoneal (58% of bleeds) were the sites needing most retransfusions wichin 24 hours. Total transfusions per bleed were most frequent in retroperitoneal (3.6) and iliopsoas (2.5) bleeds. On 181 occasions bleeds occurred into more than one site simultaneously and required 221 transfusions for complete resolution. Multiple bleeds involving the thigh (1.4) and upper arm (1.4) required most transfusions per bleeding episode.

Conclusions are that adolescent transfusion requirements peak at 15 years. Bleeds into the psoas and retroperitoneum may benefit from higher initial doses of Factor VIII and multiple bleeds require no more initial therapy than single bleeds.
Thrombolytic Properties of a Tissue Activator of Plasminogen
Authors: Andreenko G.V. , Shimonaeva E.E. , Serebryakova T.N.
Published: May 2019

Preparations of a tissue activator of plasminogen (TA) readily soluble in the physiological solution were obtained from porcine heart according to the procedure of Bachman et al. up to the stage of precipitation by Zn( C2H3O2)2. H2O. “In vitro” the TA preparations reduced the lysis time of
the rat plasma euglobulin fraction clot from 65-90 min in the control down to 7-14 min and induced the blood clot lysis. The highest rate of lysis was observed when the activator was combined with plasminogen. When TA was dissolved in rat plasma and physiological solution, the rate of the clot lysis was decreased. An intravenous injection of TA into the blood stream of rats with experimental thrombosis led to a clot lysis for 15-60 min. The rate of clot lysis was independent of the dose used. After 10 and 20 min of intravenous injection of TA the fibrinolytic activity of the plasma euglobulin fraction was increased 1,5-2-fold. The level of fibrinogen tended to a decrease. The level of degradation products was increased 1,2-1,5-fold. The fibrinolytic activity was slightly increased after 20 min. The activities of antiplasmi ns and antiactivator and the recalcification time remained unchanged.
The Effect of Drugs in Preventing Retitrombosis after Arterial Thrombectomy in Dogs
Authors: Lastoria S. , Maffei F.H.A.
Published: May 2019

Patients submitted to vascular reconstruction may be at high risk of thrombosis, possibly due to an hypercoagulable state and reduction of in and out-flow. The use of drugs to lower this risk has frequently been advocated. In order to reproduce to some extent such a situation, an experimental model was developed and the effect of some dings evaluated. Thrombosis was induced in the femoral artery of 42 dogs by endothelial injury and by reduction of flow and run-off. Twenty four hours later the animals were randomly allocated to one of six treatment groups: control, 2,500 U of subcutaneous heparin each 8 hours, 10 ml/kg of intravenous dextran, 0.5 mg/kg of dipyridamoleeach 8 hours, 0.5 U/kg of bothropase (coagulant fraction of the venom of Bothrops jararacakindly supplied by Dr.G. Rosenfeld), either in one sole dose or each 12 hours. Thirty minutes after treatment being initiated thrombectomy was performed. Arterial permeability was again verified after another 24 hours, by inspection and arteriography. Tests for clotting, fibrinolytic and platelet functions were performed sequentially. At the end of the first step of the experience there was thrombosis and alteration in coagulation and fibrinolysis in 1001 of the animals. After thrombectomy rethrombosis occurred in all animals of the control group. A significant reduction of rethrombosis was observed for the groups treated with dipyridamole and bothropase each 12 hours.
Inhibition of PF4 and ßTG Release from Platelets by Piracetam
Authors: Henry R.L. , Nalbandian R.M. , Herman G.E. , Ho T.
Published: May 2019

Platelet factor four (PF4) and beta-thromboglobulin (βTG) were released from human platelets alpha granules by ADP and epinephrine and measured by radioimmunoassay. Both release materials are antiheparins but PF4 is reported to be more potent. However, PF4 is released at about 1/4 the level of βTG in nanog rams/ml. Total release occurred with 5 ugm/rnl ADP in platelet-rich-plasma adjusted to 200,000 platelets/mm3 and with 1.25 × 10-5M epinephrine. No further release was found by freeze-thawing procedures. In one case, no release occurred although full aggregation proceeded normally with both mediators. Only minimal amounts were recorded after freeze-thawing indicating a storage pool deficiency of PF4 and βTG in an apparantly normal individual. Complete inhibition of PF4 and βTG release was obtained concurrently with elimination of the 2nd epinephrine wave by 6.4 × 10-4 M Piracetam. In contrast to aspirin, no inhibition of ADP, Collagen, or Ristocetin aggregation or release occurred with Piracetam. In previous work it was determined that Piracetam even at 6.4 × 10-3 M did not modify thrombin, prothrombin, or activated partial thromboplastin times. In addition, clot retraction was not modified in concentrations of Piracetam as high as 1.28 × 10-2 M known to eliminate the 2nd wave of platelet aggregation by epinephrine.
Platelet Regeneration time in Cardiovascular Patients
Authors: Roncucci R. , Deperon R. , Destailleur J. , Doumont J. , Lambelin G. , Larson J. , Stalle Van F. , Verlegne R.
Published: May 2019

Platelet regeneration time (PRT). based on the assessment of platelet malondialdehyde (MDA) production before and repeatly after intake of one single dose of acetylsalicylic acid (ASA). has been determined using a sensitive and semi-automated method in healthy young volunteers. old healthy subjects. patients with vascular prosthetic material and patients with occlusive vascular disease (1). The mean PRT t/2 for 9 healthy young volunteers was found to be 4.0±0.3 days. In 15 patients who had undergone either heart valve replacement surgery or aortoiliac reconstruction the mean PRT t/2 was drilmatically shorter (2.40±0.1 days; p < .001). In the group of patients with occlusive vascular disease (n = 13). the mean PRT t/2 was also shorter but the difference was not statistically significant (3.4±0.3 days; p > .05); it must however be noted that six of these patients showed a shortened PRT t/2 value comparable to that observed in patients with vascular prosthetic material. Moreover. investigations designed to compare PRT in healthy young volunteers and in old heal thy subjects suggest that age does not affect per se PRT.

(1) R. Roncucci et al., Thromb .Res., accepted for publication.
Studies on Certain Aspects of the Dynamics of Cholesterol Deposition in Rabbit Arterial Tissue
Authors: Mukherjee S. , Mukherjee C.
Published: May 2019

Rabbits were maintained on a 1% cholesterol diet for 30, 60 and 90 days and jsotope labeling of aorta and serum was attained by feeding 100 mc of 4-14C-cholesterolduring the last 4 days before sacrifice of each group. Labeled aorta and low-density lipoprotéine (LDL) isolated from sera of the various diet regimens were employed for in vitro study of rates of flux of free and esterifiedcholesterol by incubating respectively with LDL and aorta of a rabbitmaintained for similar periods on above diet but given no radiocholesterol. Influx of free and ester cholesterol into thoracic aorta of hypercholesterolemia rabbit were respectively 6 and 11 times that obtained with tissues isolated from norraocholesterolemic animals. With progressive Ingestion of hypercholesterolemia diet, a gradual increase in rate of influx with concomitant lowering of efflux rate was noticed for both free and ester cholesterol. Studies on percentage clearance of labeled cholesterol from aorta of hypercholesterolemic rabbits into serum LDL indicate that 25 to 30 percent of radioactivity of free cholesterol is removed by LDL as against 2 to 4.5 percent of ester cholesterol radioactivity. Experiments carried out with partially de-lipidated LDL of sera hypercholesterolemic rabbits reveal that efflux of cholesterol from aorta is markedly increased.
Towards a Simultaneous and Harmonized Regulation of Haemostasis and of the Cardiovascular System
Authors: Mester L. , Szabados L. , Launay J.M. , Mester M.
Published: May 2019

I-Desoxy-l-(5-hydroxytryptamino)-D-fructose is a synthetic sugar derivative of serotonin, however, its spontaneous formation under physiological conditions is quite possible (5th Inter. Congr. Thromb. Haemost., Paris, 1975, Abstr. n°233). This, and similar sugar derivatives of serotonin show a serotonin-like activity, however, a discrepancy has been observed between their affinities towards D and M type tryptaminergic receptors, when compared with the affinity of serotonin for the same receptors. The sugar derivatives have been distinguished by an increased passage of the blood-brain barrier and by a limited uptake by theplatelet. They exhibit a mechanism which mildly inhibits platelet functions, while mildly supporting haemostasis by vascular smooth muscle contraction. Besides the regulation of blood pressure, heart rate and sinusal coronary flow, some typical central effects (anti-stress activity, suppression of the carotid occlusion response, etc.) have also been observed, which have a beneficial effect on the cardiovascular system. Progressing in this way, it is hoped to have a new approach to inhibiting thrombosis without significantly interfering with haemostasis.
The Values of β-TG During the Anticoagulant Therapy in Patients with Venous Thrombosis and Myocardial Infarction
Authors: Lucic A. , Borota R. , Radujkov Z.
Published: May 2019

In 38 patients with deep venous thrombosis and 52 patients with myocardial infarction who were on long term anticoagulant therapy, the estimations of β-TG have been done by radioimmunoassay using a kit developed by the Radiochemical Centre, Amersham, England. In the group of patients with deep venous thrombosis, the increased values of β-TG /values which were higher than 80 ng/ml /have been established in 47,3% of the cases and among the patients with myocardial infarction, in 73% of the cases. From the total of 56 patients with increased level of β-TG, in 50 patients the level of prothrombin activity was higher than 20%. On the other hand, in patients with normal concentration of β-TG, the level of prothrombin activity was usually lower than 20%. Our preliminary results suggest the possible use of estimation of β-TG as an important supplementary parameter for evaluation of a substantial efficasy of applied anticoagulant therapy.
Platelet Aggregation Related to age in Diabetes Mellitus
Authors: Lecrubier C. , Scarabin P.Y. , Grauso F. , Samama H.
Published: May 2019

The relation between age and platelet sensitivity to various aggregating agents has been little explored until now. Previous studies have essentially concerned normal controls.

Platelet aggregation induced by ADP and collagen was studied in 174 diabetic patients before entering a controlled clinical trial.

The clinical characteristics have been precisely defined. The degree of retinal abnormality was assessed by fundus angiofluorography in every patient. Most patients had background retinopathy ; the remainder were normal. All results were computer analysed. The only significant relationship observed was between platelet sensitivity to ADP which increases in relation regularly to age in both insulin and non insulin treated diabetic patient with or without background retinopathy.

Spontaneous platelet aggregation was observed in 13 subjects and was not correlated to the existence of a neuropathy or any other clinical characteristics.
Dietary Sulphur-Containing Amino-Acids and Thrombophilic States
Authors: Hladovec J. , Linhart J.
Published: May 2019

Methionine, cysteine and cystine produced a thrombophilic state In rats caused by a damaging effect on endothelium. Similar damaging effect was produced by oral administration of methionine or cysteine in man as demonstrated by the counting of circulating endothelia. The effect of sulphur-oontaining amino-acids was Inhibited by simultaneous administration of high doses of pyridoxine or some endotheloprotective drugs. Estrogens produced a decreased methionine tolerance in rats which was corrected by an administration of pyridoxine. Consequently, the thrombophilic state after contraceptives is explained by the acquired defect of pyridoxine utilization caused by estrogens.
Early Changesof the Endothelial Anthrombotic Properties in Cholesterol fed Rabbits. II-Changes of Heparansulphatf and Other Gags
Authors: Abbate R. , Favilla S. , Gensini G.F. , Harinoni M. , Prisco D. , Semeri Neri G.G.
Published: May 2019

Sulphated mucopolysaccharides are synthetized by the endothelial cells and they occurr associated with the external cell surface and probably play a role in the non-thrombogenie properties of the endothelial layer. Heparansulphate (H.S.), chondroitin-6-sulphate (Ch-6-S) and hyaluronic acid (H.A.) concentrations were investigated by electrophoresis on Titan III zip zone cellulose acetate plate. Uronic acids were determined according to Dische. After 7 days of diet a significant decrease (m.v. -63%, P<0.001) of H.S..H.A. and Ch-6-S could be observed without changes of their reciprocal concentrations. After 14 days H.S., H.A. and Ch-6-S increased and no differences were observed in comparison with control rabbits. However after 28 days of diet H.S., H.A. and Ch-6-S showed a further and more pronounced decrease (m.v. -7%. P<0.001). Uronic acids showed changes tightly similar to those of sulphated glycosaminoglycans.
Speckle-Tracking-Echokardiografie – ein neues Tool für die Intensivstation?
Authors: Reckefuß Norbert , Heuer Jan , Butz Thomas
Published: May 2019

Die Beurteilung der kardialen Funktion kritisch kranker Patienten ist eine wichtige diagnostische Maßnahme auf Intensivstationen. Jedoch kann die meist angewandte detaillierte echokardiografische Untersuchung gerade Ungeübte rasch an ihre Grenzen bringen. Zusätzliche Informationen vermag die myokardiale Deformationsanalyse mittels Speckle-Tracking-Echokardiografie zu liefern – ein innovatives Verfahren, das in diesem Beitrag vorgestellt wird.
Plasma passivation of near-interface oxide traps and voltage stability in SiC MOS capacitors
Authors: Sun Yunong , Yang Chao , Yin Zhipeng , Qin Fuwen , Wang Dejun
Published: May 2019

Near-interface oxide traps severely affect the voltage stability of silicon carbide metal-oxide-semiconductor devices. In this work, electron cyclotron resonance microwave nitrogen plasma and electron cyclotron resonance microwave nitrogen-hydrogen-mixed plasma were used to passivate near-interface oxide traps in silicon carbide metal-oxide-semiconductor capacitors. An improved low-temperature midgap voltage drift method was proposed to evaluate the voltage stability of silicon carbide metal-oxide-semiconductor capacitors. Results showed that the effect of passivating near-interface oxide traps and voltage stability could be improved by increasing the nitrogen passivation time. However, excessive nitrogen passivation created deep-level interface traps that degraded the interface quality, and a small amount of hydrogen could passivate the deep-level traps produced by the excess nitrogen. As a result, the samples subjected to the passivation process with the nitrogen-hydrogen-mixed plasma had a smaller flat-band voltage drift and more stable carbide metal-oxide-semiconductor capacitors than the samples subjected to nitrogen plasma. However, the excessive introduction of hydrogen also produced additional defects, consequently making the stability of the metal-oxide-semiconductor devices sensitive to the time of the passivation process by nitrogen-hydrogen-mixed plasma. Therefore, the suitable time of mixed plasma passivation is crucial to the improvement of the stability of devices.
An ultra-fast two-terminal organic phototransistor with vertical topology for information technologies
Authors: Tzou Chen-Yang , Cai Shu-Yi , Tseng Chen-Yang , Chang Chi-Yuan , Chiang Shu-Yuan , Jiang Cing-Yu , Li Yao-Hsuan , Ma Jing-Meng , Liao Yu-Ming , Hsu Fang-Chi , Chen Yang-Fang
Published: May 2019

An organic two-terminal phototransistor structure for information technology has been designed, fabricated, and demonstrated. The device comprises a resistive random access memory (RRAM) in tandem with an organic solar cell (OSC). The transistor effect is realized by the functional integration of both individual devices; i.e., the photocurrent produced by the OSC is manipulated through the switchable RRAM. Compared with conventional phototransistors, our design possesses several intriguing features, including ultra-fast photoresponse time, controllable photocurrent, and solution processable active layers. Most importantly, these operational properties are achievable with only two vertically sandwiched electrodes, which are beneficial for high speed optical communication, circuit miniaturization, and energy saving. These unique features make it a good candidate for implementation in optical communication with diverse applications such as Li-Fi technology and security encryption.