bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring of Oral Anticoagulation by an Amidolytic Factor X Assay
Authors: Lämmle B , Bounameaux H , Marbet G A , Eichlisberger R , Duckert F 
Published: July 2018

SummaryThe validity of the amidolytic Factor X assay for the control of long term oral anticoagulation (OA) was investigated in 42 patients randomized into 2 groups; PT group (anticoagulant dosage according to PT) and F. X group (anticoagulant dosage based on F. X). An independent expert's dosage according to F. X served for analysis in the former group. In the F. X group the F. X based dosage was considered valid only when not differing by more than 15% from the expert's PT based dosage.Confirming the good correlation between PT and F. X the study further demonstrates that the changes from one control to the next one, ΔPT and ΔF. X, too, are significantly correlated (r = 0.58, p & 0.001, n = 217). In over one third of the periods the dosage proposals based on PT and F. X were identical and differed by more than 15% in only 12/217 instances.Our results justify a large trial on the control of OA by the amidolytic F. X assay.
Studies on the Activation Mechanism of Fibrinolytic Enzyme System in Plasma by Human Pancreatic Elastase
Authors: Toki N , Takasugi S , Ishizu K , Sato H , Sumi H 
Published: July 2018

SummaryIn the present study, the activation mechanism of fibrinolytic enzyme system in plasma by human pancreatic elastase was investigated. It was confirmed that human pancreatic elastase not only converted the co-existing plasminogen to low molecular weight-plasminogen which could be easily activated by the activator, but also inhibited α2-macroglobulin and α2-plasmin inhibitor which are antiactivators or fast reacting antiplasmins, and consequently, induced the activation of the fibrinolytic enzyme system in plasma.
Low Molecular Weight Trypsin-Plasmin Inhibitors Isolated from Papain Treated Urinary Trypsin Inhibitor
Authors: Sumi H , Toki N , Takasugi S , Maehara S , Maruyama M , Akazawa K , Matsuo O , Mihara H 
Published: July 2018

SummaryPapain treatment of human urinary trypsin inhibitor (UTI67; mol. wt. 43,000 by SDS-polyacrylamide gel electrophoresis, specific activity 1,897 U/mg protein) produced four new protease inhibitors, which were highly purified by gel chromatography on Sephadex G-100 and isoelectric focusing. The purified inhibitors (UTI26, UTI9-I, UTI9-II, and UTI9-III) were shown to be homogeneous by polyacrylamide disc gel electrophoresis, and had apparent molecular weights of 26,000, 9,000, 9,000, and 9,800, respectively, by sodium dodecyl sulfate gel electrophoresis. During enzymatic degradation of UTI67, the amino acid compositions changed to more basic, and the isoelectric point increased from pH 2.0 (UTI67) to pHs 4.4, 5.2, 6.6, and 8.3 (UTI26, UTI9-I, UTI9-II, and UTI9-III), respectively. Both the parent and degraded inhibitors had anti-plasmin activity as well as antitrypsin and anti-chymotrypsin activities. Much higher anti-plasmin/anti-trypsin and anti-plasmin/anti-chymotrypsin activities were observed in the degraded inhibitors than in the parent UTI67. They competitively inhibited human plasmin with Ki values of 1.13 X 10-7 - 2.12 X 10-6 M (H-D-Val-Leu-Lys-pNA substrate). The reactions were very fast and the active site of the inhibitors to plasmin was thought to be different from that to trypsin or chymotrypsin.
Biochemical and Functional Study of Antithrombin III in Newborn Infants
Authors: McDonald M M , Hathaway W E , Reeve E B , Leonard B D 
Published: July 2018

SummaryAntithrombin III (AT-III) was isolated by heparin affinity chromatography from adult venous and newborn term and preterm umbilical cord blood. The purified proteins were compared by SDS-PAGE, rocket immuno-electrophoresis, protein concentration by microbiuret relative to optical density at 280 nm, heparin cofactor specific activity, progressive neutralization of thrombin and factor Xa at 37°C and pH related antithrombin kinetics. The structural evaluations revealed a fetal AT-III of molecular weight, charge and electrophoretic migration indistinguishable from adult AT-III. The functional studies showed that, on an equimolar basis, the rates of thrombin and Xa interactions with fetal AT-III were as rapid as those with adult AT-III. The catalytic rates of various concentrations of heparin were also equal. The newborn infant, therefore, displays a quantitative but not qualitative deficiency of AT-III.
Activation of Human Coagulation Factor VIII by Activated Factor X, the Common Product of the Intrinsic and the Extrinsic Pathway of Blood Coagulation
Authors: Mertens K , Bertina R M 
Published: July 2018

SummaryThe intrinsic activation of human factor X has been studied in a system consisting of purified factors and in plasma. In both these systems factor Xa stimulated the activation of factor X by factor IXa plus factor VIII This is due to the activation of factor VIII by factor Xa. When this factor Xa is formed via the extrinsic pathway, the extrinsic factor X activator functions as a stimulator of the intrinsic factor X activator.
Increased Factor VIII Associated Activities in Cushing's Syndrome: A Probable Hypercoagulable State
Authors: Zanon R Dal Bo , Fornasiero L , Boscaro M , Cappellato G , Fabris F , Girolami A 
Published: July 2018

SummaryThirteen women and 2 men affected by Cushing’s syndrome were investigated. The following parameters were used: plasma and urinary cortisol levels, factor VIII assay (antigen, activity and von Willebrand factor) together with other coagulative assays.Samples were taken before surgery or before medical and/or radiation therapy and every 30–50 days after treatment and continued for 11 months. Cortisol and factor VIII were increased before treatment and decreased slowly after treatment to become normal in 3–4 months. Other clotting tests did not show significant changes. It seems that high plasma cortisol levels may stimulate the production of factor VIII. Patients with Cushing’s syndrome often exhibit thromboembolic complications after surgery. It is likely that the clotting abnormalities responsible for such complications is the increased factor VIII activities level.
Effect of Calcium and Synthetic Peptides on Fibrin Polymerization
Authors: Furlan M , Rupp C , Beck E A , Svendsen L 
Published: July 2018

SummaryHuman fibrinogen was subjected to limited proteolytic attack by thrombin, batroxobin or Agkistrodon contortrix thrombin-like enzyme, yielding desAB-, desA- or desB-fibrin monomers, respectively. Turbidity curves demonstrated that, with all three enzymes, the polymerization process was strongly accelerated by increasing the calcium concentration from 10−5 M to 10−4 M. Synthetic peptide Gly-His-Arg (5 mM), an analogue of the aminoterminal sequence of fibrin β-chain, inhibited aggregation of desB-fibrin monomers at physiological calcium concentration whereas it enhanced aggregation of desA- and desAB-fibrin monomers at calcium concentrations below 10−4 M. On the other hand, Gly-Pro-Arg (1 mM) corresponding to the amino-terminus of fibrin α-chain, dramatically inhibited aggregation of both desA- and desB-fibrins, but it only moderately affected the polymerization of thrombin-induced monomers. We conclude that the observed effects of Gly-Pro-Arg and Gly-His-Arg are not due solely to their competition with fibrin amino-termini for the respective binding sites in the D-domain, but rather reflect conformational changes in fibrin monomers which affect the polymerization process.
DDAVP Stimulates Prostacyclin Production
Authors: Belch J J F , Small M , McKenzie F , Hill P A , Lowe G D O , McIntyre D E , Forbes C D , Prentice C R.M 
Published: July 2018

SummaryDes-amino-D-arginine vasopressin (DDAVP) stimulates the release of factor VIII and plasminogen activator from the vascular endothelium. An infusion of exogenous factor VIII given to haemophiliacs causes an increase in platelet activation. This activation does not occur after stimulating a rise in the patient's own factor VIII level caused by DDAVP infusion. We hypothesised therefore that DDAVP could also cause the endothelial release of prostacyclin (PGI2), a potent anti-platelet agent which would counteract the aggregating effect of factor VIII. To examine this possibility we studied the effect of DDAVP on prostacyclin release, as measured by its stable metabolite 6-oxo-PGFla, in vitro and in vivo. Rabbit aortic rings were incubated with different concentrations of DDAVP using saline as control. The supernatant was assayed for 6-oxo-PGFlct by radioimmunoassay. All concentrations of DDAVP gave a significant release of 6-oxo-PGF1α. Vasopressin was much less potent. When DDAVP was infused into haemophilic patients there was a significant increase in circulating 6-oxo-PGF1α levels immediately after the infusion. The facial flushing observed as a side-effect of DDAVP could therefore be prostacyclin-mediated. We confirmed this by abolishing the DDAVP induced flushing seen in normal subjects by prior treatment with aspirin which inhibits PGI2 formation.
Platelet Factor Four and Protamine Sulfate Neutralization of Heparin Fractionated According to Anionic Charge Density
Authors: Poon Man-Chiu , Hurst Robert E , Rives Michael S 
Published: July 2018

SummaryThe role of heparin structure in neutralization by the neutralizing substances (NS) platelet factor 4 (PF4) and protamine sulfate (PS) was investigated using a thrombin clotting assay and a series of more homogeneous heparin fractions varying systematically in charge density (Z). For a given heparin, plotting inverse clotting times measured without NS, and in the presence of PF4 or PS, vs heparin concentration yielded approximately parallel straight lines displaced horizontally according to the amount of NS. Potencies of heparin fractions in the absence of NS, or in the presence of PF4 or PS, depended almost identically upon Z2. Small but significant quantitative differences in potency among equivalent fractions from different heparins showed both PF4 and PS had a slight preference for the least active subfraction of decolorized heparins, but for the most active subfraction of undecolorized heparins. Neutralization of heparin by PF4 and PS probably proceeds by similar mechanisms, but the details of structure outside the antithrombin III-binding oligosaccharide of heparin may enter in differently.
A Comparison of Plasminogen Activators Derived from Rat Plasma, Primary Rat Hepatocytes and Isolated Perfused Rat Liver
Authors: Sharoni Yoav , Topal Maria C , Tuttle Patricia R , Berger Henry 
Published: July 2018

SummaryOf the two cell types it was possible to culture from the dissociated rat liver, hepatocytes and Kupffer cells, only the former were fibrinolytically active. Rat hepatocytes during the first 24 hr in culture secreted two plasminogen activators with molecular weights identical to those found in rat plasma, an 80,000-dalton form (PA-80) and a 45,000-dalton form (PA-45). Partially purified preparations of plasminogen activators from both sources were subjected to isoelectric focusing (IEF) to compare characteristics further. There were three distinct peaks of PA-45 in each preparation with isoelectric points of 7.1, 7.2 and 7.4; all electrophoretic forms had the same low affinity to fibrin. PA-80 from both sources displayed similar IEF profiles with forms ranging from pH values of 7 to 8, all with the same high affinity to fibrin. The major form of PA-80 in the plasma preparation had an isoelectric point of 7.9 whereas that in the hepatocyte preparation had an isoelectric point of 7.6. The isolated perfused rat liver was also shown to produce both PA-80 and PA-45 emphasizing the physiological relevance of the findings with hepatocytes. It is concluded that in the rat hepatocytes contribute to the plasma profile with regard to the plasminogen activator content.
Problems by Using Whole Blood in Heparin Measurements
Authors: Talstad Ingebrigt 
Published: July 2018

SummaryProblems by using whole blood (WB) of various packed cell volume (PCV) in heparin measurements were studied. WB had to be used within 1 hr, due to influence of platelet Factor 4. The increase of Ca++ by increasing PCV, had a moderate influence by the assays studied. The recalcification time (RT) of WB was timeconsuming and had low accuracy and precision, due to different heparin response. The activated partial thromboplastin time (APTT) also had low accuracy and precision, due to different heparin response; the results were equal for WB and plasma. The thrombin clotting time (TCT) had high accuracy and precision in plasma. The TCT could also be used for WB since there was a good correlation between T20 (20 NTH U thrombin/ml) using WB, and T30 using plasma (r = 0.89, N = 61). The calcium thrombin clotting time (CaTCT) is not recommended for WB assaying.
Role of Surface Negative Charge in Platelet Function Related to the Hyperreactive State in Estrogen-Treated Prostatic Carcinoma
Authors: Jung Stephanie M , Kinoshita Kenji , Tanoue Kenjiro , Isohisa Ichiro , Yamazaki Hiroh 
Published: July 2018

SummaryThe relationship between platelet surface negative charge and hyperfunction was examined by determining electrophoretic mobility (EPM), aggregability, and sialic acid of platelets in prostatic cancer, prostatic cancer with estrogen, prostatic cancer with estrogen and aspirin, prostatic hypertrophy, and healthy aged males. Estrogen treated prostatic cancer patients had significantly higher platelet EPM. A good linear correlation was found between sialic acid and EPM (r = 0.97, p <0.001). EPM was negatively correlated with primary aggregations by adrenaline and ADP but not with secondary or maximum aggregations, suggesting increased surface negative charge may inhibit primary aggregation. Estrogen and platelet population changes influenced surface negative charge. Neuraminidase removal of platelet surface sialic acid resulted in dose-dependent decreases of EPM which paralleled decreases in sialic acid. Aspirin treated patients and platelets incubated with aspirin in vitro both showed increased platelet EPM. These results suggest that platelet surface negative charge may directly affect platelet function.
An In Vivo Model for Studying Platelet Aggregation and Disaggregation
Authors: Page C P , Paul W , Morley J 
Published: July 2018

SummaryA simple minimally invasive technique has been developed for the continuous monitoring of 111-Indium labelled homologous platelets in the thoracic (C1) and abdominal (C2) regions of experimental animals. The effects of the aggregatory agents adenosine diphosphate (ADP), collagen and platelet activating factor (PAF) and the anti-aggregatory agent, prostacyclin (PGI2) have been studied in the guinea-pig. Administration of ADP, collagen or PAF produces an increase in counts in C1, a decrease in counts in C2, and hence an increase in the ratio C1/C2. The rise in C1/C2 is more protracted after collagen administration than after ADP or PAF. PGI2 (50-500 ng/kg) reduces the response to ADP. The present technique is both simple, reproducible and although the present experiments are in the presence of heparin, the technique remains functional in the presence of minimal heparin, thus making it a suitable method for studies of platelet function and the evaluation of anti-aggregatory agents in vivo.
Surface Adsorption of Factor XI: II. Evidence that Different Mechanisms Are Involved in Binding to Glass and Plastic Materials
Authors: Mannhalter Christine , Schiffman Sandra 
Published: July 2018

SummaryBlood coagulation factors XI and XIa possess binding site(s) for glass and plastics, located in the heavy chain of the molecule. To elucidate the nature of binding, adsorption and desorption properties of factor XI and XIa to different surfaces have been studied. Desorption experiments with high salt (2.4 M NaCl) suggest participation of ionic forces in the binding to glass. This is consistent with the decreased adsorption of factor XI (pI – 9.0) to glass with increasing pH. The non-ionic detergent Triton X-100, which splits hydrophobic bonds, desorbs factor XI very well from plastics and partially from glass. The anionic detergent SDS, which will split hydrophobic as well as ionic bonds, is the most effective agent tested for the elution of factor XI from glass. We, therefore infer, that the binding of factor XI to glass is the combined effect of ionic and hydrophobic binding, whereas the adsorption of factor XI to plastics is primarily hydrophobic.
Factor II Related Antigen and Antithrombin III Levels as Indicators of Liver Failure in Consumption Coagulopathy
Authors: Sié P , Letrenne E , Caranobe C , Genestal M , Cathala B , Boneu B 
Published: July 2018

SummaryIn order to detect impaired synthesis of blood coagulation factors associated to consumption coagulopathy, a simultaneous evaluation of factor II-related antigen (II rAg) and of antithrombin III (AT III) was carried out in 16 patients affected with severe defibrination. An in vitro preliminary study on plasma and serum demonstrated that the levels of II rAg and of AT III, assessed by the Laurell technique with Behring antisera, were not reduced by the coagulation process. The patients were, a posteriori, classified into two groups according to the absence (group A) or the presence (group B) of factors predisposing to liver failure such as metastasis, cirrhosis, and prolonged shock. II rAg and AT III levels are significantly correlated; they are in the normal range in group A but reduced in group B. Thus II rAg or AT III level determinations are useful markers in the detection of liver failure associated to the consumption phenomenon. These results also suggest that part of the decreased AT III levels reported in severe cases of disseminated intravascular coagulation may be the consequence of an associated liver failure.
Mepacrine Labelling Test and Uranaffin Cytochemical Reaction in Human Megakaryocytes
Authors: Hourdillé P , Fialon P , Belloc F , Boisseau M R , Andrieu J M 
Published: July 2018

Summary5-HT storage organelles were observed by electron microscope analysis in human megakaryocytes. They were less numerous per unit of surface than in platelets. Their number depended on the visualization technique employed. Thus after fixation with calcium-enriched glutaraldehyde a higher number of very opaque organelles was observed than of uranaffin-positive organelles after the cytochemical uranaffin reaction. With conventional electron microscopy deep black granules characteristic of dense bodies were not observed.Fluorescent microscopy showed greenish-yellow granules distributed throughout the whole cytoplasm in 96 ± 1.4% of normal megacaryocytes incubated with mepacrine. In 85.6 ± 5%, 5.28 ± 1.28 granules per 10 ¼m2 were observed.With the mepacrine labelling test, 74% of the megakaryocytes of a patient with Hermansky-Pudlak syndrome contained no granules. A similar finding was made in the platelets of the same patient. This suggests that mepacrine also stains the dense bodies in the megakaryocytes and that in the Hermansky-Pudlak syndrome the platelet anomaly is secondary to a megakaryocyte anomaly.
Desensitisation in Human and Rabbit Blood Platelets
Authors: Hallam T J , Ruggles P A , Scrutton M C , Wallis R B 
Published: July 2018

Summary1. Exposure of human and rabbit blood platelets to all full agonists tested induces agonist-specific (or homologous) desensitisation except in the case of adrenaline and collagen in human platelets.2. Desensitisation to vasopressin and 5-hydroxytryptamine (5HT) develops rapidly and results from suppression of maximal responsiveness without significant shift in the dose/response curve (Type I). In rabbit platelets, maintenance of desensitisation to 5HT is correlated with the extracellular 5HT concentration. Responsiveness to other agonists is either unaffected, or is enhanced due to a shift in the dose/response curve to the left without change in maximal responsiveness.3. Homologous desensitisation to ADP, U-46619 and thrombin develops more slowly, is correlated with disaggregation and is associated with a shift in the dose/response curve to the right without suppression of maximal responsiveness (Type II). Responsiveness to most other agonists is either unaffected, or is enhanced due to a shift in the dose/response curve to the left without a change in maximal responsiveness. However, exposure to thrombin suppresses the maximal response to vasopressin without a shift in the dose/response curve, and exposure to U-46619 causes a shift in the dose/response curve for collagen to the right.4. In human platelets prolonged exposure to 5HT causes agonist non-specific (or heterologous) desensitisation in which responsiveness to all agonists except adrenaline is suppressed as a result of shifts in the dose/response curves to the right.5. We propose that Types I and II homologous desensitisation result respectively from prolonged receptor occupancy and from either activation of degradative mechanisms for the agonist or processing of the receptor to a lower affinity state.
In Vivo Platelet Release in Myeloproliferative Disorders
Authors: Ireland H , Lane D A , Wolff S , Foadi M 
Published: July 2018

SummaryThe in vivo platelet release reaction in 22 patients with myeloproliferative disorders has been studied by measuring plasma concentrations of the platelet release product β-throm-boglobulin (βTG). Mean βTG and mean βTG:whole blood platelet count ratio were significantly raised in the patient group taken as a whole compared to an age matched control group. No significant increases were observed in the plasma concentrations of thrombin and plasmin sensitive fibrinogen fragments fibrinopeptide A (FpA) and Bβ1-42. The patients were divided into those who had normal, increased or decreased responses to in vitro ADP-induced platelet aggregation. Mean βTG and the mean βTG:whole blood platelet count ratio were higher in the increased and decreased responders to ADP than in the normal aggregation group, but the differences in means were not statistically significant. Aspirin given to six patients at a dose sufficient to eliminate the secondary phase of ADP-induced platelet aggregation reduced mean βTG and the mean βTG : whole blood platelet count ratio but did not alter mean FpA and Bβ1-42. It is concluded that the enhanced platelet release reaction seen in myeloproliferative disorders is independent of plasma protease activity that arises when coagulation and fibrinolytic systems are activated.
The Role of Factor IX in Tissue Thromboplastin Induced Coagulation
Authors: van den Besselaar A M H P , Ram I E , Alderkamp G H J , Bertina R M 
Published: July 2018

SummaryTissue thromboplastin apoprotein was partially purified from human brain. The apoprotein was recombined with mixed phospholipids to yield active thromboplastin. The recombined thromboplastin induced proteolytic activation of isolated human factor IX in the presence of factor VII and Ca2+. The clotting times of various deficient plasmas were determined as a function of apoprotein concentration, keeping the phospholipid concentration constant. The clotting times of a factor XII-deficient plasma were the same as those of a factor XII/factor IX-deficient plasma, except at very low apoprotein concentrations. However, under those conditions the difference in clotting times was independent of the presence of anti-factor VII serum. Similar observations were made for factor XI-deficient plasma in comparison with factor XI/factor IX-deficient plasma. These results indicate that activation of factor IX by factor VII/tissue thromboplastin does not significantly contribute to plasma coagulation.