bluuebunny/crossref_metadata_2025_split huggingface dataset:
Purification and Partial Characterization of a Hereditary Abnormal Antithrombin III Fraction of a Patient with Recurrent Thrombophlebitis
Authors: Tran T H , Bounameaux H , Bondeli C , Honkanen H , Marbet G A , Duckert F 
Published: July 2018

SummaryA relatively low heparin cofactor activity (0.60 U/ml) was observed in a patient with recurrent superficial thrombophlebitis of the left leg. However, the antigen concentration was in the normal range (1.04 U/ml) and the progressive antithrombin activity was normal. The crossed immunoelectrophoresis in presence of heparin in agarose gel separated the patient's AT-III antigen in 2 fractions with different mobilities. The patient's AT-III was purified for further characterization. The last step of the purification procedure, a heparin-agarose chromatography, led to a separation and a purification of 2 AT-III fractions with different heparin affinities: an abnormal AT-III with reduced heparin affinity and a normal AT-III with a heparin affinity similar to that of AT-III isolated from normal plasmas. Abnormal and normal AT-III share several identical properties as molecular weight, ability to form complexes with thrombin and progressive antithrombin activity.
Catabolism of Human Fibrinogen Fragment D in Normal Subjects and Patients with Liver Cirrhosis
Authors: Ardaillou Nicole , Yvart Jeannine , Bras Philippe Le , Larrieu Marie-José 
Published: July 2018

SummaryThe catabolism of human fragment D, (FgD), obtained by plasmin digestion of fibrinogen has been investigated in normal subjects and patients with liver cirrhosis and the results compared with those obtained for fibrinogen (Fg). Fg was labelled with I-125 and Fg D with I-131 using the chloramine T method. The plasma disappearance curves of both labelled proteins fitted a two exponential curve. In controls the plasma clearance rate of Fg D was greater than that of Fg as shown by the marked difference between the half-lives of these two tracers: 8,9 and 83,5 hours for Fg D and Fg respectively. The fractional catabolic rate of Fg D was 3.38 times the plasma pool per day. In nine patients with liver cirrhosis, catabolism of Fg was not modified. In contrast, catabolism of Fg D was significantly reduced with a half life of 13.0 hours and a low fractional catabolic rate. These results suggest the role of the liver in the catabolism of Fg D in man.
Optical Density Variations and Microscopic Observations in the Evaluation of Platelet Shape Change and Microaggregate Formation
Authors: Kitek A , Breddin K 
Published: July 2018

SummaryAddition of Ristocetin to formalin-fixed platelets suspended in diluted PPP induces a marked increase in turbidity which is not caused by platelet shape change but by the formation of microaggregates. If diluted PPP of patients with severe von Willebrand's disease is used, only an initial increase in turbidity and no further decrease is observed without any form variation of the platelets but again with formation of many microaggregates. In normal PRP diluted with buffered EDTA, ADP induces an increase in turbidity without further changes in optical density. Simultaneously platelets immediately change their shape with formation of pseudopodes and sphering but at the same time also microaggregates appear. Shape change and microaggregate formation can also be observed after the addition of Collagen to undiluted PRP which is followed by the formation of large aggregates and a decrease in optical density. Increase in optical density in undiluted PRP is not a specific indicator of platelet shape changes. Microaggregates can alone or partially be responsible for these changes. For the evaluation of platelet shape changes but also for the estimation of microaggregate formation microscopic methods are preferred.
Evidence against Vitamin K Deficiency in Normal Neonates
Authors: Malia R G , Preston F E , Mitchell V E 
Published: July 2018

SummaryUmbilical cord plasmas from 24 normal full-term neonates were studied. We confirmed the prolonged prothrombin time and low levels of Vitamin K dependent clotting factors previously described (1), but using a number of recently developed immunological and coagulation techniques we could find no evidence of vitamin K deficiency. We conclude that the decreased levels of vitamin K dependent clotting factors of normal neonates are the result of decreased synthesis by the immature liver and that it is questionable whether vitamin K prophylaxis is necessary for these infants.
Anticoagulation by Constant Subcutaneous Heparin Infusion
Authors: Parrilla Nenita , Ansell Jack 
Published: July 2018

SummaryA preliminary clinical trial was conducted to determine the feasibility of achieving and regulating therapeutic anticoagulation with heparin given by continuous subcutaneous infusion. Five patients with deep venous thrombosis confirmed by impedance plethysmography and/or venography were studied. All patients received an initial heparin dose of 5000 units by IV bolus. This was followed by a continuous subcutaneous heparin infusion at a dose of 15 to 25 units per kilogram per hour. Effective levels of anticoagulation were achieved in all five patients. Regulation and maintenance of therapeutic anticoagulation were no more difficult than with intravenous therapy. No major complications were encountered during therapy.Continuous subcutaneous infusion of heparin may have advantages over standard intravenous therapy or high dose intermittent subcutaneous therapy. However, more extensive clinical evaluation is warranted.
Preactivation and Deactivation of Blood Platelets
Authors: Aursnes Ivar 
Published: July 2018

SummaryHuman blood anticoagulated with a serine protease inhibitor was centrifuged with an erythrocyte agglutinating agent in the bottom of the tube. Platelet rich plasma (PRP) obtained in this manner contained platelets with different ability to aggregate with ADP located in the various layers of the tube. Platelets in the midportion of the tube were most extensively aggregated by a standard dose of ADP (1.6 μM) and mechanical stirring. Platelets in the lowest portion aggregated least, but still showed normal “shape change” when they were stimulated. The uppermost platelets in the tube also showed somewhat reduced aggregation compared with the midportion. These observations could not be explained by differences in platelet concentrations. On a descriptive basis the platelets in the midportion of the tube are designated preactivated and the lowermost platelets deactivated.
The Role of Platelet Membrane Potential in the Initiation of Platelet Aggregation
Authors: MacIntyre D E , Rink T J 
Published: July 2018

SummaryThe membrane potential of human platelets, and the role of this potential in platelet aggregation, was assessed using the non-covalent, fluorescent probe DiS-C3-5. High K+ and Gramicidin depolarised the cells, whereas valinomycin in standard (4 mMK+) solution produced a hyperpolarisation. Very small changes in potential were observed when choline Cl replaced NaCl. These findings indicate that platelets possess a relatively K+-permselective membrane. The resting potential calculated from the “valinomycin null point” (the K+ concentration gradient at which valinomycin did not change the potential) was approximately – 60 mV. Other factors that contribute to the platelet membrane potential include a significant Cl− permeability, demonstrated by replacing Cl− with methylsulphate, and an electrogenic Na+ pump, demonstrated using strophanthidin. Little or no change in potential was observed upon addition of ADP, collagen, U44069 or thrombin. Neither strong depolarisation with high K+ or gramicidin nor hyperpolarisation with valinomycin induced platelet aggregation or altered platelet responses to agonists. It is concluded that the information transduction mechanisms involved in platelet activation do not include changes in platelet membrane potential.
Protection of Platelet Surface Bound Factors IX a and VIII Against Specific Inhibitors
Authors: Váradi Katalin , Elödi Susan 
Published: July 2018

SummaryThe rate of inactivation of factors IX a and VIII as well as of the complex formed by them on the surface of platelets, induced by specific inhibitors has been studied. After the formation of complex both factors became more protected against high molecular weight inhibitors. As evidenced by the apparent first order inactivation rate constants, after complex formation the velocity of IX a – antithrombin III + heparin reaction fell to one-fourth, that of factor VIII – VIII : C antibody reaction decreased to 1/20. Enhanced resistance toward the high molecular weight inhibitors is presumably due to a steric change, since the low molecular weight phenylmethyl sulfonyl fluoride and diethyl pyrocarbonate inhibited free and complexed factor IX a to the same extent.
Prolongation of Rat Tail Bleeding Time Caused by Oral Doses of a Thromboxane Synthetase Inhibitor Which Have Little Effect on Platelet Aggregation
Authors: Butler K D , Maguire E D , Smith J R , Turnbull A A , Wallis R B , White A M 
Published: July 2018

SummaryN (7-carboxyheptyl) imidazole is an inhibitor of platelet thromboxane synthetase that has no effect on the cyclooxygenase activity. An oral dose of the substance to rats (10 mg/kg) prolonged tail bleeding time from 170 ± 13 sec to 284 ± 22 sec. This oral dose also inhibited platelet thromboxane B2 production induced by collagen ex vivo but had little effect on the aggregation dose response curve. There was no effect on thrombin-induced aggregation.Neither the thrombocytopenia induced by the Arthus reaction nor thrombus formation on an implanted cotton thread were inhibited by oral doses of carboxyheptylimidazole up to 30 mg/kg. Similarly neither the prothrombin nor activated partial thromboplastin time were affected.It is postulated that this thromboxane synthetase inhibitor prolongs bleeding time not by inhibiting platelet aggregation or blood coagulation but rather by preventing the vasoconstriction which would normally be caused by thromboxane A2.
Effects of 8-(N, N-Diethylamino)Octyl 3,4,5-Trimethoxybenzoate HCI (TMB-8) on Washed Blood Platelets with Special Reference to a Specific Loss of Serotonin
Authors: Mürer E H , Siojo E 
Published: July 2018

Summary8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate HCl (TMB-8) has been used to indicate involvement of Ca++ in platelet activities, but possible other effects have not been investigated. This study investigates TMB-8-induced leakage of cytoplasmic content and specific loss of one granule constituent, serotonin from washed platelets. TMB-8 concentrations above 0.5 mM block secretion initially and induce leakage after short time incubation. TMB-8 (0.15 mM) enhances a slow release of serotonin, but inhibits a slow release of low affinity platelet factor 4 antigen which take place when washed platelets are incubated at pH 7.4 and 37°C. These effects should be taken into consideration when TMB-8 is used as a calcium antagonist in platelets.
The Effects of Inaccurate Blood Sample Volume on Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT)
Authors: Peterson Powers , Gottfried Eugene L 
Published: July 2018

SummaryThe results of determinations of the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are frequently used to assess hemostatic function. Accurate results for these laboratory tests depend on many variables, one of which is the ratio of plasma to anticoagulant. We studied 12 patients and 4 normal subjects to determine the effects of sample volume on PT and aPTT. We conclude that underfilling may produce profound effects, particularly on the aPTT. In contrast, overfilling rarely affects the results. The greatest effects of sample volume were observed in specimens in which the true PT or aPTT was elevated. A normal PT or aPTT result on any specimen, regardless of sample volume, strongly suggests that the true value is normal.
A Comparison of Pentosan Polysulphate and Heparin II: Effects of Subcutaneous Injection
Authors: Fischer A-M , Merton R E , Marsh N A , Williams S , Gaffney P J , Barrowcliffe T W , Thomas D P 
Published: July 2018

SummaryA comparison has been made between the effects of pentosan polysulphate (SP54) and mucosal heparin following subcutaneous injection in man. Unlike heparin, pentosan polysulphate has relatively little effect in vivo as measured by anti-factor Xa clotting assay and none by an anti-Xa amidolytic assay (S-2222). However, pentosan polysulphate is at least as potent as heparin on a weight basis in producing activation of lipoprotein lipase, shortening of the euglobulin clot lysis time and impairing the generation of factor Xa. Our data indicate that pentosan polysulphate has more marked effects in vivo than in vitro, that the action of the drug on clotting is mediated mainly via an At III-independent pathway, and that its effects are not confined to the coagulation system.
Chromatography of Antihemophilic Factor on Diaminoalkane- and Aminoalkane-Derivatized Sepharose
Authors: Morgenthaler J-J 
Published: July 2018

SummaryAntihemophilic factor was chromatographed on a homologous series of diaminoalkane- and aminoalkane-modified Sepharose beads. Both factor VIII procoagulant activity (VIII:C) and protein are retarded on these columns when compared to their elution on a column made of unmodified Sepharose. Longer chains bind VIII:C and protein more tightly than shorter chains. No bound activity could be eluted with ethylene glycol. Increasing ionic strength eluted VIII:C and protein from aminoalkane- as well as from alkane-Sepharose. It seems likely that hydrophobic, rather than ionic forces, are responsible for the binding of VIII:C to the latter carriers.
Partial Characterization of a Fibrinolytic Inhibitor Produced by Cultured Endothelial Cells Derived from Human Umbilical Vein
Authors: Esnard F , Dupuy E , Dosne A M , Bodevin E 
Published: July 2018

SummaryA preliminary characterization of a fibrinolytic inhibitor released by human umbilical vein endothelial cells in primary culture is reported. This molecule of Mr comprised between 2 × 105 and 106 and of μ2 mobility precipitates at 43% ammonium sulphate saturation and is totally adsorbed on Concanavalin A Sepharose 4 B. A possible relationship with a macroglobulins is discussed.
Factor IX Deventer-Evidence for the Heterogeneity of Hemophilia BM
Authors: Bertina R M , Linden I K van der 
Published: July 2018

SummaryFactor IX Deventer was isolated from the plasma of a patient with severe hemophilia B. The patient was classified as BM because of an abnormal prolongation (2.1 times) of the ox-brain prothrombin time, that could be corrected by addition of antifactor IX serum. Experiments with the isolated factor IX Deventer showed that one of the two peptide bonds involved in the proteolytic activation of factor IX cannot be cleaved by physiological or non-physiological activators (XIa and RVV-X, respectively). Such a defect can explain why the molecule has no procoagulant activity. At present it is not clear why this defect makes factor IX Deventer such an effective inhibitor of the ox-brain prothrombin time. It is proposed that hemophilia BM is a heterogeneous disorder.
Diagnosis of Deep Vein Thrombosis by Combination of Doppler Ultrasound Flow Examination and Strain Gauge Plethysmography
Authors: Bounameaux H , Krähenbühl B , Vukanovic S 
Published: July 2018

SummaryDoppler ultrasound flow examination, strain gauge plethysmography and contrast venography were performed in 160 lower limbs of 80 in-patients. Deep vein thrombosis (DVT) was suspected in 87 limbs. Using measurement of venous stop-flow pressure, the Doppler method had an overall sensitivity of 83%. By combined use of Doppler and Plethysmography, sensitivity was increased to 96%. Specificity was 62% and 51%, respectively. With a positive and a negative predictive value of 80% and 73%, respectively, the combination of both non-invasive methods cannot reliably replace venography in the diagnosis of DTV, although all (40/40) thromboses proximal to or involving the popliteal segment were detected by either Doppler and Plethysmography or both.After exclusion of 14 patients (18%) suffering from conditions known to alter the results of these non-invasive methods, the positive predictive value of abnormal findings in both Doppler and Plethysmography was increased to 94% for suspected limbs, whilst negative predictive value of both negative Doppler and Plethysmography was 90%, allowing the avoidance of venography in these patients.
A Thiazole Compound with Potential Antithrombotic Activity
Authors: Nishizawa E E , Mendoza A R , Honohan T , Annis K A 
Published: July 2018

SummaryA thiazole derivative, 4,5-bis(p-methoxyphenyl)-2-(trifluoromethyl)-thiazole was found to be a potent inhibitor of collagen-induced platelet aggregation, in vitro, using platelets from at least six species, including man. It was active in human platelet-rich plasma at a concentration of 1 ng/ml. While its antiplatelet activity was greater than that of flurbiprofen, its cyclooxygenase activity was equivalent to that of flurbiprofen. Also, compared to flurbiprofen, the thiazole had less anti-inflammatory activity in the hind-paw edema test. The thiazole derivative inhibited platelet aggregation following oral administration in five laboratory species. In the guinea pig it was active at 0.5 mg/kg. The LD50 in mice was greater than 1000 mg/kg (i.p.). This compound, which was designed through a systematic drug development program, may have high potential as an antithrombotic agent.
Secretion Defect in Platelets Stored at 4°C
Authors: Rao A Koneti , Murphy Scott 
Published: July 2018

SummaryTo understand the functional changes induced by storage, we have examined the adenine nucleotides of platelets stored for 72 hr at 22°C and 4°C. Ten platelet concentrates (PC) were stored at each temperature with five in each group having a final volume of 50 ml and 30 ml. The total ATP and ADP content of platelets decreased following storage in all 4 groups of PC, with the decrease being greater in the PC stored at 22°C than those at 4°C. The mean thrombin secretable ATP+ADP content of platelets from PC stored at 22°C and 4°C were 29.7% and 19.7% of the total content, respectively (p <0.001). Thus, cold stored platelets have a higher total content of ATP+ADP but secrete distinctly lesser amounts than 22°C stored platelets. Labeling of the metabolic pool adenylates with 14C-adenine revealed a greater decrease in the adenylate energy charge of the platelets stored at 4°C. The secretion defect demonstrated in cold stored platelets may be related to the inability of these platelets to maintain ATP homeostasis.
The Inhibition of Tissue Activator and Urokinase by Human Plasma
Authors: Walker J E , Ogston D 
Published: July 2018

SummaryPlasma reduced the activity of urokinase and, to a lesser extent, tissue activator on unheated fibrin plates. After depletion of plasminogen by lysine-Sepharose the inhibitory effect of plasma was increased.Normal plasma separated on DEAE-Sepharose or, after passage through lysine-Sepharose, on Sephadex G-100 provided fractions in three regions capable of inhibiting tissue activator. The high molecular weight fractions inhibited both activators, but after plasma fractionation on Sephadex 4B the inhibitory activities against tissue activator and urokinase eluted separately. Urokinase inhibition eluted with a2-macroglobulin: the inhibition of tissue activator was of higher molecular weight and of greater lability. Inhibition of tissue activator was found in two lower molecular weight regions: the fractions of one region inhibited tissue activator and coincided with the elution of fast-acting antiplasmin activity. The other region inhibited both tissue activator and urokinase. Alpha1 antitrypsin and antithrombin III eluted after both inhibitory regions.
Protein C Deficiency in a Dutch Family with Thrombotic Disease
Authors: Bertina R M , Broekmans A W , van der Linden I K , Mertens K 
Published: July 2018

SummaryA rabbit antibody against human protein C was used for the quantitative estimation of protein C in plasma. In healthy individuals protein C antigen ranged from 0.65-1.45 U/ml. Plasma protein C antigen was found to be independent of either age or sex. Under influence of oral anticoagulant treatment the protein C antigen concentration decreased to 0.47 U/ml (at low intensity treatment) or 0.33 U/ml (at high intensity treatment). Using normal ranges of protein C and protein C/factor II and protein C/factor X ratios criteria were developed for the assessment of protein C deficiency. In a Dutch family with a history of thrombotic disease two members were found to have an isolated protein C deficiency, while a third one is suspected of protein C deficiency. In one case it was possible to confirm the diagnosis of suspected protein C deficiency during temporary withdrawal of the anticoagulant therapy.
Platelet Sensitivity to Prostacyclin and Thromboxane Production in Hyperlipidemic Patients
Authors: Strano A , Davì G , Averna M , Rini G B , Novo S , Di Fede G , Mattina A , Notarbartolo A 
Published: July 2018

SummaryIn 13 type II hyperlipidemics (10 males and 3 females; mean age 50.2 ± 10.6 years), in 10 type IV hyperlipidemics (7 males and 3 females; mean age 51 ± 13.3 years) and in 23 healthy age-and sex-matched controls, the following parameters were measured: plasma cholesterol; plasma TG; plasma C-HDL; VLDL, separated in a preparative ultracentrifuge; C-LDL; Apo B, with immunoelectrophoretic method; platelet sensitivity to prostacyclin; TXB2 formation in PRP; TXB2 in serum.This study provides evidence for: 1. Reduced platelet sensitivity to prostacyclin, more evident in type II hyperlipidemia that provides an additional mechanism involved in increased platelet aggregation found in type II hyperlipidemia.
2. Enhanced TXB2 formation in PRP after thrombin stimulation (664.65 ± 142.18 pmol/108 platelets) only in type II hyperlipidemics and such enhanced formation was positively correlated to C-LDL (r = 0.53; p <0.05) and to Apo B (r = 0.62; p <0.05); serum TXB2 formation rate was also increased in type II hyperlipidemia.
Factor VIII Fractionation on Aminohexyl Sepharose with Possible Reduction in Hepatitis B Antigen
Authors: Austen D E G , Smith J K 
Published: July 2018

SummaryThe method of factor VIII purification by chromatography on aminohexyl Sepharose has been extended so that up to 100 ml of intermediate purity concentrate can be processed on an 8.6 ml column. The product has a specific activity of 1.8 International Units of factor VIII per mg of protein. Most of the fibrinogen is removed and antibodies to blood group substances A and B are not detectable by haemagglutination techniques. Hepatitis B antigen has been reduced to one sixteenth of that in the starting material, in preliminary experiments. The process has the added advantage that it concentrates the factor VIII relative to the starting material.
Inhibition of Platelet Aggregation by Ethanol in Vitro Shows Specificity for Aggregating Agent Used and Is Influenced by Platelet Lipid Composition
Authors: Fenn C G , Littleton J M 
Published: July 2018

SummaryEthanol at physiologically tolerable concentrations inhibited platelet aggregation in vitro in a relatively specific way, which may be influenced by platelet membrane lipid composition. Aggregation to collagen, calcium ionophore A23187 and thrombin (low doses) were often markedly inhibited by ethanol, adrenaline and ADP responses were little affected, and aggregation to exogenous arachidonic acid was actually potentiated by ethanol. Aggregation to collagen, thrombin and A23187 was inhibited more by ethanol in platelets enriched with saturated fatty acids than in those enriched with unsaturated fats. Platelets enriched with cholesterol showed increased sensitivity to ADP, arachidonate and adrenaline but this increase in cholesterol content did not appear to influence the inhibition by ethanol of platelet responses. The results suggest that ethanol may inhibit aggregation by an effect on membrane fluidity and/or calcium mobilization resulting in decreased activity of a membrane-bound phospholipase.