bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet Function in Hyperbetalipoproteinemia
Authors: Colman Robert W 
Published: July 2018

SummaryIndividuals with familial hyperbetalipoproteinemia are at increased risk of premature atherosclerosis and thrombosis. Although there is controversy whether platelet survival is shortened or normal in this disease, several in vitro tests of platelet function are abnormal including a decreased threshold concentration for stimulation of aggregation by ADP, epinephrine and collagen and increased release of nucleotides to the same agents. These functional changes are accompanied by an increase of cholesterol to phospholipid ratio in the platelet membrane and in low density lipoprotein in individuals with type Ha hyperlipoproteinemia. Clofibrate and halofenate reverse some of the abnormalities in vitro and the former drug, when administered for 6 weeks to patients with type II a hyperlipoproteinemia decreases platelet sensitivity to ADP and epinephrine. The platelet hypersensitivity to aggregating agents can be reproduced in vitro by increasing the cholesterol to phospholipid rather in normal platelets. These artificially hypersensitive platelets can be returned to normal by halofenate in vitro. Incorporation of cholesterol into platelet membranes increases the basal level of the membrane associated enzyme adenylate cyclase. However, the enzyme no longer responds to stimulation by prostaglandin E1 and this is associated with relative resistance of the platelet to inhibition by this pharmacologic agent. These functional alterations produced by cholesterol enrichment of platelet membranes occur is parallel with an increase in platelet membrane microviscosity suggesting that the more rigid membrane can alter the behavior of membrane associated enzymes and receptors. A correlation appears to exist between the ability of certain drugs to induce phase separation in model membranes and the potency in inhibitory platelet aggregation.
The von Willebrand Pig as a Model for Atherosclerosis Research
Authors: Fuster V , Bowie E J W 
Published: July 2018

SummaryIn order to evaluate a possible role played by platelets in the development of atherosclerosis, the aortas of 11 control pigs and 11 homozygous von Willebrand (vWd) pigs were examined for spontaneous atherosclerosis. Of the 11 normal pigs, 6 showed multiple atherosclerotic plaques with an intimal thickening of 63 to 130 μm. In contrast, none of the von Willebrand pigs had multiple plaques and only one showed a single lesion of more than 2 mm in diameter.In a prospective study 5 control pigs and 5 vWd pigs were given a high (2%) cholesterol diet from the age of 3 to 9 months. All of the controls developed atherosclerotic plaques. In 4 of the pigs the plaques exceeded 13% of the aortic surface with an intimal thickening of 50 to 390 pm. In contrast, only one of the vWd pigs developed atherosclerotic plaques which only involved 7% of the aortic surface. Most of the vWd pigs, however, developed non-atherosclerotic flat fatty lesions. These findings may be related to the imp aired platelet arterial wall interaction in vWd. The vWd pigs seem to be an ideal model for atherosclerosis research.
β-Thromboglobulin and Deep Vein Thrombosis
Authors: Smith R C , Duncanson Jeanette , Ruckley C V , Webber R G , Allan N C , Dawes Joan , Bolton A E , Hunter W M , Pepper D S , Cash J D 
Published: July 2018

SummaryThe measurement of plasma β-thromboglobulin as a potential diagnostic test for venous thrombosis has been investigated in 16 normal volunteers, 24 patients presenting with deep vein thrombosis (DVT) or pulmonary embolism and 46 patients screened by 125 I fibrinogen test (IFT) for post-operative DVT. The normal mean was 33 ng/ml (range 15-117 ng/ml). Of the 24 patients with clinical thrombotic disease 22 presented with DVT confirmed by phlebogram or IFT and 2 presented with embolism confirmed by lung scan. At the time of first presentation 12 out of 24 had βTG values greater than 70 ng/ml. All except 3 of this group of 24 patients had values of greater than 70 ng/ml at some stage during a subsequent week of daily sampling. DVT was detected in 13 out of 46 screened post-operative patients. There was a rise in βTG observed within 24 hr of the IFT becoming positive but the mean rise did not reach significance at the 5% level.An association between DVT and high βTG values has been confirmed. However, its clinical value cannot yet be fully elucidated until factors, probably related to blood sampling and clearance, are further investigated.
Platelet Metal Levels in Normal Subjects Determined by Atomic Absorption Spectrophotometry
Authors: Baker Richmond J , McNeil John J , Lander Harry 
Published: July 2018

SummaryA method has been developed for the estimation of iron, copper, zinc, calcium and magnesium in human platelets using atomic absorption spectrophotometry. Fe and Cu are either absent or present in very low concentration approaching the limit of detection: Zn, Ca and Mg are readily detectable. EDTA is preferable to ACD(A) or heparin as the anticoagulant for collection in that the platelet yield is reliable: however, slightly low results for Ca and Mg are obtained. Corrections for residual plasma and contaminating red cells are essential. Plasma and platelet metal levels in 33 normal subjects are reported together with the findings in four studies undertaken on platelets obtained from subjects with polycythemia vera.
Relationships of Adenine Nucleotide Metabolism to Platelet-Collagen Adhesion
Authors: Morin Robert J , Chen Albert F T 
Published: July 2018

SummaryAdhesion of platelets to collagen fibrils in a stirred system was inhibited by preincubation of platelets with combinations of 2-deoxy-D-glucose and oligomycin or antimycin. The inhibition of adhesion was associated with a decrease in metabolic ATP to 6% of control levels. Without metabolic inhibitors, platelets adherent to collagen fibrils were found to have catabolized approximately 57% of their metabolic ATP, and converted a major part of this to IMP. Storage pool ATP and ADP contents were also diminished in the adherent platelets. Pretreatment with imipramine resulted in 76% inhibition of the release reaction, but only 5% inhibition of adhesion. Imipramine-treated platelets that were adherent to collagen showed significant depletion of metabolic ATP, but markedly diminished conversion of ATP to IMP as compared to control adherent platelets. Inhibition of deamination of platelet AMP by coformycin or erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) did not inhibit adhesion, although platelets adherent to collagen after treatment with these agents showed depletion of metabolic ATP. These studies suggest that adhesion is an energy dependent process, occurring independently of release, and not associated with conversion of ATP to IMP. The energy dependent portions of the adhesion process are probably disc to sphere transformation and pseudopod formation, the ATP threshold requirement is relatively low, and the ATP utilized can probably be regenerated during the adhesion process via glycolysis and oxidative phosphorylation.
Quantitation of Radio-Labelled Vitamin K1 and Vitamin K1 Epoxide in Plasma by High Pressure Liquid Chromatography
Authors: Bjornsson Thorir D , Swezey Sarah E , Meffin Peter J , Blaschke Terrence F 
Published: July 2018

SummaryA convenient, accurate and reproducible high pressure liquid chromatographic method for the quantitation of radio-labelled vitamin K1 and vitamin K1 epoxide in plasma is described. The method involves the determination of total ether extractable radioactivity, and a chromatographic separation to determine the relative quantities of radio-labelled vitamin K1 and vitamin K1 epoxide. The method is useful over a wide range of ratios of the two compounds, and has a coefficient of variation of approximately 5%.
Comparison of Reagents for Determining the Activated Partial Thromboplastin Time
Authors: Hoffmann J J M L , Meulendijk P N 
Published: July 2018

SummarySix commercially available reagents for the determination of the activated partial thromboplastin time have been evaluated and compared with respect to their sensitivity to the coagulation factors VIII, IX and XI and to their response to heparin. Some variation was observed among the reagents regarding their sensitivity to factor XI and even greater differences were obtained with factors VIII and IX. It was also clear that none of the reagents was sensitive to the same extent to the factors tested. The sensitivity to heparin shows considerable variation, in terms of time as well as mode of response to increasing heparin levels. In four reagents this response is linear, it is logarithmic in one and the remaining one is yet again different.It seems unlikely that any standardization of the APTT determination is at present possible with the reagents studied.
Blood Platelets as a Possible Source of Creatine Kinase in Rat Plasma and Serum
Authors: Shibata Sachiko , Kobayashi Bonro 
Published: July 2018

SummaryThe creatine kinase (CK) activity in rat plasma was found to be correlated with that in serum or platelets. Rat serum contained higher activity not only of CK but also of lactate dehydrogenase than the corresponding plasma. The plasma CK activity decreased with increasing age of rats. Only the brain-type isoenzyme of CK was found in plasma, serum and platelets. Contamination of brain-type with muscle-type isoenzyme was detected in rather exceptional cases in which the activity was high among old rats. These results suggest the possible contribution of blood platelets to the CK activity of circulating plasma as well as to the activity in serum in rats.
Ultrastructural Studies on the Surface Coat of Human Platelet Aggregated by Polylysine and Dextran
Authors: Taketomi Y , Kuramoto A 
Published: July 2018

SummaryPositively charged macromolecule, polylysine (mol. wt. 15,000; 23,000; 180,000) could induce the platelet aggregation in low concentration but high concentration was required in the case of neutral macromolecule, dextran (mol. wt. 40,000; 250,000; 2,000,000). The larger molecules of polylysine and dextran were more effective in inducing platelet aggregation. In the dextran-induced aggregation, positively charged Thorotrast particles on the cell surface did not decrease significantly. On the other hand, the surface membranes of platelets aggregated by polylysine were essentially devoid of bound particles. Heparin in hibited the poly lysine-induced platelet aggregation but not the dextran-induced aggregation. These findings suggested that polylysine induced aggregation more effectively than dextran by reducing the negative surface charge and giving stronger adsorption force on cell surface.In platelet-rich plasma, polylysine elicited the release reaction of 14C-serotonin but dextran did not. Possible mechanism by which polylysine could elicit the release reaction is the formation of more tightly packed platelet aggregate than that by dextran in the presence of the low calcium ion concentration in citrated platelet-rich plasma. Average distance between plasma membranes of aggregated platelets, however, did not vary with the degrees of polymerization of these macromolecules.
Meseclazone, 5-Chlorosalicylic Acid and Acetylsalicvlic Acid
Authors: Diamantis William , Kohlhepp William C , Haertlein Barbara , Melton John , Sofia R Duane 
Published: July 2018

SummaryMeseclazone and its major metabolite, 5-chlorosalicylic acid (5-CSA) have been shown to possess anti-inflammatory, analgesic and antipyretic activity. The comparative effects of these compounds on platelet aggregation were evaluated in vitro and ex vitro with acetylsalicylic acid (ASA). in vitro, meseclazone and ASA exhibited almost identical inhibitory potency of secondary phase ADP aggregation while 5-CSA was less effective. Moreover, collagen aggregation was inhibited by all three agents: ASA > meseclazone > 5- CSA. Thrombin-induced aggregation was inhibited to approximately the same extent by 5- CSA and ASA while meseclazone was inactive. The in vitro effects on the release-inducing aggregants were confirmed by ex vitro experiments in rats. These demonstrated that ASA and meseclazone inhibited collagen-induced aggregation 1 and 4 hr after oral administration although ASA was three to four times more active. ASA, but not meseclazone, was still effective 24 hr after administration. Bleeding times in rats 1 and 4 hr following oral administration of meseclazone and ASA were not altered. It is concluded that meseclazone and/or 5-CSA inhibit in vitro and ex vitro platelet aggregation initiated by the release reaction similar to ASA and other non-steroidal anti-inflammatory drugs.
In Vivo Platelet Kinetics in 31 Diabetic Patients
Authors: Dassin E , Najean Y , Poirier O , Passa Ph , Bensoussan D 
Published: July 2018

SummaryIn vivo platelet survival was estimated, in 31 diabetic patients, using 51Cr-labelled autologous platelets. A mathematical analysis attempted to measure the “potential” life span (senescence process) and the degree of a superimposed aleatory destruction (consumption process).The potential platelet life span in diabetics did not differ from normal values. However, excessive consumption was observed in one third of the studied cases, without correlation with the age of the patients, the clinical duration of diabetes, and the degree of vascular impairment. Thus, platelet kinetic studies did not provide presently useful indications, in a particular patient, regarding the prognosis of the vascular disease, and the justification of anti-aggregant therapy.
The Action of Immobilized Thrombin on Factor VIII, Fibrinogen and a Synthetic Tripeptide
Authors: Brown J E , Carton C L , Dietz A S , Baugh R F , Hougie C 
Published: July 2018

SummaryBovine thrombin was insolubilized by attachment to cyanogen bromide-activated Sepharose (Sepharose-thrombin) or to activated (Affi-Gel 10) agarose containing a 10 Å long arm (Affi-Gel-thrombin). Coupling in both instances approximated 7,000 units of thrombin per ml packed gel as determined by 125I-thrombin incorporation. The thrombin beads hydrolyzed the synthetic tripeptide Bz-Phe-Val-Arg-pNA (S-2160) at different rates, with the Sepharose-thrombin more active (220 esterase units per ml) than Affi-Gel thrombin (20.4 units per ml). The Km was significantly higher for the insolubilized thrombins (2×10-3M) than uncoupled thrombin (Km = 8×10-5M). The Sepharose- thrombin activated factor VIII significantly more rapidly than Affi-Gel-thrombin. Neither matrix-bound thrombin clotted a fibrinogen solution or liberated significant amounts of fibrinopeptides over 48 hr. This data indicates that a proteolysis of factor VIII, rather than a complex with thrombin, is the method of activation of factor VIII and that factor VIII is more accessible to the action of immobilized thrombin than is fibrinogen.
An International Collaborative Assay of Factor VIII Clotting Activity
Authors: Barrowcliffe T W , Kirkwood T B L 
Published: July 2018

SummaryAn International Collaborative Study was organised to replace the first International Standard for factor VIII. A freeze-dried concentrate, 73/552, and a freeze-dried plasma, 75/510, were assayed against the International Standard, and also compared to fresh normal plasma and local standards.In assays of the concentrate 73/552 against the first I.S. the mean potency was 1.14 i.u./ ampoule and there was no significant difference between one-stage and two-stage methods. When assayed against average fresh normal plasma, the potency was 1.05 “normal plasma units” per ampoule. It was agreed by the participants that the potency of 73/552 be regarded as the mean of these two figures, i.e. 1.10 i. u./ampoule.In assays of the freeze-dried plasma, 75/510, against the first I.S. the mean potency was 0. 68 i. u./ampoule, but the one-stage assays gave significantly higher potencies (mean 0.74 1. u./ampoule) than the two-stage assays (mean 0.59 i. u./ampoule). The same trend was also seen in the fresh normal plasmas, and in the local plasma standards. This finding has important implications for the standardisation of factor VIII.Stability studies on the concentrate 73/552 gave a predicted loss of 0.02% per year at – 20° C. All participants agreed that the material was suitable to serve as an International Standard, and at the 26th meeting of the Expert Committee on Biological Standardisation of the World Health Organization, the material in ampoules coded 73/552 was established as the 2nd International Standard for factor VIII, with a potency of 1.10 i. u./ampoule.
Thromboplastin Calibration
Authors: Loeliger E A , Hoeff-van Halem R. van der , Halem-Visser L P van 
Published: July 2018

SummaryStandardization of the thromboplastin most commonly used for anticoagulant control in The Netherlands has been achieved by the Dutch Reference Laboratory for Anticoagulant Control. The system established for control indicates the performance characteristics of each batch of thromboplastin in patients relative to a national calibration batch. Calibration constants were assessed according to an ICTH/ICSH proposal and with a reproducibility of approximately 2% (CV). With the use of a given calibration constant of the International Reference Preparation of Thromboplastin (1.0) and after assessment of the calibration constant of the National Reference Preparation in international terms (0.93), the accuracy of calibration with the various modifications of the calibration procedure is of the order of magnitude of 3% (CV). On the basis of the calibration protocol, physicians will be provided with correlation tables containing, for their convenience, prothrombin (thromboplastin) times in terms of the reference thromboplastin (uniform, i. e., batch-independent, prothrombin times), conventional prothrombin activity (percentages), and in due course with International Calibrated Ratios.* With this approach current practice in the prescription of oral anticoagulants will be maintained. Opportunity is given, however, to aim at internationally proposed therapeutically optimal target values.
Activation of Bovine Factor X in the Presence of Calcium, Magnesium, Barium or Manganese ion
Authors: Yue Robert H , Gertler Menard M 
Published: July 2018

SummaryThe binding of divalent metal ions to bovine factor X, factor Xa and the coagulant protein in Russell’s viper venom was studied by the technique of fluorescence quenching. Titration of factor X with Ca+2, Mg+2 or Ba+2 revealed that these metal ions can bind to factor X. A tightly binding site(s) was observed with Kd of 79 and 98 μM for Ca+2 and Mg+2 respectively. A loosely binding site(s) was evident with Kd of 0.55, 0.50 and 0.35 mM for Ca+2, Mg+2 and Ba+2 respectively. The quenching phenomenon was also observed when Mn+2 was used as titrant but factor X precipitated out when the concentration of Mn+2 was 10 mM. The binding of Ca+2, Mg+2, Ba+2 or Mn+2 to bovine factor Xa or to the purified coagulant fraction of Russell’s viper venom was very weak in each case.In the absence of Ca+2, the coagulation fraction of Russell’s viper venom could not activate bovine factor X. Activation of factor X was achieved when Ca+2 was replaced by either Mg+2, Ba+2 or Mn+2. When the concentration of these ions were 5 mM, the efficiency of factor Xa generation was estimated to be: Ca+2> Mg+2> Ba+2> Mn+2. Higher concentration of Mg+2, Ba+2, or Mn+2 retarded the activation process. However, Ca+2, Mg+2, Ba+2 or Mn+2 has little or no influence on the esterase activity of factor Xa or purified Rusell’s viper venom.The results suggest that complexation of divalent metal ion with factor X is prerequisite in the activation process. The binding of Mg+2, Ba+2 or Mn+2 to these loosely binding sites might have altered the geometrical configuration as well as the electrostatic environment on factor X significantly. Thus, it is more difficult to form the binary complex and a slower generation of factor Xa results. Therefore, divalent metal ion serves as a dual role in the activation of factor X to factor Xa depending upon the ionic concentration.
Comparative Plasma Heparin Levels after Subcutaneous Sodium and Calcium Heparin
Authors: Low Joyce , Biggs J C 
Published: July 2018

SummaryComparative plasma heparin levels were measured in normal subjects injected subcutaneously with 5,000 units of the sodium and calcium salts of heparin. Plasma heparin levels were measured up to 7 hr post-injection by an anti-factor Xa assay (Denson and Bonnar 1973). Preliminary studies indicated that heparin levels were reproducible in subjects who received two injections of the same heparin. Peak plasma concentrations (Cmax) and the time at which peak concentration was reached (Tmax) varied greatly from subject to subject. In one group of subjects (15) two commonly used heparins, a sodium heparin (Evans) and a calcium heparin (Choay) were compared. Peak heparin concentrations were not significantly different. However the Tmax for the sodium heparin (1.5 hr) was significantly earlier than the Tmax for the calcium heparin (3 hr) and this was not due to a difference in the volume of the two heparin injections. No significant difference could be detected in the plasma clearance rate and the molecular weight distribution of the two heparins.In two other groups of subjects, sodium and calcium preparations from two manufacturers were compared. In general, the sodium salts gave rise to significantly higher plasma concentrations, which could be interpreted as a greater bioavailability of sodium salts. These results indicate that the salt of the heparin can influence the plasma concentration achieved after subcutaneous injection.
Heparin-Neutralizing Activity, Total Progressive Antithrombin and the Ethanol Gel Test in Acute Chest Pain
Authors: Raper C G L , Love H 
Published: July 2018

Summary92 patients admitted to a cardiac monitoring unit with chest pain were investigated. The mean heparin-neutralizing activity of the 34 patients with severe myocardial infarction was found to be significantly different from the mean of 70 normal controls. However, there was considerable overlap between individual observations and the normal range. Only 5 of the 34 patients with severe myocardial infarction had antithrombin levels outside the normal range. In patients with a severe myocardial infarct tested on the 2nd and 3rd day after infarction there was a significant increase in the number of positive ethanol gel tests compared with the other patients studied.
An Assay of the Antithrombotic Action of Warfarin: Its Correlation with the Inhibition of Stasis Thrombosis in Rabbits
Authors: Wessler Stanford , Gitel Sanford N , Bank Harry , Martinowitz Uri , Stephenson Ronald C 
Published: July 2018

SummaryNo assay of the antithrombotic action of warfarin has been available. Experiments were performed to determine whether Xa inhibitory activity - the reaction rate between activated factor X (Xa) and antithrombin III - could serve this function. 105 warfarin-treated patients demonstrated a significant 18% increase in Xa inhibitory activity compared to 51 controls, p <0.001, without any correlation between this activity and the prothrombin times in the treated patients. A similar increase in Xa inhibitory activity was obtained in rabbits treated with 2 mg of warfarin per day compared to control animals, p <0.001. Employing an assay which routinely produced venous thrombosis after clotting proteases were infused into warfarin-treated and control rabbits, three observations were made. 1. The extent of stasis thrombosis induced by injection of thrombin, Xa or activated factor IX, was significantly reduced in warfarin-treated rabbits compared to control animals, independent of alteration in the four established vitamin K-dependent zymogens. 2. In the rabbit, significant changes in prothrombin times and prothrombin and factor X activities preceded by 5 days both the increase in Xa inhibitory activity and the antithrombotic effect which became significant on the sixth day. 3. The correlation between Xa inhibitory activity of warfarin-treated rabbits and the extent of stasis thrombosis induced by Xa was significant, p<0.05. Xa inhibitory activity is one measure of the antithrombotic action of warfarin.