bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Components which Interfere with Ristocetin-induced Platelet Aggregation
Authors: Baugh Robert F , Brown James E , Hougie Cecil 
Published: July 2018

SummaryNormal human plasma contains a component or components which interfere with ristocetin-induced platelet aggregation. Preliminary examination suggests a protein (or proteins) which binds ristocetin and competes more effectively for ristocetin than do the proteins involved in ristocetin-induced platelet aggregation. The presence of this protein in normal human plasma also prevents ristocetin-induced precipitation of plasma proteins at levels of ristocetin necessary to produce platelet aggregation (0.5–2.0 mg/ml). Serum contains an apparent two-fold increase of this component when compared with plasma. Heating serum at 56° for one hour results in an additional 2 to 4 fold increase. The presence of a ristocetin-binding protein in normal human plasma requires that this protein be saturated with ristocetin before ristocetin-induced platelet aggregation will occur. Variations in the ristocetin-binding protein(s) will cause apparent discrepancies in ristocetin-induced platelet aggregation in normal human plasmas.
The Activation of Human Factor IX
Authors: Østerud B , Laake K , Prydz H 
Published: July 2018

SummaryThe activation of factor IX purified from human plasma has been studied. Factor XIa and kallikrein separately activated factor IX to factor IXa. In both cases factor IX a had an apparent molecular weight of about 42–45000 in sodium dodecyl sul-phate-polyacrylamide disc gel electrophoresis compared with a molecular weight of about 70000 for the native factor IX. The activation by XIa required Ca2+-ions whereas Ca2+-ions did not influence the activation by kallikrein. A mixture of tissue thromboplastin and factor VII or RusselPs-viper venom alone did not activate factor IX. Trypsin activated and plasmin inactivated factor IX.
Serologic Evidence for Hepatitis B Virus Infection in Patients with Hemophilia B
Authors: Hoofnagle Jay H , Aronson David , Roberts Harold 
Published: July 2018

SummaryAmong sera from 160 patients with hemophilia B from 9 centers in Europe and North and South America, 2.5% were positive for hepatitis B surface antigen (HBsAg), 60% for antibody to HBsAg, and 31% for antibody to the hepatitis B core antigen. Evidence of exposure to the hepatitis B virus appeared to be related to severity of disease and age rather than the source and method of manufacturer of factor IX concentrate.
Heterogeneity of Rabbit Platelets
Authors: Freedman Michael L , Karpatkin Simon 
Published: July 2018

SummaryIntravenous injection of Phenylhydrazine into intact rabbits resulted in a thrombocytosis of 1.85 fold and megathrombocytosis (large platelets) of 2.30 fold. Splenectomy markedly impaired this response. The intravenous injection of red blood cell hemo-lysates gave a response similar to that of Phenylhydrazine in both intact and splenec-tomized animals. Basal data obtained from intact and splenectomized animals; as well as kinetic data obtained following apparent splenic blockade secondary to Phenylhydrazine hemolysis revealed the presence of a splenic platelet pool with preferential splenic sequestration of megathrombocytes.It is suggested that the thrombocytosis and absolute megathrombocytosis of hemolysis is due to splenic blockade by red blood cell hemolysate.
The Platelet-Endothelial Cell – VIII Axis
Authors: Nachman R. L , Jaffe E. A 
Published: July 2018

SummaryCultured human endothelial cells synthesize and secrete a protein(s) which has factor VIII antigen and von Willebrand factor activity. Subcellular membrane and granule fractions derived from human platelets also contain the factor VIII antigen and von Willebrand factor activity. Circulating platelets constitute a significant reservoir of VIII antigen containing approximately 15 % of the amount present in platelet-poor plasma. Thus normal platelets contain surface bound as well as intracellularly stored von Willebrand factor, a protein synthesized by endothelial cells which is required for normal platelet function.
The Young Platelet Population in Children with Cyanotic Congenital Heart Disease
Authors: Goldschmidt Béla , Sørland Svein Jan 
Published: July 2018

SummarySome morphological, biochemical and functional parameters of platelet population in children with cyanotic congenital heart disease (CCHD) were studied by making comparisons of the normal platelet population in both CCHD patients and controls. The mean volume of the platelets from cyanotic patients was greater than from normals. The platelet size distribution curves demonstrated a shift towards larger than normal size in the case of CCHD. The mean protein content, as well as the mean PF3 content of platelets was increased in CCHD. Following addition of kaolin, PF3 release was more rapid and of shorter duration with platelets from CCHD patients as compared to normal platelets. They also released more PF3 than did normal platelets. After addition of ADP, collagen, or adrenalin, platelets of CCHD patients were more responsive than similarly treated platelets from normals. Platelets from CCHD showed an increased initial rate of aggregation and greater maximum aggregation. These data suggested that the platelet population of CCHD patients consists of larger, younger and functionally more active platelets than does the platelet population of normals.
The Effect of Beta Adrenergic Blockade upon Exercise-Induced Changes in Blood Coagulation and Fibrinolysis
Authors: Britton B.J , Wood W.G , Smith Muriel , Hawkey Christine , Irving M.H 
Published: July 2018

SummaryExercise stress is known to stimulate blood coagulation and fibrinolysis possibly as a result of sympatho-adrenal stimulation of the beta adrenergic receptor. In order to test this hypothesis five men exercised on four separate occasions with and without prior beta adrenergic blockade with oxprenolol, propranolol and pindolol. The increase in plasma adrenaline and noradrenaline concentration was much greater during exercise under beta blockade but activation of fibrinolysis was enhanced as well. Factor VIII levels did not change significantly during any of the experiments. These results suggest that the activation of fibrinolysis by exercise is not mediated by the beta adrenergic receptor. The influence of beta adrenergic blockade on the change in factor VTII with exercise was inconclusive.
Role of Surface Glycoproteins in Human Platelet Function
Authors: Nurden A. T , Caen J. P 
Published: July 2018

SummaryGlycoproteins present at the external surface of cells probably play specific roles in cellular function. Increasing evidence suggests that the glycoproteins span the plasma membrane with the bulk of the bound carbohydrate asymmetrically distributed on the outer surface. Micellar association of glycoproteins in membranes leads to pore formation and functional roles in transport through the membrane, while surface glycoproteins have been shown to be enzymes, to determine cell specificity and contribute to the cell surface charge. The platelet plasma membrane contains 3 major glycoproteins, glycoproteins I, II and III as characterized in order of their decreasing molecular weight. Glycoprotein I appears to have the highest sialic acid content and to give rise to a platelet specific acidic macroglycopeptide on trypsin digestion. Specific glycoprotein abnormalities in the platelets of patients with Glanzmann’s thrombasthenia suggest that the glycoproteins play a role in the mechanism of platelet aggregation. A much reduced content of glycoprotein I in the platelets of 2 patients with the Bernard Soulier syndrome may be associated with their defective adhesion to subendothelium and indicates a possible relationship on the platelet surface with the von Willebrand factor protein. Preliminary evidence suggests that in common with other plasma membranes the platelet membrane has a fluid structure and that the organization of the glycoproteins on the platelet surface is extremely sensitive to stimuli and susceptible to change.
Importance of Protease Inhibition in Studies on Purified Factor VIII (Antihaemophilic Factor)
Authors: Beck Eugen A. , Bachmann Peter , Barbier Peter , Furlan Miha 
Published: July 2018

SummaryAccording to some authors factor VIII procoagulant activity may be dissociable from carrier protein (MW~ 2 × 106) by agarose gel filtration, e.g. at high ionic strength. We were able to reproduce this phenomenon. However, addition of protease inhibitor (Trasylol) prevented the appearance of low molecular weight peak of factor VIII procoagulant activity both at high ionic strength and elevated temperature (37°C). We conclude from our results that procoagulant activity and carrier protein (von Willebrand factor, factor VIII antigen) are closely associated functional sites of native factor VIII macro molecule. Consequently, proteolytic degradation should be avoided in functional and structural studies on factor VIII and especially in preparing factor VIII concentrate for therapeutic use.
The Effects of Hepes Buffer on Clotting Tests, Assay of Factors V and VIII and on the Hydrolysis of Esters by Thrombin and Thrombokinase
Authors: Roberts Phyllis S. , Hughes Haywood N. , Fleming Patricia B. 
Published: July 2018

SummaryShorter clotting times were found in the presence of 50 mM Hepes (N-2-hydroxyethylpiper-azine-N1-2-ethanesulfonic acid) buffer than of 50 mM Imidazole buffer in one-stage assays of factors V and VIII, in modified APTT and PT tests and in tests of the clotting of human plasma by purified human thrombin. All tests were performed at ionic strength 0.155 in the presence of either Hepes. NaOH or Imidazole. HC1 buffer, pH 7.4 at 37°. The faster clotting in the presence of Hepes buffer, therefore, is probably due, at least in part, to acceleration by Hepes of thrombin’s enzymatic action on fibrinogen and/or of the polymerization of the fibrin monomers.Hepes may also have effects on other blood clotting reactions. Rates of hydrolysis of TAME or BAME (p-toluenesulfonyl-or benzoyl-L-arginine methyl ester) at pH 7.4, 37° by purified human or bovine thrombin were essentially the same in 200 mM Hepes as in 250 mM Tris. HQ buffer (rates in Hepes. NaOH or Hepes. KOH buffers were compared with those in Tris. HQ plus NaCl for KC1). However, with purified bovine thrombokinase, rates of TAME hydrolysis in Hepes buffer were accelerated and rates of BAME hydrolysis slightly inhibited. Hepes, therefore, reacts with thrombokinase but whether this accelerates (or inhibits) the rate of converting prothrombin to thrombin remains to be determined. In addition, Hepes has an inhibitory effect on clotting since increasing the concentration of Hepes from 50 mM to 200 mM inhibits clotting in the PT, APTT and bovine thrombin-human plasma tests.Hepes buffer is being added to some plasmas and to some reagents used in clotting tests. It is, therefore, important to realize that its concentration must be monitored closely or erroneous results may be obtained in clotting tests and assays of clotting factors.The clotting times were the same in the presence of 50 mM Tris. HC1 as in Imidazole. HC1 buffers in APTT tests at three ionic strengths but they differed slightly in plasma-thrombin tests. Depending upon the ionic strength, 17 mM Barbital Sodium. HC1 buffer inhibited APTT tests but accelerated plasma-thrombin tests. All the buffers tested, therefore, have individual effects on the clotting tests.
Study of a Proposed International Standard for Blood Coagulation Factor IX
Authors: Brozović Milica , Kirkwood T. B. L , Robertson Iris 
Published: July 2018

SummaryAn International Collaborative Study was organized to establish a standard for factor IX. Two freeze-dried concentrate preparations, C1 and C2, and one freeze-dried plasma P were compared with each other, with fresh normal plasmas and with local standards in 13 laboratories. One of the concentrate preparations (C1) contained heparin and this gave rise to non-parallel assays in laboratories testing concentrate C1 in dilutions containing more than 0.05 i.u. of heparin per ml.Assays of factor IX showed good precision for both plasma and concentrate in all laboratories; no systematic effect of method, operator or day of assay was detected.The plasma preparation P and the concentrate preparation C2 were compared with 59 individual fresh normal plasma samples, and a mean potency ratio of 0.78 (95% confidence Hmits 0.73-0.84) for plasma and 5.62 (95 % confidence limits 5.13-6.16) for the concentrate C2 obtained. Only 21 estimates of concentrate C1 in terms of fresh plasma were obtained giving a mean potency ratio of 3.85 (95% confidence limits 1.87—7.92).The estimated loss of potency for freeze-dried plasma stored at — 20° C is approximately 0.4% per year. The concentrate C2 is apparently more stable and only very small losses occurred even at higher storage temperatures.All participants agreed that the preparation C2 would be suitable to serve as an International Standard for factor IX; they also agreed that the figure assigned for the unitage should be based on the number of ml of ‘average fresh normal plasma’ estimated to contain the factor IX activity of one ampoule of the preparation. It is proposed to recommend to the World Health Organization that the preparation of factor IX concentrate C2, in ampoules coded 72/32, be considered for establishment as the International Standard for factor IX, and that the international unit for factor IX be assigned on the basis of 5.62 units per ampoule of this preparation.
Effect of Platelet Antiserum on the Precipitation of Soluble Fibrin by Endotoxin
Authors: Müller-Berghaus Gert , Kramer Wilfried 
Published: July 2018

SummaryRabbits were injected with a platelet antiserum to examine the role of thrombocytopenia on the precipitation of soluble fibrin by endotoxin. Platelet antiserum removed more than 98% of the circulating platelets, and the resulting thrombocytopenia with platelet counts below 10,000 per μl persisted during the entire 10 hr-period of the experiment. Leukocyte counts were not significantly influenced by the platelet antiserum. Since the rabbits were treated with high doses of heparin, activation of intravascular coagulation by the antiserum did not occur.Precipitation of soluble fibrin was achieved by injection of endotoxin into rabbits with ancrod-induced circulating soluble fibrin. Thrombocytopenia did not prevent the occurrence of glomerular microdots after ancrod and endotoxin administration. On the contrary, if endotoxin was injected into antiserum- and heparin-treated rabbits with circulating soluble fibrin, glomerular microdot formation occurred even in a higher percentage than in control rabbits treated with absorbed platelet antiserum. This investigation indicates that platelet antiserum-induced thrombocytopenia does not protect against precipitation of soluble fibrin by endotoxin.
The Estimation of the Number of Binding Sites for Antibody on Antigen Molecules with Reference to Factor VIII and its Antibody
Authors: Pool Judith , Biggs Rosemary , Miller R. G 
Published: July 2018

SummaryThe theoretical basis for determining the number of antibody sites on antigen molecules is examined. The theoretical considerations are applied to factor VIII molecules. Examples based on data available at the Oxford Haemophilia Centre are calculated to illustrate the approach. It is concluded that there are few sites on each factor VIII molecule for human antibody. The three antibodies for which reasonable data were available suggest 1–3 sites for human antibody. The data for rabbit antibody suggest 5–6 sites per factor VIII molecule.
The Influence of the Thyroid Function on the Metabolic Rate of Prothrombin, Factor VII, and Factor X in the Rat
Authors: Oosterom Allan T. van , Mattie Herman , Hermens Wim Th , Veltkamp Jan J. 
Published: July 2018

SummaryThe influence of the thyroid function on the metabolic rate of prothrombin, factor VII, and X was studied in the rat. Disappearance rates of the three coagulation factors were measured after synthesis had been blocked with appropriate doses of warfarin, and reappearance rates were assessed upon induction of synthesis by high doses of vitamin K1 injected into rats displaying coumarin induced hypocoagulability.No statistically significant difference in the disappearance and production rates of any of the factors could be found between normal euthyroid rats and thyroxin-treated hypothyroid rats proven to be euthyroid. The differences between the two euthyroid groups and the hypothyroid group were highly significant, however: hypothyroidism results in an approximately 50% decrease of the metabolic rates of the three coagulation factors under study.The reappearance of the three factors, under euthyroid as well as hypothyroid conditions, showed a biphasic pattern: in the first two hours after vitamin K1 administration to warfarin treated rats, a rapid reappearance was observed, to the same extent for all three factors, in hypo- as well as euthyroid rats. This finding suggests that in vitamin K1 deficiency an intracellular accumulation of precursor proteins (PIVKAs) occurs, which after rapid conversion into biologically active coagulation factors by vitamin K1 are shed into circulation.The subsequent phase of reappearance is much slower and reflects the synthesis rate of coagulation enzymes. It is characteristic for each factor and clearly slower in hypothyroid rats than in euthyroid rats. From this an influence of thyroid function on the synthesis rate of the protein moiety of coagulation factors can be inferred.An apparent difference between disappearance and reappearance rate of the coagulation factors in the plasma, particularly pronounced for factors VII and X in euthyroid rats, could theoretically be explained as the consequence of the model used for derivation of these rates.
The Variability of Platelet-Collagen Interaction. Its Influence on Aspirin-Induced Inhibition of Platelet Aggregation
Authors: Sack E. S , Quiroga E 
Published: July 2018

SummaryA study of platelet aggregation induced by progressive concentrations of collagen was performed in 40 normal persons, equally grouped by sex, immediately before, and 90 min after, the ingestion of 0.500 g aspirin. Simultaneously, serum ASA-esterase activity and plasmatic salicylic acid levels were investigated in the pre- and post-ASA samples respectively. Wide individual variations in platelet responsiveness to collagen were found when the minimal amount of the aggregating agent necessary to provoke significant aggregation was located. The percentage of aggregation and the slope were the most sensible indicators of both the individual variances and the ASA-induced inhibition. Correlation was found in both groups between the minimal amounts of collagen required for initiating aggregation pre- and post-ASA. Also a positive correlation was found between the minimal collagen concentration required to initiate aggregation pre-ASA and the aspirin-induced inhibition in the aggregation produced by a higher collagen concentration. Important individual and sexual differences were detected in the serum content of ASA-esterase activity. A negative significant correlation was demonstrated between the ASA-esterase activity and the differences in collagen concentrations necessary to start aggregation pre- and post-aspirin in the men group. Failure to consider individual variances in platelet reactivity may lead to false conclusions about the ASA affective-ness as an antithrombotic agent.
Spontaneous Platelet Aggregation in Arterial Insufficiency: Mechanisms and Implications
Authors: Wu Kenneth K. , Hoak John C. 
Published: July 2018

SummaryTo investigate the clinical implications and mechanisms of spontaneous platelet aggregation (SPA) in man, 150 normal subjects, 22 patient controls and 130 patients with vascular insufficiency were studied. SPA was negative in normal subjects and patient controls whereas it was positive in 36 of 66 (54%) patients with transient ischemic attacks, 6 of 32 (19%) patients with stable angina, 7 of 10 (70%) patients with acute myocardial infarction and 11 of 14 (80%) patients with acute peripheral arterial insufficiency. The SPA was inhibited with aspirin in vivo, and inhibited competitively in vitro by low concentrations of aspirin, 2-chloroadenosine, prostaglandin E1 or apyrase but only by high concentrations of heparin or hirudin. Addition of platelet-poor plasma from patients with positive SPA did not cause normal platelets to aggregate. Treatment of patients who had acute peripheral arterial insufficiency with aspirin and dipyridamole prevented SPA with notable clinical improvement of the ischemic changes.
Effects of Endotoxin in Cortisone-Treated Rabbits with a Hereditary Deficiency of the Sixth Component of Complement (C6 Deficiency)
Authors: Stafford Benjamin T. , Rapaport Samuel I. , Shen Stephen M.-C. 
Published: July 2018

SummaryEndotoxin was infused into normal rabbits and C6 deficient rabbits prepared with cortisone for the generalized Shwartzman reaction. Endotoxin produced profound granulocytopenia and moderate thrombocytopenia in both normal and C6 deficient rabbits. In normal rabbits endotoxin consistently produced extensive intravascular clotting. In C6 deficient animals endotoxin resulted in intravascular clotting of variable extent. In one group of eight C6 deficient rabbits mean fibrinogen levels fell 0.67 g per 1 over 6 hrs after endotoxin and four of eight animals developed a generalized Shwartzman reaction. In a second group of seven C6 deficient rabbits mean fibrinogen level fell only 0.17 g per 1 over 6 hrs and one animal developed a generalized Shwartzman reaction. Values for mean fibrinogen consumption, calculated from plasma fibrinogen levels and rate of disappearance of 25I-fibrinogen, were as follows: normal animals infused with saline, 10 mg per kg; C6 deficient animals infused with endotoxin, 24 mg per kg; normal animals infused with endotoxin, 58 mg per kg. Fibrinogen consumption after endotoxin was found to be related to granulocyte levels prior to endotoxin, which determined the number of granulocytes disappearing from the blood after endotoxin. The data indicate that C6 deficiency in the rabbit does not prevent intravascular clotting and the generalized Shwartzman reaction.