bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Lanosterol on Platelet Aggregation in Human Platelets
Authors: Hassall David G , Bruckdorfer K Richard , Sulpice Jean-Claude , Lutton Claude 
Published: July 2018

SummaryIt has been reported that lanosterol can sensitize isolated rat platelets to agonists such as ADP and thrombin (4). The purpose of this paper was to determine whether lanosterol had similar effects on human platelets and whether this was achieved by changes in membrane fluidity. Lanosterol did increase the sensitivity of human platelets, particularly to adrenaline and ADP at concentrations as low as 5 mg.L-1 when added from solutions in ethanol. At similar concentrations cholesterol, 4-cholesten-3-one or ethynyloestradiol had either no effect or were inhibitory. Measurement of membrane fluidity with diphenylhexatriene indicated that lanosterol did not affect membrane fluidity. Incubation of platelets with [4C]-mevalonic acid gave rise to a very small incorporation into lanosterol, squalene and farnesol. Sudden activation of the platelets did not accelerate lanosterol synthesis during or after platelet aggregation. It was concluded that lanosterol could only influence platelet behaviour if it came from the plasma. However the concentration of the steroid in both platelets and plasma is ten fold less than that required to sensitise the platelets.
Anticoagulant Activity in Cell-Free Peritoneal Fluid of an Experimental Pancreatic Ascites Tumor
Authors: Ts’ao C , Galluzzo T S , Hart S J , Ng A S , Sorenson P G , Subbarao V 
Published: July 2018

SummaryThe ascitic form of a chemically-induced pancreatic ductal adenocarcinoma in the Syrian golden hamster was very bloody and indistinguishable from blood macroscopically. Unlike blood, the bloody fluid remained unclotted at room temperature. To explore the possibility of presence of anticoagulants, we mixed 40% cell-free fluid with 60% normal human plasma and tested the clottability of the mixture with standard techniques. Plasma containing the fluid showed markedly prolonged activated partial thromboplastin time (APTT), thrombin time (TT) and recalcification time (RCT), and normal prothrombin time (PT) and reptilase time (RT). Comparing the prolongation of APTT of samples containing the fluid to those containing a commercial heparin, the fluid contained an anticoagulant activity equivalent to 0.436 ± 0.03 unit heparin per ml (mean ± SEM, n = 14). In addition to prolonging the APTT, TT and RCT, the fluid also inhibited the clotting and amidolytic activities of thrombin. “Heparsorb” had nearly completely neutralized the anticoagulant activity in fluid samples, while protamine sulfate was only partially effective. Incubation of fluid with pronase or phospholi-pase did not affect its anticoagulant activity; incubation with heparinase had only a minimal effect. Electrophoresis of an alkali digested fluid on cellulose acetate revealed the presence of heparan sulfate. The native ascitic fluid also contained other hemostatic components including platelets, fibrinogen and antithrombin III, but their concentrations were much lower than in blood. Apparently, heparan sulfate in the neoplastic effusion is largely responsible for the bloody ascites tumor remaining unclotted.
On the Composition and Function of the Carbohydrate Moiety of Tissue-Type Plasminogen Activator from Human Melanoma Cells
Authors: Rijken D C , Emeis J J , Gerwig G J 
Published: July 2018

SummaryTwo variants (I and II) of tissue-type plasminogen activator (t-PA) from human melanoma cells were separated by Lysine Sepharose chromatography. The carbohydrate compositions of the forms were determined by gas-liquid chromatography. Variant I contained 12.8 g and variant II 7.1 g of carbohydrate per 100 g protein. Both variants contained N-acetylgalactosamine, suggesting O-glycosylation in addition to N-glycosylation. The possible role of N-linked oligosaccharides for the biological activity of t-PA was studied using t-PA secreted by melanoma cells in the presence of tunicamycin, an inhibitor of N-glycosylation. The latter t-PA showed the same plasminogen activating and fibrin binding properties as normally glycosylated t-PA, indicating that N-linked carbohydrate is not involved in the fibrinolytic activity of t-PA.
Influence of β2-Glycoprotein-l Upon the Content of cAMP and cGMP in Human Blood Platelets
Authors: Nimpf Johannes , Gries Anni , Wurm Helmut , Kostner Gerhard M 
Published: July 2018

SummaryThe influence of β2-glycoprotein-I on the cyclic nucleotide content in human gel filtered platelets (GFP) was studied: 1) β2-G-I up to a concentration of 5 mg/ml does not alter the basal cAMP level in resting GFP and also does not influence the action of PGE1 which strongly inhibits platelet aggregation by elevation of cAMP.2) Collagen induced aggregation of GFP leads to an increase of the platelet cGMP content. Preincubation of GFP with 0.2 mg/ml of β2-G-I enhances significantly the cGMP increase by collagen.3) In a similar manner β2-G-I also amplifies the increase in cGMP concentration induced by ADP. In this case, a concomitant alteration of the aggregation pattern is observed.4) Thrombin produces a much higher cGMP elevation in GFP than ADP or collagen. The admixture of 0.2 mg/ml of β2-G-I is not able to enhance further the thrombin effect on cGMP. The results are discussed in view of the possible significance of these observations for platelet aggregation in vivo.
Protective Effect of Vitamin E on Immune Triggered, Granulocyte Mediated Endothelial Injury
Authors: Boogaerts M A , Broeck J Van de , Deckmyn H , Roelant C , Vermylen J , Verwilghen R L 
Published: July 2018

SummaryThe effect of alfa-tocopherol on the cell-cell interactions at the vessel wall were studied, using an in vitro model of human umbilical vein endothelial cell cultures (HUEC). Immune triggered granulocytes (PMN) will adhere to and damage HUEC and platelets enhance this PMN mediated endothelial injury. When HUEC are cultured in the presence of vitamin E, 51Cr-leakage induced by complement stimulated PMN is significantly decreased and the enhanced cytotoxicity by platelets is completely abolished (p <0.001).The inhibition of PMN induced endothelial injury is directly correlated to a diminished adherence of PMN to vitamin E- cultured HUEC (p <0.001), which may be mediated by an increase of both basal and stimulated endogenous prostacyclin (PGI2) from alfa-tocopherol-treated HUEC (p <0.025). The vitamin E-effect is abolished by incubation of HUEC with the irreversible cyclo-oxygenase inhibitor, acetylsalicylic acid, but the addition of exogenous PGI2 could not reproduce the vitamin E-mediated effects.We conclude that vitamin E exerts a protective effect on immune triggered endothelial damage, partly by increasing the endogenous anti-oxidant potential, partly by modulating intrinsic endothelial prostaglandin production. The failure to reproduce vitamin E-protection by exogenously added PGI2 may suggest additional, not yet elucidated vitamin E-effects on endothelial metabolism.
Thrombus-Related Uptake and Vascular Clearance of 131 I-Fibrin des-AABB as Compared to 125 I-Fibrinogen in Patients with Established Venous Thrombosis
Authors: Nilsen Dennis W T , Brosstad Frank , Holm Bjørn , Kierulf Peter , Gravem Karl , Godal Hans Christian 
Published: July 2018

SummaryThrombus-related uptake of 131 I-fibrin des-AABB has been compared to that of 125 I-fibrinogen in 13 patients with established venous thrombosis. Both tracers originated from a common pool of β-alanine precipitated fibrinogen. Scan-recordings were performed as a radiofibrin(ogen) uptake test. Uptake characteristics of des-AABB fibrin were similar to those of fibrinogen, when measured as percentage of concomitant radioactivity over the heart. Due to its longer circulation time, fibrinogen was superior to fibrin des-AABB for the detection of venous thrombi.Circulating des-AABB fibrin was cleared biphasically, with an initial rapid decline followed by a gradual exponential decrease. Mean half-lives were 5.5 ± SD 3.5 hr and 10 ± SD 3.5 hr, respectively. The elimination rates were uninfluenced by thrombus activity, as judged by the fibrin(ogen) uptake test. Metabolic half-life of fibrinogen in the total material was 62 ± SD 19 hr. Dissociation of fibrinogen and soluble des-AABB fibrin clearance rates was evident, describing their own, independent elimination patterns, probably reflecting different clearing mechanisms.
Studies on the Procurement of Coagulation Factor VIII: Selective Precipitation of Factor VIII with Hydrophilic Polymers
Authors: Farrugia A , Griffin B , Pepper D , Prowse C 
Published: July 2018

SummaryEarly work on the purification of factor VIII using polyethylene glycol (PEG) indicated that other polymers might also be used to precipitate factor VIII leaving fibrinogen in solution. Recently polyvinylpyrrolidone (PVP) has also been advocated for this purpose.In this study, different concentrations and molecular weights of hydroxyethyl starch, dextran, PEG, PVP, Ficoll, Percoll and albumin were examined for their ability to precipitate the factor VIII complex from cooled (not frozen) fresh CPD plasma. At optimal concentrations near quantitative recovery of VIIIR:Ag and VIII: CAg was achieved in 2 hr with minimal precipitation of fibrinogen or total protein. The best separations were observed with hydroxyethyl starch, albumin or Ficoll. PVP and PEG gave inferior purifications. Results for cryoprecipitate and intermediate-purity factor VIII concentrate were inferior to those obtained with plasma. Simple pre-concentration of plasma prior to chilling is an attractive alternative for large scale continuous production.
Congenital Deficiency of Vitamin K-Dependent Coagulation Factors and Protein C
Authors: Vicente V , Maia R , Alberca I , Tamagnim G P T , Borrasca A Lopez 
Published: July 2018

SummaryA 15-month-old girl from Coimbra (Portugal) had a history of numerous hemorrhagic episodes with multiple bruises, hematomas but not hemarthroses. On serial testing she showed deficiency of factors II, VII, IX, X and protein C. Malabsorption- induced vitamin K deficiency, liver disease or ingestion of a coumarin compound were excluded. An absence of detectable abnormalities was found among her relatives. Consanguinity was not present. The immunologic assay, immunoelectrophoresis or antibody neutralization, revealed much higher levels of these factors than the clotting assay. The non-physiological activator (Echis carinatus venom) produced higher levels of prothrombin activation than those detected by physiological activation. Twodimensional immunoelectrophoresis of the patient’s plasma in calcium showed that prothrombin had the same mobility as acarboxyprothrombin. No significant response to large doses of intravenous vitamin K3 (6 mg) was observed. Transfusion of 120 ml of frozen fresh plasma led to an immediate increase in the procoagulant activities of vitamin K dependent protein, similar to that found after perfusion of plasma plus vitamin K3. The results obtained from this patient suggest a defect in the gammacarboxylation mechanism inside the hepatocyte.
Use of Porcine Factor VIII in the Management of Seventeen Patients with Factor VIII Antibodies
Authors: Gatti Loredana , Mannucci Pier Mannuccio 
Published: July 2018

SummaryA polyelectrolyte-fractionated porcine factor VIII concentrate was given to 16 hemophiliacs with anti-F VIII antibodies (Ab) and to a woman with post-partum-acquired Ab during 24 courses of treatment including three major surgical procedures. Before treatment, antiporcine F VIII Ab was always lower than antihuman F VIII Ab, with a median cross reactivity of 32%. After treatment, the mean rise in F VIII was 1.5 U/dl/Unit infused/Kg b.w. and in vivo recovery was 50% of the theoretical values. Anamnestic rises in anti-porcine F VIII Ab (3 × the baseline titer) were seen after 9 of 22 courses of treatment with porcine F VIII only; similar rises in anti-human F VIII Ab, after 6 courses of treatment; median cross reactivity did not change significantly. Lower than expected increases in plasma F VIII without marked changes in Ab titers and severe thrombocytopenia occurred during surgery in two patients. Porcine F VIII is a rational and effective therapeutic choice for patients who have anti-human Ab titers above 10 U/ml; it can solve clinical situations that would otherwise be very difficult to manage; anamnesis is perhaps less frequent than after human F VIII; however, the incidence of thrombocytopenia, resistance and other side- effects is still higher than desirable.
The Effects of Administration of Ethyl Alcohol to Mice on Megakaryocyte and Platelet Development
Authors: Cooper G W , Dinowitz H , Cooper B 
Published: July 2018

SummaryThe effects of administration to laboratory mice of 5-20% ethyl alcohol (v:v) as drinking water on megakaryocyte and platelet development were studied and compared with data on controls given tap water.In two separate experiments, mice given 5-15% ethyl alcohol (v:v) for 13 or 11 weeks showed decreases in platelet counts and platelet 35S uptake when compared to the control groups. Mice fed 5-20% alcohol for five weeks showed platelet counts, bone marrow megakaryocyte numbers and diameters that were significantly reduced to 72% (P <0.001), 45% (P <0.001), and 71% (P <0.01), respectively.The data implied that ethyl alcohol ingestion had a direct inhibitory effect on megakaryocyte and platelet development in mice, which resulted in a marked reduction in the levels of circulating platelets.
Morphometric Analysis of Platelets in Bernard-Soulier Syndrome: Size and Configuration in Patients and Carriers
Authors: McGill M , Jamieson G A , Drouin J , Cho M S , Rock G A 
Published: July 2018

SummaryQuantitative ultrastructural morphometric analysis has been carried out on thin sections of platelets from two Bernard-Soulier sisters and their parents. Measurements were made for the major and minor axes, axial ratios, cross-sectional circumference and cross-sectional area. Platelets were collected either into CPD anticoagulant or directly into glutaraldehyde. The results confirm that Bemard-Soulier platelets are significantly larger than normals (p <0.05) in all the parameters mentioned and indicate (I) that the morphology of platelets from Bernard-Soulier patients is affected by the presence of anticoagulant, and (II) a more spherocytic configuration is characteristic of Bemard-Soulier disease both in patients and carriers.
Effect of Amino Sugars on Platelet Aggregation and on Fibrinogen Binding
Authors: Kinlough-Rathbone Raelene L , Packham Marian A , Mustard J Fraser 
Published: July 2018

SummaryThe amino sugars glucosamine, galactosamine and man- nosamine (30 mM) inhibited aggregation of human or rabbit platelets induced by ADP, collagen, thrombin, PAF or high concentrations of sodium arachidonate. 125I-fibrinogen binding during ADP-induced aggregation, and release of amine storage granule contents were also inhibited. Increasing the calcium concentration of the suspending medium to 5 mM did not overcome the inhibitory effect on the release reaction.The amino sugars deaggregated rabbit platelets that had been aggregated by ADP, collagen or thrombin, but deaggregated human platelets readily only when ADP was used as the aggregating agent. Fibrinogen-induced aggregation of chymotrypsin-treated platelets was blocked by the amino sugars. They did not inhibit platelet adherence to a collagen-coated glass surface, nor affect release of granule contents from the adherent platelets. Aggregation and release induced by low concentrations of sodium arachidonate or the divalent cation ionophore A23187 were potentiated, indicating that the effects of the amino sugars on platelets are more complex than simple inhibition of the lectinlike activity that becomes available on the surface of platelets that have undergone the release reaction. One of the effects of the amino sugars, however, is interference with the binding of fibrinogen to platelets. The effects of the amino sugars are shared by other primary amines.
Changes in Plasma Levels of Protease and Fibrinolytic Inhibitors Induced by Treatment in Acute Myeloid Leukemia
Authors: Velasco F , Torres A , Andres P , Martinez F , Gomez P 
Published: July 2018

SummaryWe have studied the main protease inhibitors of leukocytes, alpha-1-protease (α1-PI), alpha- 1-antichymotrypsin (α1-Achy) and alpha-2-macroglobulin (α2-M), as well as different parameters of coagulation and fibrinolysis in 21 cases of acute nonlymphoblastic leukemia (ANLL) before, during and after therapy.Nine of the patients presented signs of DIC, 8 of whom belonged to subtype M3 and to subtype 1 M1.The initial α1-PI and α1-Achy levels, which were elevated, increased during the treatment period. There was no significant difference between patients with and without DIC. However, those leukemic patients with DIC showed a significant decrease in plasminogen (p <0.005) and fast antiplasmin (p <0.01) only during the treatment compared with DIC free patients. All DIC cases demonstrated circulating plasmin-antiplasmin complex (P-AP) both before and during treatment.Independent of a possible proteolytic action of leukocyte enzymes on clotting factors in the clinical course of ANLL (mainly M3 subtype), our results suggest an activation of plasminmediated fibrinolysis related to the activation of plasminogen by leukocytes, reactive DIC or both.
Plasminogen Activator and Plasminogen Activator Inhibitor Associated with Granulomatous Inflammation: A Study with Murine Leprosy
Authors: Izaki S , Hibino T , Isozaki Y , Hsu P S , Izaki M , Matsuo O 
Published: July 2018

SummaryPlasminogen activator that is associated with the development of hypersensitivity granulomas (gPA) was partially purified from a saline soluble fraction of murine lepromas elicited in “resistant” mice, C57BL/6N. The gPA was shown to consist of two subspecies (23,000 and 48,000 in molecular weight) with essentially identical enzymologic properties. The gPA was found to be a relatively heat stable weakly alkaline serine proteinase with trypsin-like characteristics in the specificity for synthetic substrates and proteinase inhibitors. It showed a high affinity for H- D-Ile-Pro-Arg-pNA (Km = 1.4 × 10-4 M) H-D-Val-Leu-Lys- pNA (Km = 5.2 × 10-4 M), and L-pyroGlu-Gly-Arg-pNA (Km = 9.3 × 10-4 M). The gPA did not demonstrate antigenic cross reaction with urokinase-type or tissue-type plasminogen activator.Two distinct enzymatic regulators of the gPA were also demonstrated in the saline soluble fraction of the hypersensitivity granulomas. The gPA and its regulation are assumed to be correlated with macrophage activation in the hypersensitivity granulomas
An Immunoradiometric Assay for Factor VIII Related Antigen (VIIIRAg) Using Two Monoclonal Antibodies-Comparison with Polyclonal Rabbit Antibodies for Use in von Willebrand’s Disease Diagnosis
Authors: Sultan Y , Avner Ph , Maisonneuve P , Arnaud D , Jeanneau Ch 
Published: July 2018

SummaryTwo monoclonal antibodies raised against FVIII/von Willebrand protein were used in an immunoradiometric assay (IRMA) to measure this antigen in normal plasma and plasma of patients with different forms of von Willebrand’s disease. The first antibody, an IgG1 was used to coat polystyrene tubes, the second one, an IgG2a, iodinated and used in the second step. Both antibodies inhibit ristocetin induced platelet agglutination and react strongly with platelets, megacaryocytes and endothelial cells. The IRMA test using these antibodies showed greater sensitivity than that using rabbit polyclonal anti VIIIRAg antibodies. A good correlation between the two tests was nevertheless found when VIIIRAg was measured in the majority of patient’s plasma. However 5 patients from 3 different families showed more antigenic material in the rabbit antibody IRMA than in the monoclonal antibody IRMA. It is suggested therefore that the monoclonal antibodies identify part of the VIIIR:Ag molecule showing structural abnormalities in these vWd patients, these structural changes remaining undetected by the polyclonal antibodies.
Agglutination of Formalin-Fixed, Platelet-Type von Willebrand’s Disease Platelets by Human von Willebrand Factor
Authors: Takahashi Hoyu , Shibata Akira 
Published: July 2018

SummaryThe interaction of platelets and von Willebrand factor (vWF) in platelet-type von Willebrand’s disease (vWD) was characterized using formalin-fixed platelets from the patients. Formalin-fixed patient platelets were agglutinated directly by human vWF in normal plasma and type IIB vWD plasma, but not in type IIA vWD plasma. In the presence of a small amount of normal vWF, ristocetin-induced agglutination of patient platelets was enhanced with low concentrations of ristocetin. Wheat germ agglutinin and EDTA inhibited vWF-induced agglutination, although EDTA had no effect on ristocetin (plus vWF)-induced agglutination. These results demonstrate that vWF-induced agglutination of platelet-type vWD platelets is independent of active platelet metabolism but requires divalent cations, and suggest that platelet membrane glycoprotein I (GPI) would be involved in this agglutination.
Inhibition of Platelet Production Induced by an Antiplatelet Drug, Anagrelide, in Normal Volunteers
Authors: Andes W Abe , Noveck Robert J , Fleming J S 
Published: July 2018

SummaryAdministration of anagrelide, an antiplatelet agent, to ten normal male subjects was accompanied by an asymptomatic fall in platelet count. The drop was gradual and usually occurred within two weeks. Only a slight shortening of platelet survival was seen. Bone marrow morphology appeared normal. Measurement of platelet production rates showed a reduced response to thrombocytopenia. A substantial increase in the percentage of large platelets was observed in drug treated subjects. These observations are compatible with a selective inhibition of platelet production. Based upon these findings, the use of anagrelide will probably be best limited to short-term applications or to conditions where selective lowering of platelet count may be desired such as in polycythemia rubra vera or idiopathic thrombocytosis.
Inhibition of ADP-Induced Responses in Human Platelets by Agents Elevating the Cyclic AMP Level: Comparison of Aggregation and Shape Change
Authors: Steen Vider M , Holmsen Holm 
Published: July 2018

SummaryThe inhibitory effect of cAMP-elevating agents on shape change and aggregation in human platelets was studied to improve the understanding of the sequential relationship between these two responses.Human platelet-rich plasma was preincubated for 2 min at 37° C with prostaglandin E1 or adenosine, agents known to elevate the intracellular level of cAMP. Their inhibitory effects on ADP-induced shape change and aggregation were determined both separately and simultaneously. The dose-inhibition patterns for shape change and aggregation were similar for both PGE1 and adenosine. There was no distinct difference between the inhibitory action of these two inhibitors.These observations suggest that elevation of the intracellular concentration of cAMP interferes with an early step in the stimulus-response coupling that is common for aggregation and shape change.
Defective Fibrin Crosslinking in Acute Leukemia
Authors: Rodeghiero F , Barbui T , Belin-Peruffo A Dal , Dini E 
Published: July 2018

SummaryFibrin crosslinking was assayed in 22 patients with acute leukemia showing secondary coagulation abnormalities of variable severity. In 9 patients fibrin crosslinking was found to be normal, whereas 10 patients presented impaired polymerization of α-chains and 3 of both α- and γ-chains.Only a rough correlation was found between transamidating activity of factor XIII and the fibrin crosslinking pattern in these patients. Moreover, incomplete fibrin crosslinkage occurred at levels of factor XIII far in excess of that required for full polymerization of fibrin in “normal” plasma. This latter finding suggests that, in addition to factor XIII deficiency, other causes are responsible for thehigh rate of fibrin crosslinking impairment in acute leukemia.