bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venous Thrombosis in Suspected Pulmonary Embolism: Incidence Detectable by Doppler Ultrasound
Authors: Barnes Robert W. , Kinkead Lewis R. , Wu Kenneth K. , Hoak John C. 
Published: July 2018

SummaryDoppler ultrasound has been used to screen patients for venous thrombosis with an accuracy of 94% compared to venography. Of 168 patients with suspected pulmonary embolism, only 48 (28%) had a source of venous thrombosis detectable by Doppler examination. The calf and iliofemoral venous segments were the two most common sites of involvement. When compared to Doppler examination, clinical assessment of the legs was falsely negative in 15% and falsely positive in 54% of patients. The highest incidence of venous thrombosis detected by Doppler examination (49%) was in the group of patients with a positive lung scan and a normal chest film. Doppler evidence of venous thrombosis was present in only 21% of patients with both a positive scan and an abnormal chest film. One-third of the patients with suspected pulmonary embolism had a negative lung scan. The most common conditions mimicking pulmonary embolism were congestive heart failure, pneumonia, chronic lung disease and atelectasis. Patients with suspected pulmonary emboli frequently have no demonstrable source of thrombosis and may deserve more thorough angiographic evaluation for proper diagnosis and therapy.
Platelet Preservation. III. The Influence of Dimethylsulfoxide and Cooling Conditions on Serotonin Uptake Velocity and Response to Hypotonic Stress of Human Platelets
Authors: Odink J , Sprokholt R 
Published: July 2018

Summary1. Serotonin uptake velocity of human platelets was found to be reversibly inhibited by the presence of dimethylsulfoxide (DMSO).2. Incubation of platelet concentrates in the presence of DMSO for 90 minutes at room temperature decreased serotonin uptake velocity and response to hypotonic stress.3. The serotonin uptake velocity was not substantially influenced by the temperature of incubation with DMSO.4. The best recovery of serotonin uptake velocity after cryopreservation in the presence of DMSO was observed when DMSO was added quickly before cooling and removed quickly after thawing.5. No significant differences were observed in serotonin uptake velocity and response to hypotonic stress after cryopreservation in the presence of DMSO when cooling rates were varied from 2 to 10° C/min.
Newborn Platelet Dysfunction: a Storage Pool and Release Defect
Authors: Corby Donald G. , Zuck Thomas F. 
Published: July 2018

SummaryPer cent aggregation, release and content of adenine nucleotides, and specific radioactivity were evaluated in citrated platelet-rich plasma (PRP) prepared from paired samples of maternal and cord blood. Platelets of newborn infants aggregated normally in response to high dose ADP (20 μM), strong collagen suspensions, and thrombin; however, when compared with PRP from the mothers or from normal adults, per cent aggregation in response to lower concentrations of ADP (2 μM), weak collagen, and part particularly epinephrine was markedly reduced. Nucleotide release after stimulation of the newborns’ PRP with the latter two inducers was also impaired. ATP and ADP content of the newborns’ platelets was also significantly less than that of their mothers or of normal adults, but specific activity was normal. The data suggest that the impairment of ADP release in the platelets of newborn infants is due to decreased sensitivity to external stimuli. Since metabolic ATP is necessary for the platelet release reaction, it is postulated that the platelet dysfunction results from a lack of metabolic ATP.
The Use of a Chelating Ion-Exchange Resin to Evaluate the Effects of the Extracellular Calcium Concentration on Adenosine Diphosphate Induced Aggregation of Human Blood Platelets
Authors: Heptinstall Stanley 
Published: July 2018

Summary1. An ion-exchange resin, Chelex 100, has been used to prepare suspensions of human blood platelets in calcium and magnesium depleted plasma.2. Extracellular calcium is required for platelet aggregation when induced by adenosine diphosphate (ADP). Magnesium only supports aggregation provided that a small amount of calcium is present in the plasma.3. The extent of platelet aggregation depends upon the concentration of calcium in the plasma. There is an optimum concentration of calcium with which the maximum amount of aggregation is obtained in response to any single concentration of ADP. This optimum calcium concentration is below the physiological level. Higher calcium concentrations reduce the extent of aggregation by enhancing the rate of disaggregation and high magnesium concentrations have the same effect. It is possible that free ADP levels are reduced as a result of ADP-divalent cation complex formation.4. Platelets were found to contain 18.6 (S.D. ±1.1) × 10–6 mol Ca and 9.3 (S.D. ±1.0) × 10–6 mol Mg per 1011 cells.
Effect of Platelet Age on Adhesiveness to Collagen and Platelet Surface Charge
Authors: Castellan Robert M. , Steiner Manfred 
Published: July 2018

SummaryAdhesion to collagen was investigated as a function of platelet age in rat platelets. Platelet adherence was measured using EDTA-containing platelet- rich plasma which was added to preparations of collagen fibers clamped between magnetic stirrers by recording changes in light transmission. The plot of light transmission versus logarithm of time was linear and allowed calculation of a slope factor which related to the rate of adherence. Neither the amount of collagen nor the platelet count were limiting in the test. Young platelet populations (≤ 1 day old) were obtained during the recovery phase from immune induced thrombocytopenia. Old platelet populations were prepared by blocking thrombopoiesis with cyclophosphamide. Young platelets showed a moderate but statistically significant increase in adhesivity to collagen but old platelets did not differ significantly from randomly aged platelets in this function. The electrophoretic mobility of platelets was not affected by their age.
Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid
Authors: Fujttani Buichi , Tsuboi Toshimichi , Takeno Kazuko , Yoshida Kouichi , Shimizu Masanao 
Published: July 2018

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.
Studies of an Inhibitor of the Thrombin-Fibrinogen Reaction Localized in Rat Liver Microsomes. Interference with the Polymerization Step
Authors: Helgeland L 
Published: July 2018

SummaryA heat-stable, macromolecular inhibitor of the thrombin-fibrinogen reaction localized in rat liver microsomes has been shown to interfere with the polymerization step in the fibrinogen-fibrin conversion. The inhibitor had no effect on thrombin activity as measured with the synthetic, chromogenic substrate Bz-Phe-Val-Arg-pNA. The amount of fibrin formed and the release of fibrinopeptide A were not affected by the inhibitor. Recording of turbidity at 350 nm and 600 nm indicated an inhibition of the lateral aggregation of the end-to-end fibrin polymers. The inhibitor was localized in both the luminal and membrane fractions of the microsomes. The inhibitor activity was not affected by warfarin treatment of the rats.
Thrombin Elaboration in Endotoxin-Induced intravascular Fibrin Deposition
Authors: Lipinski Boguslaw , Gurewich Victor , Hyde Elisabeth 
Published: July 2018

SummaryIntravascular coagulation was induced by two appropriately spaced doses of endotoxin and by infusion of thromboplastin. The resulting fibrin deposition was measured by a previously described quantitative technique. Evidence of thrombin elaboration was obtained indirectly by measurement of fibrin monomer (FM) and by the detection and isolation of a thrombin-induced anticlotting activity. Venous segments were isolated at intervals and examined for thrombus formation following 40 minutes of stasis. Endotoxin triggered thrombin elaboration was not detectable in the circulation for at least one hour and was not accompanied by any thrombosis in isolated venous segments. No thrombin elaboration was found in leukopenic rabbits given endotoxin. In the thromboplastin infused animals, the quantity of fibrin deposited in the organs was comparable to that found after endotoxin. However, thrombin was found in the blood immediately and was associated with thrombosis in the isolatet venous segments. Less thrombin-induced anticoagulant activity was found after thromboplastin than after endotoxin. The findings suggest that endotoxin-induced intravascular coagulation is probably not caused by a mechanism of systemic hypercoagulability due to the release of thromboplastic material into the blood stream. A focal process of thrombin elaboration involving leukocytes is postulated. The study is believed relevant to patients with disseminated intravascular coagulation in whom venous thromboembolism is rarely found despite evidence of extensive microvascular fibrin deposition.
Impairment of ADP-Induced Platelet Aggregation by Hashish Components
Authors: Levy Rachel , Schurr Avital , Nathan Ilana , Dvilanski Alexander , Livne Avinoam 
Published: July 2018

SummaryADP-induced aggregation of washed human platelets is inhibited by the hashish components Δ1-tetrahydrocannabinol (THC) and cannabidiol (CBD). The inhibition is counteracted by added ADP. When the cannabinoids are present at concentrations higher than 10−5M, the platelets aggregate non-reversibly, independently of an added inducer, apparently due to lysis and release of endogenous inducers. THC is clearly more potent than CBD in exhibiting the biphasic effect. Collagen- and thrombin-induced aggregation of washed platelets are hardly affected by the cannabinoids. THC and CBD also curtail ADP-induced reversible aggregation in platelet-rich plasma, while serotonin release and irreversible aggregation, caused by either ADP, collagen or thrombin, are not affected by the cannabinoids in platelet-rich plasma. The data point to associated sites for ADP and the cannabinoids on the platelet membrane.
Cell Shape Change and Cytosolic Ca2+ in Human Umbilical-Vein Endothelial Cells Stimulated with Thrombin
Authors: Sago Haruhiko , linuma Kazuso 
Published: July 2018

SummaryWe quantified thrombin-induced endothelial cells shape change and investigated the role of Ca2+ in such shape change. We used the fluorescent Ca2+ indicator, fura2, to measure both shape change as cell size and intracellular free Ca2+ ([Ca2+]i), in cultured human umbilical-vein endothelial cells (HUVEC). Thrombin induced concentration-dependent decreases in cell size (percentage of cell size at 6 min after stimulation with 0.01 U/ml, 0.1 U/ml, or 1 U/ml thrombin) was 90.1 ± 1.5%, 78.1 ± 2.4%, and 40.9 ± 2.4%, respectively. Thrombin also increased [Ca2+]i in a concentration-dependent manner. Both depletion of extracellular Ca2+, and also the addition of W5, a calmodulin antagonist, inhibited thrombin-induced size reduction. These results indicate an association between shape change and [Ca2+]i mobilization in human endothelial cells stimulated by thrombin.
The Glycosaminoglycan of Recombinant Human Soluble Thrombomodulin Affects Antithrombotic Activity in a Rat Model of Tissue Factor-Induced Disseminated Intravascular Coagulation
Authors: Nawa Katsuhiko , Itani Teru , Ono Mayumi , Sakano Katsu-ichi , Marumoto Yasumasa , Iwamoto Masahiro 
Published: July 2018

SummaryPrevious studies on recombinant human soluble thrombomodulin (rsTM) from Chinese hamster ovary cells revealed that rsTM was expressed as two proteins that differed functionally in vitro due to the presence (rsTMp) or absence (rsTMa) of chondroitin-4-sulfate. The current study evaluates the in vivo behavior of rsTM in rats and in a rat model of tissue factor-induced disseminated intravascular coagulation (DIC). rsTMp was more potent than rsTMa for prolongation of the activated partial thromboplastin time (APTT) and their in vivo half-lives determined by ELISA were 20 min for rsTMp and 5.0 h for rsTMa. Injection of a tissue factor suspension (5 mg/kg) resulted in DIC as judged by decreased platelet counts and fibrinogen concentrations, prolonged APTT, and increased fibrin and fibrinogen degradation products (FDP) levels. A bolus injection of either rsTM (0.2 mg/kg) 1 min before induction of DIC essentially neutralized effects on platelets, fibrinogen, and FDP levels, and had only a moderate effect on APTT prolongation. The dose of anticoagulant to inhibit the drop in platelet counts by 50% (ED50) was 0.2 mg/kg rsTMa, 0.07 mg/kg rsTMp, and 7 U/ kg heparin. The effect of increasing concentrations of rsTM and heparin on bleeding times were compared in experiments involving incision of the rat tail. Doubling of the bleeding times occurred at 5 mg/kg rsTMa, 3 mg/kg rsTMp or 90 U/kg heparin. These values represent a 25-fold increase over the ED50 for rsTMa, 43-fold for rsTMp and 13-fold for heparin. These results suggest that rsTMp is a potent anticoagulant to inhibit the platelet reduction when injected prior to the induction of DIC in rats.
Analysis of Intrinsic Fibrinolysis in Human Plasma Induced by Dextran Sulfate
Authors: Tsuda Hiroko , Miyata Toshiyuki , Iwanaga Sadaaki , Yamamoto Tetsuro 
Published: July 2018

SummaryThe analysis of normal human plasma by fibrin autography revealed four species of plasminogen activator (PA) activity related to tissue-type PA, factor XII, prekallikrein and urokinase-type PA (u-PA). The u-PA activity increased significantly by incubating plasma with dextran sulfate. This increase was coincident with both the cleavage of factor XII and the complex formation of activated factor XII with its plasma inhibitors, which were determined by immunoblotting procedure. The dextran sulfate-dependent activation of u-PA required both factor XII and prekallikrein, but did not require either plasminogen or factor XI. High molecular weight kininogen was required only at a low concentration of dextran sulfate. Thus the results indicate that the factor XII and prekallikrein-mediated activation of single chain u-PA (scu-PA) operates as a major pathway of scu-PA activation in whole plasma in contact with dextran sulfate.
Expression and Characterization of Recombinant Human Protein S in Heterologous Cells - Studies of the Interaction of Amino Acid Residues Leu-608 to Glu-612 with Human C4b-Binding Protein
Authors: Chang Glenn T G , Ploos van Amstel Hans K , Hessing Martin , Reitsma Pieter H , Bertina Rogier M , Bouma Bonno N 
Published: July 2018

SummaryMouse C127 epithelioid cells were genetically engineered to produce biologically active ³-carboxylated human protein S. A full length human protein S cDNA was cloned into a bovine papilloma virus (BPV) based shuttle vector under the transcriptional control of the Moloney murine sarcoma virus enhancer and the mouse metallothionein promoter. Stable expression was obtained in transfected C127 cells. Expression of ³-carboxylated protein S was dependent on the presence of vitamin K in the culture medium. Protein sequence analysis showed that recombinant and plasma protein S have the same amino terminal sequence. Analysis of specific post-translationally modified amino acids shows that recombinant protein S is fully ³-carboxylated and fully p-hydroxylated. Immunoblotting analysis using polyclonal and monoclonal antibodies shows that recombinant protein S has a slightly higher molecular weight than plasma protein S. After N-Glycanase treatment, identical molecular weights are observed for recombinant and plasma protein S, indicating that the difference is caused by differences in the N-linked carbohydrate side chains. Recombinant protein S also demonstrates normal cofactor activity for activated protein C in a clotting assay. Binding studies with the complement component, C4b-binding protein (C4BP), shows that recombinant protein S binds to C4BP with the same apparent affinity as plasma protein S. Two variant molecules are also tested for their binding to C4BP. The first variant has a replacement of amino acid residue leu-608 by val and was designated B variant. The second variant has three alterations, at positions 609, 611 and 612 where the acidic amino acid residues asp, asp and glu were replaced by asn, asn and gin, respectively and this variant was designated C variant. The binding of these variants to C4BP was the same as wild type recombinant protein S. This suggests that amino acid residues leu-608, asp-609, asp-611 and glu-612 are not essential for binding of the intact full length protein to C4BP.
Characterization of Thromboxane A2/Prostaglandin H2 Receptors in Porcine Coronary Artery -The Inhibitory Effect of a Novel Dibenzoxepin Derivative, KW-3635
Authors: Miki Ichiro , Ishii Akio 
Published: July 2018

SummaryWe characterized the thromboxane A2/prostaglandin H2 receptors in porcine coronary artery. The binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to coronary arterial membranes was saturable and displaceable. Scatchard analysis of equilibrium binding showed a single class of high affinity binding sites with a dissociation constant of 18.5 ±1.0 nM and the maximum binding of 80.7 ± 5.2 fmol/mg protein. [3H]SQ 29,548 binding was concentration-dependently inhibited by thromboxane A2 antagonists such as SQ 29,548, BM13505 and BM13177 or the thromboxane A2 agonists such as U46619 and U44069. KW-3635, a novel dibenzoxepin derivative, concentration-dependently inhibited the [3H]SQ 29,548 binding to thromboxane A2/prosta-glandin H2 receptors in coronary artery with an inhibition constant of 6.0 ± 0.69 nM (mean ± S.E.M.).
Thrombospondin Levels in Patients with Malignancy
Authors: Tuszynski George P , Smith Monica , Rothman Vicki L , Capuzzi David M , Joseph Rosaline R , Katz Julian , Besa Emmanuel C , Treat Joseph , Switalska Hanna I 
Published: July 2018

SummaryThrombospondin (TSP), a large glycoprotein present in platelets, and various normal and tumor tissues, has recently been shown to promote cell adhesion and platelet aggregation. Most importantly because TSP has been shown to promote metastasis of melanoma tumor cells to the lung in a murine model (1) and since thromboembolic events commonly occur in patients afflicted with metastatic tumors, we explored the role of TSP in human cancer by measuring TSP blood levels in patients with various malignant neoplasms. Blood TSP levels were measured by indirect enzyme-linked immunoadsorbent assay (ELISA) from 20 control subjects, 22 patients with gastrointestinal (GI) cancer, 18 patients with breast cancer, and 17 patients with lung cancer. Control subjects consisted both of healthy subjects and acutely ill patients with no malignancies. TSP levels of both healthy and acutely ill controls were found to range between 245-440 μg/ml with a mean of 365 μg/ml. In contrast, elevated levels of TSP greater than the mean value of 400 μg/ml for controls ranging between 590-3,650 μg/ml were found in 20/22 (91%) patients with GI malignancies, 13/18 (72%) patients with breast cancer, and 15/17 (88%) with lung cancer. Mean TSP levels of GI, breast, and lung cancer patients were 3, 2, and 3 fold greater than controls, respectively. Increased blood TSP levels in patients were not due to increased levels of platelets since both control and patient groups had platelet counts within the normal range. These results suggest that TSP may play a role in tumor cell metastasis in man and could serve as a blood marker for metastasis.
Factor Vlla/Tissue Factor-Catalyzed Activation of Factors IX and X on a Cell Surface and in Suspension: A Kinetic Study
Authors: Rao L Vijaya Mohan , Robinson Thomas , Hoang An D 
Published: July 2018

SummaryThe kinetics of activation of factor IX and factor X by factor Vila was studied in the presence of various sources of tissue factor: (1) a surface membrane of human ovarian carcinoma cell line, OC-2008 (2) the cell lysate (of 002008) and (3) reconstituted purified human tissue factor. The rates of activation of factors IX and X were monitored in activation peptide release assays using tritiated substrates. The results indicate that the apparent K
m values for factor IX and factor X were similar for a given tissue factor, but varied with tissue factor source. The source of tissue factor greatly influenced the apparent differences in V
max for factors IX and X. When a surface of monolayer provided tissue factor, the Vmax of factor IX was only 2-3 fold lower than factor X, but when either a cell lysate or purified tissue factor was the source of cofactor activity, the difference in V
max rose to about 8-10 fold. Although, the tissue factor apoprotein in the cells was expressed entirely on the outer surface membrane, the activity of tissue factor on the intact cell surface was 50 to 100fold lower than in the lysed cell preparation.
Defibrotide Inhibits Platelet Activation by Cathepsin G Released From Stimulated Polymorphonuclear Leukocytes
Authors: Evangelista Virgilio , Piccardoni Paola , Gaetano Giovanni de , Cerletti Chiara 
Published: July 2018

SummaryDefibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.
Localization of Tissue Thromboplastin in the Human Brain
Authors: Bjørklid E , Storm-Mathisen J , Storm E , Prydz H 
Published: July 2018

SummaryMonospecific antisera against the purified protein component of tissue thromboplastin (apoprotein-III) from human brain have been raised in goats and rabbits. The antisera neutralized tissue thromboplastin prepared from brain, thyroid gland and pulmonary tissue, indicating that apoproteins in the various preparations cross-reacted immunologically and therefore were similar or identical.Comparison of the activities of tissue thromboplastin preparations from 34 different areas of the brain demonstrated a characteristic distribution pattern and a wide range of activities. White and grey matter from the same areas had similar activities. Bulbus and tractus olfac-torius, medulla oblongata, corpus pineale, hippocampus and hypothalamus contained 160–270 % of the average activity, whereas cerebellum, globus pallidus, nucleus ruber and substantia nigra contained 30–60 %. The distinct distribution pattern was unrelated to tissue vascularization, and may suggest that apoprotein-III could serve other functions, apart from the coagulation of blood. The predominance in phylogenetically older brain regions would suggest that it represents a primitive or fundamental feature.