bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Membrane Vesicles from Mouse 15091A Tumor Cells: Agent of Platelet Aggregating Activity
Authors: Gasic G.J. , Catafalmo J.L. , Gasic G.P. , Shattil S.J. , Stewart G.J. 
Published: May 2019

We reported that cells from most tumors display platelet aggregating activity (PAA) in heparinized plasma and that this activity contributes to metastasis.Recently, we demonstrated that PAA can be used as a marker of cell transformation in virally infected rat cells. The material responsible for PAA is shed into culture medium. Characterization revealed a material which is particulate and sedimentable at 50,000x g for 60 min.; it contains proteins and lipids with a free cholesterol to phospholipid ratio of 0.556.Delipida-tion as well as complete solubilization abolished PAA.SDS-ME PAGE, 7.5% slab gels, revealed 20 bands.EM studies of 50,000x g pellets shed by 15091A cells indicated they contained numerous vesicles, some solid bodies, numerous free or vesicle associated small particles, and some amorphous material. Discontinuous sucrose density gradient centrifugation of the 50,000x g pellet yielded at the 1.07-1.17 g/cm3 interface a predominantly vesicular fraction which was the most active interfacial material. The vesicles, visible with phase contrast microscopy, resemble those produced by artificial plasma membrane vesiculation in various cell systems, including normal cells. Since PAA is only shown by transformed cells, vesicles from these must be different or much more numerous. Spontaneous vesiculation by tumor cells may be potentially important in understanding cell transformation and tumor metastases.
Vitamin K and Experimental Tumour Metastases
Authors: Hilqard P. 
Published: May 2019

Evidence has accumulated that anticoagulants can reduce the incidence of metastases from malignant tumours. Coumarin derivatives have been found most effective in various experimental systems, decreased blood coagulability and direct effects on tumour cells have been considered as their mode of action.In the studies described a syngeneic, spontaneously metastasising tumour (Lewis-lung carcinoma) was used in C57/BL mice. Long-term anticoagulation with phenprocoumon resulted in a significant reduction of pulmonary metastases. In contrast, controlled anticoagulation with heparin or ancrod was ineffective in the same tumour-host system. In short-term experiments, employing intravenously inoculated tumour cells, it could be demonstrated that the antimetastatic effect of the coumarin-derivative was independent of the effect on blood coagulation and of the drug itself. Under various experimental conditions diet induced vitamin K deficiency was equally effective in reducing metastases as well from primary tumours as from intravenously injected tumour cells.The present investigations indicate that vitamin K is involved at a cellular level during the early stage of metastasis formation. It is conceivable that vitamin K dependent γ-carboxyglutamic acid residues are located on the cell surface; their absence could substantially influence certain cell characteristics responsible for the lodgement of blood-borne tumour cells.
Experimental Thrombocytopenia: Amelioration of Endothelial Pathology and Bleeding by Prednisone
Authors: Kitchens Craig S. , Weiss Leon 
Published: May 2019

Experimental thrombocytopenia results in endothelial alterations associated with bleeding. In this study, we show that prednisone (Pred) may prevent and reverse these changes supporting inference that Pred decreases capillary fragility. Rabbits (3-4 kg) given busulfan developed a 98-99% reduction in platelet count and hemorrhaged profusely. Oral Pred (0.2mg/kg or 1.Omg/kg/day) reduced hemorrhaging despite persistent thrombocytopenia. Tongue biopsies on the third Pred day were examined by EM. Normal animals served as control, one normal group received 1.0mg/kg Pred daily, one thrombocytopenic group received no Pred, and one group received Pred while thrombocytopenia was induced.100 consecutive capillaries or venules of each preparation were examined for fenestrations, “thin spots”, (<800 Å thick), and mean thickness as determined by planimetry.All preparations demonstrated normal endothelial junctions. We hypothesize that the bleeding of thrombocytopenia is caused by altered capillary and venule endothelium and that diminished bleeding observed with Pred administration is caused by alteration of these endothelial changes.
Circulating Platelet Aggregates in Normal Pregnancy and Rpeeclampsia
Authors: Rákóczi I. , Tallián F. , Cseh I. , Gáti I. 
Published: May 2019

Circulating platelet aggregates have been observed in various thromboembolic states. It is known that severe preeclamsia is associated with features of intravascular coagulation. To evaluate the role of platelets in this disorder we have determined circulating platelet aggregates in 10 patients with severe preeclampsia, in 30 patients in the third trimester of uncomplicated pregnancies and in 35 healthy nonpregnant volunteers. Platelet aggregate ratio /P.A.R./ was measured by a modification of a method described by Wu and Hoak, The mean P.A.R. of severe preeclamptic patients /0.732 ± 0,063 SEM/ was significantly lower than that of the uncomplicated pregnant women /0,860 ± 0,052 SEM/ and of the nonpregnant volunteers /0.880 ± 0,061 SEM/.The results indicate that severe preeclamptic patients have increased levels of circulating platelet aggregates and platelet activation is a feature of preeclampsia.
Interaction of Prothrombin with Phospholipids Monolayers in Presence of Ca**.
Authors: Lecompte M.F. , Miller I.R. 
Published: May 2019

The activation rate of Prothrombin and its conversion into thrombin through a proteolytic degradation is enhanced by phospholipids in the presence of Ca++. In this work, we could elucidate stoechiomet rio and structural aspects of the interaction between prothrombin. phospholipids and Ca++. We studied the adsorption equilibria of Ca++ and of prothrombin un phospholipids monolayers by a new approach which comoines two complementary methods of surface measurement.Electrochemical investigations on lipid monolayer interacting with prothrombin showed penetration of prothrombin in presence or not of Ca++ (by increasing the lipid layer capacitance). with a preferential orientation. The adsorption of Ca++ and prothrombin to the lipid layer was measured by counting the surface radioactivity of 45Ca and 3H-prothrombin. Synergetic attachment of Ca++ and prothrombin to the phospholipid water interface was observed and the number of Ca++ per attached prothromoin was determinen. The two methods give comparative results for the proposed ionic-hydrophobic interaction.
Levels of Platelet Factor 3 in Citrate Plasma and in Whole Blood as Determined by A Chromogenic Peptide Substrate Assay
Authors: Sandberg H. , Gellerbring A.-K. , Andersson L.-O. 
Published: May 2019

A newly developed sensitive method for determination of platelet factor 3 (PF 3) using a chromogenic substrate (S 2238) (Sandberg and Andersson, Thromb. Res., in press) was used for comparison of the PF 3 levels in platelet-rich plasma (PRP) in citrate with the levels in PRP in the anticoagulant EDTA/citrate/PCE 1/theophylline. It was shown that in citrate PRP, release of PF 3 was started after about 20 minutes from blood sampling. Release of β-thromboglobulin (β-tg) was found to occur simultaneously with the release of PF 3. No release of PF 3 or β-tg could be detected within 3 hours from blood sampling in PRP in the EDTA/citrate/PCE 1/theophylline anticoagulant.The PF 3 level in whole blood was measured by a method which was a modification of the method used for plasma samples. It was found that, using the same donor, the PF 3 level of plasma and blood in the EDTA/citrate/PCE 1/theophylline anticoagulant was essentially the same. The levels of PF 3 found in blood upon standing in citrate or in EDTA/citrate/PCE 1/theophy11ine anticoagulant were in accordance with the levels found in plasma. Experiments with whole blood without any anticoagulant showed that release of PF 3 begin to occur simultaneously with release of β-tg, about 5 minutes before clotting. Thus the data show that PF 3 and βtg are released in parallel.
Experience with Aspirin-Dipyridamole Prophylaxis in Sickle Cell Disease
Authors: Alkjaersig N. , Chaplin H. , Fletcher A.P. 
Published: May 2019

Crisis in sickle cell disease (SSD) patients is associated with reproducible sequential hemostatic changes indicative of intravascular fibrin formation and marked disturbance of platelet economy. With crisis onset, plasma high molecular weight fibrin(ogen) complexes are elevated and there is a transient fall in platelets. Subsequently fibrinogen and platelet counts rise, reaching their peaks respectively one and two weeks after onset. Three SSD patients have been followed by weekly clinical and laboratory examinations for a two year control and a two year prophylactic treatment period (aspirin 650 mg, dipyridamole 50 mg b.d.). Patient symptomatic status was classified weekly as 1 (asymptomatic) through 4 (hospitalized). Increase in fibrinogen concentration was significantly correlated with patient disease status. Wiile on treatment, th patients were asymptomatic or mildly symptomatic for 85% of the time compared to 73% of the control time.Analysis of the clinical status data (2 x n Chi square) showed a statistically significant difference in favor of the treatment (p < 0.01) and the time spent in hospital was significantly reduced during treatment (p < 0.02).
Specific Factor VIII Fragmentation in Commercial Factor VIII Concentrates
Authors: Montgomery R.R. 
Published: May 2019

Factor VIII antigen (VIIIag) is felt to consist of a series of oligomers that demonstrate immunologic reactions of identity with each other in normal plasma. This study demonstrates a fragment of VIIIag (VIIIag FRAG) which is present in commercial Factor VIII concentrate (VIII CONC) but not detected in cryoprecipitate (CRYO).Crossed immunoelectrophoresis of 10 bags of CRYO and 10 different VIII CONC (5 different brands) was carried out against specific antibody to VIIIag. As expected, the mobility of VIIIag was less anodic in CRYO than in VIII CONC, but a specific fragment of VIIIag (VIIIag FRAG) was detected in the VIII CONC. VIIIag FRAG is more anodic and demonstrates a reaction of partial identity with normal VIIIag. VIIIag FRAG is Immunologically distinct from our previously reported von Willebrand’s disease antigen II. None of the CRYO samples demonstrate VIIIag FRAG.Thus proteolysis in the preparation of commercial VIII CONC has produced VIII antigen that is deficient in some of the normal Factor VIII antigenic determinants. VIIIag in CRYO does not demonstrate this alteration. This proteolysis of VIIIag may contribute to the failure of VIII CONC to correct the bleeding time in von Willebrand’s disease.
Effects of PGI2 and its more Stable forms on the Aggregation and on the Camp Content of Human Platelets
Authors: Nemesánszky E. , Blaskó Gy. , Stadler I. , Sas G. , Pálos L.A. 
Published: May 2019

The authors investigated the anti-aggregating properties of some relatively stable derivatives of PGI2 concurrently determining the intracellular cAMP content of platelets. The ethyl-ester derivative of PGI2 and the complexes of PGI2-ethyl ester with β-cyclodextrine proved to be mora stable than PGI2-sodium salt. Their stimulating effect on adenyl-cyclase correlated with the potent inhibitory effect on platelet aggregation as well. The enhancing effect of these compounds for the intracellular cAMP conten t have a prolonged dura tion time -las ting 300 minutes - compared with the only a few minutes’ effect of PGE1.These stable forms of PGI2 might be clinically useful as highly effective anti-aggregating compounds.
Immunological Studies of Prothrombin in Newborns
Authors: Muntean W. , Petek W. 
Published: May 2019

Prothrombin of newborns was studied by means of the quantitative immuno-electrophoresis (QIE) and the two dimensional immunoelectrophoresis (TDIE). In the TDIE the prothrombin showed one precipitate in alpha-2-beta-globulin position when a buffer containing calcium was used. Another precipitate in alpha-1-globulin position was frequently found in preterm and term newborns. After administering vitamin K to the newborns the precipitate in alpha-1-globulin position was no longer demonstrable. When a buffer without calcium was used, in all newborns only one precipitate in the alpha-1-globulin position was found. The QIE and the activity assay gave equal results in those infants who showed only one precipitate in the TDIE. In those newborns who showed two precipitates, the QIE gave higher results than measurement of the activity.From this study no evidence of differences between the prothrombin of newborns and that of adults could be derived. Vitamin K deficiency as judged from the appearance of a second peak in alpha-1-globulin position in the TDIE was a frequent finding in newborns, even on the first day of life.
Molecular Events in the Activation of Bovine Factor V
Authors: Esmon C.T. , Gray S.F. 
Published: May 2019

The conversion of bovine Factor V (FV) to Factor Va (FVa) by thrombin appears to proceed in two steps as shown below. FV(300,000) → thrombin Factor V intermediate (FVi) 2 sub-units; 220,000 & 100,000)→FVa (2 subunits; FVa-H.C., 100,000 & FVa-L.C., 73,000)+activation peptide/s. The 220,000 Mol. wt. subunit of FVi gives rise to the FVa-L.C. EDTA dissociates both FVi and FVa into subunits, Mn2+ facilitates reassociation. Even following dissociation with EDTA, 1 mole of Ca2+ remains bound to each of the FVa subunits.Support of the above model of FV activation comes from an immunological characterization of the FV. Antibodies to FV cross react with FVa, FVi and both subunits of Fva. Antibodies to FVa cross react with FVi both subunits of FVi and both subunits of FVa. Antibodies to the FVa-L.C. cross react with FV, FVj and FVa, but do not with the FVa-H.L. Antibodies to the FVa-H.C. cross react with FV, the FVi, FVa but not with the FVa-L. C.A protease from Russell’s viper venom activated FV by making a single proteolytic cleavage. This results in the formation of two subunits of Mol. wt., 250,000 & 73,000. The 73,000 Mol. wt. subunit is functionally and immunologically identical to the FVa-L.C. the 250,000 Mol. wt. subunit contains the antigenic determinants to the FVa-H.C. and can be converted into this subunit by incubation with thrombin. The appearance of two disdinct high Mol. wt. activation products from FV; one containing the FVa-L.C.; the other containing the FVa-H.C., is compatible with placing the activation peptide region between the two subunits of Fva.
Platelet Activation : Role of Exogenous and Endogenous Phospholipases
Authors: Perret B. , Mauco G. , Simon M.F. , Chap H. , Douste-Blazy L. 
Published: May 2019

Phosoholipase A2 from bee venom induces aggregation of human platelets, provided that phospholipid hydrolysis is enabled by simultaneous incubation with sphingomyelinase C. Inhibition of the platelet response by indomethacin indicates that aggregation is due to arachidonic acid release. On another hand, this model allows to describe an asymmetrie distribution of arachidonic acid, whose only 6% is located in the outer leaflet of the plasma membrane.During platelet aggregation by phospholipase C, the diacylglycerol and its hydrolysis product 2-acyl-glycerol are phosphorylated into phosphatide and lysophosphatidic acids, respectively. As the same kinds of changes occur in the presence of thrombin, a unifying hypothesis for platelet activation is proposed, involving the stimulation of an endogenous phospholipase C, whose some properties will be reported (neutral optimal pH, Ca-requlrement, phosphatidylinositol specificity and cytosol-localization). This model can be related to the recent finding that phosphatide acid behaves as a calcium-ionophore (Gerrard, J.M. et al., Prostaglandins Med., 1978, 1, 387) and provides an alternative pathway for arachidonic acid mobilization.
The Human Complement System in Thrombin-Mediated Platelet Function; Uptake of C5-9 Complexes
Authors: Polley M. J. , Nachmon R.L. 
Published: May 2019

Thrombin-mediated platelet function is enhanced by the presence of C3, C5, C6, C7, C8 and C9 of human complement. The interaction of thrombin with its receptor on the platelet membrane initiates activation of complement on the platelet surface. Trypsin mediated platelet function is not enhanced by the addition of complement, probably since trypsin has no receptor on the platelet surface so activation of complement is triggered in the fluid phase and not on the platelet surface. Activation of complement by thrombin led to production of C5-9 complexes on the platelet surface. These complexes were eluted from the platelet membrane and were identified physicochemically and morphologically.The mechanism of the complement induced enhancement of platelet function is not clear, however It is mediated via the arachidonic acid transformation pathway since this activity wos Inhibited by known inhibitors of cycla-oxygenase namely aspirin and indomethacin.
Influence of the Amount of Platelet Bound IgG (Antibody) on Platelet Survival and Site of Sequestration in Autoimmune Thrombocytopenia
Authors: Kernoff L.M. , Blake K.C.H. , Shackleton D. 
Published: May 2019

This study aims to determine if increasing amounts of antiplatelet antibody result in progressive shortening of platelet survival and in proportionately greater hepatic sequestration. Antiplatelet antibody was measured by a quantitative antiglobulin technique using complement mediated lysis of IgG sensitised sheep RBC as an indicator system (1). Platelet survival was measured with autologous or ABO Rh compatible isologous platelets labelled with Cr-51 according to ICSH specifications (2). The survival data was fitted to linear exponential, multiple exponential and gamma functions on a Univac 1106 computer, incorporating a X2 measure of goodness-of-fit. Appropriately collimated detectors over liver and spleen were used to measure the relative uptake of labelled platelets which was expressed as the liver:spleen ratio at 48hr. after injection of the dose.In 15 untreated patients with ITP, platelet antibody was 21-213ng IgG/106 platelets (normal 1.8 - 14.8, n=47). Survival data was best described by 2 exponentials. No correlation was observed between platelet antibody levels and the 2 exponential estimate of platelet meanlifespan. A highly significant correlation (p<0.001) was obtained between platelet antibody and the liver:spleen ratio demonstrating that greater amounts of antibody are associated with progressively greater hepatic sequestration.(1) Dixon et al, New Engl.J. Med.292; 230. (2) Blood (1977) 50; 1137.Supported by the Nellie Atkinson Bequest.
The Isolation and Characterization of Platelet Fibringgen
Authors: Zimmermann R.E 
Published: May 2019

Since platelets contribute essentially to the blood clotting mechanism the question arises as to what extent their physiological role is expressed by a specified type of fibrinogen.Platelets are harvested , washed exhaustively and homogenated by freezing and thawing. After gradient centrifugation of the homogenate fibrinogen was isolated by controlled precipitation steps. According to biochemical analysis platelet
fibrinogen is of a unique polypeptid-composition, differs in its carbohydrate content and reveals a different kinetic of fibrin formation.
Atherosclerosis in Normal and Von Willebrand PIGS: Cross-Aortic Transplantation Studies
Authors: Fuster V. , Bowie E.J.W. , Josa M. , Kaye M.P. , Fass D.N. 
Published: May 2019

Pigs with homozygous severe von Willebrand’s (vW) disease appear resistant to atherosclerosis. Normal and vW pigs matched by breed and weight received a high (2%) cholesterol diet from age 3 to 9 months and then the aortas were analyzed. Experiment 1, Auto-Aortic Transplantation: in 2 normal pigs a 7 cm aortic segment proximal to the aortic bifurcation was resected, the segments were reimplanted again and the diet started both auto-transplanted segments developed atherosclerosis. Experiment 2, Cross-Aortic Transplantation: the aortic segments of 5 normal pigs were cross-transplanted with the aortic segments of 5 other normal pigs. From the 10 cross-transplanted segments, 9 developed atherosclerbsis. Similar cross-transplantation between 2 vW pigs revealed no atherosclerosis in the transplanted segment in 1 pig (the other pig died at operation). Experiment 3, Exchange Cross-Aortic Transplantation: The aortic segments of 2 normal and 2 vW pigs were exchanged. The vW aortic segments in the recipient normal pigs revealed atherosclerosis and endothelial cell vW factor (present in the capillary endothelium of the aortic segment), while the normal aortic segments in the vW pigs did not reveal atherosclerosis or endothelial cell vW factor.These preliminary findings further support the relationship between the Willebrand defect and the protection from atherosclerosis.
Effect of Serum Lipoprotein on the Functional Activity of Arterial Wall Cells
Authors: Galton D.J. , Stocks J. , Holdsworth G. , Betteridge D.J. , Krone W. 
Published: May 2019

Two main classes of lipoprotein (VLDL and LDL) have functional effects on arterial wall cells. VLDL interacts with endothelial cells and activates the surface-bound enzyme lipoprotein lipase. Lipoprotein-triglyceride is hynrolysed to free fatty acids for transport acroes the endothelium. VLDL is depleted of triglyceride to remnant particles for further catabolism by the liver. Some patients synthesiie an abnormal VLDL with deficiency of apoprotein C-II that fails to activate lipoprotein lipase and they become lipaemic. Other patiente secrete a VLDL with excess apoprotein C-III-2 [40,6 ± 4.2 (6) versus 22.6 ± 2.6 (6) percent total protein for controls], rendering the lipoprotein resistant to hydrolysis by lipoprotein lipaee.VLDL is catabolized to LDL which can penetrate the endothelial barrier. LDL transports cholesterol into arterial wall and other mesenchymal cells. LDL binds with high affinity to specific surface receptors on smooth muscle cells and is taken up and catabolized by the cell. Sterols released from LDL suppress endogenous cholesterol synthesis. Experiments with transcriptional (cardycepin) or translational (cyclohexl-mide) inhibitors suggest that LDL suppresses sterol synthesis at a poet-transcriptional level, i.e. is independent of synthesis of mRNA.
The Behaviour of Ristocetin Cofactor, F. VIIIREL. Antigen, Inhibitors of Coagulation and Platelet Aggregation in Diabetics
Authors: Scharrer T. , Lenz M. , Maas C. 
Published: May 2019

We investigated Ristocetin Cofactor(RistCof), Factor VIII related antigen (FVIIIE: AG),Plasminogen, Antiplasmin, Heparin Cofactor and Platelet Aggregation in 210 diabetics and in 57 healthy males and 99 healthy females. We obtairel the following results: The level of RistCof and FVIIIR: AG increases with advancing age. In diabetics we found a significant increase Of RistCof, FVIIIR: AG, of plaominogen, antiplasmin and heparin cofactor, independent of sex and age. We obtained a highly significant correlation between. HistCcf, FVIIIR: AG and plasminogen. Besides that we got a significant correlation between platelet aggregation and F.VIIIR: AG. The blood-sugar level showed a significant correlation to the values of F.VIIIR: AG The duration of diabetes correlated significantly to the enhanced plate-let aggregation. Conclusion: Our results suggest a stimulated synthesis cr release of RistCof and F.VIIIR:AG in diabetics.Besides that platelet aggregation, plasmiinogen, antiplasnin and heparin ccfactor were enhanced-independent of sex and age.