bluuebunny/crossref_metadata_2025 huggingface dataset:
Constriction and Damage of the Pulmonary Artery by Induced Intravascular Aggregation of Platelets
Authors: Motomiya T. , Matsubara O. , Yamazaki H.
Published: May 2019

The effect of suddenly induced intravascular aggregation of platelets on the pulmonary artery (PA) vas studied. Utilizing IS test, 7 immune thrombocytopenic and 7 aspirin pretreated rabbits, ADP was injected into the central vein. The animals were killed one hour after the Injection for histological examination. In vitro responsiveness of PA strips to rabbit aorta contracting substance (RCS) and serotonin was also studied. Histological examination of the lungs revealed that the small and medium sized PAs were characterized by reduced diameter of the lumen, increased wall thickness, convoluted and separated internal elastic lamina, vacuolated endothelial cells and split and vacuolated smooth muscle cells. Many of the affected PAs showed platelet-fibrin thrombi in the lumen. These changes were absent or rate and attenuated in the thrombocytopenic and aspirin pretreated rabbits. In vitro study: when contractile tesponses were expressed relative to the maximal tension developed by 40 mM K+, contraction of the rabbit PA strip induced by serotonin or whole products of platelet aggregation was approximately 1.5 times and one by RCS was 2 times stronger than those of the aorta. The powerful PA response to RCS and serotonin suggests that constriction and damage of the PA can be caused by these substances released from aggregated platelets.
Immunoelectrophoretic Mobility of Factor VIII in Patients Treated with DDAVP
Authors: Schmitz-Huebner U. , Balleisen L. , Sutor A.H.
Published: May 2019

5 patients suffering fr om Willebrand 's disease or mild Hemophilia A were treated once or several times with DDAVP (1-Deamino-8-D-Arginine Vasopressin), administered intravenously (0,4 μg/Kg BW). Beside other parameters like F.VIII related activities and bleeding time, the F.VIII migration pattern of each patient was examined in crossed immunoeletrophoresis before and several times after DDAVP therapy. In all cases a relatively slower mobility of this protein could be observed up to 24 hours after infusion. When the administration of DDAVP was repeated within 24 hours, the change of the F.VIII migration pattern was less pronounced than after the first therapy. The results indicate that DDAVP stimulates the release of subpopulations of F.VIII in plasma which cannot be readily detected in circulation before treatment. After repeated administrations in short intervals the portion of these slow migrating subfractions progressively decreases, probably because of a depletion of the respective stores. These observations complete those of other authors who noted the exhaustion of DDAVP effects in the course of longer treatments.
Anticoagulation Kinetics Following Bolus Heparin Injections
Authors: Mockros L F. , Hirson S.D. , Zuckerman L. , Caprini J.A. , Robinson W.P. , Vagher J.P.
Published: May 2019

Anticoagulation (AC) levels were monitored simultaneously in dogs by 3 whole blood (WB) and 2 plasma CP) clotting assays. Three levels of heparin (50,100 and 200 U/kg were tested in 26 experiments by Intravenous injection. Blood was sampled at 10 and 30 min then repeated every 30 min for 4 hours. The WB clotting tests provided more sensitivity with respect to the kinetics of neutralization of the heparin than did the P assays. The levels of AC determined by each assay method was fit to exponential curves using a computerized iterative least squares method. The points were weighted inversely with the variance and the censored data was used by fitting the known values to a gamma distribution and deriving the average and SEN of the series. The coagulation curves were dependent upon the heparin dose and test methods. Extrapolated levels of initial AC demonstrate from 3 to 67 fold increases in relative clotting times for 50 and 200 U/kg dosages respectively, depending on the assay method. The AC half lives (T½) with the three WB assays varied from 15 to 41 min for the low dosage and 24 to 34 min and 27 to 30 min for 100 and 200 U/kg dosages respectively. The shortness of these T½ is a consequence-of using data acquired at 10 to 30 tnin post injection. Reanalysis of our data using sampling periods >60 min significantly prolonged the derived T½. Finally there was a marked post heparin shortening (less than pre-heparin values) of the WB assays at 2-4 hours. The values appeared to be dose dependent, as the shortest values occurred In those animals receiving the highest heparin dose. Therefore, intravenous heparin can be associated with high Initial AC followed within 2-4 hours by a quicker than normal clot time.
Antithrombin-III Transfusion in Patients with Liver Cirrhosis
Authors: Schipper H. G. , Lamping R. , Kahlé L. , ten Cate J. W.
Published: May 2019

Purified human antithromb-III(AT-III) concentrate has been introduced in the treatment of patients with a cute severed is seminated intravascular coagulation (DIC) associated with a bleeding tendency. The effect of AT-III concentrate is further evaluated in 5 patients with liver cirrhosis and stable DIC as revealed by a shortened 125 I-fibrinogen half-life and increased fibrinopetide A (fpA) levels. After an initial dose of AT-III concentrate which rapidly corrected the decreased AT-III piasma level, plasma AT-III was maintained at this corrected level for 48 hours by continuous transfusion. This resulted in an immediate decrease of fpA levels and in an increase of plasma fibrinogen with peak levels two days after the transfusion period, de spite the fact that no significant effect on the 125I-fibrinogen turno ver could be established. The turnover of AT-III, which was established in the days following transfusion, was still increased when compared to the values obtained by Collen in normal volunteers. This study reveals that the decrease. AT-III plasma level in patients with liver cirrhosis and defective AT-III synthesis, is a cause of the low grade DIC in these patients.
Investigation of In Vivo Factors that May Influence Platelet Survival and Density
Authors: Packham M.A. , Mustard J.F. , Guccione M.A. , Winocour P. D. , Groves H.M. , Rand M. L. , Kinlough-Rathbone R.L. , Greenberg J. P. , Cieslar P.
Published: May 2019

Platelet survival CPS) is shortened in a number of conditions but the mechanisms responsible are unclear. In rabbits, removal of the aortic endothelium or injury of the neointima does not shorten PS. However, induction of thrombi in rabbit aortae with Indwelling cannulae (IDC) shortens FS (IDC 37.0 hr, control 79.6 hr), and Increases the proportion of platelets in the lightest fraction upon straetan density gradient centrifugation. Therefore we examined the effect of agents to which platelets may be exposed during thromboembolism (ADP, thrombin, plasmin) on PS and platelet density. ADP treatnent of washed rabbit platelets did not alter their survival but did increase the proportion in the lightest fraction. Treatment of platelets with thrombin did not shorten PS but increased the proportion in the lightest fraction. Treatment with plasmin in vitro shortened PS (plasmin, 57.6 ± 6.0 hr, control 80.2 ± 4,2 hr) and increased the proportion in the lightest fraction. Thus changes in platelet density are not necessarily associated with changes in PS. Of the factors investigated that are known to be involved in thromboembolism, only plasmin shortened PS. This may be due to its ability to alter major platelet membrane glycoproteins(principally glycoproteins I and II of rabbit platelets).
Expression of Factor VIII in Cultured Endothelial Cells and Somatic Cell Hybrids
Authors: Edgell Cora-Jean S. , Reisner Howard M. , Graham John B.
Published: May 2019

Somatic cell hybrids have been produced using primary cultures of human vascular endothelial cells and rodent cell strains. Production of factor VIII related antigen (VIIIR :Ag) by the cultured endothelial cells can be clearly demonstrated by a direct fluorescent antibody assay, but has not yet been detected in 10 of 10 hybrid clones. The hybrid cells do express many other human traits. Isozyme analyses for human chromosome markers demonstrate that various human chromosomes have been segregated from each of the hybrids. There are several tenable explanations for the fact that human VIIIR:Ag has not been detected in these hybrid cells. 1) Factor VIII may require a human chromosome(s) not present in any of the hyhrids ana1yzed to date. 2) Factor VIII may be expressed at lower levels in hybrid cells such that it would be detectable only by a more sensitive assay. 3) The rodent genome may block expression of this differentiated function in the hybrid cells. Since in a whole organism, only certa in cells express VIIIR:Ag, lack of its expression in hybrid cells may be ana1agous to its regulation in vivo.
Platelet Function Tests in Relation to Retinopathy and Neuropathy in Well Controlled Diabetic Patients
Authors: Pannebakker M.A.G. , Jonker J.J.C. , de Boer A.C. , den Ottolander G.J.H.
Published: May 2019

The following tests were done in 61 well controlled diabetic patients: Platelet survival time (PST), platelet aggregation ratio acc. to Wu and Hoak (PAR), platelet aggregation test 1 acc. to Breddin (PAT 1), ADP-threshold concentration and filtragometer aggregation time acc. to Hornstra (Ta). The mean PST in 20 healthy volunteers was 99 hours ± 13,4 hrs.: in 12 pat. wihtout retinopathy 88,6 ± 12,8 hrs.; in 28 pat. with non-proliferative retinopathy 103,9 ± 18,2 hrs. and in 1 par. with proliferative retinopathy 105,8 ± 7,5 hrs. In 16 pat. with a disturbed nerve conduction time the mean PST was 102,2 ± 21,5 hrs. and 96,0 ± 21,9 hrs, in 28 pat. with a normal time. The PST was shortened (mean-1 ED) in 12 pat. out of 44 pat. The mean PAR was 0,37 ± 0,11 in 27 normal volunteers and 0,78 ± 0,12 in 61 diabetics. The PAR was < 0,71 in 16 out of 61 pat. The mean PAT 1 was 1,7 in 27 normal volunteers and 1,5 in 61 diabetics; the test was abnormal in 6 out of 61 pat. The ADP-threshold concentration was < 0,75 mumol ADP/L in only 4 out of 61 pat. The mean Ta was 242 ± 50,5 sec. in 16 normal volunteers and 167 ± 83 sec. in 44 pat.; the Ta was < 150 sec. in 23 out of 44 pat. There was no correlation between the severity of retino- and/or neuropathy with the PST, PAR, PAT 1, ADP-threshold or Ta or between the laboratory values. There was no abnormal laboratory test in 2 3 pat., one in 19, two in 16 and three in 3 pat. There was no relationship between the severity of retino- and/or neuropathy and number of abnormal laboratory tests.
Hypercoagulability Associated with Breast Cancer
Authors: Caprini J.A. , Zuckerman L. , Vagher J.P. , Cohen E.
Published: May 2019

Previous thrombelastographic (TEG) studies in 262 individuals (not on medications) has resulted in the derivation and verification of a discriminant function equation which can classify individuals into a normal or accelerated coagulability range based on the TEC resultsThe significance of the separation between the groups was related to the combination individual’s TEG parameters for whole blood (WB) and their celite activated WB. The centite activated rate of clot formation appeared to be the most discriminating of the TEG variables. The equation separated the individuals with known malignancies (121) from the benign or healthy volunteers (141) with an overall accuracy of 99%. This breaks down into a 97-98% sensitivity and a 100% specificity (false positives). These findings of hypercoagulability are not specific for cancer end can be seen in other disease states e.g. sepsis or even the result of some medications. Therefore the present study was done to apply this analysis to a consecutive series of consenting patients (119) just prior to open breast biopsy, without selecting out patients on medications. 50/68 patients with ( 1 benign lesions had normal TEG results (false positive rate 26%), while 48/51 patients with pathologic evidence of malignancy had positive results. In two of the three tumor patients with a negative analysis, no invasion of the tumor was seen. The reduced specificity tourul with this group may be attributable to the presence of patients on medications or a higher than normal incidence of other disease states in this population. The results demonstrate one clinical application of TEG analysis to the identification of breast malignancies.
Platelet Aggregation and Serotonin Release, Coagulation, Fibrinolysis, Antiplasmin, Factor XIII, and Antithrombin III in Acute Transmural Non+Complicated Myo-Cardial Infarction
Authors: Bjerre Knudsen J. , Amtorp O. , Skagen K. , Gormsen J.
Published: May 2019

Platelet aggregation in vitro (ADP and adrenalin). Serotonin release, APTT, Factor VIII, Factor XIII, FE-a, plasma ethanol gelation teat, euglobulinclotlysiatime, antiplaeain and antithrombin III were estimated in 12 patients with acute transmural nob-complicated myocardial infarctions receiving no drugs with any known influence on the actual parameters. Distinct, uniform, changes were round. Initially distinct decrease in aggregation and release was present, changing within a week into increased aggregability, as estimated by threshold concentrations, and increased release function. The platelets remained “hyperactive” in above 50% at the discharge. Positive gelation test appeared after 1-2 days with peak level day 5, became afterwards negative in all. The fibrinolytic activity was within normal range day 1-2. It decreased rapidly with lowest activity on day 5-6 contemporarily with a peak activity of antiplasmin. Afterwards it increased slowly, but was still low in around 50% at the discharge. Factor VIII activity increased significantly with peak day 5-6. Factor XIII decreased biologically with lowest activity on day 5-6, increased to normal levels, Antithrombin III remained unchanged, in upper part of normal range. Thus, changes in platelet patterns are demonstrable at the onset of the infarction, while the other parameters develop later.
Effect of Suloctidil on PgI2 Production and Inhibition of Platelet Aggregation
Authors: Lansen J. , Biagi G. , Niebes P. , Gordon J. , Roncucci R.
Published: May 2019

Recent findings have suggested that the in vivo balance between the biosynthesis of proaggregating substances by blood platelets (e.g. thromboxane A2, endoperoxides) and antiaggregating substances produced by the vessel wall (PGI2) might be critical for thrombus formation. We therefore investigated the effect of suloctidil (S), indomethacin (I), acetylsalicylic acid (ASA) and tranylcypromine (T) on these parameters. Male Sprague-Dawley rats (200-300 g) fasted for 12 h were given a single i.v. dose (0.5 and 1 mg/kg) of S (glucuronate salt) or 200 mg/kg of the other compounds. Ten min after the injection, rats were killed and segments of the abdominal aorta and inferior vena cava were excised. PGI2 production by these segments vascular tissue was assessed by platelet aggregation inhibitory activity. PGI2 production was almost completely inhibited by ASA, I and T whereas S enhanced the production (or possibly the effect) of PGI2-like activity. The effect of S was dose dependent and was statistically significant at 1 mg/kg. In vitro studies showed that 100 μM S potentiated the inhibitory effect of synthetic PGI2 on platelet aggregation.
Structural Requirements for Glutamine Substrates of Factor XIIIa
Authors: Gorman J.J. , Folk J.E.
Published: May 2019

The transglutaminases catalyse hydrolysis and aminolysis of the carboxamide group of peptide bound glucamlne residues. Plasma Factor XHIa, which is a transglutaminase formed enzymically from Its zymogen, Factor XIII, catalyses the intermolecular polymerization of fibrin through ε-(γ-glutaminy)lysine crosslinks. A limited specificity of Factor XIIIa for glutamine residues is evident from its low activity toward small synthetic substrates for the liver transglutaminase. Our studies show that Factor XHIa displays a high specificity for Gin 167 of S-caseln. Peptides modeled on the sequence around Cln 167 of B-casein have been synthesized and examined as substrates for Factor Xllla and the liver transglutaminase. A peptide sequence corresponding to residues 161 through 175 of β-casein (peptide I) is an efficient substrate for Factor XIIIa (kcat/Km (app)=253 min-1) and for liver enzyme (kcat/Km (app)=328 min-1), whereas one corresponding to residues 161 through 171 (peptlde II) is not (kcat\km(app)= 40 min-1 and 7 min-1, respectively). Peptide I apparently contains the structural requirements for efficient catalysis by Factor Xllla. Synthesis of structural variants of peptide I and extensions of this peptide serve to define further these requirements for both transglutaminases.
In Vitro Effects of Dihomo-γLinolenic Acid (DHLA) on Normal and Diabetic Platelet Function
Authors: Zuzel M. , Kernoff P.B.A. , Willis A.L. , Paton R.C. , McNicol G.P.
Published: May 2019

DHLA causes a general inhibition of platelet reactions in standard in vitro tests of platelet function. Significantly more DHLA is required for the 50% inhibition (ID 50) of diabetic when compared to normal platelet reactions (Kernoff et al. Thrombosis & Haemostasis 38, 194, 1977). To investigate the cause of this difference we have studied kinetics of ADP-induced primary platelet aggregation, its inhibition by DHLA, and the formation of malondialdehyde (MDA) in the presence of DHLA in platelet-rich plasma of six healthy subjects and six diabetic patients with advanced microangiopathy. The results showed a significantly lower Km (ADP) for platelet aggregation in the diabetic group compared to normal. The (DHLA) of the competitive component of inhibition of platelet aggregation (prostaglandin production-mediated) was not significantly different In the two groups. Also, amounts of MDA formed in diabetic and normal PRP in the presence of DHLA were not significantly different. We conclude that the apparent low susceptibility of diabetic platelets to inhibition by DHLA might be a result of a primary hyper-reactivity of these platelets due to a cause other than an abnormality of the platelet PG production pathway.
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.
The D Dimer-E Complex and Its Aggregates in Crosslinked Fibrin Digests
Authors: Gaffney P.J. , Joe Franklin
Published: May 2019

In vitro data have indicated that plasmin-mediated lysis of crosslinked (XL) fibrin in vivo yields only one distinct high molecular weight complex, which has the empirical formula, 2D-E. We have compared the compositions of lysates obtained from I125 labelled and unlabelled fibrin clots in buffer, human and animal sera, and trasylol, using conventional immunological, chromatographic and electrophoretic techniques. Both trasylol (10 KI units/ml) and various animal sera stabilised the D dimer-E complex following lysis of XL fibrin and only in buffer were free D dimer and E fragments observed. The D dimer-E complex was isolated by affinity chromatography and the expect ed polypeptide chain composition, including the crosslinked γ chain remnants, was confiimed. By combining various molar ratios of D dimer and E the expected equimolar nature of the complex was confirmed and the association sites between D dimer and E may be synonymous with the polymerization sites already shown to exist in the 0 and E domains of fibrinogen. Using I125 labelled fibrin clots, covalently linked high molecular weight complexes (up to 1 x 106Mv) were observed during in vitro lysis with plasmin. At least one of these was identified as a crosslinked γ dimer while other larger fragments may be covalently linked complexes of the “D dimer-E subunit”. A hypothesis for XL fibrin lysis in vivo is proposed which complements accepted ideas on fibrin clot formation.
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.
Ristocetin Induced Platelet Factor 3 Activity
Authors: Szabó T. , Hársfalvi J. , Muszbek L.
Published: May 2019

In human platelet rich plasma a pronounced Pf 3 activity was induced by aggregating doses of ristocetin. Following centrifugation of aggregated platelets no Pf 3 activity could be detected in the supernatant, i.e, it remained associated with the altered platelet surface membrane. At a ristocetin dose that induced two wave aggregation aspirin pretreatment prevented irreversible aggregation but not Pf 3 availability. In contrast both second wave aggregation and the development of Pf 3 activity were inhibited by the potent antiaggregating agent PGI2. In platelets isolated on albumin density gradient and free of plasmatic VIIIRtWF no Pf 3 activity was induced by ristocetin, however, aggregability as well as Pf 3 availability to ristocetin could be restored by platelet poor plasma replacement. Estimation of ristocetin induced pf 3 activity appears to be a procedure of diagnostic value in von Willebrand disease.
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.
Acute Pancreatitis in Man and Blood Coagulation Disturbances
Authors: Kõtering H. , Hasenbein M. , Artmann H. , Kasten U. , Kellermann J.
Published: May 2019

The pathogenesis of blood coagulation-disturbances in patients with acute pancreatitis in man is still unknown. Therefore we studied repeatedly the blood coagulation system of all patients with acute pancreatitis, who were admitted to our clinic or were transferred from other hospitals after complications occurred. 19 patients with a severe pancreatitia were studied. Most of them showed oliguria, pancreatic lungs, thrombosis or haemorrhage. Only 9 determinations (in 5 patients) resulted an enhancement of thrombin generation in the Thrombin-Generation-Test (TGT). All the other patients showed already hypocoagulsbility in the TGT and severe signs of DIC and consumption coagulopathy with a loss of platelets, fibrinogen and prothrombin complex. In 9 patients, who died, we found histomorphologicaliy fibrin deposites and hyaline thrombi. In comparison to 58 patients with elevated amylases but no severe pancreatitiS we found, that the initial alteration of blood coagulation system in pancreatitis is a hypercoagulaoility, possibly caused by trypsin, phospholipase A or elastase.
The Effect of Autopkothrotibin II-A on the DIC Formed Animals
Authors: Emekli N.B. , uiutin O.N.
Published: May 2019

Autoprothrombin II-A vas isolated from bovine prothrombin. DIC was induced in experimental animals with thromboplastin obtained from the brains of rabbits. An hour after thromboplastin administration, which had been injected very gradually from, the ears of a group of rabbits, the comparative coagulation tests with previously taken blood vare performed. In the second group, inhibitor along with thromboplastin was injected to the ear and the same tests were repeated comparatively with blood taken previously. The autoprothrombin II anticoagulant had protective effect on DIC formation with rabbit brain thromboplastin administration. This protective effect was found to be statistically significant.
Changes in Platelet Function and Platelet Counts During Substitution Therapy in Haemophiliacs and Produced by Plasmapheresis in Patients Suffering from Inhibitors
Authors: Dumitrescu E. , Ambrus I. , Nienhaus Kh. , Podolsak B. , Wenzel E.
Published: May 2019

We noticed a systematic increase in small platelets (evaluated by electronical analysis of platelet volune distribution, using the Coulter Counter equipment, Wenzel 1977) during substitution therapy in patients suffering from haemophilia (N = 60). Laboratory investigations on these patients were performed before substitution and then 30 min., 60 min., 120 min. and 24 hours after infusion of factor-VIII-concentrationa (Inmuno, Schwab, Behring, factor-VIII-concentrates 20 U/kg b.w.). The same investigations were performed before and after plasmapheresis using a Hemonetric cell separator (N = 7}. in 48 of the patients, the clinical signs were insignificant (bleeding time, according to Duke, was found to be normall, although the platelet changes ware considerable (decrease in platelet count and increase of the percentage of platelets smaller than 4.5 μ3). However, significant test results were noticed in a haemophiliac patient suffering from inhibitory- and drug-induced platelet disorders during and after plasmapheresis. We observed bleeding complications only in 2 cases (Duke; 7 min. and 9 min.). Yet, a coneiderable decrease in platelet counts was observed as well as a significant increase in the percentages of small platelets (4.5 μ3, N = 48) in all cases. Controlling platelet function in haemophiliacs following substitution therapy could be essential as well as controlling the usual hemolysis parameters after plasmapheresis.
Histiochemical Estimation of Fibrinolytic Activity in Ulcer Disease
Authors: Helgstrand U. , Jensen H-E , Kruse-BIinkenberg H.O. , Gormsen J.
Published: May 2019

The fibrinolytic activity was investigated histiochemically in patients with ulcer disease before and after Cimetidine and parietal cell vagotomy. The method is based on the fibrin slide method described by Todd 1958. Biopsies were taken during gastroscopy before and after treatment as follows: 3 biopsies from patients with duodenal ulcer (I from greater curvature in the corpus, II from the antrum, and III close to the ulcer in the duodenum). The control material were patients with uncharacteristic dyspepsia. The fibrinolytic activity was demonstrated by covering clean microslides with a fibnn-ogensolution (human fibrinogen, grade L, AB Kabi, contaminated with plasminogen and factor XIII) clotted by thrombin. The slides were kept in moist chamber, the frozen tissue cut in 8 a sections was mounted on the film. All analyses were made double with 3-8 sections on each slide. Fixation in formalin was made 0, 10, 20, and 30 minutes after incubation in moist chamber 137°C.), and the slides stained. In the microscope the activity was graded 1 for small punctate areas of lysis, 2 for large confluent areas, and 3 for massive fibrin digestion. Results show grade 2 or 3 for biopsies taken close to the ulcer before treatment,none or grade 1 in the others. After treatment the activity close to the ulcer is reduced to none or grade 1. So far, 150 biopsies have been analysed.
Coagulation Changes in Experimental Renal Vein Thrombosis
Authors: Zimmermann R. , Zimmerhackl B. , Steinhausen M. , Dallenbach F.D. , Jäckh R.
Published: May 2019

Renal vein thrombosis is followed by dysfunction and degenerative alteration of the kidneys. The serious form may take a lethal course. In experimental bilateral renal vein thrombosis in rats death occurs within 4.5 hours in irreversible shock with the morphological presentation of fibrin clots. Coagulation and chemical analyses were performed in 34 animals with experimentally induced bilateral renal vein thrombosis and in 46 controls. A significant(p< 0.05) decrease or prolongation of fibrinogen, prothrombin time,thrombin time,reptilase time, APTT, the factors VIII and IX and a slight but not significant reduction of platelet count, factors V,IX and XII could be shown. These data exclude an early and primary occuring defibrination syndrome as cause of death. The blood loss into the kidneys and toxic substances released from the kidneys may cause refractary shock. The early, moderate impairment of the blood coagulation parameters may be the
result of an activation of the kallikrein-kinin system. Finally a massive consumption coagulopathy develops and produces disseminated intravascularc oagulation.

Supported by the GRF, SFB, 90
Effect of Ahthocyanosides and Dexamethasone on Cultured Cells from Huilan Umbilical Vein
Authors: Piovella F. , Pesenti M. , Ricetti M.M. , Castasola C. , Alnasio P.L. , Ascari E.
Published: May 2019

The effects of Vaccinium myrtillue anthocyanosides, substances which demonstrated significant effect on the formation of new capillaries in experimental animals, and of dexamethasone were evaluated on cell cultures derived from umbilical vein. According to Shearn et al, pure endothelial cell suspensions were grown as primary and passed cell cultures. In the same way suspensions of highly contaminated specimens containing both ri broblasts and smooth muscle cells together with endothelial cells were cultured. Both types of culture were exposed to different concentrations of the two stimulants. In pure endothelial cell cultures, dexamethasone enhanced cell spreading as well as protein content. Anthocyanosides demonstrated a positive effect on cell proliferation and protein content. In different cell type cultures, dexamethasone stimulated the proliferation of endothelium more actively than other cells, while anthocyanoside s showed a stimulating activity on all different cellular types.
The Morphology of Obliterative Arterial Diseases in Statu Nascendi
Authors: Marshall M. , Staubesand J. , Hese H.
Published: May 2019

The arteries of mini pigs which had been exposed to the local or systemic action of recognised ‘risk factors’ for arterial disease were examined with the light microscope, and the transmission and scanning electron microscopes.

Initially the scanning instrument revealed adhesions of platelets in different stages of development, but showed an apparently intact endothelium. With the transmission electron microscope, however, degenerative changes in the endothelium could be observed. Increased blood platelet aggregation was also present.

After a few weeks we could see a remarkable focal thickening of the intima, together with deposits on the endothelium of platelets, erythrocytes and fibrin (“mixed microparietal thrombosis”).

After 6 months fully developed arteriosclerosis of the abdominal aorta had appeared.
Studies on the Prethrombotic State of Patients with Maturity-Onset Diabetes Mellitus Undergoing Different Hypoglycemic Treatments
Authors: Grigkani C. , Gamba G. , Biancardi M. , Geroldi D. , Ferrari E. , Bossolo G. , Cinquini G. , Marco De R.
Published: May 2019

Different haemostatic parameters were investigated in 115 patients aeed 50-65 (55 males and 60 females) with maturity-onset diabetes mellitus and in 20 apparently normal control subjects. The patients were divided into 7 groups according to the hypoglycemic therapy.

VIII R:AC, fibrinogen, C1-INH and fibrinolytic activity of euglobulin precipitate were constantly increased in all groups of patients when compared to controls. AT III levels were always decreased. Plasma fibrinolytic activity and α1-Achy were almost never significantly different from controls. Other parameters did not show uniform behaviours in the different groups of patients, na~ely: ADP-induced platelet ageregation, VIII R:AC/VIII:C ratio, α2-M, I-α.-T.I. and α1.-P.I. levels.

If alterations in ADP-indfrced platelet aggregation, VIII R:AC/VIII:C ratio, fibrinogen and AT III are to be considered as index of hypercoa= gulability, the thrombotic risk of the patients was quite considerable when compared to that of controls, but no significant difference seemed to exist among the groups of patients.
Early Changes of the Emxtthelial Aotithrokibotic Properties in Cholesterol Fed Rabbits. I-Changes of A.D.P.-Ase and 5'-N.T.-Ase Activities
Authors: Abbate R. , Favilla S. , Gensini C.F. , Mugnaini C. , Runfola M. , Seffleri Neri G.G.
Published: May 2019

Severe endothelial damage is usually associated to developing atherosclerotic lesions in rabbits. However the early functional endothelial changes are poorly known, specially as far as the endothelial antithrombotic mechanisms are concerned.

In cholesterol (1 g/die) fed rabbits the endothelial aortic A.D.P.-ase and 5’-N.T.-ase activities (according to Lieberman 1977) were investigated after 7.14 and 28 days of diet. A.D.P.-ase and 5'-N.T.-ase changes occurred very early. A.D.P.-ase activity decreased already after 7 days of diet (m.v. -45%, P<0.COl) in comparison with control rabbits, but it did not show any further decrease after 14 and 24 days. A decrease of 5'-N.T.-ase activity (m.v. -36%, P<0.01) occurred only after 14 days of diet and it did not furtherly decrease after 28 days. These findings suggest that in cholesterol induced atherosclero -sis an early impairment of the antiaggregating properties of the endothelial wall occurs, but it does not increase for the length of time of our observation.
My journey from tyrosine phosphorylation inhibitors to targeted immune therapy as strategies to combat cancer
Authors: Levitzki Alexander , Klein Shoshana
Published: May 2019

Significance

This paper discusses the successes and failures of tyrosine kinase inhibitors in treating cancer, and why we believe targeted immunotherapy may provide more durable remissions. Tyrosine kinases are central to tumor development and progression. Since we originally demonstrated specific inhibition of tyrosine kinases, with minimal toxicity, a large number of tyrosine kinase inhibitors—both small molecules and antibodies—have entered the clinic. Nonetheless, tumors are heterogeneous and highly mutable, and they eventually bypass tyrosine kinase inhibition. The immune system has the ability to seek and destroy tumor cells. Tumors avoid detection by the immune system, so the goal is to reinstate immune surveillance against the tumor.
Destabilization of the human RED–SMU1 splicing complex as a basis for host-directed antiinfluenza strategy
Authors: Ashraf Usama , Tengo Laura , Le Corre Laurent , Fournier Guillaume , Busca Patricia , McCarthy Andrew A. , Rameix-Welti Marie-Anne , Gravier-Pelletier Christine , Ruigrok Rob W. H. , Jacob Yves , Vidalain Pierre-Olivier , Pietrancosta Nicolas , Crépin Thibaut , Naffakh Nadia
Published: May 2019

New therapeutic strategies targeting influenza are actively sought due to limitations in current drugs available. Host-directed therapy is an emerging concept to target host functions involved in pathogen life cycles and/or pathogenesis, rather than pathogen components themselves. From this perspective, we focused on an essential host partner of influenza viruses, the RED–SMU1 splicing complex. Here, we identified two synthetic molecules targeting an α-helix/groove interface essential for RED–SMU1 complex assembly. We solved the structure of the SMU1 N-terminal domain in complex with RED or bound to one of the molecules identified to disrupt this complex. We show that these compounds inhibiting RED–SMU1 interaction also decrease endogenous RED-SMU1 levels and inhibit viral mRNA splicing and viral multiplication, while preserving cell viability. Overall, our data demonstrate the potential of RED-SMU1 destabilizing molecules as an antiviral therapy that could be active against a wide range of influenza viruses and be less prone to drug resistance.
Learner‐adapted practice promotes skill transfer in unskilled adults learning the basketball set shot
Authors: Porter Courtney , Greenwood Daniel , Panchuk Derek , Pepping Gert‐Jan
Published: May 2019

The current study used a complex, sport‐specific movement skill to explore the effects of a win‐shift/lose‐stay practice schedule on learning and compared its effectiveness with that of blocked and random practice schedules. Thirty‐six adults (24.9 ± 3.3 years) were assigned to blocked, random and learner‐adapted training groups. Each participant performed 360 trials of the basketball set shot from multiple locations across six practice sessions. For the learner‐adapted group, switching between task variations was performance‐contingent; switching between shooting locations occurred only following a successful shot. Shooting success was calculated as the percentage of successful shots performed, and measured during pre‐acquisition (i.e. baseline), acquisition (i.e. practice) and post‐acquisition (i.e. retention and transfer). Despite scoring less shots throughout practice compared to baseline testing, the learner‐adapted group showed a significant improvement for shooting success in transfer (d = 1.02). Blocked practice demonstrated significant improvements for shooting success in immediate retention (d = 1.83), delayed retention (d = 1.69) and transfer (d = 1.39). Random practice significantly improved shooting success in both immediate (d = 1.03) and delayed retention (d = 0.81). The current findings highlight that performance during practice does not necessarily represent the permanency and adaptability of skill learning. The implications of the findings and their practical applications are discussed in the context of practice scheduling during learning of a sports skill.
‘Artificial spermatid’-mediated genome editing†
Authors: Wang Lingbo , Li Jinsong
Published: May 2019

For years, extensive efforts have been made to use mammalian sperm as the mediator to generate genetically modified animals; however, the strategy of sperm-mediated gene transfer (SMGT) is unable to produce stable and diversified modifications in descendants. Recently, haploid embryonic stem cells (haESCs) have been successfully derived from haploid embryos carrying the genome of highly specialized gametes, and can stably maintain haploidy (through periodic cell sorting based on DNA quantity) and both self-renewal and pluripotency in long-term cell culture. In particular, haESCs derived from androgenetic haploid blastocysts (AG-haESCs), carrying only the sperm genome, can support the generation of live mice (semi-cloned, SC mice) through oocyte injection. Remarkably, after removal of the imprinted control regions H19-DMR (differentially methylated region of DNA) and IG-DMR in AG-haESCs, the double knockout (DKO)-AG-haESCs can stably produce SC animals with high efficiency, and so can serve as a sperm equivalent. Importantly, DKO-AG-haESCs can be used for multiple rounds of gene modifications in vitro, followed by efficient generation of live and fertile mice with the expected genetic traits. Thus, DKO-AG-haESCs (referred to as ‘artificial spermatids’) combed with CRISPR-Cas technology can be used as the genetically tractable fertilization agent, to efficiently create genetically modified offspring, and is a versatile genetic tool for in vivo analyses of gene function.
Widespread Biases in Ecological and Evolutionary Studies
Authors: Culumber Zachary W , Anaya-Rojas Jaime M , Booker William W , Hooks Alexandra P , Lange Elizabeth C , Pluer Benjamin , Ramírez-Bullón Natali , Travis Joseph
Published: May 2019

There has been widespread discussion of biases in the sciences. The extent of most forms of bias has scarcely been confronted with rigorous data. In the present article, we evaluated the potential for geographic, taxonomic, and citation biases in publications between temperate and tropical systems for nine broad topics in ecology and evolutionary biology. Across 1,800 papers sampled from 60,000 peer-reviewed, empirical studies, we found consistent patterns of bias in the form of increased numbers of studies in temperate systems. Tropical studies were nearly absent from some topics. Furthermore, there were strong taxonomic biases across topics and geographic regions, as well as evidence for citation biases in many topics. Our results indicate a strong geographic imbalance in publishing patterns and among different taxonomic groups across a wide range of topics. The task ahead is to address what these biases mean and how they influence the state of our knowledge in ecology and evolution.
Smoking and school absenteeism among 15- to 16-year-old adolescents: a cross-section analysis on 36 European countries
Authors: Perelman Julian , Leão Teresa , Kunst Anton E.
Published: May 2019

Background

Schools have a crucial role to play in preventing youth smoking. However, the well-known long-term health consequences of youth smoking may be insufficient to convince education stakeholders to devote efforts to implement school-based programmes. However, if youth smoking were to have short-term consequences, this evidence could prompt education stakeholders’ action. In this article, we investigate the link between smoking and school absenteeism.

Methods

We used data from the 2011 wave of the European School Survey Project on Alcohol and Other Drugs, on adolescents aged 15–16. We applied logistic models to assess the risk of more than 3 missed school days, by cause, as function of smoking intensity, adjusting for age, sex, socioeconomic status, academic performance, parental involvement and other risk behaviours (alcohol and cannabis consumption). Consistency was assessed by replicating the analyses for each sex and age group and further adjusting for depression and self-esteem.

Results

Smoking more than five cigarettes per day was significantly linked to school absenteeism, with a 55% excess risk of missing more than 3 school days per month due to illness (OR = 1.55, 95% CI 1.46–1.64), and a more than two times excess risk due to skipping (OR = 2.29; 95% CI 2.16–2.43). These findings were consistent across age and sex groups.

Conclusion

We observed an association between smoking intensity and absenteeism among youth in Europe. This implies that, to the extent that this association is causal, school tobacco control policies may reduce the short-term consequences of smoking on adolescents’ education and health.
De novo assembly of the Indian blue peacock (Pavo cristatus) genome using Oxford Nanopore technology and Illumina sequencing
Authors: Dhar Ruby , Seethy Ashikh , Pethusamy Karthikeyan , Singh Sunil , Rohil Vishwajeet , Purkayastha Kakali , Mukherjee Indrani , Goswami Sandeep , Singh Rakesh , Raj Ankita , Srivastava Tryambak , Acharya Sovon , Rajashekhar Balaji , Karmakar Subhradip
Published: May 2019

Background

The Indian peafowl (Pavo cristanus) is native to South Asia and is the national bird of India. Here we present a draft genome sequence of the male blue peacock using Illumina and Oxford Nanopore technology (ONT).

Results

ONT sequencing gave ~2.3-fold sequencing coverage, whereas Illumina generated 150–base pair paired-end sequence data at 284.6-fold coverage from 5 libraries. Subsequently, we generated a 0.915-gigabase pair de novo assembly of the peacock genome with a scaffold N50 of 0.23 megabase pairs (Mb). We predict that the peacock genome contains 23,153 protein-coding genes and 75.3 Mb (7.33%) of repetitive sequences.

Conclusions

We report a high-quality assembly of the peacock genome using a hybrid approach of sequences generated by both Illumina and ONT. The long-read chemistry generated by ONT was useful for addressing challenges related to de novo assembly, particularly at regions containing repetitive sequences spanning longer than the read length, and which could not be resolved with only short-read–based assembly. Contig assembly of Illumina short reads gave an N50 of 1,639 bases, whereas with ONT, the N50 increased by >9-fold to 14,749 bases. The initial contig assembly based on Illumina sequencing reads alone gave 685,241 contigs. Further scaffolding on assembled contigs using both Illumina and ONT sequencing reads resulted in a final assembly of 15,025 super-scaffolds, with an N50 of ~0.23 Mb. Ninety-five percent of proteins predicted by homology matched with those in a public repository, verifying the completeness of our assembly. Like other phylogenetic studies of avian conserved genes, we found P. cristatus to be most closely related to Gallus gallus, followed by Meleagris gallopavo and Anas platyrhynchos. Compared with the recently published peacock genome assembly, the current, superior, hybrid assembly has greater sequencing depth, fewer non-ATGC sequences, and fewer scaffolds.