bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arterial and Venous Thromboembolism: Kinetic Characterization and Evaluation of Therapy
Authors: Harker Laurence A , Slichter Sherrill J 
Published: June 2018

SummarySurvival and turnover measurements of platelets, fibrinogen and plasminogen have been studied in eight patients with arterial and twelve patients with venous thromboembolism, and six patients with advanced, stable atherosclerotic peripheral vascular disease.Venous thrombosis is characterized by combined and equivalent consumption of platelets, fibrinogen and plasminogen. This process, the result of activation of the coagulation system, is completely reversed by heparin or warfarin anticoagulation but remains unaltered by dipyridamole. The removal of circulating plasminogen is directly reflected as fibrinogen-fibrin related antigen in the blood and is regulated by the rate of fibrin formation as evidenced by the reversal of fibrinogen and plasminogen consumption to normal following heparin therapy.In contrast, arterial thromboembolism involves selective platelet consumption presumably in the formation of platelet thrombus on non-endothelialized end-arterial surfaces. This process is interrupted by dipyridamole inhibition of platelet function but not by heparin anticoagulation. Although acetylsalicylic acid itself has little capacity to correct platelet consumption, it has a potentiating effect on dipyridamole.Stable, severe, widespread arteriosclerotic disease only minimally increases platelet consumption and produces no change in fibrinogen and plasminogen kinetics from normal. The minimal decrease in platelet survival in these patients is not corrected by dipyridamole therapy.The results of these studies demonstrate the potential usefulness of platelet and fibrinogen kinetic measurements in the differentiation of ongoing venous and arterial thromboembolism and in identifying potentially effective antithrombotic therapy.
Platelet Electrophoresis: The Present Position
Authors: Hampton J. R , Mitchell J. R. A 
Published: June 2018

SummaryMeasurements of platelet aggregation and adhesion have proved disappointing in the study of individual subjects with, or at risk from, arterial disease. In this paper the technique of platelet electrophoresis is described, and it is shown that with this technique individual patients with coronary artery disease can be identified with a high degree of accuracy. Abnormal platelet electrophoretic behaviour is also described in the relatives of subjects who have had a myocardial infarction at an early age, and it is suggested that the platelet abnormality precedes clinically-detectable disease.The platelet abnormality is shown to be secondary to changes in the plasma, and experiments are described in which a start has been made in elucidating the nature of the plasma abnormality. Two plasma components are involved: one is probably adenosine diphosphate (ADP), and it is shown that ADP has two distinct effects on platelets; the other component is associated with the plasma low-density lipoproteins.The nature of the low-density lipoprotein abnormality that induces platelet changes that can be detected by this electrophoretic technique appear of extreme importance in the understanding of thrombosis. No specific chemical abnormality has been identified in these lipoproteins, but certain detergents are shown to have a similar effect on platelet electrophoretic behaviour. It is therefore suggested that there are changes in the surface-active, or detergent, properties of the lipoproteins in subjects with, or at risk from, arterial disease.
Causes of a Negative Ethanol Gelation Test in Diffuse Intravascular Coagulation
Authors: Gerrits W. B. J , Prakke Elisabeth M , van der Meer J , Vreeken J 
Published: June 2018

SummaryThe clinical value of the ethanol gelation test (EGT) in diagnosing diffuse intravascular coagulation (DIC) has been questioned because of the occasional finding of a negative test, while other laboratory data pointed to DIC. Therefore, the behaviour of the EGT during thrombin infusions in rabbits was studied, with special reference to the fibrinogen level and activation of fibrinolysis. Fibrinolytic activity was inhibited or induced by synchronous infusion of epsilon-aminocaproic acid or plasmin respectively. The results obtained show that apart from severe depletion of fibrinogen strong activation of fibrinolysis can cause a negative EGT during thrombin infusions in rabbits. This phenomenon could not be ascribed to high levels of fibrin degradation products (fdp); it might be due to plasmin digestion of fibrin monomers. In vitro studies with human plasma confirmed that the EGT becomes negative at a fibrinogen level of less than 20 mg per 100 ml or by plasmin activity in the presence of a normal fibrinogen level.Whereas a positive EGT is highly specific for DIC, these studies show that a negative EGT does not exclude the presence of DIC.
Blood Coagulation and Platelet-function Parameters before and during Parenteral Administration of Medroxyprogesterone Acetate as a Contraceptive Agent
Authors: Baele G , Vermeulen A , Thiery M 
Published: June 2018

SummaryThe effects of medroxyprogesterone acetate on blood coagulation and platelet collagen aggregation were studied in nineteen women. After parenteral administration of the compound for 4 and 7 months, the activated partial thromboplastin time showed a significant decrease. The percentage of the prothrombin time test rose after 4 months, but not significantly after 7 months ; factor II decreased after 7 months of treatment. The reaction time during which no aggregation occurred after addition of a collagen suspension to a stirred platelet-rich plasma, was shorter after both 4 and 7 months of treatment. Other coagulation and platelet-function parameters were not altered. Although a trend toward hypercoagulability was detected, the changes were not the same as those reported for combined oral contraceptives.
Platelet Aggregation Induced by DAS in Vitro: Some Investigations on Its Mechanism of Action
Authors: Benner K. U , Schumacher K. A , Classen H. G 
Published: June 2018

SummaryThe effect of the depressor active substance (DAS) on platelets of men, cats, pigs, dogs, rats, and rabbits has been studied by the method of Born (1962). DAS was found to induce platelet aggregation only in human and feline platelet rich plasma (PRP). Nevertheless, there are some striking similarities between platelet aggregation induced by DAS and ADP (i.e. inhibition by the same compounds, such as adenosine, tosylarginine methylester, or p-chloromercuribenzoic acid). The species specifity and a marked tachyphylactic action on platelets of both species makes DAS clearly discernible from all the other aggregation inducing substances which have been studied so far. From additional experiments there is evidence that DAS acts on human and cat platelets via a release reaction of cellular substances known to enhance platelet aggregation in a second phase. This process is strongly dependent on the presence of Ca++.
Acute Phase Reaction Following Intravenous Administration of Streptokinase
Authors: Spöttl F , Kaiser R , Mosuni M. S 
Published: June 2018

SummarySK-therapy regularly is followed by a marked elevation of those plasma proteins known as “acute phase reactants” (α 1-antitrypsin, orosomucoid, β 1 C-globulin, ceruloplasmin). In short-time therapy of myocardial infarction also a transitory presence of CRP is demonstrable. After an initial decrease of fibrinogen caused by fibrinogenolysis, this protein increases significantly too. The high level of α 1-antitrypsin (slow reacting antiplasmin) and/or fibrinogen may lead to rheological consequences which may result in thrombosis.
Crosslinking of Rabbit Fibrin in Vivo
Authors: Finlayson J. S , Aronson D. L 
Published: June 2018

SummaryCrosslinking found in clots produced in vivo by inducing thrombosis in the rabbit jugular vein was compared with that in platelet-poor rabbit plasma clots formed in vitro. Polyacrylamide gel electrophoresis of the dissolved washed clots showed that the sequence of events in vivo was the same as has previously been observed in vitro and that γ dimerization was followed by α polymerization, with extensive crosslinking being evident in even the earliest clots.
Prolonged Plasma Clotting Time and Decreased Fibrinolysis after Long Term Treatment with α-Tocopherol
Authors: Korsan-Bengtsen K , Elmfeldt D , Holm T 
Published: June 2018

SummaryBlood platelet function, blood clotting and fibrinolysis were studied in a group of 9 male post myocardial infarction patients once a week for 5 consecutive weeks after which α-tocopherol 300 mg/day was given. The group was again investigated after 2, 6, 18, 44 and 64 weeks of α-tocopherol treatment. After 18, 44 and 64 weeks of treatment a highly significant prolongation of the plasma clotting time was observed. On the basis of the analyses made it is concluded that the prolongation is probably due to a decreased platelet factor 3 activity. The ability to increase fibrinolytic activity after stasis of the arm is reduced after long term α-tocopherol treatment. There were no changes in the number of platelets, platelet adhesiveness, factor II-VII-X activity, factor VIII, fibrinogen, antithrombin III, α1-antitrypsin, α2-macroglobulin, total anti-fibrinolytic activity or plasminogen. Our hypothesis to explain the results is that α-tocopherol influences on the cell membranes of the platelets and the endothelial cells and thus causes a reduced release of platelet factor 3 and activators of fibrinolysis. This is in line with many other observations indicating that α-tocopherol is of importance for the cell membrane function.
The Purification of Activated Hageman Factor from Human Granulocytes
Authors: Prokopowicz J , Wołosowicz N , Szmitkowski M 
Published: June 2018

SummaryActivated Hageman factor has been isolated from human granulocytes, utilizing aluminium hydroxide gel, diatomaceous earth, CM-cellulose. The preparation was applied on the column prepared from DEAE-Sephadex A-50. Two peaks with Hageman activity were obtained. The product was purified 4162-18750-fold as measured by the method of Schoenmakers et al.The preparation was devoid of factor I, II, III, V, VIII, IX and plasminogen. Some relationship between granulocyte and plasma Hageman factor are briefly discussed.
Potentiation by Synthetic Fibrinolytic Agents of Vascular Activator- and Urokinase-Induced Lysis of Human Plasma Clots as Demonstrated by Thrombelastography
Authors: Aoki N , von Kaulla K. N 
Published: June 2018

SummaryThe enhancement of vascular activator- and urokinase-induced lysis of human plasma clots following preincubation of the plasma with flufenamate - a fibrinolytic organic anion - was assessed by thrombelastography. Thrombelastograms clearly demonstrated an acceleration of activator-induced clot lysis by flufenamate. Based on the results of previous studies it is concluded that this chemical potentiation of activator-induced fibrinolysis results from inactivation of inhibitors of the fibrinolytic enzyme system, especially antiactivator, by the compound. The potential therapeutical implications of these findings are discussed.
14C-Warfarin Excretion in the Rat
Authors: Losito R , Rousseau Marie-Andree 
Published: June 2018

SummaryThe excretion of 14C-warfarin and its metabolites in bile and urine was studied in rats with or without biliary fistulas. After oral administration of the drug, 39.4% of the 14C could be isolated in the bile and 18.9% in the urine at the end of 96 h. After i.v. administration 47.5% and 21.3% of the 14C was found in the bile and the urine respectively. In animals without biliary fistulas, 41% of the dose was found in the urine after intravenous injection and 43% via the oral route. In bile, five radioactive components were detected; one component was identified as warfarin and represented 3.9% (oral) and 8.5% (I.V.) of the 14C in the bile. Another component of bile (17.7% to 19.6% of 14C) was identified as 6-hydroxywarfarin. In urine, three 14C components were found; the major component in urine was found to be warfarin and represented close to 75% of the 14C in the urine. Two 14C metabolites which were present in the urine were also present in the bile. Biliary fistula did not prevent radioactivity from being discharged into the urine. In feces, 9.3% of the dose could be isolated and was similar to warfarin. In the liver, at the end of four hours, 19% of the 14C could be isolated; only 74% of this could be extracted and was established as warfarin. The liver failed to show the presence of any metabolites.
Density Gradient Separation of Human Platelets from Plasma and the Role of Plasma in Adenosine Diphosphate Induced Platelet Electrophoretic Mobility Changes
Authors: Nicholls D. G , Hampton J. R 
Published: June 2018

Summary1. An albumin density gradient separation technique is described for separating human blood platelets from plasma.2. The platelet resuspensions aggregate on the addition of 10-6 M adenosine diphosphate (ADP) in the presence of calcium and fibrinogen.3. Platelet resuspension in the presence of plasma show a time dependant recovery of reversible aggregation.4. In the presence of calcium and fibrinogen platelet resuspensions show ADP- induced electrophoretic mobility changes which are the same as those of platelets not separated from their native plasma.5. Abnormal electrophoretic sensitivity to ADP in platelets from subjects with a history of occlusive arterial disease is retained on separation from plasma.6. The electrophoretic response of platelet resuspensions to phosphatidyl choline is similar to that of unwashed platelets. The use of resuspended platelets has shown that calcium and fibrinogen are not required for this response.
Bleeding Tendency with Platelet Dysfunction and Albinism
Authors: Murakami M , Odake K , Matsuda T , Manmi S , Takase M , Imura M , Toyama T 
Published: June 2018

SummaryA Japanese boy, who had combined congenital defects - a hemorrhagic disorder due to abnormal platelet function and incomplete albinism, was described. His parents were first cousins. Platelet aggregation by collagen and epinephrine was markedly defective. A rapid disaggregation was observed in ADP-induced aggregation. Platelet factor 3 availability and in vitro adhesiveness were subnormal, while platelet factor 3 activity was normal. Defective ADP release was associated with impaired aggregation by collagen. Before aggregation, labeled adenine nucleotide pattern in patient’s platelets was not different from that in normal platelets. The increase of intermediates of platelet ATP breakdown, such as AMP and IMP, was less in patient’s platelets after collagen-induced aggregation. The release of labeled ATP and ADP in patient’s plasma was less than that in normal plasma.
The Plasminogen Activator Content of the Arterial Wall in Occlusive Arterial Diseases
Authors: Constantini R , Hilbe G , Spöttl F , Holzknecht F 
Published: June 2018

SummaryThe plasminogen activator of the Arteria tibialis posterior of 8 patients with occlusive arterial diseases of the leg was determined in comparison to the plasminogen activator of normal subjects. The histochemical method of Todd (15) was used. The plasminogen activator of the pathological adventitia and the intima was significantly decreased. An impaired fibrinolytic system seems to be one of the important factors of atherogenesis. It could at least explain the frequent incidence of thrombotic complications.
Relational mobility predicts social behaviors in 39 countries and is tied to historical farming and threat
Authors: Thomson Robert , Yuki Masaki , Talhelm Thomas , Schug Joanna , Kito Mie , Ayanian Arin H. , Becker Julia C. , Becker Maja , Chiu Chi-yue , Choi Hoon-Seok , Ferreira Carolina M. , Fülöp Marta , Gul Pelin , Houghton-Illera Ana Maria , Joasoo Mihkel , Jong Jonathan , Kavanagh Christopher M. , Khutkyy Dmytro , Manzi Claudia , Marcinkowska Urszula M. , Milfont Taciano L. , Neto Félix , von Oertzen Timo , Pliskin Ruthie , San Martin Alvaro , Singh Purnima , Visserman Mariko L. 
Published: June 2018

Significance
Biologists and social scientists have long tried to understand why some societies have more fluid and open interpersonal relationships—differences in relational mobility—and how those differences influence individual behaviors. We measure relational mobility in 39 societies and find that relationships are more stable and hard to form in east Asia, North Africa, and the Middle East, while they are more fluid in the West and Latin America. Results show that relationally mobile cultures tend to have higher interpersonal trust and intimacy. Exploring potential causes, we find greater environmental threats (like disease and warfare) and sedentary farming are associated with lower relational mobility. Our society-level index of relational mobility for 39 societies is a resource for future studies.
Extreme stability in de novo-designed repeat arrays is determined by unusually stable short-range interactions
Authors: Geiger-Schuller Kathryn , Sforza Kevin , Yuhas Max , Parmeggiani Fabio , Baker David , Barrick Doug 
Published: June 2018

Significance
We apply a statistical thermodynamic formalism to quantify the cooperativity of folding of de novo-designed helical repeat proteins (DHRs). This analysis provides a fundamental thermodynamic description of folding for de novo-designed proteins and permits comparison with naturally occurring repeat protein thermodynamics. We find that individual DHR units are intrinsically stable, unlike those of naturally occurring proteins. This observation reveals local (intrarepeat) interactions as a source of high stability in Rosetta-designed proteins and suggests that different types of DHR repeats may be combined in a single polypeptide chain, expanding the repertoire of folded DHRs for applications such as molecular recognition. Favorable intrinsic stability imparts a downhill shape to the energy landscape, suggesting that DHRs fold fast and through parallel pathways.
The role of heritage tourism in the management and promotion of pilgrimage trails and routes.
Authors: Boyd S. W. 
Published: June 2018

Abstract

This chapter begins by first addressing pilgrimage as linked to trails and routes, before considering the role that heritage tourism can play regarding pilgrimage spaces. The chapter looks at both heritage tourism and pilgrimages from a theoretical and conceptual perspective, addressing the issue of whether key elements and principles of heritage tourism can enable effective management and promotion of pilgrimage routes, regardless of their type.
A Systematic Review and Meta-analysis of Ventilator-associated Pneumonia in Adults in Asia: An Analysis of National Income Level on Incidence and Etiology
Authors: Bonell Ana , Azarrafiy Ryan , Huong Vu Thi Lan , Viet Thanh Le , Phu Vu Dinh , Dat Vu Quoc , Wertheim Heiman , van Doorn H Rogier , Lewycka Sonia , Nadjm Behzad 
Published: June 2018

Abstract

Background
Ventilator-associated pneumonia (VAP) is the commonest hospital-acquired infection (HAI) in intensive care. In Asia, VAP is increasingly caused by resistant gram-negative organisms. Despite the global antimicrobial resistance crisis, the epidemiology of VAP is poorly documented in Asia.

Methods
We systematically reviewed literature published on Ovid Medline, Embase Classic, and Embase from 1 January 1990 to 17 August 2017 to estimate incidence, prevalence, and etiology of VAP. We performed a meta-analysis to give pooled rates and rates by country income level.

Results
Pooled incidence density of VAP was high in lower- and upper-middle-income countries and lower in high-income countries (18.5, 15.2, and 9.0 per 1000 ventilator-days, respectively). Acinetobacter baumannii (n = 3687 [26%]) and Pseudomonas aeruginosa (n = 3176 [22%]) were leading causes of VAP; Staphylococcus aureus caused 14% (n = 1999). Carbapenem resistance was common (57.1%).

Conclusions
VAP remains a common cause of HAI, especially in low- and middle-income countries, and antibiotic resistance is high.
A chronological pharmacovigilance network analytics approach for predicting adverse drug events
Authors: Davazdahemami Behrooz , Delen Dursun 
Published: June 2018

AbstractObjectivesThis study extends prior research by combining a chronological pharmacovigilance network approach with machine-learning (ML) techniques to predict adverse drug events (ADEs) based on the drugs’ similarities in terms of the proteins they target in the human body. The focus of this research, though, is particularly centered on predicting the drug-ADE associations for a set of 8 common and high-risk ADEs.Materials and methodslarge collection of annotated MEDLINE biomedical articles was used to construct a drug-ADE network, and the network was further equipped with information about drugs’ target proteins. Several network metrics were extracted and used as predictors in ML algorithms to predict the existence of network edges (ie, associations or relationships).ResultsGradient boosted trees (GBTs) as an ensemble ML algorithm outperformed other prediction methods in identifying the drug-ADE associations with an overall accuracy of 92.8% on the validation sample. The prediction model was able to predict drug-ADE associations, on average, 3.84 years earlier than they were actually mentioned in the biomedical literature.ConclusionWhile network analysis and ML techniques were used in separation in prior ADE studies, our results showed that they, in combination with each other, can boost the power of one another and predict better. Moreover, our results highlight the superior capability of ensemble-type ML methods in capturing drug-ADE patterns compared to the regular (ie, singular), ML algorithms.
ZBED6 negatively regulates insulin production, neuronal differentiation, and cell aggregation in MIN6 cells
Authors: Wang Xuan , Jiang Lin , Wallerman Ola , Younis Shady , Yu Qian , Klaesson Axel , Tengholm Anders , Welsh Nils , Andersson Leif 
Published: June 2018

ABSTRACTZinc finger BED domain containing protein 6 (Zbed6) has evolved from a domesticated DNA transposon and encodes a transcription factor unique to placental mammals. The aim of the present study was to investigate further the role of ZBED6 in insulin‐producing cells, using mouse MIN6 cells, and to evaluate the effects of Zbed6 knockdown on basal β‐cell functions, such as morphology, transcriptional regulation, insulin content, and release. Zbed6‐silenced cells and controls were characterized with a range of methods, including RNA sequencing, chromatin immunoprecipitation sequencing, insulin content and release, subplasma membrane Ca2+ measurements, cAMP determination, and morphologic studies. More than 700 genes showed differential expression in response to Zbed6 knockdown, which was paralleled by increased capacity to generate cAMP, as well as by augmented subplasmalemmal calcium concentration and insulin secretion in response to glucose stimulation. We identified >4000 putative ZBED6‐binding sites in the MIN6 genome, with an enrichment of ZBED6 sites at upregulated genes, such as the β‐cell transcription factors v‐maf musculoaponeurotic fibrosarcoma oncogene homolog A and Nk6 homeobox 1. We also observed altered morphology/growth patterns, as indicated by increased cell clustering, and in the appearance of axon‐like Neurofilament, medium polypeptide and tubulin β 3, class III‐positive protrusions. We conclude that ZBED6 acts as a transcriptional regulator in MIN6 cells and that its activity suppresses insulin production, cell aggregation, and neuronal‐like differentiation.—Wang, X., Jiang, L., Wallerman, O., Younis, S., Yu, Q., Klaesson, A., Tengholm, A., Welsh, N., Andersson, L. ZBED6 negatively regulates insulin production, neuronal differentiation, and cell aggregation in MIN6 cells. FASEB J. 33, 88–100 (2019). www.fasebj.org