bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binding of Anisoylated Lys-Plasminogen Streptokinase Activator Complex to Cells in Culture
Authors: Vasudevan Jayanand , Humphries John E , Gonias Steven L 
Published: July 2018

SummaryAnisoylated Lys-plasminogen streptokinase activator complex (APSAC) was purified from Eminase® by chromatography on Superose-12. Purified APSAC did not significantly deacylate within 4 h at 4° C in solution as determined by hydrolysis of D-Val-L-leu-L-lys-p-nitroanilide HCl (S-2251). At 37° C, maximum amidase activity developed in 120 min; ε-amino-n-caproic acid (EACA) did not affect the apparent rate of APSAC deacylation but stabilized the streptokinase-plasmin(ogen) complex (SkPl) which formed. APSAC bound to C6 glioma cells and human umbilical vein endothelial cells (HUVECs) in culture. Binding was completely inhibited by EACA suggesting an essential role for the plasminogen kringle domains. Cell-associated APSAC deacylated to form active SkPl which hydrolyzed S-2251 and D-Val-Leu-Lys-7-amino-4-methyl coumarin. The rate of APSAC deacylation was increased when the APSAC was cell-associated. APSAC that was initially bound to C6 cells or HUVECs also activated 125I-plasminogen. This activity may have reflected cell-associated APSAC or APSAC that dissociated into solution. Plasmin was recovered bound to cells and in solution. These studies demonstrate that APSAC associates with cell-surfaces and retains activity. In the circulation, cell-surfaces may provide a significant pharmacologic compartment for intravenously administered APSAC.
Antithrombin III, the Major Modulator of Intravascular Coagulation, Is Synthesized by Human Endothelial Cells
Authors: Chan T K , Chan Vivian 
Published: July 2018

SummaryHuman endothelial cells in culture is shown to synthesize antithrombin III (At-III). The endothelial cell At-III(EC-At-III) consists of a small fraction similar to plasma At-III and a larger fraction with decreased heparin-binding as tested by crossed immunoelectrophoresis. However, both the anti-Xa and thrombin-neutralizing activities of the EC-At-III were rapid and active even in the absence of added heparin. It is concluded that the major portion was probably bound to endogenous heparin-like substance, thus accounting for its decreased exogenous heparin binding. The presence of At-III and other antithrombotic factors in the vascular endothelium offer protection against thrombosis and possibly atherosclerosis.
The Evaluation of Plasmin and Streptokinase Activator Complexes in a New Rabbit Model of Venous Thrombosis
Authors: Dupe R J , English P D , Smith R A G , Green J 
Published: July 2018

SummaryA new quantitative model for the examination of potential thrombolytic agents is described. A thrombus was formed in the inferior vena cava of the rabbit, using 125I-labelled fibrinogen mixed with a standard amount of thromboplastin. The thrombus was anchored securely by means of a woollen thread inserted longitudinally into the lumen of the vein. Thrombotic extension of the radioactive clot and rethrombosis during the experimental period (5 h) were prevented by the administration of intravenous heparin. In control animals, the thrombus remained stable and there was no rise in the radioactivity of the circulating blood during 5 h. In animals given thrombolytic agents, lysis could be followed continuously by measuring the rise in blood radioactivity. Total lysis was determined by counting the radio-label in the residual clot after treatment.The model has been used to study the thrombolytic activity of streptokinase-human plasminogen complexes, activator-free plasmins of human and porcine origin, and human plasmin produced by streptokinase (SK) activation of human plasminogen. The role of activator complexes in the thrombolytic activity of SK-activated plasmin is discussed.
The Thrombolytic Activity of Streptokinase in the Rabbit
Authors: English P D , Smith R A G , Dupe R J , Green J , Hibbs M J 
Published: July 2018

SummaryThe activity of streptokinase (SK) has been examinEd in a rabbit model of venous thrombosis. Significant thrombolysis was observed at low doses of SK without evidence of systemic activation of the fibrinolytic system. The origidn of the specificity of SK-induced fibrinolysis in the rabbit was explored, using a chromogenic substrate coupled assay to measure the enhancement of plasmin generation in the presence of rabbit fibrin. The results obtained suggest that rabbit fibrin influences the fibrinolytic system at three points, viz: the assembly of an activator complex from rabbit plasminogen and SK; the activity of that activator complex towards further rabbit plasminogen; and the activity of the resulting rabbit plasmin in the presence of plasma inhibitors.
Effects of Suloctidil on Platelet Survival Time Following Cardiac Valve Replacement
Authors: Col-de Beys Chr , Ferrant A , Moriau M 
Published: July 2018

SummaryPlatelet functions and blood clotting parameters were examined in 23 patients with a shortened platelet survival time after cardiac valve replacement.Treatment was given at random: for a first group antivitamins K with suloctidil and for the second group antivitamin K alone.Six weeks of treatment with antivitamin K alone did not induce any significant change in the platelet survival time, platelet retention or platelet factor 4 in plasma.In contrast, the shortened platelet survival time increased significantly after 6 weeks of treatment with suloctidil. Moreover the platelet retention and the amount of platelet factor 4 in plasma were significantly reduced, indicating that normalization of platelet survival is the result of decreased destruction, presumably at the level of the prosthetic surface. The clinical benefits expected from these results remain to be validated by a longer follow up period.
Severe Thrombocytopenia Delays but Does Not Prevent the Occlusion of an Arterial Prosthesis in Rats
Authors: Reyers I , Mussoni L , Donati M B , Gaetano G de 
Published: July 2018

SummaryThis study shows that experimentally-induced immune thrombocytopenia significantly delayed occlusion of an arterial prosthesis inserted in rat abdominal aorta. Thrombocytopenia was effective when induced several hours or shortly, or even several hours after the insertion of the prosthesis. Maintenance of severe thrombocytopenia by daily administrations of antiplatelet antiserum appeared to further delay thrombotic occlusion.However, though delayed, occlusion eventually occurred in all rats, even in those with very low platelet count. This would imply that any attempt to prevent arterial prosthesis thrombosis solely by interfering with platelets is ultimately bound to fail.
Coagulation and Fibrinolysis Study in Systemic Lupus erythematosus: Haematological, Urinary and Tissue Parameters
Authors: Stratta P , Canavese C , Valmaggia P , Rotunno M , Levi E , Bulla A , Vercellone A 
Published: July 2018

SummaryHaematochemical, urinary and tissue parameters were examined in the elaboration of the coagulation and fibrinolysis profile in 33 cases of systemic lupus erythematosus in different stages of the disease. Coagulation abnormalities varied from hypo- to hyper-coagulabitity, these being often associated in the same patient, either simultaneously or at different stages of the disease. Activation of coagulation, closely related to the immunological activity of the disease, was present in 80% cases in the acute stage, and 36% of those in the remission stage. The lupus-like anticoagulant was not much involved, and platelets were the prime figures in the haemostatic abnormalities of lupus, those being the preferred target of direct antibody activities, or possibly of immune complexes as well. Activation of the coagulatory cascade is not uncommonly accompanied by a thrombophilic tendency coupled with signs of consumption, this being the expression of a continuously stimulated haemostatic balance.
Radiolabeling of Fibrinogen Using the Iodogen Technique
Authors: Knight Linda C , Budzynski Andrei Z , Olexa Stephanie A 
Published: July 2018

SummaryThe properties of human fibrinogen labeled with 125-Iodine using Iodogen (1, 3, 4, 6-tetrachloro-3α, 6α-diphenylglycoluril) as an oxidizing agent were compared with those of an iodine monochloride labeled counterpart. It was found that thrombin clottability, binding to staphylococci, the relative specific radioactivity of the Aα, Bβ, and γ chains and in vivo clearance from plasma in rabbits were the same in these two labeled fibrinogen preparations. Labeling efficiency was higher when iodogen was used. It is concluded that human fibrinogen labeled with radioiodine using the Iodogen technique is suitable for studies in vitro and in vivo.
Comparison of Progressive Antithrombin Activity and the Concentration of Three Thrombin Inhibitors in Nephrotic Syndrome
Authors: Boneu B , Bouissou F , Abbal M , Sie P , Caranobe C , Barthe P 
Published: July 2018

SummaryIn order to compare the plasmatic progressive antithrombin activity to the concentration of three thrombin inhibitors, antithrombin III (AT III), α2 macroglobulin (α2, M), α1 anti-trypsin (α1 AT) in nephrotic syndrome, a prospective study was carried out on a group of 28 children affected with the disease. A dramatic reduction of the level of AT III and of α1 AT, two inhibitors of molecular weight close to that of albumin, was observed. The decreased level of AT III was counterbalanced by an increase in α2 M. This phenomenon accounts for the increased progressive antithrombin activity observed in all the affected children. It is suggested that the above compensatory mechanism explains the absence of thrombotic accidents in this series and that the benefit of heparin therapy is doubtful in these conditions.
Studies of Phospholipid Reagents Used in Coagulation I: Some General Properties and Their Sensitivity to Factor VIII
Authors: Barrowcliffe T W , Gray Elaine 
Published: July 2018

SummarySome general properties of phospholipid reagents have been studied, particularly in relation to their use in detection and measurement of Factor VIII deficiency. There was wide variation among reagents in their total phospholipid concentration, and in the degree of contamination with tissue factor and oxidation products. Although clotting times of normal and haemophilic plasma were affected by change of phospholipid concentration, presence of oxidation products, and order of addition of reagents,
these factors did not appear to influence the efficiency of detection of the Factor VIII defect. The method of activation had a definite influence on sensitivity to Factor VIII deficiency, both the type of activator and the time of activation being important.In Factor VIII one-stage assays, use of different phospholipids with the same substrate plasma gave significant differences in precision, but the estimates of potency of a Factor VIII concentrate against a plasma standard were not significantly different.
Enhanced Antithrombotic Mechanisms in Patients with Maturity-Onset Diabetes mellitus without Thromboembolic Complications
Authors: Grignani G , Gamba G , Geroldi D , Pacchiarini L , Solerte B , Ferrari E , Ascario E 
Published: July 2018

SummarySome haemostatic parameters have been evaluated in a group of rigorously selected patients with maturity-onset diabetes mellitus without thromboembolic complications and in apparently normal subjects of the same age before and after the venous occlusion test (VOT).In basal conditions diabetics had higher levels of AT III as biological activity and higher fibrinolytic and antifibrinolytic activities than controlsAfter VOT, F VIII R:Ag increased significantly in both groups, more markedly in controls than in diabetics, while F VIII: C showed no modification.Also AT III R:Ag increased after the test, but such variation was significant only in diabetics; on the contrary, the biological activity of AT III was always significantly decreased after the test.After VOT there were also in both groups highly significant increases in the fibrinolytic and antifibrinolytic activities.Finally, HbA1c levels directly correlated with AT III as biological activity before VOT, but with no other parameter either before or after the test.These data suggest the existence in patients with diabetes mellitus without thromboembolic complications of an activated protective mechanism against intravascular clotting.
Enhancement of Thrombin-Induced Degradation of Phosphatidylcholine in Reserpinized Rabbit Platelets
Authors: Watanabe Yasuko , Soda Masako , Kobayashi Bonro 
Published: July 2018

SummaryWhen 1-14C-arachidonic acid-labeled, washed platelets from the reserpinized rabbits were exposed to thrombin, the decrease in radioactivity of phospholipids was significantly stimulated as compared with the control platelets. The increase in radioactivity of fatty acids and their oxygenated metabolites was also stimulated. TLC analysis revealed that the stimulation of the decrease in radioactivity of phospholipids was almost exclusively attributed to that of phosphatidylcholine (PC), and that thrombin induced a slight but significant increase in radioactivity of phosphatidyl ethanolamine (PE) in the reserpinized platelets. The results suggest that thrombin-induced degradation of PC is enhanced in the reserpinized platelets, and the overproduced fatty acids would be metabolized to the larger amount of oxygenated products which result in the activation of the platelets. Thrombin-induced mobilization of PC to PE in the reserpinized platelet phospholipids was also suggested.
In Vitro Effect of Ethanol on ADP and Collagen-Induced Platelet Aggregation
Authors: Bengmark Stig , Elmér Olle , Göransson Göran , Zoucas Evita 
Published: July 2018

SummaryPlatelet aggregation was measured by Born’s method. Plasma from Sprague-Dawley rats and inbred albino rabbits was used. 20% ethanol in 0.9%(w/v) NaCl was added to plasma at final concentrations of 56.5 mM, 85.9 mM 171.5 mM and 343.1 mM or to whole blood at final concentrations of 8.7 mM, 17.4 mM, 52.5 mM, 171.5 mM and 343.1 mM. Experiments using 0.9% NaCl volumes equivalent to the added ethanol volume were also conducted. Dose-response aggregation tests showed that a decrease in ADP-and collagen-induced aggregation existed when ethanol was mixed with rat or rabbit blood prior to the preparation of platelet-rich plasma. There was no effect on ADP-induced platelet aggregation when ethanol was mixed with rat or rabbit plasma. Collagen-induced aggregation was impaired only in rat plasma when ethanol concentration reached 343.1 mM. These results suggested that ethanol modified platelet function possibly via red cells.
HLA Antigens and Factor VIII Antibody in Classic Hemophilia
Authors: Frommel D , Allain J P , Saint-Paul E , Bosser C , Noël B , Mannucci P M , Pannicucci F , Blombäck M , Prou-Wartelle O , Muller J Y 
Published: July 2018

SummaryPossible interrelations between the immune response factor VIII and the major histocompatibility system were investigated in 57 multi-transfused hemophilic brothers belonging to 26 families. Linkage appears very unlikely although formal proof of independence cannot be offered. The HLA system, therefore, does not provide markers predictive for the development of antibodies to factor VIII in severe hemophilia A.
Platelet and Coagulation Function in Patients with Abnormal Cardiac Valves Treated with Sulphinpyrazone
Authors: Ludlam C A , Allan N , blandford R B , Dowdle R , Bentley N J , Bloom A L 
Published: July 2018

SummaryEight patients on warfarin with rheumatic heart disease and prosthetic cardiac valves were selected for study on the basis of persistently elevated plasma β-thromboglobulin (β-tg) and platelet factor 4 (PF4) concentrations. Platelet mean lifespan and fibrinogen half life were short, and positively correlated, and both were inversely related to the Plasma concentrations of the platelet specific proteins. Antithrombin III (ATIII) levels were also reduced. Treatment with sulphinpyrazone resulted in lengthening of both platelet and fibrinogen survival, a rise in ATIII but no change in the βtg or PF4 concentrations. It is concluded that patients with abnormal cardiac valves and raised plasma levels of βtg or PF4 have, despite warfarin, a consumption coagulopathy that can be inhibited by sulphinpyrazone.
GAGs-Potentiated Inhibition of Thrombin, Factor Xa and Plasmin in Plasma and in a Purified System Containing Antithrombin III – Correlation with Total Charge Density
Authors: Cofrancesco E , Vigo A , Pogliani E M 
Published: July 2018

SummaryThe ability of heparin and related glycosaminoglycans (GAGs) to accelerate the inhibition of thrombin, factor Xa and plasmin in plasma and in a purified system containing antithrombin III (At III) was studied using chromogenic peptide substrate assaysThere was a good correlation between the charge density of the mucopolysaccharides and the activities investigated. While the difference between potentiation of the antithrombin activity by GAGs in plasma and in the purified system was slight, the inhibition of factor Xa in plasma was more pronounced than in the presence of purified At III, indicating the mechanisms for GAGs-potentiated inhibition of thrombin and factor Xa are not identical.For the antiplasmin activity, there was a good correlation between the chemical structure and biological activity only in the pure system, confirming that the antithrombin-GAG complex plays a very limited role in the inactivation of plasmin in plasma.
Cell-autonomous regulation of astrocyte activation by the circadian clock protein BMAL1
Authors: Lananna Brian V. , Nadarajah Collin J. , Izumo Mariko , Cedeño Michelle R. , Xiong David D. , Dimitry Julie , Tso Chak Foon , McKee Celia A. , Griffin Percy , Sheehan Patrick W. , Haspel Jeffery A. , Barres Ben A. , Liddelow Shane A. , Takahashi Joseph S. , Karatsoreos Ilia N. , Musiek Erik S. 
Published: July 2018

SummaryCircadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood. Astrocyte activation occurs in response to diverse insults, and plays a critical role in brain health and disease. We report that the core clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism, and via a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1 deletion induces astrocyte activation in vitro and in vivo, mediated in part by suppression of glutathione-s-transferase signaling. Functionally, loss of Bmal1 in astrocytes promotes neuronal death in vitro. Our results demonstrate that the core clock protein BMAL1 regulates astrocyte activation and function in vivo, elucidating a novel mechanism by which the circadian clock could influence many aspects of brain function and neurologic disease.HighlightsCircadian disruption promotes astrocyte activation.Astrocyte-specific deletion of the circadian clock gene BMAL1 induces astrocyte activation.BMAL1 regulates astrocyte activation by altering glutathione-s-transferase signaling.Loss of astrocyte BMAL1 enhances neuronal cell death in a co-culture system.eTOC blurbLananna et al. show that the circadian clock protein BMAL1 regulates astrocyte activation via a cell autonomous-mechanism involving diminished glutathione-s-transferase signaling. This finding elucidates a novel function of the core circadian clock in astrocytes, and reveals a BMAL1 as a modulator of astrogliosis.
The interrelationships between self-determined motivations, memorable experiences and overall satisfaction
Authors: Sie Lintje , Phelan Kelly Virginia , Pegg Shane 
Published: July 2018

Purpose
The purpose of this study is to assess the relationships between older travelers’ self-determined motivations, memorable travel experiences and overall satisfaction with educational holidays. This study also examined the mediating effects of memorable travel experiences on the relationships between motivations and overall satisfaction.

Design/methodology/approach
An integrative model using a pre-post travel approach was used as the framework for this study. A total of 361 valid pre- and post-travel surveys were gathered from Australians 50 years or older who participated in educational tour packages.

Findings
Results found “personal development” and “learning” dimensions of intrinsic self-determined motivations were the main decision making factors for older adults to engage in educational tourism. “Learning” was the main driver to influence memorable experiences and overall satisfaction. Findings also revealed “local culture” and “excitement” dimensions of memorable experiences were found to influence their overall satisfaction with the trip. These two dimensions were found to be significant factors that partially mediated the relationship between intrinsic motivation (“learning”) and overall satisfaction.

Originality/value
This study contributed to developing a theoretical framework that assessed antecedents and outcomes of older adults’ motivations and travel-related behaviors.
Are multinational enterprises in retreat?
Authors: Vahlne Jan-Erik , Ivarsson Inge , Alvstam Claes G. 
Published: July 2018

Purpose
This paper aims to contribute to the debate concerning the asserted end of the globalization process.

Design/methodology/approach
This paper is a description of the evolution of all Swedish MNEs, the 50 largest companies and the ten truly global MNEs, building on data compiled by the authors, mainly from annual reports.

Findings
The largest Swedish MNEs have continued to globalize and have at the same time improved their financial performance during the period of study, 2010-2016.

Practical implications
The proposition that multinationals are heading home cannot be confirmed in the Swedish case. There is therefore a need to compare Swedish experiences with other national examples to better generalize the findings.

Social implications
The political decisions regarding external trade and foreign direct investment should support continuous liberalization and facilitation of cross-border economic interaction.

Originality/value
As Swedish MNEs are more globalized than the average in advanced economies, this study offers insight into the contemporary internationalization process.
The Kodak Syndrome: Risks and Opportunities Created by Decentralization of Forensic Capabilities
Authors: Casey Eoghan , Ribaux Olivier , Roux Claude 
Published: July 2018

AbstractForensic science laboratories are being challenged by the expanding decentralization of forensic capabilities, particularly for digital traces. This study recommends laboratories undertake digital transformations to capitalize on the decentralization movement, develop a more comprehensive understanding of crime and security‐relevant problems, and play a more central role in problem‐solving collaboratively with law enforcement organizations and other stakeholders. A framework for the bilateral transfer of information and knowledge is proposed to magnify the impact of forensic science laboratories on abating crime, strengthening security, and reinforcing the criminal justice system. To accomplish digital transformations, laboratories require personnel with different expertise, including investigative reasoning, knowledge codification, data analytics, and forensic intelligence. Ultimately, this study encourages managers, educators, researchers, and policymakers to look beyond the usefulness of forensic results for solving individual investigations, and to realize the value of combined forensic knowledge and intelligence for developing broader strategies to deal with crime in digitalized society.