bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-dependency of thrombin generation measured by means of calibrated automated thrombography (CAT)
Authors: Haidl Harald , Cimenti Christina , Leschnik Bettina , Zach Doris , Muntean Wolfgang 
Published: April 2006

SummaryMany coagulation parameters, such as PT or aPTT, show age-dependency. In this study we investigated if the generation of thrombin, possibly better reflecting overall haemostasis, shows an age-dependency.Thrombin generation was measured in platelet poor plasma of 121 children and 86 adults at different ages by means of calibrated automated thrombography (CAT). Correlation analysis shows that endogenous thrombin potential (ETP) (r= 0.702),lag time (r = - 0.266),peak (r = 0.533) and time to peak (r = - 0.214) are significantly correlated with age (p < 0.01).’Younger’ (age limit 35 years) and ‘older’ adults were compared with groups of children and adolescent aged between 0.5 and 6 years, 7 and 11 years and 12 to 17 years by means of the Mann-Whitney-U-Test. ETP values of all children and adolescents were significantly lower than those of adults. In the group of the youngest children,additionally shorter lag times and times to peak and lower peak levels differed significantly from those of adults. In the group of 7to 11-year-old children, lag times were significantly longer than those of both groups of adults, while lower peaks and longer times to peak differed only from the group of the ‘older’ adults. In the group of the 12to 17-yearolds, the values of ETP were lower than those of adults. In addition, both adult groups differed significantly in all studied parameters. Our results show an age-dependency of thrombin generation even beyond the juvenile period. If thrombin generation measurement is to be used asa routine method, age has to be considered. Assuming that thrombin potential is an indicator for the risk of thrombosis, our findings are in accordance with the observation of an increased incidence of thrombembolic disease with higher age.
Local delivery of soluble platelet collagen receptor glycoprotein VI inhibits thrombus formation in vivo
Authors: Bültmann Andreas , Herdeg Christian , Li Zhongmin , Münch Götz , Baumgartner Christine , Langer Harald , Kremmer Elisabeth , Geisler Tobias , May Andreas , Ungerer Martin , Gawaz Meinrad 
Published: April 2006

SummaryPlatelet-mediated thrombus formation at the site of vascular injury isa major trigger for thrombo-ischemic complications after coronary interventions. The platelet collagen receptor glycoprotein VI (GPVI) plays a critical role in the initiation of arterial thrombus formation. Endothelial denudation of the right carotid artery in rabbits was induced through balloon injury. Subsequently, local delivery of soluble, dimeric fusion protein of GPVI (GPVI-Fc) (n=7) or control Fc (n=7) at the site of vascular injury was performed with a modified double-balloon drugdelivery catheter.Thrombus area within the injured carotid artery was quantified using a computer-assisted image analysis and was used as index of thrombus formation.The extent of thrombus formation was significantly reduced in GPVI-Fc- compared with control Fc-treated carotid arteries (relative thrombus area, GPVI-Fc vs. Fc: 9.3 ± 4.2 vs. 2.3 ± 1.7, p<0.001). Local delivery of soluble GPVI resulted in reduced thrombus formation after catheter-induced vascular injury.These data suggest a selective pharmacological modulation of GPVI-collagen interactions to be important for controlling onset and progression of pathological arterial thrombosis, predominantly or even exclusively at sites of injured carotid arteries in the absence of systemic platelet therapy.
Plasminogen activator inhibitor-1 potentiates LPS-induced neutrophil activation through a JNK–mediated pathway
Authors: Kwak Sang-Hyun , Wang Xue-Qing , He Qianbin , Fang Wen-Feng , Mitra Sanchayita , Bdeir Khalil , Ploplis Victoria , Xu Zhi , Idell Steven , Cines Douglas , Abraham Edward 
Published: April 2006

SummaryPlasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor superfamily, modulates fibrinolysis by interacting with proteolytic mediators, including urokinase plasminogen activator (uPA). Although the roles of uPA and PAI-1 in plasmin generation and the degradation of fibrin are well known, recent evidence also suggests that they can participate in acute inflammatory conditions that involve neutrophil activation. In the present experiments, we found that the addition of PAI-1 to LPS-stimulated neutrophils resulted in enhanced nuclear translocation of NF-κB and increased production of the proinflammatory cytokines IL-1β,Tnf-α,and Mip-2.uPA and the kringle domain (KD) of uPA potentiated cytokine expression and NF-κB activation by neutrophils cultured with LPS, and had additive effects when combined with PAI-1. The c-Jun N-terminal kinase (JNK) was activated after exposure of resting neutrophils to PAI-1 or the uPA KD. Enhanced JNK activation, but not that of other kinases induced by LPS, was present in neutrophils cocultured with PAI-1 or uPA KD. Inhibition of JNK activation prevented the potentiation of expression of proinflammatory cytokines induced by PAI-1 or uPA KD in LPS stimulated neutrophils. These results demonstrate that PAI-1 and uPA KD enhance LPSinduced neutrophil responses through their effects on JNK mediated pathways.
In vivo antithrombotic synergy of oral heparin and arginine: Endothelial thromboresistance without changes in coagulation parameters
Authors: Daniels Bruce , Zhang Fuming , Mao Wenjun , Wice Sandra , Hiebert Linda , Linhardt Robert 
Published: April 2006

SummaryOn the basis of suggested clinical efficacy in an uncontrolled study in ninety-seven patients with unstable angina, an animal study was conducted to investigate antithrombotic synergy between orally administered heparin and arginine. A rat venous thrombosis model tested the difference in thrombus formation when heparin (7.5 mg/kg) and arginine (113 mg/kg) were administered, alone or in combination, by stomach tube with a minimum of 20 rats/group. Oral heparin, arginine, and heparin plus arginine reduced thrombus formation by 50%, 75%, and 90%, respectively,when compared to saline administration. Heparin was recovered from endothelium, yet there was little or no observable plasma anticoagulant activity. An orally administered lowmolecular-weight anticoagulant glycosaminoglycan mixture, sulodexide (7.5 mg/kg), showed an 88% reduction in stable thrombus formation when administered alone but showed no synergy with oral arginine. A 28-day study with oral sulodexide (2.9 mg/ kg) and arginine (43.9 mg/kg), 20 rats/group, showed antithrombotic activity with minimal anticoagulant activity indicating suitability for long term treatment. These findings suggest the endothelial localization of heparin and a synergistic antithrombotic effect for orally administered heparin and arginine.
Cleavage of human 7-domain VCAM-1 (CD106) by thrombin
Authors: Barthel Steven , Johansson Mats , Annis Douglas , Mosher Deane 
Published: April 2006

SummaryVascular cell adhesion molecule 1 (VCAM-1,CD106) is expressed as a type I transmembrane integrin counter-receptor on activated endothelium and mediates white blood cell attachment. The alternatively spliced 7-domain (7d) form of VCAM-1 contains a potential thrombin cleavage site. Thrombin proteolysis of 7d-VCAM-1 may help regulate adhesive activity of VCAM-1. We determined whether 7d-VCAM-1 is proteolyzed and rendered inactive by thrombin. Recombinant extracellular domain of 7d-VCAM-1 was cleaved by thrombin to generate 33- and 44-kDa products. Cleavage was in the sequence PGPR/IAAQIG near the N-terminal border of the alternatively spliced fourth immunoglobulin (Ig)-like module. There was no cleavage of 6d-VCAM-1 lacking the fourth module. Expression of full-length 7d-VCAM-1 presented on Chinese hamster ovary (CHO) monolayers, as detected by flow cytometry with an antibody directed to Ig-like modules 1–3, was reduced by thrombin treatment whereas there was no reduction in the expression of fulllength 6d-VCAM-1. Adhesion of blood eosinophils to full-length 7d-VCAM-1 was reduced after treatment of CHO cells with thrombin, whereas adhesion to full-length 6d-VCAM-1 was not affected. We conclude that cleavage of 7d-VCAM-1 by thrombin is a potential mechanism for differential regulation of VCAM-1 splice forms in white blood cell adhesion and trafficking.
Air travel and fatal pulmonary embolism
Authors: Bell Melanie , Herbison Peter , Paul Charlotte , Skegg David , Parkin Lianne 
Published: April 2006

SummaryAlthough long-distance air travel is commonly regarded as a risk factor for venous thromboembolism, the risk of clinically important events has not been well defined. We estimated the absolute risk of dying from pulmonary embolism following longdistance air travel in a national population-based descriptive study of 121 men and women who were aged 15–59 years (the age range in which the majority of international arrivals are found) and whose underlying cause of death was certified as codes 415.1, 451, or 453 of the International Classification of Diseases (ninth revision). Eleven cases had undertaken longdistance air travel in the four weeks before the onset of the fatal episode. The estimated risks of fatal pulmonary embolism following a flight of at least three hours’ duration were 0.5 (95% CI 0.2–1.2) and 0.6 (95% CI 0.2–1.4) per million arrivals for overseas visitors and New Zealand residents, respectively. For air travel of more than eight hours’ duration, the risk in New Zealand residents was 1.3 (95% CI 0.4–3.0) per million arrivals. We also conducteda case-control study based on those cases who were normally resident in New Zealand and registered on the electoral roll (n=99). For each case, four controls matched for sex, age, and electorate, were randomly selected from the electoral roll. In the key analysis (based on 88 cases and 334 controls), the adjusted odds ratio for travellers who had flown for more than eight hours was 7.9 (95% CI 1.1–55.1) compared with those who did not undertake a long-distance flight. Longdistance air travellers have a higher risk of dying from pulmonary embolism than non-travellers, but the absolute risk in people aged 15–59 years appears to be very small.
Interleukin-6 and interleukin-6 promoter polymorphism (−174) G>C in patients with spontaneous venous thromboembolism
Authors: Vormittag Rainer , Hsieh Kety , Kaider Alexandra , Minar Erich , Bialonczyk Christine , Hirschl Mirko , Mannhalter Christine , Pabinger Ingrid 
Published: April 2006

SummaryIncreased levels of interleukin-6 (IL-6) have been reported in patients with a history of venous thromboembolism (VTE); however, prospective studies did not confirm an association between inflammatory markers that are highly correlated with IL-6 and the risk of VTE. It was the aim of our study to investigate the association of IL-6 and its promoter polymorphism (−174) G>C with the risk of spontaneous VTE. IL-6 was measured in 128 patients with deep venous thrombosis (DVT, 70 w / 58 m),105 with pulmonary embolism (PE, 58w/ 47 m) and 122 healthy controls (60 w / 62 m) with a highly sensitive ELISA (Quantikine− HS Human IL-6 Immunoassay, RnDSystems®). The promoter polymorphism was determined by genotyping, allele specific PCR was followed by high resolution gel-electrophoresis. Median concentrations [interquartile ranges] were 2.37 [1.51–3.89] (pg/ ml) in patients with DVT, 2.83 [1.83–4.87] in those with PE and 2.51 [1.71–4.78] in controls (p = 0.6, p = 0.4). Hetero- or homozygous carriers of the C allele (71% in DVT, 67% in PE and 59% among controls) did not have higher IL-6 levels than homozygous carriers of the G allele (median 2.60 vs. 2.59 pg/ml, p = 0.7). In conclusion, we found no association of IL-6 and its promoter polymorphism (−174) G>C with the risk of spontaneous VTE.
Impaired dimerization of von Willebrand factor subunit due to mutation A2801D in the CK domain results in a recessive type 2A subtype IID von Willebrand disease
Authors: Hommais Antoine , Stépanian Alain , Fressinaud Edith , Mazurier Claudine , Pouymayou Katia , Meyer Dominique , Girma Jean-Pierre , Ribba Anne-Sophie 
Published: April 2006

SummaryThe CK domain of von Willebrand factor (VWF) is involved in the dimerization of the protein.We identified the homozygous substitution A2801D of the CK domain in two siblings. Patients had low levels of VWF in plasma, abnormal ristocetin-induced binding to platelets and abnormal multimeric pattern witha lack of high molecular weight (HMW) forms and the presence of intervening bands between normal multimers. Accordingly, they were classified in type 2A, subtype IID, von Willebrand disease (VWD). Both asymptomatic parents carried the mutation at the heterozygous state.Their plasmaVWF exhibited the full range of multimers found in normal plasma.When analyzed by high resolution gel electrophoresis, very faint bands corresponding to the position of intervening bands of the propositus can be observed. The mutated recombinant (r)VWF-D2801, the hybrid rVWF-A/D2801 and the mutated C-terminal VWF fragment rSPII-D2801 were expressed in COS-7 cells. rVWF-D2801 showed an abnormal multimeric distribution similar to that of the propositus’VWF with intervening bands and a lack of HMW species. rVWF-A/D2801 exhibited the full range of multimers and the aberrant sized forms observed both in propositus’VWF and in rVWF-D2801. rSPII-WT assembled correctly into a dimer of 220 kDa. rSPII-D2801 appeared as a mixture of monomeric and dimeric forms which may be related to the abnormal multimeric pattern of the propositus and both mutated rVWF. We concluded that mutation A2801D disturbs the folding of the CK domain, which may result in a mixture of monomers and dimers of VWF. Multimers containing either an odd or even number of mature subunits are produced, and the presence of monomers appears to limit the degree of multimerization. In the heterozygousVWF,the presence of normal dimers improves the multimerization process. In conclusion, the mutation A2801D appears to be responsible fora recessive type 2A, subtype IID, VWD.
A potent anti-coagulant RNA aptamer inhibits blood coagulation by specifically blocking the extrinsic clotting pathway
Authors: Gopinath Subash , Shikamoto Yasuo , Mizuno Hiroshi , Kumar Penmetcha 
Published: April 2006

SummaryA potent antidote-controlled aptamer, as an anticoagulant, has reportedly overcome the complications of acute bleeding by the administration of available anticoagulants. In the present study, we provide evidence that the aptamer binds specifically to factors IX and IXa and inhibits their functions. Furthermore, we demonstrated that the aptamer inhibits blood coagulation by interfering with the extrinsic pathway, blocking the complex of factor VIIa and tissue factor interactions with factor IX. The results from the previous and present studies suggest that the aptamer probably binds in the vicinity of the EGF1 and EGF2 domains of factor IX.
The magnitude of an iatrogenic disorder:A systematic review of the incidence of venous thromboembolism for general medical inpatients
Authors: Brenner Adam , Halm Ethan , Dunn Andrew 
Published: April 2006

SummaryVenous thromboembolism (VTE) is recognized as a potential serious complication of hospitalization, and anticoagulant prophylaxis is widely recommended for medical inpatients.The purpose of this review was to systematically inspect the literature to determine the incidence of VTE without anticoagulant prophylaxis for hospitalized general medical patients. A systematic review was performed using MEDLINE and Cochrane Collaboration searches of the English-language literature. References of the retrieved articles were reviewed for additional studies, and pharmaceutical companies were contacted directly to identify unpublished studies. Studies were eligible if they reported the incidence of symptomatic or asymptomatic VTE in hospitalized general medical patients and included a group which did not receive prophylaxis. Eight trials were identified. Study design, quality, and results were heterogeneous.The incidence of symptomatic VTE without prophylaxis was examined in three trials; the incidence was 2.3% in the only randomized trial, and was 0.8% and 6.2% in two observational studies. The incidence of asymptomatic VTE ranged from 3.7% to 26.0% (median 12.8%). Risk factors identified were older age, prior VTE, and obesity. Though there is little high quality evidence, the best estimate of the incidence of hospital-acquired VTE for general medical patients is approximately 2% for patients at moderate to high risk and <1% for patients at low risk. Further studies are needed to more precisely define a low risk group for whom anticoagulant prophylaxis is unnecessary.
ADAMTS13-binding IgG are present in patients with thrombotic thrombocytopenic purpura
Authors: Raoufi Mojgan , Zhou Wenhua , Guinto Enriqueta , Grafos Nickolas , Ranzurmal Safi , Greenfield Robert , Rand Jacob , Tsai Han-Mou 
Published: April 2006

SummaryFunctional assays are commonly used to measure the antibodies of ADAMTS13 found in patients of thrombotic thrombocytopenic purpura (TTP). In this study we used an enzyme-linked immunoassay to analyze the ADAMTS13-binding IgG levels in six groups of individuals: normal, random hospitalized patients, acute TTP,TTP after receiving plasma therapy,TTP in remission, and other types of thrombotic microangiopathy (TMA).The results showed that ADAMTS13-binding IgG levels were elevated in 100% of the acute TTP group, 75% of the TTP group after receiving plasma therapy, and 40% of the remission group. Overall, the ADAMTS13-binding IgG levels correlated with the inhibitory activity levels againstADAMTS13 (r = -0.69,P<0.0001).The assay also detected elevated IgG binding levels in 5% - 15% of the normal, random, and other TMA control groups.Addition of purified ADAMTS13 protein to the plasma samples suppressed the IgG binding in each of the acute TTP patients, but in none of the non-TTP groups. Serial measurement in a patient that had two exacerbations of TTP within the first three weeks revealed that the ADAMTS13 activity levels remained < 0.1 U/ml during this period, and the ADAMTS13-binding IgG remained elevated, suggesting that ADAMTS13 analysis may provide valuable insight to the disease status during the course of therapy. Analysis of ADAMTS13-binding IgG is helpful for the diagnosis and management of TTP.
La victimización sexual en las relaciones con los iguales en una muestra de mujeres adolescentes y jóvenes: prevalencia y creencias relacionadas con la victimización
Authors: Ramos Maribel , Fuertes Antonio , de la Orden Victoria 
Published: April 2006

Este estudio pretende conocer la prevalencia de la victimización sexual entre las mujeres adolescentes y jóvenes por parte de sus iguales conocidos varones, así como identificar la posibilidad de que determinados factores se asocien con una mayor vulnerabilidad ante este tipo de victimización. Para ello, 239 adolescentes y jóvenes escolarizadas respondieron anónimamente a un cuestionario que incluía una adaptación del Sexual Experiences Survey (SES; Koss, Gidycz y Wisniewski, 1987), y otras escalas para valorar la aceptación de determinadas actitudes y creencias que se han asociado a la vulnerabilidad ante la victimización sexual. Un 42,7% de las adolescentes y jóvenes afirma haber mantenido algún tipo de relación sexual no deseada porque un varón al que conocían utilizó algún tipo de estrategia coercitiva para ello. Las adolescentes y jóvenes que informan haberse visto implicadas en alguna situación sexualmente coercitiva muestran una aceptación significativamente mayor de determinadas creencias estereotipadas y tradicionales en torno a los roles de género, la sexualidad y la coerción sexual.
Diet, Energy, and Global Warming
Authors: Eshel Gidon , Martin Pamela A. 
Published: April 2006

Abstract
The energy consumption of animal- and plant-based diets and, more broadly, the range of energetic planetary footprints spanned by reasonable dietary choices are compared. It is demonstrated that the greenhouse gas emissions of various diets vary by as much as the difference between owning an average sedan versus a sport-utility vehicle under typical driving conditions. The authors conclude with a brief review of the safety of plant-based diets, and find no reasons for concern.
The Relationship between Biogenetic Causal Explanations and Social Distance toward People with Mental Disorders: Results from a Population Survey in Germany
Authors: Dietrich Sandra , Matschinger Herbert , Angermeyer Matthias C. 
Published: April 2006

Aims: Several studies have found an inverse relationship between people's readiness to endorse biogenetic causal explanations of mental disorder and their desire for social distance from people with mental disorders. The aim of this study is to examine why this may be the case. Method: In the spring of 2001, a population survey was carried out among German citizens aged 18 years and older, living in private households. A total of 5025 interviews were conducted, reflecting a response rate of 65.1%. At the beginning of the personal, fully structured interview, respondents were presented with a vignette containing a diagnostically unlabelled psychiatric case history, either depicting a case of schizophrenia or major depressive disorder. Using five-point Likert scales, causal attributions as well as perceived dangerousness, fear and the desire for social distance were assessed. Results: The more respondents endorse a brain disease as a cause, the more dangerous they believe the person with schizophrenia or major depression to be. Respondents who perceive the individual in the vignette as being dangerous express a higher degree of fear and a greater preference for social distance from these individuals. As compared with brain disease, the relationships between heredity and perceived dangerousness are less pronounced for both disorders. Conclusions: Our analysis showed that endorsing biogenetic explanations decreases the likelihood of social acceptance of people with schizophrenia and major depression. Rejecting behavioural responses in the form of social distance desired from people with schizophrenia and major depression result from cognitive emotional processes in which biogenetic causal attributions are linked to lack of self-control, unpredictability and dangerousness, which, in turn, are associated with fear of these people.