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Sample records for von willebrand factor

  1. Active Von Willebrand Factor, thrombocytopenia and thrombosis

    NARCIS (Netherlands)

    Hulstein, J.J.J.

    2006-01-01

    Platelets and von Willebrand factor (VWF) are unable to interact in circulation. To induce an interaction, a conversion of VWF to a platelet-binding conformation is required. At higher shear stresses, the first step in thrombus formation is binding of VWF to the subendothelium. This results in expos

  2. On the miscellaneous aspects of von Willebrand factor

    NARCIS (Netherlands)

    Groeneveld, Dafna Jordana

    2015-01-01

    Von Willebrand disease is the most common inherited bleeding disorder and is characterized by reduced plasma von Willebrand factor (VWF) levels or functionally abnormal VWF. VWF is best known for its three classical hemostatic functions: (i) as a carrier protein for coagulation factor VIII, (ii)

  3. Diurnal variation of von Willebrand factor in plasma

    DEFF Research Database (Denmark)

    Timm, Annette; Fahrenkrug, Jan; Jørgensen, Henrik L;

    2014-01-01

    BACKGROUND: Quantitation of von Willebrand factor (VWF) in plasma is a central element in assessing von Willebrand disease (VWD). VWF activity is known to vary, which has partly been ascribed to biological and preanalytical variation. However, a possible diurnal expression of VWF has not been tho...

  4. [Determination of von Willebrand factor multimers in Mexican population].

    Science.gov (United States)

    Hernández-Zamora, Edgar; Zavala-Hernández, Cesar; Viveros-Sandoval, Martha Eva; Ochoa-Rico, Angeles; Martínez-Murillo, Carlos; Reyes-Maldonado, Elba

    2014-01-01

    Antecedentes: la enfermedad de von Willebrand es un padecimiento hereditario en el que la estructura, función y concentración del factor de von Willebrand están alteradas y, en consecuencia, también la interacción plaqueta-factor de von Willebrand-endotelio. En México no hay registros epidemiológicos de la enfermedad, sólo se han efectuado algunos estudios aislados desde el punto de vista clínico y hematológico. Material y métodos: estudio retrospectivo efectuado en 155 mexicanos mestizos, 75 de ellos con diagnóstico presuntivo de enfermedad de von Willebrand, 15 con sospecha de hemofilia A y 65 donadores sanos (testigos). Se realizaron pruebas: básicas de coagulación, especiales y de clasificación: análisis de la composición multimérica. Resultados: 15 pacientes se diagnosticaron con hemofilia A; de los 75 sujetos con sospecha de enfermedad de von Willebrand se diagnosticaron 50 de la manera siguiente: tipo 1 (62%), tipo 2 (22%) [subtipos: 2A (14%), 2B (2%) y 2N (6%)] y tipo 3 (16%). Conclusión: el análisis de los multímeros del factor de von Willebrand es un método que cumple con las características adecuadas para el diagnóstico de la enfermedad de von Willebrand, por lo que es necesario implementar esta metodología para su estudio y mejorar su diagnóstico específico.

  5. Comparison of automated von Willebrand factor activity assays

    DEFF Research Database (Denmark)

    Timm, Annette; Hillarp, Andreas; Philips, Malou

    2015-01-01

    activity/antigen ratios in samples classified as having VWD (activity classification power might interfere with the interpretation......INTRODUCTION: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. Measurement of von Willebrand factor (VWF) activity in plasma is often based on platelet agglutination stimulated by the ristocetin cofactor activity. Novel assays, based on latex beads with recombinant...... glycoprotein Ib instead of platelets, have recently been developed but it is unclear whether these can improve the diagnostic capability for VWD. AIM: To compare four automated VWF activity methods in a mixed population of patients referred for evaluation of bleeding tendency. METHODS: The analytical...

  6. Von Willebrand factor deficiency reduces liver fibrosis in mice

    NARCIS (Netherlands)

    Joshi, Nikita; Kopec, Anna K.; Ray, Jessica L.; Cline-Fedewa, Holly; Groeneveld, Dafna J.; Lisman, Ton; Luyendyk, James P.

    2017-01-01

    Liver diseases are associated with complex changes in the hemostatic system and elevated levels of the platelet adhesive protein Von Willebrand factor (VWF) are reported in patients with acute and chronic liver damage. Although elevated levels of VWF are associated with fibrosis in the general popul

  7. Active von Willebrand factor in thrombotic thrombocytopenic purpura and malaria

    NARCIS (Netherlands)

    Groot, E.

    2009-01-01

    Thrombotic thrombocytopenic purpura (TTP) and malaria are two diseases of distinct origin. TTP is a rare disorder caused by a deficiency of the von Willebrand factor (VWF) cleaving protease ADAMTS13. Malaria is a poverty-related disease caused by protozoan parasites from the genus Plasmodium. TTP an

  8. No evidence for a direct effect of von Willebrand factor's ABH blood group antigens on von Willebrand factor clearance

    NARCIS (Netherlands)

    Groeneveld, D J; van Bekkum, T; Cheung, K L; Dirven, R J; Castaman, G; Reitsma, P H; van Vlijmen, B; Eikenboom, J

    2015-01-01

    BACKGROUND: One of the major determinants of von Willebrand factor (VWF) plasma levels is ABO blood group status, and individuals with blood group O have ~ 25% lower plasma levels. The exact mechanism behind this relationship remains unknown, although effects on clearance have been postulated. OBJEC

  9. Clumping factor A, von Willebrand factor-binding protein and von Willebrand factor anchor Staphylococcus aureus to the vessel wall.

    Science.gov (United States)

    Claes, J; Liesenborghs, L; Peetermans, M; Veloso, T R; Missiakas, D; Schneewind, O; Mancini, S; Entenza, J M; Hoylaerts, M F; Heying, R; Verhamme, P; Vanassche, T

    2017-02-09

    Essentials Staphylococcus aureus (S. aureus) binds to endothelium via von Willebrand factor (VWF). Secreted VWF-binding protein (vWbp) mediates S. aureus adhesion to VWF under shear stress. vWbp interacts with VWF and the Sortase A-dependent surface protein Clumping factor A (ClfA). VWF-vWbp-ClfA anchor S. aureus to vascular endothelium under shear stress.

  10. Diagnosis and classification of von Willebrand disease: a review of the differential utility of various functional von Willebrand factor assays.

    Science.gov (United States)

    Favaloro, Emmanuel J

    2011-10-01

    von Willebrand disease (VWD) is considered to be the most common inherited bleeding disorder. VWD is diagnosed following a clinical and physical review, with personal and familial evidence of (primarily mucocutaneous) bleeding, and confirmed by laboratory testing. The latter typically entails initial plasma testing of factor VIII coagulant, von Willebrand factor (VWF) protein ('antigen') and VWF function which has classically been assessed using the ristocetin cofactor (VWF:RCo) assay. More recent attention has focussed on other functional VWF assays, such as collagen binding and so-called 'VWF activity' assays, as possible replacements to the VWF:RCo, or as supplementary tests of VWF 'function'. Additional laboratory testing can comprise a battery of confirmatory and VWD-type assisting assays, including VWF:multimer and von Willebrand factor VIII binding. This review aims to update knowledge of current VWD diagnostics with a particular emphasis on 'functional' VWF assays.

  11. Screening for von Willebrand disease: contribution of an automated assay for von Willebrand factor activity.

    Science.gov (United States)

    Lasne, D; Dey, C; Dautzenberg, M-D; Cherqaoui, Z; Monge, F; Aouba, A; Torchet, M-F; Geloen, D; Landais, P; Rothschild, C

    2012-05-01

    Measuring von Willebrand factor (VWF) activity is essential to the diagnosis of von Willebrand disease (VWD). The VWF activity is usually assessed based on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging and has high intra- and inter-assay variabilities. The HemosIL VWF activity (VWF:AC) is a fully automated assay, recently proposed as a good alternative to VWF:RCo for VWD diagnosis. This study was undertaken to assess this new method. First, the analytical performance of VWF:AC on an automated coagulo-meter (ACLTop) was determined, and then this new method was compared with VWF:RCo and the platelet function analyzer (PFA100) for 160 patients referred for VWD screening. The VWF:AC achieved acceptable precision with within-run and between-run coefficients of variation ranging from 2.3% to 14.1%, and linearity from 10% to 100%. Despite some marked differences between VWF:AC and VWF:RCo for 10 plasmas tested, their agreement for VWD diagnosis was good. The VWF:AC had sensitivity similar to that of PFA100 (close to 100%), but better specificity (97.7% vs. 66% or 60%, depending on the cartridge used). The good analytical performance, and the sensitivity and specificity of VWF:AC to detect VWF deficiency renders it a suitable method for VWD screening. Our findings support VWF:AC use for the diagnostic work-up of VWD, paying close attention to concomitant clinical signs and bleeding score, as recommended for VWD. © 2011 Blackwell Publishing Ltd.

  12. [Structure and function of the factor VIII/von Willebrand factor complex].

    Science.gov (United States)

    Müller, G

    1990-03-01

    In the blood plasma factor VIII is bound to the von Willebrand factor. The primary structure of the two proteins were clarified by gene clonation. Factor VIII descends from a precursor protein with 2,351 amino acids by splitting of 19 amino acid residues and is activated by partial proteolysis. In the blood coagulation factor VIII acts as co-factor for the activation of factor X by factor IX in the presence of phospholipids and Ca++ within the intrinsic coagulation system. The formation of the von Willebrand factor takes place by splitting of 22 and 741 amino acid residues, respectively, from pre-pro-von Willebrand factor via pro-von Willebrand factor. The subunits of the von Willebrand factor consist od 2,050 amino acid residues. In the blood plasma the von Willebrand factor is existing as a mixture of multimeres. Receptors of the von Willebrand factor on the thrombocytic membrane are the glycoproteins GPIb and GPIIb/GPIIIa, by means of which the adhesion of thrombocytes at the subendoethelium of the vascular wall and the aggregation of thrombocytes are mediated.

  13. Biogenesis of Weibel-Palade bodies in von Willebrand's disease variants with impaired von Willebrand factor intrachain or interchain disulfide bond formation

    NARCIS (Netherlands)

    Wang, Jiong-Wei; Groeneveld, Dafna J; Cosemans, Guy; Dirven, Richard J; Valentijn, Karine M; Voorberg, Jan; Reitsma, Pieter H; Eikenboom, Jeroen

    2012-01-01

    BACKGROUND: Mutations of cysteine residues in von Willebrand factor are known to reduce the storage and secretion of this factor, thus leading to reduced antigen levels. However, one cysteine mutation, p.Cys2773Ser, has been found in patients with type 2A(IID) von Willebrand's disease who have norma

  14. von Willebrand factor binds to the surface of dendritic cells and modulates peptide presentation of factor VIII.

    Science.gov (United States)

    Sorvillo, Nicoletta; Hartholt, Robin B; Bloem, Esther; Sedek, Magdalena; ten Brinke, Anja; van der Zwaan, Carmen; van Alphen, Floris P; Meijer, Alexander B; Voorberg, Jan

    2016-03-01

    It has been proposed that von Willebrand factor might affect factor VIII immunogenicity by reducing factor VIII uptake by antigen presenting cells. Here we investigate the interaction of recombinant von Willebrand factor with immature monocyte-derived dendritic cells using flow cytometry and confocal microscopy. Surprisingly, von Willebrand factor was not internalized by immature dendritic cells, but remained bound to the cell surface. As von Willebrand factor reduces the uptake of factor VIII, we investigated the repertoire of factor VIII presented peptides when in complex with von Willebrand factor. Interestingly, factor VIII-derived peptides were still abundantly presented on major histocompatibility complex class II molecules, even though a reduction of factor VIII uptake by immature dendritic cells was observed. Inspection of peptide profiles from 5 different donors showed that different core factor VIII peptide sequences were presented upon incubation with factor VIII/von Willebrand factor complex when compared to factor VIII alone. No von Willebrand factor peptides were detected when immature dendritic cells were pulsed with different concentrations of von Willebrand factor, confirming lack of von Willebrand factor endocytosis. Several von Willebrand factor derived peptides were recovered when cells were pulsed with von Willebrand factor/factor VIII complex, suggesting that factor VIII promotes endocytosis of small amounts of von Willebrand factor by immature dendritic cells. Taken together, our results establish that von Willebrand factor is poorly internalized by immature dendritic cells. We also show that von Willebrand factor modulates the internalization and presentation of factor VIII-derived peptides on major histocompatibility complex class II.

  15. The effect of exercise on von Willebrand factor and ADAMTS-13 in individuals with type 1 and type 2B von Willebrand disease

    NARCIS (Netherlands)

    Stakiw, J.; Bowman, M.; Hegadorn, C.; Pruss, C.; Notley, C.; Groot, E.; Lenting, P. J.; Rapson, D.; Lillicrap, D.; James, P.

    2008-01-01

    Background: The effect of exercise on von Willebrand factor (VWF) and ADAMTS-13 levels in individuals with von Willebrand disease (VWD) has never been reported. Objectives: The aim was to quantify the effect of a standardized exercise protocol on individuals with type 1 and type 2B VWD. Patients/met

  16. An ELISA for the quantitation of von Willebrand Factor

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Overgaard, Martin; Diederichsen, Axel Cosmus Pyndt;

    2013-01-01

    with and without documented coronary calcification (total n=118). RESULTS AND CONCLUSIONS: The assay detected VWF:OPG complexes in human plasma, while no significant signal was observed when testing solutions containing VWF or recombinant OPG alone. Importantly, the ELISA assay was able to detect in vitro formed...... for measurement of von Willebrand factor-osteoprotegerin complex (VWF:OPG) in human plasma. Furthermore, the significance of VWF:OPG complex as a marker of cardiovascular disease (CVD) was evaluated. PATIENTS/METHODS: A sandwich ELISA for quantification of VWF:OPG was developed using a polyclonal rabbit anti...

  17. Human von Willebrand factor/factor VIII concentrates in the management of pediatric patients with von Willebrand disease/hemophilia A

    OpenAIRE

    Castaman G; Linari S

    2016-01-01

    Giancarlo Castaman, Silvia Linari Department of Oncology, Center for Bleeding Disorders, Careggi University Hospital, Florence, ItalyAbstract: Several plasma-derived intermediate and high-purity concentrates containing von Willebrand factor (VWF) and factor VIII (FVIII) are currently available. The main role of these products in the management of pediatric the population is represented by the replacement therapy in patients with severe or intermediate forms of von Willebrand disease, in whom ...

  18. Factor VIII and von Willebrand factor changes during normal pregnancy and puerperium.

    Science.gov (United States)

    Sánchez-Luceros, Analía; Meschengieser, Susana S; Marchese, Carlos; Votta, Roberto; Casais, Patricia; Woods, Adriana I; Nadal, María V; Salviú, María J; Lazzari, María A

    2003-10-01

    Gestation is a challenge to haemostasis and it is associated with significant haemostatic changes. Several studies have evaluated von Willebrand factor in normal pregnancy, but none considered the personal history of bleeding. We studied a group of healthy non-bleeding women (184 pregnant, 64 puerperium, 37 non-pregnant) to evaluate normal ranges and their relationship to blood group and parity. The von Willebrand factor increased markedly from non-pregnant values up to the end of early puerperium (P < 0.0001), while factor VIII only showed a slight increase. Factor VIII and von Willebrand factor activity remained within the normal range for non-pregnant women. The return to non-pregnant factor levels occurred in late puerperium, later than previously reported. Only factor VIII was significantly lower in the O blood group (P = 0.035). As regards parity, there were no differences in factor VIII, von Willebrand factor antigen and von Willebrand factor ristocetin cofactor between primigravidae and multigravidae for any period studied (P = 0.888, 0.999, and 0.237, respectively). Our results provide reference ranges that may help to design a study in von Willebrand factor disease in pregnancy.

  19. Storage and secretion of naturally occurring von Willebrand factor A domain variants

    NARCIS (Netherlands)

    Groeneveld, Dafna J; Wang, Jiong-Wei; Mourik, Marjon J; Dirven, Richard J; Valentijn, Karine M; Voorberg, Jan; Reitsma, Pieter H; Eikenboom, Jeroen

    2014-01-01

    Von Willebrand disease (VWD) is a bleeding disorder characterized by reduced plasma von Willebrand factor (VWF) levels or functionally abnormal VWF. Low VWF plasma levels in VWD patients are the result of mutations in the VWF gene that lead to decreased synthesis, impaired secretion, increased clear

  20. Flow-induced elongation of von Willebrand factor precedes tension-dependent activation.

    Science.gov (United States)

    Fu, Hongxia; Jiang, Yan; Yang, Darren; Scheiflinger, Friedrich; Wong, Wesley P; Springer, Timothy A

    2017-08-23

    Von Willebrand factor, an ultralarge concatemeric blood protein, must bind to platelet GPIbα during bleeding to mediate hemostasis, but not in the normal circulation to avoid thrombosis. Von Willebrand factor is proposed to be mechanically activated by flow, but the mechanism remains unclear. Using microfluidics with single-molecule imaging, we simultaneously monitored reversible Von Willebrand factor extension and binding to GPIbα under flow. We show that Von Willebrand factor is activated through a two-step conformational transition: first, elongation from compact to linear form, and subsequently, a tension-dependent local transition to a state with high affinity for GPIbα. High-affinity sites develop only in upstream regions of VWF where tension exceeds ~21 pN and depend upon electrostatic interactions. Re-compaction of Von Willebrand factor is accelerated by intramolecular interactions and increases GPIbα dissociation rate. This mechanism enables VWF to be locally activated by hydrodynamic force in hemorrhage and rapidly deactivated downstream, providing a paradigm for hierarchical mechano-regulation of receptor-ligand binding.Von Willebrand factor (VWF) is a blood protein involved in clotting and is proposed to be activated by flow, but the mechanism is unknown. Here the authors show that VWF is first converted from a compact to linear form by flow, and is subsequently activated to bind GPIbα in a tension-dependent manner.

  1. Characterization of a novel mutation in the von Willebrand factor propeptide in a distinct subtype of recessive von Willebrand disease

    DEFF Research Database (Denmark)

    Lanke, Elsa; Kristoffersson, Ann-Charlotte; Philips, Malou

    2008-01-01

    von Willebrand factor (VWF) is a plasma protein that consists of a series of multimers of which the high-molecular-weight VWF multimers are the most potent in platelet adhesion and aggregation. The propeptide of the VWF (VWFpp) is known to be essential in the process of multimer assembly. Genetic......, caused by a 1709G>C transition in exon 14 of the VWF gene coding for the propeptide. Three asymptomatic relatives were found to be heterozygous. In-vitro mutagenesis and expression in COS-7 cells confirmed the detrimental effect of the mutation on VWF multimerization. Our findings show that the C570S...... mutation in the VWFpp abolishes multimerization of VWF. The mutation probably disrupts the normal configuration of the VWFpp, which is essential for correct orientation of the protomers and ultimately multimerization. The mutant amino acid is located in a region that is highly conserved across several...

  2. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    Science.gov (United States)

    Abdelmagid, Nada; Bereczky-Veress, Biborka; Atanur, Santosh; Musilová, Alena; Zídek, Václav; Saba, Laura; Warnecke, Andreas; Khademi, Mohsen; Studahl, Marie; Aurelius, Elisabeth; Hjalmarsson, Anders; Garcia-Diaz, Ana; Denis, Cécile V; Bergström, Tomas; Sköldenberg, Birgit; Kockum, Ingrid; Aitman, Timothy; Hübner, Norbert; Olsson, Tomas; Pravenec, Michal; Diez, Margarita

    2016-01-01

    Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  3. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    Directory of Open Access Journals (Sweden)

    Nada Abdelmagid

    Full Text Available Herpes simplex encephalitis (HSE is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats with the asymptomatic infection of BN (Brown Norway. Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains, displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus named Hse6 towards the end of chromosome 4 (160.89-174Mb containing the Vwf (von Willebrand factor gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism. Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008 after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  4. Evaluation of von Willebrand factor in COPD patients

    Directory of Open Access Journals (Sweden)

    Thiago Prudente Bártholo

    2014-08-01

    Full Text Available OBJECTIVE: To compare the absolute serum von Willebrand factor (vWF levels and relative serum vWF activity in patients with clinically stable COPD, smokers without airway obstruction, and healthy never-smokers. METHODS: The study included 57 subjects, in three groups: COPD (n = 36; smoker (n = 12; and control (n = 9. During the selection phase, all participants underwent chest X-rays, spirometry, and blood testing. Absolute serum vWF levels and relative serum vWF activity were obtained by turbidimetry and ELISA, respectively. The modified Medical Research Council scale (cut-off score = 2 was used in order to classify COPD patients as symptomatic or mildly symptomatic/asymptomatic. RESULTS: Absolute vWF levels were significantly lower in the control group than in the smoker and COPD groups: 989 ± 436 pg/mL vs. 2,220 ± 746 pg/mL (p < 0.001 and 1,865 ± 592 pg/mL (p < 0.01. Relative serum vWF activity was significantly higher in the COPD group than in the smoker group (136.7 ± 46.0% vs. 92.8 ± 34.0%; p < 0.05, as well as being significantly higher in the symptomatic COPD subgroup than in the mildly symptomatic/asymptomatic COPD subgroup (154 ± 48% vs. 119 ± 8%; p < 0.05. In all three groups, there was a negative correlation between FEV1 (% of predicted and relative serum vWF activity (r2 = −0.13; p = 0.009. CONCLUSIONS: Our results suggest that increases in vWF levels and activity contribute to the persistence of systemic inflammation, as well as increasing cardiovascular risk, in COPD patients.

  5. Differential localization of P-selectin and von Willebrand factor during megakaryocyte maturation

    DEFF Research Database (Denmark)

    Zingariello, M; Fabucci, M E; Bosco, D;

    2010-01-01

    An important step in megakaryocyte maturation is the appropriate assembly of at least two distinct subsets of alpha-granules. The mechanism that sorts the alpha-granule components into distinct structures and mediates their release in response to specific stimuli is now emerging. P-selectin and von...... Willebrand factor are two proteins present in the alpha-granules that recognize P-selectin glycoprotein ligand on neutrophils and collagen in the subendothelial matrix. These proteins may play an important role in determining the differential release of the alpha-granule contents in response to external...... stimuli. If P-selectin and von Willebrand factor are localized in the same or different alpha-granules is not known. To clarify this question, we analyzed by immunoelectron microscopy the localization of von Willebrand factor and P-selectin during the maturation of wild-type and Gata1(low) megakaryocytes...

  6. Acquired von Willebrand Syndrome

    Institute of Scientific and Technical Information of China (English)

    郭涛

    2005-01-01

    @@ Acquired von Willebrand syndrome (AvWS) is kind of bleeding disorder with laboratory findings similar to those in congenital yon Willebrand disease (vWD).AvWS doesn's have any personal or family history of bleeding, but is associated with certain diseases or abnormal conditions or drugs. Although AvWS is being stated as a rare disease, it has gained more and more attention during the past years. Not because of the severity of the disease, but it is more common than we thought and most patients don' t have a proper diagnosis.

  7. Structural studies on the von Willebrand factor A1 and A3 domains

    NARCIS (Netherlands)

    Romijn, R.A.P.

    2003-01-01

    Von Willebrand factor (VWF), a multimeric plasma glycoprotein, mediates platelet adhesion to sites of vascular damage. In this proces, the VWF-A3 domain binds to collagen in the vessel wall. This is followed by binding of the VWF-A1 domain to platelet receptor glycoprotein (Gp) Ibalpha. The investig

  8. Binding of von Willebrand factor and plasma proteins to the eggshell of Schistosoma mansoni

    NARCIS (Netherlands)

    Dewalick, Saskia; Hensbergen, Paul J; Bexkens, Michiel L; Grosserichter-Wagener, Christina; Hokke, Cornelis H; Deelder, André M; de Groot, Philip G; Tielens, Aloysius G M; van Hellemond, Jaap J

    2014-01-01

    Schistosoma mansoni eggs have to cross the endothelium and intestinal wall to leave the host and continue the life cycle. Mechanisms involved in this essential step are largely unknown. Here we describe direct binding to the S. mansoni eggshell of von Willebrand factor and other plasma proteins invo

  9. Binding of von Willebrand factor and plasma proteins to the eggshell of Schistosoma mansoni

    NARCIS (Netherlands)

    Dewalick, Saskia; Hensbergen, Paul J; Bexkens, Michiel L; Grosserichter-Wagener, Christina; Hokke, Cornelis H; Deelder, André M; de Groot, Philip G; Tielens, Aloysius G M; van Hellemond, Jaap J

    Schistosoma mansoni eggs have to cross the endothelium and intestinal wall to leave the host and continue the life cycle. Mechanisms involved in this essential step are largely unknown. Here we describe direct binding to the S. mansoni eggshell of von Willebrand factor and other plasma proteins

  10. Determinación de los multímeros del factor von Willebrand en población mexicana

    OpenAIRE

    Edgar Hernández-Zamora; César Zavala-Hernández; Martha Eva Viveros-Sandoval; Ángeles Ochoa-Rico; Carlos Martínez-Murillo; Elba Reyes-Maldonado

    2014-01-01

    Antecedentes: la enfermedad de von Willebrand es un padecimiento hereditario en el que la estructura, función y concentración del factor de von Willebrand están alteradas y, en consecuencia, también la interacción plaqueta-factor de von Willebrand-endotelio. En México no hay registros epidemiológicos de la enfermedad, sólo se han efectuado algunos estudios aislados desde el punto de vista clínico y hematológico. Material y métodos: estudio retrospectivo efectuado en 155 mexicanos mestizos, 75...

  11. Tissue factor: A potent stimulator of Von Willebrand factor synthesis by human umbilical vein endothelial cells

    Science.gov (United States)

    Meiring, Muriel; Allers, W.; Le Roux, E.

    2016-01-01

    Inflammation and dysfunction of endothelial cells are thought to be triggers for the secretion of Von Willebrand factor. The aim of this study was to examine the effects of the inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) and the coagulation factors, tissue factor and thrombin on the release and cleavage potential of ultra-large von Willebrand factor (ULVWF) and its cleavage protease by cultured human umbilical vein endothelial cells (HUVEC). HUVEC were treated with IL-6, IL-8, and TNF-α, tissue factor (TF) and thrombin, and combinations thereof for 24 hours under static conditions. The cells were then exposed to shear stress after which the VWF-propeptide levels and the VWF cleavage protease, ADAMTS13 content were measured. All treatments and their combinations, excluding IL-6, significantly stimulated the secretion of VWF from HUVEC. The VWF secretion from the HUVEC was stimulated most by the combination of TF with TNF-α. Slightly lower levels of ADAMTS13 secretion were found with all treatments. This may explain the thrombogenicity of patients with inflammation where extremely high VWF levels and slightly lower ADAMTS13 levels are present.

  12. An integumentary mucin (FIM-B.1) from Xenopus laevis homologous with von Willebrand factor.

    Science.gov (United States)

    Probst, J C; Gertzen, E M; Hoffmann, W

    1990-07-03

    We present a new protein from X. laevis skin termed "frog integumentary mucin B.1" (FIM-B.1) with a general structure similar to FIM-A.1 (formerly "spasmolysin"). The central region consisting of tandem repeats of 11 amino acid residues is probably a target for extensive O-glycosylation, whereas the C-terminal cysteine-rich domain shows pronounced homology with the C1-C2 domains and the C-terminal end of von Willebrand factor. Furthermore, we describe homology with antistasin, an anticoagulant peptide from a leech. We also discuss some implications concerning the evolutionary origin of von Willebrand factor. In situ hybridization studies revealed the expression of FIM-B.1 exclusively in mucous glands of the skin. This is comparable with FIM-A.1 but is in contrast to all other physiologically active peptides, which are synthesized in granular glands.

  13. Von Willebrand Factor Abnormalities Studied in the Mouse Model: What We Learned about VWF Functions

    OpenAIRE

    Casari, Caterina; Lenting, Peter J.; Christophe, Olivier D.; Denis, Cécile V.

    2013-01-01

    Up until recently, von Willebrand Factor (VWF) structure-function relationships have only been studied through in vitro approaches. A powerful technique known as hydrodynamic gene transfer, which allows transient expression of a transgene by mouse hepatocytes, has led to an important shift in VWF research. Indeed this approach has now enabled us to transiently express a number of VWF mutants in VWF-deficient mice in order to test the relative importance of specific residues in different aspec...

  14. von Willebrand Disease (For Parents)

    Science.gov (United States)

    ... to classify the type of von Willebrand disease platelet function tests, which determine how well the platelets work ... for pain or fever. These drugs interfere with platelet function and can increase the risk of bleeding. It ...

  15. Binding of factor VIII to von willebrand factor is enabled by cleavage of the von Willebrand factor propeptide and enhanced by formation of disulfide-linked multimers.

    Science.gov (United States)

    Bendetowicz, A V; Morris, J A; Wise, R J; Gilbert, G E; Kaufman, R J

    1998-07-15

    von Willebrand factor (vWF) is a multimeric adhesive glycoprotein with one factor VIII binding site/subunit. Prior reports suggest that posttranslational modifications of vWF, including formation of N-terminal intersubunit disulfide bonds and subsequent cleavage of the propeptide, influence availability and/or affinity of factor VIII binding sites. We found that deletion of the vWF propeptide produced a dimeric vWF molecule lacking N-terminal intersubunit disulfide bonds. This molecule bound fluorescein-labeled factor VIII with sixfold lower affinity than multimeric vWF in an equilibrium flow cytometry assay (approximate KDs, 5 nmol/L v 0.9 nmol/L). Coexpression of propeptide-deleted vWF with the vWF propeptide in trans yielded multimeric vWF that displayed increased affinity for factor VIII. Insertion of an alanine residue at the N-terminus of the mature vWF subunit destroyed binding to factor VIII, indicating that the native mature N-terminus is required for factor VIII binding. The requirement for vWF propeptide cleavage was shown by (1) a point mutation of the vWF propeptide cleavage site yielding pro-vWF that was defective in factor VIII binding and (2) correlation between efficiency of intracellular propeptide cleavage and factor VIII binding. Furthermore, in a cell-free system, addition of the propeptide-cleaving enzyme PACE/furin enabled factor VIII binding in parallel with propeptide cleavage. Our results indicate that high-affinity factor VIII binding sites are located on N-terminal disulfide-linked vWF subunits from which the propeptide has been cleaved.

  16. Expression of von Willebrand factor Normandy: An autosomal mutation that mimics hemophilia A

    Energy Technology Data Exchange (ETDEWEB)

    Tuley, E.A.; Worrall, N.K.; Sadler, J.E. (Washington Univ. School of Medicine, St. Louis, MO (United States)); Gaucher, C.; Jorieux, S.; Mazurier, C. (Centre Regional de Transfusion Sanguine, Lille (France))

    1991-07-15

    von Willebrand disease Normandy (vWD Normandy) is a recently described phenotype in which a mutant von Willebrand factor (VWF) appears structurally and functionally normal except that is does not bind to blood coagulation factor VIII. This interaction is required for normal survival of factor VIII in the circulation; consequently, vWD Normandy can present as apparent hemophilia A but with autosomal recessive rather than X chromosome-linked inheritance. AvWF missense mutation, Thr{sup 28} {r arrow} Met, was identified in the propositus in or near the factor VIII binding site. The corresponding mutant recombinant vWF(T28M) formed normal multimers and had normal ristocetin cofactor activity. However, vWF(T28M) exhibited the same defect in factor VIII binding as natural vWF Normandy, confirming that this mutation causes the vWD Normandy phenotype. The distinction between hemophilia A and vWD Normandy is clinically important and should be considered in families affected by apparent mild hemophilia A that fail to show strict X chromosome-linked inheritance and, particularly, in potential female carriers with low factor VIII levels attributed to extreme lyonization.

  17. Conventional rapid latex agglutination in estimation of von Willebrand factor: method revisited and potential clinical applications.

    Science.gov (United States)

    Mahat, Marianor; Abdullah, Wan Zaidah; Hussin, Che Maraina Che

    2014-01-01

    Measurement of von Willebrand factor antigen (VWF : Ag) levels is usually performed in a specialised laboratory which limits its application in routine clinical practice. So far, no commercial rapid test kit is available for VWF : Ag estimation. This paper discusses the technical aspect of latex agglutination method which was established to suit the purpose of estimating von Willebrand factor (VWF) levels in the plasma sample. The latex agglutination test can be performed qualitatively and semiquantitatively. Reproducibility, stability, linearity, limit of detection, interference, and method comparison studies were conducted to evaluate the performance of this test. Semiquantitative latex agglutination test was strongly correlated with the reference immunoturbidimetric assay (Spearman's rho = 0.946, P agglutination test and the reference assay. Using the scoring system for the rapid latex test, no agglutination is with 0% VWF : Ag (control negative), 1+ reaction is equivalent to 150% VWF : Ag (when comparing with immunoturbidimetric assay). The findings from evaluation studies suggest that latex agglutination method is suitable to be used as a rapid test kit for the estimation of VWF : Ag levels in various clinical conditions associated with high levels and low levels of VWF : Ag.

  18. Conventional Rapid Latex Agglutination in Estimation of von Willebrand Factor: Method Revisited and Potential Clinical Applications

    Directory of Open Access Journals (Sweden)

    Marianor Mahat

    2014-01-01

    Full Text Available Measurement of von Willebrand factor antigen (VWF : Ag levels is usually performed in a specialised laboratory which limits its application in routine clinical practice. So far, no commercial rapid test kit is available for VWF : Ag estimation. This paper discusses the technical aspect of latex agglutination method which was established to suit the purpose of estimating von Willebrand factor (VWF levels in the plasma sample. The latex agglutination test can be performed qualitatively and semiquantitatively. Reproducibility, stability, linearity, limit of detection, interference, and method comparison studies were conducted to evaluate the performance of this test. Semiquantitative latex agglutination test was strongly correlated with the reference immunoturbidimetric assay (Spearman’s rho = 0.946, P150% VWF : Ag (when comparing with immunoturbidimetric assay. The findings from evaluation studies suggest that latex agglutination method is suitable to be used as a rapid test kit for the estimation of VWF : Ag levels in various clinical conditions associated with high levels and low levels of VWF : Ag.

  19. Doença de von Willebrand e anestesia Enfermedad de von Willebrand y anestesia Von Willebrand's disease and anesthesia

    Directory of Open Access Journals (Sweden)

    Fabiano Timbó Barbosa

    2007-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A doença de von Willebrand ocorre devido à mutação no cromossomo 12 e é caracterizada por deficiência qualitativa ou quantitativa do fator de von Willebrand. A diversidade de mutações leva ao aparecimento das mais variadas manifestações clínicas possibilitando a divisão dos pacientes em vários tipos e subtipos clínicos. A coagulopatia se manifesta basicamente através da disfunção plaquetária associada à diminuição dos níveis séricos do fator VIII coagulante. O objetivo dessa revisão foi mostrar os cuidados relacionados aos pacientes portadores da doença de von Willebrand durante o período perioperatório. CONTEÚDO: Foram definidas as características da doença de von Willebrand quanto à fisiopatologia, à classificação, ao diagnóstico laboratorial, ao tratamento atual e aos cuidados com o manuseio do paciente no período perioperatório. CONCLUSÕES: A doença de von Willebrand é o distúrbio hemorrágico hereditário mais comum, porém ela é subdiagnosticada pela complexidade da própria doença. A correta classificação do paciente, o uso apropriado da desmopressina e a transfusão do fator de von Willebrand são medidas fundamentais para a realização do procedimento anestésico bem-sucedido.JUSTIFICATIVA Y OBJETIVOS: La enfermedad de von Willebrand ocurre debido a la mutación en el cromosoma 12 y se caracteriza por la deficiencia cualitativa o cuantitativa del factor de von Willebrand. La diversidad de mutaciones conlleva al aparecimiento de las más variadas manifestaciones clínicas posibilitando la división de los pacientes en varios tipos y subtipos clínicos. La coagulopatía se manifiesta básicamente a través de la disfunción plaquetaria asociada con la disminución de los niveles séricos del factor VIII coagulante. El objetivo de esa revisión fue mostrar los cuidados relacionados con las pacientes portadoras de la enfermedad de von Willebrand durante el per

  20. Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage

    Directory of Open Access Journals (Sweden)

    Arunima Ghosh

    2012-01-01

    Full Text Available von Willebrand disease (VWD is the most common inherited human bleeding disorder and is caused by quantitative or qualitative defects in von Willebrand factor (VWF. VWF is a secreted glycoprotein that circulates as large multimers. While reduced VWF is associated with bleeding, elevations in overall level or multimer size are implicated in thrombosis. The zebrafish is a powerful genetic model in which the hemostatic system is well conserved with mammals. The ability of this organism to generate thousands of offspring and its optical transparency make it unique and complementary to mammalian models of hemostasis. Previously, partial clones of zebrafish vwf have been identified, and some functional conservation has been demonstrated. In this paper we clone the complete zebrafish vwf cDNA and show that there is conservation of domain structure. Recombinant zebrafish Vwf forms large multimers and pseudo-Weibel-Palade bodies (WPBs in cell culture. Larval expression is in the pharyngeal arches, yolk sac, and intestinal epithelium. These results provide a foundation for continued study of zebrafish Vwf that may further our understanding of the mechanisms of VWD.

  1. Collagen-bound von Willebrand factor has reduced affinity for factor VIII.

    Science.gov (United States)

    Bendetowicz, A V; Wise, R J; Gilbert, G E

    1999-04-30

    von Willebrand factor (vWf) is a multimeric adhesive glycoprotein that serves as a carrier for factor VIII in plasma. Although each vWf subunit displays a high affinity binding site for factor VIII in vitro, in plasma, only 2% of the vWf sites for factor VIII are occupied. We investigated whether interaction of plasma proteins with vWf or adhesion of vWf to collagen may alter the affinity or availability of factor VIII-binding sites on vWf. When vWf was immobilized on agarose-linked monoclonal antibody, factor VIII bound to vWf with high affinity, and neither the affinity nor binding site availability was influenced by the presence of 50% plasma. Therefore, plasma proteins do not alter the affinity or availability of factor VIII-binding sites. In contrast, when vWf was immobilized on agarose-linked collagen, its affinity for factor VIII was reduced 4-fold, with KD increasing from 0.9 to 3.8 nM. However, one factor VIII-binding site remained available on each vWf subunit. A comparable reduction in affinity for factor VIII was observed when vWf was a constituent of the subendothelial cell matrix and when it was bound to purified type VI collagen. In parallel with the decreased affinity for factor VIII, collagen-bound vWf displayed a 6-fold lower affinity for monoclonal antibody W5-6A, with an epitope composed of residues 78-96 within the factor VIII-binding motif of vWf. We conclude that collagen induces a conformational change within the factor VIII-binding motif of vWf that lowers the affinity for factor VIII.

  2. Polymorphisms in von Willebrand factor gene promoter influence the glucocorticoid-induced increase in von Willebrand factor: the lesson learned from Cushing syndrome.

    Science.gov (United States)

    Casonato, Alessandra; Daidone, Viviana; Sartorello, Francesca; Albiger, Nora; Romualdi, Chiara; Mantero, Franco; Pagnan, Antonio; Scaroni, Carla

    2008-01-01

    Cushing syndrome (CS) features high-glucocorticoid secretion and an associated hypercoagulable state often involving an increase in von Willebrand factor (VWF). To identify any influence of VWF promoter on glucocorticoid haemostatic effects, four polymorphic positions (-3267, -2708, -2659 and -2525) segregating as haplotypes 1 (GCAG) or 2 (CTGA) were analysed in 50 CS patients with high VWF (group I) and normal VWF (group II) levels, divided by ABO group. Genotype distribution differed significantly between the two groups: in group I, 25.8% had genotype 1/1, 22.6% had 2/2 and 38.7% had 1/2; in group II, 0% had genotype 1/1, 57.9% had 2/2 and 31.6% had 1/2 (P = 0.03). Patients' genotypes also differed from those of controls (P = 0.003 for group I, P = 0.03 for group II). Haplotype 1 was prevalent in group I, haplotype 2 in group II (P = 0.002), both with frequencies differing from controls (P < 0.001 and P = 0.009). By odds ratio analysis, genotype 1/1 carried a 12 times greater risk of high-VWF levels than genotype 2/2, and haplotype 1 carried a five times greater risk than haplotype 2. Our findings suggest that VWF promoter haplotypes influence the corticosteroid-mediated increase in VWF.

  3. Microsatellite (GT)(n) repeats and SNPs in the von Willebrand factor gene promoter do not influence circulating von Willebrand factor levels under normal conditions.

    Science.gov (United States)

    Daidone, Viviana; Cattini, Maria Grazia; Pontara, Elena; Sartorello, Francesca; Gallinaro, Lisa; Marotti, Alberto; Scaroni, Carla; Pagnan, Antonio; Casonato, Alessandra

    2009-02-01

    Von Willebrand factor (VWF) levels vary considerably in normal individuals, influenced by inherited and acquired modulators. ABO blood group is the major inherited determinant of VWF levels, but a role has also been attributed to the VWF gene promoter, haplotype 1 (-3268G/-2709C/-2661A/-2527G) being associated with higher VWF levels than haplotype 2 (-3268C/-2709T/-2661G/-2527A), and the polymorphic locus (GT)(n) modulating the shear stress-induced activation of the VWF promoter. We characterized the (GT)(n) of the VWF promoter in 394 healthy individuals and assessed whether its variable length influenced VWF levels in normal conditions. (GT)(n) proved highly polymorphic, with alleles from 15 to 24 repeats long. (GT)(21) and (GT)(19) were the most common variants (37.4% and 34.4%, respectively). Short GT repeats (15-19) segregated mainly with haplotype 1, long GT repeats (20-24) with haplotype 2 (p < 0.0001). The number of GT repeats did not correlate with VWF levels, nor did such levels correlate with haplotypes 1 and 2, considered alone or in association with the (GT)(n) locus. We conclude that (GT)(n) and -3268/-2709/-2661/-2527 loci are in strong linkage disequilibrium. This polymorphic region of the VWF promoter does not affect VWF levels under normal conditions, though it might represent an environmentally activable VWF regulation site.

  4. von Willebrand disease and aging : an evolving phenotype

    NARCIS (Netherlands)

    Sanders, Y. V.; Giezenaar, M. A.; Laros-van Gorkom, B. A. P.; Meijer, K.; van der Bom, J. G.; Cnossen, M. H.; Nijziel, M. R.; Ypma, P. F.; Fijnvandraat, K.; Eikenboom, J.; Mauser-Bunschoten, E. P.; Leebeek, F. W. G.

    2014-01-01

    Background: Because the number of elderly von Willebrand disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant. Objectives: To assess age-related changes in von Willebrand factor (VWF) and factor VIII (FVIII) levels and to compare age-related diff

  5. Interference from lupus anticoagulant on von Willebrand factor measurement in splenic marginal zone lymphoma

    DEFF Research Database (Denmark)

    Vinholt, Pernille J; Nybo, Mads

    2015-01-01

    We present a case concerning a patient with splenic marginal zone lymphoma (SMZL) and isolated prolonged activated partial thromboplastin time (aPTT) caused by lupus anticoagulant. Von Willebrand factor (VWF) activity and antigen were immeasurable by latex particle immunoturbidimetric assays......, and several coagulation factor levels were decreased. However, VWF activity and antigen were normal when analyzed by other methods. Also, coagulation factor levels were normal if an aPTT reagent with low lupus anticoagulant sensitivity or a chromogenic method was applied. Altogether, the initial findings were...... because of lupus anticoagulant interference and in fact, the patient had normal VWF activity and coagulation status. Interference of lupus anticoagulant in clot-based assays is well known but has not previously been described in VWF assays. This is furthermore the first report in which lupus anticoagulant...

  6. von Willebrand factor A1 domain can adequately substitute for A3 domain in recruitment of flowing platelets to collagen

    NARCIS (Netherlands)

    Bonnefoy, A.; Romijn, R. A.; Vandervoort, P. A. H.; Van Rompaey, I.; Vermylen, J.; Hoylaerts, M. F.

    2006-01-01

    Background: Binding of von Willebrand factor (VWF) to platelet GPIb alpha and to collagen is attributed to VWF A1 and A3 domains, respectively. Objectives: Using VWF, VWF lacking A1 (Delta A1-VWF) or A3 (Delta A3-VWF) and VWF with defective A3 (H1786A-VWF), in combination with recombinant A1 (residu

  7. Implications for collagen I chain registry from the structure of the collagen von Willebrand factor A3 domain complex

    NARCIS (Netherlands)

    Brondijk, T.H.C.; Bihan, D.; Farndale, R.W.; Huizinga, E.G.

    2012-01-01

    Fibrillar collagens, the most abundant proteins in the vertebrate body, are involved in a plethora of biological interactions. Plasma protein von Willebrand factor (VWF) mediates adhesion of blood platelets to fibrillar collagen types I, II, and III, which is essential for normal haemostasis. High a

  8. Von Willebrand factor in patients on mechanical circulatory support – a double-edged sword between bleeding and thrombosis

    Science.gov (United States)

    Kaczmarski, Jacek; Pacholewicz, Jerzy; Zakliczynski, Michal; Gasior, Mariusz; Zembala, Marian

    2015-01-01

    Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short- and long-term management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2- to 3-year survival in carefully selected patients is much better than with medical therapy. However, MCS therapy is hampered by sometimes life-threatening complications including bleeding and device thrombosis. Von Willebrand factor (vWF) has two major functions in haemostasis. First, it plays a crucial role in platelet-subendothelium adhesion and platelet-platelet interactions (aggregation). Second, it is the carrier of factor VIII (FVIII) in plasma. Von Willebrand factor prolongs FVIII half-time by protecting it from proteolytic degradation. It delivers FVIII to the site of vascular injury thus enhancing haemostatic process. On one hand, high plasma levels of vWF have been associated with an increased risk of thrombosis. On the other, defects or deficiencies of vWF underlie the inherited von Willebrand disease or acquired von Willebrand syndrome. Here we review the pathophysiology of thrombosis and bleeding associated with vWF. PMID:26702279

  9. Von Willebrand factor in patients on mechanical circulatory support - a double-edged sword between bleeding and thrombosis.

    Science.gov (United States)

    Hudzik, Bartosz; Kaczmarski, Jacek; Pacholewicz, Jerzy; Zakliczynski, Michal; Gasior, Mariusz; Zembala, Marian

    2015-09-01

    Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short- and long-term management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2- to 3-year survival in carefully selected patients is much better than with medical therapy. However, MCS therapy is hampered by sometimes life-threatening complications including bleeding and device thrombosis. Von Willebrand factor (vWF) has two major functions in haemostasis. First, it plays a crucial role in platelet-subendothelium adhesion and platelet-platelet interactions (aggregation). Second, it is the carrier of factor VIII (FVIII) in plasma. Von Willebrand factor prolongs FVIII half-time by protecting it from proteolytic degradation. It delivers FVIII to the site of vascular injury thus enhancing haemostatic process. On one hand, high plasma levels of vWF have been associated with an increased risk of thrombosis. On the other, defects or deficiencies of vWF underlie the inherited von Willebrand disease or acquired von Willebrand syndrome. Here we review the pathophysiology of thrombosis and bleeding associated with vWF.

  10. Severe dengue is associated with consumption of von Willebrand factor and its cleaving enzyme ADAMTS-13.

    Directory of Open Access Journals (Sweden)

    Kis Djamiatun

    Full Text Available BACKGROUND: Thrombocytopenia, bleeding and plasma leakage are cardinal features of severe dengue. Endothelial cell activation with exocytosis of Weibel-Palade bodies (WPBs may play an etiological role in this condition. METHODS AND PRINCIPAL FINDINGS: In a cohort of 73 Indonesian children with dengue hemorrhagic fever (DHF, of which 30 with dengue shock syndrome (DSS, we measured plasma levels of the WPB constituents von Willebrand factor antigen (VWF:Ag, VWF propeptide and osteoprotegerin (OPG, together with activity levels of the VWF-cleaving enzyme ADAMTS-13 and the amount of VWF in a platelet binding conformation (VWF activation factor. Compared with healthy controls (n = 17, children with DHF/DSS had significantly higher levels of VWF:Ag, VWF propeptide and OPG and decreased ADAMTS-13 activity. The VWF activation factor was also significantly higher in DHF/DSS and highest in children who died. There were significant differences in the kinetics of the various WPB constituents: VWF propeptide and OPG levels decreased toward discharge, while VWF:Ag levels were lower than expected at enrollment with plasma levels increasing toward discharge. Moreover, VWF propeptide levels correlated better with markers of disease severity (platelet count, liver enzymes, serum albumin and pleural effusion index than corresponding VWF levels. Together, these findings suggest that there is consumption of VWF in DHF/DSS. In 4 out of 15 selected children with low ADAMTS-13 levels on admission, we found a remarkable reduction in the large and intermediate VWF multimers in the discharge blood samples, consistent with an acquired von Willebrand disease. CONCLUSION: These findings suggest that severe dengue is associated with exocytosis of WPBs with increased circulating levels of VWF:Ag, VWF propeptide and OPG. High circulating levels of VWF in its active conformation, together with low ADAMTS-13 activity levels, are likely to contribute to the thrombocytopenia

  11. Evaluation of von Willebrand factor-cleaving protease activity in patients with thrombotic thrombocytopenic purpura

    Institute of Scientific and Technical Information of China (English)

    高维强; 苏健; 白霞; 王兆钺; 阮长耿

    2004-01-01

    Background Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy. In this study we investigated the von Willebrand factor-cleaving protease (vWF-cp) activity deficiency in patients with TTP.Methods The plasma or serum vWF-cp activity was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) by detecting the residual collagen binding activity (R-CBA) of von Willebrand factor (vWF) before and after digestion by vWF-cp. Multimers of vWF in plasma of patients with TTP were also analyzed by SDS-agarose electrophoresis. Moreover, the serum vWF-cp activities were compared between the patients with TTP and those with tumors.Results The coefficient of variation for intra-batch and inter-batch of the assay were 3.60% and 8.35%. The plasma and serum vWF-cp activity in healthy individuals were (78.79±9.17)% (n=30) and (79.47±10.78)% (n=53), respectively, while the plasma vWF-cp activity in 5 patients with TTP was markedly decreased [(21.83±19.98)%, P<0.001]. The unusually large vWF multimers were observed in two plasma samples of the patients with TTP. Although the vWF-cp activities in patients with benign and malignant tumors were also decreased (P<0.03 and P<0.001, respectively), they were relatively high in comparison with that of TTP patients (P<0.001).Conclusion Measurement of the vWF-cp activity using R-CBA is a simple and rapid method for diagnosing TTP. The vWF-cp activity in patients with TTP was markedly lower than those of patients with tumors.

  12. Leukocyte telomere length is inversely correlated with plasma Von Willebrand factor

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob V B; Nzietchueng, Rosine; Kimura, Masayuki;

    2010-01-01

    INTRODUCTION: Leukocyte telomere length (LTL) is short, while the plasma level of Von Willebrand (VWF) is high in persons with atherosclerosis. Moreover, both short LTLs and high VWF levels are observed in individuals who display risks for atherosclerosis, including hypertension, obesity, insulin...

  13. ADAMTS13 content in plasma-derived factor VIII/von Willebrand factor concentrates.

    Science.gov (United States)

    Peyvandi, Flora; Mannucci, Pier M; Valsecchi, Carla; Pontiggia, Silvia; Farina, Claudio; Retzios, Anastassios D

    2013-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a microangiopathy syndrome caused by a congenital or acquired deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor (VWF) and thus prevents the formation of platelet-rich thrombi in the microcirculation. TTP can be fatal if not appropriately and timely treated with the infusion of fresh frozen plasma (FFP) or exchange plasmapheresis, that reverse the process of microangiopathy by removing anti-ADAMTS13 autoantibodies and replacing functional ADAMTS13. The treatment of TTP with FFP is not free from risks and must be administered in hospitals or clinics, owing to the substantial amount of plasma volume infused or exchanged and the frequent need of catheter application. Moreover, most FFPs are not subjected to treatments to remove or inactivate blood-borne infectious agents. A number of recent reports indicate that certain plasma-derived VWF-factor VIII (FVIII) concentrates are clinically effective in the treatment of congenital TTP. In this study, we measured ADAMTS13 levels in various plasma-derived VWF-FVIII concentrates, showing that Koate(®) -DVI (Grifols), contained relatively high amounts of ADAMTS13 and that Alphanate(®) (Grifols) was the closest other product in terms of protease content. Koate(®) -DVI contains, on average (five lots tested), 0.091 ± 0.007 Units of ADAMTS13 activity per IU of FVIII. On the basis of this analysis and other reports of VWF-FVIII concentrate utilization in congenital TTP, potential dosing, and future clinical developments are discussed.

  14. The impact of von Willebrand factor on factor VIII memory immune responses.

    Science.gov (United States)

    Chen, Juan; Schroeder, Jocelyn A; Luo, Xiaofeng; Shi, Qizhen

    2017-08-22

    Immune tolerance induction (ITI) with aggressive infusion of factor VIII (FVIII) is the current strategy used to eradicate FVIII inhibitors and restore normal FVIII pharmacokinetics in inhibitor patients. Whether the use of FVIII products containing von Willebrand factor (VWF) will affect the efficacy of ITI is still controversial. In this study, we explored the impact of VWF on FVIII memory immune responses in hemophilia A (HA) mice. A T-cell proliferation assay and cytokine profile analysis were used to study FVIII-primed CD4(+) T cells. When CD4(+) T cells from primed FVIII(null) mice were restimulated with recombinant human FVIII (rhF8) plus recombinant human VWF (rhVWF) in vitro, the percentages of daughter CD4(+) T cells were significantly decreased compared with the groups cultured with rhF8 only. Levels of interferon-γ and interleukin 10 were significantly lower in the rhF8 plus rhVWF groups than in the rhF8 groups. When memory B-cell pools from primed FVIII(null) mice were cultured with rhF8 with or without rhVWF to induce differentiation of memory B cells into antibody-secreting cells (ASCs), the number of ASCs was significantly lower in the rhF8 plus VWF group than in the rhF8 group. When memory B-cell pools were transferred into NSGF8KO mice followed by rhF8 immunization with or without rhVWF, the titers of anti-F8 inhibitors and total immunoglobulin G were significantly higher in the rhF8 group than in the rhF8 plus rhVWF group, with an average difference of 2.23- and 2.04-fold. Together, our data demonstrate that VWF attenuates FVIII memory immune responses in HA mice.

  15. P-selectin can promote thrombus propagation independently of both von Willebrand factor and thrombospondin-1 in mice.

    Science.gov (United States)

    Prakash, P; Nayak, M K; Chauhan, A K

    2017-02-01

    Essentials The main receptor for platelet glycoprotein (GP) Ibα is von Willebrand factor (VWF). P-selectin and thrombospondin-1 (TSP1) have been suggested as counter receptors for GPIbα. In a laser injury model, P-selectin promotes thrombus propagation independently of VWF and TSP1. In a laser injury model, thrombus persists in interleukin-4 receptor α/GPIbα-transgenic mice.

  16. PROTEOLYTIC PROCESSING OF VON WILLEBRAND FACTOR BY ADAMTS13 AND LEUKOCYTE PROTEASES

    Directory of Open Access Journals (Sweden)

    Stefano Lancellotti

    2013-09-01

    Full Text Available ADAMTS13 is a 190 kDa zinc protease encoded by a gene located on chromosome 9q34.   This protease specifically hydrolyzes von Willebrand factor (VWF multimers, thus causing VWF size reduction. ADAMTS13 belongs to the A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS family, involved in proteolytic processing of many matrix proteins. ADAMTS13 consists of numerous domains including a metalloprotease domain, a disintegrin domain, several thrombospondin type 1 (TSP1 repeats, a cysteine-rich domain, a spacer domain and 2 CUB (Complement c1r/c1s, sea Urchin epidermal growth factor, and Bone morphogenetic protein domains. ADAMTS13 cleaves a single peptide bond (Tyr1605-Met1606 in the central A2 domain of the VWF molecule. This proteolytic cleavage is essential to reduce the size of ultra-large VWF polymers, which, when exposed to high shear stress in the microcirculation, are prone to form with platelets clumps, which cause severe syndromes called thrombotic microangiopathies (TMAs. In this review, we a discuss the current knowledge of structure-function aspects of ADAMTS13 and its involvement in the pathogenesis of TMAs, b address the recent findings concerning proteolytic processing of VWF multimers by different proteases, such as the leukocyte-derived serine and metallo-proteases and c indicate the direction of future investigations

  17. The structure of the TFIIH p34 subunit reveals a von Willebrand factor A like fold.

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    Dominik R Schmitt

    Full Text Available RNA polymerase II dependent transcription and nucleotide excision repair are mediated by a multifaceted interplay of subunits within the general transcription factor II H (TFIIH. A better understanding of the molecular structure of TFIIH is the key to unravel the mechanism of action of this versatile protein complex within these vital cellular processes. The importance of this complex becomes further evident in the context of severe diseases like xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy, that arise from single point mutations in TFIIH subunits. Here we describe the structure of the p34 subunit of the TFIIH complex from the eukaryotic thermophilic fungus Chaetomium thermophilum. The structure revealed that p34 contains a von Willebrand Factor A (vWA like domain, a fold which is generally known to be involved in protein-protein interactions. Within TFIIH p34 strongly interacts with p44, a positive regulator of the helicase XPD. Putative protein-protein interfaces are analyzed and possible binding sites for the p34-p44 interaction suggested.

  18. The use of recombinant-activated factor VII in von Willebrand disease: a case series.

    Science.gov (United States)

    von Depka, Mario; Hassan, Murtada; Blatnŷ, Jan; Smejkal, Petr; Vdovin, Vladimir

    2006-06-01

    Spontaneous and surgery-associated bleeding in patients with von Willebrand disease (vWD) cannot always be controlled with desmopressin or replacement therapy. This paper presents results on the use of recombinant-activated factor VII (rFVIIa) in patients with vWD included in the internet registry Haemostasis.com. Twenty-eight reports on the use of rFVIIa in vWD were identified from the database and included in this analysis. The bleeding episodes were classified as mild (n = 7), moderate (n = 16), or severe (n = 2), and were unspecified in three cases. The median dose of rFVIIa administered was 94 microg/kg body weight (40-127.3 microg/kg). Bleeding stopped in 23 of 27 evaluable patients (85%) and markedly decreased in three patients; the total response rate was 96% (26/27 patients). Response did not correlate with the type of vWD, the site or severity of the initial bleed, or the rFVIIa dose. Other replacement therapies were infrequently used, and their use was similar in the 24 h before and after rFVIIa administration. Eighteen patients also received antifibrinolytic treatment, but its impact on response was not recorded. Only one adverse event (mild fever) was observed. These cases suggest a role for rFVIIa as a safe and effective therapy for vWD.

  19. von Willebrand Factor and Oxidative Stress Parameters in Acute Coronary Syndromes

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    Zoran Koprivica

    2011-01-01

    Full Text Available Considering the role of von Willebrand factor (vWf in hemostasis, and the role of oxidative stress in the development of endothelial dysfunction and atherosclerotic disease, the aim of our study was to investigate the relationship between vWf, parameters of oxidative stress and different types of acute coronary syndromes (ACS. Levels of vWf activity (vWfAct, vWf antigen (vWfAg, nitric oxide (estimated through nitrites–NO2 −, superoxide anion radical (O2 −, hydrogen peroxide (H2O2, index of lipid peroxidation (estimated through thiobarbituric acid reactive substances–TBARS, superoxide dismutase (SOD and catalase (CAT activity of 115 patients were compared with those of 40 healthy controls. ACS patients had significantly higher vWfAct and vWfAg levels, as well as TBARS levels, while their levels of NO2 −, H2O2, SOD and CAT activities were lower than controls'. vWfAg showed high specificity and sensitivity as a test to reveal healthy or diseased subjects. Multivariant logistic regression marked only vWfAg and TBARS as parameters that were under independent effect of ACS type. The results of our study support the implementation of vWf in clinical rutine and into therapeutic targets, and suggest that ACS patients are in need of antioxidant supplementation to improve their impaired antioxidant defence.

  20. Von Willebrand factor and oxidative stress parameters in acute coronary syndromes.

    Science.gov (United States)

    Koprivica, Zoran; Djordjevic, Dusica; Vuletic, Milena; Zivkovic, Vladimir; Barudzic, Nevena; Andjelkovic, Nebojsa; Djuric, Dragan; Iric-Cupic, Violeta; Krkeljic, Jelena; Jakovljevic, Vladimir

    2011-01-01

    Considering the role of von Willebrand factor (vWf) in hemostasis, and the role of oxidative stress in the development of endothelial dysfunction and atherosclerotic disease, the aim of our study was to investigate the relationship between vWf, parameters of oxidative stress and different types of acute coronary syndromes (ACS). Levels of vWf activity (vWfAct), vWf antigen (vWfAg), nitric oxide (estimated through nitrites-NO(2)-), superoxide anion radical (O(2)-), hydrogen peroxide (H2O2), index of lipid peroxidation (estimated through thiobarbituric acid reactive substances-TBARS), superoxide dismutase (SOD) and catalase (CAT) activity of 115 patients were compared with those of 40 healthy controls. ACS patients had significantly higher vWfAct and vWfAg levels, as well as TBARS levels, while their levels of NO(2)-, H2O2, SOD and CAT activities were lower than controls'. vWfAg showed high specificity and sensitivity as a test to reveal healthy or diseased subjects. Multivariant logistic regression marked only vWfAg and TBARS as parameters that were under independent effect of ACS type. The results of our study support the implementation of vWf in clinical rutine and into therapeutic targets, and suggest that ACS patients are in need of antioxidant supplementation to improve their impaired antioxidant defence.

  1. Von Willebrand factor inhibits mature smooth muscle gene expression through impairment of Notch signaling.

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    He Meng

    Full Text Available Von Willebrand factor (vWF, a hemostatic protein normally synthesized and stored by endothelial cells and platelets, has been localized beyond the endothelium in vascular disease states. Previous studies have implicated potential non-hemostatic functions of vWF, but signaling mechanisms underlying its effects are currently undefined. We present evidence that vWF breaches the endothelium and is expressed in a transmural distribution pattern in cerebral small vessel disease (SVD. To determine the potential molecular consequences of vWF permeation into the vessel wall, we also tested whether vWF impairs Notch regulation of key smooth muscle marker genes. In a co-culture system using Notch ligand expressing cells to stimulate Notch in A7R5 cells, vWF strongly inhibited both the Notch pathway and the activation of mature smooth muscle gene promoters. Similar repressive effects were observed in primary human cerebral vascular smooth muscle cells. Expression of the intracellular domain of NOTCH3 allowed cells to bypass the inhibitory effects of vWF. Moreover, vWF forms molecular complexes with all four mammalian Notch ectodomains, suggesting a novel function of vWF as an extracellular inhibitor of Notch signaling. In sum, these studies demonstrate vWF in the vessel wall as a common feature of cerebral SVD; furthermore, we provide a plausible mechanism by which non-hemostatic vWF may play a novel role in the promotion of vascular disease.

  2. von Willebrand factor antigen levels in plasma of patients with malignant breast disease

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    L.M. Röhsig

    2001-09-01

    Full Text Available von Willebrand factor (vWF is a protein that mediates platelet adherence to the subendothelium during primary hemostasis. High plasma vWF concentrations have been reported in patients with various types of cancer, such as head and neck, laryngeal and prostatic cancer, probably representing an acute phase reactant. In the present study we determined the plasma levels of vWF antigen (vWF:Ag by quantitative immunoelectrophoresis in 128 female patients with breast cancer as well as in 47 women with benign breast disease and in 27 healthy female controls. The levels of vWF:Ag were 170.7 ± 78 U/dl in patients with cancer, 148.4 ± 59 U/dl in patients with benign disease and 130.6 ± 45 U/dl in controls (P<0.005. We also detected a significant increase in the levels of vWF:Ag (P<0.0001 in patients with advanced stages of the disease (stage IV = 263.3 ± 113 U/dl, stage IIIB = 194.0 ± 44 U/dl as compared to those with earlier stages of the disease (stage I = 155.3 ± 65 U/dl, stage IIA = 146.9 ± 75 U/dl. In conclusion, vWF levels were increased in plasma of patients with malignant breast disease, and these levels correlated with tumor progression.

  3. Actomyosin II contractility expels von Willebrand factor from Weibel-Palade bodies during exocytosis.

    Science.gov (United States)

    Nightingale, Thomas D; White, Ian J; Doyle, Emily L; Turmaine, Mark; Harrison-Lavoie, Kimberly J; Webb, Kathleen F; Cramer, Louise P; Cutler, Daniel F

    2011-08-22

    The study of actin in regulated exocytosis has a long history with many different results in numerous systems. A major limitation on identifying precise mechanisms has been the paucity of experimental systems in which actin function has been directly assessed alongside granule content release at distinct steps of exocytosis of a single secretory organelle with sufficient spatiotemporal resolution. Using dual-color confocal microscopy and correlative electron microscopy in human endothelial cells, we visually distinguished two sequential steps of secretagogue-stimulated exocytosis: fusion of individual secretory granules (Weibel-Palade bodies [WPBs]) and subsequent expulsion of von Willebrand factor (VWF) content. Based on our observations, we conclude that for fusion, WPBs are released from cellular sites of actin anchorage. However, once fused, a dynamic ring of actin filaments and myosin II forms around the granule, and actomyosin II contractility squeezes VWF content out into the extracellular environment. This study therefore demonstrates how discrete actin cytoskeleton functions within a single cellular system explain actin filament-based prevention and promotion of specific exocytic steps during regulated secretion.

  4. Zyxin regulates endothelial von Willebrand factor secretion by reorganizing actin filaments around exocytic granules

    Science.gov (United States)

    Han, Xiaofan; Li, Pin; Yang, Zhenghao; Huang, Xiaoshuai; Wei, Guoqin; Sun, Yujie; Kang, Xuya; Hu, Xueting; Deng, Qiuping; Chen, Liangyi; He, Aibin; Huo, Yingqing; Li, Dong; Betzig, Eric; Luo, Jincai

    2017-01-01

    Endothelial exocytosis of Weibel–Palade body (WPB) is one of the first lines of defence against vascular injury. However, the mechanisms that control WPB exocytosis in the final stages (including the docking, priming and fusion of granules) are poorly understood. Here we show that the focal adhesion protein zyxin is crucial in this process. Zyxin downregulation inhibits the secretion of von Willebrand factor (VWF), the most abundant cargo in WPBs, from human primary endothelial cells (ECs) induced by cAMP agonists. Zyxin-deficient mice exhibit impaired epinephrine-stimulated VWF release, prolonged bleeding time and thrombosis, largely due to defective endothelial secretion of VWF. Using live-cell super-resolution microscopy, we visualize previously unappreciated reorganization of pre-existing actin filaments around WPBs before fusion, dependent on zyxin and an interaction with the actin crosslinker α-actinin. Our findings identify zyxin as a physiological regulator of endothelial exocytosis through reorganizing local actin network in the final stage of exocytosis. PMID:28256511

  5. Expression of a structurally constrained von Willebrand factor variant triggers acute thrombotic thrombocytopenic purpura in mice.

    Science.gov (United States)

    Morioka, Yoko; Casari, Caterina; Wohner, Nikolett; Cho, Sungyun; Kurata, Sachiko; Kitano, Ayumi; Christophe, Olivier D; Lenting, Peter J; Li, Renhao; Denis, Cécile V; Prévost, Nicolas

    2014-05-22

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that presents with thrombocytopenia, disseminated thrombosis, hemolytic anemia, and organ dysfunction. The etiology of TTP has revealed that patients share a deficiency in plasma protease a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), the enzyme responsible for cleaving ultra-large von Willebrand factor (VWF) multimers into nonthrombogenic fragments. Therefore, existing TTP mouse models were developed by targeted disruption of the ADAMTS13 gene. ADAMTS13(-/-) mice are mostly asymptomatic in the absence of a trigger, as redundant proteases appear to take on VWF processing. As an alternative approach to creating one such model, we devised a strategy based on the expression of a cleavage-resistant VWF mutant in mice. The creation of a disulfide bond within the A2 domain of VWF was found to render VWF multimers resistant to proteolysis by plasma proteases under flow. Furthermore, mice expressing the murine VWF/p.S1494C-p.A1534C mutant present with symptoms characteristics of acute TTP such as thrombocytopenia, red cell shredding, accumulation of VWF-rich thrombi in the microvasculature, and advanced TTP symptoms such as renal dysfunction and splenomegaly. Because this model appears to faithfully emulate the pathophysiology of TTP, it should prove most useful in the study of microangiopathic diseases and their treatment. © 2014 by The American Society of Hematology.

  6. Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Soares, R.P.S. [Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, SP (Brazil); Bydlowski, S.P.; Nascimento, N.M. [Laboratório de Investigação Médica-31, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Thomaz, A.M.; Bastos, E.N.M.; Lopes, A.A. [Faculdade de Medicina, Instituto do Coração, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-04-05

    Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

  7. Effects of increased von Willebrand factor levels on primary hemostasis in thrombocytopenic patients with liver cirrhosis.

    Science.gov (United States)

    Wannhoff, Andreas; Müller, Oliver J; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A; Gotthardt, Daniel N

    2014-01-01

    In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤ 165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤ 118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180 ± 62 s with Col-Epi and 160 ± 70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027) and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥ 150/nL and hematocrit ≥ 27.0%, pathological PFA-100 results were found. In thrombocytopenic (hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future.

  8. Multiple functions of the von Willebrand Factor A domain in matrilins: secretion, assembly, and proteolysis

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    Kanbe Katsuaki

    2008-06-01

    Full Text Available Abstract The von Willebrand Factor A (vWF A domain is one of the most widely distributed structural modules in cell-matrix adhesive molecules such as intergrins and extracellular matrix proteins. Mutations in the vWF A domain of matrilin-3 cause multiple epiphyseal dysplasia (MED, however the pathological mechanism remains to be determined. Previously we showed that the vWF A domain in matrilin-1 mediates formation of a filamentous matrix network through metal-ion dependent adhesion sites in the domain. Here we show two new functions of the vWF A domain in cartilage-specific matrilins (1 and 3. First, vWF A domain regulates oligomerization of matrilins. Insertion of a vWF A domain into matrilin-3 converts the formation of a mixture of matrilin-3 tetramer, trimer, and dimer into a tetramer only, while deletion of a vWF A domain from matrilin-1 converts the formation of the native matrilin-1 trimer into a mixture of trimer and dimer. Second, the vWF A domain protects matrilin-1 from proteolysis. We identified a latent proteolytic site next to the vWF A2 domain in matrilin-1, which is sensitive to the inhibitors of matrix proteases. Deletion of the abutting vWF A domain results in degradation of matrilin-1, presumably by exposing the adjacent proteolytic site. In addition, we also confirmed the vWF A domain is vital for the secretion of matrilin-3. Secretion of the mutant matrilin-3 harbouring a point mutation within the vWF A domain, as occurred in MED patients, is markedly reduced and delayed, resulting from intracellular retention of the mutant matrilin-3. Taken together, our data suggest that different mutations/deletions of the vWF A domain in matrilins may lead to distinct pathological mechanisms due to the multiple functions of the vWF A domain.

  9. Allelic associations of two polymorphic microsatellites in intron 40 of the human von Willebrand factor gene

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    Pena, S.D.J.; De Souza, K.T. (Nucleo de Genetica Medica de Minas Gerais, Belo Horizonte (Brazil)); De Andrade, M.; Chakraborty, R. (Univ. of Texas Graduate School of Biomedical Sciences, Houston, TX (United States))

    1994-01-18

    At intron 40 of the von Willebrand factor (vWF) gene, two GATA-repeat polymorphic sites exist that are physically separated by 212 bp. At the first site (vWF1 locus), seven segregating repeat alleles were observed in a Brazilian Caucasian population, and at the second (vWF2 locus) there were eight alleles, detected through PCR amplifications of this DNA region. Haplotype analysis of individuals revealed 36 different haplotypes in a sample of 338 chromosomes examined. Allele frequencies between generations and gender at each locus were not significantly different, and the genotype frequencies were consistent with their Hardy-Weinberg expectations. Linkage disequilibrium between loci is highly significant with positive allele size association; that is, large alleles at the loci tend to occur together, and so do the same alleles. Variability at each locus appeared to have arisen in a stepwise fashion, suggesting replication slippage as a possible mechanism of production of new alleles. However, the authors observed an increased number of haplotypes, in contrast with the predictions of a stepwise production of variation in the entire region, suggesting some form of cooperative changes between loci that could be due to either gene conversion, or a common control mechanism of production of new variation at these repeat polymorphism sites. The high degree of polymorphism (gene diversity values of 72% and 78% at vWF1 and vWF2, respectively, and of 93% at the haplotype level) makes these markers informative for paternity testing, genetic counseling, and individual-identification purposes.

  10. Effects of increased von Willebrand factor levels on primary hemostasis in thrombocytopenic patients with liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Andreas Wannhoff

    Full Text Available In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF. We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100 closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤ 165 s or collagen and ADP (Col-ADP, upper limit of normal ≤ 118 s. If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4% showed a pathological result for the PFA-100. They had mean closure times (± SD of 180 ± 62 s with Col-Epi and 160 ± 70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027 and vWF-antigen levels (P = 0.010 are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥ 150/nL and hematocrit ≥ 27.0%, pathological PFA-100 results were found. In thrombocytopenic (< 150/nL patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3 ± 235.9% vs. 338.7 ± 151.6%, P = 0.021. These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the

  11. Rethinking the diagnosis of von Willebrand disease.

    Science.gov (United States)

    Favaloro, Emmanuel J

    2011-01-01

    von Willebrand disease (VWD) is the most common inherited bleeding disorder and arises from deficiencies and/or defects in the plasma protein von Willebrand factor (VWF). VWD is classified into 6 different types, with type 1 identified as a (partial) quantitative deficiency of VWF, type 3 defined by a (virtual) total deficiency of VWF, and type 2 identifying four separate types (2A, 2B, 2M, 2N) characterised by qualitative defects. The classification is based on phenotypic assays including FVIII, VWF:Ag and VWF activity, typically by ristocetin cofactor (VWF:RCo), but also increasingly by collagen binding (VWF:CB). Phenotypic testing may be supplemented by multimer analysis, RIPA, and VWF:FVIII binding. Although genetic analysis is not required to diagnose VWD or to define a classification type, it may be useful in discrete situations. The current review briefly covers this diagnostic process, with a focus on newer approaches, including extended test panels and the use of data from desmopressin challenges as a diagnostic tool. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Significance of plasma von Willebrand factor level and von Willebrand factor-cleaving protease activity in patients with chronic renal diseases

    Institute of Scientific and Technical Information of China (English)

    LU Guo-yuan; SHEN Lei; WANG Zhao-yue; GUO Xiao-fang; BAI Xia; SU Jian; RUAN Chang-geng

    2008-01-01

    Background yon Willebrand factor(vWF)mediates the initial capture of platelets to vascular subendothelium and is essential for platelet aggregation under high fluid shear stress as in arteriaI stenosis.On release frOm endothelial cells,vWF is rapidly cleaved by ADAMTSl 3/vWF-cleaving protease (vWF-CP).We investigated the clinical significance of changes in plasma vWF and vWF-CP activities in chronic renal disease.Methods Plasma vWF and vWF-CP activities were measured using enzyme-linked immunosorbent assay(ELISA)and residual collagen binding assay respectively in patients with lupus nephritis(n=31),primary nephritic syndrome(n=25),diabetic nephropathy(n=45),chronic glomerulonephritis(n=38)and 40 normal controls.The reIation of their levels with pathological and renal status was analyzed.Results In all diseased patients the levels of vWF were significantly higher and vWF-CP activity significantly lower than the controls(both P<0.01).vWF in the four subgroups did not correlate with the stage of disease but correlated negatively with vWF-CP activity.vWF-CP activity was not changed two weeks after renal transplantation.Renal biopsy demonstrated that the vWF level in stage Ⅳ was higher than in stages Ⅱ and Ⅲ while vWF-CP activity was lower in patients with lupus nephritis.After eight-week treatment,the vWF level significantly decreased and the vWF-CP activity significantly increased in systemic lupus erythema,disease activity index<9,but not with index≥9.Even though the vWF-CP activity was significantly lower in membranous nephropathy than in minimal change disease,mesangial proliferative glomerulonephritis or IgA glomerulonephritis,the vWF level was not significantly different.Conclusions The alterations of plasma vWF and vWF-CP activities were associated with different renal pathologies.Injury to endothelial cells and autoantibodies against vWF-CP activity may result in higher vWF Ievel and Iower vWF-CP activity in chronic renaI disease and thus a

  13. Acquired von Willebrand syndrome: A rare disorder of heterogeneous etiology

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    P Kasatkar

    2013-01-01

    Full Text Available Context: Acquired von Willebrand syndrome (AVWS is a rare bleeding disorder that mimics the inherited form of von Willebrand disease (VWD in terms of laboratory findings and clinical presentation. Aims: To study the etiology of acquired VWD. Settings and Design: The patients referred from various hospitals in and out of Mumbai were included in the study. Materials and Methods: Six patients with AVWS diagnosed at this center over the last 10 years were analyzed against 171 patients with inherited VWD. The differential diagnosis of AVWS was made based on reduced levels of von Willebrand antigen and von Willebrand ristocetin cofactor, decrease in ristocetin induced platelet aggregation, absence of correction in mixing studies with no prior history of bleeding problems and a negative family history for bleeding disorders. Results: In three patients, the disease was associated with systematic lupus erythematosus, out of which one was also associated with Kikuchi lymphadenitis and second with autoimmune hemolytic anemia. Fourth case was associated with hypothyroidism and fifth was a case of dermatitis and vitiligo. The last patient was a case of hemophilia A with Burkitts lymphoma, who developed autoantibodies to von Willebrand factor. Except two patients, all other patients responded to immune suppressive therapy with corticosteroids, while the patient with hypothyroidism responded to oral thyroxine. Conclusion: AVWS is a rare condition and may often be missed or diagnosed as inherited disease associated with heterogeneous disease conditions.

  14. Similarities of integumentary mucin B.1 from Xenopus laevis and prepro-von Willebrand factor at their amino-terminal regions.

    Science.gov (United States)

    Joba, W; Hoffmann, W

    1997-01-17

    Frog integumentary mucin B.1 (FIM-B.1) contains various cysteine-rich modules. In the past, a COOH-terminal "cystine knot" motif has been found that is similar to von Willebrand factor; this region is generally known to be responsible for dimerization processes. Furthermore, a "complement control protein" motif is present as an internal cysteine-rich domain in FIM-B.1. We characterize here the missing 75% toward the NH2 terminus of the FIM-B.1 precursor by molecular cloning. Analogous to prepro-von Willebrand factor, four elements with considerable similarity to D-domains are present (i.e. D1-D2-D'-D3). These domains have been described as essential for the multimerization of von Willebrand factor. Thus, the general structure of FIM-B.1 resembles that of the human mucin MUC2 as well as prepro-von Willebrand factor; these three molecules at least seem to share common structural elements allowing similar multimerization mechanisms.

  15. Von Willebrand factor and coagulation factor VIII in Moyamoya disease associated with Graves' disease: A case report

    Science.gov (United States)

    Ren, Shou-Chen; Gao, Bao-Qin; Yang, Wei-Li; Feng, Wei-Xin; Xu, Jian; Li, Shao-Wu; Wang, Yong-Jun

    2016-01-01

    The present study reported the case of a Chinese boy who was diagnosed with Moyamoya disease (MMD) associated with Graves' disease (GD). An overactivation of von Willebrand factor (vWF) and coagulation factor VIII (FVIII) was identified in the plasma of the patient. Thiamazole and metoprolol treatment was thus administrated. After 2 months of treatment, the patient's thyroid function returned to normal and the neurological symptoms improved gradually. At the same time, the activities of vWF and FVIII were depressed. During the 20-month follow-up, information regarding the neurological symptoms, cerebrovascular imaging, thyroid function, thyroid autoantibodies and coagulation parameters was collected. High levels of thyroid autoantibodies persisted throughout the follow-up period, while other coagulation parameters remained in the normal range. In conclusion, considering the vital role of vWF and FVIII in vascular diseases, it is hypothesized that these two factors may serve an important role in the occurrence of GD associated with MMD. PMID:27882137

  16. Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

    DEFF Research Database (Denmark)

    Nossent, Anne Yaël; Robben, J H; Deen, P M T

    2010-01-01

    SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of VWF....... The functionality of the G12E variant was studied in stably transfected MDCKII cells, expressing constructs of either 12G-V2R or 12E-V2R. Both V2R variants were fully glycosylated and expressed on the basolateral membrane. The binding affinity of V2R for AVP was increased three-fold in 12E-V2R-green fluorescent...

  17. Factor VIII alters tubular organization and functional properties of von Willebrand factor stored in Weibel-Palade bodies.

    Science.gov (United States)

    Bouwens, Eveline A M; Mourik, Marjon J; van den Biggelaar, Maartje; Eikenboom, Jeroen C J; Voorberg, Jan; Valentijn, Karine M; Mertens, Koen

    2011-11-24

    In endothelial cells, von Willebrand factor (VWF) multimers are packaged into tubules that direct biogenesis of elongated Weibel-Palade bodies (WPBs). WPB release results in unfurling of VWF tubules and assembly into strings that serve to recruit platelets. By confocal microscopy, we have previously observed a rounded morphology of WPBs in blood outgrowth endothelial cells transduced to express factor VIII (FVIII). Using correlative light-electron microscopy and tomography, we now demonstrate that FVIII-containing WPBs have disorganized, short VWF tubules. Whereas normal FVIII and FVIII Y1680F interfered with formation of ultra-large VWF multimers, release of the WPBs resulted in VWF strings of equal length as those from nontransduced blood outgrowth endothelial cells. After release, both WPB-derived FVIII and FVIII Y1680F remained bound to VWF strings, which however had largely lost their ability to recruit platelets. Strings from nontransduced cells, however, were capable of simultaneously recruiting exogenous FVIII and platelets. These findings suggest that the interaction of FVIII with VWF during WPB formation is independent of Y1680, is maintained after WPB release in FVIII-covered VWF strings, and impairs recruitment of platelets. Apparently, intra-cellular and extracellular assembly of FVIII-VWF complex involves distinct mechanisms, which differ with regard to their implications for platelet binding to released VWF strings.

  18. Weibel-Palade bodies: a window to von Willebrand disease.

    Science.gov (United States)

    Valentijn, K M; Eikenboom, J

    2013-04-01

    Weibel-Palade bodies (WPBs) are the storage organelles for von Willebrand factor (VWF) in endothelial cells. VWF forms multimers that assemble into tubular structures in WPBs. Upon demand, VWF is secreted into the blood circulation, where it unfolds into strings that capture platelets during the onset of primary hemostasis. Numerous mutations affecting VWF lead to the bleeding disorder von Willebrand disease. This review reports the recent findings on the effects of VWF mutations on the biosynthetic pathway of VWF and its storage in WPBs. These new findings have deepened our understanding of VWF synthesis, storage, secretion, and function.

  19. Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations

    Science.gov (United States)

    Boylan, Brian; Rice, Anne S.; De Staercke, Christine; Eyster, M. Elaine; Yaish, Hassan M.; Knoll, Christine M.; Bean, Christopher J.; Miller, Connie H.

    2015-01-01

    Summary Background Hemophilia A (HA) is an X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand Factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA, and pose a potential for misdiagnosis. Objectives Investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities, and VWF genotypes. Patients/Methods Thirty-seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These patients (cases) and 73 patients with identified F8 mutations (controls) were evaluated for VWF:Ag, patient's VWF capacity to bind FVIII (VWF:FVIIIB), and VWF sequence. Results Four cases had VWF:Ag <3 IU/dL and VWF mutations consistent with Type3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type1 VWD (VWD1) (n=5 cases and 1 control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n=1 case). One control had VWF:Ag <30 IU/dl, and seven patients (4 cases and 3 controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB. Conclusions These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy. PMID:25780857

  20. N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance.

    Science.gov (United States)

    Chion, Alain; O'Sullivan, Jamie M; Drakeford, Clive; Bergsson, Gudmundur; Dalton, Niall; Aguila, Sonia; Ward, Soracha; Fallon, Padraic G; Brophy, Teresa M; Preston, Roger J S; Brady, Lauren; Sheils, Orla; Laffan, Michael; McKinnon, Thomas A J; O'Donnell, James S

    2016-10-13

    Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. However, the molecular mechanisms underlying VWF clearance remain poorly understood. In this study, we investigated the role of VWF domains and specific glycan moieties in regulating in vivo clearance. Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. In A1-A2-A3 and full-length VWF, this macrophage-binding site is cryptic but becomes exposed following exposure to shear or ristocetin. Previous studies have demonstrated that the N-linked glycans within the A2 domain play an important role in modulating susceptibility to ADAMTS13 proteolysis. We further demonstrate that these glycans presented at N1515 and N1574 also play a critical role in protecting VWF against macrophage binding and clearance. Indeed, loss of the N-glycan at N1515 resulted in markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations. In addition, A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions also demonstrated significantly enhanced clearance. Importantly, clodronate-induced macrophage depletion significantly attenuated the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3. Finally, we further demonstrate that loss of these N-linked glycans does not enhance clearance in VWF in the presence of a structurally constrained A2 domain. Collectively, these novel findings support the hypothesis that conformation of the VWF A domains plays a critical role in modulating macrophage-mediated clearance of VWF in vivo.

  1. Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells.

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    Maartje van den Biggelaar

    Full Text Available BACKGROUND: Point mutations resulting in reduced factor VIII (FVIII binding to von Willebrand factor (VWF are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule biogenesis are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We studied intracellular trafficking of FVIII variants implicated in mild/moderate hemophilia A together with VWF in HEK293 cells and primary endothelial cells. The role of VWF binding was addressed using FVIII variants displaying reduced VWF interaction. Binding studies using purified FVIII proteins revealed moderate (Arg2150His, Del2201, Pro2300Ser to severe (Tyr1680Phe, Ser2119Tyr VWF binding defects. Expression studies in HEK293 cells and primary endothelial cells revealed that all FVIII variants were present within VWF-containing organelles. Quantitative studies showed that the relative amount of FVIII storage was independent of various mutations. Substantial amounts of FVIII variants are co-stored in VWF-containing storage organelles, presumably by virtue of their ability to interact with VWF at low pH. CONCLUSIONS: Our data suggest that the potential of FVIII co-storage with VWF is not affected in mild/moderate hemophilia A caused by reduced FVIII/VWF interaction in the circulation. These data support the hypothesis that Weibel-Palade bodies comprise the desmopressin-releasable FVIII storage pool in vivo.

  2. Doença de von Willebrand e anestesia Enfermedad de von Willebrand y anestesia Von Willebrand's disease and anesthesia

    OpenAIRE

    Fabiano Timbó Barbosa; Rafael Martins da Cunha; Luciano Timbó Barbosa

    2007-01-01

    JUSTIFICATIVA E OBJETIVOS: A doença de von Willebrand ocorre devido à mutação no cromossomo 12 e é caracterizada por deficiência qualitativa ou quantitativa do fator de von Willebrand. A diversidade de mutações leva ao aparecimento das mais variadas manifestações clínicas possibilitando a divisão dos pacientes em vários tipos e subtipos clínicos. A coagulopatia se manifesta basicamente através da disfunção plaquetária associada à diminuição dos níveis séricos do fator VIII coagulante. O objet...

  3. Fator von Willebrand e disfunção endotelial pulmonar. Implicações prognósticas von Willebrand factor and pulmonary vascular endothelial cell dysfunction. Prognostic implications

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    Antonio Augusto B. Lopes

    1998-03-01

    Full Text Available OBJETIVO: Avaliar alterações quantitativas e estruturais do fator von Willebrand (fvW circulante em 40 pacientes com hipertensão pulmonar pré-capilar e verificar possíveis implicações prognósticas dos resultados iniciais, em um ano de seguimento. MÉTODOS: A atividade antigênica plasmática do fator von Willebrand (vWF:Ag foi analisada por imunoeletroforese. A concentração de multímeros de baixo peso molecular em relação ao total de multímeros do fvW (MBPM% e o grau de fragmentação de sua subunidade principal foram analisados por Western immunoblotting. RESULTADOS: Em 40 pacientes, observamos aumento significativo de vWF:Ag em relação aos controles (pPURPOSE: To analyze quantitative and structural changes in circulating von Willebrand factor (vWF in 40 precapillary pulmonary hypertensive patients, as an attempt to identify possible correlations between endothelial cell dysfunction and patient short-term (one year survival. METHODS: Plasma antigenic activity of vWF (vWF:Ag was analyzed by immunoelectrophoresis. The relative concentration of vWF low molecular weight multimers (LMWM% and the composition of vWF subunit were determined by densitometric analysis of Western blots. RESULTS: vWF:Ag was importantly increased in patients in comparison with normals (p<0.001. Patients also had increased LMWM% (p<0.001 and increased degradation of vWF main subunit (p<0.05. At the beginning of the study, nonsurvivors (N=11 had higher vWF:Ag (p<0.001 and LMWM% (p<0.005 values in comparison with survivors. LMWM% was selected by logistic regression analysis as a predictor of death during the first year of follow-up (p<0.05. CONCLUSION: Marked changes in circulating vWF likely reflect extensive pulmonary vascular endothelial cell dysfunction and are associated with poor short-term prognosis in pulmonary hypertension.

  4. DEEP VEIN THROMBOSIS IN PATIENT WITH VON WILLEBRAND DISEASE

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    V. A. Elykomov

    2016-01-01

    Full Text Available Objective: to identify the possible factors of thrombogenic risk and ways of its prevention in patients with von Willebrand disease.Case description. Patient X., 42 years old, who suffers from von Willebrand disease type 3 with 5-years of age. Asked on reception to the traumatologist in the polyclinic of the Regional Hospital with pain in the left hip joint. Recommended planned operative treatment in the Altai Regional Clinical Hospital. Preoperative preparation included the infusion of concentrate of von Willebrand factor and coagulation factor VIII. Operation – cement total arthroplasty of the left hip joint. In the postoperative period analgesic treatment, elastic compression of the lower extremities, iron supplements, also conducted infusion of concentrate of von Willebrand factor and coagulation factor VIII for 20 days and thromboprophylactic with dabigatran. On the 3rd day after the operation the patient revealed deep vein thrombosis of the femoral segment (floating clot.Results. The patient was operated for emergency indications in the Department of endovascular surgery – installation of venous cava filter “Volan”. Dabigatran is cancelled, appointed clexane for 3 months. In our clinical example the patient lacked risk factors of pulmonary embolism as obesity, age, smoking, prolonged immobilization, estrogen therapy. Overdose of factor VIII were not observed – the level of factor did not exceed 135 % on transfusions. At the same time, the patient was found polymorphisms in the genes ITGA2, FGB, MTHFR, MTR – heterozygote, MTRR – mutant homozygote, which may indicate the genetic factors of thrombogenic risk. Also a significant risk factor was massive surgical intervention (total hip replacement. Despite preventive measures (elastic compression, thromboprophylactic dabigatran, early activation we cannot to avoid thrombotic complications.Conclusion. This article presents a case demonstrating a thrombotic complication in patients

  5. Hypercortisolism and pregnancy upregulate von Willebrand factor through different mechanisms: report on a pregnant patient with Cushing's syndrome.

    Science.gov (United States)

    Casonato, Alessandra; Daidone, Viviana; Pontara, Elena; Albiger, Nora; Cattini, Maria G; Scaroni, Carla

    2010-07-01

    Von Willebrand factor (VWF) is reportedly increased in pregnancy and Cushing's syndrome, inducing a hypercoagulable state. In Cushing's syndrome, VWF gene promoter polymorphisms modulate cortisol-dependent VWF upregulation, haplotype 1 (GCAG) and short GT-repeats (GT)(S) being the susceptible, and haplotype 2 (CTGA) and long GT-repeats (GT)(L) the protective pattern. We report on a Cushing's syndrome patient who became pregnant under hypercortisolism, in whom we monitored the evolution of her hypercoagulable state. During the active phase of Cushing's syndrome, the patient's VWF and factor VIII concentrations were normal, despite high urinary-free cortisol levels consistent with the presence of haplotype 2 and (GT)(L) alleles in the VWF gene promoter. VWF and factor VIII increased significantly and progressively after she became pregnant and peaked just before delivery, returning to normal 5 months later, while her hypercortisolism persisted. Our data indicate that two different mechanisms upregulate VWF under hypercortisolism and pregnancy, the latter being independent of the VWF promoter haplotypes sensitive to cortisol excess.

  6. Role of RNA splicing in mediating lineage-specific expression of the von Willebrand factor gene in the endothelium.

    Science.gov (United States)

    Yuan, Lei; Janes, Lauren; Beeler, David; Spokes, Katherine C; Smith, Joshua; Li, Dan; Jaminet, Shou-Ching; Oettgen, Peter; Aird, William C

    2013-05-23

    We previously demonstrated that the first intron of the human von Willebrand factor (vWF) is required for gene expression in the endothelium of transgenic mice. Based on this finding, we hypothesized that RNA splicing plays a role in mediating vWF expression in the vasculature. To address this question, we used transient transfection assays in human endothelial cells and megakaryocytes with intron-containing and intronless human vWF promoter-luciferase constructs. Next, we generated knockin mice in which LacZ was targeted to the endogenous mouse vWF locus in the absence or presence of the native first intron or heterologous introns from the human β-globin, mouse Down syndrome critical region 1, or hagfish coagulation factor X genes. In both the in vitro assays and the knockin mice, the loss of the first intron of vWF resulted in a significant reduction of reporter gene expression in endothelial cells but not megakaryocytes. This effect was rescued to varying degrees by the introduction of a heterologous intron. Intron-mediated enhancement of expression was mediated at a posttranscriptional level. Together, these findings implicate a role for intronic splicing in mediating lineage-specific expression of vWF in the endothelium.

  7. Factor VIII and von Willebrand factor co-delivery by endothelial cells

    NARCIS (Netherlands)

    Bouwens, E.A.M.|info:eu-repo/dai/nl/314061894

    2011-01-01

    A defect in coagulation factor VIII (FVIII) results in the inherited bleeding disorder hemophilia A. Current treatment of hemophilia A is hampered by the need of frequent administration of costly FVIII products. Therefore gene therapy is an attractive alternative for protein replacement to treat

  8. Factor VIII and von Willebrand factor co-delivery by endothelial cells

    NARCIS (Netherlands)

    Bouwens, E.A.M.

    2011-01-01

    A defect in coagulation factor VIII (FVIII) results in the inherited bleeding disorder hemophilia A. Current treatment of hemophilia A is hampered by the need of frequent administration of costly FVIII products. Therefore gene therapy is an attractive alternative for protein replacement to treat hem

  9. Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise.

    Directory of Open Access Journals (Sweden)

    Janine E van Loon

    Full Text Available Physical stress triggers the endothelium to release von Willebrand Factor (VWF from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise.105 healthy individuals (18-35 years were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag levels, VWF collagen binding (VWF:CB levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599, Syntaxin-2 (STX2, rs7978987 and VWF (promoter, rs7965413 were determined.The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8-1.1] and increased with 47% [IQR 25-73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1-1.8] (p<0.0001. VWF:CB levels and ADAMTS13 activity both also increased after exhaustive exercise (median increase 43% and 12%, both p<0.0001. The strongest determinants of the VWF:Ag level increase are performance related (p<0.0001. We observed a gender difference in VWF:Ag response to exercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001, which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase.VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter.

  10. Does von Willebrand factor improve the predictive ability of current risk stratification scores in patients with atrial fibrillation?

    Science.gov (United States)

    García-Fernández, Amaya; Roldán, Vanessa; Rivera-Caravaca, José Miguel; Hernández-Romero, Diana; Valdés, Mariano; Vicente, Vicente; Lip, Gregory Y. H.; Marín, Francisco

    2017-01-01

    Von Willebrand factor (vWF) is a biomarker of endothelial dysfunction. We investigated its role on prognosis in anticoagulated atrial fibrillation (AF) patients and determined whether its addition to clinical risk stratification schemes improved event-risk prediction. Consecutive outpatients with non-valvular AF were recruited and rates of thrombotic/cardiovascular events, major bleeding and mortality were recorded. The effect of vWF on prognosis was calculated using a Cox regression model. Improvements in predictive accuracy over current scores were determined by calculating the integrated discrimination improvement (IDI), net reclassification improvement (NRI), comparison of receiver-operator characteristic (ROC) curves and Decision Curve Analysis (DCA). 1215 patients (49% males, age 76 (71–81) years) were included. Follow-up was almost 7 years. Significant associations were found between vWF and cardiovascular events, stroke, mortality and bleeding. Based on IDI and NRI, addition of vWF to CHA2DS2-VASc statistically improved its predictive value, but c-indexes were not significantly different. For major bleeding, the addition of vWF to HAS-BLED improved the c-index but not IDI or NRI. DCA showed minimal net benefit. vWF acts as a simple prognostic biomarker in AF and, whilst its addition to current scores statistically improves prediction for some endpoints, absolute changes and impact on clinical decision-making are marginal. PMID:28134282

  11. Limited polymorphism in Plasmodium falciparum ookinete surface antigen, von Willebrand factor A domain-related protein from clinical isolates

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    Eisen Damon P

    2006-07-01

    Full Text Available Abstract Background As malaria becomes increasingly drug resistant and more costly to treat, there is increasing urgency to develop effective vaccines. In comparison to other stages of the malaria lifecycle, sexual stage antigens are under less immune selection pressure and hence are likely to have limited antigenic diversity. Methods Clinical isolates from a wide range of geographical regions were collected. Direct sequencing of PCR products was then used to determine the extent of polymorphisms for the novel Plasmodium falciparum sexual stage antigen von Willebrand Factor A domain-related Protein (PfWARP. These isolates were also used to confirm the extent of diversity of sexual stage antigen Pfs28. Results PfWARP was shown to have non-synonymous substitutions at 3 positions and Pfs28 was confirmed to have a single non-synonymous substitution as previously described. Conclusion This study demonstrates the limited antigenic diversity of two prospective P. falciparum sexual stage antigens, PfWARP and Pfs28. This provides further encouragement for the proceeding with vaccine trials based on these antigens.

  12. Expression of von Willebrand factor, pulmonary intravascular macrophages, and Toll-like receptors in lungs of septic foals

    Science.gov (United States)

    Harrison, Jacqueline M. E.; Quanstrom, Leah M.; Robinson, Alex R.; Wobeser, Bruce; Anderson, Stacy L.

    2017-01-01

    Sepsis causes significant mortality in neonatal foals; however, there is little data describing the cellular and molecular pathways of lung inflammation in septic foals. This study was conducted to characterize lung inflammation in septic foals. Lung tissue sections from control (n = 6) and septic (n = 17) foals were compared using histology and immunohistology. Blinded pathologic scoring of hematoxylin and eosin stained samples revealed increased features of lung inflammation such as thickened alveolar septa and sequestered inflammatory cells in septic foals. Septic foal lungs showed increased expression of von Willebrand factor in blood vessels, demonstrating vascular inflammation. Use of MAC387 antibody to detect calprotectin as a reflection of mononuclear cell infiltration revealed a significant increase in their numbers in alveolar septa of lungs from septic foals compared to those from control foals. The mononuclear cells appeared to be mature macrophages and were located in the septal capillaries, suggesting they were pulmonary intravascular macrophages (PIMs). Finally, lungs from septic foals showed increased expression of Toll-like receptor 4 and 9 in mononuclear cells relative to the control. Taken together, this study is the first to show the expression of inflammatory molecules and an increase in PIMs in lungs from foals that died from sepsis. PMID:27297419

  13. Nanomechanical Contribution of Collagen and von Willebrand Factor A in Marine Underwater Adhesion and Its Implication for Collagen Manipulation.

    Science.gov (United States)

    Yoo, Hee Young; Huang, Jun; Li, Lin; Foo, Mathias; Zeng, Hongbo; Hwang, Dong Soo

    2016-03-14

    Recent works on mussel adhesion have identified a load bearing matrix protein (PTMP1) containing von Willebrand factor (vWF) with collagen binding capability that contributes to the mussel holdfast by manipulating mussel collagens. Using a surface forces apparatus, we investigate for the first time, the nanomechanical properties of vWF-collagen interaction using homologous proteins of mussel byssus, PTMP1 and preCollagens (preCols), as collagen. Mimicking conditions similar to mussel byssus secretion (pH < 5.0) and seawater condition (pH 8.0), PTMP1 and preCol interact weakly in the "positioning" phase based on vWF-collagen binding and strengthen in "locked" phase due to the combined effects of electrostatic attraction, metal binding, and mechanical shearing. The progressive enhancement of binding between PTMP1 with porcine collagen under the aforementioned conditions is also observed. The binding mechanisms of PTMP1-preCols provide insights into the molecular interaction of the mammalian collagen system and the development of an artificial extracellular matrix based on collagens.

  14. Weibel-Palade body size modulates the adhesive activity of its von Willebrand Factor cargo in cultured endothelial cells

    Science.gov (United States)

    Ferraro, Francesco; Mafalda Lopes da, Silva; Grimes, William; Lee, Hwee Kuan; Ketteler, Robin; Kriston-Vizi, Janos; Cutler, Daniel F.

    2016-01-01

    Changes in the size of cellular organelles are often linked to modifications in their function. Endothelial cells store von Willebrand Factor (vWF), a glycoprotein essential to haemostasis in Weibel-Palade bodies (WPBs), cigar-shaped secretory granules that are generated in a wide range of sizes. We recently showed that forcing changes in the size of WPBs modifies the activity of this cargo. We now find that endothelial cells treated with statins produce shorter WPBs and that the vWF they release at exocytosis displays a reduced capability to recruit platelets to the endothelial cell surface. Investigating other functional consequences of size changes of WPBs, we also report that the endothelial surface-associated vWF formed at exocytosis recruits soluble plasma vWF and that this process is reduced by treatments that shorten WPBs, statins included. These results indicate that the post-exocytic adhesive activity of vWF towards platelets and plasma vWF at the endothelial surface reflects the size of their storage organelle. Our findings therefore show that changes in WPB size, by influencing the adhesive activity of its vWF cargo, may represent a novel mode of regulation of platelet aggregation at the vascular wall. PMID:27576551

  15. Type II PI4-kinases control Weibel-Palade body biogenesis and von Willebrand factor structure in human endothelial cells.

    Science.gov (United States)

    Lopes da Silva, Mafalda; O'Connor, Marie N; Kriston-Vizi, Janos; White, Ian J; Al-Shawi, Raya; Simons, J Paul; Mössinger, Julia; Haucke, Volker; Cutler, Daniel F

    2016-05-15

    Weibel-Palade bodies (WPBs) are endothelial storage organelles that mediate the release of molecules involved in thrombosis, inflammation and angiogenesis, including the pro-thrombotic glycoprotein von Willebrand factor (VWF). Although many protein components required for WPB formation and function have been identified, the role of lipids is almost unknown. We examined two key phosphatidylinositol kinases that control phosphatidylinositol 4-phosphate levels at the trans-Golgi network, the site of WPB biogenesis. RNA interference of the type II phosphatidylinositol 4-kinases PI4KIIα and PI4KIIβ in primary human endothelial cells leads to formation of an increased proportion of short WPB with perturbed packing of VWF, as exemplified by increased exposure of antibody-binding sites. When stimulated with histamine, these cells release normal levels of VWF yet, under flow, form very few platelet-catching VWF strings. In PI4KIIα-deficient mice, immuno-microscopy revealed that VWF packaging is also perturbed and these mice exhibit increased blood loss after tail cut compared to controls. This is the first demonstration that lipid kinases can control the biosynthesis of VWF and the formation of WPBs that are capable of full haemostatic function.

  16. Weibel-Palade body size modulates the adhesive activity of its von Willebrand Factor cargo in cultured endothelial cells.

    Science.gov (United States)

    Ferraro, Francesco; Mafalda Lopes da, Silva; Grimes, William; Lee, Hwee Kuan; Ketteler, Robin; Kriston-Vizi, Janos; Cutler, Daniel F

    2016-08-31

    Changes in the size of cellular organelles are often linked to modifications in their function. Endothelial cells store von Willebrand Factor (vWF), a glycoprotein essential to haemostasis in Weibel-Palade bodies (WPBs), cigar-shaped secretory granules that are generated in a wide range of sizes. We recently showed that forcing changes in the size of WPBs modifies the activity of this cargo. We now find that endothelial cells treated with statins produce shorter WPBs and that the vWF they release at exocytosis displays a reduced capability to recruit platelets to the endothelial cell surface. Investigating other functional consequences of size changes of WPBs, we also report that the endothelial surface-associated vWF formed at exocytosis recruits soluble plasma vWF and that this process is reduced by treatments that shorten WPBs, statins included. These results indicate that the post-exocytic adhesive activity of vWF towards platelets and plasma vWF at the endothelial surface reflects the size of their storage organelle. Our findings therefore show that changes in WPB size, by influencing the adhesive activity of its vWF cargo, may represent a novel mode of regulation of platelet aggregation at the vascular wall.

  17. New developments in lung endothelial heterogeneity: Von Willebrand factor, P-selectin, and the Weibel-Palade body.

    Science.gov (United States)

    Ochoa, Cristhiaan D; Wu, Songwei; Stevens, Troy

    2010-04-01

    Quiescent pulmonary endothelium establishes an antithrombotic, anti-inflammatory surface that promotes blood flow. However, the endothelium rapidly responds to injury and inflammation by promoting thrombosis and enabling the directed transmigration of inflammatory cells, such as neutrophils, into the alveolar airspace. Although the endothelial cell signals responsible for establishing a prothrombotic surface are distinct from those responsible for recognizing circulating neutrophils, these processes are highly interrelated. Von Willebrand factor (VWF)-stimulated secretion plays an important role in thrombus formation, and P-selectin surface expression plays a key role in neutrophil binding necessary for transmigration. Both VWF and P-selectin are located within Weibel-Palade bodies in pulmonary arteries and arterioles, yet Weibel-Palade bodies are absent in capillaries. Despite the absence of the Weibel-Palade bodies, pulmonary capillaries express both VWF and P-selectin. The physiological and pathophysiological significance of these observations is unclear. In this review, we address some anatomical and physiological features that distinguish pulmonary artery, capillary, and vein endothelium. In addition, we review our current understanding regarding the stimulated secretion of VWF and P-selectin in pulmonary artery and capillary endothelium. This information is considered in the context of vasculitis and pneumonia, two pathophysiological processes to which the stimulated secretion of VWF and P-selectin contribute.

  18. Von Willebrand Factor, ADAMTS13 and D-Dimer Are Correlated with Different Levels of Nephropathy in Type 1 Diabetes Mellitus.

    Directory of Open Access Journals (Sweden)

    Caroline Pereira Domingueti

    Full Text Available We have investigated whether von Willebrand factor, ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13, and D-Dimer were associated with different levels of renal function in patients with type 1 diabetes. Patients were classified according to level of renal function through estimated glomerular filtration rate: ≥90 and <130mL/min/1,73m2, n=52 (control group, ≥60 and <90mL/min/1,73m2, n=29 (mild renal dysfunction group, <60mL/min/1,73m2, n=28 (severe renal dysfunction group; and through urinary albumin excretion: normoalbuminuria, microalbuminuria and macroalbuminuria. Von Willebrand factor, ADAMTS13, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay. ADAMTS13 activity was determined by fluorescence resonance energy transfer assay. Von Willebrand factor levels were increased in patients with mild (P=0.001 and severe (P<0.001 renal dysfunction as compared to the control group. ADAMTS13 levels were also increased in mild (P=0.029 and severe (P=0.002 renal dysfunction groups in comparison to the control group, while ADAMTS13 activity was increased only in the severe renal dysfunction group as compared to the control group (P=0.006. No significant differences were observed among the groups regarding von Willebrand factor/ADAMTS13 ratio. ADAMTS13 activity/ADAMTS13 levels ratio was reduced in patients with mild (P=0.013 and severe (P=0.015 renal dysfunction as compared to the control group. D-Dimer levels were increased in patients with mild (P=0.006 and severe (P<0.001 renal dysfunction as compared to the control group; it was also higher in patients with severe renal dysfunction as compared to the mild renal dysfunction group (P=0.019. Similar results were found for albuminuria classification. Increased von Willebrand factor, ADAMTS13, and D-Dimer levels and decreased ADAMTS13 activity/ADAMTS13 levels ratio are associated with renal dysfunction in patients with type 1 diabetes

  19. Von Willebrand's disease: case report and review of literature ...

    African Journals Online (AJOL)

    Abstract. Von Willebrand Disease (VWD) is the most common human ... The most bleeding forms of VWD usually do not concern type 1 patients with the ... and collagen binding test and genanalysis allow diagnosing the different types of von.

  20. Subarachnoid hemorrhage associated with von Willebrand's disease--case report.

    Science.gov (United States)

    Nakau, Reiko; Nomura, Motohiro; Kida, Shinya; Yamashita, Junkoh; Kinoshita, Akira; Nitta, Hisashi; Muramatsu, Naoki

    2005-12-01

    A 59-year-old woman with type IIA von Willebrand's disease (VWD) presented with subarachnoid hemorrhage (SAH). Computed tomography showed SAH in the right sylvian fissure and intracranial hemorrhage in the right temporal lobe. Angiography demonstrated an aneurysm at the bifurcation of the right middle cerebral artery. Neck clipping was performed on the 3rd day after the onset with intra- and postoperative administration of factor VIII/von Willebrand factor concentrate. No excessive bleeding occurred. Patients with prolonged bleeding time should be screened for VWD before surgery. This is a rare case of VWD presenting with SAH secondary to ruptured intracranial aneurysm. The clinical characteristics and the management of SAH in a patient with VWD are discussed.

  1. Marshall-Stickler phenotype associated with von Willebrand disease

    Energy Technology Data Exchange (ETDEWEB)

    MacDonald, M.R.; Baker, K.S.; Schaefer, G.B. [Univ. of Nebraska Medical Center, Omaha, NE (United States)

    1997-01-20

    We report on 6 individuals from three different kindreds with Marshall-Stickler (MS) phenotype, with characteristic orofacial abnormalities, arthropathy, deafness, and eye findings, all of whom were discovered to have a mild bleeding diathesis and coagulation-study findings consistent with mild von Willebrand disease (vWD). MS syndrome has been linked in some cases to the type II procollagen gene (COL2A1) on chromosome 12q, and to the collagen XI gene (COL11A2) on chromosome 6. The von Willebrand factor (vWF) is encoded by a 180-Kb gene located on the short arm of chromosome 12. This is the first reported association of these two disorders. 26 refs., 5 figs., 1 tab.

  2. Genetic Drivers of von Willebrand Factor Levels in an Ischemic Stroke Population and Association With Risk for Recurrent Stroke.

    Science.gov (United States)

    Williams, Stephen R; Hsu, Fang-Chi; Keene, Keith L; Chen, Wei-Min; Dzhivhuho, Godfrey; Rowles, Joe L; Southerland, Andrew M; Furie, Karen L; Rich, Stephen S; Worrall, Bradford B; Sale, Michèle M

    2017-06-01

    von Willebrand factor (vWF) plays an important role in thrombus formation during cerebrovascular damage. We sought to investigate the potential role of circulating vWF in recurrent cerebrovascular events and identify genetic contributors to variation in vWF level in an ischemic stroke population. We analyzed the effect of circulating vWF on risk of recurrent stroke using survival models in the VISP trial (Vitamin Intervention for Stroke Prevention) and the use of vWF in reclassification over traditional factors. We conducted a genome-wide association study) with imputation, based on 1000 Genomes Project data, for circulating vWF levels and then interrogated loci previously associated with vWF levels. We performed expression quantitative trait locus analysis for vWF across different tissues. Elevated vWF levels were associated with increased risk for recurrent stroke in VISP. Adding vWF to traditional clinical parameters also improved recurrent stroke risk prediction. We identified single-nucleotide polymorphisms significantly associated with circulating vWF at the ABO locus (Pgenetic associations of vWF levels in humans. Expression quantitative trait locus analyses demonstrate that most associated ABO single-nucleotide polymorphisms were also associated with vWF gene expression. Elevated vWF levels are associated with recurrent stroke in VISP. In the VISP population, genetic determinants of vWF levels that impact vWF gene expression were identified. These data add to our knowledge of the pathophysiologic and genetic basis for recurrent stroke risk and may have implications for clinical care decision making. © 2017 American Heart Association, Inc.

  3. Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease

    Directory of Open Access Journals (Sweden)

    A.A. Lopes

    2011-12-01

    Full Text Available Biomarkers have been identified for pulmonary arterial hypertension, but are less well defined for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH. We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and tested for associations with survival. A cohort of 46 inoperable CHDPAH patients (age 15.0 to 60.2 years, median 33.5 years, female:male 29:17 was prospectively followed for 0.7 to 4.0 years (median 3.6 years. Plasma levels of von Willebrand factor antigen (VWF:Ag, tissue plasminogen activator (t-PA and its inhibitor (PAI-1, P-selectin, reactive C-protein, tumor necrosis factor alpha, and interleukin-6 and -10 were measured at baseline, and at 30, 90, and 180 days in all subjects. Levels of six of the eight proteins were significantly increased in patients versus controls (13 to 106% increase, P < 0.003. Interleukin-10 level was 2.06 times normal (P = 0.0003; Th2 cytokine response. Increased levels of four proteins (t-PA, PAI-1, P-selectin, and interleukin-6 correlated with disease severity indices (P < 0.05. Seven patients died during follow-up. An average VWF:Ag (mean of four determinations above the level corresponding to the 95th percentile of controls (139 U/dL was independently associated with a high risk of death (hazard ratio = 6.56, 95%CI = 1.46 to 29.4, P = 0.014. Thus, in CHDPAH, microvascular dysfunction appears to involve Th2 inflammatory response. Of the biomarkers studied, plasma vWF:Ag was independently associated with survival.

  4. Successful Aortic Aneurysm Repair in a Woman with Severe von Willebrand (Type 3 Disease

    Directory of Open Access Journals (Sweden)

    Victoria Campbell

    2015-01-01

    Full Text Available von Willebrand disease type 3 (VWD3 is a rare but the most severe form of von Willebrand disease; it is due to almost complete lack of von Willebrand factor activity (VWF:RCo. It is inherited as autosomal recessive trait; whilst heterozygote carriers have mild, or no symptoms, patients with VWD3 show severe bleeding symptoms. In the laboratory, this is characterised by undetectable VWF:Ag, VWF:RCo, and reduced levels of factor VIII < 0.02 IU/dL. The bleeding is managed with von Willebrand/FVIII factor concentrate replacement therapy. In this rare but challenging case we report on the successful excision and repair of an ascending aortic aneurysm following adequate VWF/FVIII factor concentrate replacement using Haemate-P.

  5. Neutrophil Protease Cleavage of Von Willebrand Factor in Glomeruli - An Anti-thrombotic Mechanism in the Kidney.

    Science.gov (United States)

    Tati, Ramesh; Kristoffersson, Ann-Charlotte; Manea Hedström, Minola; Mörgelin, Matthias; Wieslander, Jörgen; van Kooten, Cees; Karpman, Diana

    2017-02-01

    Adequate cleavage of von Willebrand factor (VWF) prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM) was studied as a reflection of processes occurring in the subendothelial glomerular space. VWF was incubated with human GBMs and VWF cleavage was assessed by multimer structure analysis, immunoblotting and mass spectrometry. VWF was cleaved into the smallest multimers by the GBM, which contained ADAMTS13 as well as neutrophil proteases, elastase, proteinase 3 (PR3), cathepsin-G and matrix-metalloproteinase 9. The most potent components of the GBM capable of VWF cleavage were in the serine protease or metalloprotease category, but not ADAMTS13. Neutralization of neutrophil serine proteases inhibited GBM-mediated VWF-cleaving activity, demonstrating a marked contribution of elastase and/or PR3. VWF-platelet strings formed on the surface of primary glomerular endothelial cells, in a perfusion system, were cleaved by both elastase and the GBM, a process blocked by elastase inhibitor. Ultramorphological studies of the human kidney demonstrated neutrophils releasing elastase into the GBM. Neutrophil proteases may contribute to VWF cleavage within the subendothelium, adjacent to the GBM, and thus regulate thrombus size. This anti-thrombotic mechanism would protect the normal kidney during inflammation and could also explain why most patients with ADAMTS13 deficiency do not develop severe kidney failure.

  6. Insulin resistance is accompanied by increased von Willebrand factor levels in nondiabetic women: a study of offspring of type 2 diabetic subjects compared to offspring of nondiabetic subjects

    DEFF Research Database (Denmark)

    Foss, Anne-Catherine; Vestbo, Else; Frøland, Anders

    2002-01-01

    OBJECTIVES: To examine whether levels of von Willebrand factor (vWF), fibrinogen and fibronectin are related to a parental history of type 2 diabetes and to determine possible explanatory factors for high versus low vWF and fibrinogen. DESIGN: Cross-sectional study. SUBJECTS, MAIN OUTCOME MEASURES......: We compared vWF, fibrinogen and fibronectin in 88 nondiabetic offspring of type 2 diabetic subjects (relatives) and 103 offspring of nondiabetic subjects (controls). Other measurements included urinary albumin excretion rate, blood pressure, lipid profile and insulin resistance using homeostasis....... Odds ratio for high versus low insulin resistance was 18.39 (P index (BMI) (P

  7. Common carotid intima-media thickness and von Willebrand factor serum levels in rheumatoid arthritis female patients without cardiovascular risk factors.

    Science.gov (United States)

    Daza, Leonel; Aguirre, Martin; Jimenez, Martin; Herrera, Rafael; Bollain, J J

    2007-04-01

    High atherosclerosis prevalence was found in rheumatoid arthritis (RA), and the von Willebrand factor (vWF) was shown to be a marker for endothelial damage. The aim of this study was to evaluate the association of intima-media thickness of the left common carotid artery with vWF serum levels in rheumatoid arthritis patients without cardiovascular risk factors. We included 55 RA female patients, each with at least 5 years of duration of the disease, and 20 healthy female subjects as members of the control group. The vWF, cholesterol, triglycerides, and the immune variables-rheumatoid factor and reactive C protein-were evaluated. The media thickness and intima-media thickness (IMT) in patients and in the control subjects were assessed by Doppler ultrasound of the left common carotid artery. Although the ages for RA patients and healthy female controls were not different, the IMT of the left common carotid artery (IMT CCA) in rheumatoid arthritis patients was increased in comparison with healthy control measurements, the mean being 0.67 mm (SD 0.18) vs 0.58 mm (SD 0.10) with a p value 0.01. The vWF serum levels showed differences in RA patients from those in control patients, 145.6 (SD 30.08) vs 121.8 (SD 37.17), respectively, with p=0.007. A correlation was also found between vWF with IMT CCA in the RA patients: r=0.390 and p<0.05. We concluded that the measurements of the left common carotid artery intima-media thickness together with the von Willebrand factor serum levels could give valuable information about the artery status and the atherosclerosis process in early stages in patients with rheumatoid arthritis without cardiovascular risk factors.

  8. Clinical and laboratory diagnosis of von Willebrand disease : A synopsis of the 2008 NHLBI/NIH guidelines

    NARCIS (Netherlands)

    Nichols, William L.; Rick, Margaret E.; Ortel, Thomas L.; Montgomery, Robert R.; Sadler, J. Evan; Yawn, Barbara P.; James, Andra H.; Hultin, Mae B.; Manco-Johnson, Marilyn J.; Weinstein, Mark

    2009-01-01

    Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects m

  9. Clinical phenotype in genetically confirmed von Willebrand disease type 2N patients reflects a haemophilia A phenotype

    NARCIS (Netherlands)

    Meegeren, M.E.R. van; Mancini, T.L.; Schoormans, S.C.M.; Haren, B.J.T. van; Duren, C. van; Diekstra, A.; Laros-van Gorkom, B.A.P.; Brons, P.P.; Simons, A.; Hoefsloot, L.H.; Heerde, W.L. van

    2015-01-01

    INTRODUCTION: Von Willebrand disease (VWD) type 2N is characterized by a defective binding of factor VIII (FVIII) to von Willebrand factor (VWF) resulting in diminished plasma FVIII levels and a clinical phenotype mimicking mild haemophilia A. Several mutations in the FVIII binding site of VWF have

  10. Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis and Low Cardiovascular Risk: The Role of von Willebrand Factor Activity.

    Directory of Open Access Journals (Sweden)

    Gorica G Ristić

    Full Text Available To evaluate association between von Willebrand factor (vWF activity, inflammation markers, disease activity, and subclinical atherosclerosis in patients with rheumatoid arthritis (RA and low cardiovascular risk.Above mentioned parameters were determined in blood samples of 74 non-diabetic, normotensive, female subjects, with no dyslipidemia(42 patients, 32 matched healthy controls, age 45.3±10.0 vs. 45.2±9.8 years. Intima-media thickness (IMT was measured bilaterally, at common carotid, bifurcation, and internal carotid arteries. Subclinical atherosclerosis was defined as IMT>IMTmean+2SD in controlsat each carotid level and atherosclerotic plaque as IMT>1.5 mm. Majority of RA patients were on methotrexate (83.3%, none on steroids >10 mg/day or biologic drugs. All findings were analysed in the entire study population and in RA group separately.RA patients with subclinical atherosclerosis had higher vWF activity than those without (133.5±69.3% vs. 95.3±36.8%, p<0.05. Predictive value of vWF activity for subclinical atherosclerosis was confirmed by logistic regression. vWF activity correlated significantly with erythrocyte sedimentation rate, fibrinogen, modified disease activity scores (mDAS28-ESR, mDAS28-CRP, modified Health Assessment Questionnaire (p<0.01 for all, duration of smoking, number of cigarettes/day, rheumatoid factor concentration (p<0.05 for all, and anti-CCP antibodies (p<0.01. In the entire study population, vWF activity was higher in participants with subclinical atherosclerosis (130±68% vs. 97±38%, p<0.05 or atherosclerotic plaques (123±57% vs. 99±45%, p<0.05 than in those without. Duration of smoking was significantly associated with vWF activity (β 0.026, p = 0.039.We demonstrated association of vWF activity and subclinical atherosclerosis in low-risk RA patients as well as its correlation with inflammation markers, all parameters of disease activity, and seropositivity. Therefore, vWF might be a valuable marker of

  11. Specific inhibiting effects of Ilexonin A on von Willebrand factor-dependent platelet aggregation under high shear rate

    Institute of Scientific and Technical Information of China (English)

    李敏; 吴伟康; 刘良; 廖福龙; 篠原幸人; 半田俊之介; 後藤信哉

    2004-01-01

    Background Ilexonin A (IA), purified from the Chinese herbal medicine Maodongqing (Ilex pubescens Hook, et Am) has been commonly used in south China to treat thrombotic disorders. In this study, we aimed to study the inhibiting effects and mechanism of lA on von Willebrand factor (vWF)-dependent high shear-induced platelet aggregation. Methods vWF-dependent high shear (10 800 s-1) induced aggregation of platelets obtained from normal donors in the presence or absence of lA was measured by a modified cone-plate viscometer and shear-induced vWF binding was measured by quantitative flowcytometry with monoclonal antibody known to bind exclusively to the C-terminal domain of vWF (LJ-C3) directly labeled with fluorescein isothiocyanate (FITC). P-selectin surface expression was also measured by a similar method with FITC conjugated anti-P-selectin monoclonal antibody (WGA1).Results Shear-induced platelet aggregation was inhibited by IA in a dose-dependent manner. The extent of aggregation decreased from (78.6±4.6)% in the absence of lA to (36.5±2.1 )% in the presence of lA (3.3 mmol/L) (P<0.0001, n=9) with a high shear rate of 10800 s-1. vWF binding and P-selectin expression were also inhibited by lA in a dose dependent manner. The number of binding FITC-LJ-C3 molecules increased after exposure of platelet-rich plasma to a high shear rate of 10 800 s-1 for 6 minutes, but this shear-induced increased binding platelet surface vWF molecules and P-selectin expression can be decreased in the presence of IA.Conclusion vWF binding and vWF mediated platelet activation, aggregation occurring under high shear rate were inhibited by IA. lA may be a unique antithrombotic drug inhibiting the vWF-GP Ib α interaction, and may thus facilitate drug design targeting arterial thrombosis.

  12. Temperature-dependence of Weibel-Palade body exocytosis and cell surface dispersal of von Willebrand factor and its propolypeptide.

    Directory of Open Access Journals (Sweden)

    Lindsay Hewlett

    Full Text Available BACKGROUND: Weibel-Palade bodies (WPB are endothelial cell (EC specific secretory organelles containing Von Willebrand factor (VWF. The temperature-dependence of Ca(2+-driven WPB exocytosis is not known, although indirect evidence suggests that WPB exocytosis may occur at very low temperatures. Here we quantitatively analyse the temperature-dependence of Ca(2+-driven WPB exocytosis and release of secreted VWF from the cell surface of ECs using fluorescence microscopy of cultured human ECs containing fluorescent WPBs. PRINCIPAL FINDINGS: Ca(2+-driven WPB exocytosis occurred at all temperatures studied (7-37°C. The kinetics and extent of WPB exocytosis were strongly temperature-dependent: Delays in exocytosis increased from 0.92 s at 37°C to 134.2 s at 7°C, the maximum rate of WPB fusion decreased from 10.0±2.2 s(-1 (37°C to 0.80±0.14 s(-1 (7°C and the fractional extent of degranulation of WPBs in each cell from 67±3% (37°C to 3.6±1.3% (7°C. A discrepancy was found between the reduction in Ca(2+-driven VWF secretion and WPB exocytosis at reduced temperature; at 17°C VWF secretion was reduced by 95% but WPB exocytosis by 75-80%. This discrepancy arises because VWF dispersal from sites of WPB exocytosis is largely prevented at low temperature. In contrast VWF-propolypeptide (proregion dispersal from WPBs, although slowed, was complete within 60-120 s. Novel antibodies to the cleaved and processed proregion were characterised and used to show that secreted proregion more accurately reports the secretion of WPBs at sub-physiological temperatures than assay of VWF itself. CONCLUSIONS: We report the first quantitative analysis of the temperature-dependence of WPB exocytosis. We provide evidence; by comparison of biochemical data for VWF or proregion secretion with direct analysis of WPB exocytosis at reduced temperature, that proregion is a more reliable marker for WPB exocytosis at reduced temperature, where VWF-EC adhesion is increased.

  13. Function of von Willebrand factor in children with diarrhea-associated hemolytic-uremic syndrome (D+ HUS).

    Science.gov (United States)

    Sutor, A H; Thomas, K B; Prüfer, F H; Grohmann, A; Brandis, M; Zimmerhackl, L B

    2001-06-01

    Reports on von Willebrand factor (vWF) in hemolytic-uremic syndrome (HUS) are not unequivocal. Because of potential pathogenic implications, we examined the ability of vWF to bind to collagen in vitro, which reflects its function. Plasma vWF antigen (vWF:Ag) and collagen-binding activity (vWF:CBA) were measured by enzyme-linked immunosorbent assay in children with (1) diarrhea-associated (D+) HUS (n = 27), (2) chronic renal insufficiency (CRI) (n = 8), (3) gastroenteritis (GE) not associated with HUS (n = 15), (4) immune thrombocytopenia (ITP) (n = 40) and from controls (n = 35). Structural vWF was evaluated by multimer analysis. Children with D+ HUS had vWF:Ag of 2.53 and vWF:CBA of 1.98 U/mL. The corresponding values for patients with ITP were 1.35 and 1.82 U/mL, with CRI 1.55 and 1.55 U/mL, and with GE 1.68 and 2.10 U/mL; all values were higher than in controls (1.04 and 1.16 U/mL). The mean ratio of vWF:CBA to vWF:Ag ratio in controls was 1.13; only children with HUS had a dysfunctional vWF, as indicated by a low ratio of 0.78; the ratio was elevated in children with ITP (1.36) and GE (1.27) and was normal in those with CRI (1.06). No ultralarge molecular multimers of vWF were detected in any group, including HUS. The very high concentration of plasma vWF:Ag in HUS probably reflects endothelial cell damage or irritation. In contrast to all other groups, only children with HUS had a dysfunctional vWF, caused either by a primary (due to enterohemorrhagic Escherichia coli) or secondary (due to consumption of functionally active vWF) process. This abnormality was not obvious as structural anomaly by multimer analysis.

  14. Effect of transmembrane pressure on Factor VIII yield in ATF perfusion culture for the production of recombinant human Factor VIII co-expressed with von Willebrand factor.

    Science.gov (United States)

    Kim, Seung-Chul; An, Sora; Kim, Hyun-Ki; Park, Beom-Soo; Na, Kyu-Heum; Kim, Byung-Gee

    2016-10-01

    In this study, we evaluated three cell retention devices, an alternating tangential flow (ATF) system, a spin-filter, and a Centritech Lab III centrifuge, for the production of recombinant human Factor VIII co-expressed with von Willebrand factor. From the results, it was found that the FVIII activity in bioreactor was significantly higher in the ATF perfusion culture than two other perfusion cultures. Moreover, the FVIII activity yield was unexpectedly low in the ATF perfusion culture. We have, therefore, studied the reasons for this low FVIII activity yield. It was revealed that the inactivation and the surface adsorption of FVIII onto the harvest bag were not the main reasons for the low yield in the ATF perfusion culture. The FVIII activity yield was not increased by the use of a hollow fiber filter with 0.5 μm pore size instead of 0.2 μm pore size. Additionally, the retention of FVIII molecules by the hollow fiber filter was a dominant factor in the low FVIII activity yield in the ATF perfusion culture. We demonstrated that FVIII yield was significantly improved by controlling transmembrane pressure (TMP) across the hollow fiber filter membrane. Taken together, these results suggest that TMP control could be an efficient method for the enhancement of FVIII yield in an ATF perfusion culture.

  15. Nitric oxide level and von Willebrand factor (vWF) secretion are not ...

    African Journals Online (AJOL)

    Jane

    2011-08-15

    Aug 15, 2011 ... monoclonal anti-human antibodies (eBiosciences, San Diego, CA, U.S.A.). All experiments were carried out in .... DISCUSSION. In our experiment, vWF factor was slightly decreased ... cell dysfunction should be sought in vitro based on design ... depletion associated with impaired NO production. Besides ...

  16. [Deposition of von Willebrand factor in human endothelial cells HUVEC in the endoplasmic reticulum stress induced by an excess of homocysteine in vitro].

    Science.gov (United States)

    Ignashkova, T I; Mesitov, M V; Rybakov, A S; Moskovtsev, A A; Sokolovskaia, A A; Kubatiev, A A

    2012-01-01

    Von Willebrand factor (vWF) is an adhesive glycoprotein synthesized and secreted by endothelial cells and megakaryocytes. Violation of vWF secretion by endothelial cells is a characteristic feature of endothelial dysfunction in hyperhomocysteinemia. In our study we examined to clarify the concentration-dependent effect of homocysteine (Hcy) on the expression of vWF. Our studies have shown that homocysteine excess induces changes in the intracellular deposition of von Willebrand factor in cultured human endothelial cells in vitro. Primary cultures of human umbilical vein endothelial cells (HUVEC) were incubated with the various concentrations of D,L-homocysteine (0.025 - 5 mM). Homocysteine at a concentration of 0.025 and 0.25 mM after 18 h incubation caused an increase in the intracellular fraction of vWF in HUVEC cells. High concentrations of homocysteine induced a dose-dependent decrease in the intracellular fraction of vWF. These dose-dependent variations may indicate the modulation by homocysteine of different mechanisms of the deposition, the constitutive secretion and the degradation of vWF in human endothelial cells. We proposed that Endoplasmic reticulum stress, in HUVEC cells by the action of an excess of homocysteine associated with increased intracellular levels of vWF at a relatively low concentration of the inducer. We found decline in intracellular vWF at the same duration but higher concentrations of inducer, which may be due to the ER-associated protein degradation.

  17. Associations Between Diabetic Retinopathy and Plasma Levels of High-sensitive C-reactive Protein or Von Willebrand Factor in Long-term Type 1 Diabetic Patients

    DEFF Research Database (Denmark)

    Laursen, Jonas Vejvad Nørskov; Hoffmann, Stine Skovbo; Green, Anders

    2013-01-01

    Treatment Diabetic Retinopathy Study (ETDRS) adaptation of the modified Airlie House classification of DR. Results: Median age and duration of diabetes were 58.7 and 43 years, respectively. Median levels (10th-90th percentile) of hs-CRP and von Willebrand factor antigen were 1.31 mg/l (0.37-13.3 mg/l) and 1...... a population-based cohort from Fyn County, Denmark. Plasma levels of hs-CRP and von Willebrand factor antigen were measured and related to the level of diabetic retinopathy (DR) as evaluated by dilated nine-field 45 degree monoscopic fundus photos captured by Topcon TRC-NWS6 and graded according to the Early.......27 IU/ml (0.79-2.07 IU/ml), respectively. No or minimal DR (ETDRS-levels 10-20) was found in 16.4%, mild DR (ETDRS-level 35) in 19.4%, moderate DR (ETDRS-levels 43-47) in 11.0%, and 53.2% had proliferative diabetic retinopathy (PDR) corresponding to ETDRS-level 60 or more. In an age- and sex...

  18. Prophylaxis escalation in severe von Willebrand disease: A prospective study from the von Willebrand Disease Prophylaxis Network

    NARCIS (Netherlands)

    T.C. Abshire (Thomas Calvin); J. Cox-Gill; C.L. Kempton; F.W.G. Leebeek (Frank); M. Carcao (M.); P. Kouides (P.); S. Donfield (S.); E. Berntorp

    2015-01-01

    textabstractBackground: Treatment of mucosal bleeding (epistaxis, gastrointestinal bleeding, and menorrhagia) and joint bleeding remains problematic in clinically severe von Willebrand disease (VWD). Patients are often unresponsive to treatment (e.g. desmopressin or antifibrinolytic therapy) and may

  19. von Willebrand Factor Test

    Science.gov (United States)

    ... in women Blood in urine or stool Prolonged bleeding after surgery VWF tests may be repeated when they are initially normal but suspicions of VWD remain high. When VWF testing suggests VWD, ... in bleeding disorders , such as a hematologist or coagulation specialist, ...

  20. Successful immune tolerance induction consisting of high-dose factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin: a case report

    Directory of Open Access Journals (Sweden)

    Kubisz Peter

    2012-10-01

    Full Text Available Abstract Introduction The development of factor VIII inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A. Immune tolerance induction has been accepted as the only clinically proven treatment allowing antigen-specific tolerance to factor VIII. However, some of its issues, such as patient selection, timing, factor VIII dosing, use of immunosuppressive or immunomodulatory procedures, still remain the subject of debate. Case presentation A case of a 3-year-old Caucasian boy with severe congenital hemophilia A, intron 22 inversion of the F8 gene and high-titer inhibitor, who underwent an immune tolerance induction according to the modified Bonn regimen (high doses of plasma-derived factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin is presented. The treatment lasted for 13 months and led to the eradication of inhibitor. Conclusion Addition of intravenous immunoglobulin did not negatively affect the course of immune tolerance induction and led to the rapid eradication of factor VIII inhibitor.

  1. Characterization of bitiscetin-2, a second form of bitiscetin from the venom of Bitis arietans : comparison of its binding site with the collagen-binding site on the von Willebrand factor A3-domain

    NARCIS (Netherlands)

    Obert, B.; Romijn, R. A.; Houllier, A.; Huizinga, E. G.; Girma, J. P.

    2006-01-01

    Background: Bitiscetin, a heterodimeric snake venom protein purified from Bitis arietans, binds to the A1 domain of von Willebrand factor (VWF) and induces binding of this domain to platelet glycoprotein (GP) Ib. We previously purified a distinct form of dimeric bitiscetin (herein called bitiscetin-

  2. Characterization of bitiscetin-2, a second form of bitiscetin from the venom of Bitis arietans : comparison of its binding site with the collagen-binding site on the von Willebrand factor A3-domain

    NARCIS (Netherlands)

    Obert, B.; Romijn, R. A.; Houllier, A.; Huizinga, E. G.; Girma, J. P.

    2006-01-01

    Background: Bitiscetin, a heterodimeric snake venom protein purified from Bitis arietans, binds to the A1 domain of von Willebrand factor (VWF) and induces binding of this domain to platelet glycoprotein (GP) Ib. We previously purified a distinct form of dimeric bitiscetin (herein called bitiscetin-

  3. Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy : results from the von Willebrand Disease Prophylaxis Network

    NARCIS (Netherlands)

    Holm, Elena; Abshire, Thomas C; Bowen, Joel; Álvarez, M Teresa; Bolton-Maggs, Paula; Carcao, Manuel; Federici, Augusto B; Gill, Joan Cox; Halimeh, Susan; Kempton, Christine; Key, Nigel S; Kouides, Peter; Lail, Alice; Landorph, Andrea; Leebeek, Frank; Makris, Michael; Mannucci, Pier; Mauser-Bunschoten, Eveline P; Nugent, Diane; Valentino, Leonard A; Winikoff, Rochelle; Berntorp, Erik

    Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed

  4. Contemporary issues in the management of von Willebrand disease.

    Science.gov (United States)

    Federici, Augusto B; Königs, Christoph; James, Andra H

    2016-08-31

    Von Willebrand disease (VWD) is the most common inherited bleeding disorder. Bleeding scores in VWD, focused in particular on mucosal bleeding, can be very useful in the diagnosis and validation of different types of treatment. The results of an extended prospective study with a large amount of information on clinical phenotype and implications in treatment are reviewed in this article. Treatment of mucosal and joint bleeding in severe VWD remains difficult in some patients. Due to the lack of data on the use of prophylaxis in these patients it is difficult to establish optimal treatment regimens. An overview of the literature, with a focus on the ongoing PRO.WILL study, is provided here. Furthermore, understanding the changes in von Willebrand factor (VWF) levels during pregnancy is very important for establishing the optimal management strategy for pregnancy and delivery in women with VWD. A recently published prospective observational cohort study in women with and without VWD during the postpartum period provides important data that should allow the improvement of postpartum treatment protocols.

  5. Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over von Willebrand factor and Ulex europaeus agglutinin 1.

    Science.gov (United States)

    Anthony, P P; Ramani, P

    1991-01-01

    A new monoclonal antibody, QB-END/10, raised against the CD34 antigen in human endothelial cell membranes and haemopoietic progenitor cells, was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver. QB-END/10 was both more sensitive and more specific than Von Willebrand factor (VWF) and Ulex europaeus 1 agglutinin (UEA-1) in labelling endothelial cells and it did not cross react with epithelia as UEA-1 often does. Staining was uniformly strong and clear in all histological variants of these two tumours. QB-END/10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver. Images PMID:1705261

  6. [A case of chronic inflammatory demyelinating polyradiculoneuropathy concomitant with acquired von Willebrand syndrome].

    Science.gov (United States)

    Ueda, Maki; Kawamura, Nobutoshi; Tateishi, Takahisa; Shigeto, Hiroshi; Ohyagi, Yasumasa; Kira, Jun-ichi

    2011-05-01

    We report a case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) concomitant with acquired von Willebrand syndrome. A 33-year-old man developed motor and sensory polyneuropathy with electrophysiological conduction slowing. At this time, M-protein was absent He was diagnosed with CIDP and received intravenous immunoglobulin and subsequent oral corticosteroids, which resulted in almost complete remission for over 10 years. At the age of 44, he presented with chronic anemia. Laboratory tests and colonoscopy revealed that he had acquired von Willebrand syndrome with monoclonal gammopathy of undetermined significance (IgG lambda type) and colon cancer. Bleeding symptoms were.resolved with intravenous immunoglobulin, but not with supplementation of factor VIII. Shortly after successful excision of the cancer, CIDP and acquired von Willebrand syndrome simultaneously recurred. Intravenous immunoglobulin produced rapid improvement of both neurological and hematological abnormalities. Concurring CIDP and acquired von Willebrand syndrome in the present case may indicate that the conditions have a partly common immunological background including monoclonal gammopathy and a potential common autoantibody-mediated mechanism. Alternatively, dysfunction of von Willebrand factor may increase blood-nerve barrier permeability, inducing the recurrence of CIDP.

  7. An update on the von Willebrand factor collagen binding assay: 21 years of age and beyond adolescence but not yet a mature adult.

    Science.gov (United States)

    Favaloro, Emmanuel J

    2007-11-01

    von Willebrand disease (VWD) is considered to be the most common inherited bleeding disorder. It is diagnosed after a clinical and physical review, with personal and familial evidence of (primarily mucocutaneous) bleeding, and confirmed by laboratory testing. The latter typically entails initial plasma testing of factor VIII coagulant (FVIII:C), von Willebrand factor (VWF) protein (antigen; VWF:Ag), and VWF function, which has classically been assessed using the ristocetin cofactor (VWF:RCo) assay. More recent attention has focused on another functional VWF assay, the collagen binding (VWF:CB) assay, as a possible replacement for the VWF:RCo assay or as a supplementary test of VWF adhesive "activity." Additional laboratory testing can comprise a battery of confirmatory and VWD subtype assisting assays, including assessment of VWF:multimers. This review updates our knowledge of VWD diagnostics with a particular emphasis on the VWF:CB assay. There is good evidence now in place that an optimized VWF:CB assay can significantly reduce the diagnostic error rate otherwise arising from the use of a test panel restricted to including the VWF:RCo assay as the sole functional VWF assay. Nevertheless, the VWF:CB assay should not be used to wholly replace the VWF:RCo assay in phenotypic testing but rather as a supplementary assay. However, with some thought and justification, the VWF:CB assay can be used to partly replace the VWF:RCo assay in some "screening" applications and can also be used to abrogate the need to perform routine VWF:multimers in most test cases.

  8. Using genetic diagnostics in hemophilia and von Willebrand disease.

    Science.gov (United States)

    Swystun, Laura L; James, Paula

    2015-01-01

    Most bleeding disorders encountered in clinical practice will be diagnosed, at least initially, by phenotypic assays. However, since the characterization of the genes that encode coagulation factors in the 1980s, significant progress has been made in translating this knowledge for diagnostic and therapeutic purposes. For hemophilia A and B, molecular genetic testing to determine carrier status, prenatal diagnosis, and likelihood of inhibitor development or anaphylaxis to infused coagulation factor concentrates is an established component of comprehensive clinical management. In contrast, although significant recent advances in our understanding of the molecular genetic basis of von Willebrand disease (VWD) have allowed for the development of rational approaches to genetic diagnostics, questions remain about this complex genetic disorder and how to incorporate emerging knowledge into diagnostic strategies. This article will review the state-of-the-art for molecular diagnostics for both hemophilia and VWD.

  9. Distinct roles of Ser-764 and Lys-773 at the N terminus of von Willebrand factor in complex assembly with coagulation factor VIII.

    Science.gov (United States)

    Castro-Núñez, Lydia; Bloem, Esther; Boon-Spijker, Mariëtte G; van der Zwaan, Carmen; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B

    2013-01-04

    Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766-Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764-Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism.

  10. Gender and age peculiarities of content changes of protein C, von Willebrand factor, vascular cell adhesion molecules sVCAM-1 in patients with acute left ventricle Q-wave myocardial infarction

    Directory of Open Access Journals (Sweden)

    S. M. Kyselov

    2015-04-01

    Full Text Available Markers of hemostasis have an influence on the state of postinfarction remodeling processes. Aim. In order to study the gender and age peculiarities, to determine the predictive value of the protein C, von Willebrand factor and vascular cell adhesion molecules sVCAM-1 concentration, we examined 76 patients with acute Q-wave myocardial infarction. Methods and results. On the 1st day of the disease, higher concentrations of protein C were detected in young women, vascular cell adhesion molecules sVCAM-1 - in men of any age. On the 10th day of the disease, both in men and women increase in the content of protein C, reducing the concentration of von Willebrand factor and vascular cell adhesion molecules sVCAM-1 were detected. Conclusion. Protein C has the highest prognostic potential in relation to the formation of heart aneurysm after Q-wave myocardial infarction in women of young age, and von Willebrand factor and vascular cell adhesion molecules sVCAM-1 - in older men.

  11. Atención odontológica a pacientes con enfermedad de Von Willebrand Odontologic attention for patients with von Willebrand Disease

    Directory of Open Access Journals (Sweden)

    H.D. de Miranda Chaves Netto

    2010-06-01

    Full Text Available La enfermedad de Von Willebrand, coagulopatía causada por la deficiencia de un gen que modifica la capacidad del organismo de producir factores suficientes que genere la coagulación, tienen un protocolo de tratamiento poco difundido entre los cirujanos-dentistas. El profesional debe estar alerta en pacientes con hemorragias mucocutáneas repetidas, especialmente si son asociadas a un patrón familiar, e iniciar su tratamiento multidisciplinar con el hematólogo, quien debería programar la reposición de factores que el paciente necesita para el tratamiento odontológico. En este trabajo presentamos un caso clínico de un paciente con enfermedad de Von Willebrand y discutimos el manejo odontológico para este paciente.The von Willebrand disease is a coagulopathy caused by the deficiency of the gene that modifies the organism´s ability to produce sufficient factors that promotes coagulation. What is yet unknown by dental surgeons are the means to treat these patients. This patient has au functional abilities, but a coagulation disturbs is observed. It´s a normal patient, but he bleeds excessively. The dentist showed always be attentive to the patient´s familiar and pathological background, so he can initiate the dental treatment in synergy with the hematologist; who wile program the necessity or not of factor reposition that the patient might need during the treatment. In this article we present a clinical case of von Willebrand disease and we discuss the management odontological of this patient.

  12. von Willebrand factor-cleaving protease (ADAMTS13) activity in normal non-pregnant women, pregnant and post-delivery women.

    Science.gov (United States)

    Sánchez-Luceros, Analía; Farías, Cristina E; Amaral, María M; Kempfer, Ana C; Votta, Roberto; Marchese, Carlos; Salviú, María J; Woods, Adriana I; Meschengieser, Susana S; Lazzari, María A

    2004-12-01

    ADAMTS13 dysfunction has been involved in the pathogenesis of Thrombotic Thrombocytopenic Purpura. This disorder occurs more frequently in women and, in 13% of them, is associated with pregnancy. However, there is little information on the protease behaviour in normal pregnancy. We studied von Willebrand factor and ADAMTS13 activity changes in normal non-pregnant, pregnant and post-delivery women. Fifty-five non-pregnant women, normal blood bank donors, who were not taking contraceptive pills were included as controls. A prospective cross-sectional study of 270 normal pregnant and post-delivery women was carried out. ADAMTS13 activity decreased progressively as from the period of 12-16 weeks up to the end of early puerperium (mean 52%, range 22-89, p < 0.0001), to increase slightly thereafter. Nulliparous presented mildly lower levels of ADAMTS13 activity than parous women (65% vs. 83 %, p = 0.0003), and primigravidae than multigravidae between 6-11 weeks up to 17-23 weeks of pregnancy (69% vs. 80%, p = 0.005). Although in all women the protease levels were the same by blood groups, the O blood group non-pregnant women showed a higher mean of ADAMTS13 activity than those non-O (78% vs. 69%, p = 0.064). Our results suggest that the changing levels of protease activity during pregnancy and puerperium, induced by unidentified mechanisms, could render the peripartum time more vulnerable to developed thrombotic microangiopathies.

  13. Adhesive Forces between A1 Domain of von Willebrand Factor and N-terminus Domain of Glycoprotein Ibα Measured by Atomic Force Microscopy.

    Science.gov (United States)

    Tobimatsu, Hiroaki; Nishibuchi, Yuichiro; Sudo, Ryo; Goto, Shinya; Tanishita, Kazuo

    2015-01-01

    von Willebrand factor (VWF) plays an important role in the regulation of hemostasis and thrombosis formation, particularly under a high shear rate. However, the adhesive force due to the molecular interaction between VWF and glycoprotein Ibα (GPIbα) has not been fully explored. Thus, we employed atomic force microscopy to directly measure the adhesive force between VWF and GPIbα. We measured the adhesive force between VWF and GPIbα at the molecular level using an atomic force microscope (AFM). An AFM cantilever was coated with recombinant N-terminus VWF binding site of GPIbα, whereas a cover glass was coated with native VWF. The adhesive force at the molecular level was measured using an AFM. In the presence of 1 μg/mL VWF, the adhesion force was nearly 200 pN. As per the Gaussian fit analysis, the adhesive force of a single bond could have been 54 or 107 pN. Our consideration with the Gaussian fit analysis proposed that the adhesive force of a single bond could be 54 pN, which is very close to that obtained by optical tweezers (50 pN).

  14. Pseudo (Platelet-type von Willebrand disease in pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Grover Neetu

    2013-01-01

    Full Text Available Abstract Background Pseudo (platelet-type-von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. This leads to an increased removal of VWF multimers from the circulation as well as platelets and this results in a bleeding diathesis. Worldwide, less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD. Case presentation We describe the management of platelet type von Willebrand disease in pregnancy of a 26 year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which included obstetricians, haematologists, anaesthetists and neonatologists. Care plans were made for the ante- natal, intra-partum and post-partum periods in partnership with the patient. The patient’s platelet count levels dropped significantly during the antenatal period. This necessitated the active exclusion of other causes of thrombocytopenia in pregnancy. A vaginal delivery was desired and plans were made for induction of labour at 38 weeks of gestation with platelet cover in view of the progressive fall of the platelet count. The patient however went into spontaneous labour on the day of induction. She was transfused two units of platelets before delivery. She had an unassisted vaginal delivery of a healthy baby. The successful antenatal counselling has encouraged the diagnosis of the same condition in her mother and sister. We found this to be a particularly interesting case as well as challenging to manage due to its rarity. Psuedo von Willebrand disease in pregnancy can be confused with a number of other differential diagnoses, such as gestational thrombocutopenia, idiopathatic thrombocytopenia, thrombotic thrombocytopenic purpura and pre-eclampsia; all need consideration

  15. Challenges of the management of severe hemophilia A with inhibitors: two case reports emphasizing the potential interest of a high-purity human Factor VIII/von Willebrand factor concentrate and individually tailored prophylaxis guided by thrombin-generation test.

    Science.gov (United States)

    Mathieu, Sophie; Crampe, Carine; Dargaud, Yesim; Lavigne-Lissalde, Géraldine; Escuriola-Ettingshausen, Carmen; Tardy, Brigitte; Meley, Roland; Thouvenin, Sandrine; Stephan, Jean L; Berger, Claire

    2015-12-01

    Severe hemophilia A is an X-linked bleeding disorder. Immune tolerance induction (ITI) is the best strategy of treatment when patients develop inhibitors. The objective is to illustrate the benefit of a high-purity human factor VIII/von Willebrand factor (VWF) concentrate (Octanate) in the management of ITI. We also wanted to raise the potential interest of laboratory assays such as thrombin-generation test (TGT) and epitope mapping. Two patients were treated during ITI, first with a recombinant FVIII and then with plasma-derived factor VIII without success, and, finally, with Octanate. Bypassing agents were used based on the results of TGT. Epitope mapping was performed during ITI therapy. These observations suggest the potential contribution of Octanate in the management of ITI in difficult cases. The use of bypassing agents can be necessary in prophylaxis or to treat bleedings, and may be guided by TGT results. Epitope mapping is used to describe the inhibitor. This article shows a decrease of the inhibitor directed against the C2 domain after initiation of Octanate. A high-purity human factor VIII/von Willebrand factor concentrate (Octanate) may be a valuable therapeutical option for ITI therapy. TGT and epitope mapping could be of help in the management of ITI.

  16. Von Willebrand's Disease in Two Families of Doberman Pinschers

    OpenAIRE

    Johnstone, I B; Crane, S

    1981-01-01

    The history, clinical symptoms and laboratory results in two families of Doberman pinschers with von Willebrand's disease are described. The affected animals illustrate the rather nonspecific bleeding problems that may be encountered in mild and moderate forms of this disease. In both families a bleeding diathesis was suspected when one member of the family underwent surgery with serious postoperative bleeding complications. These cases illustrate the importance of a thorough presurgical hist...

  17. Protein replacement therapy and gene transfer in canine models of hemophilia A, hemophilia B, von willebrand disease, and factor VII deficiency.

    Science.gov (United States)

    Nichols, Timothy C; Dillow, Aaron M; Franck, Helen W G; Merricks, Elizabeth P; Raymer, Robin A; Bellinger, Dwight A; Arruda, Valder R; High, Katherine A

    2009-01-01

    Dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and factor VII deficiency faithfully recapitulate the severe bleeding phenotype that occurs in humans with these disorders. The first rational approach to diagnosing these bleeding disorders became possible with the development of reliable assays in the 1940s through research that used these dogs. For the next 60 years, treatment consisted of replacement of the associated missing or dysfunctional protein, first with plasma-derived products and subsequently with recombinant products. Research has consistently shown that replacement products that are safe and efficacious in these dogs prove to be safe and efficacious in humans. But these highly effective products require repeated administration and are limited in supply and expensive; in addition, plasma-derived products have transmitted bloodborne pathogens. Recombinant proteins have all but eliminated inadvertent transmission of bloodborne pathogens, but the other limitations persist. Thus, gene therapy is an attractive alternative strategy in these monogenic disorders and has been actively pursued since the early 1990s. To date, several modalities of gene transfer in canine hemophilia have proven to be safe, produced easily detectable levels of transgene products in plasma that have persisted for years in association with reduced bleeding, and correctly predicted the vector dose required in a human hemophilia B liver-based trial. Very recently, however, researchers have identified an immune response to adeno-associated viral gene transfer vector capsid proteins in a human liver-based trial that was not present in preclinical testing in rodents, dogs, or nonhuman primates. This article provides a review of the strengths and limitations of canine hemophilia, VWD, and factor VII deficiency models and of their historical and current role in the development of improved therapy for humans with these inherited bleeding disorders.

  18. Von Willebrand Factor Antigen Predicts Response to Double Dose of Aspirin and Clopidogrel by PFA-100 in Patients Undergoing Primary Angioplasty for St Elevation Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Jacopo Gianetti

    2013-01-01

    Full Text Available Von Willebrand factor (VWF is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100 with Collagen/Epinephrine (CEPI is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR. The objective of this study was to verify the effect of double dose (DD of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n=58 or DD of aspirin and clopidogrel (DD, n=58, maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2. At Times 1 and 2 we observed a significantly higher CEPI closure times (CT in DD as compared to SD (P<0.001. Delta of CEPI-CT (T1-T0 was significantly related to VWF (P<0.001 and inversely related to ADAMTS-13 (0.01. Responders had a significantly higher level of VWF at T0. Finally, in a multivariate model analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT response (P=0.02. HRP detected by PFA-100 in acute myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF.

  19. The important role of von Willebrand factor in platelet-derived FVIII gene therapy for murine hemophilia A in the presence of inhibitory antibodies.

    Science.gov (United States)

    Shi, Q; Schroeder, J A; Kuether, E L; Montgomery, R R

    2015-07-01

    Our previous studies have demonstrated that targeting FVIII expression to platelets results in FVIII storage together with von Willebrand factor (VWF) in platelet α-granules and that platelet-derived FVIII (2bF8) corrects the murine hemophilia A phenotype even in the presence of high-titer anti-FVIII inhibitory antibodies (inhibitors). To explore how VWF has an impact on platelet gene therapy for hemophilia A with inhibitors. 2bF8 transgenic mice in the FVIII(-/-) background (2bF8(tg+/-) F8(-/-) ) with varying VWF phenotypes were used in this study. Animals were analyzed by VWF ELISA, FVIII activity assay, Bethesda assay and tail clip survival test. Only 18% of 2bF8(tg+/-) F8(-/-) VWF(-/-) animals, in which VWF was deficient, survived the tail clip challenge with inhibitor titers of 3-8000 BU mL(-1) . In contrast, 82% of 2bF8(tg+/-) F8(-/-) VWF(+/+) mice, which had normal VWF levels, survived tail clipping with inhibitor titers of 10-50,000 BU mL(-1) . All 2bF8(tg+/-) F8(-/-) VWF(-/-) mice without inhibitors survived tail clipping and no VWF(-/-) F8(-/-) mice survived this challenge. Because VWF is synthesized by endothelial cells and megakaryocytes and is distributed in both plasma and platelets in peripheral blood, we further investigated the effect of each compartment of VWF on platelet-FVIII gene therapy for hemophilia A with inhibitors. In the presence of inhibitors, 42% of animals survived tail clipping in the group with plasma-VWF and 50% survived in the platelet-VWF group. VWF is essential for platelet gene therapy for hemophilia A with inhibitors. Both platelet-VWF and plasma-VWF are required for optimal platelet-derived FVIII gene therapy for hemophilia A in the presence of inhibitors. © 2015 International Society on Thrombosis and Haemostasis.

  20. Simplagrin, a platelet aggregation inhibitor from Simulium nigrimanum salivary glands specifically binds to the Von Willebrand factor receptor in collagen and inhibits carotid thrombus formation in vivo.

    Directory of Open Access Journals (Sweden)

    Andrezza C Chagas

    2014-06-01

    Full Text Available Among the several challenges faced by bloodsucking arthropods, the vertebrate hemostatic response against blood loss represents an important barrier to efficient blood feeding. Here we report the first inhibitor of collagen-induced platelet aggregation derived from the salivary glands of a black fly (Simulium nigrimanum, named Simplagrin.Simplagrin was expressed in mammalian cells and purified by affinity-and size-exclusion chromatography. Light-scattering studies showed that Simplagrin has an elongated monomeric form with a hydrodynamic radius of 5.6 nm. Simplagrin binds to collagen (type I-VI with high affinity (2-15 nM, and this interaction does not involve any significant conformational change as determined by circular dichroism spectroscopy. Simplagrin-collagen interaction is both entropically and enthalpically driven with a large negative ΔG, indicating that this interaction is favorable and occurs spontaneously. Simplagrin specifically inhibits von Willebrand factor interaction with collagen type III and completely blocks platelet adhesion to collagen under flow conditions at high shear rates; however, Simplagrin failed to block glycoprotein VI and Iα2β1 interaction to collagen. Simplagrin binds to RGQOGVMGF peptide with an affinity (K(D 11 nM similar to that of Simplagrin for collagen. Furthermore, Simplagrin prevents laser-induced carotid thrombus formation in vivo without significant bleeding in mice and could be useful as an antithrombotic agent in thrombosis related disease.Our results support the orthology of the Aegyptin clade in bloodsucking Nematocera and the hypothesis of a faster evolutionary rate of salivary function of proteins from blood feeding arthropods.

  1. Collagen VI microfibril formation is abolished by an {alpha}2(VI) von Willebrand factor type A domain mutation in a patient with Ullrich congenital muscular dystrophy.

    Science.gov (United States)

    Tooley, Leona D; Zamurs, Laura K; Beecher, Nicola; Baker, Naomi L; Peat, Rachel A; Adams, Naomi E; Bateman, John F; North, Kathryn N; Baldock, Clair; Lamandé, Shireen R

    2010-10-22

    Collagen VI is an extracellular protein that most often contains the three genetically distinct polypeptide chains, α1(VI), α2(VI), and α3(VI), although three recently identified chains, α4(VI), α5(VI), and α6(VI), may replace α3(VI) in some situations. Each chain has a triple helix flanked by N- and C-terminal globular domains that share homology with the von Willebrand factor type A (VWA) domains. During biosynthesis, the three chains come together to form triple helical monomers, which then assemble into dimers and tetramers. Tetramers are secreted from the cell and align end-to-end to form microfibrils. The precise molecular mechanisms responsible for assembly are unclear. Mutations in the three collagen VI genes can disrupt collagen VI biosynthesis and matrix organization and are the cause of the inherited disorders Bethlem myopathy and Ullrich congenital muscular dystrophy. We have identified a Ullrich congenital muscular dystrophy patient with compound heterozygous mutations in α2(VI). The first mutation causes skipping of exon 24, and the mRNA is degraded by nonsense-mediated decay. The second mutation is a two-amino acid deletion in the C1 VWA domain. Recombinant C1 domains containing the deletion are insoluble and retained intracellularly, indicating that the mutation has detrimental effects on domain folding and structure. Despite this, mutant α2(VI) chains retain the ability to associate into monomers, dimers, and tetramers. However, we show that secreted mutant tetramers containing structurally abnormal C1 VWA domains are unable to associate further into microfibrils, directly demonstrating the critical importance of a correctly folded α2(VI) C1 domain in microfibril formation.

  2. A +220 GATA motif mediates basal but not endotoxin-repressible expression of the von Willebrand factor promoter in Hprt-targeted transgenic mice

    Science.gov (United States)

    LIU, J.; KANKI, Y.; OKADA, Y.; JIN, E.; YANO, K.; SHIH, S.-C.; MINAMI, T.; AIRD, W. C.

    2012-01-01

    Summary Background The von Willebrand factor (VWF) gene is a marker for spatial and temporal heterogeneity of the endothelium. A GATA motif at +220 has been implicated in basal VWF expression in vitro. Other studies have shown that GATA3 and VWF are transcriptionally downregulated in response to inflammatory mediators. Objectives Our goal was to determine the importance of the +220 GATA motif in mediating expression of VWF promoter in vivo, and to elucidate whether the GATA element plays a role in spatial and/or temporal regulation of VWF expression. Methods ChIP and electrophoretic mobility shift assays were carried out in human umbilical vein endothelial cells (HUVEC). Reporter gene constructs containing 3.6 kb of the human VWF promoter with and without amutation of the +220 GATA element were transfected into cultured endothelial cells or targeted to the Hprt locus of mice. The Hprt-targeted mice were subjected to endotoxemia. Results In protein-DNA binding assays, the +220 GATA motif bound GATA-2, -3 and -6. Mutation of the GATA site resulted in reduced basal promoter activity in HUVEC. When targeted to the Hprt locus of mice, the GATA mutation resulted in a significant, proportionate reduction of promoter activity in LacZ expressing vascular beds. Systemic administration of lipopolysaccharide (LPS) resulted in a widespread reduction in VWF mRNA expression and promoter activity. LPS-mediated repression of the VWF promoter was unaffected by the GATA mutation. Conclusions A region of the VWF promoter between −2182 and the end of the first intron contains information for LPS-mediated gene repression. The +220 GATA motif is important for basal, but not LPS-repressible expression of the VWF gene. PMID:19496923

  3. Posttonsillectomy hemorrhage in children with von Willebrand disease or hemophilia.

    Science.gov (United States)

    Sun, Gordon H; Auger, Katherine A; Aliu, Oluseyi; Patrick, Stephen W; DeMonner, Sonya; Davis, Matthew M

    2013-03-01

    It is uncertain whether children with bleeding disorders are at higher risk of posttonsillectomy hemorrhage compared with the general pediatric population. To estimate the national rate of posttonsillectomy hemorrhage in children previously diagnosed with von Willebrand disease (VWD) or hemophilia, and to analyze potential risk factors for postoperative bleeding in these children. A cross-sectional analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database (KID) from the Agency for Healthcare Research and Quality for 2000, 2003, 2006, and 2009. Academic and community-based nonrehabilitation hospitals from 44 states participating in the KID project. An estimated 508 children with either VWD or hemophilia. Tonsillectomy with and without adenoidectomy, and subsequent hospitalization. Treatment for posttonsillectomy hemorrhage. We extracted all cases of tonsillectomy, adenotonsillectomy, and posttonsillectomy hemorrhage in patients with VWD or hemophilia using International Classification of Diseases, Ninth Revision diagnostic and procedure codes and applied national weights to estimate rates of posttonsillectomy hemorrhage. Using data regarding patient demographic characteristics, surgical indication, blood transfusion, hospital length of stay, and mortality, we conducted bivariate analyses to identify associations between possible risk factors and posttonsillectomy hemorrhage. Mean age was 7 years, and most patients were male, white, urbanites who had private insurance and underwent tonsillectomy for airway obstruction. The hemorrhage rate within 1 day of tonsillectomy (immediate) was 1.6% while the hemorrhage rate at least 2 days after tonsillectomy (delayed) was estimated at 15%. Delayed hemorrhage was associated with older age (P < .001) and was as high as 35% in children at least 16 years old. The rate of blood transfusion was 2.4%. There were no fatalities. The frequency of immediate posttonsillectomy hemorrhage in children with VWD or

  4. Assembly and activation of alternative complement components on endothelial cell-anchored ultra-large von Willebrand factor links complement and hemostasis-thrombosis.

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    Nancy A Turner

    Full Text Available BACKGROUND: Vascular endothelial cells (ECs express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. The alternative complement pathway (AP is an important non-antibody-requiring host defense system. Thrombotic microangiopathies can be associated with defective regulation of the AP (atypical hemolytic-uremic syndrome or with inadequate cleavage by ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs (thrombotic thrombocytopenic purpura. Our goal was to determine if EC-anchored ULVWF strings caused the assembly and activation of AP components, thereby linking two essential defense mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We quantified gene expression of these complement components in cultured human umbilical vein endothelial cells (HUVECs by real-time PCR: C3 and C5; complement factor (CF B, CFD, CFP, CFH and CFI of the AP; and C4 of the classical and lectin (but not alternative complement pathways. We used fluorescent microscopy, monospecific antibodies against complement components, fluorescent secondary antibodies, and the analysis of >150 images to quantify the attachment of HUVEC-released complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs (under conditions of ADAMTS-13 inhibition. We found that HUVEC-released C4 did not attach to ULVWF strings, ruling out activation of the classical and lectin pathways by the strings. In contrast, C3, FB, FD, FP and C5, FH and FI attached to ULVWF strings in quantitative patterns consistent with assembly of the AP components into active complexes. This was verified when non-functional FB blocked the formation of AP C3 convertase complexes (C3bBb on ULVWF strings. CONCLUSIONS/SIGNIFICANCE: AP components are assembled and activated on EC-secreted/anchored ULVWF multimeric

  5. Atención odontológica a pacientes con enfermedad de Von Willebrand Odontologic attention for patients with von Willebrand Disease

    OpenAIRE

    H.D. de Miranda Chaves Netto; F. Monteiro Aarestrup; S. Olate; J.R. de Albergaria-Barbosa; R. Mazzonetto; M.G.A. Miranda Chaves

    2010-01-01

    La enfermedad de Von Willebrand, coagulopatía causada por la deficiencia de un gen que modifica la capacidad del organismo de producir factores suficientes que genere la coagulación, tienen un protocolo de tratamiento poco difundido entre los cirujanos-dentistas. El profesional debe estar alerta en pacientes con hemorragias mucocutáneas repetidas, especialmente si son asociadas a un patrón familiar, e iniciar su tratamiento multidisciplinar con el hematólogo, quien debería programar la reposi...

  6. Surface-secreted von Willebrand factor mediates aggregation of ADP-activated platelets at moderate shear stress: facilitated by GPIb but controlled by GPIIb-IIIa.

    Science.gov (United States)

    Frojmovic, M M; Kasirer-Friede, A; Goldsmith, H L; Brown, E A

    1997-03-01

    We previously showed that ADP activation of washed human platelets in plasma-free suspensions supports aggregation at moderate shear stress (0.4-1.6 Nm-2) in Poiseuille flow. Although most activated platelets expressed maximal fibrinogen-occupied GPIIb-IIIa receptors, aggregation appeared to be independent of bound fibrinogen, but blocked by the hexapeptide GRGDSP. Here, we tested the hypothesis that von Willebrand factor (vWF) secreted and expressed on activated platelets mediates aggregation at moderate shear rates from 300 to 1000 s-1 corresponding to shear stresses from 0.3 to 1.1 Nm-2. Relatively unactivated platelets (Flow cytometric measurements with monoclonal antibody (mAb) 2.2.9 reporting on surface-bound vWF, and with mAb S12 reporting on alpha-granule secreted P-selectin, showed that 65% and 80%, respectively, of all platelets were maximally activated with respect to maximal secretion and surface expression of these proteins. "Resting" washed platelets exhibited both surface-bound vWF and significant P-selectin secretion. We showed that mAbs 6D1 and NMC4, respectively blocking the adhesive domains on the GPIb receptor recognizing vWF, and on the vWF molecule recognizing the GPIb receptor, partially inhibited ADP-induced aggregation under shear in Couette flow, the degree of inhibition increasing with increasing shear stress. In contrast, mAb 10E5, blocking the vWF binding domain on GPIIb-IIIa, essentially blocked all aggregation at the shear rates tested. We conclude that vWF, expressed on ADP-activated platelets, is at least the predominant cross-bridging molecule mediating aggregation at moderate shear stress. There is an absolute requirement for free activated GPIIb-IIIa receptors, postulated to interact with platelet-secreted, surface bound vWF. The GPIb-vWF cross-bridging reaction plays a facilitative role becoming increasingly important with increasing shear stress. Since aurin tricarboxylic acid, which blocks the GPIb binding domain on vWF, was

  7. ATZ11 recognizes not only Z-α1-antitrypsin-polymers and complexed forms of non-Z-α1-antitrypsin but also the von Willebrand factor.

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    Diane Goltz

    Full Text Available AIMS: The ATZ11 antibody has been well established for the identification of α1-anti-trypsin (AAT molecule type PiZ (Z-AAT in blood samples and liver tissue. In this study, we systematically analyzed the antibody for additional binding sites in human tissue. METHODS AND RESULTS: Ultrastructural ATZ11 binding was investigated immunoelectron microscopically in human umbilical vein endothelial cells (HUVECs and in platelets of a healthy individual. Human embryonic kidney (HEK293 cells were transiently transfected with Von Willebrand factor (VWF and analyzed immunocytochemically using confocal microscopy and SDS-PAGE electrophoresis followed by western blotting (WB. Platelets and serum samples of VWF-competent and VWF-deficient patients were investigated using native PAGE and SDS-PAGE electrophoresis followed by WB. The specificity of the ATZ11 reaction was tested immunohistochemically by extensive antibody-mediated blocking of AAT- and VWF-antigens. ATZ11-positive epitopes could be detected in Weibel-Palade bodies (WPBs of HUVECs and α-granules of platelets. ATZ11 stains pseudo-WBP containing recombinant wild-type VWF (rVWF-WT in HEK293 cells. In SDS-PAGE electrophoresis followed by WB, anti-VWF and ATZ11 both identified rVWF-WT. However, neither rVWF-WT-multimers, human VWF-multimers, nor serum proteins of VWF-deficient patients were detected using ATZ11 by WB, whereas anti-VWF antibody (anti-VWF detected rVWF-WT-multimers as well as human VWF-multimers. In human tissue specimens, AAT-antigen blockade using anti-AAT antibody abolished ATZ11 staining of Z-AAT in a heterozygous AAT-deficient patient, whereas VWF-antigen blockade using anti-VWF abolished ATZ11 staining of endothelial cells and megakaryocytes. CONCLUSIONS: ATZ11 reacts with cellular bound and denatured rVWF-WT and human VWF as shown using immunocytochemistry and subsequent confocal imaging, immunoelectron microscopy, SDS-PAGE and WB, and immunohistology. These immunoreactions are

  8. Plaur and Plat in vascular tissues induce von Willebrand factor release to promote deep venous thrombosis%血管组织中Plaur和Plat诱导血管性血友病因子释放促血栓形成

    Institute of Scientific and Technical Information of China (English)

    胡继红; 吴雪梅; 李宏昆; 李兴国; 周如丹; 赵学凌; 王兵

    2012-01-01

    BACKGROUND: At present, the core control network, molecular etiology and mechanism of deep vein thrombosis is still not completely clear, furthermore, there is no ideal method for early diagnosis of deep venous thrombosis.OBJECTIVE: To observe the prothrombotic role of Plaur and Plat in the vein endothelial cells in rats with traumatic deep vein thrombosis.METHODS: Clamps plus lower limb immobilization with plaster spica were used to establish rat traumatic deep vein thrombosis models. Based on time points and whether thrombosis occurred, the experiment animals were divided into pre-thrombosis, thrombosis, and non-thrombosis groups, and then femoral vein endothelial cells were harvested at 2.5 and 25 hours after modeling.RESULTS AND CONCLUSION: Gene chip analysis and real-time PCR results showed that after trauma 2.5 hours, mRNA expressions of Plaur, Plau and von Willebrand factor in the femoral vein were raised. In the process of thrombosis, Plaur, Plau and Von Willebrand factor mRNA expressions were significantly increased. Signal path analysis showed that the Plaur and Plau were upstream regulation genes for von Willebrand factor, and von Willebrand factor was the key gene for triggering platelet adhesion, aggregation and thrombosis. These findings imply that Plaur and Plau can be raised by up-regulation of von Willebrand factor expression, further to cause platelet adhesion and aggregation, and to promote traumatic deep vein thrombosis in rats.%背景:目前,深静脉血栓形成的分子病因学机制及其形成的核心调控网络仍未完全阐明,对于深静脉血栓的早期诊断预测也无理想的方法.目的:观察创伤性深静脉血栓形成大鼠静脉内皮细胞中Plaur和Plat的促血栓形成作用.方法:采用股静脉钳夹联合下肢石膏制动构建大鼠创伤性深静脉血栓模型.依据取材时间及是否有血栓形成分为血栓形成前组、血栓形成组和血栓不形成组,分别于造模后2.5,25 h取大鼠股静

  9. Acquired von Willebrand disease as a cause of recurrent mucocutaneous bleeding in primary thrombocythemia: Relationship with platelet count

    NARCIS (Netherlands)

    P.J.J. van Genderen (Perry); J.J. Michiels (Jan); S.C. van der Poel-van de Luytgaarde (Sonja); H.H.D.M. van Vliet (Huib)

    1994-01-01

    textabstractWe present a 4-year follow-up of a 42-year-old patient with primary thrombocythemia whose clinical course was complicated by two major mucocutaneous bleeding episodes. On both occasions an acquired functional von Willebrand factor deficiency was demonstrated. In contrast to what is repor

  10. Detection of heterozygotes in both parents of homozygous patients with Von Willebrand's disease.

    Science.gov (United States)

    Sultan, Y; Simeon, J; Caen, J P

    1975-01-01

    Three patients with severe Von Willebrand's disease are shown to be homozygotes. They were born from unaffected parents. New techniques using a factor-VIII-related antigen assay by the Laurell method and a ristocetin-induced platelet aggregation assay demonstrated abnormalities in these two tests in both parents of the probands. Factor-VIII-related of heterogotes could not be differentiated from normal factor-VIII-related antigen by the immunodiffusion technique, crossed immunoelectrophoresis, and filtration on a sepharose 4b column. Images PMID:805164

  11. First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study.

    Science.gov (United States)

    Kreuz, W; Escuriola Ettingshausen, C; Vdovin, V; Zozulya, N; Plyushch, O; Svirin, P; Andreeva, T; Bubanská, E; Campos, M; Benedik-Dolničar, M; Jiménez-Yuste, V; Kitanovski, L; Klukowska, A; Momot, A; Osmulskaya, N; Prieto, M; Šalek, S Z; Velasco, F; Pavlova, A; Oldenburg, J; Knaub, S; Jansen, M; Belyanskaya, L; Walter, O

    2016-01-01

    Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment. The ongoing, international, open-label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI, the standard of care in patients with inhibitors. Forty-eight prospective patients in this interim analysis received a single plasma-derived, von Willebrand factor-stabilized, FVIII concentrate (pdFVIII/VWF) for ITI. According to recommended Bonn protocol, 'low responders' at ITI start (2 years since inhibitor diagnosis, inhibitor titre ≥10 BU at the start of ITI, or prior ITI failure). Nonetheless, 34 patients (70.8%) achieved complete success, 3 (6.3%) partial success, 1 (2.1%) partial response; ITI failed in 10 patients (20.8%), all with poor prognosis factors. All six low responders achieved complete success. ITI outcome was significantly associated with inhibitor titre level at ITI start (P = 0.0068), number of poor prognosis factors for ITI success (P = 0.0187), monthly bleeding rate during ITI (P = 0.0005) and peak inhibitor titre during ITI (P = 0.0007). Twenty-two of 35 high responder patients (62.9%) with ≥1 poor prognosis factor achieved complete success. Treatment with a single pdFVIII/VWF concentrate, mainly according to the Bonn protocol, resulted in a high ITI success rate in haemophilia A patients with inhibitors and poor prognosis for ITI success. © 2015 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  12. Structural basis of type 2A von Willebrand disease investigated by molecular dynamics simulations and experiments.

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    Gianluca Interlandi

    Full Text Available The hemostatic function of von Willebrand factor is downregulated by the metalloprotease ADAMTS13, which cleaves at a unique site normally buried in the A2 domain. Exposure of the proteolytic site is induced in the wild-type by shear stress as von Willebrand factor circulates in blood. Mutations in the A2 domain, which increase its susceptibility to cleavage, cause type 2A von Willebrand disease. In this study, molecular dynamics simulations suggest that the A2 domain unfolds under tensile force progressively through a series of steps. The simulation results also indicated that three type 2A mutations in the C-terminal half of the A2 domain, L1657I, I1628T and E1638K, destabilize the native state fold of the protein. Furthermore, all three type 2A mutations lowered in silico the tensile force necessary to undock the C-terminal helix α6 from the rest of the A2 domain, the first event in the unfolding pathway. The mutations F1520A, I1651A and A1661G were also predicted by simulations to destabilize the A2 domain and facilitate exposure of the cleavage site. Recombinant A2 domain proteins were expressed and cleavage assays were performed with the wild-type and single-point mutants. All three type 2A and two of the three predicted mutations exhibited increased rate of cleavage by ADAMTS13. These results confirm that destabilization of the helix α6 in the A2 domain facilitates exposure of the cleavage site and increases the rate of cleavage by ADAMTS13.

  13. Spontaneous hemarthrosis in combined Glanzmann thrombasthenia and type 2N von Willebrand disease.

    Science.gov (United States)

    Pontara, Elena; Gresele, Paolo; Cattini, Maria Grazia; Daidone, Viviana; Barbon, Giovanni; Girolami, Antonio; Zanon, Ezio; Casonato, Alessandra

    2014-06-01

    Glanzmann thrombasthenia is a rare autosomal recessive inherited bleeding disorder characterized by the lack of platelet aggregation, caused by deficiencies and/or abnormalities of platelet GPIIb-IIIa receptor. We report a case of Glanzmann thrombasthenia combined with type 2N von Willebrand disease (VWD), a variant characterized by an impaired capacity of FVIII to bind von Willebrand factor (VWF), which results in an autosomally transmitted reduction in circulating FVIII levels. Glanzmann thrombasthenia stems from compound T1214C and G1234A mutations in the ITGA2B gene; the type 2N VWD is due to a heterozygous G2561A mutation in the VWF gene (R854Q). The haemostatic phenotype of a 48-year-old female patient was unusually characterized by a severe chronic arthropathy with loss of cartilage and the presence of subchondrial cysts involving both ankles. The arthropathy was quantified with the compatible MRI scoring system (currently used to assess arthropathy in haemophilia), reaching almost the highest score. These haemorrhagic complications are very rare in Glanzmann thrombasthenia and resemble those seen in severe haemophilia; for such, a reason we decided to explore the patient's FVIII and VWF parameters. Our findings suggest that the type 2N R854Q mutation, which is normally asymptomatic at the heterozygous level, may be expressed in the presence of a combined impairment of primary haemostasis.

  14. Preoperative screening for von Willebrand disease type 1: low yield and limited ability to predict bleeding.

    Science.gov (United States)

    Biron, C; Mahieu, B; Rochette, A; Capdevila, X; Castex, A; Amiral, J; D'Athis, F; Schved, J F

    1999-12-01

    Type 1 von Willebrand disease (vWd) is the most common hereditary bleeding disorder. The objective of this study was to measure the von Willebrand factor antigen (vWf:Ag) in a large cohort of patients who underwent surgery to assess the role of a new rapid immunoassay in a screening procedure for vWd in preoperative conditions. We studied 832 consecutive patients (540 children, 292 adults) referred to the surgical departments. For each patient we determined the vWf:Ag level with two different assays, an enzyme-linked immunosorbent assay (ELISA)(Asserachrom vWf:Ag; Diagnostica Stago, France) and a rapid immunoassay (Liatest vWf:Ag; Diagnostica Stago). Using the reference test, we found 30 of 832 patients with a vWf:Ag value below the lower limits (21 U/dL to 46 U/dL). The coefficient of correlation between the two tests was 0.77 (P = .001). When receiver operating characteristic curves were used, the cutoff value calculated to detect vWf:Ag defect with the rapid assay was 68.5 U/dL, leading to 0.36% false negatives and 9.7% false positives. Thus the rapid immunoassay appears to be a useful and easy method that is adaptable to urgent situations. Among the 30 patients with low values in ELISA, 8 had personal or familial bleeding history. Repeat blood samples confirmed the diagnosis of vWd in 5 cases, leading to a prevalence of vWd type 1 of 0.6%. However, in our series the absence of severe bleeding complications raises the question of the screening and the management of patients bearing a type 1 Willebrand disease during surgery.

  15. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial

    Directory of Open Access Journals (Sweden)

    Jensen GS

    2016-10-01

    Full Text Available Gitte S Jensen,1 Miki Lenninger,1 Michael P Ero,2 Kathleen F Benson,1 1NIS Labs, Klamath Falls, OR, 2Machaon Diagnostics, Inc., Oakland, CA, USA Objective: The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations.Materials and methods: A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD, a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF, and platelet factor-4. Seventy-four people completed the study with good compliance.Results: Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (P<0.05, and reached a high level of significance for males consuming nattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg (P<0.006. A decrease in vWF was seen in the female population consuming nattokinase (P<0.1. In the subpopulation with low plasma renin activity levels at baseline (<0.29 ng/mL/h, an increase was seen for 66% of the people after 8-week consumption of nattokinase (P

  16. Evaluation of laboratory methods to improve characterization of dogs with von Willebrand disease.

    Science.gov (United States)

    Burgess, Hilary J; Woods, J Paul; Abrams-Ogg, Anthony C G; Wood, R Darren

    2009-10-01

    The objective of the study was to investigate the value of additional tests [platelet count, partial thromboplastin time (PTT), platelet function analysis using the PFA-100, Collagen binding assay (vWF:CBA), and Factor VIII activity], for use in conjunction with the von Willebrand factor antigen enzyme-linked immunosorbent assay (ELISA), as part of a newly developed diagnostic profile for improved characterization of patients with von Willebrand disease (vWD). The study population included 183 clinically healthy canines ranging in vWF:Ag concentration from 1% to 125%. The Asserachrom vWF:Ag ELISA assay was used as an external control for the determination of vWD status. Degree of association between the additional tests and vWF concentration was evaluated, and associations between the additional tests were also assessed, including their ability to distinguish dogs with vWD from those without vWD. In addition, a reference interval was determined for the PFA-100 platelet function analyzer. Strong associations were found between the PFA-100, vWF:CBA, and Asserachrom vWF:Ag assay, and a significant association was found between the PFA-100 and vWF:CBA. An association was detected between Factor VIII activity and the Asserachrom vWF:Ag assay, the vWF:CBA and the PFA-100; however, a corresponding pattern was not visually apparent in the raw data, making the association clinically irrelevant. The association between the platelet count and the PTT with the other additional tests was negligible. Based on our results, the vWF:CBA and PFA-100 would be valuable assets, in conjunction with a vWF:Ag assay, in a canine vWD diagnostic profile to further characterize patients with this disease.

  17. The 80th anniversary of von Willebrand's disease: history, management and research.

    Science.gov (United States)

    Federici, A B; Berntorp, E; Lee, C A

    2006-11-01

    The history of von Willebrand's disease (VWD) is fascinating because it demonstrates how good clinical observations, genetic studies and biochemical skills can improve basic understanding of a disease and its management. The continuous efforts of scientists and clinicians during the last 80 years have significantly improved the knowledge of von Willebrand factor (VWF) structure and function and the management of VWD. Diagnosis of phenotype and genotype is now available in many countries and treatment is becoming more specific according to the VWD type. Any therapeutic agents must correct the dual defect of haemostasis, i.e. the abnormal platelet adhesion due to reduced and/or dysfunctional and low levels of factor VIII (FVIII) associated with VWF defects. Desmopressin (DDAVP) is the treatment of choice for type 1 VWD because it induces release of VWF from cellular compartments. Plasma virally inactivated VWF concentrates containing FVIII are effective and safe in patients unresponsive to DDAVP. There are advanced plans to develop a recombinant VWF but this product will require the concomitant administration of FVIII for the control of acute bleeds. Basic research studies on cellular biology, biochemistry and immunology have confirmed the role of VWF as a crucial participant in both haemostasis and thrombosis as its main biological activity is to support platelet adhesion-aggregation in the circulation. Retrospective and prospective clinical research studies, including bleeding history and laboratory markers for diagnosis as well as the use of DDAVP and VWF concentrates to manage or prevent bleeds in patients with VWD have been essential to provide general guidelines for VWD management. The large number of publications quoting VWD and VWF emphasizes the important role of VWF in medicine.

  18. Prevalence and spectrum of von Willebrand disease in Eastern Uttar Pradesh

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    Kumar Sandip

    2010-07-01

    Full Text Available Context: Von Willebrand disease is the most common inherited bleeding disorder with a prevalence of ≈ 1% in the general population. Studies available from India are limited, showing a prevalence of ≈ 10% of vWD amongst inherited bleeding disorders. Aims: This study aims to know the prevalence and subtypes of vWD in patients presenting with various bleeding manifestations to university hospital. Settings and Design: We investigated 840 patients presenting with bleeding manifestations in the period from August 2004 to August 2008 for bleeding disorders. Materials and Methods: Tests performed for the diagnosis of vWD included platelet count, bleeding time (BT, prothrombin time (PT, activated partial thromboplastin time (APTT, Factor VIII:C assay, von Willebrand Factor Antigen assay and Ristocetin-induced platelet aggregation. Results: Amongst 840 patients, 230 (27.38% had inherited bleeding disorder. Out of these, 40 (17.39% patients were identified as vWD. Type 1 in 17 (42.5%, Type 2 in 11 (27.5% and Type 3 vWD was present in 12 (30.0% patients. Patients′ age ranged from five months to 45 years, with 17 males and 23 females. Positive family history was seen in 12 patients (30%. Muco-cutaneous bleeding was the most common presentation. Menorrhagia was present in 100% women of reproductive age group, and hemarthrosis was seen in two male patients. Conclusions: We felt that Type I vWD with infrequent and mild bleeding episodes remain undiagnosed either because of unawareness of the disease in society or due to paucity of diagnostic facilities available in our country. Therefore, an awareness program along with enhancement of diagnostic facilities for vWD is required in our country to identify these patients for proper management thus avoiding hemorrhagic complications.

  19. High-Affinity DNA Aptamer Generation Targeting von Willebrand Factor A1-Domain by Genetic Alphabet Expansion for Systematic Evolution of Ligands by Exponential Enrichment Using Two Types of Libraries Composed of Five Different Bases.

    Science.gov (United States)

    Matsunaga, Ken-Ichiro; Kimoto, Michiko; Hirao, Ichiro

    2017-01-11

    The novel evolutionary engineering method ExSELEX (genetic alphabet expansion for systematic evolution of ligands by exponential enrichment) provides high-affinity DNA aptamers that specifically bind to target molecules, by introducing an artificial hydrophobic base analogue as a fifth component into DNA aptamers. Here, we present a newer version of ExSELEX, using a library with completely randomized sequences consisting of five components: four natural bases and one unnatural hydrophobic base, 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds). In contrast to the limited number of Ds-containing sequence combinations in our previous library, the increased complexity of the new randomized library could improve the success rates of high-affinity aptamer generation. To this end, we developed a sequencing method for each clone in the enriched library after several rounds of selection. Using the improved library, we generated a Ds-containing DNA aptamer targeting von Willebrand factor A1-domain (vWF) with significantly higher affinity (KD = 75 pM), relative to those generated by the initial version of ExSELEX, as well as that of the known DNA aptamer consisting of only the natural bases. In addition, the Ds-containing DNA aptamer was stabilized by introducing a mini-hairpin DNA resistant to nucleases, without any loss of affinity (KD = 61 pM). This new version is expected to consistently produce high-affinity DNA aptamers.

  20. Effect of fibrinolysis on bleeding phenotype in moderate and severe von Willebrand disease

    NARCIS (Netherlands)

    De Wee, E. M.; Klaij, K.; Eikenboom, H. C. J.; Van der Bom, J. G.; Fijnvandraat, K.; Laros-Van Gorkom, B. A. P.; Mauser-Bunschoten, E. P.; Meijer, K.; Goverde, G.; Van der Linden, P. W. G.; Rijken, D. C.; Leebeek, F. W. G.

    Patients with von Willebrand disease (VWD), the most common inherited bleeding disorder, display large variation in bleeding tendency, which is not completely related to VWF levels. The cause of variability in clinical expression is largely unknown. The effect of plasma fibrinolytic capacity on

  1. A systematic review of the effects of hemophilia and von Willebrand disease on arterial trombosis

    NARCIS (Netherlands)

    Biere-Rafi, Sara; Zwiers, M.; Peters, Marjolein; Van Der Meer, Jan; Rosendaal, Frits R; Buller, Harry R; Kamphuisen, Pieter W

    2009-01-01

    Background: Patients with hemophilia and von Willebrand disease (VWD) may be protected against arterial thrombosis, through a hy-pocoagulable state or atherosclerosis. We performed a systematic review to assess the association between these clotting disorders, arterial thrombosis and the prevalence

  2. Acquired von Willebrand syndrome in a patient with monoclonal gammopathy of undetermined significance.

    Science.gov (United States)

    Puronen, Camille E; Josephson, Neil C; Broudy, Virginia C

    2013-06-01

    Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that typically presents as mucocutaneous bleeding in individuals with no personal or family history of bleeding disorder. Here we present a case in which a patient presented with profound epistaxis and was found to have AVWS in the setting of monoclonal gammopathy of undetermined significance (MGUS).

  3. Technological advances in diagnostic testing for von Willebrand disease: new approaches and challenges.

    Science.gov (United States)

    Hayward, C P M; Moffat, K A; Graf, L

    2014-06-01

    Diagnostic tests for von Willebrand disease (VWD) are important for the assessment of VWD, which is a commonly encountered bleeding disorder worldwide. Technical innovations have been applied to improve the precision and lower limit of detection of von Willebrand factor (VWF) assays, including the ristocetin cofactor activity assay (VWF:RCo) that uses the antibiotic ristocetin to induce plasma VWF binding to glycoprotein (GP) IbIXV on target platelets. VWF-collagen-binding assays, depending on the type of collagen used, can improve the detection of forms of VWD with high molecular weight VWF multimer loss, although the best method is debatable. A number of innovations have been applied to VWF:RCo (which is commonly performed on an aggregometer), including replacing the target platelets with immobilized GPIbα, and quantification by an enzyme-linked immunosorbent assay (ELISA), immunoturbidimetric, or chemiluminescent end-point. Some common polymorphisms in the VWF gene that do not cause bleeding are associated with falsely low VWF activity by ristocetin-dependent methods. To overcome the need for ristocetin, some new VWF activity assays use gain-of-function GPIbα mutants that bind VWF without the need for ristocetin, with an improved precision and lower limit of detection than measuring VWF:RCo by aggregometry. ELISA of VWF binding to mutated GPIbα shows promise as a method to identify gain-of-function defects from type 2B VWD. The performance characteristics of many new VWF activity assays suggest that the detection of VWD, and monitoring of VWD therapy, by clinical laboratories could be improved through adopting newer generation VWF assays.

  4. In vivo gene transfer strategies to achieve partial correction of von Willebrand disease.

    Science.gov (United States)

    Wang, Lan; Rosenberg, Jonathan B; De, Bishnu P; Ferris, Barbara; Wang, Rui; Rivella, Stefano; Kaminsky, Stephen M; Crystal, Ronald G

    2012-06-01

    von Willebrand disease (VWD), the most common hereditary coagulation disorder, results from mutations in the 52-exon gene for von Willebrand factor (VWF), which encodes an 8.4-kB cDNA. Studies with VWF cDNA plasmids have demonstrated that in vivo gene transfer to the liver will correct the coagulation dysfunction in VWF(-/-) mice, but the correction is transient. To develop gene therapy for VWF that would mediate long-term expression of the VWF cDNA in liver, we first evaluated segmental pre-mRNA trans-splicing (SPTS) with two adeno-associated virus (AAV) serotype 8 vectors, each delivering one-half of the VWF cDNA. However, although the two vectors functioned well to generate VWF multimers after infection of cells in vitro, the efficiency of SPTS was insufficient to correct the VWF(-/-) mouse in vivo. As an alternative, we assessed the ability of a lentiviral vector to transfer the intact murine VWF cDNA in vivo directly to the neonatal liver of VWF(-/-) mice, using generation of VWF multimers, bleeding time, and bleeding volume as efficacy parameters. The VWF lentivirus generated VWF multimers and partially or completely corrected the coagulation defect on a persistent basis in 33% of the treated VWF-deficient mice. On the basis of the concept that partial persistent correction with gene transfer could be beneficial in VWD patients, these observations suggest that lentiviral delivery of VWF cDNA should be explored as a candidate for gene therapy in patients with a severe form of VWD.

  5. LIM kinase/cofilin dysregulation promotes macrothrombocytopenia in severe von Willebrand disease-type 2B

    Science.gov (United States)

    Poirault-Chassac, Sonia; Adam, Frédéric; Muczynski, Vincent; Aymé, Gabriel; Casari, Caterina; Bordet, Jean-Claude; Soukaseum, Christelle; Rothschild, Chantal; Proulle, Valérie; Pietrzyk-Nivau, Audrey; Berrou, Eliane; Christophe, Olivier D.; Rosa, Jean-Philippe; Lenting, Peter J.; Bryckaert, Marijke; Baruch, Dominique

    2016-01-01

    von Willebrand disease type 2B (VWD-type 2B) is characterized by gain-of-function mutations of von Willebrand factor (vWF) that enhance its binding to platelet glycoprotein Ibα and alter the protein’s multimeric structure. Patients with VWD-type 2B display variable extents of bleeding associated with macrothrombocytopenia and sometimes with thrombopathy. Here, we addressed the molecular mechanism underlying the severe macrothrombocytopenia both in a knockin murine model for VWD-type 2B by introducing the p.V1316M mutation in the murine Vwf gene and in a patient bearing this mutation. We provide evidence of a profound defect in megakaryocyte (MK) function since: (a) the extent of proplatelet formation was drastically decreased in 2B MKs, with thick proplatelet extensions and large swellings; and (b) 2B MKs presented actin disorganization that was controlled by upregulation of the RhoA/LIM kinase (LIMK)/cofilin pathway. In vitro and in vivo inhibition of the LIMK/cofilin signaling pathway rescued actin turnover and restored normal proplatelet formation, platelet count, and platelet size. These data indicate, to our knowledge for the first time, that the severe macrothrombocytopenia in VWD-type 2B p.V1316M is due to an MK dysfunction that originates from a constitutive activation of the RhoA/LIMK/cofilin pathway and actin disorganization. This suggests a potentially new function of vWF during platelet formation that involves regulation of actin dynamics. PMID:27734030

  6. Genetic heterogeneity in a large cohort of Indian type 3 von Willebrand disease patients.

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    Priyanka Kasatkar

    Full Text Available Though von Willebrand disease (VWD is a common coagulation disorder, due to the complexity of the molecular analysis of von Willebrand factor gene (VWF, not many reports are available from this country. Large size of the gene, heterogeneous nature of mutations and presence of a highly homologous pseudogene region are the major impediments in the genetic diagnosis of VWD. The study is aimed at unravelling the molecular pathology in a large series of VWD patients from India using an effective strategy.We evaluated 85 unrelated Indian type 3 VWD families to identify the molecular defects using a combination of techniques i.e. PCR-RFLP, direct DNA sequencing and multiple ligation probe amplification (MLPA.Mutations could be characterized in 77 unrelated index cases (ICs. 59 different mutations i.e. nonsense 20 (33.9%, missense 13 (22%, splice site 4 (6.8%, gene conversions 6 (10.2%, insertions 2 (3.4%, duplication 1 (1.7%, small deletions 10 (17% and large deletions 3 (5.1% were identified, of which 34 were novel. Two common mutations i.e. p.R1779* and p.L970del were identified in our population with founder effect. Development of alloantibodies to VWF was seen in two patients, one with nonsense mutation (p.R2434* and the other had a large deletion spanning exons 16-52.The molecular pathology of a large cohort of Indian VWD patients could be identified using a combination of techniques. A wide heterogeneity was observed in the nature of mutations in Indian VWD patients.

  7. Establishment of reference intervals for von Willebrand factor antigen and eight coagulation factors in a Korean population following the Clinical and Laboratory Standards Institute guidelines.

    Science.gov (United States)

    Jang, Ja-Hyun; Seo, Ja-Young; Bang, Sung-Hwan; Park, In-Ae; Kim, Hee-Jin; Kim, Sun-Hee

    2010-04-01

    Establishment of reference intervals for coagulation molecules is important but is costly and sometimes not feasible. Since reference intervals from manufacturers or the literature are mostly out of date or involved Western populations, the authors determined reference intervals for VWF: Ag and eight factors in a Korean population. VWF: Ag, factor VIII (FVIII), FII, FV, FVII, FIX, FX, FXI, and FXII were determined in Korean individuals visiting for routine checkup following the CLSI (Clinical and Laboratory Standards Institute) guidelines. Reagents by Diagnostica Stago were used on the STA Compact Analyzer (Diagnostica Stago). Exclusion criteria were medical history or laboratory findings that could affect the factor levels. Influence of demographic factors was analyzed. Mean +/- 2 x SD or central 95 percentile was used, as appropriate. We obtained data from 266 adults for VWF: Ag, 371 adults for FVIII, and minimum 136 adults for the rest. Reference interval for VWF was 51-176% (52-155% in blood group O and 71-186% for non-O). Reference interval for FVIII was 64-197% (55-150% in O and 77-205% in non-O). Reference interval for FII was 77-121%, FV 81-160%, FVII 68-149%, FIX 67-154%, FX 69-126%, FXI 59-138%, and FXII 48-177%. The medians of VWF: Ag, FVIII, and FIX were significantly higher in the elderly group (> or =60 years). We established local reference intervals for VWF: Ag and eight coagulation factors in a Korean population according to the CLSI guidelines. Significantly, different reference intervals were obtained in blood group O vs. non-O for VWF: Ag and FVIII. The reference intervals obtained in this study could be adopted in other clinical laboratories after appropriate validation.

  8. Rinoplastia em paciente com doença de Von Willebrand: relato de caso Rinoplastia en paciente con enfermedad de Von Willebrand: relato de caso Rhinoplasty in a patient with Von Willebrand disease: case report

    Directory of Open Access Journals (Sweden)

    Roberto Martins Matos Junior

    2007-12-01

    aprovado pelo FDA, tem sido uma prática utilizada somente em circunstâncias emergenciais, devido ao risco relativo de contaminação viral. A 1-desamino, 8-D-arginina vasopressina (DDAVP-desmopressina estimula o aumento da concentração do fator VIII, tendo a vantagem de eliminar a exposição aos patógenos transmitidos pelo sangue, além da possibilidade de administração por vias nasal, subcutânea e venosa.JUSTIFICATIVA Y OBJETIVOS: Los pacientes portadores de la enfermedad de von Willebrand presentan sangramiento anormal después de heridas y procedimientos quirúrgicos, ya que esta afecta la hemostasia primaria y secundaria debido a la alteración del factor VIII. El objetivo de este relato es elucidar el manoseo pre, peri y postoperatorio de pacientes con tal enfermedad. RELATO DEL CASO: Paciente del sexo femenino, 42 años, blanca, 165 cm, 61kg, ASA II, fue sometida a la evaluación preanestésica para la realización de rinoplastia, con diagnóstico previo de enfermedad de von Willebrand del tipo 1, siendo liberada para la intervención quirúrgica después de la evaluación hematológica, con test de DDAVP IN26 responsivo. El día de la operación, y después de la medicación preanestésica y del monitoreo adecuado, se le dio oxígeno por catéter nasal e infundida la solución de desmopresina (0,4 µg.kg-1 en 100 mL de NaCl a 0,9% por vía venosa 30 minutos antes de la operación. Enseguida se inició la inducción anestésica con sufentanil (1 µg.kg-1, propofol (4 mg.kg-1 y rocuronio (0,6 mg.kg-1 por vía venosa. A continuación se realizó la intubación traqueal seguida de ventilación controlada mecánica en sistema con absorción de CO2, mantenida con O2, N2O y sevoflurano. El acto quirúrgico duró noventa minutos. En el intraoperatorio la paciente se mantuvo hemodinámicamente estable, presentando sangramiento sin importancia. Al final de la operación fue extubada y llevada a la sala de recuperación post anestésica, donde permaneció por 120

  9. A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets.

    Science.gov (United States)

    Haji-Valizadeh, Hassan; Modery-Pawlowski, Christa L; Sen Gupta, Anirban

    2014-05-01

    There is substantial clinical interest in synthetic platelet analogs for potential application in transfusion medicine. To this end, our research is focused on self-assembled peptide-lipid nanoconstructs that can undergo injury site-selective adhesion and subsequently promote site-directed active platelet aggregation, thus mimicking platelet's primary hemostatic actions. For injury site-selective adhesion, we have utilized a coagulation factor FVIII-derived VWF-binding peptide (VBP). FVIII binds to VWF's D'-D3 domain while natural platelet GPIbα binds to VWF's A1 domain. Therefore, we hypothesized that the VBP-decorated nanoconstructs will adhere to VWF without mutual competition with natural platelets. We further hypothesized that the adherent VBP-decorated constructs can enhance platelet aggregation when co-decorated with a fibrinogen-mimetic peptide (FMP). To test these hypotheses, we used glycocalicin to selectively block VWF's A1 domain and, using fluorescence microscopy, studied the binding of fluorescently labeled VBP-decorated nanoconstructs versus platelets to ristocetin-treated VWF. Subsequently, we co-decorated the nanoconstructs with VBP and FMP and incubated them with human platelets to study construct-mediated enhancement of platelet aggregation. Decoration with VBP resulted in substantial construct adhesion to ristocetin-treated VWF even if the A1-domain was blocked by glycocalicin. In comparison, such A1-blocking resulted in significant reduction of platelet adhesion. Without A1-blocking, the VBP-decorated constructs and natural platelets could adhere to VWF concomitantly. Furthermore, the constructs co-decorated with VBP and FMP enhanced active platelet aggregation. The results indicate significant promise in utilizing the FVIII-derived VBP in developing synthetic platelet analogs that do not interfere with VWF-binding of natural platelets but allow site-directed enhancement of platelet aggregation when combined with FMP.

  10. 血管性血友病因子抗原检测参考物质的研制与评价%Preparation and Evaluation of the Reference Materials for Plasma von Willebrand Factor Antigen Testing

    Institute of Scientific and Technical Information of China (English)

    崔皓园; 李臣宾; 周文宾; 高倩; 彭明婷

    2015-01-01

    Objective To prepare and evaluate the reference materials for plasma von Willebrand Factor antigen testing with fresh frozen plasma.Methods The candidates were prepared by low temperature centrifugation in 5 different concentration levels.The homogeneity and stability of the preparation was evaluated according to the ISO Guide35 and CNAS-GL03.The comparability between STAGO and IL system was evaluated according to the WS/T 356-2011.Then the preparations were characterized by six laboratories with the Secondary Coagulation Standard established by NIBSC(SSCLOT4).Results Homogeneity evaluation of the preparation showed that there was no statistically significant difference between the groups (P >0.05),the F values of factor analysis of variance were 0.317~0.844,the uncertainty range was 1.01% ~2.06%.A linear regression based on stability evaluation indicated that the linear trend (within 24 weeks)was insignificant (P >0.05). The uncertainty range of long-term (within 24 weeks)stability was 0.79% ~ 1.20%.The results of the preparations on STAGO and IL system were comparable.The certificated values of the candidates were range from 12.2% to 138.9% with uncertainties were 0.06%~0.09%,respectively.The range of combined standard uncertainty was 0.03% ~ 0.16% while the expanded uncertainty was 2.2%~6.7%.Conclusion The reference materials for von Willebrand Factor antigen testing were stable and homogenous with comparability between STAGO and IL.The method of characterization was accurate and reliable.%目的:利用新鲜冰冻血浆制备血管性血友病因子(von willebrand factor,vWF)抗原检测参考物质并进行评价。方法采用低温离心法制备5个浓度水平的参考物质。按照 ISO Guide35及 CNAS-GL03的要求,评价参考物质的均匀性和稳定性;依据行业标准 WS/T 356-2011对参考物质在 STAGO 和 IL 检测系统的互通性进行评价;依据 ISO Guide 35的要求以 NIBSC 凝血标准品(SSCLOT4

  11. [A patient with coexistence of primary hyperparathyroidism, Marfan's syndrome and von Willebrand's disease].

    Science.gov (United States)

    Bednarek-Tupikowska, Grazyna; Rakowska-Chort, Anna; Adamarczuk-Janczyszyn, Maria

    2008-01-01

    We presented a case of a 58 year old women suffering from three diseases: primary hyperparathyroidism, Marfan's syndrome and von Willebrand's disease. The coexistence of these diseases is not mentioned in medical literature. Because of the coexistence of Marfan's syndrome with primary hyperparathyroidism, the examinations of other endocrinopathy including multiple endocrine neoplasia (MEN). Their coexistence was not confirmed at the present time. In this paper the new views on both patogenesis and treatment of the mentioned diseases were included.

  12. Rinoplastia em paciente com doença de Von Willebrand: relato de caso Rinoplastia en paciente con enfermedad de Von Willebrand: relato de caso Rhinoplasty in a patient with Von Willebrand disease: case report

    OpenAIRE

    Roberto Martins Matos Junior; Rogério da Costa Godoy; Mônica da Cunha Gobbo; João Lian Junior; Gilson Luis Duz

    2007-01-01

    JUSTIFICATIVA E OBJETIVOS: Os pacientes portadores da doença de von Willebrand apresentam sangramento anormal após ferimentos e procedimentos cirúrgicos, já que esta afeta a hemostasia primária e secundária devido à alteração do fator VIII. O objetivo deste relato é elucidar o manuseio pré-, peri- e pós-operatório de pacientes com tal doença. RELATO DO CASO: Paciente do sexo feminino, 42 anos, branca, 165 cm, 61 kg, ASA II, foi submetida à avaliação pré-anestésica para realização de rinoplast...

  13. Cesariana em paciente com doença de von Willebrand associada à infecção pelo HIV: relato de caso Cesárea en paciente con enfermedad de von Willebrand asociada a la infección por el HIV: relato de caso Anesthesia for cesarean section in patient with von Willebrand's disease and HIV infection: case report

    Directory of Open Access Journals (Sweden)

    Vanessa Rezende Balle

    2004-12-01

    Willebrand y HIV positiva sometida a cesárea. RELATO DEL CASO: Paciente de 24 años, portadora de anemia microcítica, enfermedad de von Willebrand y HIV, llegó a la emergencia obstétrica en inicio de trabajo de alumbramiento. No realizó prenatal. Fue indicada cesárea a fin de disminuir los riesgos de transmisión vertical en paciente con carga vírica de HIV desconocida. Presentaba hematomas por el cuerpo e historia de hematoma de pared abdominal en cesárea anterior. Los tests de coagulación estaban un poco alterados. Después de infusión de concentrado de factor VIII fue realizada anestesia general. Madre y recién nacido presentaron evolución satisfactoria. CONCLUSIONES: La evaluación de manifestaciones clínicas en pacientes con coagulopatia es fundamental en la decisión del tipo de anestesia que será indicada para cada paciente. La evaluación debe ser individualizada, considerando los riesgos y beneficios de la técnica escogida. En estas pacientes, se debe siempre restringir al máximo la indicación de interrupción de la gestación por vía alta, optándose siempre por los métodos menos invasivos. La terapia con concentrado de factor VIII es actualmente la mejor opción de tratamiento, corrigiendo la deficiencia específica y dismunuyendo los riesgos de transmisión vírica.BACKGROUND AND OBJECTIVES: Von Willebrand's disease is the most common hereditary coagulation disorder in young women. The incidence of HIV infection among women has been progressively increasing, and vertical transmission may account for 25% of cases. This report aimed at describing the case of an HIV-positive patient with von Willebrand's disease scheduled for cesarean section. CASE REPORT: Female HIV-positive patient, 24 years old, with microcytic anemia and von Willebrand's disease, admitted to the emergency room in early labor. She had no pre-natal care. Cesarean section was indicated to lower vertical transmission risks since HIV viral count was unknown. Patient had hematomas

  14. Doença de von Willebrand e gestação

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    Juliana Tannuri Hobeika

    2007-05-01

    Full Text Available A doença de von Willebrand (vWD é patologia autossômica dominante caracterizada por alterações da hemostasia. Dificulta a adesão das plaquetas ao endotélio lesado. Apresenta diferentes fenótipos clínicos, sendo o sangramento mucocutâneo o mais comum, principalmente epistaxe e menorragia¹. Sangramentos em outros locais, como no sistema gênito-urinário e aparelho digestivo, também ao relatados, embora menos freqüentemente. A prevalência da Doença é cerca de 1%. Classifica-se em três tipos, de acordo com o defeito do Fator de von Willebrand (vWF. Para diagnóstico e classificação da vWD, são relevantes os dados da história de sangramento pessoal e familiar, além da completa análise laboratorial que inclui: Tempo de Sangramento (TS, Tempo de Tromboplastina Parcial Ativada (TTPA, métodos de filtragem sob alta pressão (“high shear stress”, Dosagem do antígeno do Fator de von Willebrand (vWF:Ag, Atividade Cofatora da Ristocetina (vWF:RCo e padrão multimérico do vWF. Para o tratamento da deficiência do fator de von Willebrand pode-se utilizar a administração endovenosa tanto de desmopressina (DDAVP: 12/12h, com efeito restrito a duas a duas repetições como Concentrados de fator VIII (livres de contaminação virótica que elimina a necessidade de plasma fresco congelado ou crioprecipitado. Os estudos da associação doença de von Willebrand e ciclo gravídico-puerperal são escassos na literatura alienígena e menos ainda na nacional. Nessas pacientes muitos autores preconizam o parto por via vaginal com o intuito de evitar maior risco de sangramento que, normalmente, é maior na cesárea, entretanto, há relatos de partos bem sucedidos ultimados por cesárea por indicação obstétrica, quando tratados profilaticamente de maneira adequada com o fator VIII. Recentemente, desaconselha-se às pacientes portadoras da doença de von Willebrand que engravidem. Relataremos, neste artigo, um caso de gestação em

  15. Successful Ultrasound-Guided Femoral Nerve Blockade and Catheterization in a Patient with Von Willebrand Disease

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    Youmna E. DiStefano

    2015-01-01

    Full Text Available Peripheral nerve blockade (PNB is superior to neuraxial anesthesia and/or opioid therapy for perioperative analgesia in total knee replacement (TKR. Evidence on the safety of PNB in patients with coagulopathy is lacking. We describe the first documented account of continuous femoral PNB for perioperative analgesia in a patient with Von Willebrand Disease (vWD. Given her history of opioid tolerance and after an informative discussion, a continuous femoral PNB was planned for in this 34-year-old female undergoing TKR. A Humate-P intravenous infusion was started and the patient was positioned supinely. Using sterile technique with ultrasound guidance, a Contiplex 18 Gauge Tuohy needle was advanced in plane through the fascia iliaca towards the femoral nerve. A nerve catheter was threaded through the needle and secured without complications. Postoperatively, a levobupivacaine femoral catheter infusion was maintained, and twice daily Humate-P intravenous infusions were administered for 48 hours; enoxaparin thromboprophylaxis was initiated thereafter. The patient was discharged uneventfully on postoperative day 4. Given documentation of delayed, unheralded bleeding from PNB in coagulopathic patients, we recommend individualized PNB in vWD patients. Multidisciplinary team involvement is required to guide factor supplementation and thromboprophylaxis, as is close follow-up to elicit signs of bleeding throughout the delayed postoperative period.

  16. Outcomes in Patients With Hemophilia and von Willebrand Disease Undergoing Invasive or Surgical Procedures.

    Science.gov (United States)

    Chapin, John; Bamme, Jaqueline; Hsu, Fraustina; Christos, Paul; DeSancho, Maria

    2017-03-01

    Adults with hemophilia A (HA), hemophilia B (HB), and von Willebrand disease (VWD) frequently require surgery and invasive procedures. However, there is variability in perioperative management guidelines. We describe our periprocedural outcomes in this setting. A retrospective chart review from January 2006 to December 2012 of patients with HA, HB, and VWD undergoing surgery or invasive procedures was conducted. Type of procedures, management including the use of continuous factor infusion, and administration of antifibrinolytics were reviewed. Adverse outcomes were defined as acute bleeding (patients with HA and HB. In all, 24 patients had severe hemophilia and 12 had mild/moderate hemophilia. Twelve patients had inhibitors. There were also 5 female carriers of HA and 6 patients with VWD. There were 34 major surgeries (26 orthopedic, 8 nonorthopedic) and 129 minor surgeries. Continuous infusion was used in 55.9% of major surgeries versus 8.5% of minor surgeries. Antifibrinolytics were administered in 14.7% of major surgeries versus 23.2% of minor surgeries. In all, 4 patients developed acute bleeding and 10 patients developed delayed bleeding. Delayed bleeding occurred in 28.6% of genitourinary procedures and in 16.1% of dental procedures. Five patients acquired an inhibitor and 2 had thrombosis. In conclusion, patients with HA, HB, or VWD had similar rates of adverse outcomes when undergoing minor surgeries or major surgeries. This finding underscores the importance of an interdisciplinary management and procedure-specific guidelines for patients with hemophilia and VWD prior to even minor invasive procedures.

  17. Characterization of conformation-sensitive antibodies to ADAMTS13, the von Willebrand cleavage protease.

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    Zuben E Sauna

    Full Text Available BACKGROUND: The zinc metalloprotease ADAMTS13 is a multidomain protein that cleaves von Willebrand Factor (VWF and is implicated in Thrombotic Thrombocytopenic Purpura (TTP pathogenesis. Understanding the mechanism of this protein is an important goal. Conformation sensitive antibodies have been used to monitor protein conformation and to decipher the molecular mechanism of proteins as well as to distinguish functional and non-functional mutants. METHODOLOGY/PRINCIPAL FINDINGS: We have characterized several antibodies against ADAMTS13, both monoclonal and polyclonal. We have used flow cytometry to estimate the binding of these antibodies to ADAMTS13 and demonstrate that antibodies raised against the TSP and disintegrin domains detect conformation changes in the ADAMTS13. Thus for example, increased binding of these antibodies was detected in the presence of the substrate (VWF, mainly at 37 degrees C and not at 4 degrees C. These antibodies could also detect differences between wild-type ADAMTS13 and the catalytically deficient mutant (P475S. The flow cytometry approach also allows us to estimate the reactivity of the antibody as well as its apparent affinity. CONCLUSIONS/SIGNIFICANCE: Our results suggest that these antibodies may serve as useful reagents to distinguish functional and non-functional ADAMTS13 and analyze conformational transitions to understand the catalytic mechanism.

  18. A comparison of nano-electrospray gas-phase electrophoretic mobility macromolecular analysis and matrix-assisted laser desorption/ionization linear time-of-flight mass spectrometry for the characterization of the recombinant coagulation glycoprotein von Willebrand factor.

    Science.gov (United States)

    Kemptner, Jasmin; Marchetti-Deschmann, Martina; Müller, Roland; Ivens, Andreas; Turecek, Peter; Schwarz, Hans Peter; Allmaier, Günter

    2010-03-01

    Von Willebrand factor (VWF), an adhesive glycoprotein with an approximate molecular weight (MW) of the monomer of 260 kDa, circulates in human blood plasma as a series of multimers ranging in size up to 20.000 kDa; thus the determination of the accurate MW of the monomer is of great importance and due to its high MW quite challenging. In this study accurate MW determination of intact recombinant VWF monomer (rVWF) was performed with GEMMA (gas-phase electrophoretic mobility macromolecular analysis) and MALDI TOF MS (matrix-assisted laser desorption/ionization linear time-of-flight mass spectrometry). Three rVWF preparations with differing buffer systems and glycoprotein concentrations were analyzed. First investigations directed towards heterogeneity determination by means of capillary gel electrophoresis (CGE)-on-the-chip with a laser-induced fluorescence detector revealed two compounds (MW of 277 kDa (migration time 44.3 s) and 341 kDa (migration time 49.5 s)) present in each sample to varying extents, namely mature and pro-rVWF. MALDI MS analysis in the linear positive ion mode allowed the detection of mature rVWF with an exact MW of 256.1 kDa (+/-0.8%) and pro-rVWF with a MW of 349.8 kDa (+/-0.8%). Two samples containing pro-rVWF in very minor concentration resulted in GEMMA detection of the mature rVWF with a MW of 227.4 kDa (+/-2.5%), derived from the measured globular size of 10.9 nm. For one sample containing both rVWF species in almost equal concentrations no differentiation of the two species was possible with GEMMA. Due to its lower resolution only a peak representing a mixture of both species at 11.8 nm could be observed, yielding a MW of 298.8 kDa (+/-1.6%).

  19. Influence of glycated low density lipoprotein on the proliferation,expression of intercellular adhesion molecule-1,von Willebrand factor of human umbilical endothelial cells

    Institute of Scientific and Technical Information of China (English)

    LU Jun; LIU Hui-ying; ZHANG Xiu-zhen; LEI Tao

    2009-01-01

    @@ Diabetes mellitus known as its macro-and microangiopathy has caused thousands of mortality per year.Recent researches showed that hyperglycemia,advanced glycation end products(AGEs)and some other factors acted on the process of atherogenesis.AGEs can combine with receptors of AGEs(RAGEs),which exist on the vascular endothelium,smooth muscle cells,macrophage,lymphocyte and so on.

  20. Activation of pathways involved in HUVEC apoptosis and proliferation. Sex hormones agonist related. Effect of hormones on von Willebrand factor and ADAMTS 13 release

    OpenAIRE

    Powazniak, Yanina

    2008-01-01

    El VWF es una glicoproteína adhesiva, sintetizada en las CE y megacariocitos. Se sintetiza en forma monomérica, luego se organiza en dímeros y se multimeriza. El VWF media la adhesión de plaquetas al subendotelio vascular dañado y lel transporte del factor FVIII. La ADAMTS13, proteasa que cliva al VWF, pertenece a la familia de metaloproteasas ADAMTS, llamadas así por la combinación característica de una desintegrina y una metaloproteasa con motivos trombospondina tipo 1. La ADAMTS13 es sinte...

  1. Enfermedad de von Willebrand como manifestación clínica inhabitual del hipotiroidismo primario: Caso clínico

    OpenAIRE

    Concha N,Rodrigo; Borzone V,María Alejandra; Castillo N,Marcelo; Rossle S,Alberto; Quevedo L,Iván

    2005-01-01

    Patients with hypothyroidism may have a minor increase in their bleeding tendency, causing easy bruising and menorrhagia. There is a positive correlation between factor VIII coagulant activity and thyroxin serum levels. Thus, patients with hypothyroidism have an acquired coagulation defect that is reversible with thyroxin supplementation. We report two sisters, aged 13 and 11 years, who met the criteria for von Willebrand's disease at the age of eight. Both sisters had a primary hypothyroidis...

  2. Cesariana em paciente com doença de von Willebrand associada à infecção pelo HIV: relato de caso Cesárea en paciente con enfermedad de von Willebrand asociada a la infección por el HIV: relato de caso Anesthesia for cesarean section in patient with von Willebrand's disease and HIV infection: case report

    OpenAIRE

    Vanessa Rezende Balle; Sheila Braga Machado; Marcos Emanuel Wortmann Gomes; Florentino Fernandes Mendes

    2004-01-01

    JUSTIFICATIVA E OBJETIVOS: A doença de von Willebrand é a alteração inata da coagulação mais freqüente em mulheres jovens. A infecção por HIV tem mostrado incidência progressivamente maior em mulheres, constatando-se transmissão vertical em até 25% dos casos. O objetivo deste relato é mostrar o caso de uma paciente com doença de von Willebrand e HIV positivo submetida à cesariana. RELATO DO CASO: Paciente de 24 anos, portadora de anemia microcítica, doença de von Willebrand e HIV, chegou à em...

  3. Anestesia para septoplastia e turbinectomia em paciente portador de doença de von Willebrand: relato de caso Anestesia para septoplastia y turbinectomia en paciente portador de enfermedad de von Willebrand: relato de caso Anesthesia for septoplasty and turbinectomy in von Willebrand disease patient: case report

    OpenAIRE

    Múcio Paranhos Abreu; André de Moraes Porto; Alexandre Leite Minari; Henrique Gonçalves Caseli

    2003-01-01

    JUSTIFICATIVA E OBJETIVOS: Embora a doença de von Willebrand seja o mais comum dos distúrbios hemorrágicos hereditários, as publicações nacionais, relacionando esta doença e a prática anestésica, são escassas. O objetivo deste relato é apresentar um caso de anestesia geral para septoplastia e turbinectomia em paciente portador de doença de von Willebrand - Tipo I, tratado profilaticamente com desmopressina (1-deamino-8-D-arginina vasopressina, DDAVP) nos períodos pré e pós-operatório. RELATO ...

  4. Severe transfuse related acute lung injury (TRALI) syndrome in a 14 years old girl with a history of type I von Willebrand disease.

    Science.gov (United States)

    Arghir, Oana C; Ionescu, Florin C; Apostol, Adriana

    2012-01-01

    Von Willebrand disease (vWD) is the most common inherited bleeding disorder based on an autosomal abnormality of von Willebrand factor. Transfusion is a lifesaving medical intervention among patients with bleeding disorders. Patients with vWD are exposed to Transfuse Related Acute Lung Injury (TRALI) when they become recipients of multiple blood products and repeated transfusions. TRALI is a non-hemolytic transfusion reaction induced by infusions of intravenous immunoglobulin, platelets (suspended in plasma), whole blood, cryoprecipitates, and fresh frozen plasma (FFP). We report a 14 years old white girl, with a history of type 1 von Willebrand disease (vWd), recipient of 2 units' fresh-frozen plasma (FFP) and 1 unit whole blood transfusion who developed an acute respiratory distress with severe hypoxemia and bilateral pulmonary infiltrate on chest X-ray within 3 hours of the whole blood transfusion, completely reversible after mechanical ventilation. Concluding, patients with vWd who received recurrent transfusions have an increased risk of TRALI. Physicians must be familiar with it as a cause of white lung X-ray pattern.

  5. [Acute epidural hematoma of the posterior fossa in a case of von Willebrand's disease].

    Science.gov (United States)

    Takenaka, N; Mine, T; Ikeda, E; Iwai, H; Kusano, S

    1988-01-01

    A rare case of acute epidural hematoma of the posterior fossa associated with von Willebrand's disease is reported. A 9-year-old boy fell down and hit his occipital region against a floor. Soon after he came home and slept, but three hours later he began to vomit and became drowsiness. He visited our hospital and his Glasgow Coma Scale showed 13 points. CT scan on admission showed acute epidural hematoma of left posterior fossa and contusional hematoma in the right temporal lobe. The bleeding time was over 18 minutes. He had been suspected to be suffering from von Willebrand's disease two years ago. Then fresh blood, fresh frozen plasma and anti-hemophilic globulin were prepared. Ten hours after injury, the operation was begun. Fresh epidural hematoma existed as a clot beyond transverse sinus. During the procedure of dural tenting suture, diffuse bleeding from bone, muscle, subcutaneous tissue and dura occurred and it was difficult to stop the bleeding. By using fresh blood and anti-hemophilic globulin, the bleeding was controlled, and then the operation was achieved. In the postoperative course a new epidural hematoma was found in the left temporal region and a new but asymptomatic retinal hemorrhage was found in his right eye. He was discharged without any neurological deficits 25 days after operation.

  6. Effect of Tongmai Jiangzhi Oral Liquid (通脉降脂口服液) on Serum P-selectin,von Willebrand Factors and D-Dimer in Patients with Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    沈晓君; 史云菊; 王玲

    2004-01-01

    Objective: To explore the role of cytokines on the pathogenesis of atherosclerosis, and the lectins (Ps), von Willebrand (vWF), and D-dimer (D-D) in atherosclerosis (AS) patients. Methods: Sixtythree AS patients were randomly divided into the treated group ( n = 33, treated with TMJZ, 10 ml each time, three times a day) and the control group (n = 30, treated with Lovastatin, 10 mg, once daily). The levels of serum lipids (enzymatic methods), Ps, vWF, and D-D were measured before and after 8 weeks of treatment. Results: Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), apo-protein B-100 (apoB-100) were significantly decreased (P<0.05 or P< 0.01) and high-density lipoprotein cholesterol (HDL-C) was significantly raised (P<0.05) after TM JZ treatment. Serum Ps,vWF, and D-D also declined (P<0.05) after treatment. There was no significant difference between the treated and the control groups in these parameters except serum HDL-C level. Conclusion: TMJZ has good therapeutic effect in regulating serum lipids, improving endothelial cell function, inhibiting activation of platelets, and preventing the disturbance of blood coagulation/fibrinolysis function in patients with AS.

  7. 儿童肾病综合征患者血小板和血浆von Willebrand因子的变化%The changes of plasma von Willebrand factor and platelet count in children with nephrotic syndrome

    Institute of Scientific and Technical Information of China (English)

    秦雪; 詹灵凌; 甘宝文

    2001-01-01

    目的:观察儿童肾病综合征患者血小板计数和血浆von Willebrand因子的变化.方法:采用ELISA法检测58例NS患儿血浆vWF及血小板计数,并与正常对照组进行比较.结果:NS患儿vwF水平及血小板计数均明显高于正常对照组,两组有显著性差异(P<0.01).结论:血浆vWF与血小板计数同步升高与NS患儿的高凝状态及血栓形成有一定关系.

  8. Platelet-type von Willebrand disease: new insights into the molecular pathophysiology of a unique platelet defect.

    Science.gov (United States)

    Othman, Maha; Kaur, Harmanpreet; Emsley, Jonas

    2013-09-01

    Compared with coagulation factor defects, little attention is given to defects of platelet function as causes of rare bleeding disorders. Platelet-type von Willebrand disease (PT-VWD) is an autosomal dominant bleeding disorder and is unique among platelet disorders because it is characterized by platelet hyperresponsiveness rather than decreased function. The disease is caused by gain-of-function mutations in the platelet GP1BA gene, which codes for the platelet von Willebrand factor (VWF) receptor, GPIbα. Only five mutations (four missense and one deletion) have so far been reported. Affected patients suffer from mild to moderate mucocutaneous bleeding, low VWF activity compared with antigen, decreased high-molecular-weight VWF multimers, variable degree of thrombocytopenia and typically platelet aggregation in response to low concentrations of ristocetin. All reported PT-VWD missense mutations occur within the R-loop of GPIbα and it was speculated that the introduction of short branched chain mutations such as Val in PT-VWD stabilized the extended β-hairpin. Examination of this theory by surveying all the available GPIbα structures showed that a distinct conformation predominates for the R-loop when GPIbα is not bound to VWF-A1 and this provides the framework of a new hypothesis for the molecular basis of PT-VWD. Worldwide efforts to improve diagnosis of PT-VWD continue, and international systematic studies are required to further our understanding of the phenotype and the influence of the hyperresponsive GPIbα beyond hemostasis.

  9. Bleeding spectrum in children with moderate or severe von Willebrand disease : Relevance of pediatric-specific bleeding

    NARCIS (Netherlands)

    Sanders, Yvonne V.; Fijnvandraat, Karin; Boender, Johan; Mauser-Bunschoten, Evelien P.; van der Bom, Johanna G.; de Meris, Joke; Smiers, Frans J.; Granzen, Bernd; Brons, Paul; Tamminga, Rienk Y J; Cnossen, Marjon H.; Leebeek, Frank W G

    2015-01-01

    The bleeding phenotype of children with von Willebrand disease (VWD) needs to be characterized in detail to facilitate diagnosis during childhood and aid in the planning and assessment of treatment strategies. The objective was to evaluate the occurrence, type, and severity of bleeding in a large

  10. Bleeding spectrum in children with moderate or severe von Willebrand disease: Relevance of pediatric-specific bleeding

    NARCIS (Netherlands)

    Sanders, Yvonne V.; Fijnvandraat, Karin; Boender, Johan; Mauser-Bunschoten, Evelien P.; van der Bom, Johanna G.; de Meris, Joke; Smiers, Frans J.; Granzen, Bernd; Brons, Paul; Tamminga, Rienk Y J; Cnossen, Marjon H.; Leebeek, Frank W G

    2015-01-01

    The bleeding phenotype of children with von Willebrand disease (VWD) needs to be characterized in detail to facilitate diagnosis during childhood and aid in the planning and assessment of treatment strategies. The objective was to evaluate the occurrence, type, and severity of bleeding in a large co

  11. Bleeding spectrum in children with moderate or severe von Willebrand disease : Relevance of pediatric-specific bleeding

    NARCIS (Netherlands)

    Sanders, Yvonne V.; Fijnvandraat, Karin; Boender, Johan; Mauser-Bunschoten, Evelien P.; van der Bom, Johanna G.; de Meris, Joke; Smiers, Frans J.; Granzen, Bernd; Brons, Paul; Tamminga, Rienk Y J; Cnossen, Marjon H.; Leebeek, Frank W G

    2015-01-01

    The bleeding phenotype of children with von Willebrand disease (VWD) needs to be characterized in detail to facilitate diagnosis during childhood and aid in the planning and assessment of treatment strategies. The objective was to evaluate the occurrence, type, and severity of bleeding in a large co

  12. Acute cerebrovascular accident in an 18-year-old male with von Willebrand disease.

    Science.gov (United States)

    Novick, Andrew; McGrann, Sean; Lamfers, Randall

    2014-05-01

    Compared to the older populations, stroke is an infrequent occurrence in children, adolescents, and young adults. Furthermore, individuals who have hypocoagulability disorders, such as von Willebrand disease (vWD), appear to possess a degree of protection against thrombotic events. Here, we describe an 18-year-old male with a history of vWD who presented to the emergency department with left sided hemiparesis that occurred shortly after being placed in a headlock while wrestling. MRI revealed a right paramedian pontine stroke. The relationship between vWD and stroke is discussed as well as the role of neck trauma in vertebral artery injury. While vWD does appear to decrease the incidence of thrombotic events, such patients are still at risk, especially in the context of common inciting events such as neck trauma.

  13. IgG kappa monoclonal gammopathy of undetermined significance presenting as acquired type III Von Willebrand syndrome.

    Science.gov (United States)

    Howard, Christin R; Lin, Tara L; Cunningham, Mark T; Lipe, Brea C

    2014-09-01

    Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder associated with hematoproliferative disorders, autoimmune conditions, neoplasia and cardiovascular disorders that often present a diagnostic challenge. Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common causes of AVWS that typically presents later in life with mucocutaneous or postsurgical bleeding and multimers consistent with type I or II von Willebrand disease (VWD). Here, we present the case of a patient with a 32-year history of type III VWD that was ultimately found to be AVWS related to an IgG MGUS. In this case report, we highlight the diagnostic challenges of AVWS to ensure proper identification and potentially lifesaving treatment of this rare disorder.

  14. Thalidomide for treatment of gastrointestinal bleedings due to angiodysplasia : a case report in acquired von Willebrand syndrome and review of the literature

    NARCIS (Netherlands)

    Engelen, E T; van Galen, K P M; Schutgens, R E G

    2015-01-01

    INTRODUCTION: Acquired von Willebrand syndrome is a rare bleeding disorder and treatment of the associated gastrointestinal (GI) bleeding due to angiodysplasia is challenging. AIM: The aim of this study was to present a new case on the successful use of thalidomide in a patient with acquired von Wil

  15. GENÉTICA MOLECULAR DE LA HEMOFILIA A EN UNA FAMILIA COLOMBIANA CON DIAGNÓSTICO DE ENFERMEDAD DE VON WILLEBRAND Y DE HEMOFILIA A

    Directory of Open Access Journals (Sweden)

    Diana Carolina Polanía Villanueva

    2014-12-01

    Full Text Available El Factor von Willebrand circula en el plasma formando un complejo con el Factor VIII de coagulación por enlaces no covalentes. Esta interacción evita la degradación enzimática del Factor VIII y asegura su transporte al lugar de formación del coágulo de fibrina. Debido a su estrecha relación, la disminución de la actividad de un factor puede afectar la actividad del otro, lo que genera un diagnóstico clínico equivocado en cuanto a qué enfermedad se padece, si Hemofilia A o Enfermedad de von Willebrand. Este estudio reporta el caso de una familia colombiana que según diagnóstico clínico de su fenotipo, padecía las dos enfermedades. Sin embargo, dicha familia carecía de un estudio genético que permitiera verificar y contrastar el diagnóstico que hacen las entidades de salud. Por tal razón, se realizó un diagnóstico genético por pruebas moleculares que detectan mutaciones, como las inversiones en los intrones 1 y 22 por PCR de fragmentos largos y la secuenciación del gen del Factor VIII, esta última no aplicada y publicada en Colombia hasta el momento. Se encontraron dos mutaciones sinónimas en los exones 14 y 26 que no alteran la secuencia de aminoácidos en la proteína; por tanto, se descarta la presencia de Hemofilia A en la familia. Se plantea la posibilidad de un caso de Enfermedad de von Willebrand únicamente. El estudio demuestra la necesidad que hay en el país de ampliar las pruebas clínicas y de incluir el diagnóstico genético en casos de ambigüedad en el diagnóstico de estas coagulopatías.

  16. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.

    LENUS (Irish Health Repository)

    Larkin, Deirdre

    2009-03-01

    Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF) and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20) and cerebral (n = 13) P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag) level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB) was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU\\/ml versus 1.9 IU\\/ml; p<0.005). This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005). Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1). These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.

  17. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.

    Directory of Open Access Journals (Sweden)

    Deirdre Larkin

    2009-03-01

    Full Text Available Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20 and cerebral (n = 13 P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU/ml versus 1.9 IU/ml; p<0.005. This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005. Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1. These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.

  18. Establishment of an assay for active von Willebrand factor in plasma and its application%血浆活化血管性vWF测定方法的建立与应用

    Institute of Scientific and Technical Information of China (English)

    韩纪举; 潘少东; 吴亚平; de GROOT Evelyn; de GROOT Philip G; 王云; 蔡洪信; 赵晓民; 夏作理

    2010-01-01

    机制提供重要依据.%Objective To establish an double-antibody sandwich method to detect the amount of active vWF in the plasma of healthy people and diabetic patients.Methods A double-antibody sandwich method has been established using llama-derived anti-active vWF antibody and horseradish peroxidaselabelled rabbit anti-human vWF polyclonal antibodies.The study randomly selected 66 healthy people,30 diabetic patients,10 cases of von Willebrand disease 2B(vWD-2B),5 cases of congenital thrombotic thrombocytopenic purpura(TIP),13 cases of acquired TIPs and 13 cases of malaria.The activated vWF level were described as the ratio of absorbance value(A)representing activated vWF value using AU/vWFa-11 antibody-based ELISA method to the concentrations of vWF antigen.At the same time,the absorbance values representing the concentrations of active vWF were measured when the concentrations of vWF antigen were 62,125,250μg/L respectively.The data were analyzed with GraphPad Prism 4 software.Under the premise of reaching a good linear regression,plasma active vWF values were calculated as the slope ratio of the sample plasma to the standard plasma.Accordingly to the ratio evaluated the levels of active vWF in plasma.Results The coefficients of variation(CVs)for intra assays were 4.21%,4.98% and 6.32% respectively.The CVs for interassays were 6.34%,7.02% and 7.69% respectively.In healthy adults,the level of active vWF in plasma was 0.74±0.35.There was no significant difference of the vWF levels[male (7.29±5.15)×10~3μg/L,female(9.42±4.67)×10~3μg/L]and active vWF levels(male 0.74±0.34,female 0.73±0.35)between male and female in healthy people(t=1.35,0.04,P>0.05).The vWF levels of the group over 40 years old[(10.64±5.39)×10~3μg/L]were higher than these below 40 years old[(6.11 ±2.84)×10~3 μL)(t=8.24,P < 0.01)],but there was no significant difference of the active vWF levels difference between these groups(over 40 years old 0.70±0.38,under 40 years old 0.78 ± 0.29,t=1.02,P>0.05).The plasma

  19. Subcutaneous palivizumab (Synagis® administration in an infant with congenital type 2B von Willebrand disease

    Directory of Open Access Journals (Sweden)

    Karel Allegaert

    2015-01-01

    Full Text Available Intramuscular injections are contra-indicated in infants with either acquired or congenital bleeding disorders. In such patients, it is unlicensed practice to administer vaccines by subcutaneous route. However, there are no reports on subcutaneous administration of palivizumab (Synagis®. We report on the tolerance and effects of subcutaneous palivizumab administration in a former preterm girl with type 2B von Willebrand disease. Repeated subcutaneous injections of palivizumab were well tolerated with minor local reactions and no systemic side effects. Consequently, we suggest to consider the subcutaneous instead of the intramuscular route in a setting of a valid indication for palivizumab, but a contraindication for intramuscular administration. More importantly, off-label or unlicensed practices should be reported to share and improve pharmacotherapy or at least illustrate knowledge gaps.

  20. Anestesia para septoplastia e turbinectomia em paciente portador de doença de von Willebrand: relato de caso Anestesia para septoplastia y turbinectomia en paciente portador de enfermedad de von Willebrand: relato de caso Anesthesia for septoplasty and turbinectomy in von Willebrand disease patient: case report

    Directory of Open Access Journals (Sweden)

    Múcio Paranhos de Abreu

    2003-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Embora a doença de von Willebrand seja o mais comum dos distúrbios hemorrágicos hereditários, as publicações nacionais, relacionando esta doença e a prática anestésica, são escassas. O objetivo deste relato é apresentar um caso de anestesia geral para septoplastia e turbinectomia em paciente portador de doença de von Willebrand - Tipo I, tratado profilaticamente com desmopressina (1-deamino-8-D-arginina vasopressina, DDAVP nos períodos pré e pós-operatório. RELATO DO CASO: Paciente com 19 anos, sexo feminino, 58 kg, portadora de hipotiroidismo, controlado com L-tiroxina (75 mg, e de doença de von Willebrand, que se manifestou há três anos, após extração dentária dos sisos, com sangramento persistente no período pós-operatório. Com o objetivo de se evitar novos episódios hemorrágicos nos períodos per e pós-operatório da cirurgia de septoplastia e turbinectomia a que foi submetida, a paciente foi tratada profilaticamente com desmopressina (0,3 µg.kg-1. A indução anestésica foi realizada com midazolam (2,5 mg, fentanil (150 µg, droperidol (2,5 mg, lidocaína (60 mg, atracúrio (30 mg e metoprolol (4 mg, seguida de intubação traqueal e ventilação sob pressão positiva intermitente. A manutenção da anestesia foi realizada com mistura de oxigênio e óxido nitroso a 50% e sevoflurano a 2%. Esta técnica proporcionou um bom controle da freqüência cardíaca e dos níveis pressóricos durante a cirurgia. A paciente permaneceu com tampão nasal por 24 horas e, quando este foi retirado, não houve sangramento. A paciente recebeu alta hospitalar no dia seguinte ao da cirurgia, sem intercorrências. Não houve episódio hemorrágico no período pós-operatório imediato ou tardio. CONCLUSÕES: O tratamento profilático com DDAVP associado à técnica anestésica utilizada nesse caso, mostrou-se eficaz no controle do sangramento per e pós-operatório.JUSTIFICATIVA Y OBJETIVOS: Aun cuando

  1. Pif97, a von Willebrand and Peritrophin Biomineralization Protein, Organizes Mineral Nanoparticles and Creates Intracrystalline Nanochambers.

    Science.gov (United States)

    Chang, Eric P; Evans, John Spencer

    2015-09-01

    The formation of the mollusk nacre layer involves the assembly and organization of mineral nanoparticles into fracture-toughened mesoscale-sized aragonite tablets that possess intracrystalline nanoporosities. At least one nacre protein family, known as the framework proteome, is strategically located as part of a macromolecular coating around each nacre tablet and is believed to participate in tablet formation. Here, we report new studies of a recombinant form (rPif97) of a unique Japanese pearl oyster (Pinctada fucata) nacre framework biomineralization protein, Pif97. This unique protein possesses both a von Willlebrand factor type A domain (vWA, F23-Y161) and a Peritrophin A chitin-binding domain (PAC, E234-D298). rPif97 self-associates or aggregates to form amorphous protein phases that organize both amorphous and single-crystal calcium carbonate nanoparticles in vitro. Further, in the presence of nucleating calcite crystals, rPif97 protein phases deposit onto these crystals and become occluded over time, forming nanochambers within the crystal interior. The formation of these mineral-modifying amorphous protein phases is linked to the presence of intrinsic disorder and amyloid-like cross-β-strand aggregation-prone regions, and three-dimensional modeling indicates that both the vWA and PAC domains are accessible for intermolecular interactions. Thus, the vWA- and PAC-containing Pif97 protein exhibits key functionalities that would allow its participation in mollusk nacre layer tablet assembly and porosity formation.

  2. Cyclical thrombocytosis, acquired von Willebrand syndrome and aggressive non-melanoma skin cancers are common in patients with Philadelphia-negative myeloproliferative neoplasms treated with hydroxyurea.

    Science.gov (United States)

    Verner, Emma; Forsyth, Cecily; Grigg, Andrew

    2014-05-01

    Abstract Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea complications have been reported in Philadelphia-negative myeloproliferative neoplasms (MPNs), but their incidence and clinical consequences have not been defined in a large cohort of patients. We conducted a retrospective analysis of 188 consecutive patients with MPNs specifically addressing the incidence of these complications. Cyclical thrombocytosis was documented in 29 patients (15%), the majority of whom were receiving hydroxyurea. Acquired von Willebrand syndrome was identified in 17 of the 84 screened patients (20%), but was not associated with any major bleeding complications. Non-melanoma skin cancers were reported in 51 patients (27%). Hydroxyurea-related fever occurred in nine of 149 patients (6%) who received hydroxyurea. Seventy-three patients (39%) experienced a total of 98 major thrombotic events, with the majority of these occurring prior to or within 3 months of the diagnosis. Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea-related complications are not infrequent in MPNs and have important clinical consequences for management.

  3. 冠心病患者 PCI 治疗前后内皮素、血管性假血友病因子改变与早期并发症的关系%Correlation between Endothelin and the von Willebrand Factor Changes with the Presence of Complications in Patients with Coronary Heart Disease After the PCI Procedure

    Institute of Scientific and Technical Information of China (English)

    苏布道

    2015-01-01

    Objective]To study the changes of endothelin (ET)and the von Willebrand factor (vWF)before and af-ter interventional therapy in patients with coronary heart disease and the use of the two variables in predicting the presence of postoperative complications.[Methods]Two hundred and seventy-three patients with coronary heart disease in our hos-pital from January 2014 to January 2010 were selected,and the levels of serum ET and vWF were carefully monitored at certain time intervals.Additionally,the presence of postoperative complications after one year were compared with the changes of serum ET and vWF to find any correlation.[Results]Serum ET and vWF levels in the Acute Myocardia Infarc-tion (AMI)group,Unstable Angina Pectoris (UAP)group,and Stable Angina Pectoris (SAP)group before surgery,30 minutes after,and 24 hours after surgery were all significantly higher than those of the control group.The difference was statistically significant (all P <0.05).The serum Et and vWF levels in the AMI,UAP,SAP groups before surgery,30 minutes after,24 hours after,and three days after surgery were presented first as increasing and then decreasing.,The serum ET level reached its peak 30 min after the surgery while the serum vWF level peaks at 24 hours after the surgery. Peak levels of serum ET and vWF in patients with complications were significantly higher than the peak levels in the pa-tients without complications (P <0.05).Logistic regression analysis of hypertension (RR = 1.752,P =0.033),diabe-tes (RR = 1.325,P =0.038),preoperative ET level (RR = 2.896,P =0.041),and preoperative vWF levels (RR =2.336,P =0.035)were statistically significant (P <0.05)in predicting PCI complications.[Conclusion]Endothelin and the von Willebrand factor can reflect the damage of endothelium to provide value for predicting the presence of postopera-tive complications in patients with coronary heart disease..%【目的】研究冠心病患者行经皮冠状动脉介入术(PCI)前后内皮素(ET)、血

  4. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

    Directory of Open Access Journals (Sweden)

    Jacqueline Stockley

    Full Text Available The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12 could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =, both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =. Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder.

  5. The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study.

    Science.gov (United States)

    Rodeghiero, F; Castaman, G; Tosetto, A; Batlle, J; Baudo, F; Cappelletti, A; Casana, P; De Bosch, N; Eikenboom, J C J; Federici, A B; Lethagen, S; Linari, S; Srivastava, A

    2005-12-01

    The aim of this study was the validation of the criteria defining a significant mucocutaneous-bleeding history in type 1 von Willebrand disease (VWD). To avoid selection bias, 42 obligatory carriers (OC) of type 1 VWD were identified from a panel of 42 families with type 1 VWD enrolled by 10 expert centers. OC were identified by the presence of an offspring and another first degree relative with type 1 VWD (affected subjects, AFF). A standardized questionnaire was administered to evaluate hemorrhagic symptoms at the time of first examination, using a bleeding score ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion). Sensitivity, specificity, diagnostic likelihood ratios, positive and negative predictive values for the diagnosis of type 1 VWD were calculated from the data collected in OC and in 215 controls. Having at least three hemorrhagic symptoms or a bleeding score of 3 in males and 5 in females was very specific (98.6%) for the bleeding history of type 1 VWD, although less sensitive (69.1%). None of the misclassified OC had life-threatening bleeding episodes after diagnosis. We suggest that the use of a standardized questionnaire and bleeding score may be useful for the identification of subjects requiring laboratory evaluation for VWD.

  6. [Applying uncertainty theory in caring for the family of a von Willebrand disease patient experiencing first time upper gastrointestinal bleeding].

    Science.gov (United States)

    Chung, Ai-Lun; Shun, Shiow-Ching; Lin, Chih-Yu

    2009-10-01

    The purpose of this report was to describe the nursing experience in helping a primary caregiver cope with uncertainty as his mother experienced upper gastrointestinal (UGI) bleeding underlying von Willebrand disease and Scleromyxedema in an Emergency Department between 10 and 18 July 2008. Mishel's Uncertainty Theory was applied to assess the caregiver's uncertainty and patient disease progression. Data were collected through clinical observation, chart review, and interviews. The caregiver's nursing problems were identified as (1) uncertainty caused by symptoms of the rare disease and the probability of recurrent bleeding in the future; (2) uncertainty caused by lack of knowledge about the disease; (3) uncertainty caused by lack of confidence in home caring issues after UGI bleeding. During the nursing period, we provided clinical information related to the disease and offered psychological support to the caregiver based on our Mishel's Uncertainty Scale assessment. Successful strategies utilized by our intervention helped the caregiver reduce level of uncertainty, increase confidence to care for his mother, and improve the quality of further home care.

  7. 血管性血友病因子及P-选择素对狼疮肾炎患者疾病严重程度的评估作用研究%Value of Von Willebrand Factor and P-selectin in Assessing Severity of Illness in Lupus Nephritis Patients

    Institute of Scientific and Technical Information of China (English)

    杨军; 郭明好; 刘云; 张燕

    2013-01-01

    Objective To explore the value of von Willebrand Factor ( vWF ) and P - selectin in assessing severity of illness in lupus nephritis patients. Methods The level of vWF and P - selectin in 46 cases of lupus nephritis were determined. Disease activity index, renal histological activity index, and disease chronicity index were compared between the study group ( lupus nephritis patients ) and the control group ( 10 cases of health checkups ) . Results There were 5 cases of type Ⅱ lupus nephritis, 12 cases of type Ⅲ , 20 cases of type Ⅳ , and 9 cases of type V. Patients of type Ⅳ lupus nephritis had the highest disease activity index, renal histological activity index, and disease chronic index, while type Ⅱ had the lowest. The expression of vWF and P - selectin in type Ⅳ and V lupus nephritis patients were higher than that of type Ⅱ and type Ⅲ ( P < 0. 05 ) and that of the control group ( P <0. 05 ). Correlation analysis showed that vWF was positively correlated with renal histological activity index, and nearly correlated with disease activity index. P - selectin was positively correlated with disease activity index, renal histological activity index, and disease chronicity index. Conclusion The expression of vWF and P - selectin indicates disease activity and severity in lupus nephritis patients, therefore can be used as a marker to guide clinical therapy.%目的 研究血管性血友病因子(vWF)及P-选择素对狼疮肾炎患者疾病严重程度的评估作用.方法 检测我院46例狼疮肾炎患者vWF及P-选择素水平,测量疾病活动指数(SLEDAI)、肾组织活动指数、疾病慢性指数,并与健康体检者进行对比分析.结果 纳入狼疮肾炎患者Ⅱ型5例,Ⅲ型12例,Ⅳ型20例,Ⅴ型9例.不同分型的狼疮肾炎患者SLEDAI评分、肾组织活动指数均以Ⅳ型最高,Ⅱ型最低.vWF、P-选择素在Ⅳ及Ⅴ型狼疮肾炎患者中表达水平最高,且与其他两组患者相比差异有统计学意义(P<0

  8. 前肽缺失体vWF改善FⅧ基因断裂转移细胞的重链和活性分泌%Propeptide-deleted von Willebrand Factor Improves Heavy Chain Secretion and Bioactivity by Split FⅧ Gene Co-transfected Cells

    Institute of Scientific and Technical Information of China (English)

    朱甫祥; 刘泽隆; 缪静; 屈慧鸽; 迟晓艳

    2012-01-01

    Dual-vector based FVIII gene split delivery has been developped as an altenative strategy to overcome the packaging limitation of adeno-associated virus (AAV) vectors in hemophilia A gene therapy but the efficacy is undesired for the inefficient secretion of heavy chain. A propeptide-deleted mutant of von Willebrand factor (vWF-△Pro) , which functions as a carrier of FVIII was tested for its effect on dual - vector FVIII gene delivery. 48 hours post-transfection of HEK293 cell with vWF-△Pro, heavy and light chain genes of a B-domain deleted FVIII (BDD-FVIII) , a chain-specific ELISA showed high levels of heavy chain secretion of 142 ±29ng/ ml in the culture supernatant, greater than that of cell without vWF-APro co-transfection(87 + 15ng/ml). The heavy chain transfected cells showed a very low levels of heavy chain secretion in absence of vWF-△Pro although improved in presence of vWF-△Pro, but lower than that of heavy and light chain co-transfected cells indicating a pro-secretion effect of light chain on heavy chain in trans. The light chain showed higher efficient secretion in light chain gene transfection alone or co-transfection with heavy chain, which was not affected by vWF-△Pro. The Coatest assay showed an obviously higher bioactivity (0. 80 ±0. 15IU/ml) in supernatant of vWF-△Pro, heavy and light chain genes co-transfected cell, compared to vWF-APro-free co-transfection cell (0.41 ±0.08IU/ml). The supernatant from combined cells separately transfected with heavy and light chain displayed FVIII bioactivity of 0. 23 ±0. 09IU/ml in presence of vWF-APro, suggesting a function of vWF-△Pro in assembly of secreted heavy and light chain into a functional hetero-dimer. The data demonstrated that vWF-△Pro transfection could improve dual-vector mediated FVIII gene delivery forming a basis for ongoing in vivo study.%通过转von Willebrand因子(vWF)的前肽缺失突变体(vWF-△Pro)基因,探讨了vWF-△Pro对双载体转凝血Ⅷ因子(FⅧ)

  9. Changes in Content of Von Willebrand Factor and Its Catenase in Placental-Abruption Preterm Infants Cord Blood and Maternal Blood%胎盘早剥早产儿脐血与产妇静脉血血管性血友病因子及其裂解酶水平的变化

    Institute of Scientific and Technical Information of China (English)

    许靖; 李秋平; 孔祥永; 孔令凯; 陈冲; 杨璐; 周丽; 马兴娜; 封志纯

    2012-01-01

    目的 观察胎盘早剥新生儿脐血与产妇静脉血血管性血友病因子(VWF)及血管性血友病因子裂解酶(ADAMTS13)水平变化,探讨胎盘早剥新生儿凝血功能异常的病理机制.方法 北京军区总医院、北京妇产医院、北京市海淀医院产科2010年11月-2011年11月产科住院病人中,纳入发生胎盘早剥的产妇及新生儿作为胎盘早剥观察组(早剥组);非胎盘早剥观察组(非早剥组)为上述单位早剥组每例患者后2名产科入院患者,以办理入院登记时间为准.采集产妇的静脉血及新生儿脐静脉血、脐动脉血,并收集胎盘组织,用ELISA法检测其VWF、ADAMTS13水平.结果 早剥组共纳入58例,非早剥组共纳入116例.根据非早剥组检测值计算出单侧95%参考值.产妇静脉血:VWF< 857.80 U·L-1,ADAMTS13> 119.63 U·L-1;脐静脉血:VWF<852.71 U·L-1,ADAMTS13 >28.12 U·L-1;脐动脉血:VWF<1416.96 U·L-1,ADAMTS13> 147.90 U·L-1;胎盘组织VWF<760.66 U·L-1,ADAMTS13 >27.53 U·L-1.早剥组各项VWF高于非早剥组(Pa<0.05);早剥组产妇血及脐血ADAMTS13水平均低于非早剥组(Pa<0.05).结论 胎盘早剥孕妇/产妇及胎儿/新生儿体内ADAMTS13水平随VWF水平的升高而下降,VWF是胎盘早剥发生时母儿高凝状态的因素之一,ADAMTS13具有保护作用.%Objective To observe the changes in content of von willebrand factor( VWF) and its catenase(a disintegrin and metallopro-teinase with a thrombospondin type 1 motif, member 13, ADAMTS13) in the umbilical cord blood and maternal blood after placental abruption happening and to explore the pathophysiological mechanisms of the coagulation abnormalities of placental abruption. Methods The placental abruption group included the cases admitted to the General Hospital of Beijing Military Region, Obstetrics and Gynecology Hospital of Beijing and Haidian Obstetrics and Gynecology Hospital of Beijing from Nov. 2010 to Nov. 2011 ,and the 2 non

  10. The expression of von Willebrand factor and interleukin-8 in severe pulmonary contusion patients%严重肺挫伤患者冯·维勒布兰德因子,白介素8的动态变化及其意义

    Institute of Scientific and Technical Information of China (English)

    钱进先; 陆骏灏; 陆士奇; 赵益明

    2011-01-01

    Objective To study the clinical changes of von Willebrand factor( vWF) and interleukin-8 (IL-8) in patients with severe pulmonary contusion. Methods Sixty-three patients with severe pulmonary contusion were divided into three different classifications for the sake of comparison in different respects, namely (1) severe pulmonary contusion with ARDS group and severe pulmonary contusion without ARDS group, (2) survival group and non-survival group, and (3) ISS score <20 group and ISS scored 20 group. In addition, the normal control group was set up. The levels of plasma vWF and serum IL-8 were respectively detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) within 24 hours of injury and 1,3,5 and 7days after injury. The regularity of their changes was observed and the correlation factors were analyzed from the data. Results Compared with normal controls, the concentrations of plasma vWF and serum IL-8 were significantly increased in patients with severe pulmonary contusion in all intervals of detection. The concentrations of plasma vWF escalated gradually in severe pulmonary contusion with ARDS, and reached significantly higher levels in 5 days and 7 days after injury compared with those without ARDS group (P <0. 05). The increase in concentrations of serum IL-8 peaked in 5day after injury, and then declined. The levels of serum IL-8 were higher in patients with severe pulmonary contusion with ARDS group than those in this kind of patients without ARDS group. The levels of plasma vWF and serum IL-8 were higher in non - survival group than those in survival group (P < 0.05). The increase in levels of plasma vWF and serum IL-8 peaked and then declined in 5 days in ISS score 3:20 group, whereas it peaked and declined in 3 days after injury in ISS score < 20 group. The level of plasma vWF was positively correlated with platelets and negatively correlated with oxygenation index. The levels of serum IL-8 was positively correlated with white blood

  11. Cuidados nos pacientes com hemofilia e doença de von Willebrand na cirurgia eletiva otorrinolaringológica

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    Marques Marise P. C.

    2003-01-01

    Full Text Available FORMA DE ESTUDO Clínico prospectivo. MATERIAL E MÉTODO: Foi realizado um estudo prospectivo de 10 anos de 20 pacientes com hemofilias ou doença de von Willebrand (DvW com indicação de cirurgia otorrinolaringológica. Os pacientes foram submetidos a um total de 25 cirurgias otorrinolaringológicas eletivas. A idade média foi de 23,75 anos (2 a 62 anos. O grupo de estudo consistiu em 14 hemofílicos, 11 com hemofilia A grave (1 do sexo feminino, uma portadora com 30% de atividade de fator VIII (FVIII, um hemofílico B leve e uma com deficiência grave de fator X; 6 com DvW, 4 tinham o tipo 1 (3 mulheres, um o tipo 2A e um o tipo 3. Treze hemofílicos tinham síndrome de imunodeficiência adquirida. A duração média do procedimento foi de 1 hora e 37 minutos (15 minutos a 12 horas. O defeito da coagulação foi corrigido com desmopressina (DDAVP, com concentrado de FVIII de pureza intermediária 8Y, com criopreciptado ou com complexo protrombínico não ativado (PPSB, de acordo com os níveis plasmáticos do fator e da severidade da cirurgia. O ácido épsilon aminocapróico também foi usado em associação. Em 1 hemofílico A grave houve sangramento pós-operatório que se resolveu com a elevação do nível mínimo de FVIII para 80% e em 1 paciente com DvW do Tipo 3 houve sangramento pós-operatório pela dificuldade de identificação do melhor concentrado a ser reposto. Após o uso do concentrado de pureza intermediária 8Y, houve controle do sangramento. RESULTADO: Todos os outros pacientes apresentaram a hemostasia considerada normal ou excelente. CONCLUSÃO: Concluiu-se que pacientes com hemofilias ou DvW não apresentam um risco cirúrgico aumentado se for realizada uma terapia adequada.

  12. Le rôle du médecin anesthésiste-réanimateur dans la prise en charge de la femme enceinte porteuse de la maladie de Von Willebrand

    Science.gov (United States)

    Baouahi, Hanane; Zerqouni, Yassine; Doumiri, Mouhcine; Oudghiri, Nezha; Saoud, Anas Tazi

    2015-01-01

    La maladie de Von Willebrand (VWD) est la maladie hémorragique constitutionnelle de l'hémostase la plus fréquente. Elle est liée à un déficit, soit quantitatif, soit qualitatif en facteur willebrand (VWF). Elle se caractérise par son extrême hétérogénéité sur les plans clinique, phénotypique et génotypique. La grossesse et surtout le péri-partum représente une période à risque hémorragique pour ces femmes. Nous rapportons le cas d'une parturiente présentant une maladie de Von Willebrand de type 1 documentée, la difficulté du choix du mode d'accouchement et de la technique anesthésique a été revue. PMID:26977242

  13. A subpopulation of large granular von Willebrand Ag negative and CD105 positive endothelial cells, isolated from abdominal aortic aneurysms, overexpress ICAM-1 and Fas antigen.

    Science.gov (United States)

    Páez, Araceli; Archundia, Abel; Méndez Cruz, René; Rodríguez, Emma; López Marure, Rebeca; Masso, Felipe; Aceves, José Luis; Flores, Leopoldo; Montaño, Luis F

    2002-01-01

    The aim of this work was to determine whether there is a pre-established basal condition of the endothelial cells isolated from aortic abdominal aneurysm that might augment immune effector mechanisms and thus provide us an insight into the possible causes of aneurysm rupture. Endothelial cells isolated from saccular aortic aneurysm fragments were analyzed by cytofluorometry for the expression of different immune response-related molecules. Our results showed that there is a subpopulation of granule-rich, CD105 positive and von Willebrand antigen negative endothelial cells that have an enhanced basal expression of ICAM-1, and Fas antigen, but, interestingly, no apoptotic bodies were detected. Control endothelial cells derived from healthy areas of the same abdominal aortas did not show such enhanced expression. We conclude that in the endothelium that lines abdominal aorta aneurysms there is, at least, one endothelial cell subpopulation with an apparent inhibition of programmed cell death and in a proinflammatory activation status.

  14. Crystallization and preliminary X-ray analysis of the complex of the first von Willebrand type C domain bound to bone morphogenetic protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Li-yan; Zhang, Jin-li [Lehrstuhl für Physiologische Chemie II, Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Am Hubland, D-97074 Würzburg (Germany); Kotzsch, Alexander [Lehrstuhl für Molekulare Pflanzenphysiologie und Biophysik, Julius-von-Sachs Institut der Universität Würzburg, Julius-von-Sachs Platz 2, D-97082 Würzburg (Germany); Sebald, Walter [Lehrstuhl für Physiologische Chemie II, Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Am Hubland, D-97074 Würzburg (Germany); Rudolf-Virchow-Zentrum (DFG Forschungszentrum) der Universität Würzburg, Versbacher Strasse 9, D-97070 Würzburg (Germany); Mueller, Thomas D., E-mail: mueller@botanik.uni-wuerzburg.de [Lehrstuhl für Molekulare Pflanzenphysiologie und Biophysik, Julius-von-Sachs Institut der Universität Würzburg, Julius-von-Sachs Platz 2, D-97082 Würzburg (Germany); Rudolf-Virchow-Zentrum (DFG Forschungszentrum) der Universität Würzburg, Versbacher Strasse 9, D-97070 Würzburg (Germany); Lehrstuhl für Physiologische Chemie II, Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Am Hubland, D-97074 Würzburg (Germany)

    2008-04-01

    Crystals of the complex of the first von Willebrand type C domain (VWC1) of crossveinless 2 (CV2) bound to bone morphogenetic protein 2 (BMP2) exist in two tetragonal crystal forms belonging to either space group P4{sub 1}2{sub 1}2 or I4{sub 1}, with one complete BMP2 dimer and two CV2 VWC1 domains per asymmetric unit, and diffract to 2.6 Å resolution. Crossveinless 2 (CV2) is a member of the chordin family, a protein superfamily that modulates the activity of bone morphogenetic proteins such as BMP2. The BMPs represent a large group of secreted proteins that control many steps during embryonal development and in tissue and organ homeostasis in the adult organism. The gene encoding the first von Willebrand type C domain (VWC1) of CV2 was cloned, expressed in Escherichia coli and purified to homogeneity. The binary complex of CV2 VWC1 and BMP2 was purified and subjected to crystallization. Crystals of SeMet-labelled proteins were obtained in two different forms belonging to the tetragonal space groups P4{sub 1}2{sub 1}2 and I4{sub 1}, with unit-cell parameters a = b = 86.7, c = 139.2 Å and a = b = 83.7, c = 139.6 Å, respectively. Initial analysis suggests that a complete binary complex consisting of one BMP2 dimer bound to two CV2 VWC1 domains is present in the asymmetric unit.

  15. Sangramento uterino anormal pós operatório em paciente portadora de doença de Von Willebrand: relato de caso

    Directory of Open Access Journals (Sweden)

    Eduardo Borges Coscia

    2016-10-01

    Full Text Available Introdução: O sangramento uterino anormal (S.U.A pode ser uma queixa presente em até 1/3 das consultas ginecológicas. A Doença de von Willebrand é a coagulopatia hereditária mais comum, cujo diagnóstico muitas vezes só é obtido à menarca, com constatação de sangramento abundante (menorragia, anemia e prejuízo na qualidade de vida. Relato de caso: S.G.M, 36 anos, parda, casada, nuligesta. Possui diagnóstico de Doença de von Willebrand (vWD há aproximadamnte 20 anos. Em uso de ácido tranexâmico e contraceptivo oral combinado com boa resposta terapêutica. Foi encaminhada ao ambulatório de patologia Trato genital inferior com diagnóstico de biópsia do colo uterino compatível com NIC III. O tratamento indicado foi a realização de excisão da zona de transformação do colo uterino através de cirurgia de alta frequência (CAF, com confirmação de NIC III e margens livres. Evoluiu com sangramento pós operatório abundante por 3 dias e necessitou infusão de fator VIII para controle hemostático. Discussão: A menorragia pode ser o único sintoma nas mulheres com DvW. O diagnóstico baseia-se na história pessoal e familiar de sangramento e nos exames laboratoriais que demonstrem defeito qualitativo e/ou quantitativo do fator de von Willebrad (FvW. Recomenda-se monitorar o fator VIII a cada 12 horas, no dia da cirurgia e diariamente a partir do primeiro dia pós-operatório.O tratamento inicial objetiva a elevação do FvW para níveis acima de 50% e da atividade do fator VIII à nível clinicamente aceitável.

  16. Laboratory testing for von Willebrand's disease: an assessment of current diagnostic practice and efficacy by means of a multi-laboratory survey. RCPA Quality Assurance Program (QAP) in Haematology Haemostasis Scientific Advisory Panel.

    Science.gov (United States)

    Favaloro, E J; Smith, J; Petinos, P; Hertzberg, M; Koutts, J

    1999-10-01

    We report an evaluation of current laboratory practice for the diagnosis of von Willebrand's disease (VWD) by means of a multilaboratory survey. This assessment was undertaken with the RCPA Quality Assurance Program (QAP) in Haematology, which covers a wide geographic area encompassing Australia, New Zealand and Asia. A total of 25 laboratories actively involved in testing for VWD were selected to participate in a sample testing assessment exercise. Samples comprised 10 plasmas: (i) a normal plasma pool (in duplicate), (ii) this pool diluted to 50% (in duplicate), (iii) a normal individual (X1), (iv) severe Type 1 VWD (X1), (v) Type 2B VWD (x2 unrelated donors), (vi) Type 3 VWD (x1), (vii) Type 2A VWD (x1). Laboratories were asked to perform all tests available to them in order to establish a laboratory diagnosis of VWD, and then to comment on the possibility or otherwise of VWD. Overall findings indicated a wide variation in test practice, in the effectiveness of various test procedures in detecting VWD, and in the ability of various composite test panels to identify type 2 VWD subtypes. Firstly, while all laboratories (n = 25) performed tests for FVIII:C activity, von Willebrand factor 'antigen' (VWF:Ag) and a functional VWF assay [using the ristocetin cofactor assay (VWF:RCo; n = 23) and/or the collagen binding assay (VWF:CBA; n = 12)], only three laboratories carried out VWF:Multimer analysis. Secondly, for the three quantitative VWF assays, 10/25 (40%) laboratories performed all three, whereas 15/25 (60%) performed only two [VWF:Ag and VWF:RCo (n = 13); VWF:Ag and VWF:CBA (n = 2)]. Thirdly, a variety of assay methodologies were evident for VWF:Ag [ELISA, electro-immuno diffusion (EID), latex immuno-assay (LIA), and VIDAS assay] and VWF:RCo (platelet agglutination/'aggregometry' and a 'functional VWF:RCo-alternative' ELISA assay). Between method analysis for the quantitative VWF assays showed that the VWF:RCo yielded the greatest degree of inter

  17. Primary postpartum haemorrhage in women with von Willebrand disease or carriership of haemophilia despite specialised care: a retrospective survey.

    Science.gov (United States)

    Stoof, S C M; van Steenbergen, H W; Zwagemaker, A; Sanders, Y V; Cannegieter, S C; Duvekot, J J; Leebeek, F W G; Peters, M; Kruip, M J H A; Eikenboom, J

    2015-07-01

    Pregnant women with bleeding disorders require specialised peripartum care to prevent postpartum haemorrhage (PPH). If third trimester coagulation factor levels are complicated by PPH. We found an increased PPH risk in deliveries given prophylactic treatment compared with deliveries without (OR 2.7, 95% CI 1.2-6.3). In conclusion, PPH incidence was highest in deliveries with the lowest factor levels in the third trimester. Currently, delivery outcome in women with bleeding disorders is unsatisfactory, given the high PPH incidence despite specialised care. Future studies are required to optimise management of deliveries in this patient population.

  18. Structural studies on B2-glycoprotein I and von Willebrand factor A3 domain

    NARCIS (Netherlands)

    Bouma, B.

    2000-01-01

    The integrity of blood circulation is a prerequisite for life; its malfunctioning is a leading cause of morbidity and mortality in developed countries. For that reason the haemostatic system is a critical component of homeostasis. In Chapter I an overview is given of the biophysical and biochemical

  19. Transient von Willebrand factor-mediated platelet influx stimulates liver regeneration after partial hepatectomy in mice

    NARCIS (Netherlands)

    Kirschbaum, Marc; Jenne, Craig N; Veldhuis, Zwanida J; Sjollema, Klaas A; Lenting, Peter J; Giepmans, Ben N G; Porte, Robert J; Kubes, Paul; Denis, Cécile V; Lisman, Ton

    2017-01-01

    BACKGROUND & AIMS: In addition to their function in thrombosis and hemostasis, platelets play an important role in the stimulation of liver regeneration. It has been suggested that platelets deliver mitogenic cargo to the regenerating liver, and accumulation of platelets in the regenerating liver

  20. The Influence of Genetic Variation on Von Willebrand Factor levels and the Risk of Stroke

    NARCIS (Netherlands)

    M.C. van Schie (Marianne)

    2012-01-01

    markdownabstract__Abstract__ Cardiovascular disease (CVD), primarily due to arterial thrombus formation resulting in vascular occlusion, is one of the most important causes of morbidity and mortality in the world]. In the Netherlands, every day on average 51 males and 57 females die as

  1. von Willebrand Factor is elevated in HIV patients with a history of thrombosis

    NARCIS (Netherlands)

    Dries, L.W. van den; Gruters, R.A.; Hövels-van der Borden, S.B.C.; Kruip, M.J.; Maat, M.P. de; Gorp, E.C. van; Ende, M.E. van der

    2015-01-01

    BACKGROUND: Arterial and venous thrombotic events are more prevalent in HIV infected individuals compared to the general population, even in the era of combination antiretroviral therapy. Although the mechanism is not fully understood, recent evidence suggests a role for chronic immune activation. M

  2. Severe Dengue Is Associated with Consumption of von Willebrand Factor and Its Cleaving Enzyme ADAMTS-13

    NARCIS (Netherlands)

    Djamiatun, Kis; van der Ven, Andre J. A. M.; de Groot, Philip G.; Faradz, Sultana M. H.; Hapsari, D.; Dolmans, Wil M. V.; Sebastian, Silvie; Fijnheer, Rob; de Mast, Quirijn

    2012-01-01

    Background: Thrombocytopenia, bleeding and plasma leakage are cardinal features of severe dengue. Endothelial cell activation with exocytosis of Weibel-Palade bodies (WPBs) may play an etiological role in this condition. Methods and Principal Findings: In a cohort of 73 Indonesian children with deng

  3. Severe dengue is associated with consumption of von Willebrand factor and its cleaving enzyme ADAMTS-13.

    NARCIS (Netherlands)

    Djamiatun, K.; Ven, A.J.A.M. van der; Groot, P.G. de; Faradz, S.M.H.; Hapsari, D.; Dolmans, W.M.V.; Sebastian, S.; Fijnheer, R.; Mast, Q. de

    2012-01-01

    BACKGROUND: Thrombocytopenia, bleeding and plasma leakage are cardinal features of severe dengue. Endothelial cell activation with exocytosis of Weibel-Palade bodies (WPBs) may play an etiological role in this condition. METHODS AND PRINCIPAL FINDINGS: In a cohort of 73 Indonesian children with deng

  4. Transient von Willebrand factor-mediated platelet influx stimulates liver regeneration after partial hepatectomy in mice

    NARCIS (Netherlands)

    Kirschbaum, Marc; Jenne, Craig N; Veldhuis, Zwanida J; Sjollema, Klaas A; Lenting, Peter J; Giepmans, Ben N G; Porte, Robert J; Kubes, Paul; Denis, Cécile V; Lisman, Ton

    2017-01-01

    BACKGROUND & AIMS: In addition to their function in thrombosis and hemostasis, platelets play an important role in the stimulation of liver regeneration. It has been suggested that platelets deliver mitogenic cargo to the regenerating liver, and accumulation of platelets in the regenerating liver ha

  5. Structural studies on B2-glycoprotein I and von Willebrand factor A3 domain

    NARCIS (Netherlands)

    Bouma, B.

    2001-01-01

    The integrity of blood circulation is a prerequisite for life; its malfunctioning is a leading cause of morbidity and mortality in developed countries. For that reason the haemostatic system is a critical component of homeostasis. In Chapter I an overview is given of the biophysical and biochemical

  6. Von Willebrand factor, ADAMTS13 levels and prediction of venous thromboembolism in patients with cancer

    NARCIS (Netherlands)

    Pepin, M.; Kleinjan, A.; Hajage, D.; Büller, H.R.; DiNisio, M.; Kamphuisen, P.W.; Mahe, I.; Stepanian, A.

    2013-01-01

    Background: Cancer patients are at high risk for venous thromboembolism (VTE). However, thromboprophylaxis in these patients is associated with an increased hemorrhagic risk. The Khorana score is a risk scoring model for prediction of VTE that includes clinical and laboratory parameters. It has been

  7. Cellular fibronectin and von Willebrand factor concentrations in plasma of rats treated with monocrotaline pyrrole

    NARCIS (Netherlands)

    Schultze, A.E.; Emeis, J.J.; Roth, R.A.

    1996-01-01

    The monocrotaline pyrrole (MCTP)-treated rat is a useful model for the study of certain chronic pulmonary vascular diseases. A single, i.v. administration of a low dose of MCTP causes pneumotoxicity, pulmonary vascular remodeling, sustained increases in pulmonary arterial pressure, and right ventric

  8. Mutation analysis and clinical implications of von Willebrand factor-cleaving protease deficiency.

    NARCIS (Netherlands)

    Assink, K.F.H.; Schiphorst, R.H.M.; Allford, S.; Karpman, D.; Etzioni, A.; Brichard, B.; Kar, N.C.A.J. van de; Monnens, L.A.H.; Heuvel, L.P.W.J. van den

    2003-01-01

    BACKGROUND: The pentad of thrombocytopenia, hemolytic anemia, mild renal dysfunction, neurologic signs, and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults as an acquired form but a congenital form in children has also been des

  9. Exercise induced hypercoagulability, increased von Willebrand factor and decreased thyroid hormone concentrations in sled dogs

    DEFF Research Database (Denmark)

    Krogh, Anne Kirstine Havnsøe; Legind, Pernille; Kjelgaard-Hansen, Mads;

    2014-01-01

    Sled dogs performing endurance races have been reported to have a high incidence of gastric erosions or ulcerations and an increased risk of gastro intestinal bleeding leading to death in some cases. In addition, these dogs also become hypothyroid during training and exercise. Canine hypothyroidi...

  10. β3 Integrin Haplotype Influences Gene Regulation and Plasma von Willebrand Factor Activity

    Science.gov (United States)

    Payne, Katie E; Bray, Paul F; Grant, Peter J; Carter, Angela M

    2008-01-01

    The Leu33Pro polymorphism of the gene encoding β3 integrin (ITGB3) is associated with acute coronary syndromes and influences platelet aggregation. Three common promoter polymorphisms have also been identified. The aims of this study were to (1) investigate the influence of the ITGB3 −400C/A, −425A/C and −468G/A promoter polymorphisms on reporter gene expression and nuclear protein binding and (2) determine genotype and haplotype associations with platelet αIIbβ3 receptor density. Promoter haplotypes were introduced into an ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear proteins was assessed by electrophoretic mobility shift assay. The association of ITGB3 haplotype with platelet αIIbβ3 receptor density was determined in 223 subjects. Species conserved motifs were identified in the ITGB3 promoter in the vicinity of the 3 polymorphisms. The GAA, GCC, AAC, AAA and ACC constructs induced ~50% increased luciferase expression relative to the GAC construct in both cell types. Haplotype analysis including Leu33Pro indicated 5 common haplotypes; no associations between ITGB3 haplotypes and receptor density were found. However, the GCC-Pro33 haplotype was associated with significantly higher vWF activity (128.6 [112.1–145.1]%) compared with all other haplotypes (107.1 [101.2–113.0]%, p=0.02). In conclusion, the GCC-Pro33 haplotype was associated with increased vWF activity but not with platelet αIIbβ3 receptor density, which may indicate ITGB3 haplotype influences endothelial function. PMID:18045606

  11. von Willebrand Factor and Prekallikrein in Plasma Are Associated With Thrombus Volume in Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

    Ghulam, Qasam M; Bredahl, Kim K; Gram, Jørgen B;

    2016-01-01

    anticoagulant therapy, renal impairment, or nonappearance, thus leaving 30 patients for further analysis. All patients had computed tomography angiography, and intraluminal volume was quantified off-line by OsiriX 6.5. RESULTS: Median intraluminal thrombus volume was 42.7 mL. Spearman correlation analysis...

  12. Factor VIII/V C-domain swaps reveal discrete C-domain roles in factor VIII function and intracellular trafficking.

    Science.gov (United States)

    Ebberink, Eduard H T M; Bouwens, Eveline A M; Bloem, Esther; Boon-Spijker, Mariëtte; van den Biggelaar, Maartje; Voorberg, Jan; Meijer, Alexander B; Mertens, Koen

    2017-04-01

    Factor VIII C-domains are believed to have specific functions in cofactor activity and in interactions with von Willebrand factor. We have previously shown that factor VIII is co-targeted with von Willebrand factor to the Weibel-Palade bodies in blood outgrowth endothelial cells, even when factor VIII carries mutations in the light chain that are associated with defective von Willebrand factor binding. In this study, we addressed the contribution of individual factor VIII C-domains in intracellular targeting, von Willebrand factor binding and cofactor activity by factor VIII/V C-domain swapping. Blood outgrowth endothelial cells were transduced with lentivirus encoding factor V, factor VIII or YFP-tagged C-domain chimeras, and examined by confocal microscopy. The same chimeras were produced in HEK293-cells for in vitro characterization and chemical foot-printing by mass spectrometry. In contrast to factor VIII, factor V did not target to Weibel-Palade bodies. The chimeras showed reduced Weibel-Palade body targeting, suggesting that this requires the factor VIII C1-C2 region. The factor VIII/V-C1 chimera did not bind von Willebrand factor and had reduced affinity for activated factor IX, whereas the factor VIII/V-C2 chimera showed a minor reduction in von Willebrand factor binding and normal interaction with activated factor IX. This suggests that mainly the C1-domain carries factor VIII-specific features in assembly with von Willebrand factor and activated factor IX. Foot-printing analysis of the chimeras revealed increased exposure of lysine residues in the A1/C2- and C1/C2-domain interface, suggesting increased C2-domain mobility and disruption of the natural C-domain tandem pair orientation. Apparently, this affects intracellular trafficking, but not extracellular function. Copyright© Ferrata Storti Foundation.

  13. 可吸收镁合金支架植入后犬冠状动脉C-反应蛋白、基质金属蛋白酶9和血管性血友病因子的表达%Effect of absorbable magnesium alloy stenting on expression of C-reactive protein, matrix metalloproteinase-9 and von Willebrand factor in dogs

    Institute of Scientific and Technical Information of China (English)

    王汝朋; 杨水祥

    2015-01-01

    BACKGROUND:Our previous study have verified the biosafety of absorbable magnesium aloy stents from a macro perspective. OBJECTIVE:To study the expressions of C-reactive protein, matrix metaloproteinase-9 and von Wilebrand factor in local vascular tissue after magnesium aloy stenting, and to explore the histocompatibility and safety of magnesium aloy stents at the molecular expression level. METHODS:Twenty-five absorbable magnesium aloy stents were implanted into the left anterior descending artery or circumflex artery of 25 epidemic prevention mongrel dogs. Five dogs with no stenting served as control group. Five dogs were sacrificed respectively at 24 hours, 3 days, 5 days, 1 week, 1 month after stenting, and vascular specimens were taken for preparation of pathological sections. The expressions of C-reactive protein, matrix metaloproteinase-9 and von Wilebrand factor within the coronary artery wal were determined by immunohistochemical staining method. RESULTS AND CONCLUSION: Compared with the control group, the number of cels positive for C-reactive protein, matrix metaloproteinase-9 and von Wilebrand factor was significantly increased at different times after stenting (P 0.01). The inflammatory reactions induced by absorbable magnesium aloy stents are slight and last for short time, which suggests that the absorbable magnesium aloy stents have good histocompatibility and safety.%背景:课题组前期研究从宏观角度验证了可吸收镁合金支架的生物安全性。目的:观察可吸收镁合金支架植入后局部血管组织C-反应蛋白、基质金属蛋白酶9及血管性血友病因子的表达情况,从分子表达水平深层次探讨镁合金支架的组织相容性及安全性。方法:将25枚可吸收镁合金支架植入25只防疫杂种犬冠状动脉前降支或左回旋支,未植入支架的5只犬冠状动脉作为正常对照组,支架植入后24 h、3 d、5 d、1周、1个月各处死动物5只,取支架植入后的

  14. Expressão imunoistoquímica da endoglina (CD105 e do fator de von Willebrand em carcinoma epidermoide oral e sua relação com parâmetros clinicopatológicos

    Directory of Open Access Journals (Sweden)

    Rodrigo Porpino Mafra

    2016-03-01

    Full Text Available Resumo Contexto A angiogênese tem sido associada à progressão de neoplasias malignas e, embora haja estudos acerca de marcadores angiogênicos no carcinoma epidermoide oral (CEO, existem resultados conflitantes na literatura. Objetivos Avaliar a expressão imunoistoquímica do CD105 e do fator de von Willebrand (FvW em CEO e sua relação com parâmetros clínicos do tumor. Métodos A imunoexpressão dos referidos biomarcadores foi analisada em 30 casos de CEO e correlacionada a parâmetros clínicos do tumor (idade e sexo dos pacientes, localização anatômica e estadiamento clínico Tumor, Nodo e Metástase, TNM. Resultados A imunomarcação com o anticorpo anti-FvW foi mais efetiva que a do CD105 no CEO. No que concerne à localização anatômica, o assoalho bucal e a região retromolar apresentaram diferenças estatisticamente significativas quanto aos índices angiogênicos (p = 0,004, determinados pela técnica de contagem microvascular (MVC. Não houve relação estatisticamente significativa entre o estadiamento clínico TNM e os índices angiogênicos, com os dois biomarcadores. Conclusões Com base nos achados deste estudo, sugere-se um envolvimento da neoformação vascular na carcinogênese oral, embora não tenha sido evidenciada associação significativa com o estágio clínico da lesão.

  15. Von Willebrand factor in patients on mechanical circulatory support – a double-edged sword between bleeding and thrombosis

    OpenAIRE

    Hudzik, Bartosz; Kaczmarski, Jacek; Pacholewicz, Jerzy; Zakliczynski, Michal; Gasior, Mariusz; Zembala, Marian

    2015-01-01

    Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short- and long-term management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2- to 3-year survival in carefully...

  16. Increased von Willebrand factor, P-selectin and fibrin content in occlusive thrombus resistant to lytic therapy.

    Science.gov (United States)

    Sambola, Antonia; García Del Blanco, Bruno; Ruiz-Meana, Marisol; Francisco, Jaume; Barrabés, José A; Figueras, Jaume; Bañeras, Jordi; Otaegui, Imanol; Rojas, Angeles; Vilardosa, Úrsula; Montaner, Joan; García-Dorado, David

    2016-06-01

    Therapeutic fibrinolysis is ineffective in 40 % of ST-segment elevation acute myocardial infarction (STEMI) patients, but understanding of the mechanisms is incomplete. It was our aim to compare the composition of coronary thrombus in lysis-resistant STEMI patients with that of lysis-sensitive patients. Intracoronary thrombi (n=64) were obtained by aspiration in consecutive STEMI patients. Of them, 20 had received fibrinolysis and underwent rescue percutaneous coronary intervention (r-PCI, lysis-resistant patients) and 44 underwent primary PCI (p-PCI). Lysis-sensitivity was determined in vitro by clot permeability measurements and turbidimetric lysis in plasma of 44 patients undergoing p-PCI and 20 healthy donors. Clot-lysis sensitivity was defined as a clot-lysis time not greater than 1 SD over the mean of healthy donors. Coronary thrombus composition in 20 lysis-resistant and in 20 lysis-sensitive patients was analysed by immunofluorescence with confocal microscopy. Plasma biomarkers (P-selectin, VWF, PAI-1, t-PA, D-dimer, TF pathway markers, plasmin and CD34+) were measured simultaneously on peripheral blood. Lysis-resistant clots had higher levels of fibrin (p=0.02), P-selectin (p=0.03) and VWF (p=0.01) than lysis-sensitive clots. Among thrombi obtained ≤ 6 hours after onset of symptoms, those from lysis-resistant patients showed a higher content in fibrin than those from p-PCI patients (p=0.01). Plasma PAI-1 (p=0.02) and D-dimer levels were significantly higher (p=0.003) in lysis-resistant patients, whereas plasmin levels were lower (p=0.03). Multivariate analysis showed the content of fibrin and VWF within thrombus as predictors of thrombolysis resistance. In conclusion, coronary thrombi in STEMI patients resistant to fibrinolysis are characterised by higher fibrin, P-selectin and VWF content than lysis-sensitive thrombi.

  17. How Is von Willebrand Disease Diagnosed?

    Science.gov (United States)

    ... may not be diagnosed unless they have heavy bleeding after surgery or some other trauma. On the other hand, ... following the injury. Any prolonged, heavy, or repeated bleeding that required medical care after surgery or dental extractions. Any bruising with little or ...

  18. How Is von Willebrand Disease Treated?

    Science.gov (United States)

    ... blood clots. They're mostly used to stop bleeding after minor surgery, tooth extraction, or an injury. These medicines may be used alone or with desmopressin and replacement therapy. Fibrin glue is ... to stop bleeding. Treatments for Women Treatments for women who have ...

  19. Factor B structure provides insights into activation of the central protease of the complement system

    NARCIS (Netherlands)

    Milder, F.J.; Gomes, L.; Schouten, A.; Janssen, B.J.C.; Huizinga, E.G.; Romijn, R.A.; Hemrika, W.; Roos, A; Daha, M.R.; Gros, P.

    2007-01-01

    Factor B is the central protease of the complement system of immune defense. Here, we present the crystal structure of human factor B at 2.3-A° resolution, which reveals how the five-domain proenzyme is kept securely inactive. The canonical activation helix of the Von Willebrand factor A (VWA) domai

  20. Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bouwens, E.A.M.; Kootstra, N.A.; Hebbel, R.P.; Voorberg, J.; Mertens, K.

    2009-01-01

    Background Gene therapy provides an attractive alternative for protein replacement therapy in hemophilia A patients. Recent studies have shown the potential benefit of directing factor (F)VIII gene delivery to cells that also express its natural carrier protein von Willebrand factor (VWF). In this

  1. Vascular endothelial cell function and cardiovascular risk factors in patients with chronic renal failure

    DEFF Research Database (Denmark)

    Haaber, A B; Eidemak, I; Jensen, T

    1995-01-01

    Cardiovascular risk factors and markers of endothelial cell function were studied in nondiabetic patients with mild to moderate chronic renal failure. The transcapillary escape rate of albumin and the plasma concentrations of von Willebrand factor, fibrinogen, and plasma lipids were measured in 29...

  2. Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bouwens, E.A.M.; Kootstra, N.A.; Hebbel, R.P.; Voorberg, J.; Mertens, K.

    2009-01-01

    Background Gene therapy provides an attractive alternative for protein replacement therapy in hemophilia A patients. Recent studies have shown the potential benefit of directing factor (F)VIII gene delivery to cells that also express its natural carrier protein von Willebrand factor (VWF). In this s

  3. Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bouwens, E.A.M.; Kootstra, N.A.; Hebbel, R.P.; Voorberg, J.; Mertens, K.

    2009-01-01

    Background Gene therapy provides an attractive alternative for protein replacement therapy in hemophilia A patients. Recent studies have shown the potential benefit of directing factor (F)VIII gene delivery to cells that also express its natural carrier protein von Willebrand factor (VWF). In this s

  4. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

    DEFF Research Database (Denmark)

    Lipsky, Andrew H; Farooqui, Mohammed Z H; Tian, Xin

    2015-01-01

    , suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional...

  5. The C1 and C2 domains of blood coagulation factor VIII mediate its endocytosis by dendritic cells

    Science.gov (United States)

    Gangadharan, Bagirath; Ing, Mathieu; Delignat, Sandrine; Peyron, Ivan; Teyssandier, Maud; Kaveri, Srinivas V.; Lacroix-Desmazes, Sébastien

    2017-01-01

    The development of inhibitory antibodies to therapeutic factor VIII is the major complication of replacement therapy in patients with hemophilia A. The first step in the initiation of the anti-factor VIII immune response is factor VIII interaction with receptor(s) on antigen-presenting cells, followed by endocytosis and presentation to naïve CD4+ T cells. Recent studies indicate a role for the C1 domain in factor VIII uptake. We investigated whether charged residues in the C2 domain participate in immunogenic factor VIII uptake. Co-incubation of factor VIII with BO2C11, a monoclonal C2-specific immunoglobulin G, reduced factor VIII endocytosis by dendritic cells and presentation to CD4+ T cells, and diminished factor VIII immunogenicity in factor VIII-deficient mice. The mutation of basic residues within the BO2C11 epitope of C2 replicated reduced in vitro immunogenic uptake, but failed to prevent factor VIII immunogenicity in mice. BO2C11 prevents factor VIII binding to von Willebrand factor, thus potentially biasing factor VIII immunogenicity by perturbing its half-life. Interestingly, a factor VIIIY1680C mutant, that does not bind von Willebrand factor, demonstrated unaltered endocytosis by dendritic cells as well as immunogenicity in factor VIII-deficient mice. Co-incubation of factor VIIIY1680C with BO2C11, however, resulted in decreased factor VIII immunogenicity in vivo. In addition, a previously described triple C1 mutant showed decreased uptake in vitro, and reduced immunogenicity in vivo, but only in the absence of endogenous von Willebrand factor. Taken together, the results indicate that residues in the C1 and/or C2 domains of factor VIII are implicated in immunogenic factor VIII uptake, at least in vitro. Conversely, in vivo, the binding to endogenous von Willebrand factor masks the reducing effect of mutations in the C domains on factor VIII immunogenicity. PMID:27758819

  6. Factorization and dilation problems for completely positive maps on von Neumann algebras

    DEFF Research Database (Denmark)

    Haagerup, Uffe; Musat, Magdalena

    2011-01-01

    We study factorization and dilation properties of Markov maps between von Neumann algebras equipped with normal faithful states, i.e., completely positive unital maps which preserve the given states and also intertwine their automorphism groups. The starting point for our investigation has been...... for all small values of t > 0. As applications, we solve in the negative an open problem in quantum information theory concerning an asymptotic version of the quantum Birkhoff conjecture, as well as we sharpen the existing lower bound estimate for the best constant in the noncommutative little...

  7. Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II)

    DEFF Research Database (Denmark)

    Klovaite, Jolanta; Gustafsson, Finn; Mortensen, Svend A

    2009-01-01

    OBJECTIVES: This study investigated the influence of the mechanical blood pump HeartMate II (HMII) (Thoratec Corporation, Pleasanton, California) on blood coagulation and platelet function. BACKGROUND: HMII is an implantable left ventricular assist device used for the treatment of heart failure...

  8. Dogs with hearth diseases causing turbulent high-velocity blood flow have changes in patelet function and von Willebrand factor multimer distribution

    DEFF Research Database (Denmark)

    Tarnow, Inge; Kristensen, Annemarie Thuri; Olsen, Lisbeth Høier

    2005-01-01

    and echocardiography were performed in all dogs. PFA100 closure times (the ability of platelets to occlude a hole in a membrane at high shear rates), platelet activation markers (plasma thromboxane B2 concentration, platelet surface P-selectin expression), platelet aggregation (in whole blood and platelet-rich plasma...

  9. Influence of atrial fibrillation on plasma von Willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure

    DEFF Research Database (Denmark)

    Freestone, B.; Gustasson, F.; Chong, A.Y.;

    2008-01-01

    Background: Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. it is unknown whether AF influences the degree of endothelial dysfunction in pati...

  10. Distribution of von Willebrand factor levels in young women with and without bleeding symptoms: influence of ABO blood group and promoter haplotypes

    DEFF Research Database (Denmark)

    Lethagen, S.; Hillarp, A.; Ekholm, C.;

    2008-01-01

    . It was the objective of the present study to evaluate the distribution of VWF levels in young females with or without bleeding symptoms in this population, and the influence of ABO blood group and promoter haplotypes on VWF levels and to identify a possible increased prevalence of VWD in females with bleeding symptoms.......4%) (p = 0.017). Blood group O was found in 14/18 girls with low VWF:RCo. There was a highly significant correlation between VWF:RCo and blood group O and non-O genotypes. Two common VWF promoter haplotypes did not contribute to the VWF:RCo variation. VWF levels did not correlate with time during...... menstrual cycle, or the use of oral contraceptives. No case fulfilled the diagnostic criteria for VWD. In conclusion, low VWF:RCo was significantly more frequent in females with bleeding symptoms. However, we found no case fulfilling strict diagnostic criteria for VWD. The ABO blood group was a strong...

  11. MAPS PRESERVING STRONG SKEW LIE PRODUCT ON FACTOR VON NEUMANN ALGEBRAS

    Institute of Scientific and Technical Information of China (English)

    Cui Jianlian; Choonkil Park

    2012-01-01

    Let A be a factor von Neumann algebra and Φ be a nonlinear surjective map from A onto itself.We prove that,if Φ satisfies that Φ(A)Φ(B) - Φ(B)Φ(A)* =AB - BA* for all A,B ∈ A,then there exist a linear bijective map Ψ:A - A satisfying Ψ(A)Ψ(B) - Ψ(B)Ψ(A)* =AB - BA* for A,B ∈ A and a real functional h on A with h(0) =0 such that Φ(A) =Ψ(A) + h(A)I for every A ∈ A.In particular,if A is a type Ⅰ factor,then,Φ(A) =cA + h(A)I for every A ∈ A,where c =±-1.

  12. Patient with von Willebrand Disease for Gynaecologic Surgery - Perianaesthetic Concerns

    Directory of Open Access Journals (Sweden)

    Rakesh Garg

    2008-01-01

    Patients with vWD do not carry an increased operative risk during elective procedures if appropriate prophylac-tic and corrective therapy is administered. Although the administration of cryoprecipitate and other blood products has traditionally been the cornerstone of treatment for vWD, the recent development of desmopressin(DDAVP for clinical use may provide an effective alternative to replacement therapy with blood products. Further laparaoscopic procedures, taking care during ryle′s tube and foley′s catheter insertion, in such patients are the safer alternative for all kind of gynecologic surgeries.

  13. 因子von Neumann代数上Jordan正交可导映射%Jordan orthogonal derivable mappings on factor von Neumann algebra

    Institute of Scientific and Technical Information of China (English)

    张芳娟

    2012-01-01

    Let.M be a factor von Neumann algebra acting on a complex separable Hilbert space .H with dim.H>2. Let φ: M→M be a Jordan orthogonal derivable bounded linear mapping from .M to itself, then there exist μ∈R, λ∈C and M∈M,M +M * =μ1 , such that φ>(A) = AM - MA + λA for all A∈M. If φ:M→M be a Jordan -* derivable mapping, then there exist μ∈ R and T ∈M,T +T* =μJ, such that φ(A) = AT-TA for all A∈M.%设M是作用在维数大于2的复可分Hilbert空间M上的因子von Neumann代数.若φ:M→M上有界的Jordan正交可导线性映射,则存在数μ∈R,λ∈C和算子M∈M,且M+M*=μl,使得对所有的A∈M,有φ(A) =AM-MA +λA.若φ:M→M上有界的Jordan -*可导线性映射,则存在数μ∈R和算子T∈M,且7+ T*=μl,使得对所有的A∈M,有φ(A) =AT- TA.

  14. Van Willebrand's disease in the Western Cape

    African Journals Online (AJOL)

    History of a bleeding tendency; bleeding ... protein which facilitates platelet adhesion to damaged vessel walls ... classification is an over-simplification, it forms a useful clinical basis. ... Twenty-two people from 11 families with a history of VWD .... Hemostatic effect of normal platelet function in severe Van Willebrand disease.

  15. Effects of benazepril on yon Willebrand factor and albuminuria in patients with type 2 diabetes mellitus associated with hypertension%盐酸贝那普利对2型糖尿病并高血压患者血管性血友病因子及尿白蛋白的影响

    Institute of Scientific and Technical Information of China (English)

    李淑英; 魏刚; 李岳华; 冀秋娣

    2008-01-01

    Fifty-six hypertensive diabetic patients (glyeosylated hemoglobin A1c130/80 mm Hg.All the patients were treated for 12 weeks.In both groups,plasma yon Willebrand factor and urine albumin decreased significantly from baseline.Except for urine albumin,no significant inter-group difference in plasma van Willebrand factor and target blood pressure was observed.Benazepril and amledipine seem to show similar efficacy in lowering blood pressure and improving endothelial function,but benazepril may be more effective in kidney protection.%对56例血糖控制达标(糖化血红蛋白<7%)伴白蛋白(ALS)尿的2型糖尿病并高血压患者,分别予盐酸贝那普利(10 ms/d)、氨氯地平(5 mg/d)治疗.治疗后,血浆血管性血友病因子(vWF)浓度和尿ALB含量均有下降(P<0.01);两组间血浆vWF浓度、血压达标率差异无统计学意义,尿ALB含量差异有统计学意义(P<0.05).贝那普利降压及修复内皮损伤与氨氯地平相当,且对肾脏有更好的保护作用.

  16. Quantifying the Binding Interaction between the Hypoxia-Inducible Transcription Factor and the von Hippel-Lindau Suppressor.

    Science.gov (United States)

    Domene, Carmen; Jorgensen, Christian; Vanommeslaeghe, Kenno; Schofield, Christopher J; MacKerell, Alexander

    2015-08-11

    The hypoxia-inducible transcription factors (HIF) play a central role in the human oxygen sensing signaling pathway. The binding of the von Hippel-Lindau tumor suppressor protein (pVHL)-ElonginC-ElonginB complex (VCB) to HIF-1α is highly selective for the trans-4-hydroxylation form of when Pro564 in the C-terminal oxygen-dependent degradation domain (ODDD) of HIF-1α. The binding of HIFα for VCB is increased by ∼1000-fold upon addition of a single hydroxyl group to either of two conserved proline-residues. Here, we address how this addition governs selective recognition and characterizes the strength of the interaction of this "switch-like" signaling event. A new set of molecular mechanics parameters for 4-hydroxyproline has been developed following the CHARMM force field philosophy. Using the free energy perturbation (FEP) formalism, the difference in the binding free energies between HIF-1α in the nonhydroxylated and hydroxylated forms with the VCB complex was estimated using over 3 μs of MD trajectories. These results can favorably be compared to an experimental value of ∼4 kcal mol(-1). It is observed that the optimized hydrogen bonding network to the buried hydroxyprolyl group confers precise discrimination between hydroxylated and unmodified prolyl residues. These observations provide insight that will aid in developing therapeutic agents that block HIF-α recognition by pVHL.

  17. IFN-α, IFN-β, and IFN-γ Have Different Effect on the Production of Proinflammatory Factors Deposited in Weibel-Palade Bodies of Endothelial Cells Infected with Herpes Simplex Virus Type 1.

    Science.gov (United States)

    Shcheglovitova, O N; Boldyreva, N V; Sklyankina, N N; Babayants, A A; Frolova, I S

    2016-06-01

    We demonstrated similarities and differences in the effects of IFN-α and IFN-β compared to IFN-γ on the production of factors deposited in the Weibel-Palade bodies in cultures of endothelial cells (intact and infected with herpes simplex virus 1). IFN-α and IFN-β reduced the content of von Willebrand factor, endothelin-1, and soluble P-selectin and increased IL-8 concentration in the culture medium of human umbilical vein endothelial cells. IFN-γ reduced the content of all studied factors in the endothelial cell culture medium. Possible mechanisms of these effects are discussed.

  18. The VITRO Score (Von Willebrand Factor Antigen/Thrombocyte Ratio as a New Marker for Clinically Significant Portal Hypertension in Comparison to Other Non-Invasive Parameters of Fibrosis Including ELF Test.

    Directory of Open Access Journals (Sweden)

    Stephanie Hametner

    Full Text Available Clinically significant portal hypertension (CSPH, defined as hepatic venous pressure gradient (HVPG ≥10 mmHg, causes major complications. HVPG is not always available, so a non-invasive tool to diagnose CSPH would be useful. VWF-Ag can be used to diagnose. Using the VITRO score (the VWF-Ag/platelet ratio instead of VWF-Ag itself improves the diagnostic accuracy of detecting cirrhosis/ fibrosis in HCV patients.This study tested the diagnostic accuracy of VITRO score detecting CSPH compared to HVPG measurement.All patients underwent HVPG testing and were categorised as CSPH or no CSPH. The following patient data were determined: CPS, D'Amico stage, VITRO score, APRI and transient elastography (TE.The analysis included 236 patients; 170 (72% were male, and the median age was 57.9 (35.2-76.3; 95% CI. Disease aetiology included ALD (39.4%, HCV (23.4%, NASH (12.3%, other (8.1% and unknown (11.9%. The CPS showed 140 patients (59.3% with CPS A; 56 (23.7% with CPS B; and 18 (7.6% with CPS C. 136 patients (57.6% had compensated and 100 (42.4% had decompensated cirrhosis; 83.9% had HVPG ≥10 mmHg. The VWF-Ag and the VITRO score increased significantly with worsening HVPG categories (P<0.0001. ROC analysis was performed for the detection of CSPH and showed AUC values of 0.92 for TE, 0.86 for VITRO score, 0.79 for VWF-Ag, 0.68 for ELF and 0.62 for APRI.The VITRO score is an easy way to diagnose CSPH independently of CPS in routine clinical work and may improve the management of patients with cirrhosis.

  19. Factor substitution in the paper industry within the context of the introduction of machine tax and energy tax; Faktorsubstitution in der Papierindustrie bei Einfuehrung von Maschinen- und Energiesteuern

    Energy Technology Data Exchange (ETDEWEB)

    Lang, G.

    1991-05-01

    The cellulose-, wood pulp- paper- and cardboard industry is supposed to be one of the most capital-intensive industries within the national economy; the capital investment per gainfully employed person was 258.000 DM in 1980 whereas it was only 108.000 DM in the processing industries. But next to capital energy is a large factor in paper manufacturing: processing industries used about 153 kg coal equivalent per 1000,- DM in 1980, the paper industry used 702 kg. This booklet attempts to analyse the manufacturing relations and find possibilities to substitute between the input factors labour, capital, energy and other intermediate inputs. This is to be the basis for te paper industry`s reaction to the introduction of a machine tax and higher taxes on energy. The attempt to see energy as an input factor is an extension of the small amount of work on a disaggregated level for the West German processing industry. (orig./UA). [Deutsch] Die Zellstoff-, Holzschliff-, Papier- und Pappeerzeugende Industrie gilt als einer der kapital-intensivsten Wirtschaftsbereiche der Volkswirtschaft: auf jeden Erwerbstaetigen kam im Jahr 1980 ein Kapitaleinsatz von 258.000 DM, waehrend es im gesamten Verarbeitenden Gewerbe lediglich 108.000 DM waren. Neben dem Inputfaktor Kapital wird der Produktionsfaktor Energie in hohem Masse in der Papierproduktion eingesetzt: das Verarbeitende Gewerbe setzte in jenem Jahr insgesamt durchschnittlich 153 kg SKE pro 1000,- DM Bruttowertschoepfung im Produktionsprozess ein, die Papierindustrie jedoch 702 kg. Diese ueberdurchschnittliche Bedeutung von Energie und Kapital zeigt die hohe Betroffenheit dieser Branche von zwei wirtschaftpolitischen Ueberlegungen: die Forderung nach der Einfuehrung von `Maschinensteuern` und `Oekosteuern`. Die vorliegende Ausarbeitung setzt sich zum Ziel, ueber die Analyse der Produktionsbeziehungen Substitutionsmoeglichkeiten zwischen den Inputfaktoren Arbeit, Kapital, Energie und Sonstige Vorleistungen abzuschaetzen. Auf

  20. Planning of medium-voltage networks considering optimized power factor control of distributed generators; Planung von Mittelspannungsnetzen unter Beruecksichtigung von Blindleistungssteuerung dezentraler Erzeugungsanlagen

    Energy Technology Data Exchange (ETDEWEB)

    Rotering, Niklas; Schroeders, Christian; Moser, Albert [RWTH Aachen (Germany). IAEW

    2011-07-01

    Distributed generation causes new challenges in medium voltage networks. Especially voltage stability is becoming an issue. Conventional planning measures, like network expansion, can be used to address these challenges but they should planned with great care due to their high costs. Power factor control of distributed generators is an alternative to such measures. Therefore it should also be considered in long term distribution network planning. It is the purpose of this paper to present a new approach for long term medium-voltage network optimization that integrates near optimal power factor control. The structural optimization is heuristic and based on a Delaunay triangulation in combination with an ant colony algorithm. Power factor control is predicated on dynamic programming. It is shown how near optimal results can easily be realized under German law with present technologies. A case study illustrates the impacts and advantages of an integrated planning approach. The integrated optimization results in network costs that are 2.5% lower than the costs of the best topology found by conventional planning. (orig.)

  1. von Neumann Morgenstern Preferences

    DEFF Research Database (Denmark)

    Vind, Karl

    von Neumann Morgenstern utility is generalized to von Neumann Morgenstern preferences. The proof is an application of simple hyperplane theorems......von Neumann Morgenstern utility is generalized to von Neumann Morgenstern preferences. The proof is an application of simple hyperplane theorems...

  2. von Neumann Morgenstern Preferences

    DEFF Research Database (Denmark)

    Vind, Karl

    2000-01-01

    von Neumann Morgenstern utility is generalized to von Neumann Morgenstern preferences. The proof is an application of simple hyperplane theorems......von Neumann Morgenstern utility is generalized to von Neumann Morgenstern preferences. The proof is an application of simple hyperplane theorems...

  3. Range of application of epidemiological studies with aggregate data for assessment of risk factors; Anwendungsbereich von epidemiologischen Studien mit zusammengefassten Daten zur Bestimmung von Risikofaktoren

    Energy Technology Data Exchange (ETDEWEB)

    Kaiser, J.C.; Jacob, P. [GSF-Forschungszentrum fuer Umwelt und Gesundheit, Neuherberg (Germany). Inst. fuer Strahlenschutz; Blettner, M. [Johannes Gutenberg-Univ. Mainz (DE). Inst. fuer Medizinische Biometrie, Epidemiologie und Informatik] (and others)

    2006-07-01

    Epidemiological studies are either studies with individual data (cohort studies, case control studies), or studies with aggregate data (ecologic studies). The first-mentioned method has the advantage that methods for investigating risk models, e.g. dose-effect relationship studies, are available and mathematically validated also in consideration of confounders, but they have the drawback of high cost, while aggregate studies provide larger data sets at less cost and time. On the other hand, ecologic studies have significant methodological problems (''ecological bias''), especially if causal statements are required. It is well known that variation of a confounding factor (e.g. smoking in case of lung cancer caused by radon) may lead to non-valid results. On the other hand, studies with aggregate data in the Chernobyl region so far have been the only studies that provided quantitative results on the risk of thyroid cancer after exposure to 131-I in infant age. In view of this situation, the report investigates the problem of validity and the potential range of applications of ecological studies. (orig.)

  4. Measurement of Blood Coagulation Factor Synthesis in Cultures of Human Hepatocytes.

    Science.gov (United States)

    Heinz, Stefan; Braspenning, Joris

    2015-01-01

    An important function of the liver is the synthesis and secretion of blood coagulation factors. Within the liver, hepatocytes are involved in the synthesis of most blood coagulation factors, such as fibrinogen, prothrombin, factor V, VII, IX, X, XI, XII, as well as protein C and S, and antithrombin, whereas liver sinusoidal endothelial cells produce factor VIII and von Willebrand factor. Here, we describe methods for the detection and quantification of most blood coagulation factors in hepatocytes in vitro. Hepatocyte cultures indeed provide a valuable tool to study blood coagulation factors. In addition, the generation and expansion of hepatocytes or hepatocyte-like cells may be used in future for cell-based therapies of liver diseases, including blood coagulation factor deficiencies.

  5. Experimental studies of factors influencing the self-ignition of gaseous and liquid fuel free jets; Experimentelle Untersuchungen von Einflussfaktoren auf die Selbstzuendung von gasfoermigen und fluessigen Brennstofffreistrahlen

    Energy Technology Data Exchange (ETDEWEB)

    Pfeifer, Christian

    2010-07-01

    In the present work, the investigation of influencing factors on the auto-ignition of gaseous and liquid free fuel jets are presented. The fuel dimethyl ether (DME) is injected into a high pressure/high temperature atmosphere. The temperature of up to 770 K and pressure of 40 bar enable auto-ignition of the transient free fuel jet during the inflow. To study the influences on the auto-ignition of the gaseous free jet, an extended autoignition probability is established. It includes the time and space resolved auto-ignition probability concerning the ignition limit of the fuel/air-mixture. This state of the autoignition probability is expanded by the auto-ignition probability concerning the local mixture temperature. To gain information of the local temperature, the molar mixture is applied as database. Therefrom the adiabatic local temperature is calculated. To determine a limiting temperature, above which auto-ignition of the local mixture is feasible, a numerical study with the software package HOMREA is performed. Additionally the influence of the flow field on the auto-ignition probability is investigated. As experimental database the time resolved velocity field of the instationary fuel jet is applied and the local strain rate is obtained. To define a critical strain rate, above which an auto-ignition is not possible, a numerical simulation with INSFLA is performed. A coupling of these three single ignition probabilities yield an extended auto-ignition probability. It reveals an abrupt rise in the local ignition probability over a large spatial extend. This time and space resolved rise of the calculated ignition probability shows an excellent agreement with high-speed video sequences of the auto-ignition of the free fuel jet and also with studies of the Laser-induced fluorescence (LIF) of formaldehyde. It turns out that the influence of the flow on the auto-ignition under the conditions of the experiment is negligible. To study the characteristics of the

  6. Tissue factor pathway inhibitor relates to fibrin degradation in patients with acute deep venous thrombosis

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Bladbjerg, Else-Marie; Gram, Jørgen

    2008-01-01

    Reduced concentration of tissue factor pathway inhibitor is a risk factor for development of deep venous thrombosis, whereas elevated concentrations of tissue factor pathway inhibitor are observed in patients with acute myocardial infarction and disseminated intravascular coagulation. Presently, we...... studied the association between inflammation, endothelial cell perturbation, fibrin degradation and the concentration of tissue factor pathway inhibitor in patients suspected for acute deep venous thrombosis. We determined the tissue factor pathway inhibitor -33T/C polymorphism, free and total tissue...... factor pathway inhibitor, C-reactive protein, von Willebrand factor and D-Dimer in 160 consecutive patients admitted to hospital with a tentative diagnosis of acute deep venous thrombosis. Deep venous thrombosis was identified in 57 patients (18 distal and 39 proximal). The distribution of the tissue...

  7. Effects of Modified Qing'e Pill () on expression of adiponectin, bone morphogenetic protein 2 and coagulation-related factors in patients with nontraumatic osteonecrosis of femoral head.

    Science.gov (United States)

    Li, Cheng-Gang; Shen, Lin; Yang, Yan-Ping; Xu, Xiao-Juan; Shuai, Bo; Ma, Chen

    2017-03-01

    To observe the regulation of Chinese herbal medicine, Modifified Qing'e Pill (, MQEP), on the expression of adiponectin, bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG) and other potentially relevant risk factors in patients with nontraumatic osteonecrosis of the femoral head (ONFH). A total of 96 patients with nontraumatic ONFH were unequal randomly divided into treatment group (60 cases) and control group (36 cases). The treatment group were treated with MQEP while the control group were treated with simulated pills. Both groups were given caltrate D. Six months were taken as a treatment course. Patients were followed up every 2 months. The levels of plasma adiponectin, BMP2, OPG, von Willebrand factor (vWF), von Willebrand factor cleaving protease (vWF-cp), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), C-reactive protein (CRP), blood rheology, bone mineral density (BMD) of the femoral head and Harris Hip Score were measured before and after treatment. After 6 months of treatment, compared with the control group, patients in the treatment group had signifificantly higher adiponectin and BMP2 levels (Padiponectin showed a positive association with BMP2 (r=0.231, P=0.003) and a negative association with PAI-1 (r=-0.159, Padiponectin, regulating bone metabolism and improving the hypercoagulation state, which may provide an experimental base for its clinical effects.

  8. Nordic Haemophilia Council's practical guidelines on diagnosis and management of von Willebrand disease

    DEFF Research Database (Denmark)

    Lassila, Riitta; Holme, Pål André; Landorph, Andrea

    2011-01-01

    subtyping may also be problematic. This article summarizes the guidelines of the Nordic Haemophilia Council (NHC), which are intended to serve as a practical tool and provide the standards for diagnosing and treating VWD patients. The complete Nordic Guidelines on VWD are available at the NHC Web site (http://nordhemophilia.org)....

  9. Odonaten von Sumatra, gesammelt von Edward Jacobson

    NARCIS (Netherlands)

    Ris, F.

    1927-01-01

    Die folgende Bearbeitung sumatranischer Libellen schliesst sich an zwei frühere Aufsätze über Libellen von Java und von Simalur an, die mir Herr Jacobson anvertraute. Die hier beschriebene wesentlich grössere Sammlung aus den Jahren 1913—15 kam gegen Ende 1920 in meine Hände, sie hätte also längst e

  10. Nasal administration of interleukin-33 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma surrogate.

    Science.gov (United States)

    Shan, Shan; Li, Yan; Wang, Jingjing; Lv, Zhe; Yi, Dawei; Huang, Qiong; Corrigan, Chris J; Wang, Wei; Quangeng, Zhang; Ying, Sun

    2016-05-01

    The T-helper cell type 2-promoting cytokine interleukin-33 (IL-33) has been implicated in asthma pathogenesis. Angiogenesis is a feature of airways remodelling in asthma. We hypothesized that IL-33 induces airways angiogenesis and expression of angiogenic factors in an established murine surrogate of asthma. In the present study, BALB/c mice were subjected to serial intranasal challenge with IL-33 alone for up to 70 days. In parallel, ovalbumin (OVA) -sensitized mice were subjected to serial intranasal challenge with OVA or normal saline to serve as positive and negative controls, respectively. Immunohistochemical analysis of expression of von Willebrand factor and erythroblast transformation-specific-related gene, both blood vessel markers, and angiogenic factors angiogenin, insulin-like growth factor-1, endothelin-1, epidermal growth factor and amphiregulin was performed in lung sections ex vivo. An established in-house assay was used to test whether IL-33 was able to induce microvessel formation by human vascular endothelial cells. Results showed that serial intranasal challenge of mice with IL-33 or OVA resulted in proliferation of peribronchial von Willebrand factor-positive blood vessels to a degree closely related to the total expression of the angiogenic factors amphiregulin, angiogenin, endothelin-1, epidermal growth factor and insulin-like growth factor-1. IL-33 also induced microvessel formation by human endothelial cells in a concentration-dependent fashion in vitro. Our data are consistent with the hypothesis that IL-33 has the capacity to induce angiogenesis at least partly by increasing local expression of multiple angiogenic factors in an allergen-independent murine asthma surrogate, and consequently that IL-33 or its receptor is a potential novel molecular target for asthma therapy.

  11. Histologic Chorioamnionitis, Amniotic Fluid Interleukin 6, Krebs von den Lungen 6, and Transforming Growth Factor β for the Development of Neonatal Bronchopulmonary Dysplasia

    Directory of Open Access Journals (Sweden)

    Hisako Matsumura

    2017-03-01

    Full Text Available Background: Chorioamnionitis (CAM is an important risk factor for the development of bronchopulmonary dysplasia (BPD in preterm infants. Objectives: To evaluate the effects of CAM on the development of BPD using interleukin 6 (IL-6, Krebs von den Lungen 6 (KL-6, and transforming growth factor β 1 (TGF-β 1 in the amniotic fluid as markers for inflammation, lung injury, and fibrosis/remodeling, respectively. Methods: Amniotic fluid concentrations of IL-6, KL-6, and TGF-β 1 were measured with enzyme-linked immunosorbent assay or electrochemiluminescence immunoassay. Results: Of the 36 preterm infants, 18 were exposed to histologically confirmed CAM. Of these, 12 were later diagnosed as having BPD. The IL-6, KL-6, and TGF-β 1 levels in the amniotic fluid significantly increased with increasing histologic severity of CAM. Moreover, these markers were higher in the BPD group with histologic CAM than those without. Conclusions: Our study suggests that CAM is likely to induce inflammatory, injury, and remodeling processes in the fetal lung.

  12. Rheologie von Beschichtungen

    Science.gov (United States)

    Schäffler, Michael

    Die Rheologie beschreibt die Fließ- und Deformationseigenschaften von Materialien. Der Begriff Rheologie ist aus dem Griechischen abgeleitet: rhein - fließen. Erst im Jahre 1930 entwickelte E.C. Bingham und M. Reiner in Easton (USA) die Rheologie zu einer eigenständigen Wissenschaft. Aber bereits seit dem 17. Jahrhundert wurden wesentliche Einzelbeiträge zu Fließphänomenen veröffentlich, so z.B. 1676 von R. Hooke (Hookesches Gesetz) und 1687 von I. Newton (Newtonsches Gesetz). Die Rheologie hat sich bis heute immer mehr zu einer interdisziplinären Wissenschaft entwickelt, die die mechanischen Eigenschaften von Materialien charakterisiert.

  13. Von Hippel-Lindau (VHL inactivation in sporadic clear cell renal cancer: associations with germline VHL polymorphisms and etiologic risk factors.

    Directory of Open Access Journals (Sweden)

    Lee E Moore

    2011-10-01

    Full Text Available Renal tumor heterogeneity studies have utilized the von Hippel-Lindau VHL gene to classify disease into molecularly defined subtypes to examine associations with etiologic risk factors and prognosis. The aim of this study was to provide a comprehensive analysis of VHL inactivation in clear cell renal tumors (ccRCC and to evaluate relationships between VHL inactivation subgroups with renal cancer risk factors and VHL germline single nucleotide polymorphisms (SNPs. VHL genetic and epigenetic inactivation was examined among 507 sporadic RCC/470 ccRCC cases using endonuclease scanning and using bisulfite treatment and Sanger sequencing across 11 CpG sites within the VHL promoter. Case-only multivariate analyses were conducted to identify associations between alteration subtypes and risk factors. VHL inactivation, either through sequence alterations or promoter methylation in tumor DNA, was observed among 86.6% of ccRCC cases. Germline VHL SNPs and a haplotype were associated with promoter hypermethylation in tumor tissue (OR = 6.10; 95% CI: 2.28-16.35, p = 3.76E-4, p-global = 8E-5. Risk of having genetic VHL inactivation was inversely associated with smoking due to a higher proportion of wild-type ccRCC tumors [former: OR = 0.70 (0.20-1.31 and current: OR = 0.56 (0.32-0.99; P-trend = 0.04]. Alteration prevalence did not differ by histopathologic characteristics or occupational exposure to trichloroethylene. ccRCC cases with particular VHL germline polymorphisms were more likely to have VHL inactivation through promoter hypermethylation than through sequence alterations in tumor DNA, suggesting that the presence of these SNPs may represent an example of facilitated epigenetic variation (an inherited propensity towards epigenetic variation in renal tissue. A proportion of tumors from current smokers lacked VHL alterations and may represent a biologically distinct clinical entity from inactivated cases.

  14. Von Triers kristendom

    DEFF Research Database (Denmark)

    Søndergaard, Leif

    2009-01-01

    Lars von Trier er i hans film Antichrist i sin negation af kristendommen stærkt bundet til kristendommens dualistiske verdensbillede. Samtidig er filmen kvindefjendsk. Udgivelsesdato: 2. september......Lars von Trier er i hans film Antichrist i sin negation af kristendommen stærkt bundet til kristendommens dualistiske verdensbillede. Samtidig er filmen kvindefjendsk. Udgivelsesdato: 2. september...

  15. Planung von Hochschulbibliotheken - Tagungsbericht

    Directory of Open Access Journals (Sweden)

    Felicitas Hundhausen

    2015-07-01

    Full Text Available Am 18. November 2014 veranstalteten das HIS-Institut für Hochschulentwicklung und die beiden Herausgeber des "Handbuchs Hochschulbibliothekssysteme", Konstanze Söllner und Wilfried Sühl-Strohmenger, in Hannover eine Tagung zum Thema "Planung von Hochschulbibliotheken". Hier ging es um ausgewählte Aspekte der Planung und Steuerung von Hochschulbibliotheken.

  16. Oligocaene Gastropoden von Buton

    NARCIS (Netherlands)

    Martin, K.

    1935-01-01

    Vor einiger Zeit besehrieb ich eine kleine, eigenartige Molluskenfauna aus tertiären Asphaltkalken von der unbedeutenden Insel Buton, im Südosten von Celebes¹). Seither empfing Herr Prof. Ir. Chr. K. Visser in Delft weitere Versteinerungen aus den Asphaltkalken des Eilands, die nach ihm wahrscheinli

  17. Untersuchungen ueber den Bau von Orbitolina (Patellina auct.) von Borneo

    NARCIS (Netherlands)

    Martin, K.

    1884-01-01

    Vor einer Reihe von Jahren (1856—57) entdeckte Everwijn am Seberoeang, linken Nebenflusse des Kapoeas, in der West-Abtheilung von Borneo, Schichten mit Versteinerungen, welche von ihm für Nummuliten gehalten wurden. Der Fundort befand sich am rechten Ufer, 4—5 Kilometer von der Mündung des

  18. Success factors for the acceptance of renewable energy production plants; Erfolgsfaktoren fuer die Akzeptanz von Erneuerbare-Energie-Anlagen

    Energy Technology Data Exchange (ETDEWEB)

    Walter, Goetz [Zuerich Univ. (Switzerland). Lehrstuhl Sozialpsychologie; Krauter, Sven; Schwenzer, Andreas [The Advisory House GmbH, Muenchen (Germany)

    2011-03-15

    The majority of the German population is in support of the expansion of renewable energies. However, when it comes to construction work, project developers often meet with fierce opposition from the local population. One success factor in raising local acceptance of renewable energy production plants lies in planning projects such that citizens' interests and concerns are taken into account and well-conceived means of public participation are provided. Moreover, municipalities themselves can take on a pivotal role by becoming actively involved in the planning and development process and advertising renewable energy as a way towards municipal emancipation. This gives citizens less reasons to make a stand against such projects.

  19. Soil chemical and physical factors of mycorrhiza mycel growth. Pt. 1 and 2. Pt. 1: Soil structure, soil aeration and spatial distribution of hyphae. - Pt. 2: Development of mycorrhizas in connection to nutrients, water and oxygen in soil and localization of cation uptake; Verteilung und Aktivitaet von Mykorrhizen in Abhaengigkeit von der Naehrelement-, Wasser- und Sauerstoffverfuegbarkeit. T. 1 und 2. T. 1: Bodenchemische und -physikalische Faktoren des Myzelwachstums von Mykorrhizapilzen: Bodenstruktur, Gashaushalt und Hyphenverteilung. - T. 2: Entwicklung von Mykorrhizen in Abhaengigkeit von der Naehrelement-, Wasser- und Sauerstoffverfuegbarkeit in unterschiedlich aggregierten Boeden sowie Lokalisation der Kationenaufnahme

    Energy Technology Data Exchange (ETDEWEB)

    Wilpert, K. v. [Forstliche Versuchs- und Forschungsanstalt Baden-Wuerttemberg, Freiburg im Breisgau (Germany). Abt. Bodenkunde und Waldernaehrung; Schack-Kirchner, H. [Forstliche Versuchs- und Forschungsanstalt Baden-Wuerttemberg, Freiburg im Breisgau (Germany). Abt. Bodenkunde und Waldernaehrung; Hoch, R. [Forstliche Versuchs- und Forschungsanstalt Baden-Wuerttemberg, Freiburg im Breisgau (Germany). Abt. Bodenkunde und Waldernaehrung; Guenther, S. [Forstliche Versuchs- und Forschungsanstalt Baden-Wuerttemberg, Freiburg im Breisgau (Germany). Abt. Bodenkunde und Waldernaehrung; Hildebrand, E.E. [Forstliche Versuchs- und Forschungsanstalt Baden-Wuerttemberg, Freiburg im Breisgau (Germany). Abt. Bodenkunde und Waldernaehrung; Kottke, I. [Tuebingen Univ. (Germany). Lehrstuhl Spezielle Botanik/Mykologie; Leontovycova, J. [Tuebingen Univ. (Germany). Lehrstuhl Spezielle Botanik/Mykologie

    1996-09-01

    This report consists of two parts. In part I, the interaction between distribution patterns of hyphae and the soil structure is discussed. Physiological limits of spreading of hyphae are discussed with regard to the aeration status of macropores and the structure-dependent distribution of nutrient pools. Part II deals with mycorrhizal development and the mycorrhizasoil interface. Soil samples were infiltrated by lanthanum nitrate solution and development of root systems and state of mycorrhizas were evaluated. (FK) [Deutsch] Dieser Bericht besteht aus zwei Teilen. Im ersten wird dargestellt, inwieweit Dichte und Verteilungsmuster von Pilzhyphen Abhaengigkeiten von der Aggregatstruktur des Bodens aufweisen. Physiologische Ausbreitungsgrenzen wurden anhand des Belueftungsstatus im Makroporenraum und der strukturabhaengigen Verteilung von Naehrelementpools interpretiert und diskutiert. Der zweite Teil berichtet ueber Mykorrhiza- und Myzelentwicklung sowie die durch Zugabe von Lanthanionen stimulierte Kationenaufnahme in Abhaengigkeit von der Ionenverfuegbarkeit und vom Wasserstress. (FK)

  20. Ellis Von Creveld Syndrome

    Directory of Open Access Journals (Sweden)

    Afshar H

    1999-01-01

    Full Text Available One patient with Ellis Von Creveld syndrome contains: dwarfism, congenital heart"ndisease, ectodermal dysplasia, polyductyly, an abnormally wide labial frenum and maxillary"nmolars with single root.

  1. Determination of emission factors for benzol and particles of passenger cars in urban areas; Ermittlung von Pkw-Emissionsfaktoren fuer Benzol und Partikel im Ballungsraum

    Energy Technology Data Exchange (ETDEWEB)

    Hitzler, G.; Essers, U. [Forschungsinstitut fuer Kraftfahrwesen und Fahrzeugmotoren Stuttgart (FKFS) (Germany)

    1997-10-01

    In this project real velocity curves from the city of Stuttgart are used to investigate the emission behaviour for both benzene and particulates of passenger cars. The driving cycles, which are carried out by the ISV, represent the style of driving for several types of city streets. The types of city streets are chosen in order to describe all occuring common traffic conditions. Vehicles from the passenger car population, both with Otto-engine and Diesel-engine will be selected by the FKFS. By means of these cars the emissions of CO, HC and NO{sub x}, benzene and particulates will be measured on the exhaust gas roller test bench of the Institute. Emissions factors for several groups of engine displacements and different classes of technologies to reduce noxious components in the exhaust gas are developed from the measuring results. By means of these factors it is possible to evaluate the emissions of passenger cars both related to car population and the types of city streets and even ascending routes the vehicles are driving on. The influence of the cold-start phase on the emissions is also taken into account and will be declared as a selfstanding factor. The interpretation of the results shows the great progress of technical research in emission reduction since the begin of the eighties. (orig.) 17 tabs., 30 figs., 17 refs. [Deutsch] In diesem Vorhaben werden reale Fahrprofile des Ballungsraumes Stuttgart fuer die Bestimmung des Emissionsverhaltens von Pkw fuer die Stoffe Benzol und Partikel verwendet. Die vom Institut fuer Strassen- und Verkehrswesen aus Messfahrten ermittelten Fahrprofile geben das Fahrverhalten auf verschiedenen Strassentypen wieder. Die Strassentypen wurden so ausgewaehlt, dass die im Ballungsraum vorkommenden Strassenverkehrsverhaeltnisse damit beschrieben werden koennen. Aus dem Fahrzeugkollektiv der Personenkraftwagen werden vom FKFS repraesentative Fahrzeuge sowohl mit Otto- als auch mit Dieselmotor ausgewaehlt und auf dem

  2. Lars von Triers film

    DEFF Research Database (Denmark)

    Nielsen, Lisbeth Overgaard

    2007-01-01

    Afhandlingen undersøger Lars von Triers filmæstetik, som den kommer til udtryk i spillefilmene fra perioden 1984-2007. Afhandlingen analyserer de enkelte films stil, virkningsstrategi og betydningsdannelse.......Afhandlingen undersøger Lars von Triers filmæstetik, som den kommer til udtryk i spillefilmene fra perioden 1984-2007. Afhandlingen analyserer de enkelte films stil, virkningsstrategi og betydningsdannelse....

  3. Energetisches Verhalten von Doppelfassaden

    OpenAIRE

    2002-01-01

    Durch die Forderung nach einer natürlichen Lüftung von Bürogebäuden und einem effektiven Sonnenschutz in Hochhäusern haben Doppelfassaden einen hohen Stellenwert erreicht. Das energetische Verhalten von Doppelfassaden ist Gegenstand zahlreicher Veröffentlichungen. Bisher liegen jedoch nur wenige Messungen in ausgeführten Gebäuden vor.Im Rahmen dieser Arbeit wurden drei Gebäude mit Doppelfassaden detailliert vermessen. Die Langzeitmessungen erfassten über mindestens ein Jahr unter anderem die ...

  4. Kontextualisierung von Queer Theory

    Directory of Open Access Journals (Sweden)

    Anna Voigt

    2008-03-01

    Full Text Available Christine M. Klapeer legt in diesem Einführungsband dar, aus welchen politischen und theoretischen Kontexten heraus sich ‚queer‘ zu einem Begriff mit besonderem politischem und theoretischem Gehalt entwickelt hat. Wesentlich zielt sie dabei auf eine kritische Kontextualisierung von „queer theory”. Die Autorin geht zunächst auf das Gay Liberation Movement ein, grenzt die Queer Theory vom Poststrukturalismus, von feministischen Theorien und den Lesbian and Gay Studies ab, beleuchtet Eckpunkte queeren Denkens und zeichnet schließlich die Entwicklungen in Österreich sowohl politisch-rechtlich als auch bewegungsgeschichtlich und in der Wissenschaftslandschaft nach.

  5. Determination of factors influencing the outcome of radioiodine therapy in patients with Graves` disease; Bestimmung von Einflussgroessen fuer den Therapieerfolg der Radioiodtherapie bei Patienten mit Morbus Basedow

    Energy Technology Data Exchange (ETDEWEB)

    Sabri, O.; Schulz, G.; Zimny, M.; Schreckenberger, M.; Zimny, D.; Wagenknecht, G.; Kaiser, H.J.; Dohmen, B.M.; Bares, R.; Buell, U. [Rheinisch-Westfaelische Technische Hochschule (RWTH), Aachen (Germany). Klinik fuer Nuklearmedizin

    1998-05-01

    Aim of this study was to determine whether success of radioiodine therapy (RIT) in Graves` disease depends on thyroid volume, function, thyroideal receptor antibodies (TRAK), thyresotasis, therapeutic dosage, {sup 131}I uptake, or effective half-life. Method: 78 patients received an average of 626{+-}251 MBq of iodine-131 orally for tyroid ablation. 60 were assessed for successful therapy 3 months after RIT. Results: In patients showing hyperthyreosis or a TRAK value >11 U/l at the beginning of RIT, a significantly lower therapeutic doseage and effective iodine half-life were found than in non-hyperthyreotic patients or patients with TRAK{<=}11 U/l. Patients with a thyroid volume {<=}25 ml showed a significantly lower {sup 131}I uptake, but a significantly higher relative uptake ({sup 131}I uptake/volume) than patients with a tyroid volume >25 ml. All failures were treated thyreostatically during RIT and showed a signifiantly lower therapeutic iodine dosage and relative uptake, as well as a significantly higher thyroid volume than patients with a successful therapy. RIT caused a thyroid volume reduction of 44%, with therapy failures showing a significantly lower volume reduction. Patients who received a therapeutic doseage of {<=}250 Gy showed significantly worse results than did those who had received >250 Gy. Only one case of therapy failure received a dosage >250 Gy, while 50% of failures received dosages >200 Gy but <250 Gy. Multivariate analyses (MANOVA, factor analyses) showed thyreostasis as the decisive negative factor for a successful course of therapy. Conclusions: Since most treatment failures occurred in patients under thyreostatic medication, we recommend raising the target dosage to 250 Gy for these cases. (orig.) [Deutsch] Ziel der Studie war es, zu pruefen, inwieweit der Erfolg einer Radioiodtherapie (RIT) des Morbus Basedow (MB) von verschiedenen Parametern (Schilddruesenvolumen [SDVol], Funktion, TRAK, Thyreostase, Therapiedosis, {sup 131}I

  6. Energetische Verwertung von Biomasse

    Science.gov (United States)

    Zahoransky, Richard; Allelein, Hans-Josef; Bollin, Elmar; Oehler, Helmut; Schelling, Udo

    Etwa 0,1% der Solarenergie wandeln sich durch Photosynthese aus dem Kohlendioxid der Luft in Biomasse um. Die Biomassen sind als Festbrennstoff nutzbar oder zu gasförmigen Brennstoffen weiterverarbeitbar. Zwei Arten von Biomassen sind zu unterscheiden: Anfallende Biomasse

  7. Rhizostomeen von Manila

    NARCIS (Netherlands)

    Stiasny, G.

    1924-01-01

    Die hier beschriebene kleine Scyphomedusen-Sammlung wurde von Herrn Director P. B. Sivickis, Dept. of Zoology, University of Philippines, Manila, dem Rijksmuseum van Natuurlijke Historie in Leiden überwiesen. Das Material wurde im December 1922 in Manila-bay gefischt und befindet sich in bestem Erha

  8. The crucial factors for success. From remote meter reading through to aggregate energy data management services; Die kritischen Erfolgsfaktoren. Von der Zaehlerfernauslesung zum Energiedaten-Service

    Energy Technology Data Exchange (ETDEWEB)

    Martini, J. [Enseco GmbH, Muenchen (Germany)

    2001-11-05

    The article discusses the development of an aggregate energy data management service offered to electric utilities and transmission and distribution system operating companies by the Enseco GmbH. Pioneering of the first product, which then was a metering and accounting service, was in 1999. Continuous development in line with practical experience finally has led to an all-inclusive energy data-related service package ranging from commercial data clearing, acquisition and accounting activities through to provision and maintenance of measuring and IT systems, and services for network-wide data management and use-of-system management. (orig./CB) [German] Erstmals im Jahre 1999 wurde von der damaligen Ebit GmbH, heute Enseco GmbH, die bundesweite Beschaffung, Verarbeitung und Bereitstellung von Energiedaten als umfassende Dienstleistung im liberalisierten Strommarkt unter der Bezeichnung MessService angeboten und auf der VDEW-Fachtagung Zaehlen - Messen - Pruefen 1999 vorgestellt. In den zurueckliegenden zwei Jahren konnten wertvolle Erfahrungen und Impulse aus dem Markt gesammelt werden, die die Produktentwicklung massgebend beeinflussten. Letztendlich haben die Anforderungen aus der taeglichen Praxis zur erfolgreichen Platzierung eines stimmigen Serviceangebots zum Energiedaten-Service gefuehrt. (orig.)

  9. Abschied von Ingeborg Pomp

    OpenAIRE

    Hänsel, Rosemarie

    2007-01-01

    Am 4. Juni 2007 erhielten wir die traurige Nachricht, dass Ingeborg Barbara Pomp, Leiterin i. R. der Stenografischen Sammlung von 1996 bis 2006 nach kurzer schwerer Krankheit verstorben ist. Die Mitarbeiterinnen und Mitarbeiter der Sächsischen Landesbibliothek – Staats- und Universitätsbibliothek trauern um eine liebenswerte Kollegin, die sich immer mit einem Höchstmaß an persönlichem Einsatz für die Weiterentwicklung der Stenografischen Sammlung engagiert hat.

  10. Determination of uranium transfer factors from soils contaminated with natural uranium along the Vereinigten Mulde in Zwickau; Bestimmung von Transferfaktoren von Uran aus natuerlich belasteten Boeden entlang der Zwickauer und Vereinigten Mulde

    Energy Technology Data Exchange (ETDEWEB)

    Brand, Andreas

    2011-07-01

    According to IAEA the food chain soil-plants-human is the predominant radionuclide ingestion path. The consumption of contaminated vegetarian food causes a continuous radiation exposure. In this context the problem of contaminated meadows in the Zwickauer and Vereinigten Mulde that is used for agriculture is of predominant interest. In this area intensive uranium mining has caused severe environmental contamination. The agricultural crop land and the grass land were studied with respect to the radionuclides U-238 and U-234. Following the radiochemical separation using ion chromatography the samples were analyzed by alpha-spectrometry. Compared to non-contaminated areas significant specific activities were measured. The transfer factors of the radionuclides U-238 and U-234 were determined for different plant parts. The transfer factors decrease with increasing radioactive contamination of the soils.

  11. Introduction of energy management and renewable energy sources. An investigation of factors of success in German communities; Einfuehrung von Energiemanagement und erneuerbaren Energien. Eine Untersuchung von Erfolgsfaktoren in deutschen Kommunen

    Energy Technology Data Exchange (ETDEWEB)

    Bolay, Sebastian

    2009-07-01

    Energy management and renewable energy sources have come into the focus of local actors in Germany. This study is the first to investigate boundary conditions and reasons for community actions on a large scale, as well as the state of implementation in both fields. It identifies factors of success with positive effects on the introduction of energy management and renewable energy sources in communities and also presents recommendations for communal actors. Models developed on the basis of scientific theories and concepts are investigated by the author on the basis of expert interviews, case studies, and an online enquiry. (orig.)

  12. Nutzerorientiertes Management von materiellen und immateriellen Informationsobjekten

    OpenAIRE

    Hübsch, Chris

    2001-01-01

    Schaffung einer stabilen, erweiterbaren und skalierbaren Infrastruktur für die Bereitstellung von Diensten im Umfeld von Bibliotheken und ähnlichen wissensanbietenden Einrichtungen unter Verwendung von XML-RPC und Python.

  13. Nutzerorientiertes Management von materiellen und immateriellen Informationsobjekten

    OpenAIRE

    Hübsch, Chris

    2001-01-01

    Schaffung einer stabilen, erweiterbaren und skalierbaren Infrastruktur für die Bereitstellung von Diensten im Umfeld von Bibliotheken und ähnlichen wissensanbietenden Einrichtungen unter Verwendung von XML-RPC und Python.

  14. Fresh frozen plasma in the pediatric age group and in congenital coagulation factor deficiency.

    Science.gov (United States)

    Muntean, Wolfgang

    2002-10-31

    Generally, the rules of good practice in transfusion medicine apply also to the pediatric age group. However, the frequency of specific diseases that might necessitate the administration of fresh frozen plasma (FFP) differs from that in adults. Physiologic differences to the later age exist in the neonatal period and in young infants, especially with respect to the hemostatic system, that must be recognized when considering administration of FFP. The plasma levels of many procoagulant factors and important anticoagulants are lower in neonates than in other age groups. Despite these findings, healthy neonates show no easy bruising, no increased bleeding during surgery, and excellent wound healing. The same discrepancy obtains between in vitro and clinical findings with primary hemostasis in neonates. The good primary hemostasis in neonates despite poor in vitro platelet function seems to be due mainly to a very high von Willebrand factor and the presence of more high-multimeric subunits of von Willebrand factor than later in life. We must assume that these particular plasma levels of procoagulant and anticoagulant proteins are essential for the correct function of neonatal hemostasis. Evidence that the hemostatic system of neonates works best with physiologic concentrations of procoagulants and anticoagulants can also be inferred from studies where the administration of clotting factor concentrates gave poor results.Since healthy neonates and young infants have excellent hemostasis, there is absolutely no indication to 'correct' these values to adult's norms prior to invasive procedures by administering FFP. Indications for FFP, met more frequently in the pediatric age group than later in life, are exchange transfusion and extracorporeal membrane oxygenation. Indications applying equally to adults are other extracorporeal life support systems, disseminated intravascular coagulation, hepatic coagulopathy, and 'complex unclear coagulopathies'. In congenital clotting

  15. Theodore von Karman

    Science.gov (United States)

    1950-01-01

    Dr. Theodore von Karman, co-founder of the Jet Propulsion Laboratory (JPL) Pasadena, California was an aeronautical theoretician. His contributions in the fields of aerodynamics and aeronautical engineering are well documented and well known to every aerospace engineer. He was the first winner of the prestigious U.S. Medal of Science presented to him by President John F. Kennedy. As well as being co-founder of JPL, he also was principal founder of a major rocket propulsion firm (Aerojet-General Corp.), the top science advisor to the U.S. Air Force during its transition to jet propulsion aircraft and the top science advisor to NATO. He was, during much of this time, the fountainhead of aerodynamic thought as head of the Guggenheim Aeronautical Laboratory at the California Institute of Technology (GALCIT) in Pasadena, California. In the May 1956 issue of the Journal of Aeronautical Sciences, it was said of him that 'No other man has had so great an impact on the development of aeronautical science in this country. Hundreds of young men became his students and scientific collaborators and were inspired to greater effort.' Dr. William H. Pickering, then director of JPL said in 1960 'We wouldn't have an aeronautical science as we know it today, if it weren't for Dr. Thoedore von Karman.' Under his guidance, Caltech's 10 foot wind tunnel was designed, built and operated. Industry firms such as Douglas, Northrop, Hughes, Lockheed, North American, Vultee and Consolidated all tested new aeronautical designs and concepts in GALCIT's tunnel. Even Boeing's own high-speed wind tunnel was heavily influenced by suggestions from von Karman. The National Advisory Committee for Aeronautics (NACA) became so concerned about GALCIT's growing influence over West coast aviation, it erected the Ames Laboratory in Sunnyvale, California in part to deter an ever widening aeronautical gap that had formed between NACA and GALCIT. From 1936 to 1940, Caltech stood alone as the only university

  16. 血管性假血友病因子和细胞间黏附分子-1在急性呼吸窘迫综合征中的动态变化及早期诊断的意义%Variations and early prediction of von willebrand factor and soluble intercellular adhesion molecule-1 in acute respiratory distress syndrome

    Institute of Scientific and Technical Information of China (English)

    李锐; 曹书华; 王今达

    2004-01-01

    目的检测血管性假血友病因子、可溶性细胞间黏附分子-1浓度变化,以研究其在ARDS早期诊断中的意义.方法以ELISA法检测非ARDS组和ARDS组于0、2、3、5和7d血浆vWF和sICAM-1浓度.结果ARDS组vWF和sICAM-1浓度高于非ARDS组,前四个时点的中性粒细胞活化计数ARDS组高于非ARDS组.血浆vWF和sICAM-1水平具有相关性.结论血浆vWF和sICAM-1浓度及中性粒细胞活化计数在ARDS的早期即升高,对ARDS早期诊断有预警作用.

  17. vWF和Ⅳ型胶原纤维及层粘连蛋白在肝细胞肝癌中的表达及意义%Expression of von Willebrand factor, type IV collagen and laminin in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    朱立新; 刘弋; 范上达

    2003-01-01

    目的探讨血管新生指标vWF和IV胶原纤维(Coll IV)及层粘连蛋白(Lam)在肝细胞肝癌中的表达及意义.方法采用免疫组化方法,对53例肝细胞肝癌的标本进行肝血窦vWF,Coll IV及Lam的染色、计数,并用检测数据与患者的临床资料进行相关性统计分析.结果 vWF染色的血管面积与肿瘤的TNM分期及肝内门静脉浸润呈正相关;Coll IV染色的血管面积与肝内门静脉浸润呈正相关、与术后生存期呈负相关;Lam染色的血管面积与肝硬化及术中出血量呈负相关、与术后生存期呈正相关.结论虽然vWF,Coll IV及Lam同为血管新生指标,但在肝细胞肝癌中,vWF及Coll IV的表达量可作为血管新生指标,并与血管浸润有关、为预后的负性指标;而Lam的表达量则与血管新生无关,其结果反映的是肝硬化程度及术中出血量,并与预后呈正性相关.

  18. 切应力作用下联合培养的血管内皮细胞血管假性血友病因子的含量变化%The changes of von Willebrand factor content in endothelial cells co-cultured with vascular smooth muscle cells under shear stress

    Institute of Scientific and Technical Information of China (English)

    张炎; 丛兴忠

    2000-01-01

    Objective:To investigate the effect of the shear stress onanti-coagulation and.adhesion ability of ECs co-cultured with VSMCs.Methods:ECs co-cultured with VSMCs were exposed to physiological laminar shear stress,vWF in ECs were detected by immunohistochemical method and computer image analysis.Results:The changes of vWF in ECs was correlated with the shear stress.The larger the shear stress was,the smaller the quantity of vWF,especially in the 1st hour.Conclusion:The physiological laminar shear stress probably decrease the expression of vWF in Ecs or accelerate the release of vWF in ECs in short time,which facilitate the enhancing of anti-coagulation and the adhesion ability of ECs co-cultured with VSMCs.%目的:研究切应力对与血管平滑肌细胞联合培养的内皮细胞的抗凝血和粘附的影响。方法:对与平滑肌细胞联合培养的内皮细胞施加生理范围的切应力,用免疫组化及图像分析法检测内皮细胞的血管假性血友病因子(vWF)含量。结果:联合培养的内皮细胞vwF的变化与切应力大小及作用时间有关,随切应力增大,胞内vWF含量逐渐减少,且切应力作用的第1小时减少的最快。结论:生理范围的切应力作用,可能减少与平滑肌细胞联合培养的内皮细胞的vWF表达,或促使vWF短时释放加快,有利于增强抗凝血功能及内皮细胞的粘附。

  19. Regulation of FoxO transcription factors by environmental NO(x). Influence of metal ions and polycyclic aromatic hydrocarbons; Regulation von FoxO-Transkriptionsfaktoren durch Umweltnoxen. Einfluss von Metallionen und polyzyklischen aromatischen Kohlenwasserstoffen

    Energy Technology Data Exchange (ETDEWEB)

    Eckers, Anna

    2009-12-15

    FoxO transcription factors are crucial modulators of various cellular processes, controlling the expression of target genes such as those coding for manganese superoxide dismutase (MnSOD) and selenoprotein P (SeP), thereby supporting defense against oxidative stress. Environmental stimuli such as heavy metal ions and polycyclic aromatic hydrocarbons (PAH) modulate signaling pathways both by interaction with proteins or by inducing the generation of reactive oxygen species (ROS). Exposure of hepatoma cells to nickel ions at subcytotoxic doses did not translate into modulation of FoxO activity despite an activation of the Ser/Thr-kinase Akt. The cellular response to nickel ions under these conditions is most likely independent of the formation of ROS, since there were no increased levels of glutathione disulfide detectable. FoxO activity was then found to be modulated in response to exposure of cells to PAH or the tryptophan photoproduct FICZ. Both PAH and FICZ caused an increased activity of a FoxO-responsive promoter construct as well as of glucose 6-phosphatase promoter activity. In contrast, the activities of promoters of genes coding for MnSOD or SeP were decreased in response to exposure to the PAH 3-methylcholanthrene (3-MC). In line with the promoter effects, 3-MC also decreased steady-state levels of SeP mRNA. The response of the SeP promoter to 3-MC was abrogated by point mutations introduced at the two identified FoxO binding elements of the SeP promoter, implying that interaction of FoxO proteins with these sites is essential for the downregulation of promoter activity. In addition to FoxO activity being modulated by xenobiotics, it was then demonstrated that FoxO expression was also modulated by exposure of cells to PAH or FICZ. FoxO4 mRNA levels were downregulated in hepatoma cells exposed to 3-MC or FICZ. Similarly, insulin treatment caused a downregulation of mRNA levels of FoxO 1a, 3a and 4 in hepatoma cells. (orig.)

  20. Struktur von ABCE1

    OpenAIRE

    Karcher, Annette

    2007-01-01

    ABCE1 ist ein Mitglied der ATP Binding Cassette (ABC) Superfamilie. ABC Proteine binden und hydrolysieren ATP und verändern dabei ihre Konformation. Dadurch können sie mechanochemische Arbeit leisten. Durch drei zusätzliche Domänen unterscheidet sich ABCE1 von allen bislang bekannten und charakterisierten Mitgliedern dieser Familie. Neben den ATP-bindenden Regionen enthält ABCE1 eine cysteinreiche, N-terminale Domäne, welche zwei Eisen-Schwefel-Cluster bindet. Diese Domäne hat hohe s...

  1. Remarks on the continuous L^2-cohomology of von Neumann algebras

    CERN Document Server

    Alekseev, Vadim

    2011-01-01

    We prove that norm continuous derivations from a von Neumann algebra into the algebra of operators affiliated with its tensor square are automatically continuous for the strong operator topology as well. From this we rederive previously known computational results regarding the first continuous L^2-Betti number for von Neumann algebras, and furthermore prove that it vanishes whenever the von Neumann algebra in question is a property (T) factor.

  2. Alejandro Von Humboldt

    Directory of Open Access Journals (Sweden)

    Gerardo Paz Otero

    1965-09-01

    Full Text Available Diverso fue y sigue siéndolo, el destino de los dos hermanos Humboldt, Guillermo y Alejandro. Sino que se inicia con el nacimiento: Guillermo, el mayor, nace el 22 de junio de 1767 en Potsdam, residencia de los emperadores prusianos, la ciudad de los palacios imperiales, el imperio del militarismo germano; su cuna se meció cerca al palacete de Sans-Soussi, donde Federico el Grande forja ba el poderío de Prusia, cultivaba las ciencias y las artes, anfitrionaba a los intelectuales de Europa, y era "vasallo espiritual de Volta ire", según la aguda frase de Goethe. Alejandro viene al mundo dos años después (14 de septiembre de 1769 en Berlín, en la casa burguesa de la Jagerstrasse (calle del cazador que su madre Elizabeth von Humboldt heredara de su primer esposo.

  3. Mikrochirurgische Entfernung von Hirnstammkavernomen

    Directory of Open Access Journals (Sweden)

    Pfisterer W

    2002-01-01

    Full Text Available Der Anteil der Kavernome an allen intrakraniellen vaskulären Malformationen beträgt 14 %. Davon liegen etwa 20 % im Hirnstamm. Bei einer Rezidivblutungsrate von 21 % jährlich ist auch eine Exstirpation im Hirnstamm indiziert. Wir berichten über 3 Patienten mit Hirnstammkavernomen, die in mikrochirurgischer Technik bei geringer Morbidität und ohne Mortalität an unserer Abteilung total exstirpiert wurden. Wir halten die subakute Phase für den besten Zeitpunkt zur Entfernung des Kavernoms, wenn dies der klinisch-neurologische Zustand des Patienten erlaubt. Die mikrochirurgische Exstirpation wurde durch Elektrophysiologie (akustisch und somatosensorisch evozierte Potentiale, Endoskopie und Neuronavigation unterstützt.

  4. Kleben von Kunststoff mit Metall

    CERN Document Server

    Brockmann, W; Käufer, H

    1989-01-01

    Das Buch behandelt das Kleben von Kunststoffen mit Metallen in einer fur den Praktiker verstandlichen und umsetzbaren Form. Es leitet zu Klebeverfahren an, die optimale Ergebnisse hinsichtlich Qualitat, Dauerhaftigkeit und Wirtschaftlichkeit liefern.

  5. Planung und Bewertung von Montagesystemen

    Science.gov (United States)

    Hartel, Marko; Lotter, Bruno

    Die Gestaltung von Montagesystemen ist eine wesentliche Aufgabenstellung an die planenden Bereiche eines Unternehmens. Anhand von Praxis-beispielen werden Planungssystematiken and Bewertungsverfahren — sei es fur die Effizienzsteigerung einer bestehenden Montage oder die Entscheidung zwischen Varianten eines geplanten Montagesystems — aufzeigt. Die folgende Planungssystematik nach REFA wird für Produktionssysteme im Allgemeinen angewandt; die Planungssystematik nach Lotter ist speziell auf Montagesysteme ausgelegt.

  6. Theorie und Praxis von Hochschulrankings

    OpenAIRE

    Hornbostel, Stefan

    2007-01-01

    Der Beitrag gibt einen Überblick über die theoretische Grundlage von Hochschulrankings, welche in der qualitativ stark differenzierten Hochschullandschaft in Deutschland entscheidend für öffentliche Reputationsurteile sein können. Ausgehend von einem formal gleichrangigen Institutionengefüge der Hochschullandschaft in Deutschland haben die Stichworte Profilbildung, Exzellenz und Wettbewerb in den letzten Jahren zunehmend an Bedeutung gewonnen. Der daraus resultierende große Informationsbedarf...

  7. Plasma-derived versus recombinant factor concentrates in PUPs: a never ending debate?

    Science.gov (United States)

    Berntorp, Erik

    2017-01-31

    Inhibitor development in haemophilia is a serious complication to treatment with factor concentrates. Since the advent of more pure products, especially developed using recombinant DNA technology, some studies have shown an increased incidence of inhibitors in previously untreated patients (PUPs) receiving recombinant products whereas plasma-derived concentrates sometimes have been claimed to have a protective role, probably due to the content of von Willebrand factor (VWF). In fact, experiments indicate that the VWF may block uptake of factor VIII into macrophages for further processing to the immune system. Also, a competition between VWF and inhibitor binding to the C2 domain of factor VIII has been suggested. Recently, large cohort and surveillance studies have created a vigorous debate about the role of product class for inhibitor development as results have been conflicting. The only randomised prospective study, the SIPPET study, was published in 2016, and substantiated previous reports claiming that plasma derived concentrates give less inhibitors in patients with severe haemophilia A, previously not exposed to factor VIII. The debate will continue.

  8. Vergleich von simulierten und reellen Schleppkurven von Landmaschinen

    Directory of Open Access Journals (Sweden)

    Steffen Hürter

    2014-02-01

    Full Text Available An das landwirtschaftliche Wegenetz werden durch die kontinuierliche Größenentwicklung von Landmaschinen neue Anforderungen gestellt. Die Maschinen werden breiter und länger und besitzen mehr Achsen und komplexere Lenksysteme als in der Vergangenheit. Beim landwirtschaftlichen Wegebau hat dies insbesondere Auswirkungen auf die Planung der Kurven. In der Untersuchung wurden die Schleppkurven aktueller Landmaschinen aufgenommen und es wurde geprüft, ob sie mithilfe einer Software simuliert werden können. Dabei zeigt sich, dass die verwendete Simulationssoftware für die Bestimmung von Schleppkurven für Landmaschinen mit komplexen Lenksystemen hinreichend genau ist.

  9. Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell's Viper Bites with Coagulopathy.

    Directory of Open Access Journals (Sweden)

    Geoffrey K Isbister

    Full Text Available Russell's viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell's viper envenoming.In a prospective cohort of 146 patients with Russell's viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT, activated partial thromboplastin time (aPTT, coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39 y (16-82 y and 111 were male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13, associated with low fibrinogen [median,3 at 6 h post-antivenom but had reduced to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec at 24 h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02 and aPTT (r = 0.19, p = 0.03 were correlated (non-parametric Spearman analysis.Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48 h. Severity of clotting abnormalities was associated with venom concentrations.

  10. Is ABO blood group truly a risk factor for thrombosis and adverse outcomes?

    Science.gov (United States)

    Zhou, Shan; Welsby, Ian

    2014-01-01

    ABO blood type is one of the most readily available laboratory tests, and serves as a vital determinant in blood transfusion and organ transplantation. The ABO antigens are expressed not only on red blood cell membranes, determining the compatibility of transfusion, but also on the surface of other human cells, including epithelium, platelet and vascular endothelium, therefore extending the research into other involvements of cardiovascular disease and postoperative outcomes. ABO blood group has been recognized as a risk factor of venous thrombosis embolism since the 1960’s, effects now understood to be related to ABO dependent variations are procoagulant factor VIII (FVIII) and von Willebrand factor (vWF) levels. Levels of vWF, mostly genetically determined, are strongly associated with venous thromboembolism (VTE). It mediates platelet adhesion aggregation and stabilizes FVIII in plasma. Moreover, many studies have tried to identify the relationship between ABO blood types and ischemic heart disease. Unlike the clear and convincing associations between VTE and ABO blood type, the link between ABO blood type and ischemic heart disease is less consistent and may be confusing. Other than genetic factors, ischemic heart disease is strongly related to diet, race, lipid metabolism and economic status. In this review, we’ll summarize the data relating race and genetics, including ABO blood type, to VTE, ischemic heart disease and postoperative bleeding after cardiac surgery. PMID:25276299

  11. Ethnographische Filme und die Darstellung von Frauen

    Directory of Open Access Journals (Sweden)

    Judith Keilbach

    2002-03-01

    Full Text Available In dieser Filmographie werden ethnographische und koloniale Filme aus dem Bestand des Nederlands Filmmuseum kommentiert, die für die Frage nach der Darstellung von Frauen und Geschlechterverhältnissen von Interesse sind.

  12. Bibliographie der Werke von Herbert Spencer

    OpenAIRE

    Schmid, Michael (Prof.)

    1991-01-01

    Bibliographie der Werke von Herbert Spencer / bearb., hrsg., mit e. Einl. u. e. Kurzbiogr. vers. von Michael Schmid u. Margit Weihrich. - München : Inst. für Soziologie u. Gesellschaftspolitik, Univ. d. Bundeswehr, 1991. - 159 S.

  13. Role of pigment epithelium-derived factor on proliferation and migration of choroidal capillary endothelium induced by vascular endothelial growth factor in vitro

    Institute of Scientific and Technical Information of China (English)

    WANG Feng-hua; SUN Xiao-dong; ZHANG Xi; XU Xun; ZHU Qi; HUANG Jian-nan; FAN Ying; GU Qing; LIU Hai-yang

    2007-01-01

    Background Pigment epithelium-derived factor (PEDF) is expressed in several normal organs and identified as an inhibitor of neovascularization. In the present study, we investigated the effect of PEDF in an in vitro model of ocular choroidal neovascularization.Methods Microdissection was used to isolate the human choroidal endothelial cells (CECs), followed by the use of superparamagnetic beads (Dynabeads) coated with the CD31 antibody, which selectively binds to the endothelial cell surface. The mitogenic and motogenic effects of vascular endothelial growth factor (VEGF) on cultured choroidal capillary endothelial cells were examined in the presence or absence of PEDF (1, 10, 100, and 1000 ng/ml) using cell counts and migration assays.Results Cells bound to the beads were isolated using a magnetic particle concentrator and they were successfully cultured and characterized to be endothelial cells that possessed greater than 95% immunoreactivity to von Willebrand factor. PEDF suppressed the proliferation and migration of VEGF-induced choroidal capillary endothelial cells. However,the concentration of PEDF which we used has little effect on normal CECs.Conclusions PEDF played an important role on the growth and migration of VEGF-stimulated choroidal endothelial cell.These findings suggest that PEDF may be an effective approach to the treatment of choroidal neovascular disorders.

  14. Diskriminierung von Enantiomeren mit chiralen Selektoren

    OpenAIRE

    Würthner, Stefan

    2007-01-01

    Die vorliegende Dissertation befasst sich mit der systematischen Aufklärung von zwischenmolekularen Wirt-Gast-Wechselwirkungen von Arzneistoffen mit Cyclodextrinen. In einem sich trichterförmig verengenden Erkenntnisprozeß wird im ersten Schritt eine breite Datenbasis von Kapillarelektrophorese-Daten von 86 chiralen Arzneistoffen mit 3 nativen CDs (alpha, beta und gamma) sowie 11 CD-Derivaten gewonnen. Sowohl die Trennfaktoren der Enantiomeren (alpha_m) als auch die Retardierungsfaktoren (R_m...

  15. [Pheochromocytoma and von Recklinghausen's disease].

    Science.gov (United States)

    Rabii, R; Fekak, H; Moufid, K; Joual, A; Bennani, S; el Mrini, M; Benjelloun, S

    2002-07-01

    The association between von Recklinghausen's disease and pheochromocytoma is present about 10% of cases. We report a case of 49 years old women who presented with elevated blood pressure and von Recklinghausen's neurofibromatosis. Laboratory examination showed a marked level in the urinary excretion of cathecholamine. The computed tomography showed a right adrenal tumor suggesting a pheochromocytoma. The adrenalectomy was realised by transabdominal approach and the histological examination confirmed a benign pheochromocytoma. The authors discuss the pathogenetic hypothesis of this rare pathological association, the diagnostic methods and the therapeutic procedure.

  16. An Invitation from Lars von Trier

    DEFF Research Database (Denmark)

    Skadhauge, Troels; Tønder, Lars

    2015-01-01

    Translation of Martin Krasnik interview with Lars von Trier broadcast on DR2, January 12, 2015. The following is an interview of Lars von Trier (LvT) by the Danish journalist Martin Krasnik (MK). The interview took place in Lars von Trier’s home in Brede, a small town just outside Copenhagen...

  17. Homopteren von Java, gesammelt von Herrn Edw. Jacobson

    NARCIS (Netherlands)

    Melichar, L.

    1914-01-01

    Herr Edw. Jacobson hat auf Java in den Jahren 1908— 1910 Homopteren gesammelt und mir die Bearbeitung des gesammelten Materiales übertragen. Die Jacobson’sche Ausbeute ist insoferne bemerkenswert, als dieselbe viele Mikrohomopteren enthält, welche von nichtfachkundigen Sammlern gewöhnlich nicht

  18. Homopteren von Java, gesammelt von Herrn Edw. Jacobson

    NARCIS (Netherlands)

    Melichar, L.

    1914-01-01

    Herr Edw. Jacobson hat auf Java in den Jahren 1908— 1910 Homopteren gesammelt und mir die Bearbeitung des gesammelten Materiales übertragen. Die Jacobson’sche Ausbeute ist insoferne bemerkenswert, als dieselbe viele Mikrohomopteren enthält, welche von nichtfachkundigen Sammlern gewöhnlich nicht beac

  19. Integration von Erkennung und Interpretation von gesprochener Sprache

    OpenAIRE

    Fink, Gernot A.; Kummert, Franz; Sagerer, Gerhard; Kunze, Jürgen

    1994-01-01

    Die Mehrzahl der heutigen sprachverstehenden Systeme sind aus zwei sehr unterschiedlichen Verarbeitungskomponenten aufgebaut, einer meist statistischen Spracherkennungskomponente und einer in der Regel wissensbasiert arbeitenden Komponente zur Interpretation. Die Kommunikation zwischen diesen Verarbeitungseinheiten ist stark eingeschränkt. In der Regel werden von der Spracherkennung nur Worthypothesenmengen berechnet und an die Interpretationskomponente weitergereicht ohne weitere Interaktion...

  20. Regulatory components of the alternative complement pathway in endothelial cell cytoplasm, factor H and factor I, are not packaged in Weibel-Palade bodies.

    Directory of Open Access Journals (Sweden)

    Nancy A Turner

    Full Text Available It was recently reported that factor H, a regulatory component of the alternative complement pathway, is stored with von Willebrand factor (VWF in the Weibel-Palade bodies of endothelial cells. If this were to be the case, it would have therapeutic importance for patients with the atypical hemolytic-uremic syndrome that can be caused either by a heterozygous defect in the factor H gene or by the presence of an autoantibody against factor H. The in vivo Weibel-Palade body secretagogue, des-amino-D-arginine vasopressin (DDAVP, would be expected to increase transiently the circulating factor H levels, in addition to increasing the circulating levels of VWF. We describe experiments demonstrating that factor H is released from endothelial cell cytoplasm without a secondary storage site. These experiments showed that factor H is not stored with VWF in endothelial cell Weibel-Palade bodies, and is not secreted in response in vitro in response to the Weibel-Palade body secretagogue, histamine. Furthermore, the in vivo Weibel-Palade body secretagogue, DDAVP does not increase the circulating factor H levels concomitantly with DDAVP-induced increased VWF. Factor I, a regulatory component of the alternative complement pathway that is functionally related to factor H, is also located in endothelial cell cytoplasm, and is also not present in endothelial cell Weibel-Palade bodies. Our data demonstrate that the factor H and factor I regulatory proteins of the alternative complement pathway are not stored in Weibel-Palade bodies. DDAVP induces the secretion into human plasma of VWF--but not factor H.

  1. Regulatory components of the alternative complement pathway in endothelial cell cytoplasm, factor H and factor I, are not packaged in Weibel-Palade bodies.

    Science.gov (United States)

    Turner, Nancy A; Sartain, Sarah E; Hui, Shiu-Ki; Moake, Joel L

    2015-01-01

    It was recently reported that factor H, a regulatory component of the alternative complement pathway, is stored with von Willebrand factor (VWF) in the Weibel-Palade bodies of endothelial cells. If this were to be the case, it would have therapeutic importance for patients with the atypical hemolytic-uremic syndrome that can be caused either by a heterozygous defect in the factor H gene or by the presence of an autoantibody against factor H. The in vivo Weibel-Palade body secretagogue, des-amino-D-arginine vasopressin (DDAVP), would be expected to increase transiently the circulating factor H levels, in addition to increasing the circulating levels of VWF. We describe experiments demonstrating that factor H is released from endothelial cell cytoplasm without a secondary storage site. These experiments showed that factor H is not stored with VWF in endothelial cell Weibel-Palade bodies, and is not secreted in response in vitro in response to the Weibel-Palade body secretagogue, histamine. Furthermore, the in vivo Weibel-Palade body secretagogue, DDAVP does not increase the circulating factor H levels concomitantly with DDAVP-induced increased VWF. Factor I, a regulatory component of the alternative complement pathway that is functionally related to factor H, is also located in endothelial cell cytoplasm, and is also not present in endothelial cell Weibel-Palade bodies. Our data demonstrate that the factor H and factor I regulatory proteins of the alternative complement pathway are not stored in Weibel-Palade bodies. DDAVP induces the secretion into human plasma of VWF--but not factor H.

  2. Platelets interact with tissue factor immobilized on surfaces: effects of shear rate.

    Science.gov (United States)

    Tonda, R; Lopez-Vilchez, I; Navalon, F; Pino, M; Hernandez, M R; Escolar, G; Galan, A M

    2008-01-01

    While procoagulant activities of Tissue Factor (TF) have been widely investigated, its possible pro-adhesive properties towards platelets have not been studied in detail. We explored the interaction of platelets with human Tissue Factor (hTF) firmly adsorbed on a synthetic surface of polyvinilidene difluoride (PVDF) using different shear rates. For studies at 250 and 600 s(-1), TF firmly adsorbed was exposed to flowing anticoagulated blood in flat perfusion devices. Deposition of platelets and fibrin were evaluated by morphometric, immunocytochemical and ultrastructural methods. Prothrombin fragment 1 + 2 (F1 + 2) levels were also measured. Experiments at 5000 s(-1), were performed on the Platelet Function Analyzer (PFA-100) with experimental cartridges with collagen (COL) or collagen-hTF (COL + TF). Haemostatic effect of recombinant activated FVIIa (rFVIIa) was assessed in the same experimental settings. Platelet deposition on hTF reached 19.8 +/- 1.3% and 26.1 +/- 3.4% of the total surface, at 250 and 600 s(-1), respectively. Fibrin formation was significantly higher at 250 s(-1) than at 600 s(-1) (P hTF (154.09 +/- 14.69 s vs. 191.45 +/- 16.09 s COL alone; P hTF is an adhesive substrate for platelets and suggest that the von Willebrand factor could mediate these interactions. At low and intermediate shear rates, rFVIIa enhanced the procoagulant action of hTF, but this effect was not observed at very high shear rates.

  3. Expression of vascular endo- thelial growth factor in rat uterus during peri- implantation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The first distinct mark of rodent implantation is the increased vascular permeability and significant angiogenesis at the sites of blastocyst implantation, but its mechanism is not clearly defined. Vascular endothelial growth factor (VEGF) is the key mediator for angiogenesis during embryogenesis and adult span and also serves as a vascular permeability factor. The aim of this study is to explore VEGF regulation mechanism and the possible role that VEGF plays in implantation by studying the VEGF expression and angio-genesis in the rat uterus during estrous cycle, ovarioecto-mized and peri-implantation stages using in situ message RNA hybridization and confocal laser scanning techniques. The results indicated that VEGF was regulated by ovarian steroid hormones. VEGF expression before implantation was localized at luminal epithelium, shifted to stroma as implan-tation initiated and extensively located at the decidualizing stroma region after implantation. Bandeiraea simplicifolia-1 (BS-1) agglutinin and antibody against von Willebrand fac-tor (vWF) were used to mark the endothelial cells and blood vessels. The results showed that the active angiogenesis oc-curred during the implantation process and this effect was probably mediated by VEGF. The results suggest that under the regulation of ovarian steroid hormones, VEGF plays an essential role in angiogenesis and increasing vascular perme-ability in endometrium, which are necessary for successful implantation.

  4. Age relations of cardiovascular risk factors in a traditional Melanesian society: the Kitava Study.

    Science.gov (United States)

    Lindeberg, S; Berntorp, E; Nilsson-Ehle, P; Terént, A; Vessby, B

    1997-10-01

    This study examined cross-sectional age relations of blood pressure, anthropometric indexes, serum lipids, and hemostatic variables in 203 subsistence horticulturists aged 20-86 y in Kitava, Trobriand Islands, Papua New Guinea. The population is characterized by extreme leanness (despite food abundance), low blood pressure, low plasma plasminogen activator inhibitor 1 activity, and rarity of cardiovascular disease. Tubers, fruit, fish, and coconut are dietary staples whereas dairy products, refined fat and sugar, cereals, and alcohol are absent and salt intake is low. Although diastolic blood pressure was not associated with age in Kitavans, systolic blood pressure increased linearly after 50 y of age in both sexes. Body mass index decreased with age in both sexes. Serum total cholesterol, triacylglycerol, low-density-lipoprotein cholesterol, and apolipoprotein B increased in males between 20 and 50 y of age, whereas high-density-lipoprotein cholesterol and apolipoprotein A-I decreased. There were no significant differences in these indexes with age in the few females studied. A slight linear age-related increase of lipoprotein(a) was present in males. Plasma fibrinogen, factor VII clotting activity, factor VIII clotting activity, and von Willebrand factor antigen increased with age in both sexes but plasminogen activator inhibitor 1 activity did not. The modest or absent relations between the indexes measured and age are apparently important explanations of the virtual nonexistence of stroke and ischemic heart disease in Kitava.

  5. Sindrom Von Hippel–Lindau

    Directory of Open Access Journals (Sweden)

    E V Ershova

    2011-06-01

    Full Text Available Von Hippel-Lindau syndrome - a systemic disease manifesting with multiple tumor growth, inherited by autosomal-dominant type with high penetrance. Understanding the pathogenesis of the disease is important for determining the start time of screening for the presence of the tumors and adequate treatment, including metabolic disorders.

  6. Zur Soziologie von Ctenidium molluscum

    NARCIS (Netherlands)

    Zijlstra, Gea

    1979-01-01

    Bei einer Untersuchung in einer Anzahl von niederländischen „blauwgraslanden“ (d. h. „blaue Wiesen“, Cirsio-Molinietum, Junco-Molinion) wurde Ctenidium molluscum angetroffen, eine Art, welche in den Niederlanden mehr oder weniger zum Mesobromion gerechnet wird. Untersuchungen an altem Herbarmaterial

  7. [Friedrich Ludwig von Maydelli pildid Baltimaade ajaloost = Friedrich Ludwig von Maydells Baltische Geschichte in Bildern = Friedrich Ludwig von Maydell ́s Baltic history in images] / Ulrike Plath

    Index Scriptorium Estoniae

    Plath, Ulrike, 1972-

    2014-01-01

    Arvustus: Friedrich Ludwig von Maydelli pildid Baltimaade ajaloost = Friedrich Ludwig von Maydells Baltische Geschichte in Bildern = Friedrich Ludwig von Maydell ́s Baltic history in images. Eesti kunstimuuseum, Kadrioru kunstimuuseum. Tallinn 2013

  8. [Friedrich Ludwig von Maydelli pildid Baltimaade ajaloost = Friedrich Ludwig von Maydells Baltische Geschichte in Bildern = Friedrich Ludwig von Maydell ́s Baltic history in images] / Ulrike Plath

    Index Scriptorium Estoniae

    Plath, Ulrike, 1972-

    2014-01-01

    Arvustus: Friedrich Ludwig von Maydelli pildid Baltimaade ajaloost = Friedrich Ludwig von Maydells Baltische Geschichte in Bildern = Friedrich Ludwig von Maydell ́s Baltic history in images. Eesti kunstimuuseum, Kadrioru kunstimuuseum. Tallinn 2013

  9. Schätzung von Vegetationsparametern aus multispektralen Fernerkundungsdaten

    OpenAIRE

    2007-01-01

    In der vorliegenden Arbeit wird ein Verfahren zur Schätzung von Vegetationsparametern aus multispektralen Fernerkundungsdaten unter Verwendung von physikalischen Strahlungstransfer-Modellen und einer geringen Anzahl von Bodenmessungen vorgestellt. Dieses Verfahren wurde über einen Zeitraum von zwei Jahren exemplarisch an verschiedenen Winterweizenfeldern getestet, die mit einem Daedalus ATM Multispektralscanner aufgenommen wurden. Von besonderem Interesse sind hierbei die Schwankungen der Veg...

  10. Shock, diaschisis and von Monakow

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    2013-07-01

    Full Text Available The concept of shock apparently emerged in the middle of the 18th century (Whyett as an occurrence observed experimentally after spinal cord transection, and identified as "shock" phenomenon one century later (Hall. The concept was extended (Brown-Séquard and it was suggested that brain lesions caused functional rupture in regions distant from the injured one ("action à distance". The term "diaschisis" (von Monakow, proposed as a new modality of shock, had its concept broadened, underpinned by observations of patients, aiming at distinguishing between symptoms of focal brain lesions and transitory effects they produced, attributable to depression of distant parts of the brain connected to the injured area. Presently, diaschisis is related mainly to cerebrovascular lesions and classified according to the connection fibers involved, as proposed by von Monakow. Depression of metabolism and blood flow in regions anatomically separated, but related by connections with the lesion, allows observing diaschisis with neuroimaging.

  11. Moose von Inselbergen in Benin

    OpenAIRE

    Frahm, Jan-Peter; Porembski, Stefan

    1998-01-01

    Acht Leber- und zehn Laubmoosarten werden von Inselbergen aus Benin angegeben. Fünf der Lebermoose (Acrolejeunea emergens, Riccia atropurpurea, R. congoana, R. discolor, R. moenkemeyeri) und alle Laubmoose (Archidium ohioense, Brachymenium acuminatum, B. exile, Bryum arachnoideum, B. argenteum, Bryum deperssum, Garckea moenkemeyeri, Hyophila involuta, Philonotis mniobryoides und Weissia cf. edentula) werden neu für Benin angegeben. Eight liverworts and ten mosses are reported from inselber...

  12. Prolyl hydroxylase 2 dependent and Von-Hippel-Lindau independent degradation of Hypoxia-inducible factor 1 and 2 alpha by selenium in clear cell renal cell carcinoma leads to tumor growth inhibition

    Directory of Open Access Journals (Sweden)

    Chintala Sreenivasulu

    2012-07-01

    Full Text Available Abstract Background Clear cell renal cell carcinoma (ccRCC accounts for more than 80% of the cases of renal cell carcinoma. In ccRCC deactivation of Von-Hippel-Lindau (VHL gene contributes to the constitutive expression of hypoxia inducible factors 1 and 2 alpha (HIF-α, transcriptional regulators of several genes involved in tumor angiogenesis, glycolysis and drug resistance. We have demonstrated inhibition of HIF-1α by Se-Methylselenocysteine (MSC via stabilization of prolyl hydroxylases 2 and 3 (PHDs and a significant therapeutic synergy when combined with chemotherapy. This study was initiated to investigate the expression of PHDs, HIF-α, and VEGF-A in selected solid cancers, the mechanism of HIF-α inhibition by MSC, and to document antitumor activity of MSC against human ccRCC xenografts. Methods Tissue microarrays of primary human cancer specimens (ccRCC, head & neck and colon were utilized to determine the incidence of PHD2/3, HIF-α, and VEGF-A by immunohistochemical methods. To investigate the mechanism(s of HIF-α inhibition by MSC, VHL mutated ccRCC cells RC2 (HIF-1α positive, 786–0 (HIF-2α positive and VHL wild type head & neck cancer cells FaDu (HIF-1α were utilized. PHD2 and VHL gene specific siRNA knockdown and inhibitors of PHD2 and proteasome were used to determine their role in the degradation of HIF-1α by MSC. Results We have demonstrated that ccRCC cells express low incidence of PHD2 (32%, undetectable PHD3, high incidence of HIF-α (92%, and low incidence of VEGF-A compared to head & neck and colon cancers. This laboratory was the first to identify MSC as a highly effective inhibitor of constitutively expressed HIF-α in ccRCC tumors. MSC did not inhibit HIF-1α protein synthesis, but facilitated its degradation. The use of gene knockdown and specific inhibitors confirmed that the inhibition of HIF-1α was PHD2 and proteasome dependent and VHL independent. The effects of MSC treatment on HIF-α were associated with

  13. Trp[superscript 2313]-His[superscript 2315] of Factor VIII C2 Domain Is Involved in Membrane Binding Structure of a Complex Between the C[subscript 2] Domain and an Inhibitor of Membrane Binding

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhuo; Lin, Lin; Yuan, Cai; Nicolaes, Gerry A.F.; Chen, Liqing; Meehan, Edward J.; Furie, Bruce; Furie, Barbara; Huang, Mingdong (Harvard-Med); (UAH); (Maastricht); (Chinese Aca. Sci.)

    2010-11-03

    Factor VIII (FVIII) plays a critical role in blood coagulation by forming the tenase complex with factor IXa and calcium ions on a membrane surface containing negatively charged phospholipids. The tenase complex activates factor X during blood coagulation. The carboxyl-terminal C2 domain of FVIII is the main membrane-binding and von Willebrand factor-binding region of the protein. Mutations of FVIII cause hemophilia A, whereas elevation of FVIII activity is a risk factor for thromboembolic diseases. The C2 domain-membrane interaction has been proposed as a target of intervention for regulation of blood coagulation. A number of molecules that interrupt FVIII or factor V (FV) binding to cell membranes have been identified through high throughput screening or structure-based design. We report crystal structures of the FVIII C2 domain under three new crystallization conditions, and a high resolution (1.15 {angstrom}) crystal structure of the FVIII C2 domain bound to a small molecular inhibitor. The latter structure shows that the inhibitor binds to the surface of an exposed {beta}-strand of the C2 domain, Trp{sup 2313}-His{sup 2315}. This result indicates that the Trp{sup 2313}-His{sup 2315} segment is an important constituent of the membrane-binding motif and provides a model to understand the molecular mechanism of the C2 domain membrane interaction.

  14. Didaktische Konzeption von Serious Games: Zur Verknüpfung von Spiel- und Lernangeboten

    Directory of Open Access Journals (Sweden)

    Michael Kerres

    2009-08-01

    Full Text Available Serious Games versuchen Spielen mit Lernen zu verbinden. Der Beitrag problematisiert die Machbarkeit einer solchen Verknüpfung in digitalen Welten und diskutiert verschiedene didaktische Konzepte einer Nutzbarmachung digitaler Spiele für das Lernen und Lehren. Ausgehend von einer Analyse des Erlernens von Spielen werden drei didaktische Konzepte von Serious Games im Hinblick auf ihre didaktischen Potenziale untersucht: (1 der unmittelbare Transfer von Wissen, das im Spiel erworben wird (keine zusätzliche Didaktisierung, (2 Didaktisierung durch Einbettung des Spiels in einer Lernsituation oder (3 Didaktisierung durch Einbettung von Lernaufgaben in ein Spiel. Ergebnisse zur Nutzung von Spielen, bei denen Lernaufgaben in eine Spielwelt eingebettet sind, zeigen, dass Personen die Aufnahme von Wissen in einem expliziten Lernmodus eher zu reduzieren versuchen, um möglichst zügig wieder in den Spielmodus zu wechseln. Diskutiert werden die Konsequenzen dieser Problematik für die didaktische Konzeption von Serious Games.

  15. Concentration changes during venous occlusion of proteins with affinity for extracellular matrix in insulin-dependent diabetes mellitus A sign of vascular damage in patients with diabetic nephropathy?

    NARCIS (Netherlands)

    Myrup, B.; Rossing, P.; Jensen, T.; Gram, J.; Kluft, C.; Jespersen, J.

    1999-01-01

    Objective: To investigate protein concentration changes during venous occlusion of proteins with reported affinity for extracellular matrix (plasminogen activator inhibitor type 1, antithrombin III, fibronectin and von Willebrand factor) in comparison with proteins with no reported affinity (albumin

  16. Concentration changes during venous occlusion of proteins with affinity for extracellular matrix in insulin-dependent diabetes mellitus A sign of vascular damage in patients with diabetic nephropathy?

    NARCIS (Netherlands)

    Myrup, B.; Rossing, P.; Jensen, T.; Gram, J.; Kluft, C.; Jespersen, J.

    1999-01-01

    Objective: To investigate protein concentration changes during venous occlusion of proteins with reported affinity for extracellular matrix (plasminogen activator inhibitor type 1, antithrombin III, fibronectin and von Willebrand factor) in comparison with proteins with no reported affinity

  17. Immune recognition of ADAMTS13 in acquired TTP

    NARCIS (Netherlands)

    Verbij, F.C.

    2017-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a severe thrombotic micro-angiopathy presenting with hemolytic anemia and thrombocytopenia that results from an acquired or congenital functional deficiency of the von Willebrand factor cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with

  18. Glial cell line-derived neurotrophic factor induced the differentiation of amniotic fluid-derived stem cells into vascular endothelial-like cells in vitro.

    Science.gov (United States)

    Zhang, Ruyu; Lu, Ying; Li, Ju; Wang, Jia; Liu, Caixia; Gao, Fang; Sun, Dong

    2016-02-01

    Amniotic fluid-derived stem cells (AFSCs) are a novel source of stem cells that are isolated and cultured from second trimester amniocentesis. Glial cell line-derived neurotrophic factor (GDNF) acts as a tissue morphogen and regulates stem cell proliferation and differentiation. This study investigated the effect of an adenovirus-mediated GDNF gene, which was engineered into AFSCs, on the cells' biological properties and whether GDNF in combination with AFSCs can be directionally differentiated into vascular endothelial-like cells in vitro. AFSCs were isolated and cultured using the plastic adherence method in vitro and identified by the transcription factor Oct-4, which is the primary marker of pluripotent stem cells. AFSCs were efficiently transfected by a GFP-labeled plasmid system of an adenovirus vector carrying the GDNF gene (Ad-GDNF-GFP). Transfected AFSCs stably expressed GDNF. Transfected AFSCs were cultured in endothelial growth medium-2 containing vascular endothelial growth factor. After 1 week, AFSCs were positive for von Willebrand factor (vWF) and CD31, which are markers of endothelial cells, and the recombinant GDNF group was significantly higher than undifferentiated controls and the GFP only group. These results demonstrated that AFSCs differentiated into vascular endothelial-like cells in vitro, and recombinant GDNF promoted differentiation. The differentiation-induced AFSCs may be used as seed cells to provide a new manner of cell and gene therapies for transplantation into the vascular injury site to promote angiogenesis.

  19. Idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in a 17-year-old woman: a case report

    Directory of Open Access Journals (Sweden)

    Patschan Daniel

    2011-12-01

    Full Text Available Abstract Introduction Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome is a life-threatening condition with various etiopathogeneses. Without therapy approximately 90% of all patients die from the disease. Case presentation We report the case of a 17-year-old Caucasian woman with widespread hematomas and headache. Due to hemolytic anemia, thrombocytopenia, and schistocytosis, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected and plasma exchange therapy was initiated immediately. Since her thrombocyte level did not increase during the first week of therapy, plasma treatment had to be intensified to a twice-daily schedule. Further diagnostics showed markedly reduced activities of both ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 - also known as von Willebrand factor-cleaving protease and factor H. Test results for antibodies against both proteins were positive. While plasma exchange therapy was continued, rituximab was given once weekly for four consecutive weeks. After the last dose, thrombocytes and activities of ADAMTS-13 and factor H increased into the normal range. Our patient improved and was discharged from the hospital. Conclusions Since no clinical symptoms/laboratory findings indicated a malignant or specific autoimmune-mediated disorder, the diagnosis made was thrombotic thrombocytopenic purpura-hemolytic uremic syndrome due to idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency.

  20. Dr. von Braun Briefing Walt Disney

    Science.gov (United States)

    1965-01-01

    Dr. von Braun began his association with Walt Disney in the 1950s when the rocket scientist appeared in three Disney television productions related to the exploration of space. Years later, Dr. von Braun invited Disney and his associates to tour the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. This photograph is dated April 13, 1965. From left are R.J. Schwinghamer from the MSFC, Disney, B.J. Bernight, and Dr. von Braun.

  1. Reflexionseigenschaften von Windenergieanlagen im Funkfeld von Funknavigations- und Radarsystemen

    Science.gov (United States)

    Sandmann, S.; Divanbeigi, S.; Garbe, H.

    2015-11-01

    Die hier behandelte Untersuchung befasst sich mit den Störungen des elektrischen Feldes einer Doppler Very High Frequency Omnidirectional Radio Range Navigationsanlage (DVOR) in der Gegenwart von Windenergieanlagen (WEA). Hierfür wird die Feldstärke auf 25 konzentrischen Kreisbahnen, sog. Orbit Flights verschiedener Höhen und mit verschiedenen Radien rund um die DVOR-Anlage numerisch simuliert. Insbesondere werden die Einflüsse diverser Parameter der WEA wie deren Anzahl, Position, Rotorwinkel, Turmhöhe und Rotordurchmesser auf die Feldverteilung herausgestellt, sowie die Anwendbarkeit der Simulationsmethode Physical Optics (PO) durch Vergleich der Simulationsergebnisse mit denen der Multi Level Fast Multipol Method (MLFMM) untersucht.

  2. Amla (Emblica officinalis Gaertn.) extract inhibits lipopolysaccharide-induced procoagulant and pro-inflammatory factors in cultured vascular endothelial cells.

    Science.gov (United States)

    Rao, Theertham Pradyumna; Okamoto, Takayuki; Akita, Nobuyuki; Hayashi, Tatsuya; Kato-Yasuda, Naomi; Suzuki, Koji

    2013-12-01

    Amla (Emblica officinalis Gaertn.) has been used for many centuries in traditional Indian Ayurvedic formulations for the prevention and treatment of many inflammatory diseases. The present study evaluated the anti-inflammatory and anticoagulant properties of amla fruit extract. The amla fruit extract potentially and significantly reduced lipopolysaccharide (LPS)-induced tissue factor expression and von Willebrand factor release in human umbilical vein endothelial cells (HUVEC) in vitro at clinically relevant concentrations (1-100 μg/ml). In a leucocyte adhesion model of inflammation, it also significantly decreased LPS-induced adhesion of human monocytic cells (THP-1) to the HUVEC, as well as reduced the expression of endothelial-leucocyte adhesion molecule-1 (E-selectin) in the target cells. In addition, the in vivo anti-inflammatory effects were evaluated in a LPS-induced endotoxaemia rat model. Oral administration of the amla fruit extract (50 mg/kg body weight) significantly decreased the concentrations of pro-inflammatory cytokines, TNF-α and IL-6 in serum. These results suggest that amla fruit extract may be an effective anticoagulant and anti-inflammatory agent.

  3. Factors Associated with Early Platelet Activation in Obese Children

    Science.gov (United States)

    García, Anel Gómez; Núñez, Guillermina García; Sandoval, Martha Eva Viveros; Castellanos, Sergio Gutierrez; Aguilar, Cleto Alvarez

    2014-01-01

    Objective To investigate the factors associated with platelet activation in obese children. Design Cross-sectional study. Setting Department of Pediatrics of Regional Hospital N∘ 1 of Mexican Institute of Social Security in Morelia, Michoacán, Mexico. Participants 79 obese and 64 non-obese children between the ages of 5 and 10 years. Main Outcomes Measures Obese children (body mass index [BMI] >85 in growth curves for Centers for Disease Control/National Center for Health Statistics), and the control group of 64 non-obese children (percentile <85), % body fat, platelet activation was assessed by sP-selectin. Other measures were leptin, uric acid (UA), von Willebrand Factor (vWF), plasminogen activator inhibitor (PAI-1), lipid profile, and glucose. Results Obese children displayed higher plasma sP-selectin, leptin, PAI-1, and vWF than non-obese children. In the univariate logistic regression analysis, leptin, vWF, UA, and high density lipoprotein (HDL), but not with PAI-1, were factors associated with platelet activation. By stepwise linear regression analysis adjusted by sex and age, the best predictor variables for platelet activation were leptin (β:0.381; t:4.665; P=0.0001), vWF (β:0.211; t:2.926; P=0.004), UA (β:0.166; t:2.146; P=0.034), and HDL (β:−0.215; t:−2.819; P=0.006). Conclusions Obese children have a higher risk of developing early platelet activation. Factors associated with platelet activation were Leptin, vWF, UA, and HDL. Further studies involving larger numbers of patients over a longer duration are needed to understand the possible molecular mechanism underlying the association between leptin, vWF, and UA and endothelial activation and/or endothelial damage/dysfunction in obese children and its influence in cardiovascular disease in adults. PMID:24415745

  4. Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release

    Directory of Open Access Journals (Sweden)

    Marco eGoeijenbier

    2015-03-01

    Full Text Available Puumala virus (PUUV infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The mechanism by which this hantavirus influences the coagulation system remains unknown. Therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during PUUV infection. By using low passage PUUV isolates to infect primary human umbilical vein endothelial cells (HUVECs we were able to show alterations in the regulation of primary- and secondary hemostasis and in the release of fibrinolysis regulators. Our main finding was an activation of secondary hemostasis due to increased tissue factor expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVECs and subsequently specifically to PUUV virus particles. Infection of HUVECs with PUUV did not result in increased von Willebrand factor while they produced more plasminogen activator inhibitor type-1 (PAI-1 compared to controls. The PAI-1 produced in this model formed complexes with vitronectin. This is the first report that reveals a potential mechanism behind the pro-coagulant changes in PUUV patients, which could be the result of increased thrombin generation due to an increased tissue factor expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis.

  5. Pigment epithelium derived factor inhibits the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro.

    Directory of Open Access Journals (Sweden)

    Yanmei Sun

    Full Text Available Angiogenesis is a prerequisite for the formation and development of endometriosis. Pigment epithelium derived factor (PEDF is a natural inhibitor of angiogenesis. We previously demonstrated a reduction of PEDF in the peritoneal fluid, serum and endometriotic lesions from women with endometriosis compared with women without endometriosis. Here, we aim to investigate the inhibitory effect of PEDF on human endometriotic cells in vivo and in vitro. We found that PEDF markedly inhibited the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro by up-regulating PEDF expression and down-regulating vascular endothelial growth factor (VEGF expression. Moreover, apoptotic index was significantly increased in endometriotic lesions in vivo and endometriotic stromal cells in vitro when treated with PEDF. In mice treated with PEDF, decreased microvessel density labeled by Von Willebrand factor but not by α-Smooth Muscle Actin was observed in endometriotic lesions. And it showed no increase in PEDF expression of the ovary and uterus tissues. These findings suggest that PEDF gene therapy may be a new treatment for endometriosis.

  6. Planung von CLIL-Unterricht

    Directory of Open Access Journals (Sweden)

    Josef Leisen

    2015-10-01

    Full Text Available Der Beitrag formuliert die Sprachlernbedingungen und die Leitlinien des Sprachlernens im Fach und nennt Merkmale des guten integrierten Fach- und Sprachlehrens. Ausgehend von den Sprachproblemen, die sich im CLIL-Unterricht auftun, wird der sprachsensible CLIL-Unterricht definiert, und es werden Anregungen zur Gestaltung gegeben. Sprachliche Standardsituationen umfassen die kommunikativen Situationen im CLIL-Unterricht, die beim fachlichen Lernen auftreten und von der CLIL-Lehrkraft professionell bewältigt werden müssen. Im Beitrag wird ein Lehr-Lern-Modell ausführlich beschrieben und erläutert. Die Steuerungen von Sprachlernprozessen im CLIL durch Aufgabenstellungen, Methoden-Werkzeuge, Moderation und Diagnose/Rückmeldung werden ausführlich beschrieben. Die Planung einer Lernlinie in sechs Schritten wird dargestellt und erläutert. Planungsraster für CLIL-Lernlinien schließen den Beitrag ab. The article sets out the conditions for language learning in general as well as guiding principles of language learning in the subject and puts forward criteria for successfully integrated content and language learning. Based on typical language problems arising in CLIL-classrooms, the language-sensitive CLIL-classroom is defined and organisational suggestions are given. Linguistic standard situations comprise the communicative situations in the CLIL-classroom which are encountered in subject-related learning and have to be professionally mastered by the CLIL-teacher. The article extensively describes and explains a model of teaching and learning that can be used for the CLIL-classroom. It gives detailed information on managing language learning processes in CLIL by means of tasks, resources and methods as well as discourse facilitation, evaluation and feedback. In addition, a six-step lesson unit is outlined and explained. The article concludes by giving a planning matrix for CLIL lesson units.

  7. Walt Disney and Dr. Wernher von Braun

    Science.gov (United States)

    1954-01-01

    Dr. Werhner von Braun, then Chief, Guided Missile Development Operation Division at Army Ballistic Missile Agency (ABMA) in Redstone Arsenal, Alabama, was visited by Walt Disney in 1954. In the 1950's, von Braun worked with Disney Studio as a technical director, making three films about space exploration for television. A model of the V-2 rocket is in background.

  8. Von Neumann Was Not a Quantum Bayesian

    CERN Document Server

    Stacey, Blake C

    2014-01-01

    Wikipedia has claimed for over two years now that John von Neumann was the "first quantum Bayesian." In context, this reads as stating that von Neumann inaugurated QBism, the approach to quantum theory promoted by Fuchs, Mermin and Schack. This essay explores how such a claim is, historically speaking, unsupported.

  9. Kultuuriakadeemias saab kaeda Von Krahli ime tabamist

    Index Scriptorium Estoniae

    2006-01-01

    Marianne Kõrver, Jaak Kilmi, Andres Maimik, Marko Raat, Rainer Sarnet ja Arbo Tammiksaar tegid Eduard Vilde näidendist "Tabamata ime" kuus lühimängufilmi Von Krahli teatris ettekandmiseks. 25. mail tuleb Von Krahli Teater Viljandisse ja näitab teatrifilmi Kultuuriakadeemias

  10. Mixing subalgebras of finite von Neumann algebras

    CERN Document Server

    Cameron, Jan; Mukherjee, Kunal

    2010-01-01

    Jolissaint and Stalder introduced the definitions of mixing and weak mixing for von Neumann subalgebras of finite von Neumann algebras. In this paper, we study various algebraic and analytical properties of mixing and weakly mixing von Neumann subalgebras. We prove some basic results about mixing inclusions of von Neumann algebras and establish a connection between mixing properties and normalizers of von Neumann subalgebras. The special case of mixing subalgebras arising from inclusions of group von Neumann algebras finds applications to ergodic theory. For a finite von Neumann algebra $M$ and von Neumann subalgebras $A$, $B$ of $M$, we introduce a notion of weak mixing of $B\\subseteq M$ relative to $A$. If $B$ is abelian and $A\\subset B$, we show that weak mixing of $B \\subset M$ relative to $A$ is equivalent to the following property: if $x\\in M$ and $xAx^*\\subset B$ then $x\\in B$. In the general case, we show that weak mixing of $B\\subset M$ relative to $A$ is equivalent to the following property: if $x\\i...

  11. Ludwig von Mises: An Annotated Bibliography.

    Science.gov (United States)

    Gordon, David

    A 117-item annotated bibliography of books, articles, essays, lectures, and reviews by economist Ludwig von Mises is presented. The bibliography is arranged chronologicaly, and is followed by an alphabetical listing of the citations, excluding books. An index and information on the Ludwig von Mises Institute at Auburn University (Alabama) are…

  12. AGREGACIÓN PLAQUETARIA EN GESTANTE: IMAGEN EN CELLAVISION DM8

    Directory of Open Access Journals (Sweden)

    Cuevas-Ruiz B

    2012-09-01

    Full Text Available Von Willebrand Disease (VWD groups different varieties depending on the qualitative or quantitative alteration of von Willebrand Factor. The diagnosis is based on a medical history of bleeding symptoms and a consistent analytical study. 2B subtype may occur with platelet aggregation in certain situations as DDAVP infusion, with exercise or surgery and pregnancy. We report a patient with platelet aggregation in pregnancy and type 2B VWD.

  13. Evaluation of the reliability concerning the identification of human factors as contributing factors by a computer supported event analysis (CEA); Einfluss des Menschen auf die Sicherheit von Kernkraftwerken - Bewertung der Zuverlaessigkeit einer computergestuetzten Ereignisanalyse (CEA) in der Kernindustrie

    Energy Technology Data Exchange (ETDEWEB)

    Wilpert, B.; Maimer, H.; Loroff, C.

    2000-05-01

    The project's objectives are the evaluation of the reliability concerning the identification of Human Factors as contributing factors by a computer supported event analysis (CEA). CEA is a computer version of SOL (Safety through Organizational Learning). Parts of the first step were interviews with experts from the nuclear power industry and the evaluation of existing computer supported event analysis methods. This information was combined to a requirement profile for the CEA software. The next step contained the implementation of the software in an iterative process of evaluation. The completion of this project was the testing of the CEA software. As a result the testing demonstrated that it is possible to identify contributing factors with CEA validly. In addition, CEA received a very positive feedback from the experts. (orig.) [German] Ziel des Vorhabens ist die Entwicklung und Bewertung der Zuverlaessigkeit einer computergestuetzten Ereignisanalyse (CEA) in der Kernindustrie. CEA stellt eine Umsetzung des Ursachenanalyseverfahrens SOL (Sicherheit durch Organisationales Lernen) in eine Computerversion dar. In diesem Zusammenhang wurde ein an der Praxis orientiertes Anforderungsprofil an die Software erstellt. Grundlage bildeten hierfuer Interviews mit Experten aus der Kerntechnik und die Betrachtung bereits vorhandener computergestuetzter Verfahren. In einem iterativen Verbesserungsprozess wurde die Software erstellt. Den Abschluss bildete die Erprobung der Software. Es liess sich feststellen, dass mit CEA valide kontribuierende Faktoren identifiziert werden. Auch das Feedback der Experten zu CEA war ausnahmslos positiv. (orig.)

  14. Searching for preventive measures of cardiovascular events in aged Japanese taxi drivers--the daily rhythm of cardiovascular risk factors during a night duty day.

    Science.gov (United States)

    Hattori, M; Azami, Y

    2001-12-01

    Previous studies have shown that Japanese taxi drivers are exposed to more risk factors and have a higher mortality rate due to cardiovascular disease than other occupational groups. We investigated the effect of night taxi driving with a view to preventing acute events of cardiovascular disease among aged taxi drivers. Twenty-nine taxi drivers (41-67 years old) were examined for urine normetanephrine/creatinine, von Willebrand factor, anti-thrombin III, t-plasminogen activator-plasminogen activator inhibitor 1-complex, hematocrit, blood glucose and blood pressure in the morning and at midnight during a duty day and in the following morning. At the same time, the blood pressure and blood glucose of 46 taxi drivers (43-67 years old) in the morning after a night duty with little sleep and in the morning after daytime work and subsequent night sleep were compared. The results obtained indicate that the aggravation of sympathetic nervous system functions with disturbed circadian rhythms, increased blood coagulation and blood concentration, endothelial injury and the elevation of blood glucose at midnight or the next morning were induced by their night work. These conditions are supposed to favour acute vascular events in aged taxi drivers. Preventive measures considered include social support for anticoagulant food and water intake, short exercise and walking as well as taking a rest and a nap during night work.

  15. Regulation of archaella expression by the FHA and von Willebrand domain-containing proteins ArnA and ArnB in Sulfolobus acidocaldarius.

    Science.gov (United States)

    Reimann, Julia; Lassak, Kerstin; Khadouma, Sunia; Ettema, Thijs J G; Yang, Nuan; Driessen, Arnold J M; Klingl, Andreas; Albers, Sonja-Verena

    2012-10-01

    The ability of microorganisms to sense and respond to sudden changes in their environment is often based on regulatory systems comprising reversible protein phosphorylation. The archaellum (former: archaeal flagellum) is used for motility in Archaea and therefore functionally analogous to the bacterial flagellum. In contrast with archaellum-mediated movement in certain members of the Euryarchaeota, this process, including its regulation, remains poorly studied in crenarchaeal organisms like Sulfolobus species. Recently, it was shown in Sulfolobus acidocaldarius that tryptone limiting conditions led to the induction of archaella expression and assembly. Here we have identified two proteins, the FHA domain-containing protein ArnA and the vWA domain-containing protein ArnB that are involved in regulating archaella expression in S. acidocaldarius. Both proteins are phosphorylated by protein kinases in vitro and interact strongly in vivo. Phenotypic analyses revealed that these two proteins are repressors of archaella expression. These results represent the first step in understanding the networks that underlie regulation of cellular motility in Crenarchaeota and emphasize the importance of protein phosphorylation in the regulation of cellular processes in the Archaea.

  16. Regulation of archaella expression by the FHA and von Willebrand domain-containing proteins ArnA and ArnB in Sulfolobus acidocaldarius

    NARCIS (Netherlands)

    Reimann, Julia; Lassak, Kerstin; Khadouma, Sunia; Ettema, Thijs J. G.; Yang, Nuan; Driessen, Arnold J. M.; Klingl, Andreas; Albers, Sonja-Verena

    2012-01-01

    The ability of microorganisms to sense and respond to sudden changes in their environment is often based on regulatory systems comprising reversible protein phosphorylation. The archaellum (former: archaeal flagellum) is used for motility in Archaea and therefore functionally analogous to the bacter

  17. Eyelid retraction, lid lag, lagophthalmos, and von Graefe's sign quantifying the eyelid features of Graves' ophthalmopathy.

    Science.gov (United States)

    Gaddipati, Ramakrishna V; Meyer, Dale R

    2008-06-01

    To report the frequency and relationship of eyelid retraction, lid lag, lagophthalmos, and von Graefe's sign in a group of patients with Graves' ophthalmopathy and compare these findings to those in a group of normal individuals. Retrospective comparative cohort study. Fifty consecutive Graves' ophthalmopathy patients were compared to a control group of 50 normal individuals. Measurements were made of eyelid position in primary gaze and downgaze to assess eyelid retraction and lid lag, and the presence of lagophthalmos and von Graefe's sign was noted when present. Eyelid position in primary gaze and downgaze and presence of lagophthalmos and von Graefe's sign. In the Graves' group, eyelid retraction (38%), von Graefe's sign (36%) and lagophthalmos (16%) were observed at a significantly greater frequency (P<0.01) than in normals, whereas true eyelid lag was observed in only 8% (P = 0.67). The terms lid lag and von Graefe's sign have been used interchangeably in the past; however, they are distinct signs of downgaze-related upper eyelid static position and dynamic movement, respectively. Although von Graefe's sign was commonly exibited in Graves' patients, the relatively low frequency of lid lag suggests that factors other than restriction/fibrosis are likely responsible for the etiology of eyelid retraction in many cases.

  18. Is there an effect of folic acid supplementation on the coagulation factors and C-reactive protein concentrations in subjects with atherosclerosis risk factors

    Directory of Open Access Journals (Sweden)

    Artur Mierzecki

    2012-10-01

    Full Text Available Introduction:Folic acid (FA may delay the formation of atherosclerotic lesions. Increased plasma levels of von Willebrand factor (VWF are observed in cardiovascular disease, which leads to higher risk of thrombosis. Fibrinogen (Fb is a well-documented risk factor of cardiovascular disease. The aim of this study was to analyze the effect of FA supplementation on the Fb, VWF and C-reactive protein (CRP plasma concentrations in subjects with atherosclerosis risk factors.Material/Methods:The study enrolled 124 Caucasian individuals (60 M, 64 F with atherosclerosis risk factors – family history of premature ischaemic stroke, arterial hypertension, dyslipidaemia, overweight and obesity, cigarette smoking and low physical activity. The participants were asked to take FA in the low dose of 0.4 mg/24 h for three months.Results:After FA supplementation a significant reduction of the VWF concentrations in females (76.6 vs 72.3�20p=0.028 and in males (75.5 vs 66.9�20p=0.001 was observed. Among women and men with dyslipidaemia concentrations of VWF decreased after FA supplementation (76.8�0vs 69.6�20p=0.003 and 76.7�0vs 67.8�20p=0.001 respectively. Among females and males with BMI ≥25 kg/m2 concentrations of VWF decreased only in men (77.6�0vs 66.5�20p=0.001. In female and male smokers supplementation of FA decreased VWF concentrations (82.5�0vs 74.4�20p=0.012 and 76.6�0vs 69.5�20p=0.036 respectively.Discussion:The results of our study suggest that there is an effect of FA supplementation on VWF concentrations in subjects with atherosclerosis risk factors

  19. Jacob Stael von Holstein ja palladionism eesti arhitektuuris / Ants Hein

    Index Scriptorium Estoniae

    Hein, Ants, 1952-

    2005-01-01

    Sõjaväeinsenerist ja arhitektist Jacob Stael von Holsteinist (1628, Pärnu-1679), tema kavandatud hoonetest ja rollist 17. sajandi II poole arhitektuuris. Fabian von Ferseni Toompeal Lossiplatsil asunud elamust (lammutati 1894) ja Maardu mõisahoonest, Hans von Ferseni Mäo mõisahoonest Järvamaal, Otto Wilhelm von Ferseni majast Toompeal, Axel von Roseni majast Tallinnas Pikk t. 28 (1670-74), Otto Reinhold von Taube majast Tartus (hävinud), J. S. von Holsteini enda hoonetest: majast Tallinnas Toompea 1, Anija mõisahoonest, elamust Riias jm. Bibliograafia lk. 452

  20. Jacob Stael von Holstein ja palladionism eesti arhitektuuris / Ants Hein

    Index Scriptorium Estoniae

    Hein, Ants, 1952-

    2005-01-01

    Sõjaväeinsenerist ja arhitektist Jacob Stael von Holsteinist (1628, Pärnu-1679), tema kavandatud hoonetest ja rollist 17. sajandi II poole arhitektuuris. Fabian von Ferseni Toompeal Lossiplatsil asunud elamust (lammutati 1894) ja Maardu mõisahoonest, Hans von Ferseni Mäo mõisahoonest Järvamaal, Otto Wilhelm von Ferseni majast Toompeal, Axel von Roseni majast Tallinnas Pikk t. 28 (1670-74), Otto Reinhold von Taube majast Tartus (hävinud), J. S. von Holsteini enda hoonetest: majast Tallinnas Toompea 1, Anija mõisahoonest, elamust Riias jm. Bibliograafia lk. 452

  1. [Von Hippel-Lindau syndrome].

    Science.gov (United States)

    Reich, H; Hollwich, F

    1984-06-01

    The von Hippel-Lindau syndrome is an autosomal dominant condition that comprises, apart from angiomas of the retina, the cerebellum, the spinal cord, and the cerebrum, also cystic and blastomatous dysplasias resulting from maldevelopment, namely cystic kidney and pancreas, hypernephroma, and pheochromocytoma. Early observers of the syndrome were the English neurologist John Hughlings Jackson (1872) and the German ophthalmologist Hugo Magnus (1874). The typical association of angiomas of the retina with the cerebellum was first described in 1905 by the Prague ophthalmologist Wilhelm Czermak, long before Lindau (1926). The fact that hypernephromas and pheochromocytomas may form parts of it characterizes the syndrome as a polyneoplastic hereditary disease and the sufferers as members of families at risk. Since the ophthalmologist is often the first to recognize this disease by direct inspection of the fundi, he is responsible for ensuring proper medical care for the affected person and his or her entire family.

  2. The Digital Von Fahrenheid Pyramid

    Science.gov (United States)

    Bura, M.; Janowski, J.; Wężyk, P.; Zięba, K.

    2017-08-01

    3D Scanners Lab from Digital Humanities Laboratory at the University of Warsaw initiated the scientific project, the purpose of which was to call attention to systematically penetrated and devastated pyramid-shaped tomb from the XVIII/XIX century, of family von Fahrenheid in Rapa in Banie Mazurskie commune (NE Poland). By conducting a series of non-invasive studies, such as 3D inventory using terrestrial laser scanning (TLS), thermal imaging, georadar measurements (around and inside the tomb) and anthropological research of mummified remains as well - the complete dataset was collected. Through the integration of terrestrial (TLS) and airborne laser scanning (ALS) authors managed to analyse the surroundings of Fahrenheid pyriamid and influence of some objects (like trees) on the condition and visibility of the Pyramids in the landscape.

  3. Neues über das Tertiär von Java und die mesozoischen Schichten von West-Borneo

    NARCIS (Netherlands)

    Martin, K.

    1888-01-01

    Die Monographie, welche unter dem Titel Die Fossilien von Java herausgegeben wird ¹), ist so weit fortgeschritten, dass sich aus den in ihr beschriebenen Gastropoden bereits eine Anzahl von Schlussfolgerungen ableiten lässt, welche für die in Bearbeitung begriffene, geologische Karte von Java von

  4. Neues über das Tertiär von Java und die mesozoischen Schichten von West-Borneo

    NARCIS (Netherlands)

    Martin, K.

    1888-01-01

    Die Monographie, welche unter dem Titel Die Fossilien von Java herausgegeben wird ¹), ist so weit fortgeschritten, dass sich aus den in ihr beschriebenen Gastropoden bereits eine Anzahl von Schlussfolgerungen ableiten lässt, welche für die in Bearbeitung begriffene, geologische Karte von Java von Be

  5. Einfluss der Koordination von Spurenelementen in Silikatschmelzen auf Verteilungsprozesse

    OpenAIRE

    Sebastian Simon

    2016-01-01

    Das Wissen um die lokale Struktur von Seltenen Erden Elementen (SEE) in silikatischen und aluminosilikatischen Schmelzen ist von fundamentalem Interesse für die Geochemie der magmatischen Prozesse, speziell wenn es um ein umfassendes Verständnis der Verteilungsprozesse von SEE in magmatischen Systemen geht. Es ist allgemein akzeptiert, dass die SEE-Verteilungsprozesse von Temperatur, Druck, Sauerstofffugazität (im Fall von polyvalenten Kationen) und der Kristallchemie kontrolliert werden. All...

  6. Charakterisierung von Radiolyseprodukten in gammabestrahlten Polyamiden Thermodesorption-Gaschromatographie Massenspekroskopie

    OpenAIRE

    Selmi, Hany

    2008-01-01

    Der Verbrauch von Polyamiden in allen technischen Bereichen, darunter im Bereich der Verpackung von Lebensmitteln sowie im Bereich der Herstellung von medizinischen Artikeln und Geräten steigt stetig an. Dies beruht auf ihren Eigenschaften wie hohe Festigkeit, ausgezeichnete Thermoformbarkeit, hohe Wärmeformbeständigkeit, Sterilisierbarkeit und sehr gute Barriereeigenschaften gegen Gase, insbesondere gegenüber Sauerstoff und Aromen. Die Anwendung von Gammastrahlen zur Sterilisation von Verpac...

  7. Von Laue's theorem and its applications

    CERN Document Server

    Wang, Changbiao

    2012-01-01

    Von Laue's theorem is strictly proved in detail to clarify confusions in textbook and literature. This theorem is used to analyze the classical electron and the static electric field confined in a finite region of space.

  8. Arbeit von Frauen in Zeiten der Globalisierung

    NARCIS (Netherlands)

    D. Grunow

    2010-01-01

    Hohe Erwerbsquote, Dienstleistungsberufe und Minijobs: Die weibliche Erwerbstätigkeit hat sich in den letzten Jahrzehnten in Deutschland stark verändert. Wie hängen die Prozesse zusammen mit der Globalisierung von Wirtschaft und Arbeit?

  9. Titanisierung von Implantatoberflächen

    Science.gov (United States)

    Zimmermann, Hanngörg; Heinlein, Markus; Guldner, Norbert W.

    Titan gilt seit Jahrzehnten als einer der wichtigsten Implantatwerkstoffe in der Medizin. Neben den guten mechanischen Eigenschaften (Leichtigkeit, hohe Festigkeit etc.), besitzen Titanimplantate vor allem eine hervorragende Körperverträglichkeit, so dass die Implantate optimal in den humanen Organismus integriert werden [1]. Ist jedoch aufgrund der Anforderungen an das Implantat eine hohe Flexibilität und/ oder Elastizität gefragt, so scheidet der Werkstoff Titan aufgrund seiner spröden und unflexiblen Materialeigenschaften aus. Die Folge ist der Einsatz von Implantatmaterialien, sowohl künstlichen als auch biologischen Ursprungs, welche nicht selten eine unzureichende Biokompatibilität aufweisen und somit zu Fremdköper- und immunologischen Reaktionen und Einkapselung des Implantates führen können. Die Erhöhung der Körperverträglichkeit, eine Adaption an das biologische Umfeld und eine hohe Biokompatibilität sind demzufolge die wichtigsten Eigenschaften bei der bedarfsgerechten Herstellung von Implantaten und Implantatoberflächen. Zur Gestaltung von innovativen, biokompatiblen Oberflächen stehen unterschiedliche technische Lösungsansätze zur Verfügung. Zum einen besteht die Möglichkeit, geeignete Oberflächeneigenschaften aus dem Grundmaterial selbst zu optimieren. Dies geschieht unter anderem durch Modifikation der Werkstoffoberflächen in Form von Texturierungen und Oberflächenrauhigkeiten. Zum anderen können die Oberflächeneigenschaften unabhängig von denen des Trägermaterials gestaltet werden. Durch Funktionalisierung der Oberflächen mit geeigneten Beschichtungen oder der Zugabe von Medikamenten (Drug Eluting) werden die Kunststoffimplantate dahingehend verändert, dass eine Steigerung der Körperakzeptanz erreicht wird. Die Titanbeschichtung von Implantatoberflächen kombiniert die positiven Materialeigenschaften von Titan und Polymer.

  10. Beschichtung von Kohlenstofffasern durch Chemische Gasphasenabscheidung (CVD)

    OpenAIRE

    Schmidt, Stephan

    2005-01-01

    Der Einsatz faserverstärkter Verbundwerkstoffe mit metallischer und keramischer Matrix bietet den Vorteil von Kombination und optimaler Ausnutzung verschiedenster Werkstoffeigenschaften. Die Verwendung einer durch Kohlenstofffasern verstärkten keramischen Matrix erlangte dabei in der kürzeren Vergangenheit vermehrtes Interesse. Grundlegend für den erfolgreichen Einsatz von Faserverbundwerkstoffen ist dabei ein optimiertes Faser-Matrix-Interface, also eine "optimale" Haftung der Fasern innerha...

  11. Studien zur didaktischen Nutzung von Concept Maps

    OpenAIRE

    Jüngst, Karl Ludwig

    1995-01-01

    In einer ersten Studie wurde geprüft, ob elaborierendes Durcharbeiten von Concept Maps lerneffektiver ist als elaborierendes Durcharbeiten von analogen Texten. Es wurden 13 Exemplare in unterschiedlichen Schulfächern im Sekundarschulwesen durchgeführt. Die Versuchs- Klassen arbeiten Concept Maps zu einem bestimmten Begriff durch, die Kontrollklassen analoge Texte. Die Behaltensleistung auf einfacherem Anforderungsniveau war in den Klassen mit Concept Maps besser als in den Klassen mit Texten....

  12. Hullud päevad von Krahlis

    Index Scriptorium Estoniae

    2006-01-01

    Von Krahli Teatris mängitakse neil päevi neli korda Peeter Jalaka lavastuses Tõnu Kõrvitsa kammeroopereid "Tuliaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libreto autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  13. 50th birthday of Christian von Ferber

    Directory of Open Access Journals (Sweden)

    2011-06-01

    Full Text Available On May 15, 2011 Christian von Ferber - member of the Editorial Board of "Condensed Matter Physics" and renowned expert in the fields of soft matter physics and complex systems - celebrated his 50th birthday. The Editorial board of CMP, colleagues and friends warmy congratulate Christian von Ferber and wish him and his family continuing good health and to enjoy many adventures and discoveries in his future scientific travels!

  14. Charakterisierung von Wechselwirkungsprozessen in sensitiven Schichten

    OpenAIRE

    Rathgeb, Frank

    1999-01-01

    Die vorliegende Arbeit soll verschiedene Strategien aufzeigen, um eine selektive Anreicherung gasförmiger Analytmoleküle in sensitiven Schichten zu erzielen. Im Mittelpunkt des Interesses lagen hierbei pH-responsive Polymere, mikroporöse Schichten und Cyclohexapeptide. Mit den pH-responsiven Polymeren konnte eine selektive und sensitive Detektion von Ammoniak mit Nachweisgrenzen von 150 ppb erreicht werden. Die Stabilität der sensitiven Schicht konnte im Vergleich zu farbstoffdotie...

  15. Hullud päevad von Krahlis

    Index Scriptorium Estoniae

    2006-01-01

    Von Krahli Teatris mängitakse neil päevi neli korda Peeter Jalaka lavastuses Tõnu Kõrvitsa kammeroopereid "Tuliaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libreto autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  16. Kadison-Kastler stable factors

    DEFF Research Database (Denmark)

    Cameron, Jan; Christensen, Erik; Sinclair, Allan M.;

    2014-01-01

    It is proven that a pair of continuous finite von Neumann algebra factors are unitarily equivalent if sufficiently close and one satisfies a certain cohomological condition.......It is proven that a pair of continuous finite von Neumann algebra factors are unitarily equivalent if sufficiently close and one satisfies a certain cohomological condition....

  17. Relevance of hemostatic risk factors on coronary morphology in patients with diabetes mellitus type 2

    Directory of Open Access Journals (Sweden)

    Peters Ansgar J

    2009-05-01

    Full Text Available Abstract Objective The influence hemostatitc parameters on the morphological extent and severity of coronary artery disease were studied in patients with and without DM type 2. Background It is known that patients with diabetes (DM have abnormal metabolic and hemostatic parameters Methods Of 150 consecutive patients with angiographically proven coronary artery disease 29 presented with DM. Additionally to parameters of lipid-metabolism fibrinogen, tissue-plasminogenactivator (t-PA, plasminogen-activator-inhibitor (PAI, plasmin-a-antiplasmin (PAP, prothrombin-fragment 1+2 (F1+2, thrombin-antithrombin (TAT, von-willebrand-factor (vWF, platelet factor 4 (PF4, glykomembranproteine 140 (GMP140 and the rheologic parameters plasma viscosity and red blood cell aggregation were evaluated. The extent and severity of CAD was evaluated according to the criteria of the American Heart Association. Results Patients with DM presented with a higher number of conventional risk factors as compared to non-diabetic patients. Additionally there were significant differences for F1+2, red blood cell aggregation and PAI. Diabetic patients showed a more severe extent of coronary arteriosclerosis, which also could be found more distally. A significant relationship between blood-glucose, thrombocyte-activation (vWF, endogenous fibrinolysis (PAI and the severity of CAD and a more distal location of stenoses could be found (r = 0.6, p Conclusion Patients with coronary artery disease and DM type 2 showed marked alterations of metabolic, hemostatic, fibrinolytic and rheologic parameters, which can produce a prothrombogenic state. A direct association of thrombogenic factors on coronary morphology could be shown. This can be the pathophysiologic mechanism of more severe and distal pronounced coronary atherosclerosis in these patients.

  18. ADAMTS13 activity as a novel risk factor for incident type 2 diabetes mellitus: a population-based cohort study.

    Science.gov (United States)

    de Vries, Paul S; van Herpt, Thijs T W; Ligthart, Symen; Hofman, Albert; Ikram, M Arfan; van Hoek, Mandy; Sijbrands, Eric J G; Franco, Oscar H; de Maat, Moniek P M; Leebeek, Frank W G; Dehghan, Abbas

    2017-02-01

    ADAMTS13 is a protease that breaks down von Willebrand factor (VWF) multimers into smaller, less active particles. VWF has been associated with an increased risk of incident type 2 diabetes mellitus. Here, we determine whether ADAMTS13 activity and VWF antigen are associated with incident diabetes. This study included 5176 participants from the Rotterdam Study, a prospective population-based cohort study. Participants were free of diabetes at baseline and followed up for more than 20 years. Cox proportional hazards models were used to examine the association of ADAMTS13 activity and VWF antigen with incident diabetes. ADAMTS13 activity was associated with an increased risk of incident diabetes (HR 1.17 [95% CI 1.08, 1.27]) after adjustment for known risk factors and VWF antigen levels. Although ADAMTS13 activity was positively associated with fasting glucose and insulin, the association with incident diabetes did not change when we adjusted for these covariates. ADAMTS13 activity was also associated with incident prediabetes (defined on the basis of both fasting and non-fasting blood glucose) after adjustment for known risk factors (HR 1.11 [95% CI 1.03, 1.19]), while the VWF antigen level was not. VWF antigen was associated with incident diabetes, but this association was attenuated after adjustment for known risk factors. ADAMTS13 activity appears to be an independent risk factor for incident prediabetes and type 2 diabetes. As the association between ADAMTS13 and diabetes did not appear to be explained by its cleavage of VWF, ADAMTS13 may have an independent role in the development of diabetes.

  19. An MRI Von Economo - Koskinas atlas.

    Science.gov (United States)

    Scholtens, Lianne H; de Reus, Marcel A; de Lange, Siemon C; Schmidt, Ruben; van den Heuvel, Martijn P

    2016-12-28

    The cerebral cortex displays substantial variation in cellular architecture, a regional patterning that has been of great interest to anatomists for centuries. In 1925, Constantin von Economo and George Koskinas published a detailed atlas of the human cerebral cortex, describing a cytoarchitectonic division of the cortical mantle into over 40 distinct areas. Von Economo and Koskinas accompanied their seminal work with large photomicrographic plates of their histological slides, together with tables containing for each described region detailed morphological layer-specific information on neuronal count, neuron size and thickness of the cortical mantle. Here, we aimed to make this legacy data accessible and relatable to in vivo neuroimaging data by constructing a digital Von Economo - Koskinas atlas compatible with the widely used FreeSurfer software suite. In this technical note we describe the procedures used for manual segmentation of the Von Economo - Koskinas atlas onto individual T1 scans and the subsequent construction of the digital atlas. We provide the files needed to run the atlas on new FreeSurfer data, together with some simple code of how to apply the atlas to T1 scans within the FreeSurfer software suite. The digital Von Economo - Koskinas atlas is easily applicable to modern day anatomical MRI data and is made publicly available online.

  20. Positive Effekte von NSAR auf den Gastrointestinaltrakt

    Directory of Open Access Journals (Sweden)

    Lang M

    2015-01-01

    Full Text Available Ein protektiver Effekt von nichtsteroidalen Antirheumatika (NSAR auf die Tumorentstehung im Kolon wird in diversen präklinischen, epidemiologischen und auch randomisierten Arbeiten postuliert. Der Hauptwirkungsmechanismus von NSAR wird der Hemmung der Prostaglandinsynthese über die Cyclooxygenasen (COX zugeschrieben. Es existieren aber auch COX-unabhängige Mechanismen. Hier wollen wir einen Überblick über die Studienlage mit Aspirin, Sulindac und COX-2-Hemmern im Hinblick auf die Entstehung von Adenomen und Kolorektalkarzinomen geben. Die Wirkung dieser Substanzen ist besonders für Patienten mit familiärer Disposition relevant, aber auch für Patienten, die NSAR oder Aspirin aufgrund anderer Indikationen einnehmen. Es bestehen Abhängigkeiten von Dosis und Zeit sowie Interaktionen mit speziellen Mutationen (BRAF, PI3K und der zellulären COX-2-Expression. Beim Lynch-Syndrom ist die Wirksamkeit von Aspirin letztlich nicht sicher und eine multinationale klinische Studie mit 5-Aminosalizylsäure (Mesalazin wurde vom europäischen TRANSCAN-Programm gefördert.

  1. Hypothyroidism in coronary heart disease and its relation to selected risk factors

    Directory of Open Access Journals (Sweden)

    Otto Mayer Jr

    2006-12-01

    Full Text Available Otto Mayer Jr1, Jaroslav Šimon1, Jan Filipovský1, Markéta Plášková2, Richard Pikner11Center of Preventive Cardiology, 2nd Department of Internal Medicine, Charles University, Medical Faculty, Plze , Czech Republic; 2Department of Preventive Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech RepublicIntroduction: Hypothyroidism (HT has been found a predictor of cardiovascular diseases. We aimed to ascertain the prevalence of HT in patients with manifest coronary heart disease (CHD, and to establish its association with conventional risk factors.Methods: 410 patients, 6–24 months after hospitalization for acute coronary syndrome, and/or revascularization, were included into the cross-sectional study.Results: The prevalence of thyroid dysfunction was found in males and females as follows: overt HT, ie, thyroid stimulating hormone (TSH > 3.65 mIU/L and free thyroxine (fT4 < 9 pmol/L and/or L-thyroxine substitution, in 2.6% and 8.4%, respectively; subclinical HT (TSH >3.65, fT4 9–23 and no substitution in 4.3% and 15.0%, respectively. Higher prevalence of HT was found in females with hypercholesterolemia, and in males and females with concomitant positive thyroid peroxydase antibodies. Hypothyroid subjects had higher total homocysteine in both genders and von Willebrand factor in males only. Hypothyroid females had higher total  and LDL cholesterol, and were more often treated for diabetes.Conclusions: HT was found highly prevalent in patient with clinical coronary heart disease, mainly in females, and was associated with several cardiovascular risk factors.Keywords: hypothyroidism, coronary heart disease, cholesterol, homocysteine, diabetes

  2. The Effect of Carbon Dioxide Insufflation Applied at Different Pressures and Periods on Thrombotic Factors.

    Science.gov (United States)

    Sen, Mehmet Celal; Turkyilmaz, Zafer; Sonmez, Kaan; Karabulut, Ramazan; Kaya, Zuhre; Yenicesu, Idil; Gursel, Turkiz; Basaklar, Abdullah Can

    2016-03-01

    The aim of this experimantal study which is applied on rats, is to determine the differences on the clotting factors over the application of low and high intraabdominal pressure (IAP) values in different periods of time in carbon dioxide (CO2) pneumoperitoneum. Thirty rats were randomized into five groups (n = 6): a control group (Group K) and 1 h and 6 mm Hg IAP (Group A), 2 h and 6 mm Hg IAP (Group B), 1 h and 12 mm Hg IAP (Group C) and 2 h and 12 mm Hg IAP were created with CO2 pneumoperitoneum (Group D). At the end of the experiment, plasma samples taken from subjects and fibrinogen, FII (prothrombin), FV, FVII, FVIII, FIX, FX, FXI, FXII, von willebrand's factor (vWF), ristocetin cofactor, protein C, protein S, antithrombin III (AT III) levels are studied. There were statistically significant differences in the mean levels of FII, FV, FVII, FVIII, FIX, FX, FXI, FXII, and protein S between the groups. A hypercoagulable state occurred with the following: increase in the coagulation parameters compared to the control group; increase in FVII in the group only Group C; decrease in AT III in all groups compared to the control group; decrease in protein C in the group only XII Group D compared to control group; decrease in protein S in all groups except group D compared to control group. CO2 insufflation predisposes to thromboembolic events both by inducing coagulation factors and by suppressing the fibrinolytic system contrary to the controversies in the literature.

  3. Von Bertalanffy's dynamics under a polynomial correction: Allee effect and big bang bifurcation

    Science.gov (United States)

    Leonel Rocha, J.; Taha, A. K.; Fournier-Prunaret, D.

    2016-02-01

    In this work we consider new one-dimensional populational discrete dynamical systems in which the growth of the population is described by a family of von Bertalanffy's functions, as a dynamical approach to von Bertalanffy's growth equation. The purpose of introducing Allee effect in those models is satisfied under a correction factor of polynomial type. We study classes of von Bertalanffy's functions with different types of Allee effect: strong and weak Allee's functions. Dependent on the variation of four parameters, von Bertalanffy's functions also includes another class of important functions: functions with no Allee effect. The complex bifurcation structures of these von Bertalanffy's functions is investigated in detail. We verified that this family of functions has particular bifurcation structures: the big bang bifurcation of the so-called “box-within-a-box” type. The big bang bifurcation is associated to the asymptotic weight or carrying capacity. This work is a contribution to the study of the big bang bifurcation analysis for continuous maps and their relationship with explosion birth and extinction phenomena.

  4. Kerttu Wagner. Die historischen romane von Jaan Kross / Wolfgang Drechsler

    Index Scriptorium Estoniae

    Drechsler, Wolfgang, 1963-

    2001-01-01

    Arvustus: Wagner, Kerttu. Die historischen Romane von Jaan Kross : am Beispiel einer Untersuchung der deutschen und englischen Übersetzungen von "Professor Martensi ärasõit" (1984). Frankfurt am Main [etc.] : P. Lang, 2001.

  5. Kerttu Wagner. Die historischen romane von Jaan Kross / Wolfgang Drechsler

    Index Scriptorium Estoniae

    Drechsler, Wolfgang, 1963-

    2001-01-01

    Arvustus: Wagner, Kerttu. Die historischen Romane von Jaan Kross : am Beispiel einer Untersuchung der deutschen und englischen Übersetzungen von "Professor Martensi ärasõit" (1984). Frankfurt am Main [etc.] : P. Lang, 2001.

  6. Gemeinsam hilfreich oder einsam lästig? Beurteilung von praktikumsbegleitenden Weblogs von angehenden Lehrpersonen

    Directory of Open Access Journals (Sweden)

    Nives Egger

    2017-02-01

    Full Text Available Weblogs werden an Hochschulen vermehrt zur Unterstützung von Lern- und Reflexionsprozessen eingesetzt, in der Lehrer/innenbildung auch zunehmend während der berufspraktischen Ausbildung. Die Studierenden beurteilen den Einsatz von Weblogs jedoch unterschiedlich. Dabei ist wenig bekannt, welchen Einfluss die Vergabe und das Erhalten von Peerfeedback auf den Beurteilungsprozess von praktikumsbegleitenden Weblogs sowie auf den Umfang von Blogpostings haben. Im folgenden Beitrag wird dieser Frage mittels einer Befragung von 74 angehenden Lehrpersonen nachgegangen, die praktikumsbegleitende Weblogs mit oder ohne Peerfeedback nutzten, um über herausfordernde Ereignisse im Praktikum zu reflektieren. Die Ergebnisse zeigen, dass Studierende, die Peerfeedback erhielten und andere Blogbeiträge kommentierten, den Weblogeinsatz nützlicher einschätzen sowie eine höhere Motivation und positivere Einstellung gegenüber den Einsatz von Weblogs aufweisen als Studierende, die ohne Peerfeedback bloggen. Keinen Einfluss hat Peerfeedback auf den Umfang der Blogbeiträge und auf die dafür aufgewendete Zeit.

  7. Liouville-von Neumann molecular dynamics

    Science.gov (United States)

    Jakowski, Jacek; Morokuma, Keiji

    2009-06-01

    We present a novel first principles molecular dynamics scheme, called Liouville-von Neumann molecular dynamics, based on Liouville-von Neumann equation for density matrices propagation and Magnus expansion of the time-evolution operator. The scheme combines formally accurate quantum propagation of electrons represented via density matrices and a classical propagation of nuclei. The method requires a few iterations per each time step where the Fock operator is formed and von Neumann equation is integrated. The algorithm (a) is free of constraint and fictitious parameters, (b) avoids diagonalization of the Fock operator, and (c) can be used in the case of fractional occupation as in metallic systems. The algorithm is very stable, and has a very good conservation of energy even in cases when a good quality conventional Born-Oppenheimer molecular dynamics trajectories is difficult to obtain. Test simulations include initial phase of fullerene formation from gaseous C2 and retinal system.

  8. Gasification of liquid manure; Vergasung von Guelle

    Energy Technology Data Exchange (ETDEWEB)

    Gudenau, H.W.; Hoberg, H.; Hirsch, U. [Technische Hochschule Aachen (Germany). Inst. fuer Eisenhuettenkunde

    1996-12-31

    The potential of thermal use of liquid manure is investigated. It is recommended to separate the liquid and solid fraction. While the liquid fraction can be used as fertilizer, the solid fraction can be used for generating a fuel gas for combined heat and power generation. (orig) [Deutsch] Die Untersuchungen haben ergeben, dass in der thermischen Verwertung von Guelle ein bisher nur wenig genutztes Potential vorliegt. Die zum Anbau von Getreide notwendige Duengung kann durch Separation von Guelle in Fest- und Duennfraktion effektiver und kostenguenstiger durchgefuehrt werden. Der Naehrstoffgehalt des Guellefeststoffs sollte durch thermische Aufbereitung aufkonzentriert werden, so dass eine Vermarktung auch mit laengeren Transpoertwegen darstellbar ist. Die bei der thermischen Behandlung gewonnene Waerme kann prozessintern genutzt und ueberschuessige Waerme an Abnehmer in der naeheren Umgebung geliefert werden. Genauso besteht die Moeglichkeit, ein Brenngas zu erzeugen und die Energie mit Kraft-Waerme-Kopplung zu nutzen. (orig)

  9. Multivariate Herkunftsanalyse von Marmor auf petrographischer und geochemischer Basis

    OpenAIRE

    Cramer, Thomas

    2004-01-01

    Am Beispiel von aus Kleinasien stammenden Grabungsfunden in der Antikensammlung Berlin wird die Methodik der Herkunftsanalyse von Marmoren, d.h. der Zuordnung zu ihren Lagerstätten, weiterentwickelt und erprobt. Dazu wird der aktuelle Forschungsstand kritisch gewürdigt, die Voraussetzungen, Bedingungen und Grenzen der Provenienzbestimmung werden systematisiert und von den zahlreichen Gesteinsmerkmalen und Untersuchungsmethoden die geeignetsten ausgewählt. Marmore von 38 Sammlungsobjekten, die...

  10. Experimentelle Untersuchung von Konzentrations- und Verweilzeiteffekten in Membranreaktoren

    OpenAIRE

    Tota, A.; Hamel, C.; Thomas, S.; Joshi, M.; Klose, F.; Seidel-Morgenstern, A.

    2003-01-01

    Heterogen katalysierte Oxidationsreaktionen von kurzkettigen Kohlenwasserstoffen werden in der Industrie zur Erzeugung von Ausgangsmaterialien für wertvollere Syntheseprodukte (selektive Oxidation) oder zur Entsorgung von Abgasen eingesetzt. Bei selektiven Oxidationen ist das gewünschte Produkt gewöhnlich ein thermodynamisch instabiles Zwischenprodukt. Mit dem Einsatz von Membranreaktoren verspricht man sich hohe Selektivitäten. bei gleichzeitig hohen Ausbeuten. Als Modellreaktion für systema...

  11. Approximate equivalence in von Neumann algebras

    Institute of Scientific and Technical Information of China (English)

    DING; Huiru; Don; Hadwin

    2005-01-01

    One formulation of D. Voiculescu's theorem on approximate unitary equivalence is that two unital representations π and ρ of a separable C*-algebra are approximately unitarily equivalent if and only if rank o π = rank o ρ. We study the analog when the ranges of π and ρ are contained in a von Neumann algebra R, the unitaries inducing the approximate equivalence must come from R, and "rank" is replaced with "R-rank" (defined as the Murray-von Neumann equivalence of the range projection).

  12. Von Mumien, Cyborgs und Röntgenbildern

    Directory of Open Access Journals (Sweden)

    Regina Schleicher

    2004-03-01

    Full Text Available Unter dem Titel Techniken der Reproduktion liegt ein Sammelband vor, der die Beiträge einer Tagung an der Universität Paderborn vom Dezember 2001 enthält. In enger Verknüpfung verschiedener disziplinärer Perspektiven werden Schlaglichter auf eine Vielzahl von Themen geworfen, die sich mit dem Begriff „Reproduktion“ verbinden. Dabei wird deutlich, wie eng die Geschichte der Medien und die Entwicklung von Technologien der biologischen Fortpflanzung miteinander verzahnt sind.

  13. Verwertung von Prozessbieren in der Brauerei

    OpenAIRE

    Schneeberger, Mark

    2007-01-01

    Die betriebsinterne Verwertung von Prozessbieren (PB) zur Minimierung des Bierschwandes stellt den Kern der Arbeit dar. Als mengenmäßig bedeutsamste PB haben sich Hefebiere (HB), Vor-, Zwischen- und Nachläufe (VZNL) aus der Filtration, Biere aus unterfüllten bzw. falsch etikettierten Flaschen aus der Abfüllung sowie Rückbiere herausgestellt. Verschiedene Indikatoren in Hefezellen und im HB wurden zur Kontrolle von Hefebierrückgewinnungsanlagen ermittelt. Um eine hohe Qualität der wiedergewinn...

  14. [Anja Wilhelmi. Lebensweltlen von Frauen der deutschen Oberschicht im Baltikum (1800-1939). Eine Untersuchung anhand von Autobiographien] / Alexander Ewig

    Index Scriptorium Estoniae

    Ewig, Alexander, 1980-

    2011-01-01

    Arvustus: Wilhelmi, Anja. Lebenswelten von Frauen der deutschen Oberschicht im Baltikum (1800-1939). Eine Untersuchung anhand von Autobiographien. (Veröffentlichungen des Nordost-Instituts, 10.) (Wiesbaden : HArrassowitz 2008)

  15. [Anja Wilhelmi. Lebensweltlen von Frauen der deutschen Oberschicht im Baltikum (1800-1939). Eine Untersuchung anhand von Autobiographien] / Alexander Ewig

    Index Scriptorium Estoniae

    Ewig, Alexander, 1980-

    2011-01-01

    Arvustus: Wilhelmi, Anja. Lebenswelten von Frauen der deutschen Oberschicht im Baltikum (1800-1939). Eine Untersuchung anhand von Autobiographien. (Veröffentlichungen des Nordost-Instituts, 10.) (Wiesbaden : HArrassowitz 2008)

  16. Therapeutic and routine prophylactic properties of rFactor VIII Fc (efraloctocog alfa, Eloctate®) in hemophilia A

    Science.gov (United States)

    Chowdary, Pratima; Fosbury, Emma; Riddell, Anne; Mathias, Mary

    2016-01-01

    rFVIIIFc (efraloctocog alfa, Eloctate®) is an extended half-life (EHL) factor VIII licensed for use in patients with hemophilia A for prophylaxis and treatment of bleeding and surgical episodes. Pharmacokinetic studies in adults have shown a mean 1.5-fold increase in half-life compared to full-length factor VIII. When compared to adults, the half-life is decreased by 8% in adolescents between 12 and 17 years, by 18% in children 6 to <12 years, and by 33% in children between the ages of 2 and <6 years. There is a considerable interindividual variation in the prolongation of the half-life particularly in children and across the age groups, the range extending from no increase to a 2.5-fold increase. In addition to age, von willebrand factor (VWF) antigen level has demonstrated a significant impact on rFVIIIFc half-life, with higher VWF levels associated with greater prolongation of half-life. The pivotal and pediatric clinical trials have demonstrated the efficacy and safety of rFVIIIFc for use in regular prophylaxis and in management of bleeds and surgery. In these studies, just under half the participants showed a zero annualized bleed rate (ABR), and the median ABR (1.6 in the pivotal study for the individualized prophylaxis arm) showed a further decrease in the extension study. On average, the patients required fewer infusions (reduced by at least a third), and the mean weekly consumption seems to be in keeping with standard recombinant factor VIII. EHL rFVIIIFc has made decreased infusion frequency a possibility. However, the interindividual variability in dose and infusion frequency highlights the need for a personalized approach based on individual patient’s half-life and/or response to treatment. PMID:27695377

  17. Ex vivo effects of low-dose rivaroxaban on specific coagulation assays and coagulation factor activities in patients under real life conditions.

    Science.gov (United States)

    Mani, Helen; Hesse, Christian; Stratmann, Gertrud; Lindhoff-Last, Edelgard

    2013-01-01

    Global coagulation assays display variable effects at different concentrations of rivaroxaban. The aim of this study is to quantify the ex vivo effects of low-dose rivaroxaban on thrombophilia screening assays and coagulation factor activities based on the administration time, and to show how to mask possible interferences. Plasma samples from 40 patients receiving rivaroxaban 10 mg daily were investigated to measure activities of clotting factor II, V, VII, VIII, IX, XI, XII and XIII; protein C- and protein S-levels; lupus anticoagulants; anticardiolipin IgG and IgM; D-dimer, heparin-platelet factor 4 (HPF4) antibodies and screening tests for von Willebrand disease (VWD). Two hours after rivaroxaban administration, the activities of clotting factors were significantly decreased to different extents, except for factor XIII. Dilution of plasma samples resulted in neutralisation of these interferences. The chromogenic protein C activity assay was not affected by rivaroxaban. Depending on the timing of tablet intake in relation to blood sampling protein S activity was measured falsely high when a clotting assay was used. False-positive results for lupus anticoagulants were observed depending on the assay system used and the administration time of rivaroxaban. ELISA-based assays such as anticardiolipin IgG and IgM, D-dimer, HPF4-antibodies and the turbidimetric assays for VWD were not affected by rivaroxaban. Specific haemostasis clotting tests should be performed directly prior to rivaroxaban intake. Assay optimisation in the presence of rivaroxaban can be achieved by plasma dilution. Immunologic assays are not influenced by rivaroxaban, while chromogenic assays can be used, when they do not depend on factor Xa.

  18. Tracial gauge norms on finite von Neumann algebras satisfying the weak Dixmier property

    CERN Document Server

    Fang, Junsheng; Nordgren, Eric; Shen, Junhao

    2007-01-01

    In this paper we set up a representation theorem for tracial gauge norms on finite von Neumann algebras satisfying the weak Dixmier property in terms of Ky Fan norms. Examples of tracial gauge norms on finite von Neumann algebras satisfying the weak Dixmier property include unitarily invariant norms on finite factors (type ${\\rm II}\\sb 1$ factors and $M_n(\\cc)$) and symmetric gauge norms on $L^\\infty[0,1]$ and $\\cc^n$. As the first application, we obtain that the class of unitarily invariant norms on a type ${\\rm II}\\sb 1$ factor coincides with the class of symmetric gauge norms on $L^\\infty[0,1]$ and von Neumann's classical result \\cite{vN} on unitarily invariant norms on $M_n(\\cc)$. As the second application, Ky Fan's dominance theorem \\cite{Fan} is obtained for finite von Neumann algebras satisfying the weak Dixmier property. As the third application, some classical results in non-commutative $L^p$-theory (e.g., non-commutative H$\\ddot{\\text{o}}$lder's inequality, duality and reflexivity of non-commutative...

  19. Die Verteilung und Eigenschaften von Bodenformen in der Deutschen Bucht, eine Rekonstruktion der Karten von Ulrich (1973)

    DEFF Research Database (Denmark)

    Winter, Christian; Lefebvre, Alice; Benninghoff, Markus

    2015-01-01

    Entstehung, Gestalt und Dynamik von Bodenformen in vergleichsweise kleinen Untersuchungsgebieten ist die Arbeit von ULRICH (1973) über die Verteilung von Bodenformen in der Deutschen Bucht bis heute die einzige verfügbare zusammenhängende Darstellung für die deutsche Nordseeküste. Die analogen Karten und die...

  20. Herstellung von Bio-Fleisch- und Wurstwaren ohne Einsatz von Pökelstoffen

    OpenAIRE

    2008-01-01

    Bei der ökologischen Herstellung von Fleisch- und Wurstwaren werden vielfach auf die in der konventionellen Wurstherstellung verwendeten Konservierungsstoffe E 250 (Natriumnitrit) bzw. E 252 (Kaliumnitrat) verzichtet oder reduzierte Zugabemengen der Zusatzstoffe verwendet.

  1. Der Briefwechsel zwischen Alexander von Humboldt und Karl Ernst von Baer

    Directory of Open Access Journals (Sweden)

    Thomas Schmuck

    2012-10-01

    Full Text Available Zusammenfassung Der kurze, nicht vollständig erhaltene Briefwechsel zwischen Alexander von Humboldt und Karl Ernst von Baer behandelt sehr verschiedene Themen: Politik, Kriegsgefahr, den Wissenschaftsbetrieb, Auszeichnungen und Tagungen, Embryologie und Cholera. Gemeinsam mit Briefen und Reden ergibt sich dabei ein differenziertes Bild der Beurteilung der beiden Wissenschaftler durch den jeweils anderen. Während Baer sich als Bewunderer Humboldts erweist, erscheint umgekehrt Humboldts Einschätzung Baers als ambivalent. Abstract The short, not completely preserved correspondence between Alexander von Humboldt and Karl Ernst von Baer deals with a wide range of subjects: politics and the danger of war, academic activities, scientific awards and conferences, aspects of embryology and the cholera. Letters to third persons and speeches, together with the correspondence between Humboldt and Baer show a differentiated pattern of mutual appraisal: While Baer always remained an admirer of the elder naturalist, Humboldt’s estimation was characterized by ambivalence.

  2. Von der Medienwirkungsbehauptung zur erziehungswissenschaftlichen Medienrezeptionsforschung. Vorschlag zur Analyse von Filmkommunikaten

    Directory of Open Access Journals (Sweden)

    Barbara Drinck

    2001-04-01

    Full Text Available Im Hinblick auf die Erforschung spezifischer Zusammenhänge von Medienkonsum und der Herausbildung von Einstellungen und Handlungen wird eine konstruktivistische Theorieorientierung plausibilisiert, indem zunächst auf den Stand der Medienwirkungsforschung eingegangen und vor dem Hintergrund einer begründeten Kritik des Wirkungsverständnisses auf die Notwendigkeit einer medienrezeptionswissenschaftlichen Forschungsalternative hingewiesen wird. Weiterhin wird der Stand der (erziehungswissenschaftlichen Medienrezeptionsforschung erörtert. Sodann werden Elemente einer konstruktivistischen Methodologie von Medienrezeptionsforschung beschrieben, die am Beispiel der Rezeption von Filmen konkretisiert werden. Dabei wird das Konzept des Kommunikates (S.J. Schmidt als Ausgangspunkt genommen, ein Vorschlag für eine Beschreibungssprache für (Film- Kommunikate entwickelt und eine Adaption des Ansatzes filmischer Narration zur Sprache gebracht.

  3. Auswirkung von Umweltchemikalien auf die Biologie von Chironomiden und Fischen als deren Prädatoren

    OpenAIRE

    Langer-Jaesrich, Miriam

    2012-01-01

    Im Rahmen der Dissertation wurden in mehreren Teilprojekten die Auswirkungen von Umweltchemikalien auf Chironomiden als Schlüsselorganismen in aquatisch-benthischen Lebensräumen untersucht. Dabei lag der Fokus besonders auf der Erfassung von nicht-standardisierten Endpunkten und Bioindikatoren sowie auf der Bearbeitung einer weiterführenden ökologisch relevanten Fragestellung zum Räuber-Beute-Verhältnis unter Schadstoffeinfluss. Im ersten Teil der Dissertation wurde das herkömmliche Standa...

  4. Synthese von grenzflächenaktiven Monomeren zur Herstellung von funktionalen Metall-Chalkogenid/Polymer-Hybridnanopartikeln

    OpenAIRE

    Fischer, V.

    2013-01-01

    In dieser Arbeit wurde gezeigt, wie oberflächenfunktionalisierte Polystyrolnanopartikel zur Herstellung von Metallchalkogenid/Polymer-Hybridnanopartikeln eingesetzt werden können. Dazu wurden zunächst phosphonsäure- und phosphorsäurefunktionalisierte Surfmere synthetisiert, die anschließend bei der Miniemulsionspolymerisation von Styrol verwendet wurden. Die Surfmere dienten dabei zugleich zur Stabilisierung und als Comonomer. Die oberflächenfunktionalisierten Polystyrolnanopartikel wurden an...

  5. Untersuchung der Rolle von Rhodopsin 7 und Cryptochrom im Sehprozess von Drosophila melanogaster

    OpenAIRE

    Grebler, Rudi

    2015-01-01

    Ausgangspunkt für die Detektion von Licht ist im gesamten Tierreich die Absorption von Photonen durch photorezeptive Proteine, die sogenannten Opsine und in geringerem Ausmaß die Typ 1 Cryptochrome. Die Taufliege Drosophila melanogaster besitzt sechs eingehend charakterisierte, auch als Rhodopsine bezeichnete Opsine (Rh1-Rh6) und ein Cryptochrom (CRY). Neben den Ocellen und den Hofbauer-Buchner Äuglein werden die Rhodopsine in erster Linie in den Photorezeptorzellen der Komplexaugen, den Haup...

  6. Untersuchungen zur Trockenentschwefelung von Brenngasen durch Partialoxidation von H2S an Herdofenkoks

    OpenAIRE

    Bauersfeld, Dirk

    2009-01-01

    Die vorliegende Arbeit befasst sich mit Untersuchungen zur Trockenentschwefelung von Brenngasen durch Partialoxidation von H2S an Herdofenkoks. Hierzu wurden Versuche in der Technikumsanlage VTE 2004 mit einem simulierten PHTW Gas durchgeführt. Es zeigte sich, dass der COS-Abbau nicht wie bisher angenommen durch die COS-Partialoxidation sondern durch die COS-Hydrolyse erfolgt. Die COS-Hydrolyse gewinnt dabei mit abnehmender Raumbelastung an Bedeutung. Der Entschwefelungsgrad erhöht sich mit s...

  7. Dentinhaftung von Zementen. Der Haftverbund von Zementen mit Dentin in Kombination mit verschiedenen indirekten Restaurationsmaterialien

    OpenAIRE

    Peutzfeldt, Anne; Sahafi, Alireza; Flury, Simon

    2011-01-01

    Einleitung: Die Anzahl zahnärztlicher Zemente sowie Restaurationsmaterialien steigt stetig. Die richtige Zementwahl für einen zuverlässigen Haftverbund zwischen Restaurationsmaterial und Zahnsubstanz ist von Interesse für den Kliniker. Ziel der vorliegenden in vitro-Studie war es daher, den Dentinhaftverbund von verschiedenen Zementen in Kombination mit verschiedenen indirekten Restaurationsmaterialien zu untersuchen. Material und Methoden: Zylindrische Probekörper aus sechs Restaurations...

  8. Influence of air pollutants and other factors of stress on phytohormone concentrations in trees. Final report. Pt. 2; Einfluss von Luftschadstoffen und weiteren Stressfaktoren auf Phytohormonkonzentrationen in Baeumen. Abschlussbericht. T. 2

    Energy Technology Data Exchange (ETDEWEB)

    Hock, B.; Schneider, P.; Horn, K.

    1990-04-01

    den Einzelproben zurueckzufuehren. Die gewonnenen Daten des Standortes `Wank` ergaben keine statistisch absicherbaren Zusammenhaenge einer Schaedigung eines Baumes bzw. des Einflusses der Hoehenlage auf den GA-Gehalt. Lediglich Analysen symptomfreier und vergilbter Nadeln belegten einen signifikanten Einfluss auf den Gibberellingehalt, der vermutlich auf eine jahreszeitliche GA{sub 3}-Fluktuation zurueckzufuehren ist. Aus dem vorliegenden Datenmaterial ist eine relevante physiologische Bedeutung der Gibberelline GA{sub 3} und GA{sub 1} fuer eine Fruehindikation von Waldschaeden nicht ableitbar. (orig./UWA)

  9. [The Costantin Von Economo's lethargic encefalitis

    Science.gov (United States)

    Pistacchio, E.

    1998-01-01

    Starting from the Constantin Von Economo's description of a "new" disease, the lethargic encephalitis, the author delineates the history of an infectious sleeping sickness that caused epidemics in Europe from 1917 to 1928 and led to create, in Italy, the "Institutes for Encephalitis".

  10. Die larvale Entwicklung von Chirocentrus dorab (Forsk.)

    NARCIS (Netherlands)

    Delsman, H.C.

    1922-01-01

    Wer sich mit dem Studium der Lebensweise indischer Fische befassen will, hat dabei den grossen Vorteil, sich beim Bestimmen der Species auf die zahlreichen Arbeiten BLEEKER’S stützen zu können, während ihm das Determinieren ganz besonders erleichtert wird durch das von dichotomischen Tabellen

  11. Soolopartiid Von Krahli katuse all / Kristi Eberhart

    Index Scriptorium Estoniae

    Eberhart, Kristi

    2007-01-01

    Von Krahli Teatri kolmest lavastusest: "Erki ja Tiina" (lavastaja Mart Kangro, tantsivad Erki Laur ja Tiina Tauraite), "Faust" (J. W. Goethe ainetel tekst ja lavastus Taavi Eelmaa, muusika ja laulud Chalice, osades Jarek Kasar ja Rein Pakk), "Hamletid" (William Shakespeare'i ainetel kontseptsiooni, lavastuse, koreograafia, kujunduse, valguse autor Sasha Pepeljajev, video- ja helikunstnik Taavet Jansen. Esitaja Juhan Ulfsak)

  12. Drei neue Chelonarium-Arten von Sumatra

    NARCIS (Netherlands)

    Reitter, Edm.

    1886-01-01

    Die Arten dieser Gattung kommen vorherschend in Central- und Süd-Amerika vor, doch sind in neuerer Zeit auch drei Arten: Ch. orientale Reitt. 1), conspersum Reitt. 2) und adspersum Chevrl.3) von den grossen Sunda-Inseln und Malakka bekannt geworden, zu denen nun weitere 3 Arten treten, die ich nachf

  13. Ueber eine Anomalie von Acromitus flagellatus (Stiasny)

    NARCIS (Netherlands)

    Stiasny, G.

    1934-01-01

    Bei erneuter Durchsicht des reichhaltigen Materiales von Acromitus flagellatus (Stiasny) in der Scyphomedusen-Sammlung des Rijksmuseum van Natuurlijke Historie in Leiden (vergl. meine Mitteilungen daruber, 1920, Uebersichtstabelle III und 1921, p. 131/136) fand ich ein Exemplar, das eine

  14. Ueber zwei neue Vogelarten von Java

    NARCIS (Netherlands)

    Finsch, O.

    1902-01-01

    Die beiden nachstehend beschriebenen Vögel wurden mir von Herrn Max Bartels als muthmasslich neu zugesandt. Die genaue Untersuchung hat dies bestätigt. Ich freue mich daher eine der Arten zu Ehren des Entdeckers benennen zu können. Seit einigen Jahren als Leiter der Plantage Pangerango bei Pasir Dat

  15. The von Bertalanffy growth model for horticulture

    NARCIS (Netherlands)

    Tijskens, L.M.M.; Schouten, R.E.; Unuk, T.; Šumak, D.

    2017-01-01

    Traditionally, crop load and fruit yield from previous seasons are used as indicators for prediction of fruit size. Disregarding the inevitable biological variation between fruit, von Bertalanffy (1938) described the growth, expressed as length, of virtually any living organism. The model is here

  16. Von Kalifornien nach Taxham / Katri Soe

    Index Scriptorium Estoniae

    Soe, Katri, 1971-

    2005-01-01

    Neljas osa magistritööst "Von Kalifornien nach Taxham: Formen und Strukturen der Kommunikation in Peter Handkes Romanen "Der kurze Brief zum langen Abschied" und "In einer dunklen Nacht ging ich aus meinem stillen Haus"" (Tartu, 2000. Juhendaja: Claus Sommerhage)

  17. Ueber eine Anomalie von Acromitus flagellatus (Stiasny)

    NARCIS (Netherlands)

    Stiasny, G.

    1934-01-01

    Bei erneuter Durchsicht des reichhaltigen Materiales von Acromitus flagellatus (Stiasny) in der Scyphomedusen-Sammlung des Rijksmuseum van Natuurlijke Historie in Leiden (vergl. meine Mitteilungen daruber, 1920, Uebersichtstabelle III und 1921, p. 131/136) fand ich ein Exemplar, das eine bemerkenswe

  18. Zustandsschätzung von aktiven Fahrwerkregelsystemen

    NARCIS (Netherlands)

    Leenen, R.; Maurice, J.P.

    2010-01-01

    Eine Weiterentwicklung von Fahrdynamikregelung, Überroll- und Seitenaufprallschutz sowie Pre-Crash-Funktionen und Kollisionsminderung verspricht TNO. Mit einem System zur Beobachtung des aktuellen Fahrzeugzustands (Vehicle State Estimator – VSE) bietet der niederländische Zulieferer ein zentrales Mo

  19. Ueberreste vorweltlicher Proboscidier von Java und Banka

    NARCIS (Netherlands)

    Martin, K.

    1884-01-01

    Junghuhn führte in seinem Werke über Java nur einen einzigen Wirbelthierrest, Carcharias megalodon, an (7, IV, pag. 97); es war ihm nicht gelungen bei seinem ersten Aufenthalte auf der Insel Reste von Säugethieren zu finden, so eifrig er auch darnach in den Höhlen des Tertiaergebirges suchte (7, IV,

  20. Entendendo a entropia de von Neumann

    OpenAIRE

    Maziero, Jonas

    2015-01-01

    Revisamos os postulados da mecânica quântica necessários para discutir a entropia de von Neumann, que é introduzida como uma generalização da entropia de Shannon e propomos um jogo simples que facilita o entendimento do seu significado físico.

  1. Das Haarkleid eines Fetus von Schimpanse

    NARCIS (Netherlands)

    Bolk, L.

    1919-01-01

    In seiner ausführlichen Arbeit über die Richtung der Haare bei den Affenembryonen nebst allgemeinen Erörterungen über die Ursachen der Haarrichtungen, hat Schwalbe eine Fülle von Tatsachen und eine wertvolle kritische Betrachtung über das Problem der Haarrichtungen geliefert. Leider war der Autor ni

  2. Jungen als Verlierer? Die Diskussion um die Benachteiligung von Jungen in der Schule

    Directory of Open Access Journals (Sweden)

    Hilde von Balluseck

    2009-03-01

    Full Text Available Die im Vergleich zu den Mädchen schlechteren Schulleistungen von Jungen werden in der öffentlichen Diskussion häufig dem weiblichen Geschlecht von pädagogischen Fachkräften angelastet. Das Leistungs- und Sozialverhalten der meisten Jungen ist jedoch weitaus stärker durch Männer- und Frauenbilder in ihrem sozialen Umfeld bedingt. Wenn diese sich an hegemonialen Vorstellungen von Männlichkeit – gerade auch in der gesellschaftlich ohnmächtigen Unterschicht – orientieren, geraten Jungen in der Schule in einen Konflikt. Dieser wird verstärkt, wenn sie – statistisch häufiger als Mädchen – zu Hause geschlagen werden. Der im Vergleich zu Mädchen weitaus intensivere Konsum von Gewalt verherrlichenden Medien ist ein weiterer Faktor für die größere Schuldistanz von Jungen. Die pauschalisierende Annahme, das weniger angepasste Leistungsverhalten von Jungen stehe im direkten Zusammenhang mit dem weiblichen Geschlecht der Lehrkräfte, geht somit an den eigentlichen Problemen vorbei.In the public discussions about the relatively poor school achievements of boys as compared to girls, the female gender of the pedagogical specialists is often blamed. Most of the boys’ social performance and attitude toward achievement is, however, conditioned through images of men and women in their immediate social surroundings. Boys often find themselves in conflict at school when these images are oriented toward hegemonic conceptions of masculinity, in particular when found in the socially powerless underclass. This conflict is heightened when the boys are abused at home, statistically more likely to happen than in the case of girls. Another factor for the boys’ greater distancing from schools is their higher consumption of media forms that glorify violence. The trivializing assumption that the poorer achievements of boys are directly related to the female gender of the teachers thus ignores the true problems.

  3. [Autopsy case of von Recklinghausen's disease associated with lung cancer, gastrointestinal stromal tumor of the stomach, and duodenal carcinoid tumor].

    Science.gov (United States)

    Satoh, Miki; Wakabayashi, Osamu; Araya, Yoshikazu; Jinushi, Eisei; Yoshida, Fumiaki

    2009-09-01

    A 58-year-old man with von Recklinghausen's disease was admitted for further investigation of right chest pain. Chest X-ray revealed multiple emphysematous bullae in both lungs and a tumor shadow in the right upper lobe. Bronchofiberscopy was performed, but an adequate specimen was not obtained. The tumor was diagnosed as a non-small-cell lung cancer with direct invasion to the adjacent rib. Although chemotherapy and radiotherapy resulted in decrease in tumor size, the tumor subsequently increased in size and the patient died 14 months after the first admission. Autopsy revealed multiple emphysematous bullae, poorly differentiated adenosquamous cell carcinoma of the lung, gastrointestinal stromal tumor of the stomach, and duodenal carcinoid tumor. This case suggests the possibility that von Recklinghausen's disease associated with emphysematous bullae is a risk factor for lung cancer. It has also been suggested that the genetic abnormality responsible for von Recklinghausen's disease increases the risk for various types of malignancy. Although von Recklinghausen's disease is reportedly associated with various malignant tumors, it is quite rare for von Recklinghausen's disease to be associated with triple non-neurogenic tumors. Careful observation is mandatory for patients with von Recklinghausen's disease.

  4. Factor VIII Is Synthesized in Human Endothelial Cells, Packaged in Weibel-Palade Bodies and Secreted Bound to ULVWF Strings.

    Directory of Open Access Journals (Sweden)

    Nancy A Turner

    Full Text Available The cellular synthesis site and ensuing storage location for human factor VIII (FVIII, the coagulation protein deficient in hemophilia A, has been elusive. FVIII stability and half-life is dependent on non-covalent complex formation with von Willebrand factor (VWF to avoid proteolysis and clearance. VWF is synthesized in megakaryocytes and endothelial cells, and is stored and secreted from platelet alpha granules and Weibel-Palade bodies of endothelial cells. In this paper we provide direct evidence for FVIII synthesis in 2 types of primary human endothelial cells: glomerular microvascular endothelial cells (GMVECs and umbilical vein endothelial cells (HUVECs. Gene expression quantified by real time PCR revealed that levels of F8 and VWF are similar in GMVECs and HUVECs. Previous clinical studies have shown that stimulation of vasopressin V2 receptors causes parallel secretion of both proteins. In this study, we found that both endothelial cell types express AVPR2 (vasopressin V2 receptor gene and that AVPR2 mRNA levels are 5-fold higher in GMVECs than HUVECs. FVIII and VWF proteins were detected by fluorescent microscopy in Weibel-Palade bodies within GMVECs and HUVECs using antibodies proven to be target specific. Visual presence of FVIII and VWF in Weibel-Palade bodies was confirmed by correlation measurements. The high extent of correlation was compared with negative correlation values obtained from FVIII detection with cytoplasmic proteins, β-actin and Factor H. FVIII activity was positive in GMVEC and HUVEC cell lysates. Stimulated GMVECs and HUVECs were found to secrete cell-anchored ultra-large VWF strings covered with bound FVIII.

  5. Factor VIII Is Synthesized in Human Endothelial Cells, Packaged in Weibel-Palade Bodies and Secreted Bound to ULVWF Strings.

    Science.gov (United States)

    Turner, Nancy A; Moake, Joel L

    2015-01-01

    The cellular synthesis site and ensuing storage location for human factor VIII (FVIII), the coagulation protein deficient in hemophilia A, has been elusive. FVIII stability and half-life is dependent on non-covalent complex formation with von Willebrand factor (VWF) to avoid proteolysis and clearance. VWF is synthesized in megakaryocytes and endothelial cells, and is stored and secreted from platelet alpha granules and Weibel-Palade bodies of endothelial cells. In this paper we provide direct evidence for FVIII synthesis in 2 types of primary human endothelial cells: glomerular microvascular endothelial cells (GMVECs) and umbilical vein endothelial cells (HUVECs). Gene expression quantified by real time PCR revealed that levels of F8 and VWF are similar in GMVECs and HUVECs. Previous clinical studies have shown that stimulation of vasopressin V2 receptors causes parallel secretion of both proteins. In this study, we found that both endothelial cell types express AVPR2 (vasopressin V2 receptor gene) and that AVPR2 mRNA levels are 5-fold higher in GMVECs than HUVECs. FVIII and VWF proteins were detected by fluorescent microscopy in Weibel-Palade bodies within GMVECs and HUVECs using antibodies proven to be target specific. Visual presence of FVIII and VWF in Weibel-Palade bodies was confirmed by correlation measurements. The high extent of correlation was compared with negative correlation values obtained from FVIII detection with cytoplasmic proteins, β-actin and Factor H. FVIII activity was positive in GMVEC and HUVEC cell lysates. Stimulated GMVECs and HUVECs were found to secrete cell-anchored ultra-large VWF strings covered with bound FVIII.

  6. Type III von Neumann Algebras associated with $\\O_\\theta$

    CERN Document Server

    Yang, Dilian

    2011-01-01

    Let $\\Fth$ be a 2 graph generated by $m$ blue edges and $n$ red edges, and $\\omega$ be the distinguished faithful state associated with its graph C*-algebra $\\O_\\theta$. In this paper, we characterize the factorness of the von Neumann algebra $\\pi_\\omega(\\O_\\theta)"$ induced from the GNS representation of $\\omega$ under a certain condition. Moreover, when $\\pi_\\omega(\\O_\\theta)"$ is a factor, then it is of type III$_{m^{-\\frac{1}{b}}}$ (or III$_{n^{-\\frac{1}{a}}}$) if $\\frac{\\ln m}{\\ln n}\\in\\bQ$, where $a,b\\in\\bN$ with $\\gcd(a,b)=1$ satisfy $m^a=n^b$, and of type III$_1$ if $\\frac{\\ln m}{\\ln n}\

  7. Prevention of gas escape from abandoned mines; Vermeidung von Gaszutritten aus stillgelegten Grubenfeldern

    Energy Technology Data Exchange (ETDEWEB)

    Kunz, E.; Meiners, H.; Christensen, H.J.; Litte, B.; Luhmann, L.; Opahle, M.; Pollak, R.; Sheta, H. [Deutsche Montan Technologie GmbH, Essen (Germany). Gas and Fire Div.

    2003-07-01

    Many mines were abandoned in the Ruhr district during the past decade. Methane is still released from abandoned mines, although the termination of forced ventilation and backfilling of shafts have largely prevented it, so that only barometric gas release will take place. This project started by identifying the relevant influencing factors of gas release from abandoned mines. Knowledge of residual gas volumes and cavity volumes is of prime importance. For an exemplary coal mine in the central Ruhr district, the remaining coal and gas volumes were estimated in order to calculate residual gas emissions. Gas flow underground and to the surface is governed by available flow paths and obstacles. For this reason, the flow resistance of dams, backfilled shafts and ventilation lines was measured, and fundamental studies on permeability of the top rock were carried out. The influence of technical pressure sinks (blowers, gas removal) on underground gas flow was investigated. Finally, gas flow in different conditions was simulated by model calculations. (orig.) [German] Der aktive Steinkohlenbergbau im Ruhrrevier hat sich sowohl durch Zusammenfuehrung von einzelnen Bergwerken zu Verbundbergwerken als auch durch Anschlussbergwerke flaechenmaessig in noerdlicher Richtung weiter ausgedehnt. Zwangslaeufig folgte eine Zunahme stillgelegter Feldesteile, in denen auch nach Beendigung des Abbaus weiterhin eine Methanabgabe des Gebirges stattfindet. Durch das Beenden der technischen Zwangsbelueftung (=Bewetterung) und Verfuellen der Schaechte wird das kontrollierte Abstroemen des Gases zur Tagesoberflaeche allerdings weitgehend unterbunden. Zu Beginn des Vorhabens stand die Erkundung und Untersuchung der fuer die Ausgasung aus stillgelegten Bereichen relevanten Einflussgroessen im Mittelpunkt. Da nach der Schliessung von Bergwerken nur noch eine barometrische Ausgasung vorhanden ist, ist die Kenntis von Restgasmengen und Hohlraumvolumina von vorrangiger Bedeutung. Daher wurden

  8. Ultraproducts of von Neumann algebras

    DEFF Research Database (Denmark)

    Ando, Hiroshi; Haagerup, Uffe

    2014-01-01

    this connection, we show that the ultraproduct action of the modular automorphism group of a normal faithful state φ of M   on the Ocneanu ultraproduct is the modular automorphism group of the ultrapower state (... that the ultrapower MωMω of a Type III0 factor is never a factor. Moreover we settle in the affirmative a recent problem by Ueda about the connection between the relative commutant of M   in MωMω and Connes' asymptotic centralizer algebra MωMω....

  9. Retrospective canine skin peripheral nerve sheath tumors data with emphasis on histologic, immunohistochemical and prognostic factors

    Directory of Open Access Journals (Sweden)

    Gisele S. Boos

    2015-12-01

    Full Text Available Abstract: In this retrospective study was determined the frequency of canine skin peripheral nerve sheath tumors (PNST in cases diagnosed by the Setor de Patologia Veterinária of the Universidade Federal do Rio Grande do Sul (SPV-UFRGS, Brazil, between the years 2000 and 2012. The canine profiles, as well as histological, immunohistochemical and prognostic aspects of the tumors were based on 70 samples, comprising 40 females, 29 males and one unspecified sample. Between 2000 and 2012, 2,984 skin tumors of dogs were diagnosed in the SPV-UFRGS, totaling 2.34% of skin neoplasms in dogs. Animals that comprised the largest amount of samples (43% were those with no breed (SRD, followed by German Shepherds (10%. Females were more affected than males (40/70 - 57% and 29/70 - 41% respectively. Skin PNST of this research showed predominant localization on the limbs (40% in the forelimbs and 29% in the hindlimbs; affecting adult dogs, mostly aged between 8 and 11 years (54%. The samples were routinely processed for hematoxylin and eosin, and were also evaluated by toluidine blue and Masson's trichrome staining, and immunohistochemistry (IHC anti-vimentin, -S-100, -GFAP, -actin, von Willebrand factor and neurofilament. Anisocytosis and anisokaryosis, mitotic index, intratumoral necrosis, invasion of adjacent tissues, tumor location, local recurrence and metastasis were related to the diagnosis of benign (49/70 or malignant tumor (21/70. The Antoni A histological pattern was observed more frequently in benign tumors. The immunohistochemistry helped to diagnose PNST, and anti-vimentin and anti-protein S-100 showed the highest rates of immunostaining. Throughout statistical analysis of animals with tumor recurrence, it was found that the chance of an animal with a malignant peripheral nerve sheath tumor to develop recurrence is 4.61 times higher than in an animal that had a benign tumor.

  10. [Hemostatic coronary risk factors in a healthy population of Maracaibo, Venezuela].

    Science.gov (United States)

    Diez-Ewald, María; Campos, Gilberto; Rivero, Francisco; Alvarez, Luis; Torres, Enrique; Arocha-Piñango, Carmen L; Ryder, Elena; Arteaga-Vizcaíno, Melvis; Vizcaíno, Gilberto; Fernández, Nelson

    2003-03-01

    The purpose of the present work was to determine the plasma concentrations of fibrinogen and Von Willebrand Factor (VWF) as well as platelet aggregation, in an apparently healthy population of 306 men and 41 women, 33 to 65 years of age, workers of the national oil industry (PDVSA, Maracaibo), as a base investigation in a 5-year prospective national collaborative study. The participants were previously subjected to a thorough clinical examination with cardiovascular evaluation and laboratory tests. Clottable fibrinogen and VWF concentrations were determined in platelet poor plasma, the last one by immunoclectrophoresis, and a multimeric analysis of VWF was performed on those plasmas with concentrations higher than 150 U/dL by SDS agarose electrophoresis, followed by cellulose membrane transference. Platelet aggregation was studied in platelet rich plasma with no addition of stimulants and after collagen and ristocetin were added. Forty per cent of men and 65.8% of women, showed fibrinogen concentrations above 300 mg/dL (p < 0.01) and 12.2% of men and 15.4% of women had VWF values higher than 150 U/dL, with normal multimeric distribution. Fourteen individuals presented spontancous platelet aggregation and increased aggregation in 12 and 13 of them, after induction with collagen and ristocetin respectively. Comparing these findings with those of previous collaborative studies from other countries, the present results could mean that an important proportion of the population here studied, could be at risk for a future coronary event; however, as these are the base findings in Maracaibo, the significance of our results will be better evaluated at the end of the five year study.

  11. Endothelial cell processing and alternatively spliced transcripts of factor VIII: potential implications for coagulation cascades and pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Claire L Shovlin

    Full Text Available BACKGROUND: Coagulation factor VIII (FVIII deficiency leads to haemophilia A. Conversely, elevated plasma levels are a strong predictor of recurrent venous thromboemboli and pulmonary hypertension phenotypes in which in situ thromboses are implicated. Extrahepatic sources of plasma FVIII are implicated, but have remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemistry of normal human lung tissue, and confocal microscopy, flow cytometry, and ELISA quantification of conditioned media from normal primary endothelial cells were used to examine endothelial expression of FVIII and coexpression with von Willebrand Factor (vWF, which protects secreted FVIII heavy chain from rapid proteloysis. FVIII transcripts predicted from database mining were identified by RT-PCR and sequencing. FVIII mAb-reactive material was demonstrated in CD31+ endothelial cells in normal human lung tissue, and in primary pulmonary artery, pulmonary microvascular, and dermal microvascular endothelial cells. In pulmonary endothelial cells, this protein occasionally colocalized with vWF, centered on Weibel Palade bodies. Pulmonary artery and pulmonary microvascular endothelial cells secreted low levels of FVIII and vWF to conditioned media, and demonstrated cell surface expression of FVIII and vWF Ab-reacting proteins compared to an isotype control. Four endothelial splice isoforms were identified. Two utilize transcription start sites in alternate 5' exons within the int22h-1 repeat responsible for intron 22 inversions in 40% of severe haemophiliacs. A reciprocal relationship between the presence of short isoforms and full-length FVIII transcript suggested potential splice-switching mechanisms. CONCLUSIONS/SIGNIFICANCE: The pulmonary endothelium is confirmed as a site of FVIII secretion, with evidence of synthesis, cell surface expression, and coexpression with vWF. There is complex alternate transcription initiation from the FVIII gene. These findings provide a

  12. Hypoxia, leptin, and vascular endothelial growth factor stimulate vascular endothelial cell differentiation of human adipose tissue-derived stem cells.

    Science.gov (United States)

    Bekhite, Mohamed M; Finkensieper, Andreas; Rebhan, Jennifer; Huse, Stephanie; Schultze-Mosgau, Stefan; Figulla, Hans-Reiner; Sauer, Heinrich; Wartenberg, Maria

    2014-02-15

    The plasticity of human adipose tissue-derived stem cells (hASCs) is promising, but differentiation in vitro toward endothelial cells is poorly understood. Flow cytometry demonstrated that hASCs isolated from excised fat tissue were positive for CD29, CD44, CD70, CD90, CD105, and CD166 and negative for the endothelial marker CD31, and the hematopoietic cell markers CD34 and CD133. hASCs differentiated into adipocytes after cultivation in adipogenic medium. Exposure of hASCs for 10 days under hypoxia (3% oxygen) in combination with leptin increased the percentage of CD31(+) endothelial cells as well as CD31, VE-Cadherin, Flk-1, Tie2, von Willebrand factor, and endothelial cell nitric oxide synthase mRNA expression. This was enhanced on co-incubation of vascular endothelial growth factor (VEGF) and leptin, whereas VEGF alone was not sufficient. Moreover, hASCs cultured on a matrigel surface under hypoxia/VEGF/leptin, showed a stable branching network. Hypoxic conditions significantly decreased apoptosis as evaluated by cleaved caspase-3, and increased prolyl hydroxylase domain 3 mRNA expression. Hypoxia increased expression of VEGF as well as leptin transcripts, which were significantly inhibited on co-incubation with either VEGF or leptin or a combination of both. Furthermore, leptin treatment of hypoxic cells increased the expression of the long/signaling form of the leptin receptor (ObRL), which was augmented on co-incubation with VEGF. The observed endothelial differentiation was dependent on the Akt pathway, as co-administration with Akt inhibitor abolished the observed effects. In conclusion, our data demonstrate that hASCs can be efficiently differentiated to endothelial cells by mimicking the hypoxic and pro-angiogenic microenvironment of adipose tissue.

  13. Immunohistochemical expression of vascular endothelial growth factor and matrix metalloproteinase-9 in radicular and residual radicular cysts

    Directory of Open Access Journals (Sweden)

    Patrícia Alvarez Ruiz

    2010-12-01

    Full Text Available OBJECTIVE: This study assessed and compared the immunoexpression of vascular endothelial growth factor (VEGF and matrix metalloproteinase-9 (MMP-9 in radicular cysts (RCs and residual radicular cysts (RRCs, relating them to the angiogenic index and the intensity of the inflammatory infiltrate. MATERIAL AND METHODS: Twenty RCs and 10 RRCs were evaluated by immunohistochemistry using anti-VEGF and anti-MMP-9 antibodies. The angiogenic index was determined by microvessel count (MVC using anti-von Willebrand factor antibody. RESULTS: The expression of both VEGF and MMP-9 was higher in RCs than in RRCs. RCs and RRCs presented strong epithelial expression of VEGF, irrespective of the intensity of the inflammatory infiltrate. Lesions with strong expression of MMP-9 showed significantly higher number of immunopositive cells for VEGF (p<0.05 and higher MVC (p<0.05. Lesions with dense inflammatory infiltrate exhibited significantly higher MVC (p<0.05 and higher number of immunopositive cells for VEGF (p<0.05. There was a positive correlation between both MVC (p<0.05 and the quantity of immunopositive cells for VEGF (p<0.05, with intensity of the inflammatory infiltrate. In addition, it was observed a positive correlation between the number of immunopositive cells for VEGF and MVC (p<0.05. CONCLUSIONS: VEGF and MMP-9 might play important roles in the angiogenesis in RCs and RRCs. In these lesions, the expression of these molecules and the MVC is closely related to the intensity of the inflammatory infiltrate. The expression of VEGF in the epithelial lining of RCs and RRCs might be important for the enlargement of these lesions.

  14. Wir zeigen andere Bilder von Frauen ...

    Directory of Open Access Journals (Sweden)

    Bettina Rulofs

    2010-03-01

    Full Text Available Der vorliegende Beitrag beleuchtet die Bedeutung der Geschlechterordnung im Prozess der sportmedialen Kommunikation. Im Kern geht es um die Frage, inwiefern im Prozess der medialen Vermittlung von Sport traditionelle Geschlechterstereotype aufrechterhalten werden oder Möglichkeiten der Irritation solcher Stereotype bestehen. Dazu werden verschiedene Ebenen des massenmedialen Kommunikationsprozesses in den Blick genommen: die Medienprodukte, die Öffentlichkeitsarbeit und Selbst-Präsentation der Sportler/innen, die Medienrezeption und die Herstellungsprozesse von Medien in den Sportredaktionen. This article illustrates the relevance of gender in processes of sports media communication. The question in focus is in what way traditional gender stereotypes are perpetuated in the process of media communication in sport and how such stereotypes can be irritated. Therefore different levels of mass media communication are considered: the media products, the public relations of athletes and the presentation of themselves as athletes, the media-reception and the production processes in sport departments of media institutions.

  15. Von Neumann's Quantization of General Relativity

    CERN Document Server

    Arbuzov, A B; Cirilo-Lombardo, D J; Nazmitdinov, R G; Han, Nguyen Suan; Pavlov, A E; Pervushin, V N; Zakharov, A F

    2015-01-01

    Von Neumann's procedure is applied for quantization of General Relativity. We quantize the initial data of dynamical variables at the Planck epoch, where the Hubble parameter coincides with the Planck mass. These initial data are defined via the Fock simplex in the tangent Minkowskian space-time, the Dirac conformal interval. The Einstein cosmological principle is applied for the average of the spatial metric determinant logarithm over the spatial volume of the visible Universe. We derive the splitting of the general coordinate transformations into the diffeomorphisms (as the object of the second Noether theorem) and the initial data transformations (as objects of the first Noether theorem). Following von Neumann, we suppose that the vacuum state is a quantum ensemble. The vacuum state is degenerated with respect to quantum numbers of non-vacuum states with the distribution function that yields the Casimir effect in gravidynamics in analogy to the one in electrodynamics. The generation functional of the pertu...

  16. Integrales Lernen in und von Organisationen

    Directory of Open Access Journals (Sweden)

    Wendelin Kupers

    2006-06-01

    Full Text Available Bezogen auf das integrale Models von Ken Wilber untersucht der Beitrag die Bedeutung des Lernens in und von Organisationen. Nach einer Darstellung der Relevanz und des Grundverständnisses des Lernens im Organisationskontext, werden integrale Dimensionen des Lernens dargestellt. Im Einzelnen werden die verschiedenen Sphären eines inneren-subjektiven und äusseren-„objektiven“ Lernens des Einzelnen als auch ein gemeinschaftliches Lernen und Lernen im System auf der kollektiven Ebene dargestellt sowie deren interrelationaler Zusammenhang diskutiert. Schließlich beschreibt der Beitrag noch integrale Lernprozesse sowie integrale Gestaltungsfelder zur Förderung des Lernens in den verschiedenen Bereichen. Abschließend spricht der Artikel noch Schwierigkeiten und Probleme an sowie nimmt im Fazit ein perspektivischen Ausblick vor.

  17. NOTIZ USER EIN GNETUM VON BORNEO

    Directory of Open Access Journals (Sweden)

    Fr. Markgraf

    2015-11-01

    Full Text Available Diese Varietat, die ich friiher nach unvollstandigem Material zu G. diminutum gerechnet habe, besitzt in beiden Geschlechtern verzweigte Blutenstande. Dieses Merkmal kommt in der Gruppe mit sitzenden Fruch-ten (Subsection Sessiles nur bei G. leptostachyum, vor, zu dem auch die Friichte der neuen Varietat gut passen. Sie ist eine Nebelwaldpflanze grosserer Hohen und hat bei reduzierten Massen der Blatter und Bliitenstande die schmalen, kurzen mannlichen Katzchen der Tieflands-Varietat leptostachyum mit den kurzgliedrigen, grossfriichtigen weiblichen Bluten-standen der Tieflands-Varietat robustum vereinigt. In Indochina und Siam lebt eine zweite Berg-Varietat — entsprechend der weiteren Ent-fernung vom Aquator in etwas geringeren Hohen die umgekehrt die dicken mannlichen Katzchen von der Varietat robustum mit den lang-gliedrigen weiblichen Bliitenstanden von der Varietat leptostachyum vereinigt. In beiden Fallen sind die Verkiirzungs- und Verlangerungs-Tenden-zen bei den Berg-Varietaten starker als bei denen des Tieflandes.

  18. Evolution equations of von Karman type

    CERN Document Server

    Cherrier, Pascal

    2015-01-01

    In these notes we consider two kinds of nonlinear evolution problems of von Karman type on Euclidean spaces of arbitrary even dimension. Each of these problems consists of a system that results from the coupling of two highly nonlinear partial differential equations, one hyperbolic or parabolic and the other elliptic. These systems take their name from a formal analogy with the von Karman equations in the theory of elasticity in two dimensional space. We establish local (respectively global) results for strong (resp., weak) solutions of these problems and corresponding well-posedness results in the Hadamard sense. Results are found by obtaining regularity estimates on solutions which are limits of a suitable Galerkin approximation scheme. The book is intended as a pedagogical introduction to a number of meaningful application of classical methods in nonlinear Partial Differential Equations of Evolution. The material is self-contained and most proofs are given in full detail. The interested reader will gain a ...

  19. Measurements of emission rates of hydrocarbons from sunflower as a function of temperature, light intensity and stress (ozone levels); Bestimmung von Emissionsraten pflanzlicher Kohlenwasserstoffe bei Sonnenblumen in Abhaengigkeit von Temperatur, Lichtintensitaet und Stress, insbesondere von der Belastung mit Ozon

    Energy Technology Data Exchange (ETDEWEB)

    Schuh, G.; Wildt, J.; Kley, D.

    1996-08-01

    The emission rates of isoprene, mono- and sesquiterpenes from sunflower (Helianthus annuus L. cv. giganteus) were determined in an environmental chamber, a continuously stirred tank reactor. {alpha}-pinene, {beta}-caryophyllene and two oxygenated compounds were emitted. The emission rates of all terpenes increased exponentially with temperature. Substance specific differences of the rate of increase of the emission rates were observed. For all substances the dependence of their emission rates on temperature increased with increasing light intensity. Increasing lightflux resulted in an increase of the emission rates for all substances. The raise of emission rates with lightflux was dependent on temperature and increased with increasing temperature. During periods without plant stress the emission rates exhibited a good correlation with the rate of transpiration as well as with the rate of net photosynthesis. Sunflowers emitted higher amounts of terpenes when they were stressed by mechanical, wounding and ozone treatment as well as nutrient- or water deficiency. The emission rates increased by a factor of 5-300. Exposure with ozone had an effect on hydrocarbon emission rates with a delay-time. 3-4 h after exposure with 25-120 ppb ozone the emission rates increased by factor of 5-100. This increase was only observed on the first day of exposure. Nutrient deficiency resulted in an increase of emission rates by a factor of 10-300. In situations of mechanical, wounding and ozone stress, substance specific changes in the emission spectrum were observed. A model was developed to explain the observed phenomena. The main pathway of ozone loss in the chamber is caused by the uptake through the stomata of the plants. However, up to 50% of the ozone loss must be explained by other processes indirectly caused by the plants. (orig./MG) [Deutsch] In Laborversuchen wurden Emissionsraten biogener Kohlenwasserstoffe von Sonnenblumen gemessen. Die groessten Emissionsraten wiesen die

  20. Metabolisierung von Lebensmittelinhaltsstoffen im simulierten Verdauungsmodell

    OpenAIRE

    Hageböck, Martin

    2013-01-01

    Mit Hilfe eines in vitro Modells, basierend auf 4 hintereinander geschalteten Bioreaktoren, war es möglich, komplexe Vorgänge der Verdauung modellhaft nachzustellen. Somit konnte die stufenweise Metabolisierung von ausgewählten Lebensmittelinhaltsstoffen unter definierten physikochemischen, enzymatischen und mikrobiellen Bedingungen der einzelnen Verdauungsstufen verfolgt werden. Beim Einsatz der polyphenolischen Reinsubstanzen wurden zunächst charakteristische Abbaureaktionen wie Hydrolyse v...

  1. La Medea de Lars von Trier

    Directory of Open Access Journals (Sweden)

    Iratxe Fresneda Delgado

    2013-04-01

    Full Text Available El presente artículo analiza el modo en el que Lars von Trier recrea para el cine el estereotipo de Medea. Mediante el análisis fílmico de la película y apoyándose en los estudios culturales, el texto se interroga acerca de la importancia y el poder potencial del cine a la hora recuperar el antiguo mito y demostrar su vigencia. El análisis amplía horizontes para la compresión de los mecanismos que articulan el entramado de significados de la película, donde Von Trier aporta una nueva visión del arquetipo de Medea uniéndola, a la tradición pictórica del Romanticismo. Una influencia que habita en las posteriores obras del director danés, donde el paisaje, la naturaleza, se erige en elemento catalizador de las pulsiones humanas, en su cómplice y testigo.This paper explores the way that Lars von Trier’s film recreates the stereotype of Medea. Using film analysis and based on cultural studies the article asks about the importance and potential power of cinema to recover the ancient myth and show their effects. The analysis expands horizons for the understanding of the mechanisms that link the network of meanings of the film, where the author offers a new vision of Medea's archetype attaching it to the pictorial tradition tied to the Romanticism. An influence that can be seen in the later works of Lars von Trier, where the landscape, the nature, stands as a catalyst of human drives, as his accomplice and witness.

  2. Diskretfrequente Synthese von Nachhall-Prozessen

    OpenAIRE

    Boesnecker, Robert

    2008-01-01

    Die Arbeit verfolgt einen neuartigen Ansatz zur digitalen Nachhallsynthese. Es wird dabei von folgender Beobachtung ausgegangen: Ruft man in ein Klavier, dessen Saiten unbedämpft sind, so antwortet das Instrument mit einem aus diskreten Einzeltönen bestehenden Nachklang, der ähnlich wie ein raumakustischer Nachhall klingt. Verbreitert man bei einer diskretfrequenten Synthese nun die spektrale Breite eines jeden "Klaviertons" auf einen schmalbandigen Bandpass, so dass nicht 12 Töne, sondern 12...

  3. Von Medien, Übertragungen und Automaten

    Directory of Open Access Journals (Sweden)

    Alessandro Barberi

    2013-12-01

    Full Text Available Im Zuge der Debatten zum Medialen Habitus wurde vielfach betont, dass die >Theorie der Praxispraxeologischen Medientheorie< des Medialen Habitus avant la lettre gesprochen werden kann. Dieser Artikel untersucht – ausgehend von den Debatten zur "Medienkompetenz" – wie Bourdieu Sprache, Sprechen und Diskurs, sowie Akteure, Felder und Habitus als Medien begreift und betont dabei die Nützlichkeit der Bourdieuschen Bildungssoziologie im Rahmen einer sozialwissenschaftlichen Grundlegung der Medienpädagogik.

  4. Bettina von Zwehl: Made up Love Song

    OpenAIRE

    Brown, Camilla

    2012-01-01

    This article considers an exhibition of work made whilst the artist Bettina von Zwehl was on a residency at the Victoria and Albert Museum London. Influenced by their miniature collection she made a new series of work and for the first time made one longer series of work with the same person. This essay considers how this development evolved from the artist's previous practice over a period of 10 years.

  5. Herstellung von Chitosan und einige Anwendungen

    Science.gov (United States)

    Struszczyk, Marcin Henryk

    2001-05-01

    1. Die Deacetylierung von crabshell - Chitosan führte gleichzeitig zu einem drastischen Abfall der mittleren viscosimetrischen Molmasse ( Mv), insbesondere wenn die Temperatur und die Konzentration an NaOH erhöht werden. Diese Parameter beeinflussten jedoch nicht den Grad der Deacetylierung (DD). Wichtig ist jedoch die Quelle des Ausgangsmaterials: Chitin aus Pandalus borealis ist ein guter Rohstoff für die Herstellung von Chitosan mit niedrigem DD und gleichzeitig hoher mittlerer Mv, während Krill-Chitin (Euphausia superba) ein gutes Ausgangsmaterial zur Herstellung von Chitosan mit hohem DD und niedrigem Mv ist. Chitosan, das aus Insekten (Calliphora erythrocephala), unter milden Bedingungen (Temperatur: 100°C, NaOH-Konzentration: 40 %, Zeit: 1-2h ) hergestellt wurde, hatte die gleichen Eigenschaften hinsichtlich DD und Mv wie das aus Krill hergestellte Chitosan. Der Bedarf an Zeit, Energie und NaOH ist für die Herstellung von Insekten-Chitosan geringer als für crabshell-Chitosan vergleichbare Resultaten für DD und Mv. 2. Chitosan wurde durch den Schimmelpilz Aspergillus fumigatus zu Chitooligomeren fermentiert. Die Ausbeute beträgt 25%. Die Chitooligomere wurden mit Hilfe von HPLC und MALDI-TOF-Massenspektrmetrie identifiziert. Die Fermentationsmischung fördert die Immunität von Pflanzen gegen Bakterien und Virusinfektion. Die Zunahme der Immunität schwankt jedoch je nach System Pflanze-Pathogen. Die Fermentation von Chitosan durch Aspergillus fumigatus könnte eine schnelle und billige Methode zur Herstellung von Chitooligomeren mit guter Reinheit und Ausbeute sein. Eine partiell aufgereinigte Fermentationsmischung dieser Art könnte in der Landwirtschaft als Pathogeninhibitor genutzt werden. Durch kontrollierte Fermentation, die Chitooligomere in definierter Zusammensetzung (d.h. definierter Verteilung des Depolymerisationsgrades) liefert, könnte man zu Mischungen kommen, die für die jeweilige Anwendung eine optimale Bioaktivität besitzen. 3

  6. Optimierung von Mehrkörpersystemen

    OpenAIRE

    Theis, Winfried; Räbiger, Klaus

    2009-01-01

    Auf Grund der ständig steigenden Anforderungen während der Entwicklung neuartiger Produkte ist es oftmals schwierig einen optimalen Entwurf zu finden. Die vorliegende Arbeit soll deshalb einen Einblick in die Welt der mathematischen Optimierung geben und anhand von ausgewählten Beispielen aus der Mehrkörperdynamik die nötigen Schritte einer Optimierungsrechnung genauer erklären. Spezielle Aufmerksamkeit wird hierbei der Ermittlung der Bewegungsgleichungen, der Formulierung der Optimierungsauf...

  7. Influence of region and site-specific factors on the degree of general validity of ecological and primary-energy-related assessments of biogas; Einfluss regionaler und standortspezifischer Faktoren auf die Allgemeingueltigkeit oekologischer und primaerenergetischer Bewertungen von Biogas

    Energy Technology Data Exchange (ETDEWEB)

    Dressler, Daniela

    2015-11-01

    As described in this publication, since the early 1990s numerous studies based on the life cycle assessment methodology have been dedicated to assessments of different kinds of bioenergy in comparison with fossil energy resources in terms of their energy balance and environmental impact. On reviewing the results of these studies one finds a strikingly wide range of variation. One major factor of influence on the results of life cycle assessments, besides methodological factors such as the choice of allocation method, is the representativeness of the data used. Thus, widely varying results are also obtained when balance calculations and assessments are performed on energy crops with due consideration to regional and site-specific factors. To address this problem the present study endeavoured to identify region and site-specific factors and assess them in terms of their influence on the life cycle assessment of the cultivation and conversion to biogas of different kinds of energy crops. For this purpose the following questions were explored: What influence do region, site and equipment-specific factors have on the results of ecological and primary-energy-related assessments; and how large are the differences in results between region and site-specific assessments on the one hand and assessments based on general assumptions on the other? It transpires that the results of region and site-specific assessments differ from one another in terms of both the assessment of energy cropping and the assessment of the entire process chain of biogas production and conversion to electricity.

  8. Mechthild von Lutzau: Schulleiterinnen. Opladen u.a.: Verlag Barbara Budrich 2008

    Directory of Open Access Journals (Sweden)

    Sandra Struthmann

    2009-03-01

    Full Text Available Als eine der ersten empirischen Studien zur Thematik in Deutschland untersucht die Arbeit von Mechthild von Lutzau den biographischen Prozess des Aufstiegs von Schulleiterinnen. Sozialisationsfaktoren, Unterstützungssysteme und Leistungsbereitschaft werden ebenso wie Hindernisse in Interviews erfasst. Ergebnisse sind unter anderem, dass Motivationen zum Aufstieg oft schon in der Kindheit gelegt sein können, dass die für Frauen typischen Brüche im Lebenslauf durchaus nicht immer hinderlich sein müssen und dass schließlich Schulleiterinnen neue Formen der Kooperation begründen können.Mechthild von Lutzau presents an empirical study on the biographical process that takes place in the professional advancement of heads of school, one of the first on this topic in Germany. Interviews capture socialization factors, support systems, and motivation as well as barriers. Results of this study include the possibility that motivations for promotion are already solidified in childhood, that typical interruptions in women’s résumés must not always be obstructive, and finally that heads of school can establish new forms of cooperation.

  9. Katheterablation von Vorhofflimmern - Neue Technologien und Strategien

    Directory of Open Access Journals (Sweden)

    Rolf S

    2011-01-01

    Full Text Available Die Katheterablation von symptomatischem Vorhofflimmern hat sich zu einem Therapieverfahren mit reproduzierbaren Erfolgsraten und überschaubarem Risiko bei selektierten Patientenkollektiven entwickelt. Hinsichtlich der Effektivität ist sie der Antiarrhythmika-Therapie schon heute überlegen. Die Verfahrenstechnik wird stetig weiterentwickelt, um die langfristige Erfolgsrate zu erhöhen, die Rate an Re-Interventionen zu reduzieren, die Komplikationsraten zu senken, die Prozedur selber zu vereinfachen und die Prozedurzeit zu verkürzen. Beispiele für solche Neuerungen sind die zielorientierte CT-Integration in elektro-anatomische Mappingsysteme, die optimierte Schaffung und Validierung linearer Läsionen mit der Pace-and-Ablate-Strategie, der effizientere Energietransfer ins Gewebe durch Verwendung steuerbarer transseptaler Schleusen und Berücksichtigung des elektrischen Kontaktes, sowie die strategische Planung von Linienkonzepten bei atrialen Makro-Reentry-Tachykardien durch Erstellung farbkodierter Entrainment- Maps. Diese Behandlungsinnovationen haben sich als wirkungsvoll erwiesen und in den vergangenen Jahren Einzug in den klinischen Alltag der Katheterablation von Vorhofflimmern im Herzzentrum Leipzig gefunde

  10. Engagement und Beanspruchung von Lehrpersonen in der Phase des Berufseintritts

    OpenAIRE

    Affolter-Huber, Benita Barbara

    2017-01-01

    Die Dissertation untersucht die Entstehung von Engagement und Beanspruchung von Lehrpersonen am Übergang von der Ausbildung in den Beruf. Das Job Demands-Resources Modell wird durch die Lern- und Vermeidungsleistungszielorientierung, die allgemeine Selbstwirksamkeits- sowie die Lehrerselbstwirksamkeitserwartung, die Extraversion und den Neurotizismus ergänzt und empirisch mittels Pfadanalysen geprüft. Aus den Befunden geht hervor, dass das Engagement und die Beanspruchung durch unterschiedlic...

  11. Studien zur Kinetik der Fehlfaltung un Aggregation von Proteinen

    OpenAIRE

    Modler, Andreas Johannes

    2003-01-01

    Diese Arbeit befasst sich mit der Kinetik der Fehlfaltung und Aggregation von Proteinen. Anhand dreier Beispiele, der Phosphoglyceratkinase (PGK) aus Hefe, einer Variante von Barstar und des Prion-Proteins des Syrischen Hamsters (SHaPrP(90-232)) wurde insbesondere die Kinetik der Bildung von Amyloidfibrillen und deren kinetischer Vorläuferstrukturen mittels dynamischer und statischer Lichtstreuung, Circulardichroismus, Infrarotspektroskopie, Elektronenmikroskopie und teilweise analytischer Ch...

  12. From regular modules to von Neumann regular rings via coordinatization

    Directory of Open Access Journals (Sweden)

    Leonard Daus

    2014-07-01

    Full Text Available In this paper we establish a very close link (in terms of von Neu- mann's coordinatization between regular modules introduced by Zel- manowitz, on one hand, and von Neumann regular rings, on the other hand: we prove that the lattice L^{fg}(M of all finitely generated submodules of a finitely generated regular module M, over an arbitrary ring, can be coordinatized as the lattice of all principal right ideals of some von Neumann regular ring S.

  13. Thomas-Fermi-von Weizsaecker theory of atoms and molecules

    Energy Technology Data Exchange (ETDEWEB)

    Benguria, R.; Brezis, H.; Lieb, E.H.

    1981-11-02

    We place the Thomas-Fermi-von Weizsaecker model of atoms on a firm mathematical footing. We prove existence and uniqueness of solutions of the Thomas-Fermi-von Weizsaecker equation as well as the fact that they minimize the Thomas-Fermi-von Weizsaecker energy functional. Moreover, we prove the existence of bindings for two very dissimilar atoms in the frame of this model.

  14. Portrait of Dr. Von Braun with Walt Disney, 1954.

    Science.gov (United States)

    1954-01-01

    Marshall Center Director Dr. Wernher Von Braun is pictured with Walt Disney during a visit to the Marshall Space Flight Center in 1954. In the 1950s, Dr. Von Braun while working in California on the Saturn project, also worked with Disney studios as a technical director in making three films about Space Exploration for television. Disney's tour of Marshall in 1965 was Von Braun's hope for a renewed public interest in the future of the Space Program at NASA.

  15. Saage tuttavaks : Elisabeth ja Karl von Hoerschelmann / Mai Levin

    Index Scriptorium Estoniae

    Levin, Mai, 1942-

    2004-01-01

    Kuraator M. Levin kuni 10. X 2004 Adamson-Ericu muuseumis avatud näitusest "Tuntud ja tundmatud Elisabeth von Rosendorff-Hoerschelmann ja Karl von Hoerschelmann". Enamik töid on kunstnike laste Konstantin Hoerschelmanni ja Anna Röder-Hoerschelmanni omand. Elisabeth Rosendorff (1898-1984) sündis Virumaal Maidlas eesti perekonnas, Karl von Hoerschelmann (1899-1951) Sevastoopolis saksa perekonnas

  16. Saage tuttavaks : Elisabeth ja Karl von Hoerschelmann / Mai Levin

    Index Scriptorium Estoniae

    Levin, Mai, 1942-

    2004-01-01

    Kuraator M. Levin kuni 10. X 2004 Adamson-Ericu muuseumis avatud näitusest "Tuntud ja tundmatud Elisabeth von Rosendorff-Hoerschelmann ja Karl von Hoerschelmann". Enamik töid on kunstnike laste Konstantin Hoerschelmanni ja Anna Röder-Hoerschelmanni omand. Elisabeth Rosendorff (1898-1984) sündis Virumaal Maidlas eesti perekonnas, Karl von Hoerschelmann (1899-1951) Sevastoopolis saksa perekonnas

  17. Sicherheitskriterien bei der Auswahl von ERP-Systemen

    OpenAIRE

    Wollersheim, Jan;Konstantinidis, Christos;Krcmar, Helmut

    2014-01-01

    Bei Auswahl und Anpassung von Software as a Service (SaaS) basierten ERP-Systemen (SaaS-ERP) kann auf bew?hrte und erprobte Kriterien zur?ckgegriffen werden. Dieser Beitrag strukturiert exemplarisch ausgew?hlte Sicherheits- und Risiko-Kriterien (S&R-Kriterien) anhand von f?nf Perspektiven. Dabei wird zuerst die Auswahl und im Folgenden die Anpassung von SaaS basierten ERP-Systemen betrachtet.

  18. Preiswettbewerb im deutschen Lebensmitteleinzelhandel: Empirische Analysen anhand von Scannerdaten

    OpenAIRE

    Hoffmann, Angela

    2012-01-01

    Der deutsche Lebensmitteinzelhandel ist durch eine hohe Konzentration und einen intensiven Preiswettbewerb gekennzeichnet. Ziel dieser Arbeit ist es, die Preissetzung von Discountern, Super- und Verbrauchermärkten unter Beachtung von Sonderangeboten und den daraus resultierenden Preiswettbewerb zu analysieren. Vier empirische Studien anhand von Scannerdaten werden durchgeführt. Es zeigt sich, dass das Ausmaß der Preissynchronisation bei Milchprodukten im deutschen Handel deutlich größer i...

  19. Solares Recyceln von Aluminium in einem direkt bestrahlten Drehrohrofen

    OpenAIRE

    Neises-von Puttkamer, Martina; Roeb, Martin; Beyer, T.; Reinhold, Jan Philipp; Willsch, Christian; Thelen, Martin; Raeder, Christian; Oliveira,Lamark de; TESCARI, Stefania; Breuer, Stefan; Sattler, Christian

    2016-01-01

    Das Aufschmelzen von Metallen ist ein energieintensiver Prozess, da hier hohe Temperaturen benötigt werden. Konventionell wird diese Energie mit fossilen Energieträgern zur Verfügung gestellt. Mit einem solaren Schmelzverfahren von Metallen können der Ausstoß von CO2 und die Energiekosten der Gießereien erheblich gesenkt werden. Insbesondere Länder mit hoher direkter Solarstrahlung wie Südafrika, können ein solches Verfahren zum Schmelzen und Wiederverwerten von Metallschrott einsetzten. ...

  20. Influence of S, P, C on grain boundary diffusion and creep properties of Alloy 800; Einfluss von S, P, C auf die Korngrenzendiffusion und Kriecheigenschaften von Alloy 800

    Energy Technology Data Exchange (ETDEWEB)

    Lindemann, J.; Hannesen, K.; Mast, R.; Viefhaus, H. [Max-Planck-Institut fuer Eisenforschung GmbH, Duesseldorf (Germany); Grabke, H.J.

    1998-12-31

    The paper reports examinations of Alloy 800 and specific commercially available variants known under the names of 800H, 800HT, and 800LC, differing in their concentrations of C, Al, and Ti. In addition, melts also containing phosphorus (0.09 wt-%) or sulfur (0.04 wt-%) as additional alloying materials have been prepared for the experiments. The volume diffusion and the grain boundary diffusion of {sup 59}Fe in those alloys was measured at temperatures between 800 and 1000 C by means of a radioactive tracer method combined with residual activity measurements. It was found that accompanying elements like phosphorus and sulfur increase the activation energy of the grain boundary diffusion of the iron and thus delay the grain boundary self-diffusion in Alloy 800. Creep curves were measured of the same materials after age-hardening treatment for 100 hours at 800 C, measurements performed at constant temperature but at three different, constant creep stress loads. The results showed that addition of phosphorus markedly increases the lifetime of Alloy 800, and reduces the creep rupture strain. The minimum strain rate in Alloy 800 containing 0.09 wt-% of phosphorus was found to be lower by a factor of 100, as compared to the other Alloy 800 materials used. (orig./CB) [Deutsch] Alloy 800 ist ein austenitischer Fe-Ni-Cr Stahl, der relativ geringe, aber wichtige Konzentrationen von Kohlenstoff, Aluminium und Titan enthaelt. Besondere Varianten von Alloy 800, bekannt als 800H, 800HT und 800LC, unterscheiden sich in den Konzentrationen dieser Elemente. Diese kommerziellen Legierungen wurden untersucht, und zusaetzlich wurden Schmelzen mit zulegiertem Phosphor (0,09 Gew-%) bzw. Schwefel (0,04 Gew-%) hergestellt. Mittels einer radioaktiven Tracermethode in Verbindung mit Restaktivitaetsmessungen wurde die Volumen- und Korngrenzendiffusion von {sup 59}Fe in diesen Legierungen im Temperaturbereich 800-1000 C gemessen. Es wurde gefunden, dass Begleitelemente wie Phosphor und

  1. Zielgerechte Logistikkonzepte in Betrachtung von LNG- Umschlageplätzen unter Berücksichtigung von Industrie 4.0

    OpenAIRE

    Jenne, Christian; Noche, Bernd

    2016-01-01

    Logistikkonzepte in der Spedition und Transportgewerbe spielen heutzutage eine immer wichtigere Rolle, um Lohnnebenkosten so niedrig wie möglich zu halten. Gerade in der Spedition entsteht ein Zusammenspiel aus zeitnaher Lieferung von Konsumgütern und Optimierung der Lagerhaltungskosten bei dem die modulare Integration von Logistik, Informationstechnischen Systemen und vernetzter Kommunikation eine ganz spezifische Rolle hat. Anbindung von der Industrie zum Kunden wird dadurch immer mehr vers...

  2. WIE PREISSENSIBEL REAGIEREN DEUTSCHE VERBRAUCHER? AKTUELLE SCHÄTZUNGEN VON PREIS- UND AUSGABENELASTIZITÄTEN AUF DER BASIS VON HAUSHALTSPANELDATEN

    OpenAIRE

    2012-01-01

    Der Beitrag untersucht das Nachfrageverhalten der deutschen Privathaushalte anhand von Daten zweier Haushaltspanels der Gesellschaft für Konsumforschung. Es wird ein Almost Ideal Demand System (AIDS) mit 13 Lebensmittelgruppen für den Zeitraum von 2004 bis 2008 geschätzt. Der Fokus der Analyse liegt auf den geschätzten Eigenpreis- und Ausga-benelastizitäten und deren Einordnung in die Literatur. Mit Ausnahme von Kaffee und Eiern zeigt sich die Nachfrage in allen Lebensmittelgruppen, darunter ...

  3. Produktion von pharmakologischen Sekundärmetabolite - Am Beispiel von mikrobiellen β-Lactam-Antibiotika und pflanzlichen Triterpenen

    OpenAIRE

    Ludwig, Benjamin

    2015-01-01

    Durch das Entstehen von neuen Infektionskrankheiten und das Auftreten von Resistenzen können bisher verwendete Medikamente ihren pharmazeutischen Nutzen verlieren. Daher ist eine konstante Weiterentwicklung von bioaktiven Pharmazeutika lebensrettend. Viele pflanzli-che und mikrobielle Sekundärmetabolite besitzen gesundheitsfördernde Wirkungen und kön-nen als Ressourcen für die Entwicklung neuer Arzneimittel herangezogen werden. Da Pflan-zen und Mikroorganismen ein sehr umfangreiches Repertoir...

  4. Assoziation des arteriellen Sauerstoffpartialdrucks mit dem Auftreten von Erythroblasten im peripheren Blut von Patienten einer chirurgischen Intensivstation

    OpenAIRE

    Kuert, Sandra

    2012-01-01

    Erythroblasten (EBL) treten im peripheren Blut eines gesunden Erwachsenen gewöhnlich nicht auf. Studien zeigten, dass das Auftreten von EBL bei hospitalisierten Patienten auf ein erhöhtes Mortalitätsrisiko hinweist. Die zugrundeliegenden Mechanismen sind bisher unbekannt. Es ergaben sich Hinweise, dass EBL bei Zuständen von Hypoxie und Inflammation auftreten. Die vorliegende Studie untersucht den Einfluss des arteriellen Sauerstoffpartialdruckes (pO2) auf das Auftreten von EBL ...

  5. Optimized detection and characterization of liver metastases. The role of current MRI contrast agents; Optimierte Detektion und Charakterisierung von Lebermetastasen. Leistungsvermoegen aktueller MRT-Kontrastmittel

    Energy Technology Data Exchange (ETDEWEB)

    Weinrich, J.M.; Well, L.; Bannas, P. [Universitaetsklinikum Hamburg-Eppendorf, Zentrum fuer Radiologie und Endoskopie, Klinik und Poliklinik fuer diagnostische und interventionelle Radiologie und Nuklearmedizin, Hamburg (Germany)

    2017-05-15

    Metastases are the most common malignant lesions of the liver. The presence of liver metastases is an important prognostic factor and is decisive for the further management, especially in patients with colorectal cancer. Detection and characterization of liver metastases as well as differentiation from benign lesions are of high importance and a daily challenge in clinical radiology. Contrast-enhanced magnetic resonance imaging (MRI) has the highest sensitivity in detecting liver metastases. The sensitivity of MRI has been further increased due to the development of liver-specific contrast agents. This article describes the role of extracellular and hepatobiliary contrast agents for the detection and characterization of liver metastases. Moreover, the current knowledge on safety, sequence optimization, transient severe dyspnea and the combination of hepatobiliary with intravascular contrast agents for liver imaging is discussed. (orig.) [German] Metastasen sind die haeufigsten malignen Leberlaesionen. Das Vorhandensein von Lebermetastasen ist entscheidend fuer die Prognose und weitere Therapieplanung von Tumorpatienten, insbesondere von Patienten mit kolorektalen Karzinomen. Die Detektion von Lebermetastasen sowie deren Unterscheidung von anderen Leberlaesionen sind daher von hoechster Bedeutung und stellen eine alltaegliche Herausforderung fuer den Radiologen dar. Die Bildgebung mit der hoechsten Sensitivitaet fuer die Detektion von Lebermetastasen stellt die dynamische kontrastmittelgestuetzte Magnetresonanztomographie (MRT) dar. Die bereits hohe Sensitivitaet der MRT wird durch den Einsatz leberspezifischer Kontrastmittel noch weiter gesteigert. Dieser Artikel beleuchtet die Rolle der aktuellen unspezifischen und leberspezifischen MRT-Kontrastmittel fuer die Detektion und Charakterisierung von Lebermetastasen. Weiterhin werden Erkenntnisse zur Sicherheit, Sequenzoptimierung, zu transienten Atemartefakten und zur Kombination von MRT-Kontrastmitteln fuer die

  6. Philologie im Horizont der Geschichtlichkeit von Sprache und Text: zum Tagungsband von Wulf Oesterreicher und Maria Selig

    Directory of Open Access Journals (Sweden)

    Olaf Müller

    2016-03-01

    Full Text Available Wulf Oesterreicher und Maria Selig, Hrsg., Geschichtlichkeit von Sprache und Text: Philologien – Disziplingenese – Wissenschaftshistoriographie (Paderborn: Wilhelm Fink, 2014, 332 S.

  7. Novel cryogenic Penning trap for the detection of spin transitions of a proton and determination of its g-factor; Neuartige kryogene Penning-Falle fuer den Nachweis von Spin-Uebergaengen eines Protons und Bestimmung seines g-Faktors

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho Rodegheri, Cricia de

    2014-07-31

    This thesis presents the design, development, commissioning and characterization of a novel Penning trap in the framework of the experiment for the direct Determination of the g-factor of a single proton. This trap is distinguished by the fact that the field lines of an external homogeneous magnetic field are distorted around the trap Center by means of a ferromagnetic ring electrode. The inhomogeneous part of the resulting magnetic field, the so-called magnetic bottle, can be quantified by the the coefficient B{sub 2}=297(10) mT/mm{sup 2} of the second-order term in the series expansion describing the field. Such an exceptionally strong field inhomogeneity is a fundamental prerequisite for the detection of the proton spin orientation via the continuous Stern-Gerlach effect. This effect is based upon the coupling of the spin degree of freedom of the trapped proton to one of its eigenfrequencies, which occurs in the presence of the inhomogeneous magnetic field. Thus, a transition between the spin states can be detected as a frequency jump. The measurable change in frequency is proportional to B{sub 2} and to the in the case of the Proton extremely small ratio between its magnetic moment and its mass. The technical challenges due to the needed high magnetic inhomogeneity require a well-founded understanding and control of the the properties of the Penning trap and experimental conditions. The Penning trap developed in the present work allowed the first non-destructive detection of spin quantum jumps of a single trapped proton, which represented a breakthrough in the experiment for the direct determination of the g-factor with the aimed relative uncertainty of 10{sup -9}. By means of a statistical method the Larmor and the cyclotron frequency of the proton could be measured in the inhomogeneous magnetic field of the trap, from which the g-factor could be determined with a relative uncertainty of 8.9 x 10{sup -6}.The experimental techniques and setup presented here can

  8. Influencing factors on the design, optimal operation as well as on maintenance strategies of devices under economic aspects; Einflussfaktoren auf das Design, den optimalen Betrieb sowie die Instandhaltungsstrategien von Anlagen unter wirtschaftlichen Gesichtspunkten

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Hans Christian; Harder, Hans-Otto [TUeV SUeD Industrie Service GmbH, Mannheim (Germany). Kraftwerks- und Anlagenservice

    2008-07-01

    There are many causes and mode of actions which result in damages and a reduction of the lifetime of process engineering plants. Here, planning, design, production, assembly, acceptance, operation and maintenance play an important role. These factors play an important role in the case of future expecting operation temperatures above 600 C. Under this aspect, the authors of the contribution under consideration present the changes which can be expected regarding to the design concepts and to the operationally enhanced operating stresses from the aspect of a certified supervisory board.

  9. Unterschiedliche beta-blockierende Wirkungen von Carvedilol, Metoprolol und Bisoprolol

    Directory of Open Access Journals (Sweden)

    Stoschitzky K

    2001-01-01

    Full Text Available Metoprolol und Bisoprolol sind beta1-selektive Beta-Blocker, Carvedilol ist ein nicht-selektiver Beta-Blocker mit zusätzlicher alpha1-blockierender Wirkung. Wir verglichen die Wirkungen von klinisch empfohlenen Dosen von Carvedilol (25, 50 und 100 mg, Metoprolol (50, 100 und 200 mg und Bisoprolol (2,5, 5 und 10 mg mit Placebo in einer randomisierten, überkreuzten, placebokontrollierten Doppelblind-Studie an 12 gesunden männlichen Freiwilligen. Zwei Stunden (Bisoprolol: drei Stunden nach oraler Applikation der jeweiligen Substanzen wurden arterieller Blutdruck und Herzfrequenz in Ruhe, nach 10 Minuten Belastung und nach weiteren 15 Minuten Erholung gemessen. Verglichen mit Placebo führten ansteigende Dosen von Metoprolol und Bisoprolol in Ruhe zu ansteigenden Wirkungen auf die Herzfrequenz (jeweils -13 %, -15 % und -18 % während ansteigende Dosen von Carvedilol abfallende Wirkungen zeigten (-13 %, -7 % und -3 %. Die Herzfrequenz unter Belastung wurde von Metoprolol (-21 %, -25 % und -24 %, Bisoprolol (-17 %, -21 % und -25 % und Carvedilol gesenkt (-16 %, -16 % und -18 %, die Wirkung von Metoprolol erschien dabei etwas ausgeprägter als jene von Carvedilol. Der systolische Blutdruck wurde sowohl von Metoprolol (-9 %, -16 %, -16 % unter Belastung und -7 %, -7 %, -9 % nach 15 min Erholung, Bisoprolol (-8 %, -12 %, -15 % unter Belastung als auch von Carvedilol (-7 %, -17 %, -20 % unter Belastung und -8 %, -11 %, -14 % nach 15 min Erholung deutlich gesenkt. Auf den diastolischen Blutdruck zeigten die Substanzen (mit Ausnahme von 50 und 100 mg Carvedilol in Ruhe jedoch keine signifikanten Wirkungen. Wir schließen aus unseren Ergebnissen, daß klinisch empfohlene Dosen von Carvedilol bei gesunden Freiwilligen klinisch relevante beta-blockierende Wirkungen nur unter Belastung zeigen, während die von Carvedilol bewirkte Beta-Blockade in Ruhe bestenfalls als schwach zu bezeichnen ist. Auf der anderen Seite zeigen Metoprolol und Bisoprolol sowohl in

  10. Von den Liven von Oesel / August Ludwig Schlözer

    Index Scriptorium Estoniae

    Schlözer, August Ludwig

    2008-01-01

    Avaldatud Eberhard Winkleri initsiatiivil A. L. Schlözeri teose põhjal: Gesammelte Nachrichten von den Ueberresten der Liven, in Livland und Kurland. (1770), mis moodustab osa teosest: Schlözer, August Ludwig. M. Johann Joseph Haigold's Beylagen zum Neuveränderten Russland. Zweiter Theil. Riga und Leipzig, 1770

  11. Ööklubi Club von Überlingen = Club von Überlingen

    Index Scriptorium Estoniae

    2008-01-01

    Ööklubi Club von Überlingen (Madara 22A, Tallinn) sisekujundusest. Sisearhitekt: Taavi Aunre (Boom.ee OÜ). Taavi Aunrest, tema tähtsamad tööd. I-II korruse plaan, 11 värv. vaadet, foto T. Aunrest

  12. Aino Lepik von Wiren / Aino Lepik von Wiren ; interv. Kadi Alatalu

    Index Scriptorium Estoniae

    Lepik von Wirén, Aino, 1961-

    2007-01-01

    Heinrich Marga eksiilvalitsuse (20.06.1990-7.10.1992) kohtuminister Aino Lepik von Wiren pagulaslapse elust Rootsis, haridusest ja elukutse valikust, tööst eksiilvalitsuses, tööleasumisest Eestisse 1992. aastal, seadusandlikust tegevusest ning aluse panekust välismaalaste- ja kodakondsuspoliitikale, naiste võimalustest poliitilisse tippu tõusmiseks, kodu- ja väliseestlaste vastandamisest

  13. Von den Liven von Oesel / August Ludwig Schlözer

    Index Scriptorium Estoniae

    Schlözer, August Ludwig

    2008-01-01

    Avaldatud Eberhard Winkleri initsiatiivil A. L. Schlözeri teose põhjal: Gesammelte Nachrichten von den Ueberresten der Liven, in Livland und Kurland. (1770), mis moodustab osa teosest: Schlözer, August Ludwig. M. Johann Joseph Haigold's Beylagen zum Neuveränderten Russland. Zweiter Theil. Riga und Leipzig, 1770

  14. Association analysis between endothelial function related factors and coronary artery stenosis degree in coronary heart disease patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Li, Quanmin; Zhang, Zhifang; Du, Ruiqin; Hu, Xiaoqiang; Yan, Yan; Gao, Qing; Fan, Yanting

    2012-01-01

    To investigate the relationship between soluble intercellular adhesion molecule (sICAM-1), vascular endothelial cell adhesion molecule (VCAM-1), monocytes chemotactic protein (MCP-1), von Willebrand factor (vWF), and coronary artery stenoses degree in coronary heart disease (CHD) within type 2 diabetes mellitus (T2DM) patients. A total of 92 subjects were treated with coronary angiography (CAG), including 62 subjects with CHD. The individuals were divided into three groups, group A (32 patients with CHD and T2DM), group B (30 patients with CHD but no T2DM) and group C (30 patients with no CHD and T2DM). All patients were treated with a Gensini coronary angiography check. The correlations between sICAM-1, VCAM-1, MCP-1 and vWF in peripheral blood and coronary artery stenosis degree were analyzed. The average score of coronary artery stenosis degree was 30.75 +/-12.67 in group A, which was significantly higher than group B (11.20 +/-7.51) and group C (2.40 +/- 1.23) (p coronary artery stenosis and the mean level of sICAM-1, VCAM-1, MCP-1, vWF in group A (p 0.05). Association analysis shown that the level of sICAM-1, VCAM-1, MCP-1 and vWF elevated in CHD with T2DM patients. Vascular endothelial dysfunction could be caused to the coronary artery stenosis pathophysiological process. Results from this study suggested that sICAM-1, VCAM-1, MCP-1 and vWF may contribute to the occurrence and development of vascular lesions in T2DM. These endothelial function related factors could be acceptable as a prediction and testing index of vascular complications in T2DM.

  15. Six amino acid residues in a 1200 A2 interface mediate binding of factor VIII to an IgG4κ inhibitory antibody.

    Directory of Open Access Journals (Sweden)

    Jasper C Lin

    Full Text Available The development of neutralizing anti-factor VIII (FVIII antibodies complicates the treatment of many hemophilia A patients. The C-terminal C2 domain is a particularly antigenic FVIII region. A crystal structure of recombinant FVIII-C2 bound to an Fab fragment of the patient-derived monoclonal antibody BO2C11, which recognizes an immunodominant inhibitor epitope on FVIII and blocks its ability to bind von Willebrand factor (VWF and phospholipids, revealed that 15 amino acids in FVIII contact this antibody. Forty-three recombinant FVIII-C2 proteins, each with a surface-exposed side chain mutated to alanine or another residue, were generated, and surface plasmon resonance studies were carried out to evaluate effects of these substitutions on BO2C11/FVIII-C2 binding affinity. Thermodynamic analysis of experiments carried out at three temperatures indicated that one beta hairpin turn at the antigen-antibody interface (FVIII-F2196, N2198, M2199 and F2200 plus two non-contiguous arginines (FVIII-R2215 and R2220, contributed appreciably to the affinity. B-domain-deleted (BDD FVIII-F2196A, FVIII-F2196K and FVIII-M2199A were generated and characterized. Their pro-coagulant activities and binding to VWF were similar to those of WT-BDD-FVIII, and FVIII-F2196K avoided neutralization by BO2C11 and murine inhibitory mAb 1B5. This study suggests specific sites for amino acid substitutions to rationally design FVIII variants capable of evading immunodominant neutralizing anti-FVIII antibodies.

  16. Correlation between expressions of hypoxia -inducible factor (HIF-1α, blood vessels density, cell proliferation, and apoptosis intensity in canine fibromas and fibrosarcomas

    Directory of Open Access Journals (Sweden)

    Madej Janusz A.

    2014-03-01

    Full Text Available The study aimed to demonstrate the expression of hypoxia-inducible factor (HIF-1α in soft tissue mesenchymal tumours (fibroma and fibrosarcoma in dogs. An attempt was made to correlate the obtained results with density of blood vessels (expression of von Willebrand Factor, vWF, expression of Ki-67 proliferation antigen, and with intensity of apoptosis in studied tumours. The study was performed on paraffin sections of 15 fibromas and 40 fibrosarcomas sampled from 55 female dogs aged 6 to 16 years. Immunohistochemical staining against HIF-1α, vWF, and Ki-67 was performed. Apoptosis was detected with the use of TUNEL reaction. A significantly higher HIF-1α expression was noted in fibrosarcomas in comparison to fibromas (P < 0.0001. HIF-1α expression in fibromas manifested strong positive correlation with tumour vascularity (r = 0.67, P = 0.007. Moreover, HIF-1α expression in fibrosarcomas manifested a moderate positive correlation with tumour malignancy grade (r = 0.44, P = 0.004, tumour vascularity (r = 0.52, P < 0.001, Ki-67 antigen expression (r = 0.42; P = 0.007, and TUNELpositive cells (r = 0.37, P = 0.017. Expression of HIF-1α was detected in 86.7% of fibroma type tumours and in 100% of fibrosarcomas. In all studied tumours expression of HIF-1α manifested positive correlation with the density of blood vessels, and in fibrosarcomas it correlated also with malignancy grade, intensity of Ki-67 expression, and with intensity of apoptosis in tumour cells.

  17. A single chain variant of factor VIII Fc fusion protein retains normal in vivo efficacy but exhibits altered in vitro activity.

    Directory of Open Access Journals (Sweden)

    Yang Buyue

    Full Text Available Recombinant factor VIII Fc (rFVIIIFc is a fusion protein consisting of a single B-domain-deleted (BDD FVIII linked recombinantly to the Fc domain of human IgG1 to extend half-life. To determine if rFVIIIFc could be further improved by maintaining the heavy and light chains within a contiguous single chain (SC, we evaluated the activity and function of SC rFVIIIFc, an isoform that is not processed at residue R1648. SC rFVIIIFc showed equivalent activity in a chromogenic assay compared to rFVIIIFc, but approximately 40% activity by the one-stage clotting assay in the presence of von Willebrand Factor (VWF, with full activity in the absence of VWF. Moreover, SC rFVIIIFc demonstrated markedly delayed thrombin-mediated release from VWF, but an activity similar to that of rFVIIIFc upon activation in FXa generation assays. Therefore, the apparent reduction in specific activity in the aPTT assay appears to be primarily due to delayed release of FVIII from VWF. To assess whether stability and activity of SC rFVIIIFc were affected in vivo, a tail vein transection model in Hemophilia A mice was utilized. The results demonstrated similar pharmacokinetic profiles and comparable efficacy for SC rFVIIIFc and rFVIIIFc. Thus, while the single chain configuration did not promote enhanced half-life, it reduced the rate of release of FVIII from VWF required for activation. This impaired release may underlie the observed reduction in the one-stage clotting assay, but does not appear to affect the physiological activity of SC rFVIIIFc.

  18. Die Felsfassadengräber von Kyrene

    OpenAIRE

    Greve, Anika

    2006-01-01

    Die griechische Kolonie Kyrene wurde im letzten Drittel des 7. Jhs. v. Chr. einige Kilometer vom Mittelmeer entfernt im libyschen Innenland gegründet. Die Siedler waren dorische Griechen aus Thera im Süden der Kykladen. Nicht nur die erhaltenen innerstädtischen Gebäude zeugen von einem einstigen Wohlstand, auch die Nekropole nahm im Laufe der Zeit gewaltige Ausmaße mit aufwendig gestalteten Grabanlagen an, die sich rund um die urbane Bebauung entlang der Ausfallstraßen ausbreitete. Viele Ruhe...

  19. Authentifizierung von Bio-Milch im Labor

    OpenAIRE

    2008-01-01

    In Deutschland ist die Nachfrage nach Bio-Lebensmitteln in den letzten Jahren stetig gestiegen. So erhöhte sich der Absatz von Bio-Trinkmilch in 2007 im Vergleich zum Vorjahr erneut kräftig um 34 Prozent (ZMP, Bonn) und der Bio-Anteil beträgt inzwischen bei Frischmilch knapp elf Prozent. Aufgrund sporadisch resultierender Lieferengpässe bei Bio-Milch sowie der vorhandenen Handelspreisdifferenz besteht zunehmend ein potenzielles Risiko der Falschdeklaration konventionell erzeugter Milch als Bi...

  20. Key contributors: Ernst von Glasersfeld's radical constructivism

    Science.gov (United States)

    Tobin, Kenneth

    2007-07-01

    This article reviews the significance of the contributions of Ernst von Glasersfeld to research in science education, especially through his theoretical contributions on radical constructivism. As a field shaper, Glasersfeld's subversive ideas catalyzed debate in the science education community and fuelled transformation of many facets including research methods, ways of thinking about teaching and learning, curriculum, and science teacher education. Perturbations emanating from the debates on constructivism forged new pathways that led to the development and use of many of the sociocultural frameworks employed by authors in Cultural Studies of Science Education.

  1. Synthese und Applikation von magnetisch verformbaren Hydrogelkompositen

    OpenAIRE

    Bolle, Jens

    2011-01-01

    Als „intelligent“ bezeichnete Materialien sind in der Lage, mit steuerbaren Form- oder Eigenschaftsänderungen auf Zielreize zu reagieren, ohne dafür einen zusätzlichen Sensor zu benötigen. Man bezeichnet sie daher auch als Sensor-Aktor-Systeme. Da sie ohne äußere Sensorsysteme auskommen, können diese Werkstoffe als kleine, einfach anwendbare und preisgünstige Bauteile für eine Vielzahl von Applikationen dienen. Ihre Entwicklung gestattet sowohl die fortschreitende Miniaturisierung tech-nische...

  2. Von Krahli Teater hakkab koolitama näitlejaid

    Index Scriptorium Estoniae

    2007-01-01

    Von Krahli Teater hakkab osalema järgmisel sügisel TÜ Viljandi Kultuuriakadeemia teatrikunsti erialale õppima asuvate tudengite koolitamises. Tudengeid hakkavad juhendama Von Krahli juht Peeter Jalakas, näitlejad Taavi Eelmaa ja Juhan Ulfsak, vene tantsija ja koreograaf Sasha Pepeljajev ning soome lavastaja Kristian Smeds

  3. Von Krahli teatris etenduvad Tõnu Kõrvitsa kammerooperid / Esme Kassak

    Index Scriptorium Estoniae

    Kassak, Esme

    2006-01-01

    20. apr. esietenduvad Von Krahli Teatris Peeter Jalaka lavastuses Tõnu Kõrvitsa uued kammerooperid "Tuleaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libretode autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  4. Von Krahli teater mängib Kõrvitsa kammeroopereid

    Index Scriptorium Estoniae

    2006-01-01

    20. apr. esietenduvad Von Krahli Teatris Peeter Jalaka lavastuses Tõnu Kõrvitsa uued kammerooperid "Tuleaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libretode autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  5. Von Krahli teatris etenduvad Tõnu Kõrvitsa kammerooperid / Esme Kassak

    Index Scriptorium Estoniae

    Kassak, Esme

    2006-01-01

    20. apr. esietenduvad Von Krahli Teatris Peeter Jalaka lavastuses Tõnu Kõrvitsa uued kammerooperid "Tuleaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libretode autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  6. Victor or Villain? Wernher von Braun and the Space Race

    Science.gov (United States)

    O'Brien, Jason L.; Sears, Christine E.

    2011-01-01

    Set during the Cold War and space race, this historical role-play focuses on Wernher von Braun's involvement in and culpability for the use of slave laborers to produce V-2 rockets for Nazi Germany. Students will grapple with two central questions. Should von Braun have been allowed to emigrate to the United States given his affiliation with the…

  7. Die baltischen Kapitulationen von 1710 : Kontext, Wirkungen, Interpretationen / Marten Seppel

    Index Scriptorium Estoniae

    Seppel, Marten, 1979-

    2015-01-01

    Arvustus: Die baltischen Kapitulationen von 1710 : Kontext, Wirkungen, Interpretationen, hrsg. von Karsten Brüggemann, Mati Laur und Pärtel Piirimäe, Queleln und Studien zur baltischen Geschichte, Bd 23 (Köln u.a: Böhlau Verlag, 2014)

  8. Von Krahli teater mängib Kõrvitsa kammeroopereid

    Index Scriptorium Estoniae

    2006-01-01

    20. apr. esietenduvad Von Krahli Teatris Peeter Jalaka lavastuses Tõnu Kõrvitsa uued kammerooperid "Tuleaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libretode autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  9. Entwicklung eines amperometrischen Biosensors zur Erfassung von Polyphenolen

    OpenAIRE

    2013-01-01

    In der durchgeführten Arbeit wurden neue Immobilisierungsstrategien zur Etablierung eines amperometrischen Biosensors, welcher Polyphenole erfasst, untersucht. Ziel war es eine „Handheld-Unit“ unter Verwendung einer Dickschichtelektrode (Thick-Film Technology, TFT) zu entwickeln. Zur Erfassung von Polyphenolen wurde das Enzym Laccase ausgewählt, welche die Oxidation von Phenolen zu Chinonen katalysiert. Dabei wurden in dieser Arbe...

  10. Von Stryk : halb oli nii aadlikel kui talupoegadel / Margus Haav

    Index Scriptorium Estoniae

    Haav, Margus, 1969-

    2007-01-01

    Rets. rmt.: Stryk, Wolf Dietmar von. Morsel-Podrigel, das Stammhaus der familie von Stryk in Livland/Estland 1562-1919-2003. : die Geschichte eines Gutes im Wandel der Zeiten der Jahrhunderte bis zur Gegenwart. Viljandi : W. Stryk, 2006. Artikkel ilmunud ka: Valgamaalane, 3. märts 2007, lk 4

  11. Erfahrungen an der Schnittstelle von Medienarbeit und Praxisforschung

    Directory of Open Access Journals (Sweden)

    Peter Holzwarth

    2007-11-01

    Full Text Available Der Beitrag reflektiert die Verbindung von praktischer Medienarbeit und Forschung am Beispiel eines internationalen EU-Forschungsprojekts zum Thema Medien und Migration. Neben didaktischen Prinzipien und Konzepten für die aktive Medienarbeit im Forschungskontext geht es um die Kooperation von medienpädagogischer Begleitung (MB und wissenschaftlicher Begleitung (WB sowie um deren spezifische Kompetenzen.

  12. Auf den Schultern von Riesen und Zwergen Einsteins unvollendete Revolution

    CERN Document Server

    Renn, Jürgen

    2006-01-01

    Dies ist die Geschichte von Einsteins unvollendeter Revolution, einer tiefgreifenden Veränderung unserer Begriffe von Raum, Zeit, Materie und Strahlung. Diese Revolution begann in Einsteins Wunderjahr 1905, wurde durch seine allgemeine Relativitätstheorie aus dem Jahre 1915 fortgesetzt und wirkt in den heutigen Versuchen der Wissenschaft, die Entstehung und das Schicksal des Universums zu verstehen, weiter. Vor dem Hintergrund einer historischen Theorie des wissenschaftlichen Fortschritts wird Einsteins bis heute nicht abgeschlossene Revolution als das Ergebnis einer langfristigen Entwicklung des Wissens verständlich. Anhand der spannenden Geschichte von Einsteins Entdeckungen wird nachvollziehbar, warum große Denker wie Einstein weiter gesehen haben als ihre Vorgänger. Sie standen nicht nur auf den Schultern von Riesen, also den wissenschaftlichen Leistungen einzelner großer Vorgänger wie Newton, sondern auch auf den Schultern von "Zwergen", dem wissenschaftlichen Wissen, dem technischen Wissen, und d...

  13. Suitability of tracers; Eignung von Tracern

    Energy Technology Data Exchange (ETDEWEB)

    Klotz, D. [GSF - Forschungszentrum fuer Umwelt und Gesundheit GmbH, Neuherberg (Germany). Inst. fuer Hydrologie

    1999-02-01

    Hydrological tracer techniques are a means of making statements on the direction and speed of underground water. One of the simpler tasks is to find out whether there is hydrological communication between two given points. This requires a determination of the direction of flow, which places less exacting demands on the properties of the tracer than does the task of determining the flow velocity of underground water. Tracer methods can serve to infer from flow velocity the distance (flow) velocity, which is defined as the ratio between the distance between two points located in flow direction and the actual time it takes water to flow from one to the other. [Deutsch] Mit Hilfe der hydrologischen Markierungstechniken koennen Aussagen ueber die Richtung und die Geschwindigkeit von Bewegungen des unterirdischen Wassers gemacht werden. Der einfachere Fall liegt vor, wenn festgestellt werden soll, ob zwischen zwei Punkten eine hydrologische Verbindung besteht. Bei dieser Fliessrichtungsbestimmung sind die Forderungen an die Eigenschaften der einzusetzenden Tracer geringer als bei der Bestimmung der Geschwindigkeit des unterirdischen Wassers. Von den Geschwindigkeiten des unterirdischen Wassers ist die Abstands-(Fliess)geschwindigkeit, die definiert ist durch das Verhaeltnis aus dem Abstand und der wahren Fliesszeit zwischen zwei in Bewegungsrichtung gelegenen Punkten, durch Tracermethoden zu bestimmen. (orig.)

  14. Guy von Dardel 1919-2009

    CERN Multimedia

    2009-01-01

    Guy von Dardel, a well-known figure at CERN and in the international particle physics community, passed away on 28 August. Guy von Dardel came to CERN when it was founded in 1954 and was a full-time staff member until 1964, performing several experiments and working on technical developments. These included the first measurement of the neutral pion’s life-time. Called to Lund University in 1964, he became professor there in 1965 and director of the 1.2 GeV electron accelerator. In the late 1960s, he performed an experiment at CERN’s PS that measured the decays of the Λ. Then, in the early 1970s, he involved the Lund group in a series of experiments at the Intersecting Storage Rings (ISR), where he measured the production of various types of particles. In particular, he participated in a series of experiments that observed the production of a high abundance of particles with large transverse momenta. This required an explanation...

  15. Approximate von Neumann entropy for directed graphs.

    Science.gov (United States)

    Ye, Cheng; Wilson, Richard C; Comin, César H; Costa, Luciano da F; Hancock, Edwin R

    2014-05-01

    In this paper, we develop an entropy measure for assessing the structural complexity of directed graphs. Although there are many existing alternative measures for quantifying the structural properties of undirected graphs, there are relatively few corresponding measures for directed graphs. To fill this gap in the literature, we explore an alternative technique that is applicable to directed graphs. We commence by using Chung's generalization of the Laplacian of a directed graph to extend the computation of von Neumann entropy from undirected to directed graphs. We provide a simplified form of the entropy which can be expressed in terms of simple node in-degree and out-degree statistics. Moreover, we find approximate forms of the von Neumann entropy that apply to both weakly and strongly directed graphs, and that can be used to characterize network structure. We illustrate the usefulness of these simplified entropy forms defined in this paper on both artificial and real-world data sets, including structures from protein databases and high energy physics theory citation networks.

  16. Kontextualisierung von Queer Theory Contextualizing Queer Theory

    Directory of Open Access Journals (Sweden)

    Anna Voigt

    2008-03-01

    Full Text Available Christine M. Klapeer legt in diesem Einführungsband dar, aus welchen politischen und theoretischen Kontexten heraus sich ‚queer‘ zu einem Begriff mit besonderem politischem und theoretischem Gehalt entwickelt hat. Wesentlich zielt sie dabei auf eine kritische Kontextualisierung von „queer theory”. Die Autorin geht zunächst auf das Gay Liberation Movement ein, grenzt die Queer Theory vom Poststrukturalismus, von feministischen Theorien und den Lesbian and Gay Studies ab, beleuchtet Eckpunkte queeren Denkens und zeichnet schließlich die Entwicklungen in Österreich sowohl politisch-rechtlich als auch bewegungsgeschichtlich und in der Wissenschaftslandschaft nach.Christine M. Klapeer’s introductory volume demonstrates the manner in which ‘queer’ grew out of various political and theoretical contexts to become a term with special political and theoretical content. She focuses primarily on a critical contextualization of “queer theory.” The author begins by approaching the Gay Liberation Movement and then distinguishes Queer Theory from poststructuralism, from feminist theories, and from Lesbian and Gay Studies. She continues on to illuminate the key aspects of queer thought and concludes by sketching the development in Austria in terms of politics and the law, the history of movements, and within the landscape of knowledge.

  17. Integrales Lernen in und von Organisationen

    Directory of Open Access Journals (Sweden)

    Wendelin Küpers

    2006-06-01

    Full Text Available Bezogen auf das integrale Models von Ken Wilber untersucht der Beitrag die Bedeutung des Lernens in und von Organisationen. Nach einer Darstellung der Relevanz und des Grundverständnisses des Lernens im Organisationskontext, werden integrale Dimensionen des Lernens dargestellt. Im Einzelnen werden die verschiedenen Sphären eines inneren-subjektiven und äusseren-„objektiven“ Lernens des Einzelnen als auch ein gemeinschaftliches Lernen und Lernen im System auf der kollektiven Ebene dargestellt sowie deren interrelationaler Zusammenhang diskutiert. Schließlich beschreibt der Beitrag noch integrale Lernprozesse sowie integrale Gestaltungsfelder zur Förderung des Lernens in den verschiedenen Bereichen. Abschließend spricht der Artikel noch Schwierigkeiten und Probleme an sowie nimmt im Fazit ein perspektivischen Ausblick vor. Abstract: Related to the integral model of Ken Wilber, this paper investigates the role of learning in and of organisations. After describing the relevance and basic understanding of learning in the context of organisations, integral dimensions of learning will be outlined. In particular learning in the sphere of an inner-subjective and exterior-objective learning of the individual and a communal learning and learning within a system on the collective level as well as its interrelations will be discussed. Afterwards integral learning processes and various measurements for enhancing integral learning in the different sphere will be discussed. Finally, difficulties and problems will be addressed and in conclusion some perspectives and implications are presented.

  18. Katheterablation von supraventrikulären Tachykardien

    Directory of Open Access Journals (Sweden)

    Strohmer S

    2011-01-01

    Full Text Available Supraventrikuläre Tachykardien (SVT spielen in der klinischen Praxis aufgrund ihrer Häufigkeit und Symptomatik eine große Rolle. Obwohl diese Arrhythmien im Allgemeinen nicht lebensbedrohlich sind, führen sie aufgrund ihres unvorhersehbaren Auftretens zu einer beträchtlichen Unsicherheit und Einschränkung der Lebensqualität. Die elektrophysiologische Untersuchung inklusive Katheterablation hat sich in den vergangenen 20 Jahren als kurative und sichere Erstlinientherapie für Patienten mit hochsymptomatischen bzw. wiederholten Anfällen etabliert. Heutzutage liegen die Erfolgsraten für die Radiofrequenzablation der regulären SVT über 95 % bei einer sehr niedrigen Rezidivrate von weniger als 5 %. Eine antiarrhythmische Therapie für das Langzeitmanagement ist aufgrund der geringen Effektivität und Gefahr von ernsthaften Nebenwirkungen weitgehend obsolet und nur in Ausnahmefällen erforderlich. Der folgende Artikel gibt eine aktuelle Übersicht über die häufigsten rhythmischen Schmalkomplextachykardien, die verschiedenen Mechanismen und moderne nicht-pharmakologische Therapieansätze.

  19. Die Krakauer Kirche von Karmeliten und Karmelitaninnen

    Directory of Open Access Journals (Sweden)

    Józef Szymon Wronski

    2004-12-01

    Full Text Available 1. Die Klosterkirche der unbeschuhten Karmelitinnen Zum Heiligen Josef. Ein glücklicher Auftakt und somit die charakteristische Einführung in das 20. Jh. für den Kirchenbau von Krakau war die Errichtung der Karmeliterinnen St. Josephs-Kirche an der Lobzowska-Straße 40, in der die Architekten (Tadeusz Stryjeński (1849-1943 - Projektant der Kirche und Franciszek Mączyński (1874-1947 - Ausführer des Bauprojektes mit eigenen Verbesserungen die historisch- eklektizistischen Formen d.h. die mittelalterlichen Formen vor allem des sog. Übergangsstils vereinfachten. Die Kirche, die in den Jahren 1903-1905 errichtet wurde, steht inmitten vom Baukomplex des Klosters, dessen Grundriss das Quadrat ist49. Der Kirchenbau ist ein dem Gesamtbau des Klosters eingefügter Längsraum. Hinter dem Chor liegt das Oratorium des Konvents. Das Material Backstein (mit Verwendung von Stein erinnert an die Baukunst eines der besten Architekten jener Zeit, nämlich Teodor Talowskis (1857-1910, der viele Kirchen in Südpolen, aber auch viele Bürgerhäuser nicht nur in Krakau im ausgehenden 19. Jh. baute. Die Architektur der Karmeliterinnen St. Josephs-Kirche ist immer noch im Malerischen begriffen. Aber die Vereinfachung der historischen Formen führt zu ihrer „Beruhigung” und dadurch zur Wuchtigkeit des Ausdrucks. Bemerkenswert ist die in dieser Zeit (in der Anlage noch seltene ausgewogene Proportionierung des Baukörpers. Das methodische Prinzip jener Zeit ist der Kontrast. Im Kontrast zu den gedrungenen und wuchtigen Formen des Baukörpers stehen z.B. die sich verjüngenden obeliskenförmigen und pylonenartigen Türmchen, die nicht nur die Eingangsfassade der Kirche flankieren, sondern auch an den Ecken des Querhauses der Kirche stehen. Die ingravierten weißen Steine an der Fassade in der Zahl von Zehn erinnern an das Gebot des Karmelterinnenordens: Bete täglich den Rosenkranz und sind zugleich ein Vanitativmotiv. 2. Die Klosterkirche der unbeschuhten

  20. [Heinz von zur Mühlen. Das Bürgertum Fordert Blut. Ein Bolschewistiches Flugblatt von 1918] / Paul Kaegbein

    Index Scriptorium Estoniae

    Kaegbein, Paul

    2007-01-01

    Arvustus: Heinz von zur Mühlen. Das Bürgertum Fordert Blut. Ein Bolschewistiches Flugblatt von 1918. In : Ostseeprovinzen, baltische Staaten und das Nationale. Münster : LIT, 2005, lk. 403-414. 1918. aastast pärit lendlehest, mille käekirja järgi otsustades on kirjutanud Viktor Kingissepp