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Sample records for factor procoagulant activity

  1. Elevated circulating soluble thrombomodulin activity, tissue factor activity and circulating procoagulant phospholipids: new and useful markers for pre-eclampsia?

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    Rousseau, Aurélie; Favier, Rémi; Van Dreden, Patrick

    2009-09-01

    One of the most frequently proposed mechanisms for pre-eclampsia refers to uteroplacental thrombosis. However, the contribution of classical thrombotic risk factors remains questionable. The aims of this study were to investigate the activities of thrombomodulin, tissue factor and procoagulant phospholipids to assess endothelial cell injury in pregnant women with pre-eclampsia and to compare them with other classical markers of vascular injury and thrombotic risk. Using three new functional assays we studied the plasma levels of these new markers in 35 healthy women, 30 healthy pregnant women, and 35 women with pre-eclampsia. We found that plasma levels of thrombomodulin activity, tissue factor activity and procoagulant phospholipids were significantly elevated in women with pre-eclampsia versus normal pregnant and non-pregnant women. It is thus suggested that elevated levels of these parameters in pre-eclampsia may reflect vascular endothelium damage, and may be a more valuable biomarker than antigen for the assessment of endothelial damage in pre-eclampsia. The high increased levels of procoagulant phospholipids and tissue factor activities in pre-eclampsia could suggest that the procoagulant potential may be implicated in this complication and makes these markers very promising for the understanding, follow-up and therapeutic handling of complicated pregnancy.

  2. Air pollution upregulates endothelial cell procoagulant activity via ultrafine particle-induced oxidant signaling and tissue factor expression.

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    Snow, S J; Cheng, W; Wolberg, A S; Carraway, M S

    2014-07-01

    Air pollution exposure is associated with cardiovascular events triggered by clot formation. Endothelial activation and initiation of coagulation are pathophysiological mechanisms that could link inhaled air pollutants to vascular events. Here we investigated the underlying mechanisms of increased endothelial cell procoagulant activity following exposure to soluble components of ultrafine particles (soluble UF). Human coronary artery endothelial cells (HCAEC) were exposed to soluble UF and assessed for their ability to trigger procoagulant activity in platelet-free plasma. Exposed HCAEC triggered earlier thrombin generation and faster fibrin clot formation, which was abolished by an anti-tissue factor (TF) antibody, indicating TF-dependent effects. Soluble UF exposure increased TF mRNA expression without compensatory increases in key anticoagulant proteins. To identify early events that regulate TF expression, we measured endothelial H2O2 production following soluble UF exposure and identified the enzymatic source. Soluble UF exposure increased endothelial H2O2 production, and antioxidants attenuated UF-induced upregulation of TF, linking the procoagulant responses to reactive oxygen species (ROS) formation. Chemical inhibitors and RNA silencing showed that NOX-4, an important endothelial source of H2O2, was involved in UF-induced upregulation of TF mRNA. These data indicate that soluble UF exposure induces endothelial cell procoagulant activity, which involves de novo TF synthesis, ROS production, and the NOX-4 enzyme. These findings provide mechanistic insight into the adverse cardiovascular effects associated with air pollution exposure. Published by Oxford University Press on behalf of Toxicological Sciences 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  3. Platelet-rich plasma stimulated by pulse electric fields: Platelet activation, procoagulant markers, growth factor release and cell proliferation.

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    Frelinger, A L; Torres, A S; Caiafa, A; Morton, C A; Berny-Lang, M A; Gerrits, A J; Carmichael, S L; Neculaes, V B; Michelson, A D

    2016-01-01

    Therapeutic use of activated platelet-rich plasma (PRP) has been explored for wound healing, hemostasis and antimicrobial wound applications. Pulse electric field (PEF) stimulation may provide more consistent platelet activation and avoid complications associated with the addition of bovine thrombin, the current state of the art ex vivo activator of therapeutic PRP. The aim of this study was to compare the ability of PEF, bovine thrombin and thrombin receptor activating peptide (TRAP) to activate human PRP, release growth factors and induce cell proliferation in vitro. Human PRP was prepared in the Harvest SmartPreP2 System and treated with vehicle, PEF, bovine thrombin, TRAP or Triton X-100. Platelet activation and procoagulant markers and microparticle generation were measured by flow cytometry. Released growth factors were measured by ELISA. The releasates were tested for their ability to stimulate proliferation of human epithelial cells in culture. PEF produced more platelet-derived microparticles, P-selectin-positive particles and procoagulant annexin V-positive particles than bovine thrombin or TRAP. These differences were associated with higher levels of released epidermal growth factor after PEF than after bovine thrombin or TRAP but similar levels of platelet-derived, vascular-endothelial, and basic fibroblast growth factors, and platelet factor 4. Supernatant from PEF-treated platelets significantly increased cell proliferation compared to plasma. In conclusion, PEF treatment of fresh PRP results in generation of microparticles, exposure of prothrombotic platelet surfaces, differential release of growth factors compared to bovine thrombin and TRAP and significant cell proliferation. These results, together with PEF's inherent advantages, suggest that PEF may be a superior alternative to bovine thrombin activation of PRP for therapeutic applications.

  4. Comparative study of anticoagulant and procoagulant properties of 28 snake venoms from families Elapidae, Viperidae, and purified Russell's viper venom-factor X activator (RVV-X).

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    Suntravat, Montamas; Nuchprayoon, Issarang; Pérez, John C

    2010-09-15

    Snake venoms consist of numerous molecules with diverse biological functions used for capturing prey. Each component of venom has a specific target, and alters the biological function of its target. Once these molecules are identified, characterized, and cloned; they could have medical applications. The activated clotting time (ACT) and clot rate were used for screening procoagulant and anticoagulant properties of 28 snake venoms. Crude venoms from Daboia russellii siamensis, Bothrops asper, Bothrops moojeni, and one Crotalus oreganus helleri from Wrightwood, CA, had procoagulant activity. These venoms induced a significant shortening of the ACT and showed a significant increase in the clot rate when compared to the negative control. Factor X activator activity was also measured in 28 venoms, and D. r. siamensis venom was 5-6 times higher than those of B. asper, B. moojeni, and C. o. helleri from Wrightwood County. Russell's viper venom-factor X activator (RVV-X) was purified from D. r. siamensis venom, and then procoagulant activity was evaluated by the ACT and clot rate. Other venoms, Crotalus atrox and two Naja pallida, had anticoagulant activity. A significant increase in the ACT and a significant decrease in the clot rate were observed after the addition of these venoms; therefore, the venoms were considered to have anticoagulant activity. Venoms from the same species did not always have the same ACT and clot rate profiles, but the profiles were an excellent way to identify procoagulant and anticoagulant activities in snake venoms.

  5. Procoagulant activity of leukocytes pretreated with radiodetoxified endotoxin

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    Szilagyi, T; Csernyanszky, H; Gazdy, E [Debreceni Orvostudomanyi Egyetem (Hungary); Bertok, L [Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszseguegyi Kutato Intezet, Budapest (Hungary)

    1980-09-30

    Rabbits were treated with Escherichia coli 089 endotoxin detoxified by ionizing irradiation (/sup 60/Co-gamma). The leukocytes (PMNs in 90%) obtained from rabbits treated with the mother endotoxin elicited a well defined activity; those obtained from rabbits pretreated with detoxified endotoxin elicited a less pronounced, procoagulant activity. It is suggested that the procoagulant effect may play a part in the mechanism of the local Shwartzman phenomenon.

  6. Effect of cigarette smoke on monocyte procoagulant activity: Focus on platelet-derived brain-derived neurotrophic factor (BDNF).

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    Amadio, Patrizia; Baldassarre, Damiano; Sandrini, Leonardo; Weksler, Babette B; Tremoli, Elena; Barbieri, Silvia S

    2017-01-01

    Cigarette smoke (CS) activates platelets, promotes vascular dysfunction, and enhances Tissue Factor (TF) expression in blood monocytes favoring pro-thrombotic states. Brain-derived neurotrophic factor (BDNF), a member of the family of neurotrophins involved in survival, growth, and maturation of neurons, is released by activated platelets (APLTs) and plays a role in the cardiovascular system. The effect of CS on circulating levels of BDNF is controversial and the function of circulating BDNF in atherothrombosis is not fully understood. Here, we have shown that human platelets, treated with an aqueous extract of CS (CSE), released BDNF in a dose-dependent manner. In addition, incubation of human monocytes with BDNF or with the supernatant of platelets activated with CSE increased TF activity by a Tropomyosin receptor kinase B (TrkB)-dependent mechanism. Finally, comparing serum and plasma samples of 12 male never smokers (NS) and 29 male active smokers (AS) we observed a significant increase in microparticle-associated TF activity (MP-TF) as well as BDNF in AS, while in serum, BDNF behaved oppositely. Taken together these findings suggest that platelet-derived BDNF is involved in the regulation of TF activity and that CS plays a role in this pathway by favoring a pro-atherothrombotic state.

  7. Fibrinolytic and procoagulant activities of Yersinia pestis and Salmonella enterica.

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    Korhonen, T K

    2015-06-01

    Pla of the plague bacterium Yersinia pestis and PgtE of the enteropathogen Salmonella enterica are surface-exposed, transmembrane β-barrel proteases of the omptin family that exhibit a complex array of interactions with the hemostatic systems in vitro, and both proteases are established virulence factors. Pla favors fibrinolysis by direct activation of plasminogen, inactivation of the serpins plasminogen activator inhibitor-1 and α2-antiplasmin, inactivation of the thrombin-activable fibrinolysis inhibitor, and activation of single-chain urokinase. PgtE is structurally very similar but exhibits partially different functions and differ in expression control. PgtE proteolysis targets control aspects of fibrinolysis, and mimicry of matrix metalloproteinases enhances cell migration that should favor the intracellular spread of the bacterium. Enzymatic activity of both proteases is strongly influenced by the environment-induced variations in lipopolysaccharide that binds to the β-barrel. Both proteases cleave the tissue factor pathway inhibitor and thus also express procoagulant activity. © 2015 International Society on Thrombosis and Haemostasis.

  8. Graft Product for Autologous Peripheral Blood Stem Cell Transplantation Enhances Thrombin Generation and Expresses Procoagulant Microparticles and Tissue Factor.

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    Sidibe, Fatoumata; Spanoudaki, Anastasia; Vanneaux, Valerie; Mbemba, Elisabeth; Larghero, Jerome; Van Dreden, Patrick; Lotz, Jean-Pierre; Elalamy, Ismail; Larsen, Annette K; Gerotziafas, Grigoris T

    2018-05-01

    The beneficial effect of autologous peripheral blood stem cell transplantation (APBSCT) may be compromised by acute vascular complications related to hypercoagulability. We studied the impact of graft product on thrombin generation of normal plasma and the expression of tissue factor (TF) and procoagulant platelet-derived procoagulant microparticles (Pd-MPs) in samples of graft products. Graft products from 10 patients eligible for APBSCT were mixed with platelet-poor plasma (PPP) or platelet-rich plasma (PRP) from healthy volunteers and assessed for in vitro thrombin generation. In control experiments, thrombin generation was assessed in (1) PPP and PRP without any exogenous TF and/or procoagulant phospholipids, (2) PPP with the addition of TF (5 pM) and procoagulant phospholipids (4 μM), (3) in PRP with the addition of TF (5 pM). Graft products were assessed with Western blot assay for TF expression, with a specific clotting assay for TF activity and with flow cytometry assay for Pd-MPs. The graft product enhanced thrombin generation and its procoagulant activity was related to the presence of Pd-MPs and TF. The concentration of Pd-MPs in the graft product was characterized by a significant interindividual variability. The present study reveals the need for a thorough quality control of the graft products regarding their procoagulant potential.

  9. Development of Coagulation Factor Probes for the Identification of Procoagulant Circulating Tumor Cells

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    Tormoen, Garth W.; Cianchetti, Flor A. [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR (United States); Bock, Paul E. [Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN (United States); McCarty, Owen J. T., E-mail: tormoeng@ohsu.edu [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR (United States); Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR (United States); Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health and Science University, Portland, OR (United States)

    2012-09-06

    Metastatic cancer is associated with a hypercoagulable state, and pathological venous thromboembolic disease is a significant source of morbidity and the second leading cause of death in patients with cancer. Here we aimed to develop a novel labeling strategy to detect and quantify procoagulant circulating tumor cells (CTCs) from patients with metastatic cancer. We hypothesize that the enumeration of procoagulant CTCs may be prognostic for the development of venous thrombosis in patients with cancer. Our approach is based on the observation that cancer cells are capable of initiating and facilitating cell-mediated coagulation in vitro, whereby activated coagulation factor complexes assemble upon cancer cell membrane surfaces. Binding of fluorescently labeled, active site-inhibited coagulation factors VIIa, Xa, and IIa to the metastatic breast cancer cell line, MDA-MB-231, non-metastatic colorectal cell line, SW480, or metastatic colorectal cell line, SW620, was characterized in a purified system, in anticoagulated blood and plasma, and in plasma under conditions of coagulation. We conclude that a CTC labeling strategy that utilizes coagulation factor-based fluorescent probes may provide a functional assessment of the procoagulant potential of CTCs, and that this strategy is amenable to current CTC detection platforms.

  10. Moojenactivase, a novel pro-coagulant PIIId metalloprotease isolated from Bothrops moojeni snake venom, activates coagulation factors II and X and induces tissue factor up-regulation in leukocytes.

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    Sartim, Marco A; Costa, Tassia R; Laure, Helen J; Espíndola, Milena S; Frantz, Fabiani G; Sorgi, Carlos A; Cintra, Adélia C O; Arantes, Eliane C; Faccioli, Lucia H; Rosa, José C; Sampaio, Suely V

    2016-05-01

    Coagulopathies following snakebite are triggered by pro-coagulant venom toxins, in which metalloproteases play a major role in envenomation-induced coagulation disorders by acting on coagulation cascade, platelet function and fibrinolysis. Considering this relevance, here we describe the isolation and biochemical characterization of moojenactivase (MooA), a metalloprotease from Bothrops moojeni snake venom, and investigate its involvement in hemostasis in vitro. MooA is a glycoprotein of 85,746.22 Da, member of the PIIId group of snake venom metalloproteases, composed of three linked disulfide-bonded chains: an N-glycosylated heavy chain, and two light chains. The venom protease induced human plasma clotting in vitro by activating on both blood coagulation factors II (prothrombin) and X, which in turn generated α-thrombin and factor Xa, respectively. Additionally, MooA induced expression of tissue factor (TF) on the membrane surface of peripheral blood mononuclear cells (PBMC), which led these cells to adopt pro-coagulant characteristics. MooA was also shown to be involved with production of the inflammatory mediators TNF-α, IL-8 and MCP-1, suggesting an association between MooA pro-inflammatory stimulation of PBMC and TF up-regulation. We also observed aggregation of washed platelets when in presence of MooA; however, the protease had no effect on fibrinolysis. Our findings show that MooA is a novel hemostatically active metalloprotease, which may lead to the development of coagulopathies during B. moojeni envenomation. Moreover, the metalloprotease may contribute to the development of new diagnostic tools and pharmacological approaches applied to hemostatic disorders.

  11. In vitro effects of recombinant activated factor VII on thrombin generation and coagulation following inhibition of platelet procoagulant activity by prasugrel.

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    Mazzeffi, Michael; Szlam, Fania; Jakubowski, Joseph A; Tanaka, Kenichi A; Sugidachi, Atsuhiro; Levy, Jerrold H

    2013-07-01

    Prasugrel is a thienopyridyl P2Y12 antagonist with potent antiplatelet effects. At present, little is known about its effects on thrombin generation or what strategies may emergently reverse its anticoagulant effects. In the current study we evaluated whether recombinant activated factor VII may reverse prasugrel induced effects and increase thrombin generation in an in vitro model. The effect of prasugrel active metabolite, PAM (R-138727), was evaluated on platelet aggregation, thrombin generation, and rotational thromboelastometry parameters using blood from 20 healthy volunteers. Additionally, we evaluated the effects of adenosine diphosphate (ADP) and recombinant activated factor VII on restoring these parameters towards baseline values. PAM reduced maximum platelet aggregation and led to platelet disaggregation. It also decreased peak thrombin, increased lag time, and increased time to peak thrombin. Treatment with recombinant activated factor VII restored all three parameters of thrombin generation towards baseline. ADP decreased lag time and time to peak thrombin, but had no effect on peak thrombin. When recombinant activated factor VII and ADP were combined they had a greater effect on thrombin parameters than either drug alone. PAM also increased thromboelastometric clotting time and clot formation time, but had no effect on maximum clot firmness. Treatment with either recombinant activated factor VII or ADP restored these values towards baseline. Recombinant activated factor VII restores thrombin generation in the presence of PAM. In patients taking prasugrel with life-threatening refractory bleeding it has the potential to be a useful therapeutic approach. Additional clinical studies are needed to validate our findings. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity.

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    Ashis K Mukherjee

    Full Text Available Proteases from Russell's viper venom (RVV induce a variety of toxic effects in victim. Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. These proteases were found to be different from previously reported factor V activators isolated from snake venoms. These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. Their Km and Vmax values towards fibrinogen were determined in the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein, respectively. On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis.

  13. Elevated procoagulant endothelial and tissue factor expressing microparticles in women with recurrent pregnancy loss.

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    Rucha Patil

    Full Text Available BACKGROUND: 15% of reproducing couples suffer from pregnancy loss(PL and recurs in 2-3%. One of the most frequently hypothesized causes of unexplained PL refers to a defective maternal haemostatic response leading to uteroplacental thrombosis. Hereditary thrombophilia and antiphospholipid antibodies have been extensively described as risk factors for PL in women with unknown aetiology. Recently, a new marker has emerged: the cell-derived procoagulant circulating microparticles(MPs which have been reported to have a major role in many thrombosis complicated diseases. This study aims to analyze the significance of procoagulant MPs in women suffering from unexplained recurrent pregnancy loss(RPL, and characterize their cellular origin. METHOD AND FINDINGS: 115 women with RPL were analyzed for common thrombophilia markers and different cell derived MPs-total annexinV, platelet(CD41a, endothelial(CD146,CD62e, leukocyte(CD45, erythrocyte(CD235a and tissue factor(CD142(TF expressing MPs and were compared with 20 healthy non-pregnant women. Methodology for MP analysis was standardized by participating in the "Vascular Biology Scientific and Standardization Committee workshop". RESULTS: Total annexinV, TF and endothelial MPs were found significantly increased(p<0.05, 95% confidence interval in women with RPL. The procoagulant activity of MPs measured by STA-PPL clotting time assay was found in correspondence with annexinV MP levels, wherein the clot time was shortened in samples with increased MP levels. Differences in platelet, leukocyte and erythrocyte derived MPs were not significant. Thirty seven of 115 women were found to carry any of the acquired or hereditary thrombophilia markers. No significant differences were seen in the MP profile of women with and without thrombophilia marker. CONCLUSION: The presence of elevated endothelial, TF and phosphatidylserine expressing MPs at a distance (at least 3 months from the PL suggests a continued chronic

  14. Histones Induce the Procoagulant Phenotype of Endothelial Cells through Tissue Factor Up-Regulation and Thrombomodulin Down-Regulation.

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    Kim, Ji Eun; Yoo, Hyun Ju; Gu, Ja Yoon; Kim, Hyun Kyung

    2016-01-01

    The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF) and anticoagulant thrombomodulin (TM). Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. TF and TM activity were measured using procoagulant activity, thrombin generation, or chromogenic assays. Involvement of the toll-like receptor (TLR) was assessed using the neutralizing antibodies. Histones dose-dependently induced surface antigens, activity and mRNA levels of endothelial TF. Histone-treated endothelial cells significantly shortened the lag time and enhanced the endogenous thrombin potential of normal plasma, which was normalized by a TF neutralizing antibody. Histones induced phosphatidylserine and protein-disulfide isomerase expression in endothelial cells. Histones also reduced the surface antigen, activity, and mRNA levels of endothelial TM. Polysialic acid and heparin reversed the histone-induced TF up-regulation and TM down-regulation. Activated protein C did not affect the TF up-regulation, but interrupted TM down-regulation. TLR2, and TLR4 inhibitors partially blocked the TF up-regulation. Histones induced the endothelial procoagulant phenotype through TF up-regulation and TM down-regulation. The effects of histones were partly mediated by TLR2, TLR4. Strategies to inhibit the harmful effects of histones in endothelial cells may be required in order to prevent a thrombotic environment.

  15. In Vitro Screening of Synthetic Fluorogenic Substrates for Detection of Cancer Procoagulant Activity.

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    Krause, Jason; Frost, Carminita L

    2018-04-01

    Cancer procoagulant (CP), a direct activator of coagulation factor X, is among one of the tumour cell products or activities which may promote fibrin formation and has been suggested to be selectively associated with the malignant phenotype. At present, the most reliable assay for the quantification of CP activity is the three-stage chromogenic assay which utilises the ability of CP to activate factor X. In this assay, the activation of factor X leads to the formation of activated thrombin from prothrombin and the eventual hydrolyses of a thrombin chromogenic substrate which contains a p-nitroaniline leaving group. The complexity of the three-stage chromogenic assay suggests a need for a direct method of assaying CP activity. This study focuses on the design of a fluorogenic substrate that would enable the direct quantification of CP activity. The results of the study show two promising substrates for the determination of CP activity: Boc-PQVR-AMC and PQVR-AMC. Further analysis showed that Boc-PQVR-AMC could be excluded as a potential substrate for CP since it was also cleaved by collagenase.

  16. Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

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    Federica Novelli

    Full Text Available Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons. Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations. Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor

  17. Von Willebrand factor indicates bacterial translocation, inflammation, and procoagulant imbalance and predicts complications independently of portal hypertension severity.

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    Mandorfer, M; Schwabl, P; Paternostro, R; Pomej, K; Bauer, D; Thaler, J; Ay, C; Quehenberger, P; Fritzer-Szekeres, M; Peck-Radosavljevic, M; Trauner, M; Reiberger, T; Ferlitsch, A

    2018-04-01

    Elevated plasma von Willebrand factor antigen (vWF) has been shown to indicate the presence of clinically significant portal hypertension, and thus, predicts the development of clinical events in patients with cirrhosis. To investigate the impact of bacterial translocation and inflammation on vWF, as well as the association between vWF and procoagulant imbalance. Moreover, we assessed whether vWF predicts complications of cirrhosis, independent of the severity of portal hypertension. Our study population comprised 225 patients with hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg without active bacterial infections or hepatocellular carcinoma. vWF correlated with markers of bacterial translocation (lipopolysaccharide-binding protein [LBP; ρ = 0.201; P = 0.021]), inflammation (interleukin 6 [IL-6; ρ = 0.426; P protein [CRP; ρ = 0.249; P protein C ratio; ρ = 0.507; P model for transplant-free mortality. Finally, the independent prognostic value of vWF/CRP groups for mortality was confirmed by competing risk analysis. Our results demonstrate that vWF is not only a marker of portal hypertension but also independently linked to bacterial translocation, inflammation and procoagulant imbalance, which might explain its HVPG-independent association with most clinical events. Prognostic groups based on vWF/CRP efficiently discriminate between patients with a poor 5-year survival and patients with a favourable prognosis. © 2018 John Wiley & Sons Ltd.

  18. Comparative analysis of procoagulant and fibrinogenolytic activity of crude protease fractions of turmeric species.

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    Shivalingu, B R; Vivek, H K; Nafeesa, Zohara; Priya, B S; Swamy, S Nanjunda

    2015-08-22

    Turmeric rhizome is a traditional herbal medicine, which has been widely used as a remedy to stop bleeding on fresh cuts and for wound healing by the rural and tribal population of India. To validate scientific and therapeutic application of turmeric rhizomes to stop bleeding on fresh cuts and its role in wound healing process. The water extracts of thoroughly scrubbed and washed turmeric rhizomes viz., Curcuma aromatica Salisb., Curcuma longa L., Curcuma caesia Roxb., Curcuma amada Roxb. and Curcuma zedoria (Christm.) Roscoe. were subjected to salting out and dialysis. The dialyzed crude enzyme fractions (CEFs) were assessed for proteolytic activity using casein as substrate and were also confirmed by caseinolytic zymography. Its coagulant activity and fibrinogenolytic activity were assessed using human citrated plasma and fibrinogen, respectively. The type of protease(s) in CEFs was confirmed by inhibition studies using specific protease inhibitors. The CEFs of C. aromatica, C. longa and C. caesia showed 1.89, 1.21 and 1.07 folds higher proteolytic activity, respectively, compared to papain. In contrast to these, C. amada and C. zedoria exhibited moderate proteolytic activity. CEFs showed low proteolytic activities compared to trypsin. The proteolytic activities of CEFs were confirmed by caseinolytic zymography. The CEFs of C. aromatica, C. longa and C. caesia showed complete hydrolysis of Aα, Bβ and γ subunits of human fibrinogen, while C. amada and C. zedoria showed partial hydrolysis. The CEFs viz., C. aromatica, C. longa, C. caesia, C. amada and C. zedoria exhibited strong procoagulant activity by reducing the human plasma clotting time from 172s (Control) to 66s, 84s 88s, 78s and 90s, respectively. The proteolytic activity of C. aromatica, C. longa, C. caesia and C. amada was inhibited (>82%) by PMSF, suggesting the possible presence of a serine protease(s). However, C. zedoria showed significant inhibition (60%) against IAA and moderate inhibition (30

  19. High-Dose Vitamin C Injection to Cancer Patients May Promote Thrombosis Through Procoagulant Activation of Erythrocytes.

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    Kim, Keunyoung; Bae, Ok-Nam; Koh, Sung-Hee; Kang, Seojin; Lim, Kyung-Min; Noh, Ji-Yoon; Shin, Sue; Kim, Inho; Chung, Jin-Ho

    2015-10-01

    Potential risk of high-dose vitamin C consumption is often ignored. Recently, gram-dose vitamin C is being intravenously injected for the treatment of cancer, which can expose circulating blood cells to extremely high concentrations of vitamin C. As well as platelets, red blood cells (RBCs) can actively participate in thrombosis through procoagulant activation. Here, we examined the procoagulant and prothrombotic risks associated with the intravenous injection of gram-dose vitamin C. Vitamin C (0.5-5 mM) increased procoagulant activity of freshly isolated human RBCs via the externalization of phosphatidylserine (PS) to outer cellular membrane and the formation of PS-bearing microvesicles. PS exposure was induced by the dysregulation of key enzymes for the maintenance of membrane phospholipid asymmetry, which was from vitamin C-induced oxidative stress, and resultant disruption of calcium and thiol homeostasis. Indeed, the intravenous injection of vitamin C (0.5-1.0 g/kg) in rats in vivo significantly increased thrombosis. Notably, the prothrombotic effects of vitamin C were more prominent in RBCs isolated from cancer patients, who are at increased risks of thrombotic events. Vitamin C-induced procoagulant and prothrombotic activation of RBCs, and increased thrombosis in vivo. RBCs from cancer patients exhibited increased sensitivity to the prothrombotic effects of vitamin C, reflecting that intravenous gram-dose vitamin C therapy needs to be carefully revisited. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Procoagulant Activity of Blood and Endothelial Cells via Phosphatidylserine Exposure and Microparticle Delivery in Patients with Diabetic Retinopathy

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    Ying Su

    2018-03-01

    Full Text Available Background/Aims: The mechanisms for thrombosis in diabetic retinopathy (DR are complex and need to be further elucidated. The purpose of this study was to test phosphatidylserine (PS exposure on microparticles (MPs and MP-origin cells from the circulation and to analyze cell-/MP-associated procoagulant activity (PCA in DR patients. Methods: PS-positive MPs and cells from healthy controls (n = 20 and diabetic patients (n = 60 were analyzed by flow cytometry and confocal microscopy. Clotting time and purified coagulation complex assays were used to measure PCA. Results: PS exposure on platelets and monocytes was higher in proliferative DR (PDR patients than in non-PDR patients or controls. The highest levels of MPs (derived from platelets [30%], erythrocytes [13%], leukocytes [28%], and endothelial cells [10%] were found in patients with PDR. In addition, PS exposure on blood cells and shed MPs in DR patients led to significantly increased FXa and FIIa generation, fibrin formation, and markedly shortened coagulation time. Moreover, lactadherin reduced 70% of PCA by blocking PS, while an anti-tissue factor antibody had a smaller effect. Conclusion: Our results confirmed that PCA in DR patients may be partly ascribed to PS exposure and MP release from blood and endothelial cells. Lactadherin may act as an efficient anticoagulant factor in this process.

  1. Roles of Platelet STIM1 and Orai1 in Glycoprotein VI- and Thrombin-dependent Procoagulant Activity and Thrombus Formation*

    Science.gov (United States)

    Gilio, Karen; van Kruchten, Roger; Braun, Attila; Berna-Erro, Alejandro; Feijge, Marion A. H.; Stegner, David; van der Meijden, Paola E. J.; Kuijpers, Marijke J. E.; Varga-Szabo, David; Heemskerk, Johan W. M.; Nieswandt, Bernhard

    2010-01-01

    In platelets, STIM1 has been recognized as the key regulatory protein in store-operated Ca2+ entry (SOCE) with Orai1 as principal Ca2+ entry channel. Both proteins contribute to collagen-dependent arterial thrombosis in mice in vivo. It is unclear whether STIM2 is involved. A key platelet response relying on Ca2+ entry is the surface exposure of phosphatidylserine (PS), which accomplishes platelet procoagulant activity. We studied this response in mouse platelets deficient in STIM1, STIM2, or Orai1. Upon high shear flow of blood over collagen, Stim1−/− and Orai1−/− platelets had greatly impaired glycoprotein (GP) VI-dependent Ca2+ signals, and they were deficient in PS exposure and thrombus formation. In contrast, Stim2−/− platelets reacted normally. Upon blood flow in the presence of thrombin generation and coagulation, Ca2+ signals of Stim1−/− and Orai1−/− platelets were partly reduced, whereas the PS exposure and formation of fibrin-rich thrombi were normalized. Washed Stim1−/− and Orai1−/− platelets were deficient in GPVI-induced PS exposure and prothrombinase activity, but not when thrombin was present as co-agonist. Markedly, SKF96365, a blocker of (receptor-operated) Ca2+ entry, inhibited Ca2+ and procoagulant responses even in Stim1−/− and Orai1−/− platelets. These data show for the first time that: (i) STIM1 and Orai1 jointly contribute to GPVI-induced SOCE, procoagulant activity, and thrombus formation; (ii) a compensating Ca2+ entry pathway is effective in the additional presence of thrombin; (iii) platelets contain two mechanisms of Ca2+ entry and PS exposure, only one relying on STIM1-Orai1 interaction. PMID:20519511

  2. Roles of platelet STIM1 and Orai1 in glycoprotein VI- and thrombin-dependent procoagulant activity and thrombus formation.

    Science.gov (United States)

    Gilio, Karen; van Kruchten, Roger; Braun, Attila; Berna-Erro, Alejandro; Feijge, Marion A H; Stegner, David; van der Meijden, Paola E J; Kuijpers, Marijke J E; Varga-Szabo, David; Heemskerk, Johan W M; Nieswandt, Bernhard

    2010-07-30

    In platelets, STIM1 has been recognized as the key regulatory protein in store-operated Ca(2+) entry (SOCE) with Orai1 as principal Ca(2+) entry channel. Both proteins contribute to collagen-dependent arterial thrombosis in mice in vivo. It is unclear whether STIM2 is involved. A key platelet response relying on Ca(2+) entry is the surface exposure of phosphatidylserine (PS), which accomplishes platelet procoagulant activity. We studied this response in mouse platelets deficient in STIM1, STIM2, or Orai1. Upon high shear flow of blood over collagen, Stim1(-/-) and Orai1(-/-) platelets had greatly impaired glycoprotein (GP) VI-dependent Ca(2+) signals, and they were deficient in PS exposure and thrombus formation. In contrast, Stim2(-/-) platelets reacted normally. Upon blood flow in the presence of thrombin generation and coagulation, Ca(2+) signals of Stim1(-/-) and Orai1(-/-) platelets were partly reduced, whereas the PS exposure and formation of fibrin-rich thrombi were normalized. Washed Stim1(-/-) and Orai1(-/-) platelets were deficient in GPVI-induced PS exposure and prothrombinase activity, but not when thrombin was present as co-agonist. Markedly, SKF96365, a blocker of (receptor-operated) Ca(2+) entry, inhibited Ca(2+) and procoagulant responses even in Stim1(-/-) and Orai1(-/-) platelets. These data show for the first time that: (i) STIM1 and Orai1 jointly contribute to GPVI-induced SOCE, procoagulant activity, and thrombus formation; (ii) a compensating Ca(2+) entry pathway is effective in the additional presence of thrombin; (iii) platelets contain two mechanisms of Ca(2+) entry and PS exposure, only one relying on STIM1-Orai1 interaction.

  3. An immunoradiometric assay for procoagulant factor VIII antigen: results in haemophilia, von Willebrand's disease and fetal plasma and serum

    International Nuclear Information System (INIS)

    Peake, I.R.; Bloom, A.L.; Giddings, J.C.; Ludlam, C.A.

    1979-01-01

    An immunoradiometric assay (IRMA) has been developed based on the inhibitor which arose in a polytransfused severe haemophiliac. The two-site IRMA measured antigens closely associated with the procoagulant parts of the factor VIII complex, which are termed FVIIIC antigens or FVIIICAG. FVIIICAG was present in normal plasma and also, at a slightly lower concentration, in normal serum. In 37 patients with haemophilia A, 36 had FVIIICAG levels of less than 10% of the normal plasma pool. In patients with von Willebrand's disease the levels of FVIIIC and FVIIICAG were in good agreement, both before and after treatment with cryoprecipitate or DDAVP. FVIIICAG was relatively stable in plasma at 37 0 C and could also be detected in cord and fetal serum. The assay is of potential value for detecting reduced levels of factor VIII, for carrier detection and for the prenatal diagnosis of haemophilia. (author)

  4. Membrane Type 1–Matrix Metalloproteinase/Akt Signaling Axis Modulates TNF-α-Induced Procoagulant Activity and Apoptosis in Endothelial Cells

    Science.gov (United States)

    Ohkawara, Hiroshi; Ishibashi, Toshiyuki; Sugimoto, Koichi; Ikeda, Kazuhiko; Ogawa, Kazuei; Takeishi, Yasuchika

    2014-01-01

    Membrane type 1–matrix metalloproteinase (MT1-MMP) functions as a signaling molecule in addition to a proteolytic enzyme. Our hypothesis was that MT1-MMP cooperates with protein kinase B (Akt) in tumor necrosis factor (TNF)-α-induced signaling pathways of vascular responses, including tissue factor (TF) procoagulant activity and endothelial apoptosis, in cultured human aortic endothelial cells (ECs). TNF-α (10 ng/mL) induced a decrease in Akt phosphorylation within 60 minutes in ECs. A chemical inhibitor of MMP, TIMP-2 and selective small interfering RNA (siRNA)-mediated suppression of MT1-MMP reversed TNF-α-triggered transient decrease of Akt phosphorylation within 60 minutes, suggesting that MT1-MMP may be a key regulator of Akt phosphorylation in TNF-α-stimulated ECs. In the downstream events, TNF-α increased TF antigen and activity, and suppressed the expression of thrombomodulin (TM) antigen. Inhibition of Akt markedly enhanced TNF-α-induced expression of TF antigen and activity, and further reduced the expression of TM antigen. Silencing of MT1-MMP by siRNA also reversed the changed expression of TF and TM induced by TNF-α. Moreover, TNF-α induced apoptosis of ECs through Akt- and forkhead box protein O1 (FoxO1)-dependent signaling pathway and nuclear factor-kB (NF-kB) activation. Knockdown of MT1-MMP by siRNA reversed apoptosis of ECs by inhibiting TNF-α-induced Akt-dependent regulation of FoxO1 in TNF-α-stimulated ECs. Immunoprecipitation demonstrated that TNF-α induced the changes in the associations between the cytoplasmic fraction of MT1-MMP and Akt in ECs. In conclusion, we show new evidence that MT1-MMP/Akt signaling axis is a key modifier for TNF-α-induced signaling pathways for modulation of procoagulant activity and apoptosis of ECs. PMID:25162582

  5. Membrane type 1-matrix metalloproteinase/Akt signaling axis modulates TNF-α-induced procoagulant activity and apoptosis in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Hiroshi Ohkawara

    Full Text Available Membrane type 1-matrix metalloproteinase (MT1-MMP functions as a signaling molecule in addition to a proteolytic enzyme. Our hypothesis was that MT1-MMP cooperates with protein kinase B (Akt in tumor necrosis factor (TNF-α-induced signaling pathways of vascular responses, including tissue factor (TF procoagulant activity and endothelial apoptosis, in cultured human aortic endothelial cells (ECs. TNF-α (10 ng/mL induced a decrease in Akt phosphorylation within 60 minutes in ECs. A chemical inhibitor of MMP, TIMP-2 and selective small interfering RNA (siRNA-mediated suppression of MT1-MMP reversed TNF-α-triggered transient decrease of Akt phosphorylation within 60 minutes, suggesting that MT1-MMP may be a key regulator of Akt phosphorylation in TNF-α-stimulated ECs. In the downstream events, TNF-α increased TF antigen and activity, and suppressed the expression of thrombomodulin (TM antigen. Inhibition of Akt markedly enhanced TNF-α-induced expression of TF antigen and activity, and further reduced the expression of TM antigen. Silencing of MT1-MMP by siRNA also reversed the changed expression of TF and TM induced by TNF-α. Moreover, TNF-α induced apoptosis of ECs through Akt- and forkhead box protein O1 (FoxO1-dependent signaling pathway and nuclear factor-kB (NF-kB activation. Knockdown of MT1-MMP by siRNA reversed apoptosis of ECs by inhibiting TNF-α-induced Akt-dependent regulation of FoxO1 in TNF-α-stimulated ECs. Immunoprecipitation demonstrated that TNF-α induced the changes in the associations between the cytoplasmic fraction of MT1-MMP and Akt in ECs. In conclusion, we show new evidence that MT1-MMP/Akt signaling axis is a key modifier for TNF-α-induced signaling pathways for modulation of procoagulant activity and apoptosis of ECs.

  6. The proteolytic profile of human cancer procoagulant suggests that it promotes cancer metastasis at the level of activation rather than degradation.

    Science.gov (United States)

    Kee, Nalise Low Ah; Krause, Jason; Blatch, Gregory L; Muramoto, Koji; Sakka, Kazuo; Sakka, Makiko; Naudé, Ryno J; Wagner, Leona; Wolf, Raik; Rahfeld, Jens-Ulrich; Demuth, Hans-Ulrich; Mielicki, Wojciech P; Frost, Carminita L

    2015-10-01

    Proteases are essential for tumour progression and many are over-expressed during this time. The main focus of research was the role of these proteases in degradation of the basement membrane and extracellular matrix (ECM), thereby enabling metastasis to occur. Cancer procoagulant (CP), a protease present in malignant tumours, but not normal tissue, is a known activator of coagulation factor X (FX). The present study investigated the function of CP in cancer progression by focussing on its enzymatic specificity. FX cleavage was confirmed using SDS-PAGE and MALDI-TOF MS and compared to the proteolytic action of CP on ECM proteins, including collagen type IV, laminin and fibronectin. Contrary to previous reports, CP cleaved FX at the conventional activation site (between Arg-52 and Ile-53). Additionally, degradation of FX by CP occurred at a much slower rate than degradation by conventional activators. Complete degradation of the heavy chain of FX was only visible after 24 h, while degradation by RVV was complete after 30 min, supporting postulations that the procoagulant function of CP may be of secondary importance to its role in cancer progression. Of the ECM proteins tested, only fibronectin was cleaved. The substrate specificity of CP was further investigated by screening synthetic peptide substrates using a novel direct CP assay. The results indicate that CP is not essential for either cancer-associated blood coagulation or the degradation of ECM proteins. Rather, they suggest that this protease may be required for the proteolytic activation of membrane receptors.

  7. Protein-Rich Fraction of Cnidoscolus urens (L. Arthur Leaves: Enzymatic Characterization and Procoagulant and Fibrinogenolytic Activities

    Directory of Open Access Journals (Sweden)

    Yamara A. S. de Menezes

    2014-03-01

    Full Text Available Proteolytic enzymes are important macromolecules in the regulation of biochemical processes in living organisms. Additionally, these versatile biomolecules have numerous applications in the industrial segment. In this study we have characterized a protein-rich fraction of Cnidoscolus urens (L. Arthur leaves, rich in proteolytic enzymes, and evaluated its effects on the coagulation cascade. Three protein-rich fractions were obtained from the crude extract of C. urens leaves by precipitation with acetone. Fraction F1.0 showed higher proteolytic activity upon azocasein, and thus, was chosen for subsequent tests. The proteolytic activity of F1.0 on fibrinogen was dose-dependent and time-dependent. The extract demonstrated procoagulant activity on citrated plasma and reduced the APTT, not exerting effects on PT. Despite the fibrin(ogenolytic activity, F1.0 showed no defibrinogenating activity in vivo. The fraction F1.0 did not express hemorrhagic nor hemolytic activities. The proteolytic activity was inhibited by E-64, EDTA and in the presence of metal ions, and increased when pretreated with reducing agents, suggesting that the observed activity was mostly due to cysteine proteases. Several bands with proteolytic activity were detected by zymography with gelatin, albumin and fibrinogen. The optimal enzymatic activity was observed in temperature of 60 °C and pH 5.0, demonstrating the presence of acidic proteases. In conclusion, these results could provide basis for the pharmacological application of C. urens proteases as a new source of bioactive molecules to treat bleeding and thrombotic disorders.

  8. Procoagulant expression in platelets and defects leading to clinical disorders.

    Science.gov (United States)

    Solum, N O

    1999-12-01

    Hemostasis is a result of interactions between fibrillar structures in the damaged vessel wall, soluble components in plasma, and cellular elements in blood represented mainly by platelets and platelet-derived material. During formation of a platelet plug at the damaged vessel wall, factors IXa and VIIIa form the "tenase" complex, leading to activation of factor X on the surface of activated platelets. Subsequently, factors Xa and Va form the "prothrombinase" complex, which catalyzes the formation of thrombin from prothrombin, leading to fibrin formation. An enhanced expression of negatively charged phosphatidylserine in the outer membrane leaflet resulting from a breakdown of the phospholipid asymmetry is essential for the formation of the procoagulant surface. An ATP-driven and inward-acting aminophospholipid "translocase" and a "floppase" counterbalancing this have been postulated to maintain the dynamic state of phospholipid asymmetry. A phospholipid-nonspecific "scramblase," believed to be responsible for the fast breakdown of the asymmetry during cell activation, has recently been isolated from erythrocytes, cloned, and characterized. An intracellular calcium-binding segment and one or more thioesterified fatty acids are probably of importance for calcium-induced activation of this transporter protein. Cytosolic calcium ions also activate the calcium-dependent protease calpain associated with shedding of microvesicles from the transformed platelet membrane. These are shed with a procoagulant surface and with surface-exposed P-selectin from the alpha-granules. Theoretically, therefore, microvesicles can be involved in both coagulation and inflammation. Scott syndrome is probably caused by a defect in the activation of an otherwise normal scramblase, resulting in a relatively severe bleeding tendency. In Stormorken syndrome, the patients demonstrate a spontaneous surface expression of aminophospholipids. Activated platelets and the presence of procoagulant

  9. Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis

    NARCIS (Netherlands)

    Weisfelt, Martijn; Determann, Rogier M.; de Gans, Jan; van der Ende, Arie; Levi, Marcel; van de Beek, Diederik; Schultz, Marcus J.

    2007-01-01

    OBJECTIVES: This study investigated levels of coagulation and fibrinolysis factors in cerebrospinal fluid (CSF) from adults with bacterial meningitis in relation to development of brain infarction. METHODS: CSF was collected from 92 adults with community-acquired bacterial meningitis, who

  10. Rapid Purification and Procoagulant and Platelet Aggregating Activities of Rhombeobin: A Thrombin-Like/Gyroxin-Like Enzyme from Lachesis muta rhombeata Snake Venom

    Science.gov (United States)

    Torres-Huaco, Frank Denis; Werneck, Cláudio C.; Vicente, Cristina Pontes; Vassequi-Silva, Talita; Nery-Diez, Ana Cláudia Coelho; Mendes, Camila B.; Antunes, Edson; Marangoni, Sérgio; Damico, Daniela C. S.

    2013-01-01

    We report a rapid purification method using one-step chromatography of SVSP Rhombeobin (LMR-47) from Lachesis muta rhombeata venom and its procoagulant activities and effects on platelet aggregation. The venom was fractionated by a single chromatographic step in RP-HPLC on a C8 Discovery BIO Wide Pore, showing high degree of molecular homogeneity with molecular mass of 47035.49 Da. Rhombeobin showed amidolytic activity upon BAρNA, with a broad optimum pH (7–10) and was stable in solution up to 60°C. The amidolytic activity was inhibited by serine proteinase inhibitors and reducing agents, but not chelating agents. Rhombeobin showed high coagulant activity on mice plasma and bovine fibrinogen. The deduced amino acid sequence of Rhombeobin showed homology with other SVSPs, especially with LM-TL (L. m. muta) and Gyroxin (C. d. terrificus). Rhombeobin acts, in vitro, as a strong procoagulant enzyme on mice citrated plasma, shortening the APTT and PT tests in adose-dependent manner. The protein showed, “ex vivo”, a strong defibrinogenating effect with 1 µg/animal. Lower doses activated the intrinsic and extrinsic coagulation pathways and impaired the platelet aggregation induced by ADP. Thus, this is the first report of a venom component that produces a venom-induced consumptive coagulopathy (VICC). PMID:24058917

  11. Rapid Purification and Procoagulant and Platelet Aggregating Activities of Rhombeobin: A Thrombin-Like/Gyroxin-Like Enzyme from Lachesis muta rhombeata Snake Venom

    Directory of Open Access Journals (Sweden)

    Frank Denis Torres-Huaco

    2013-01-01

    Full Text Available We report a rapid purification method using one-step chromatography of SVSP Rhombeobin (LMR-47 from Lachesis muta rhombeata venom and its procoagulant activities and effects on platelet aggregation. The venom was fractionated by a single chromatographic step in RP-HPLC on a C8 Discovery BIO Wide Pore, showing high degree of molecular homogeneity with molecular mass of 47035.49 Da. Rhombeobin showed amidolytic activity upon BAρNA, with a broad optimum pH (7–10 and was stable in solution up to 60°C. The amidolytic activity was inhibited by serine proteinase inhibitors and reducing agents, but not chelating agents. Rhombeobin showed high coagulant activity on mice plasma and bovine fibrinogen. The deduced amino acid sequence of Rhombeobin showed homology with other SVSPs, especially with LM-TL (L. m. muta and Gyroxin (C. d. terrificus. Rhombeobin acts, in vitro, as a strong procoagulant enzyme on mice citrated plasma, shortening the APTT and PT tests in adose-dependent manner. The protein showed, “ex vivo”, a strong defibrinogenating effect with 1 µg/animal. Lower doses activated the intrinsic and extrinsic coagulation pathways and impaired the platelet aggregation induced by ADP. Thus, this is the first report of a venom component that produces a venom-induced consumptive coagulopathy (VICC.

  12. Bioassay of procoagulant albumin in human plasma.

    Science.gov (United States)

    Grosset, A; Liu, L; Parker, C J; Rodgers, G M

    1994-09-01

    Procoagulant albumin (P-Al) is present in normal human plasma and increases monocyte and endothelial cell expression of tissue factor activity. To develop a bioassay for P-Al, we partially purified plasma from healthy volunteers and several patient groups using BaCl2 and (NH4)2SO4 precipitation. The samples were assayed for tissue factor (TF) inducing activity, expressed as a percentage increase compared to a serum-free media control. Over six months, the assay was reproducible in stored samples and in serial samples from normal volunteers. The plasma P-Al activities of 35 volunteers averaged 141 +/- 8.2% (SEM). There was no diurnal variation. There was no difference in the P-Al activity after a 12 hour fast and 2 hours after a large meal in 4 healthy volunteers. There was no increase in activity (r = 0.16) with the subject's age. The average activity from 16 poorly-controlled diabetics was 131 +/- 11% (SEM). No alteration in activity was seen with samples from patients with uremia, liver dysfunction, hemophilia, thrombotic events, or adenocarcinoma. These results indicate that P-Al activity can be bioassayed in individual patient samples; however, pathologic states associated with abnormal P-Al-induced tissue factor activity presently remain unidentified.

  13. Effect of individual dietary fatty acids on postprandial activation of blood coagulation factor VII and fibrinolysis in healthy young men

    DEFF Research Database (Denmark)

    Tholstrup, T.; Miller, G.J.; Bysted, Anette

    2003-01-01

    Background: Hypertriglyceridemia may represent a procoagulant state involving disturbances to the hemostatic system. Plasminogen activator inhibitor type 1 (PAI-1) is increased in the presence of hypertriglyceridemia. Free fatty acids (FFAs) in plasma may promote factor VII (FVII) activation...

  14. Protein C inhibitor acts as a procoagulant by inhibiting the thrombomodulin-induced activation of protein C in human plasma

    NARCIS (Netherlands)

    Elisen, M. G.; von dem Borne, P. A.; Bouma, B. N.; Meijers, J. C.

    1998-01-01

    Protein C inhibitor (PCI), which was originally identified as an inhibitor of activated protein C, also efficiently inhibits coagulation factors such as factor Xa and thrombin. Recently it was found, using purified proteins, that the anticoagulant thrombin-thrombomodulin complex was also inhibited

  15. The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors: a systematic review and meta-analysis.

    Science.gov (United States)

    Stuijver, Danka J F; van Zaane, Bregje; Romualdi, Erica; Brandjes, Dees P M; Gerdes, Victor E A; Squizzato, Alessandro

    2012-12-01

    Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis on the coagulation and fibrinolytic system in vivo . Data sources included MEDLINE (2006-2012), EMBASE (2006-2012), and reference lists. The sources were combined with our previous search containing studies from 1980-2006. Eligible studies were all observational or experimental studies. Two investigators independently extracted data and rated study quality. Weighted mean proportion and 95% confidence intervals were calculated and pooled using a fixed and a random-effects model. A total of 29 articles consisting of 51 studies were included, as in several articles more than one study was described. We included four intervention (before and after treatment in hyperthyroid patients), five cross-sectional (hyperthyroid subjects and euthyroid controls), and four experimental (before and after use of thyroid hormone in euthyroid subjects) medium/high quality studies for meta-analysis. We found that thyrotoxicosis shifts the haemostatic balance towards a hypercoagulable and hypofibrinolytic state with a rise in factors VIII and IX, fibrinogen, von Willebrand factor, and plasminogen activator inhibitor-1. This was observed in endogenous and exogenous thyrotoxicosis, and in subclinical as well as overt hyperthyroidism. We conclude that both subclinical and overt hyperthyroidism induce a prothrombotic state, which is therefore likely to be a risk factor for venous thrombosis.

  16. Catch a tiger snake by its tail: Differential toxicity, co-factor dependence and antivenom efficacy in a procoagulant clade of Australian venomous snakes.

    Science.gov (United States)

    Lister, Callum; Arbuckle, Kevin; Jackson, Timothy N W; Debono, Jordan; Zdenek, Christina N; Dashevsky, Daniel; Dunstan, Nathan; Allen, Luke; Hay, Chris; Bush, Brian; Gillett, Amber; Fry, Bryan G

    2017-11-01

    A paradigm of venom research is adaptive evolution of toxins as part of a predator-prey chemical arms race. This study examined differential co-factor dependence, variations relative to dietary preference, and the impact upon relative neutralisation by antivenom of the procoagulant toxins in the venoms of a clade of Australian snakes. All genera were characterised by venoms rich in factor Xa which act upon endogenous prothrombin. Examination of toxin sequences revealed an extraordinary level of conservation, which indicates that adaptive evolution is not a feature of this toxin type. Consistent with this, the venoms did not display differences on the plasma of different taxa. Examination of the prothrombin target revealed endogenous blood proteins are under extreme negative selection pressure for diversification, this in turn puts a strong negative selection pressure upon the toxins as sequence diversification could result in a drift away from the target. Thus this study reveals that adaptive evolution is not a consistent feature in toxin evolution in cases where the target is under negative selection pressure for diversification. Consistent with this high level of toxin conservation, the antivenom showed extremely high-levels of cross-reactivity. There was however a strong statistical correlation between relative degree of phospholipid-dependence and clotting time, with the least dependent venoms producing faster clotting times than the other venoms even in the presence of phospholipid. The results of this study are not only of interest to evolutionary and ecological disciplines, but also have implications for clinical toxinology. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Exogenous modification of platelet membranes with the omega-3 fatty acids EPA and DHA reduces platelet procoagulant activity and thrombus formation.

    Science.gov (United States)

    Larson, Mark K; Tormoen, Garth W; Weaver, Lucinda J; Luepke, Kristen J; Patel, Ishan A; Hjelmen, Carl E; Ensz, Nicole M; McComas, Leah S; McCarty, Owen J T

    2013-02-01

    Several studies have implicated the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in inhibition of normal platelet function, suggesting a role for platelets in EPA- and DHA-mediated cardioprotection. However, it is unclear whether the cardioprotective mechanisms arise from alterations to platelet-platelet, platelet-matrix, or platelet-coagulation factor interactions. Our previous results led us to hypothesize that EPA and DHA alter the ability of platelets to catalyze the generation of thrombin. We tested this hypothesis by exogenously modifying platelet membranes with EPA and DHA, which resulted in compositional changes analogous to increased dietary EPA and DHA intake. Platelets treated with EPA and DHA showed reductions in the rate of thrombin generation and exposure of platelet phosphatidylserine. In addition, treatment of platelets with EPA and DHA decreased thrombus formation and altered the processing of thrombin precursor proteins. Furthermore, treatment of whole blood with EPA and DHA resulted in increased occlusion time and a sharply reduced accumulation of fibrin under flow conditions. These results demonstrate that EPA and DHA inhibit, but do not eliminate, the ability of platelets to catalyze thrombin generation in vitro. The ability of EPA and DHA to reduce the procoagulant function of platelets provides a possible mechanism behind the cardioprotective phenotype in individuals consuming high levels of EPA and DHA.

  18. Extracellular Histones Increase Tissue Factor Activity and Enhance Thrombin Generation by Human Blood Monocytes.

    Science.gov (United States)

    Gould, Travis J; Lysov, Zakhar; Swystun, Laura L; Dwivedi, Dhruva J; Zarychanski, Ryan; Fox-Robichaud, Alison E; Liaw, Patricia C

    2016-12-01

    Sepsis is characterized by systemic activation of inflammatory and coagulation pathways in response to infection. Recently, it was demonstrated that histones released into the circulation by dying/activated cells may contribute to sepsis pathology. Although the ability of extracellular histones to modulate the procoagulant activities of several cell types has been investigated, the influence of histones on the hemostatic functions of circulating monocytes is unknown. To address this, we investigated the ability of histones to modulate the procoagulant potential of THP-1 cells and peripheral blood monocytes, and examined the effects of plasmas obtained from septic patients to induce a procoagulant phenotype on monocytic cells. Tissue factor (TF) activity assays were performed on histone-treated THP-1 cells and blood monocytes. Exposure of monocytic cells to histones resulted in increases in TF activity, TF antigen, and phosphatidylserine exposure. Histones modulate the procoagulant activity via engagement of Toll-like receptors 2 and 4, and this effect was abrogated with inhibitory antibodies. Increased TF activity of histone-treated cells corresponded to enhanced thrombin generation in plasma determined by calibrated automated thrombography. Finally, TF activity was increased on monocytes exposed to plasma from septic patients, an effect that was attenuated in plasma from patients receiving unfractionated heparin (UFH). Our studies suggest that increased levels of extracellular histones found in sepsis contribute to dysregulated coagulation by increasing TF activity of monocytes. These procoagulant effects can be partially ameliorated in sepsis patients receiving UFH, thereby identifying extracellular histones as a potential therapeutic target for sepsis treatment.

  19. Delayed-onset of procoagulant signalling revealed by kinetic analysis of COAT platelet formation.

    Science.gov (United States)

    Alberio, Lorenzo; Ravanat, Catherine; Hechler, Béatrice; Mangin, Pierre H; Lanza, François; Gachet, Christian

    2017-06-02

    The combined action of collagen and thrombin induces the formation of COAT platelets, which are characterised by a coat of procoagulant and adhesive molecules on their surface. Although recent work has started to highlight their clinical relevance, the exact mechanisms regulating the formation of procoagulant COAT platelets remain unclear. Therefore, we employed flow cytometry in order to visualise in real time surface and intracellular events following simultaneous platelet activation with convulxin and thrombin. After a rapid initial response pattern characterised by the homogenous activation of the fibrinogen receptor glycoprotein IIb/IIIa in all platelets, starting with a delay of about 2 minutes an increasing fraction transforms to procoagulant COAT platelets. Their surface is characterised by progressive loss of PAC-1 binding, expression of negative phospholipids and retention of α-granule von Willebrand factor. Intracellular events in procoagulant COAT platelets are a marked increase of free calcium into the low micromolar range, concomitantly with early depolarisation of the mitochondrial membrane and activation of caspase-3, while non-COAT platelets keep the intracellular free calcium in the nanomolar range and maintain an intact mitochondrial membrane. We show for the first time that the flow-cytometrically distinct fractions of COAT and non-COAT platelets differentially phosphorylate two signalling proteins, PKCα and p38MAPK, which may be involved in the regulation of the different calcium fluxes observed in COAT versus non-COAT platelets. This study demonstrates the utility of concomitant cellular and signalling evaluation using flow cytometry in order to further dissect the mechanisms underlying the dichotomous platelet response observed after collagen/thrombin stimulation.

  20. Procoagulant imbalance in patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Tripodi, Armando; Fracanzani, Anna L; Primignani, Massimo; Chantarangkul, Veena; Clerici, Marigrazia; Mannucci, Pier Mannuccio; Peyvandi, Flora; Bertelli, Cristina; Valenti, Luca; Fargion, Silvia

    2014-07-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by increased risk of cardiovascular events and liver-fibrosis. Both could be explained by a procoagulant-imbalance that was surmised but never directly demonstrated. We investigated 113 patients with varying histological liver damage [steatosis (n=32), steatohepatitis (n=51), metabolic-cirrhosis (n=30)], 54 with alcoholic/viral-cirrhosis and 179 controls. Plasma was evaluated for levels of pro- and anti-coagulants, and for thrombin-generation assessed as endogenous-thrombin-potential (ETP) with and without thrombomodulin or Protac® as protein C activators. The procoagulant-imbalance was defined as ETP-ratio (with-to-without thrombomodulin) or as Protac®-induced-coagulation-inhibition (PICI%). High ETP-ratios or low PICI% indicate resistance to thrombomodulin or Protac® and hence a procoagulant-imbalance. ETP-ratio increased from controls [0.57 (0.11-0.89)] to steatosis [0.72 (0.33-0.86)] and metabolic-cirrhosis [0.80 (0.57-0.95)], (pimbalance detected as ETP-ratio greater or PICI% lower than the median value of controls tended to have a higher risk of metabolic-syndrome, higher intima-media thickness, fibrosis, steatosis or lobular inflammation, all considered clinical manifestations of NAFLD. NAFLD is characterized by a procoagulant-imbalance progressing from the less severe (steatosis) to the most severe form of the disease (metabolic-cirrhosis). This imbalance appears to result from increased factor VIII and reduced protein C and might play a role in the risk of cardiovascular events and liver-fibrosis commonly observed in NAFLD. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  1. Low level of procoagulant platelet microparticles is associated with impaired coagulation and transfusion requirements in trauma patients

    DEFF Research Database (Denmark)

    Windeløv, Nis Agerlin; Johansson, Pär Ingemar; Sørensen, Anne Marie

    2014-01-01

    BACKGROUND: Following activation, platelets release small vesicles called platelet-derived microparticles (PMPs). PMPs accelerate thrombin generation and thus clot formation at sites of injury by exposing the procoagulant membrane phospholipid phosphatidylserine (PS). The role of PMPs in coagulop......BACKGROUND: Following activation, platelets release small vesicles called platelet-derived microparticles (PMPs). PMPs accelerate thrombin generation and thus clot formation at sites of injury by exposing the procoagulant membrane phospholipid phosphatidylserine (PS). The role of PMPs...

  2. Circulating procoagulant microparticles in cancer patients

    OpenAIRE

    Thaler, Johannes; Ay, Cihan; Weinstabl, Harald; Dunkler, Daniela; Simanek, Ralph; Vormittag, Rainer; Freyssinet, Jean-Marie; Zielinski, Christoph; Pabinger, Ingrid

    2010-01-01

    Abstract Accumulating evidence indicates that microparticles (MPs) are important mediators of the interaction between cancer and the hemostatic system. We conducted a large prospective cohort study to determine whether the number of circulating procoagulant MPs is elevated in cancer patients and whether the elevated MP levels are predictive of occurrence of venous thrombembolism (VTE). We analyzed plasma samples of 728 cancer patients from the ongoing prospective observational Vien...

  3. Population Divergence in Venom Bioactivities of Elapid Snake Pseudonaja textilis: Role of Procoagulant Proteins in Rapid Rodent Prey Incapacitation

    Science.gov (United States)

    Skejić, Jure; Hodgson, Wayne C.

    2013-01-01

    This study looked at how toxic proteins in venoms of adult Australian eastern Brown snakes Pseudonaja textilis from South Australian and Queensland populations interact with physiological functions of the lab SD rat Rattus norvegicus. Circulatory collapse and incoagulable blood occurred instantly after injection of venom under the dorsal skin of anaesthetised and mechanically ventilated rats in an imitation of a P. textilis bite. Intravenous injection of purified P. textilis (Mackay, QLD) venom prothrombin activator proteins caused instant failure of circulation, testifying of high toxicity of these proteins and suggesting their role in rapid incapacitation of rodent prey. The hypothesis is further supported by circulatory collapse occurring instantly despite artificial respiration in envenomed rats and the finding of extremely high venom procoagulant potency in rat plasma. LC-MS and physiology assays revealed divergent venom composition and biological activity of South Australian (Barossa locality) and Queensland (Mackay locality) populations, which may be driven by selection for different prey. The Queensland venom of P. textilis was found to be more procoagulant and to exhibit predominately presynaptic neurotoxicity, while the South Australian venom contained diverse postsynaptic type II and III α-neurotoxins in addition to the presynaptic neurotoxins and caused significantly faster onset of neuromuscular blockade in the rat phrenic nerve-diaphragm preparation. LC-MS analysis found evidence of multiple coagulation factor X-like proteins in P. textilis venoms, including a match to P. textilis coagulation factor X isoform 2, previously known to be expressed only in the liver. PMID:23691135

  4. Population divergence in venom bioactivities of elapid snake Pseudonaja textilis: role of procoagulant proteins in rapid rodent prey incapacitation.

    Directory of Open Access Journals (Sweden)

    Jure Skejić

    Full Text Available This study looked at how toxic proteins in venoms of adult Australian eastern Brown snakes Pseudonaja textilis from South Australian and Queensland populations interact with physiological functions of the lab SD rat Rattus norvegicus. Circulatory collapse and incoagulable blood occurred instantly after injection of venom under the dorsal skin of anaesthetised and mechanically ventilated rats in an imitation of a P. textilis bite. Intravenous injection of purified P. textilis (Mackay, QLD venom prothrombin activator proteins caused instant failure of circulation, testifying of high toxicity of these proteins and suggesting their role in rapid incapacitation of rodent prey. The hypothesis is further supported by circulatory collapse occurring instantly despite artificial respiration in envenomed rats and the finding of extremely high venom procoagulant potency in rat plasma. LC-MS and physiology assays revealed divergent venom composition and biological activity of South Australian (Barossa locality and Queensland (Mackay locality populations, which may be driven by selection for different prey. The Queensland venom of P. textilis was found to be more procoagulant and to exhibit predominately presynaptic neurotoxicity, while the South Australian venom contained diverse postsynaptic type II and III α-neurotoxins in addition to the presynaptic neurotoxins and caused significantly faster onset of neuromuscular blockade in the rat phrenic nerve-diaphragm preparation. LC-MS analysis found evidence of multiple coagulation factor X-like proteins in P. textilis venoms, including a match to P. textilis coagulation factor X isoform 2, previously known to be expressed only in the liver.

  5. Disseminated intravascular coagulation caused by moojenactivase, a procoagulant snake venom metalloprotease.

    Science.gov (United States)

    Sartim, Marco A; Cezarette, Gabriel N; Jacob-Ferreira, Anna L; Frantz, Fabiani G; Faccioli, Lucia H; Sampaio, Suely V

    2017-10-01

    Snake venom toxins that activate coagulation factors are key players in the process of venom-induced coagulopathy, and account for severe clinical manifestations. The present study applies a variety of biochemical, hematological, and histopathological approaches to broadly investigate the intravascular and systemic effects of moojenactivase (MooA), the first described PIIId subclass metalloprotease isolated from Bothrops sp. venom that activates coagulation factors. MooA induced consumption coagulopathy with high toxic potency, characterized by prolongation of prothrombin and activated partial thromboplastin time, consumption of fibrinogen and the plasma coagulation factors X and II, and thrombocytopenia. MooA promoted leukocytosis and expression of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-α, accompanied by tissue factor-dependent procoagulant activity in peripheral blood mononuclear cells. This metalloprotease also caused intravascular hemolysis, elevated plasma levels of creatine kinase-MB, aspartate transaminase, and urea/creatinine, and induced morphopathological alterations in erythrocytes, heart, kidney, and lungs associated with thrombosis and hemorrhage. Diagnosis of MooA-induced disseminated intravascular coagulation represents an important approach to better understand the pathophysiology of Bothrops envenomation and develop novel therapeutic strategies targeting hemostatic disturbances. Copyright © 2017. Published by Elsevier B.V.

  6. β cell membrane remodelling and procoagulant events occur in inflammation-driven insulin impairment: a GLP-1 receptor dependent and independent control.

    Science.gov (United States)

    Gleizes, Céline; Kreutter, Guillaume; Abbas, Malak; Kassem, Mohamad; Constantinescu, Andrei Alexandru; Boisramé-Helms, Julie; Yver, Blandine; Toti, Florence; Kessler, Laurence

    2016-02-01

    Inflammation and hyperglycaemia are associated with a prothrombotic state. Cell-derived microparticles (MPs) are the conveyors of active procoagulant tissue factor (TF) and circulate at high concentration in diabetic patients. Liraglutide, a glucagon-like peptide (GLP)-1 analogue, is known to promote insulin secretion and β-cell preservation. In this in vitro study, we examined the link between insulin impairment, procoagulant activity and plasma membrane remodelling, under inflammatory conditions. Rin-m5f β-cell function, TF activity mediated by MPs and their modulation by 1 μM liraglutide were examined in a cell cross-talk model. Methyl-β-cyclodextrine (MCD), a cholesterol depletor, was used to evaluate the involvement of raft on TF activity, MP shedding and insulin secretion as well as Soluble N-éthylmaleimide-sensitive-factor Attachment protein Receptor (SNARE)-dependent exocytosis. Cytokines induced a two-fold increase in TF activity at MP surface that was counteracted by liraglutide. Microparticles prompted TF activity on the target cells and a two-fold decrease in insulin secretion via protein kinase A (PKA) and p38 signalling, that was also abolished by liraglutide. Large lipid raft clusters were formed in response to cytokines and liraglutide or MCD-treated cells showed similar patterns. Cells pre-treated by saturating concentration of the GLP-1r antagonist exendin (9-39), showed a partial abolishment of the liraglutide-driven insulin secretion and liraglutide-decreased TF activity. Measurement of caspase 3 cleavage and MP shedding confirmed the contribution of GLP-1r-dependent and -independent pathways. Our results confirm an integrative β-cell response to GLP-1 that targets receptor-mediated signalling and membrane remodelling pointing at the coupling of insulin secretion and inflammation-driven procoagulant events. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and

  7. Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.

    Science.gov (United States)

    Nadir, Yona; Brenner, Benjamin; Fux, Liat; Shafat, Itay; Attias, Judith; Vlodavsky, Israel

    2010-11-01

    Heparanase is an endo-β-D-glucuronidase dominantly involved in tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is involved in the regulation of the hemostatic system. Our hypothesis was that heparanase is directly involved in activation of the coagulation cascade. Activated factor X and thrombin were studied using chromogenic assays, immunoblotting and thromboelastography. Heparanase levels were measured by enzyme-linked immunosorbent assay. A potential direct interaction between tissue factor and heparanase was studied by co-immunoprecipitation and far-western assays. Interestingly, addition of heparanase to tissue factor and activated factor VII resulted in a 3- to 4-fold increase in activation of the coagulation cascade as shown by increased activated factor X and thrombin production. Culture medium of human embryonic kidney 293 cells over-expressing heparanase and its derivatives increased activated factor X levels in a non-enzymatic manner. When heparanase was added to pooled normal plasma, a 7- to 8-fold increase in activated factor X level was observed. Subsequently, we searched for clinical data supporting this newly identified role of heparanase. Plasma samples from 35 patients with acute leukemia at presentation and 20 healthy donors were studied for heparanase and activated factor X levels. A strong positive correlation was found between plasma heparanase and activated factor X levels (r=0.735, P=0.001). Unfractionated heparin and an inhibitor of activated factor X abolished the effect of heparanase, while tissue factor pathway inhibitor and tissue factor pathway inhibitor-2 only attenuated the procoagulant effect. Using co-immunoprecipitation and far-western analyses it was shown that heparanase interacts directly with tissue factor. Overall, our results support the notion that heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated

  8. Procoagulant snake venoms have differential effects in animal plasmas: Implications for antivenom testing in animal models.

    Science.gov (United States)

    Maduwage, Kalana P; Scorgie, Fiona E; Lincz, Lisa F; O'Leary, Margaret A; Isbister, Geoffrey K

    2016-01-01

    Animal models are used to test toxic effects of snake venoms/toxins and the antivenom required to neutralise them. However, venoms that cause clinically relevant coagulopathy in humans may have differential effects in animals. We aimed to investigate the effect of different procoagulant snake venoms on various animal plasmas. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were measured in seven animal plasmas (human, rabbit, cat, guinea pig, pig, cow and rat). In vitro clotting times were then used to calculate the effective concentration (EC50) in each plasma for four snake venoms with different procoagulant toxins: Pseudonaja textilis, Daboia russelli, Echis carinatus and Calloselasma rhodostoma. Compared to human, PT and aPTT were similar for rat, rabbit and pig, but double for cat and cow, while guinea pig had similar aPTT but double PT. Fibrinogen and D-dimer levels were similar for all species. Human and rabbit plasmas had the lowest EC50 for P. textilis (0.1 and 0.4 μg/ml), D. russelli (0.4 and 0.1 μg/ml), E. carinatus (0.6 and 0.1 μg/ml) venoms respectively, while cat plasma had the lowest EC50 for C. rhodostoma (11 μg/ml) venom. Cow, rat, pig and guinea pig plasmas were highly resistant to all four venoms with EC50 10-fold that of human. Different animal plasmas have varying susceptibility to procoagulant venoms, and excepting rabbits, animal models are not appropriate to test procoagulant activity. In vitro assays on human plasma should instead be adopted for this purpose. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Circulating endothelial cells and procoagulant microparticles in patients with glioblastoma: prognostic value.

    Directory of Open Access Journals (Sweden)

    Gaspar Reynés

    Full Text Available AIM: Circulating endothelial cells and microparticles are prognostic factors in cancer. However, their prognostic and predictive value in patients with glioblastoma is unclear. The objective of this study was to investigate the potential prognostic value of circulating endothelial cells and microparticles in patients with newly diagnosed glioblastoma treated with standard radiotherapy and concomitant temozolomide. In addition, we have analyzed the methylation status of the MGMT promoter. METHODS: Peripheral blood samples were obtained before and at the end of the concomitant treatment. Blood samples from healthy volunteers were also obtained as controls. Endothelial cells were measured by an immunomagnetic technique and immunofluorescence microscopy. Microparticles were quantified by flow cytometry. Microparticle-mediated procoagulant activity was measured by endogen thrombin generation and by phospholipid-dependent clotting time. Methylation status of MGMT promoter was determined by multiplex ligation-dependent probe amplification. RESULTS: Pretreatment levels of circulating endothelial cells and microparticles were higher in patients than in controls (p<0.001. After treatment, levels of microparticles and thrombin generation decreased, and phospholipid-dependent clotting time increased significantly. A high pretreatment endothelial cell count, corresponding to the 99(th percentile in controls, was associated with poor overall survival. MGMT promoter methylation was present in 27% of tumor samples and was associated to a higher overall survival (66 weeks vs 30 weeks, p<0.004. CONCLUSION: Levels of circulating endothelial cells may have prognostic value in patients with glioblastoma.

  10. Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.

    Science.gov (United States)

    Mast, Alan E

    2016-01-01

    Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF-factor VIIa complexes that initiate blood coagulation. The TFPIα isoform is present in platelets. TFPIα contains a stretch of 9 amino acids nearly identical to those found in the B-domain of factor V that are well conserved in mammals. These amino acids provide exosite binding to activated factor V, which allows for TFPIα to inhibit prothrombinase during the initiation phase of blood coagulation. Endogenous inhibition at this point in the coagulation cascade was only recently recognized and has provided a biochemical rationale to explain the pathophysiological mechanisms underlying several clinical disorders. These include the east Texas bleeding disorder that is caused by production of an altered form of factor V with high affinity for TFPI and a paradoxical procoagulant effect of heparins. In addition, these findings have led to ideas for pharmacological targeting of TFPI that may reduce bleeding in hemophilia patients. © 2015 American Heart Association, Inc.

  11. Histones induce phosphatidylserine exposure and a procoagulant phenotype in human red blood cells.

    Science.gov (United States)

    Semeraro, F; Ammollo, C T; Esmon, N L; Esmon, C T

    2014-10-01

    Extracellular histones exert part of their prothrombotic activity through the stimulation of blood cells. Besides platelets, histones can bind to red blood cells (RBCs), which are important contributors to thrombogenesis, but little is known about the functional consequences of this interaction. To evaluate the effect of histones on the procoagulant potential of human RBCs with particular regard to the expression of surface phosphatidylserine (PS). PS exposure on human RBCs treated with a natural mixture of histones or recombinant individual histones was evaluated with fluorescein isothiocyanate-annexin-V binding and measured with flow cytometry. Calcium influx in RBCs loaded with the calcium-sensitive fluorophore Fluo-4 AM was assessed with flow cytometry. The procoagulant potential of histone-treated RBCs was evaluated with a purified prothrombinase assay and a one-stage plasma recalcification clotting test. Natural histones induced PS exposure on RBCs in a dose-dependent manner, and neutralization or cleavage of histones by heparin or activated protein C, respectively, abolished PS externalization. H4 was mainly responsible for the stimulating activity of histones, whereas the other subtypes were almost ineffective. Similarly, natural histones and H4 induced influx of calcium into RBCs, whereas the other individual histones did not. Histone-induced exposure of PS on RBCs translated into increased prothrombinase complex-mediated prothrombin activation and accelerated fibrin formation in plasma. Histones induce RBCs to express a procoagulant phenotype through the externalization of PS. This finding provides new insights into the prothrombotic activity of extracellular histones. © 2014 International Society on Thrombosis and Haemostasis.

  12. Procoagulant State in Current and Former Anabolic Androgenic Steroid Abusers

    DEFF Research Database (Denmark)

    Chang, Simon; Rasmussen, Jon J; Frandsen, Mikkel N

    2018-01-01

    BACKGROUND:  Anabolic androgenic steroid (AAS) abusers are considered at increased risk of cardiovascular morbidity and mortality. We hypothesized that current and former AAS abuse would induce a procoagulant shift in the haemostatic balance. METHODS:  Men 18 to 50 years of age were included...

  13. A new manufacturing process to remove thrombogenic factors (II, VII, IX, X, and XI) from intravenous immunoglobulin gamma preparations.

    Science.gov (United States)

    Park, Dong Hwarn; Kang, Gil Bu; Kang, Dae Eun; Hong, Jeung Woon; Lee, Min Gyu; Kim, Ki Yong; Han, Jeung Whan

    2017-01-01

    Coagulation factors (II, VII, IX, X, and particularly XIa) remaining in high concentrations in intravenous immunoglobulin (IVIG) preparations can form thrombi, causing thromboembolic events, and in serious cases, result in death. Therefore, manufacturers of biological products must investigate the ability of their production processes to remove procoagulant activities. Previously, we were able to remove coagulation factors II, VII, IX, and X from our IVIG preparation through ethanol precipitation, but factor XIa, which plays an important role in thrombosis, remained in the intermediate products. Here, we used a chromatographic process using a new resin that binds with high capacity to IgG and removes procoagulant activities. The procoagulant activities were reduced to low levels as determined by the thrombin generation assay: 250 s, FXI/FXIa ELISA: <0.31 ng/mL. Even after spiking with FXIa at a concentration 32.5 times higher than the concentration in normal specimens, the procoagulant activities were below the detection limit (<0.31 ng/mL). These results demonstrate the ability of our manufacturing process to remove procoagulant activities to below the detection limit (except by NaPTT), suggesting a reduced risk of thromboembolic events that maybe potentially caused by our IVIG preparation. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  14. Levels of procoagulant microvesicles are elevated after traumatic injury and platelet microvesicles are negatively correlated with mortality

    Directory of Open Access Journals (Sweden)

    Nicola Curry

    2014-10-01

    Full Text Available Background: Microvesicles (MV have been implicated in the development of thrombotic disease, such as acute respiratory distress syndrome (ARDS and multiple organ failure (MOF. Trauma patients are at increased risk of late thrombotic events, particularly those who receive a major transfusion. The aims of this study were: (a to determine whether there were increased numbers of pro-coagulant MV following injury; (b to determine their cellular origin; and (c to explore the effects of MV with clinical outcomes; in particular red cell transfusion requirements and death. Methods: Trauma patients were recruited at a Level 1 trauma centre. The presence of MV procoagulant phospholipid (PPL was assessed using 2 activity assays (PPL and thrombin generation. Enumeration and MV cellular origin was assessed using 2 colour flow cytometry. Results: Fifty consecutive patients were recruited; median age 38 (IQR: 24–55, median ISS 18 (IQR: 9–27. Circulating procoagulant MV, rich in phospholipid, were significantly elevated following traumatic injury relative to controls and remained elevated at 72 h post-injury. Red cell/AnnV+ and platelet/AnnV+ MV numbers were 6-fold and 2-fold higher than controls, respectively. Patients who died (n=9, 18% had significantly fewer CD41/AnnV+ MV and lower endogenous thrombin potential relative to patients who survived. Conclusions: MV are elevated following traumatic injury and may be implicated in the increased risk of trauma patients to pro-thrombotic states such as MOF and ARDS. Lower levels of procoagulant MV are associated with mortality and further investigation of this association is warranted.

  15. Dual mechanism of integrin αIIbβ3 closure in procoagulant platelets.

    Science.gov (United States)

    Mattheij, Nadine J A; Gilio, Karen; van Kruchten, Roger; Jobe, Shawn M; Wieschhaus, Adam J; Chishti, Athar H; Collins, Peter; Heemskerk, Johan W M; Cosemans, Judith M E M

    2013-05-10

    Inactivation of integrin αIIbβ3 reverses platelet aggregate formation upon coagulation. Platelets from patient (Scott) and mouse (Capn1(-/-) and Ppif(-/-)) blood reveal a dual mechanism of αIIbβ3 inactivation: by calpain-2 cleavage of integrin-associated proteins and by cyclophilin D/TMEM16F-dependent phospholipid scrambling. These data provide novel insight into the switch mechanisms from aggregating to procoagulant platelets. Aggregation of platelets via activated integrin αIIbβ3 is a prerequisite for thrombus formation. Phosphatidylserine-exposing platelets with a key role in the coagulation process disconnect from a thrombus by integrin inactivation via an unknown mechanism. Here we show that αIIbβ3 inactivation in procoagulant platelets relies on a sustained high intracellular Ca(2+), stimulating intracellular cleavage of the β3 chain, talin, and Src kinase. Inhibition of calpain activity abolished protein cleavage, but only partly suppressed αIIbβ3 inactivation. Integrin αIIbβ3 inactivation was unchanged in platelets from Capn1(-/-) mice, suggesting a role of the calpain-2 isoform. Scott syndrome platelets, lacking the transmembrane protein TMEM16F and having low phosphatidylserine exposure, displayed reduced αIIbβ3 inactivation with the remaining activity fully dependent on calpain. In platelets from Ppif(-/-) mice, lacking mitochondrial permeability transition pore (mPTP) formation, agonist-induced phosphatidylserine exposure and αIIbβ3 inactivation were reduced. Treatment of human platelets with cyclosporin A gave a similar phenotype. Together, these data point to a dual mechanism of αIIbβ3 inactivation via calpain(-2) cleavage of integrin-associated proteins and via TMEM16F-dependent phospholipid scrambling with an assistant role of mPTP formation.

  16. Treatment of Ebola Virus Infection With a Recombinant Inhibitor of Factor Vlla/Tissue Factor: A Study in Rhesus Monkeys

    National Research Council Canada - National Science Library

    Geisbert, Thomas W; Hensley, Lisa E; Jahrling, Peter B; Larsen, Tom; Geisbert, Joan B

    2003-01-01

    Infection with the Ebola virus induces overexpression of the procoagulant tissue factor in primate monocytes and macrophages, suggesting that inhibition of the tissue-factor pathway could ameliorate...

  17. The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors

    NARCIS (Netherlands)

    Stuijver, Danka J. F.; van Zaane, Bregje; Romualdi, Erica; Brandjes, Dees P. M.; Gerdes, Victor E. A.; Squizzato, Alessandro

    2012-01-01

    Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis

  18. Cell-based laboratory evaluation of coagulation activation by antineoplastic drugs for the treatment of lymphoid tumors

    Directory of Open Access Journals (Sweden)

    Misae Tsunaka

    2016-07-01

    Full Text Available Objectives: Combining vorinostat, L-asparaginase, and doxorubicin (Dox led to improved response rates in the treatment of lymphoid tumors. However, deep-vein thrombosis has been noted as one of the most serious side effects with these drugs, and how these regimens cause deep-vein thrombosis is unclear. Methods: We investigated the procoagulant effects of vorinostat, L-asparaginase, and doxorubicin in lymphoid tumors, focusing on tissue factor, phosphatidylserine, and antithrombin. The human vascular endothelial cell line EAhy926 as well as the lymphoid neoplastic cell lines HUT78 (cutaneous T-cell lymphoma, Molt4 (acute T-lymphoblastic leukemia, and Ramos (Burkitt lymphoma were employed to investigate these procoagulant effects. Results: Vorinostat, L-asparaginase, and doxorubicin induced exposure of phosphatidylserine and procoagulant activity on the surface of lymphoid tumor cells. Vorinostat and doxorubicin also induced phosphatidylserine exposure and increased procoagulant activity on EAhy926 cells. Expression of tissue factor antigen was induced by doxorubicin on the surface of each type of cells, whereas expression of tissue factor mRNA was unchanged. Secretion of antithrombin from HepG2 cells was reduced only by L-asparaginase. Conclusion: These data suggest that vorinostat and doxorubicin may induce procoagulant activity in vessels through apoptosis of tumor cells and through phosphatidylserine exposure and/or tissue factor expression on vascular endothelial cells. L-asparaginase may induce a thrombophilic state by reducing the secretion of anticoagulant proteins such as antithrombin. The laboratory methods described here could be useful to evaluate the procoagulant effects of antineoplastic drugs.

  19. Enhancement of proinflammatory and procoagulant responses to silica particles by monocyte-endothelial cell interactions

    Directory of Open Access Journals (Sweden)

    Liu Xin

    2012-09-01

    particles was not mediated by soluble factors but was dependent on the direct contact between monocytes and HUVECs. Furthermore, flow cytometry analysis showed that SiO2 particles could markedly increase CD40L expression in HUVECs. Our data also demonstrated that the stimulation of cocultures with SiO2 particles strongly enhanced c-Jun NH2-terminal kinase (JNK phosphorylation and NF-κB activation in both HUVECs and THP-1 cells, whereas the phosphorylation of p38 was not affected. Conclusions Our data demonstrate that SiO2 particles can significantly augment proinflammatory and procoagulant responses through CD40–CD40L-mediated monocyte-endothelial cell interactions via the JNK/NF-κB pathway, which suggests that cooperative interactions between particles, endothelial cells, and monocytes may trigger or exacerbate cardiovascular dysfunction and disease, such as atherosclerosis and thrombosis. These findings also indicate that the monocyte-endothelial cocultures represent a sensitive in vitro model system to assess the potential toxicity of particles and provide useful information that may help guide the future design and use of inorganic particles in biomedical applications.

  20. Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular Vesicles

    Directory of Open Access Journals (Sweden)

    Jiong-Wei Wang

    2017-12-01

    Full Text Available Plasma extracellular vesicles (EVs are lipid membrane vesicles involved in several biological processes including coagulation. Both coagulation and lipid metabolism are strongly associated with cardiovascular events. Lowering very-low- and low-density lipoprotein ((VLDL particles via dextran sulphate LDL apheresis also removes coagulation proteins. It remains unknown, however, how coagulation proteins are removed in apheresis. We hypothesize that plasma EVs that contain high levels of coagulation proteins are concomitantly removed with (VLDL particles by dextran sulphate apheresis. For this, we precipitated (VLDL particles from human plasma with dextran sulphate and analyzed the abundance of coagulation proteins and EVs in the precipitate. Coagulation pathway proteins, as demonstrated by proteomics and a bead-based immunoassay, were over-represented in the (VLDL precipitate. In this precipitate, both bilayer EVs and monolayer (VLDL particles were observed by electron microscopy. Separation of EVs from (VLDL particles using density gradient centrifugation revealed that almost all coagulation proteins were present in the EVs and not in the (VLDL particles. These EVs also showed a strong procoagulant activity. Our study suggests that dextran sulphate used in LDL apheresis may remove procoagulant EVs concomitantly with (VLDL particles, leading to a loss of coagulation proteins from the blood.

  1. Maternal malaria induces a procoagulant and antifibrinolytic state that is embryotoxic but responsive to anticoagulant therapy.

    Directory of Open Access Journals (Sweden)

    John W Avery

    Full Text Available Low birth weight and fetal loss are commonly attributed to malaria in endemic areas, but the cellular and molecular mechanisms that underlie these poor birth outcomes are incompletely understood. Increasing evidence suggests that dysregulated hemostasis is important in malaria pathogenesis, but its role in placental malaria (PM, characterized by intervillous sequestration of Plasmodium falciparum, proinflammatory responses, and excessive fibrin deposition is not known. To address this question, markers of coagulation and fibrinolysis were assessed in placentae from malaria-exposed primigravid women. PM was associated with significantly elevated placental monocyte and proinflammatory marker levels, enhanced perivillous fibrin deposition, and increased markers of activated coagulation and suppressed fibrinolysis in placental plasma. Submicroscopic PM was not proinflammatory but tended to be procoagulant and antifibrinolytic. Birth weight trended downward in association with placental parasitemia and high fibrin score. To directly assess the importance of coagulation in malaria-induced compromise of pregnancy, Plasmodium chabaudi AS-infected pregnant C57BL/6 mice were treated with the anticoagulant, low molecular weight heparin. Treatment rescued pregnancy at midgestation, with substantially decreased rates of active abortion and reduced placental and embryonic hemorrhage and necrosis relative to untreated animals. Together, the results suggest that dysregulated hemostasis may represent a novel therapeutic target in malaria-compromised pregnancies.

  2. Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia.

    Science.gov (United States)

    Pawlinski, Rafal; Pedersen, Brian; Schabbauer, Gernot; Tencati, Michael; Holscher, Todd; Boisvert, William; Andrade-Gordon, Patricia; Frank, Rolf Dario; Mackman, Nigel

    2004-02-15

    Sepsis is associated with a systemic activation of coagulation and an excessive inflammatory response. Anticoagulants have been shown to inhibit both coagulation and inflammation in sepsis. In this study, we used both genetic and pharmacologic approaches to analyze the role of tissue factor and protease-activated receptors in coagulation and inflammation in a mouse endotoxemia model. We used mice expressing low levels of the procoagulant molecule, tissue factor (TF), to analyze the effects of TF deficiency either in all tissues or selectively in hematopoietic cells. Low TF mice had reduced coagulation, inflammation, and mortality compared with control mice. Similarly, a deficiency of TF expression by hematopoietic cells reduced lipopolysaccharide (LPS)-induced coagulation, inflammation, and mortality. Inhibition of the down-stream coagulation protease, thrombin, reduced fibrin deposition and prolonged survival without affecting inflammation. Deficiency of either protease activated receptor-1 (PAR-1) or protease activated receptor-2 (PAR-2) alone did not affect inflammation or survival. However, a combination of thrombin inhibition and PAR-2 deficiency reduced inflammation and mortality. These data demonstrate that hematopoietic cells are the major pathologic site of TF expression during endotoxemia and suggest that multiple protease-activated receptors mediate crosstalk between coagulation and inflammation.

  3. Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models

    Science.gov (United States)

    Siner, Joshua I.; Samelson-Jones, Benjamin J.; Crudele, Julie M.; French, Robert A.; Lee, Benjamin J.; Zhou, Shanzhen; Merricks, Elizabeth; Raymer, Robin; Camire, Rodney M.; Arruda, Valder R.

    2016-01-01

    Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645–1648) in the design of B-domain–deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by furin is in fact deleterious to FVIII-BDD secretion and procoagulant activity. Inhibition of furin increases the secretion and decreases the intracellular retention of FVIII-BDD protein in mammalian cells. Our new variant (FVIII-ΔF), in which this recognition motif is removed, efficiently circumvents furin. FVIII-ΔF demonstrates increased recombinant protein yields, enhanced clotting activity, and higher circulating FVIII levels after adeno-associated viral vector–based liver gene therapy in a murine model of severe hemophilia A (HA) compared with FVIII-BDD. Moreover, we observed an amelioration of the bleeding phenotype in severe HA dogs with sustained therapeutic FVIII levels after FVIII-ΔF gene therapy at a lower vector dose than previously employed in this model. The immunogenicity of FVIII-ΔF did not differ from that of FVIII-BDD as a protein or a gene therapeutic. Thus, contrary to previous suppositions, FVIII variants that can avoid furin processing are likely to have enhanced translational potential for HA therapy. PMID:27734034

  4. Measurement of microparticle tissue factor activity in clinical samples: A summary of two tissue factor-dependent FXa generation assays.

    Science.gov (United States)

    Hisada, Yohei; Alexander, Wyeth; Kasthuri, Raj; Voorhees, Peter; Mobarrez, Fariborz; Taylor, Angela; McNamara, Coleen; Wallen, Hakan; Witkowski, Marco; Key, Nigel S; Rauch, Ursula; Mackman, Nigel

    2016-03-01

    Thrombosis is a leading cause of morbidity and mortality. Detection of a prothrombotic state using biomarkers would be of great benefit to identify patients at risk of thrombosis that would benefit from thromboprophylaxis. Tissue factor (TF) is a highly procoagulant protein that under normal conditions is not present in the blood. However, increased levels of TF in the blood in the form of microparticles (MPs) (also called extracellular vesicles) are observed under various pathological conditions. In this review, we will discuss studies that have measured MP-TF activity in a variety of diseases using two similar FXa generation assay. One of the most robust signals for MP-TF activity (16-26 fold higher than healthy controls) is observed in pancreatic cancer patients with venous thromboembolism. In this case, the TF+ MPs appear to be derived from the cancer cells. Surprisingly, cirrhosis and acute liver injury are associated with 17-fold and 38-fold increases in MP-TF activity, respectively. Based on mouse models, we speculate that the TF+ MPs are derived from hepatocytes. More modest increases are observed in patients with urinary tract infections (6-fold) and in a human endotoxemia model (9-fold) where monocytes are the likely source of the TF+ MPs. Finally, there is no increase in MP-TF activity in the majority of cardiovascular disease patients. These studies indicate that MP-TF activity may be a useful biomarker to identify patients with particular diseases that have an increased risk of thrombosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Factor VII-activating protease

    DEFF Research Database (Denmark)

    Ramanathan, Ramshanker; Gram, Jørgen B; Sand, Niels Peter R

    2017-01-01

    : Factor VII-activating protease (FSAP) may regulate development of cardiovascular disease (CVD). We evaluated sex differences in FSAP measures and examined the association between FSAP and coronary artery calcification (CAC) in a middle-aged population. Participants were randomly selected citizens...

  6. Activation of human factor V by factor Xa and thrombin

    International Nuclear Information System (INIS)

    Monkovic, D.D.; Tracy, P.B.

    1990-01-01

    The activation of human factor V by factor Xa and thrombin was studied by functional assessment of cofactor activity and sodium dodecyl sulfate-polycarylamide gel electrophoresis followed by either autoradiography of 125 I-labeled factor V activation products or Western blot analyses of unlabeled factor V activation products. Cofactor activity was measured by the ability of the factor V/Va peptides to support the activation of prothrombin. The factor Xa catalyzed cleavage of factor V was observed to be time, phospholipid, and calcium ion dependent, yielding a cofactor with activity equal to that of thrombin-activated factor V (factor Va). The cleavage pattern differed markedly from the one observed in the bovine system. The factor Xa activated factor V subunits expressing cofactor activity were isolated and found to consist of peptides of M r 220,000 and 105,000. Although thrombin cleaved the M r 220,000 peptide to yield peptides previously shown to be products of thrombin activation, cofactor activity did not increase. N-Terminal sequence analysis confirmed that both factor Xa and thrombin cleave factor V at the same bond to generate the M r 220,000 peptide. The factor Xa dependent functional assessment of 125 I-labeled factor V coupled with densitometric analyses of the cleavage products indicated that the cofactor activity of factor Xa activated factor V closely paralleled the appearance of the M r 220,000 peptide. The data indicate that factor Xa is as efficient an enzyme toward factor V as thrombin

  7. Psychosocial factors underlying physical activity

    Directory of Open Access Journals (Sweden)

    Ji Cheng-Ye

    2007-09-01

    of physical activity on academic achievement and other factors beyond physical health; barriers of not having enough time and having too many assignments perceived to hinder frequent physical activity; and parental approval. More rigorous research on psychosocial determinants with close-ended items developed from these open-ended data and with larger sample sizes of students is necessary. Research with parents and school staff will be needed to understand the perceptions of these stakeholder groups key to creating the students' social environment.

  8. Psychosocial factors underlying physical activity.

    Science.gov (United States)

    Zhang, Juan; Middlestadt, Susan E; Ji, Cheng-Ye

    2007-09-19

    factors beyond physical health; barriers of not having enough time and having too many assignments perceived to hinder frequent physical activity; and parental approval. More rigorous research on psychosocial determinants with close-ended items developed from these open-ended data and with larger sample sizes of students is necessary. Research with parents and school staff will be needed to understand the perceptions of these stakeholder groups key to creating the students' social environment.

  9. Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease

    Science.gov (United States)

    van Beers, Eduard J.; Schaap, Marianne C.L.; Berckmans, René J.; Nieuwland, Rienk; Sturk, Augueste; van Doormaal, Frederiek F.; Meijers, Joost C.M.; Biemond, Bart J.

    2009-01-01

    Background Sickle cell disease is characterized by a hypercoagulable state as a result of multiple factors, including chronic hemolysis and circulating cell-derived microparticles. There is still no consensus on the cellular origin of such microparticles and the exact mechanism by which they may enhance coagulation activation in sickle cell disease. Design and Methods In the present study, we analyzed the origin of circulating microparticles and their procoagulant phenotype during painful crises and steady state in 25 consecutive patients with sickle cell disease. Results The majority of microparticles originated from platelets (GPIIIa,CD61) and erythrocytes (glycophorin A,CD235), and their numbers did not differ significantly between crisis and steady state. Erythrocyte-derived microparticles strongly correlated with plasma levels of markers of hemolysis, i.e. hemoglobin (r=−0.58, pmicroparticles (r=0.63, p0.05). The extent of factor XI inhibition was associated with erythrocyte-derived microparticles (r=0.50, p=0.023). Conclusions We conclude that the procoagulant state in sickle cell disease is partially explained by the factor XI-dependent procoagulant properties of circulating erythrocyte-derived microparticles. PMID:19815831

  10. Canine lymphocyte activating factor (LAF)

    International Nuclear Information System (INIS)

    Shifrine, M.; Whaley, C.B.; Wilson, F.D.; Taylor, N.J.

    1979-01-01

    The immune response of an animal is the sum of the result of the interaction of various cells mainly through soluble mediators. It is not enough to look at specific cell populations, it is also necessary to study the interactions between purified cell population. The effect of one subpopulation on another is via soluble mediators. We have been studying one (of several) such mediators in its relation to radiation effects on the immune response. Lymphocyte activating factor (LAF) is defined functionally as a potentiator of the response of thymocytes to phytohemagglutinin (PHA) or concanavalin (con-A). It can also elicit response of unstimulated subpopulations separated from the thymus. It is a product of adherent populations, presumably macrophages. It has been shown to be produced by human, rabbit, and mouse cells, but has not been reported in the dog. It also was shown to be present in higher concentrations in irradiated mice than in comparable unirradiated mice. We have shown that LAF is produced by plastic-adherent populations derived from peripheral blood. Currently we are working to determine the lymphocyte subpopulations with which LAF interacts

  11. Vitamin D modulates tissue factor and protease-activated receptor 2 expression in vascular smooth muscle cells.

    Science.gov (United States)

    Martinez-Moreno, Julio M; Herencia, Carmen; Montes de Oca, Addy; Muñoz-Castañeda, Juan R; Rodríguez-Ortiz, M Encarnación; Díaz-Tocados, Juan M; Peralbo-Santaella, Esther; Camargo, Antonio; Canalejo, Antonio; Rodriguez, Mariano; Velasco-Gimena, Francisco; Almaden, Yolanda

    2016-03-01

    Clinical and epidemiologic studies reveal an association between vitamin D deficiency and increased risk of cardiovascular disease. Because vascular smooth muscle cell (VSMC)-derived tissue factor (TF) is suggested to be critical for arterial thrombosis, we investigated whether the vitamin D molecules calcitriol and paricalcitol could reduce the expression of TF induced by the proinflammatory cytokine TNF-α in human aortic VSMCs. We found that, compared with controls, incubation with TNF-α increased TF expression and procoagulant activity in a NF-κB-dependent manner, as deduced from the increased nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells protein 65 (p65-NF-κB) and direct interaction of NF-κB to the TF promoter. This was accompanied by the up-regulation of TF signaling mediator protease-activated receptor 2 (PAR-2) expression and by the down-regulation of vitamin D receptor expression in a miR-346-dependent way. However, addition of calcitriol or paricalcitol blunted the TNF-α-induced TF expression and activity (2.01 ± 0.24 and 1.32 ± 0.14 vs. 3.02 ± 0.39 pmol/mg protein, P < 0.05), which was associated with down-regulation of NF-κB signaling and PAR-2 expression, as well as with restored levels of vitamin D receptor and enhanced expression of TF pathway inhibitor. Our data suggest that inflammation promotes a prothrombotic state through the up-regulation of TF function in VSMCs and that the beneficial cardiovascular effects of vitamin D may be partially due to decreases in TF expression and its activity in VSMCs. © FASEB.

  12. Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells.

    Science.gov (United States)

    Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

    2009-12-15

    Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.

  13. Extracellular histones induce tissue factor expression in vascular endothelial cells via TLR and activation of NF-κB and AP-1.

    Science.gov (United States)

    Yang, Xinyu; Li, Lin; Liu, Jin; Lv, Ben; Chen, Fangping

    2016-01-01

    Extracellular histones have been recognized recently as proinflammatory mediators; they are released from dying cells in response to inflammatory challenge, contributing to endothelial cell dysfunction, thrombin formation, organ failure, and death during sepsis. Clinical studies suggest that the plasma concentration of the histone-DNA complex is correlated with the severity of DIC and is a poor independent prognostic marker in sepsis. In addition, platelet activation stimulates thrombus formation. Whether histones contribute to procoagulant activity in other ways remains elusive. In this study, we confirmed that histones induce tissue factor (TF) expression in a concentration- and time-dependent manner in vascular endothelial cells (ECs) and macrophages. However, histones did not affect TF pathway inhibitor expression. Moreover, blocking the cell surface receptors TLR4 and TLR2 with specific neutralizing antibodies significantly reduced histone-induced TF expression. Furthermore, histones enhanced the nuclear translocation of NF-κB (c-Rel/p65) and AP-1 expression in a time-dependent manner in ECs. Mutating NF-κB and AP-1 significantly reduced histone-induced TF expression. Altogether, our experiments suggest that histone induces TF expression in ECs via cell surface receptors TLR4 and TLR2, simultaneously depending on the activation of the transcription factors NF-κB and AP-1. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. A simple clot based assay for detection of procoagulant cell-derived microparticles.

    Science.gov (United States)

    Patil, Rucha; Ghosh, Kanjaksha; Shetty, Shrimati

    2016-05-01

    Cell-derived microparticles (MPs) are important biomarkers in many facets of medicine. However, the MP detection methods used till date are costly and time consuming. The main aim of this study was to standardize an in-house clot based screening method for MP detection which would not only be specific and sensitive, but also inexpensive. Four different methods of MP assessment were performed and the results correlated. Using the flow cytometry technique as the gold standard, 25 samples with normal phosphatidylserine (PS) expressing MP levels and 25 samples with elevated levels were selected, which was cross checked by the commercial STA Procoag PPL clotting time (CT) assay. A simple recalcification time and an in-house clot assay were the remaining two tests. The in-house test measures the CT after the addition of calcium chloride to MP rich plasma, following incubation with Russell viper venom and phospholipid free plasma. The CT obtained by the in-house assay significantly correlated with the results obtained by flow cytometry (R2=0.87, p<0.01). Though preliminary, the in-house assay seems to be efficient, inexpensive and promising. It could definitely be utilized routinely for procoagulant MP assessment in various clinical settings.

  15. The nonenzymatic subunit of pseutarin C, a prothrombin activator from eastern brown snake (Pseudonaja textilis) venom, shows structural similarity to mammalian coagulation factor V.

    Science.gov (United States)

    Rao, Veena S; Swarup, Sanjay; Kini, R Manjunatha

    2003-08-15

    Pseutarin C is a group C prothrombin activator from the venom of the eastern brown snake Pseudonaja textilis. It is a multi-subunit protein complex consisting of catalytic and nonenzymatic subunits similar to coagulation factor Xa and factor Va, respectively. Here we describe the complete sequence of the nonenzymatic subunit. Based on the partial amino acid sequence of the nonenzymatic subunit, degenerate primers were designed. Using a "walking" strategy based on sequentially designed primers, we determined the complete cDNA sequence of the nonenzymatic subunit. The cDNA encodes a protein of 1461 amino acid residues, which includes a 30-residue signal peptide, a mature protein of 1430 amino acid residues, and a stop codon. cDNA blot analysis showed a single transcript of approximately 4.6 kb. The deduced amino acid sequence shows approximately 50% identity to mammalian factor V and by homology has a similar domain structure consisting of domains A1-A2-B-A3-C1-C2. Interestingly, the B domain of pseutarin C is shorter than that of mammalian factor V (FV). Although most of the proteolytic activation sites are conserved, 2 of 3 proteolytic sites cleaved by activated protein C are mutated, and thus activated protein C is not able to inactivate this procoagulant toxin. The predicted posttranslational modifications, including disulfide bonds, N-glycosylation, phosphorylation, and sulfation, in pseutarin C are significantly different compared with bovine factor V. Thus, our data demonstrate that the nonenzymatic subunit of group C prothrombin activators is structurally similar to mammalian FV.

  16. Key factors of enterprise innovation activity

    Directory of Open Access Journals (Sweden)

    Pichugina Maryna Anatoliivna

    2015-02-01

    Full Text Available The article deals with the studies of factors and conditions that define enterprise innovative activity. It is distinguished factors that influence the orientation on innovation of a company and factors that influence the innovation ability. It is noted an interdependence between innovative ability, orientation and activity. The article is also dedicated to analyses of influence specific industry characteristics and inner view of enterprise. It is discussed the influence of such factors as knowledge base, the organizational learning mechanisms, an external openness and the structure of innovative connections on the company opportunities to innovate. It is tried to focus on the impact of the environment on enterprise capabilities.

  17. Activated Protein C Drives the Hyperfibrinolysis of Acute Traumatic Coagulopathy.

    Science.gov (United States)

    Davenport, Ross A; Guerreiro, Maria; Frith, Daniel; Rourke, Claire; Platton, Sean; Cohen, Mitchell; Pearse, Rupert; Thiemermann, Chris; Brohi, Karim

    2017-01-01

    Major trauma is a leading cause of morbidity and mortality worldwide with hemorrhage accounting for 40% of deaths. Acute traumatic coagulopathy exacerbates bleeding, but controversy remains over the degree to which inhibition of procoagulant pathways (anticoagulation), fibrinogen loss, and fibrinolysis drive the pathologic process. Through a combination of experimental study in a murine model of trauma hemorrhage and human observation, the authors' objective was to determine the predominant pathophysiology of acute traumatic coagulopathy. First, a prospective cohort study of 300 trauma patients admitted to a single level 1 trauma center with blood samples collected on arrival was performed. Second, a murine model of acute traumatic coagulopathy with suppressed protein C activation via genetic mutation of thrombomodulin was used. In both studies, analysis for coagulation screen, activated protein C levels, and rotational thromboelastometry (ROTEM) was performed. In patients with acute traumatic coagulopathy, the authors have demonstrated elevated activated protein C levels with profound fibrinolytic activity and early depletion of fibrinogen. Procoagulant pathways were only minimally inhibited with preservation of capacity to generate thrombin. Compared to factors V and VIII, proteases that do not undergo activated protein C-mediated cleavage were reduced but maintained within normal levels. In transgenic mice with reduced capacity to activate protein C, both fibrinolysis and fibrinogen depletion were significantly attenuated. Other recognized drivers of coagulopathy were associated with less significant perturbations of coagulation. Activated protein C-associated fibrinolysis and fibrinogenolysis, rather than inhibition of procoagulant pathways, predominate in acute traumatic coagulopathy. In combination, these findings suggest a central role for the protein C pathway in acute traumatic coagulopathy and provide new translational opportunities for management of

  18. Biomaterials trigger endothelial cell activation when co-incubated with human whole blood.

    Science.gov (United States)

    Herklotz, Manuela; Hanke, Jasmin; Hänsel, Stefanie; Drichel, Juliane; Marx, Monique; Maitz, Manfred F; Werner, Carsten

    2016-10-01

    Endothelial cell activation resulting from biomaterial contact or biomaterial-induced blood activation may in turn also affect hemostasis and inflammatory processes in the blood. Current in vitro hemocompatibility assays typically ignore these modulating effects of the endothelium. This study describes a co-incubation system of human whole blood, biomaterial and endothelial cells (ECs) that was developed to overcome this limitation. First, human endothelial cells were characterized in terms of their expression of coagulation- and inflammation-relevant markers in response to various activators. Subsequently, their capacity to regulate hemostasis as well as complement and granulocyte activation was monitored in a hemocompatibility assay. After blood contact, quiescent ECs exhibited anticoagulant and anti-inflammatory properties. When they were co-incubated with surfaces exhibiting pro-coagulant or pro-inflammatory characteristics, the ECs down-regulated coagulation but not complement or leukocyte activation. Analysis of intracellular levels of the endothelial activation markers E-selectin and tissue factor showed that co-incubation with model surfaces and blood significantly increased the activation state of ECs. Finally, the coagulation- and inflammation-modulating properties of the ECs were tested after blood/biomaterial exposure. Pre-activation of ECs by biomaterials in the blood induced a pro-coagulant and pro-inflammatory state of the ECs, wherein the pro-coagulant response was higher for biomaterial/blood pre-activated ECs than for TNF-α-pre-activated cells. This work provides evidence that biomaterials, even without directly contacting the endothelium, affect the endothelial activation state with and have consequences for plasmatic and cellular reactions in the blood. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. 76 FR 14413 - Risk Mitigation Strategies To Address Potential Procoagulant Activity in Immune Globulin...

    Science.gov (United States)

    2011-03-16

    .../visit for directions, visitor parking, and public transportation information. Contact Person: Rhonda.... A transcript of the public workshop will be available on the Internet at http://www.fda.gov...

  20. Activation of factor VII bound to tissue factor: a key early step in the tissue factor pathway of blood coagulation.

    OpenAIRE

    Rao, L V; Rapaport, S I

    1988-01-01

    Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and factor IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. Our earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were ma...

  1. Activation of factor VII bound to tissue factor: A key early step in the tissue factor pathway of blood coagulation

    International Nuclear Information System (INIS)

    Rao, L.V.M.; Rapaport, S.I.

    1988-01-01

    Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. The earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were made with purified factor VII, X, and tissue factor; in some experiments antithrombin III and heparin were added to prevent back-activation of factor VII. Factor X was activated at similar rates in reaction mixtures containing either VII or factor VIIa after an initial 30-sec lag with factor VII. In reaction mixtures with factor VII a linear activation of factor X was established several minutes before cleavage of 125 I-labeled factor VII to the two-chain activated molecule was demonstrable on gel profiles. These data suggest that factor VII/tissue factor cannot activate measurable amounts of factor X over several minutes. Overall, the results support the hypothesis that a rapid preferential activation of factor VII bound to tissue factor by trace amounts of factor Xa is a key early step in tissue factor-dependent blood coagulation

  2. Activated human neutrophils release hepatocyte growth factor/scatter factor.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Hepatocyte growth factor or scatter factor (HGF\\/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+\\/-216, 484+\\/-221 and 565+\\/-278 pg\\/ml, respectively) compared to controls (118+\\/-42 pg\\/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.

  3. Platelet activating factor activity in the phospholipids of bovine spermatozoa

    Energy Technology Data Exchange (ETDEWEB)

    Parks, J.E.; Hough, S.; Elrod, C. (Cornell Univ., Ithaca, NY (USA))

    1990-11-01

    Platelet activating factor (PAF) has been detected in sperm from several mammalian species and can affect sperm motility and fertilization. Because bovine sperm contain a high percentage of ether-linked phospholipid precursors required for PAF synthesis, a study was undertaken to determine the PAF activity of bovine sperm phospholipids. Total lipids of washed, ejaculated bull sperm were extracted, and phospholipids were fractionated by thin-layer chromatography. Individual phospholipid fractions were assayed for PAF activity on the basis of (3H)serotonin release from equine platelets. PAF activity was detected in the PAF fraction (1.84 pmol/mumol total phospholipid) and in serine/inositol (PS/PI), choline (CP), and ethanolamine phosphoglyceride (EP) and cardiolipin (CA) fractions. Activity was highest in the CP fraction (8.05 pmol/mumol total phospholipid). Incomplete resolution of PAF and neutral lipids may have contributed to the activity in the PS/PI and CA fractions, respectively. Phospholipids from nonsperm sources did not stimulate serotonin release. Platelet activation by purified PAF and by sperm phospholipid fractions was inhibited by the receptor antagonist SRI 63-675. These results indicate that bovine sperm contain PAF and that other sperm phospholipids, especially CP and EP, which are high in glycerylether components, are capable of receptor-mediated platelet activation.

  4. Plasma triacylglycerol and coagulation factor concentrations predict the anticoagulant effect of dietary fish oil in overweight subjects

    DEFF Research Database (Denmark)

    Vanschoonbeek, Kristof; Feijge, Marion A H; Saris, Wim H M

    2007-01-01

    fish-oil effects. In study 1, 54 overweight subjects consumed 3.1 g (n-3) PUFA daily. In study 2, which involved 42 overweight patients with type 2 diabetes, 20 subjects consumed (n-3) PUFA, whereas 22 others ingested a preparation rich in (n-6) PUFA. Tissue factor-induced thrombin generation (thrombin...... potential) was determined as an integrated measure of plasma coagulant activity. In both studies, multivariate analysis indicated a strong clustering of fasting concentrations of triacylglycerols, prothrombin, factor V, factor VII, and factor X with one another at baseline. This cluster of factors......-induced lowering of triacylglycerol and coagulation factor V, VII, and X concentrations, and thrombin generation. We conclude that high fasting triacylglycerol concentrations predict high procoagulant activity and a lowering of thrombin potential with dietary fish oil....

  5. Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma

    International Nuclear Information System (INIS)

    Morrison, S.A.; Jesty, J.

    1984-01-01

    A comparism was made of the tissue factor-dependent activation of tritium-labeled factor IX and factor X in a human plasma system and a study was made of the role of proteases known to stimulate factor VII activity. Plasma was defibrinated by heating and depleted of its factors IX and X by passing it through antibody columns. Addition of human brain thromboplastin, Ca2+, and purified 3H-labeled factor X to the plasma resulted, after a short lag, in burst-like activation of the factor X, measured as the release of radiolabeled activation peptide. The progress of activation was slowed by both heparin and a specific inhibitor of factor Xa but factor X activation could not be completely abolished by such inhibitors. In the case of 3H-factor IX activation, the rate also increased for approximately 3 min after addition of thromboplastin, but was not subsequently curtailed. A survey of proteases implicated as activators of factor VII in other settings showed that both factor Xa and factor IXa could accelerate the activation of factor IX. However, factor Xa was unique in obliterating activation when present at concentrations greater than approximately 1 nM. Heparin inhibited the tissue factor-dependent activation of factor IX almost completely, apparently through the effect of antithrombin on the feedback reactions of factors Xa and IXa on factor VII. These results suggest that a very tight, biphasic control of factor VII activity exists in human plasma, which is modulated mainly by factor Xa. At saturation of factor VIIa/tissue factor, factor IX activation was significantly more rapid than was previously found in bovine plasma under similar conditions. The activation of factor X at saturation was slightly more rapid than in bovine plasma, despite the presence of heparin

  6. Activation of 125I-Factor IX and 125I-Factor X: Effect of tissue factor and Factor VII, Factor Xsub(a) and thrombin

    International Nuclear Information System (INIS)

    Oesterud, B.; Rapaport, S.I.

    Activation of Factor IX and Factor X was studied by adding 125 I-Factor IX or 125 I-Factor X to reaction mixtures and quantitating cleavage products by reduced sodium dodecylsulfate gel electrophoresis. Thrombin failed to activate Factors IX or X; Factor Xsub(a) produced insignificant amounts of cleavage products of both factors. In contrast, the reaction product of tissue factor and Factor VII cleaved large amounts of both Factor IX and Factor X in purified systems and in plasma. In incubation mixtures of plasma containing added 125 I-Factor IX or 125 I-Factor X, tissue factor and Ca 2+ ions, the percentage of total radioactivity in the heavy chain peak of 125 I-IXsub(a) and the heavy chain of 125 I-Xsub(a) increased at a similar rate. When the tissue factor was diluted, similar curves were obtained for percent cleavage of 125 I-Factor IX and percent cleavage of 125 I-Factor X plotted against tissue factor concentration. These findings support the hypothesis that activation of Factor IX by the tissue factor-Factor VII reaction product represents a physiologically significant step in normal haemostasis. (author)

  7. The role of stress hormones in the relationship between resting blood pressure and coagulation activity.

    Science.gov (United States)

    Wirtz, Petra H; Ehlert, Ulrike; Emini, Luljeta; Rüdisüli, Katharina; Groessbauer, Sara; Mausbach, Brent T; von Känel, Roland

    2006-12-01

    Systemic hypertension confers a hypercoagulable state. We hypothesized that resting mean blood pressure (MBP) interacts with stress hormones in predicting coagulation activity at rest and with acute mental stress. We measured plasma clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, epinephrine and norepinephrine, and saliva cortisol in 42 otherwise healthy normotensive and hypertensive medication-free men (mean age 43 +/- 14 years) at rest, immediately after stress, and twice during 60 min of recovery from stress. At rest, the MBP-by-epinephrine interaction predicted FVII:C (beta = -0.33, P AUC) predicted D-dimer AUC (beta = 0.34, P = 0.04) independent of MBP. The MBP-by-epinephrine AUC interaction predicted FVII:C AUC (beta = 0.28) and fibrinogen AUC (beta = -0.30), and the MBP-by-norepinephrine AUC interaction predicted FVIII:C AUC (beta = -0.28), all with borderline significance (Ps < 0.09) and independent of age and BMI. MBP significantly altered the association between stress hormones and coagulation activity at rest and, with borderline significance, across the entire stress and recovery interval. Independent of MBP, catecholamines were associated with procoagulant effects and cortisol reactivity dampened the acute procoagulant stress response.

  8. Role of hepsin in factor VII activation in zebrafish.

    Science.gov (United States)

    Khandekar, Gauri; Jagadeeswaran, Pudur

    2014-01-01

    Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, factor VII and in small amounts in its activated form, factor VIIa. However, the mechanism of initial generation of factor VIIa is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases factor VII activating protease and hepsin play a role in activating factor VII, however, it has remained controversial. In this paper we estimated the levels of factor VIIa and factor VII for the first time in zebrafish adult population and also reevaluated the role of the above two serine proteases in activating factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease and hepsin was performed followed by assaying for their effect on factor VIIa concentration and extrinsic coagulation as measured by the kinetic prothrombin time. Factor VII activating protease knockdown showed no change in kinetic prothrombin time and no effect on factor VIIa levels while hepsin knockdown increased the kinetic prothrombin time and significantly reduced the factor VIIa plasma levels. Our results thus indicate that hepsin plays a physiologically important role in factor VII activation and hemostasis in zebrafish. © 2013.

  9. Edible bird’s nest attenuates procoagulation effects of high-fat diet in rats

    Directory of Open Access Journals (Sweden)

    Yida Z

    2015-07-01

    Full Text Available Zhang Yida,1,2 Mustapha Umar Imam,1 Maznah Ismail,1,3 Norsharina Ismail,1 Zhiping Hou1 1Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Cardiology Department, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, People’s Republic of China; 3Faculty of Medicine and Health Sciences, Department of Nutrition and Dietetics, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Edible bird’s nest (EBN is popular in Asia, and has long been used traditionally as a supplement. There are, however, limited evidence-based studies on its efficacy. EBN has been reported to improve dyslipidemia, which is closely linked to hypercoagulation states. In the present study, the effects of EBN on high-fat diet- (HFD- induced coagulation in rats were evaluated. Rats were fed for 12 weeks with HFD alone or in combination with simvastatin or EBN. Food intake was estimated, and weight measurements were made during the experimental period. After sacrifice, serum oxidized low-density lipo­protein (oxLDL, adiponectin, leptin, von willibrand factor, prostacyclin, thromboxane and lipid profile, and whole blood coagulation indices (bleeding time, prothrombin time, activated partial thromboplastin time, red blood count count, and platelet count were estimated. Furthermore, hepatic expression of coagulation-related genes was evaluated using multiplex polymerase chain reaction. The results indicated that EBN could attenuate HFD-induced hypercholesterolemia and coagulation similar to simvastatin, partly through transcriptional regulation of coagulation-related genes. The results suggested that EBN has the potential for lowering the risk of cardiovascular disease-related hypercoagulation due to hypercholesterolemia. Keywords: edible bird’s nest, coagulation, high-fat diet, hypercholesterolemia, nutrigeno­mics

  10. Co-factor activated recombinant adenovirus proteinases

    Science.gov (United States)

    Anderson, Carl W.; Mangel, Walter F.

    1996-08-06

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  11. Fibrinolytic response to tumor necrosis factor in healthy subjects

    NARCIS (Netherlands)

    van der Poll, T.; Levi, M. [=Marcel M.; Büller, H. R.; van Deventer, S. J.; de Boer, J. P.; Hack, C. E.; ten Cate, J. W.

    1991-01-01

    Tumor necrosis factor (TNF) may be involved in the disturbance of the procoagulant-fibrinolytic balance in septicemia, leading to microvascular thrombosis. To assess the dynamics of the fibrinolytic response to TNF in humans, we performed a crossover saline-controlled study in six healthy men,

  12. 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

  13. Synthesis of Phosphatidylserine and Its Stereoisomers: Their Role in Activation of Blood Coagulation.

    Science.gov (United States)

    Mallik, Suman; Prasad, Ramesh; Bhattacharya, Anindita; Sen, Prosenjit

    2018-05-10

    Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein-lipid interactions.

  14. Model of a ternary complex between activated factor VII, tissue factor and factor IX.

    Science.gov (United States)

    Chen, Shu-wen W; Pellequer, Jean-Luc; Schved, Jean-François; Giansily-Blaizot, Muriel

    2002-07-01

    Upon binding to tissue factor, FVIIa triggers coagulation by activating vitamin K-dependent zymogens, factor IX (FIX) and factor X (FX). To understand recognition mechanisms in the initiation step of the coagulation cascade, we present a three-dimensional model of the ternary complex between FVIIa:TF:FIX. This model was built using a full-space search algorithm in combination with computational graphics. With the known crystallographic complex FVIIa:TF kept fixed, the FIX docking was performed first with FIX Gla-EGF1 domains, followed by the FIX protease/EGF2 domains. Because the FIXa crystal structure lacks electron density for the Gla domain, we constructed a chimeric FIX molecule that contains the Gla-EGF1 domains of FVIIa and the EGF2-protease domains of FIXa. The FVIIa:TF:FIX complex has been extensively challenged against experimental data including site-directed mutagenesis, inhibitory peptide data, haemophilia B database mutations, inhibitor antibodies and a novel exosite binding inhibitor peptide. This FVIIa:TF:FIX complex provides a powerful tool to study the regulation of FVIIa production and presents new avenues for developing therapeutic inhibitory compounds of FVIIa:TF:substrate complex.

  15. Activity of recombinant factor VIIa under different conditions in vitro

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, Jørgen

    2008-01-01

    Recombinant activated factor VII (NovoSeven; Novo Nordisk A/S, Måløv, Denmark) is an effective drug for treatment of bleeding in patients with haemophilia A or B and inhibitors. Little is known about physiological conditions influencing the efficacy of recombinant activated factor VII. We...... investigated the in-vitro effects of pH, temperature, and haemodilution on the activity of recombinant activated factor VII. Samples from eight healthy volunteers were spiked with recombinant activated factor VII (final concentration 1.7 microg/ml) and adjusted to pH 6.0, 6.5, 7.0, and 7.4 or analysed at 30......, 33, 37, and 40 degrees C, or diluted 0, 10, 20, 40, and 60% with dextran before analysis. Samples were analysed as rotational thromboelastometry in whole blood (clotting time, clot formation time, and maximum clot firmness) with and without Innovin (tissue factor), and as factor VII coagulant...

  16. Kinetics of the Factor XIa catalyzed activation of human blood coagulation Factor IX

    International Nuclear Information System (INIS)

    Walsh, P.N.; Bradford, H.; Sinha, D.; Piperno, J.R.; Tuszynski, G.P.

    1984-01-01

    The kinetics of activation of human Factor IX by human Factor XIa was studied by measuring the release of a trichloroacetic acid-soluble tritium-labeled activation peptide from Factor IX. Initial rates of trichloroacetic acid-soluble 3 H-release were linear over 10-30 min of incubation of Factor IX (88 nM) with CaCl 2 (5 mM) and with pure (greater than 98%) Factor XIa (0.06-1.3 nM), which was prepared by incubating human Factor XI with bovine Factor XIIa. Release of 3 H preceded the appearance of Factor IXa activity, and the percentage of 3 H released remained constant when the mole fraction of 3 H-labeled and unlabeled Factor IX was varied and the total Factor IX concentration remained constant. A linear correlation (r greater than 0.98, P less than 0.001) was observed between initial rates of 3 H-release and the concentration of Factor XIa, measured by chromogenic assay and by radioimmunoassay and added at a Factor IX:Factor XIa molar ratio of 70-5,600. Kinetic parameters, determined by Lineweaver-Burk analysis, include K/sub m/ (0.49 microM) of about five- to sixfold higher than the plasma Factor IX concentration, which could therefore regulate the reaction. The catalytic constant (k/sub cat/) (7.7/s) is approximately 20-50 times higher than that reported by Zur and Nemerson for Factor IX activation by Factor VIIa plus tissue factor. Therefore, depending on the relative amounts of Factor XIa and Factor VIIa generated in vivo and other factors which may influence reaction rates, these kinetic parameters provide part of the information required for assessing the relative contributions of the intrinsic and extrinsic pathways to Factor IX activation, and suggest that the Factor XIa catalyzed reaction is physiologically significant

  17. Physical activity and cardiovascular disease risk factors among ...

    African Journals Online (AJOL)

    Background: Cardiovascular diseases (CVD) risk factors are increasing at an unprecedented rate in developing countries. However, fewer studies have evaluated the role of physical activity in preventing CVD in these countries. We assessed level physical activity and its relationship with CVD risk factors among young and ...

  18. Stem cell factor stimulates chicken osteoclast activity in vitro

    NARCIS (Netherlands)

    van't Hof, R. J.; von Lindern, M.; Nijweide, P. J.; Beug, H.

    1997-01-01

    Stem cell factor (SCF) is a polypeptide growth factor active on multiple cell types, mainly of hematopoietic origin. We studied the effects of avian SCF on the differentiation of chicken osteoclasts from their putative progenitors as well as on the bone-resorbing activity of terminally

  19. Factors Associated with Physical Activity Behaviors Among Rural Adolescents

    OpenAIRE

    Urruty, Kenli A.

    2009-01-01

    The "obesity epidemic" in the United States is a current health concern that has sparked research interest in physical activity as a means of weight management. However, little research has examined the physical activity behaviors of rural adolescents. The goal of the current study was to use a biopsychosocial framework to examine the physical activity behaviors of a sample of rural adolescents, and explore factors associated with physical activity participation. A sample of 162 ninth- an...

  20. Coagulation activation anc microparticle-associated coagulant activity in cancer patients An exploratory prospective study

    NARCIS (Netherlands)

    van Doormaal, Frederiek F.; Kleinjan, Ankie; Berckmans, René J.; Mackman, Nigel; Manly, David; Kamphuisen, Pieter W.; Richel, Dick J.; Büller, Harry R.; Sturk, Auguste; Nieuwland, Rienk

    2012-01-01

    Cancer increases the risk of venous thromboembolism (VTE). Here, we investigated the contribution of microparticle (MP)-dependent procoagulant activity to the prothrombotic state in these patients. In 43 cancer patients without VIE at study entry and 22 healthy volunteers, markers of in vivo and

  1. Nutrition, Physical Activity, and Obesity - Behavioral Risk Factor Surveillance System

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset includes data on adult's diet, physical activity, and weight status from Behavioral Risk Factor Surveillance System. This data is used for DNPAO's Data,...

  2. [Factors influencing research activity of Andalusian nurses and improvement strategies].

    Science.gov (United States)

    López Alonso, Sergio R; Gálvez González, María; Amezcua, Manuel

    2013-04-01

    To identify factors influencing research activity of Andalusian nurses and to find improvement strategies. Qualitative research using SWOT analysis (weaknesses, threats, strengths, opportunities). Nurses were selected deliberately in eight groups according to predetermined criteria. Analysis included categorization and relationship of factors and strategies. 81 participants were included in groups of 7-12 range. 45 categories were identified with 212 factors: 12 weaknesses (50 factors), 10 strengths (44 factors), 12 threats (68 factors) and 11 opportunities (50 factors). In addition, 32 categories were identified with 53 strategies: 14 categories of W-T strategies (42 strategies), 3 categories of S-T strategies (11 strategies), 5 categories of W-O strategies (13 strategies) and 10 categories of S-O strategies (41 strategies). Nurses identified numerous factors, mainly threats. The strategies are focused on W-T but they also suggest many but weak 5-0 strategies due to the low potential of the opportunities and strengths perceived.

  3. Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma

    Science.gov (United States)

    Herrero-Martin, David; Fourtouna, Argyro; Niedan, Stephan; Riedmann, Lucia T.; Schwentner, Raphaela; Aryee, Dave N. T.

    2011-01-01

    Ewing's sarcoma family tumors (ESFT) are characterized by specific chromosomal translocations, which give rise to EWS-ETS chimeric proteins. These aberrant transcription factors are the main pathogenic drivers of ESFT. Elucidation of the factors influencing EWS-ETS expression and/or activity will guide the development of novel therapeutic agents against this fatal disease. PMID:22135504

  4. Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma

    Directory of Open Access Journals (Sweden)

    David Herrero-Martin

    2011-01-01

    Full Text Available Ewing's sarcoma family tumors (ESFT are characterized by specific chromosomal translocations, which give rise to EWS-ETS chimeric proteins. These aberrant transcription factors are the main pathogenic drivers of ESFT. Elucidation of the factors influencing EWS-ETS expression and/or activity will guide the development of novel therapeutic agents against this fatal disease.

  5. Physical Activity : The interplay between individual and neighbourhood factors

    NARCIS (Netherlands)

    M.A. Beenackers (Marielle)

    2013-01-01

    textabstractPhysical inactivity is among the most important and prevalent risk factors of many major diseases. Although the health benefits of regular exercise and a physically active lifestyle are well known, many people are still not active. Understanding why some population groups are physically

  6. Increased Nucleosomes and Neutrophil Activation Link to Disease Progression in Patients with Scrub Typhus but Not Murine Typhus in Laos.

    Science.gov (United States)

    Paris, Daniel H; Stephan, Femke; Bulder, Ingrid; Wouters, Diana; van der Poll, Tom; Newton, Paul N; Day, Nicholas P J; Zeerleder, Sacha

    2015-01-01

    Cell-mediated immunity is essential in protection against rickettsial illnesses, but the role of neutrophils in these intracellular vasculotropic infections remains unclear. This study analyzed the plasma levels of nucleosomes, FSAP-activation (nucleosome-releasing factor), and neutrophil activation, as evidenced by neutrophil-elastase (ELA) complexes, in sympatric Lao patients with scrub typhus and murine typhus. In acute scrub typhus elevated nucleosome levels correlated with lower GCS scores, raised respiratory rate, jaundice and impaired liver function, whereas neutrophil activation correlated with fibrinolysis and high IL-8 plasma levels, a recently identified predictor of severe disease and mortality. Nucleosome and ELA complex levels were associated with a 4.8-fold and 4-fold increased risk of developing severe scrub typhus, beyond cut off values of 1,040 U/ml for nucleosomes and 275 U/ml for ELA complexes respectively. In murine typhus, nucleosome levels associated with pro-inflammatory cytokines and the duration of illness, while ELA complexes correlated strongly with inflammation markers, jaundice and increased respiratory rates. This study found strong correlations between circulating nucleosomes and neutrophil activation in patients with scrub typhus, but not murine typhus, providing indirect evidence that nucleosomes could originate from neutrophil extracellular trap (NET) degradation. High circulating plasma nucleosomes and ELA complexes represent independent risk factors for developing severe complications in scrub typhus. As nucleosomes and histones exposed on NETs are highly cytotoxic to endothelial cells and are strongly pro-coagulant, neutrophil-derived nucleosomes could contribute to vascular damage, the pro-coagulant state and exacerbation of disease in scrub typhus, thus indicating a detrimental role of neutrophil activation. The data suggest that increased neutrophil activation relates to disease progression and severe complications, and

  7. Potential Role of Activating Transcription Factor 5 during Osteogenesis

    Directory of Open Access Journals (Sweden)

    Luisa Vicari

    2016-01-01

    Full Text Available Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2, encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  8. Potential Role of Activating Transcription Factor 5 during Osteogenesis.

    Science.gov (United States)

    Vicari, Luisa; Calabrese, Giovanna; Forte, Stefano; Giuffrida, Raffaella; Colarossi, Cristina; Parrinello, Nunziatina Laura; Memeo, Lorenzo

    2016-01-01

    Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB) family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2), encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  9. Detecting Differential Transcription Factor Activity from ATAC-Seq Data

    Directory of Open Access Journals (Sweden)

    Ignacio J. Tripodi

    2018-05-01

    Full Text Available Transcription factors are managers of the cellular factory, and key components to many diseases. Many non-coding single nucleotide polymorphisms affect transcription factors, either by directly altering the protein or its functional activity at individual binding sites. Here we first briefly summarize high-throughput approaches to studying transcription factor activity. We then demonstrate, using published chromatin accessibility data (specifically ATAC-seq, that the genome-wide profile of TF recognition motifs relative to regions of open chromatin can determine the key transcription factor altered by a perturbation. Our method of determining which TFs are altered by a perturbation is simple, is quick to implement, and can be used when biological samples are limited. In the future, we envision that this method could be applied to determine which TFs show altered activity in response to a wide variety of drugs and diseases.

  10. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin

    International Nuclear Information System (INIS)

    Hill-Eubanks, D.C.; Parker, C.G.; Lollar, P.

    1989-01-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. The authors isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as judged by NaDodSO 4 /PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated 125 I-fVIII to function as a cofactor in the activation of factor X by factor IXa, they found that fVIII is activated by the venom enzyme. The venom enzyme-activated fVIII was isolated in stable form by cation-exchange HPLC. von Willebrand factor inhibited venom enzyme-activated fVIII but not thrombin-activated fVIII. These results suggest that the binding of fVIII to von Willebrand factor depends on the presence of an intact light chain and that activated fVIII must dissociate from von Willebrand factor to exert its cofactor effect. Thus, proteolytic activation of fVIII-von Willebrand factor complex appears to be differentially regulated by light-chain cleavage to dissociate the complex and heavy-chain cleavage to activate the cofactor function

  11. Psychosocial factors and theory in physical activity studies in minorities.

    Science.gov (United States)

    Mama, Scherezade K; McNeill, Lorna H; McCurdy, Sheryl A; Evans, Alexandra E; Diamond, Pamela M; Adamus-Leach, Heather J; Lee, Rebecca E

    2015-01-01

    To summarize the effectiveness of interventions targeting psychosocial factors to increase physical activity (PA) among ethnic minority adults and explore theory use in PA interventions. Studies (N = 11) were identified through a systematic review and targeted African American/Hispanic adults, specific psychosocial factors, and PA. Data were extracted using a standard code sheet and the Theory Coding Scheme. Social support was the most common psychosocial factor reported, followed by motivational readiness, and self-efficacy, as being associated with increased PA. Only 7 studies explicitly reported using a theoretical framework. Future efforts should explore theory use in PA interventions and how integration of theoretical constructs, including psychosocial factors, increases PA.

  12. Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Skouby, Sven O; Kluft, Cornelis

    2011-01-01

    Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...... progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P=0.001). OC use increased FSAP antigen by 25% and FSAP activity...

  13. Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Skouby, Sven O.; Kluft, Cornelis

    2011-01-01

    progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P≤0.001). OC use increased FSAP antigen by 25% and FSAP activity......Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...... by 59% (P0.05). The relative increase in FSAP activity was significantly higher in women carrying the 1601GG genotype (63%) than in women carrying 1601GA genotype (50%) (P=0.01) and was associated with an increased activation of FVII. In conclusion: OC use increases the plasma measures of FSAP...

  14. Radiation activation of transcription factors in mammalian cells

    International Nuclear Information System (INIS)

    Kraemer, M.; Stein, B.; Mai, S.; Kunz, E.; Koenig, H.; Ponta, H.; Herrlich, P.; Rahmsdorf, H.J.; Loferer, H.; Grunicke, H.H.

    1990-01-01

    In mammalian cells radiation induces the enhanced transcription of several genes. The cis acting elements in the control region of inducible genes have been delimited by site directed mutagenesis. Several different elements have been found in different genes. They do not only activate gene transcription in response to radiation but also in response to growth factors and to tumor promoter phorbol esters. The transcription factors binding to these elements are present also in non-irradiated cells, but their DNA binding activity and their transactivating capability is increased upon irradiation. The signal chain linking the primary radiation induced signal (damaged DNA) to the activation of transcription factors involves the action of (a) protein kinase(s). (orig.)

  15. Formation of tissue factor activity following incubation of recombinant human tissue factor apoprotein with plasma lipoproteins

    International Nuclear Information System (INIS)

    Sakai, T.; Kisiel, W.

    1990-01-01

    Incubation of recombinant human tissue factor apoprotein (Apo-TF) with human plasma decreased the recalcified clotting time of this plasma in a time-and dose-dependent manner suggesting relipidation of the Apo-TF by plasma lipoproteins. Incubation of Apo-TF with purified preparations of human very low density, low density and high density lipoproteins resulted in tissue factor activity in a clotting assay. The order of effectiveness was VLDL greater than LDL much greater than HDL. Tissue factor activity generated by incubation of a fixed amount of Apo-TF with plasma lipoproteins was lipoprotein concentration-dependent and saturable. The association of Apo-TF with lipoprotein particles was supported by gel filtration studies in which 125 I-Apo-TF coeluted with the plasma lipoprotein in the void volume of a Superose 6 column in the presence and absence of calcium ions. In addition, void-volume Apo-TF-lipoprotein fractions exhibited tissue factor activity. These results suggest that the factor VIII-bypassing activity of bovine Apo-TF observed in a canine hemophilic model may be due, in part, to its association with plasma lipoproteins and expression of functional tissue factor activity

  16. Contributions of procoagulants and anticoagulants to the international normalized ratio and thrombin generation assay in patients treated with warfarin: potential role of protein Z as a powerful determinant of coagulation assays.

    Science.gov (United States)

    Choi, Qute; Kim, Ji-Eun; Hyun, Jungwon; Han, Kyou-Sup; Kim, Hyun Kyung

    2013-07-01

    The effects of warfarin are measured with the international normalized ratio (INR). However, the thrombin generation assay (TGA) may offer more information about global coagulation. We analyzed the monitoring performance of the TGA and INR and investigated the impact of procoagulants (fibrinogen, factor (F)II, FVII, FIX, and FX) and anticoagulants (proteins C, S, and Z) on them. The TGA was performed on a calibrated automated thrombogram, producing lag time, endogenous thrombin potential (ETP), and peak thrombin in 239 patients treated with warfarin. Pro- and anticoagulant levels were also measured. The INR was significantly and inversely correlated with ETP. The therapeutic range of ETP comparable to an INR range of 2.0-3.0 was 290.1-494.6. ETP showed comparable performance to the INR as a warfarin-monitoring parameter with respect to clinical complication rate. The median levels of FII, FVII, FIX, and FX and proteins C and Z tended to decrease gradually with increasing anticoagulation intensity according to the INR or ETP. Of note, protein Z levels decreased dramatically with increasing anticoagulation status. INRs were significantly determined by FII, FVII, and protein Z. ETP was significantly dependent on FVII, and proteins C and Z concentration. Protein Z significantly reduced the total amount of thrombin generation and prolonged PT value in vitro. The INR and ETP exhibit similar efficacy for warfarin monitoring according to the clinical complication rate. Protein Z is considered to be a significant determinant of INR and ETP in patients on warfarin therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Influence Of Dilution Factor For Activity Measurement Of 60CO

    International Nuclear Information System (INIS)

    Hermawan-Candra; Nazaroh; Ermi-Juita

    2003-01-01

    Influence of dilution factor for activity measurement of 60 Co has been studied. The aim of this research is to determine influence between activity measurement result of 60 Co before and after diluted. Measurement were done by using ionization chamber detectors system and gamma spectrometry system with NaI(TI) detector. Discrepancy within three ionization chambers measurements were 0.2% - 2.1% and NaI(Tl) were 3.5% - 6%. (author)

  18. Factoring in Factor VIII With Acute Ischemic Stroke.

    Science.gov (United States)

    Siegler, James E; Samai, Alyana; Albright, Karen C; Boehme, Amelia K; Martin-Schild, Sheryl

    2015-10-01

    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. © The Author(s) 2015.

  19. The Relevant Factors in Promoting Reading Activities in Elementary Schools

    Science.gov (United States)

    Huang, Han-Chen; Tsai, Yao-Hsu; Huang, Shih-Hsiang

    2015-01-01

    In order to help students absorb knowledge, schools often conduct reading activities. Thorough planning and strategies, however, are needed to insure the effect of reading promotions, and make them a deeply-rooted part of life. This study adopted the analytic hierarchy process (AHP) to discuss the relevant factors in promoting reading activities…

  20. Prevalence and risk factors for Active Convulsive Epilepsy in ...

    African Journals Online (AJOL)

    Introduction: epilepsy is common in sub-Saharan Africa, but there is little data in West Africa, to develop public health measures for epilepsy in this region. Methods: we conducted a three-stage cross-sectional survey to determine the prevalence and risk factors for active convulsive epilepsy (ACE), and estimated the ...

  1. The significance of human factors in nuclear activities

    International Nuclear Information System (INIS)

    Weil, L.; Berg, H.P.

    1999-01-01

    Human factors is an aspect increasingly investigated in the last few years in efforts and programmes for enhancing the operational safety of nuclear systems. Methodology has been elaborated for analysis and evaluation of human reliability, or development of instruments supporting the decisions to be taken by the operators at the man-control room interface of nuclear installations, as well as initial approaches to introduce organisational factors which may influence the man-machine function allocation, and thus are an element of the safety culture concept. The significance of human factors in nuclear activities, as well as activities at the national and international level for optimisation of the man-machine interface and the man-organisation interface are discussed. (orig./CB) [de

  2. Selected cultural factors associated with physical activity among Latino women.

    Science.gov (United States)

    Jurkowski, Janine M; Mosquera, Margarita; Ramos, Blanca

    2010-01-01

    In the United States, Latinos are the largest ethnic group after non-Hispanic whites. Latinos currently represent 15% of the U.S. population and their numbers are growing in nontraditional areas. Latino women (Latinas) disproportionately experience chronic disease risk factors and report low levels of leisure time physical activity. This study examined cultural factors associated with leisure time physical activity among Latinas living in a new Latino destination in northeastern New York. Community-based participatory research, a collaborative approach in which community members are equitably and actively involved in the research process, was employed for this study. The Latina Health Survey was administered in Spanish and English to 289 Latina adults through snowball sampling. Women reported that their national origin was predominantly Puerto Rican (58.7%) or Dominican (18.2%). Only 6.6% of women met American College of Sports Medicine's physical activity recommendations of exercising 5 days a week; 25% participated in physical activity two or more times per week. Acculturation and religious service attendance at least once a week was positively associated and fast food consumption one or more times a week was negatively associated with physical activity. This study implicates the need for physical activity promotion efforts among Latinas who are culturally responsive and that address fast food consumption. In addition to acculturation, other, more specific cultural factors need to be examined to understand physical activity correlates among Latinas. Research among Latinas living in new Latino destinations is important for understanding behavior and tailoring health interventions among Latinos living in nontraditional areas. Copyright 2010 Jacobs Institute of Women

  3. Mechanism of action of recombinant activated factor VII: an update.

    Science.gov (United States)

    Hedner, Ulla

    2006-01-01

    Bleeding episodes in patients with hemophilia and inhibitors must be managed using agents that are hemostatically active in the absence of factor VIII or IX. Activated prothrombin complex concentrates have long been used in this context. However, the search for safer and more effective agents has led to the development of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). This paper presents an update on the mechanism of action of rFVIIa, and describes how pharmacologic doses of this agent enhance thrombin production and thus contribute to the development of a stable, lysis-resistant fibrin plug at the site of vessel damage. This mechanism explains the reported efficacy of rFVIIa in a range of clinical situations characterized by impaired thrombin generation.

  4. Factors predicting physical activity among children with special needs.

    Science.gov (United States)

    Yazdani, Shahram; Yee, Chu Tang; Chung, Paul J

    2013-07-18

    Obesity is especially prevalent among children with special needs. Both lack of physical activity and unhealthful eating are major contributing factors. The objective of our study was to investigate barriers to physical activity among these children. We surveyed parents of the 171 children attending Vista Del Mar School in Los Angeles, a nonprofit school serving a socioeconomically diverse group of children with special needs from kindergarten through 12th grade. Parents were asked about their child's and their own physical activity habits, barriers to their child's exercise, and demographics. The response rate was 67%. Multivariate logistic regression was used to examine predictors of children being physically active at least 3 hours per week. Parents reported that 45% of the children were diagnosed with attention deficit hyperactivity disorder, 38% with autism, and 34% with learning disabilities; 47% of children and 56% of parents were physically active less than 3 hours per week. The top barriers to physical activity were reported as child's lack of interest (43%), lack of developmentally appropriate programs (33%), too many behavioral problems (32%), and parents' lack of time (29%). However, child's lack of interest was the only parent-reported barrier independently associated with children's physical activity. Meanwhile, children whose parents were physically active at least 3 hours per week were 4.2 times as likely to be physically active as children whose parents were less physically active (P = .01). In this group of students with special needs, children's physical activity was strongly associated with parental physical activity; parent-reported barriers may have had less direct effect. Further studies should examine the importance of parental physical activity among children with special needs.

  5. Changes in CVD risk factors in the activity counseling trial

    Directory of Open Access Journals (Sweden)

    Meghan Baruth

    2011-01-01

    Full Text Available Meghan Baruth1, Sara Wilcox1, James F Sallis3, Abby C King4,5, Bess H Marcus6, Steven N Blair1,21Department of Exercise Science, 2Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Public Health Research Center, Columbia, SC, USA; 3Department of Psychology, San Diego State University, San Diego, CA, USA; 4Department of Health Research and Policy, 5Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; 6Behavioral and Social Sciences Section, Brown University Program in Public Health, Providence, RI, USAAbstract: Primary care facilities may be a natural setting for delivering interventions that focus on behaviors that improve cardiovascular disease (CVD risk factors. The purpose of this study was to examine the 24-month effects of the Activity Counseling Trial (ACT on CVD risk factors, to examine whether changes in CVD risk factors differed according to baseline risk factor status, and to examine whether changes in fitness were associated with changes in CVD risk factors. ACT was a 24-month multicenter randomized controlled trial to increase physical activity. Participants were 874 inactive men and women aged 35–74 years. Participants were randomly assigned to one of three arms that varied by level of counseling, intensity, and resource requirements. Because there were no significant differences in change over time between arms on any of the CVD risk factors examined, all arms were combined, and the effects of time, independent of arm, were examined separately for men and women. Time × Baseline risk factor status interactions examined whether changes in CVD risk factors differed according to baseline risk factor status. Significant improvements in total cholesterol, high-density lipoprotein cholesterol (HDL-C and low-density lipoprotein cholesterol, the ratio of total cholesterol to HDL-C, and triglycerides were seen in

  6. [Factors conditioning taking up sport activity by disabled people].

    Science.gov (United States)

    Plinta, Ryszard; Sobiecka, Joanna

    2002-01-01

    The aim of the study was to answer the following questions: What factors determine that disabled people take up systematic sport activity or should make such a decision? What reasons are able to eliminate the handicapped from process of regular going in for sport? Three groups of men participated. The group of disabled sportsmen included 39 subjects, the group of non-active disabled people 36 subjects and the group of able-bodied students 45 subjects. All the involved people answered the questions of the questionnaire, which concerned factors associated with sport activity of the handicapped and their socio-demographic characteristics, among other things. The opportunity of improvement of the health status is the main advantage of the sport for disabled people (53%). The chance of self-testing and sport competition was pointed out by 47% of subjects. The most common reason for taking up sport activity was sport passion (over 50%). The others were: possibility of creating new contacts with people, improvement of the physical condition, chance of self-testing and passing free time (23%). The lack of free time was the factor eliminating from sport activity in the second group (28%). The other problem was the shortage of appropriate clubs, equipment, infrastructure etc. (almost 25%). Students concluded that sport for disabled people aims to improve the mental condition mainly (42%). Quite similar percentage of the group (38%) didn't see any reason that was able to exclude the handicapped from goingin for sport. (1) Not only does active going in for sport improve the physical condition of the handicapped but strengthen them psychically as well. (2) The lack of sport activity in disabled people is to a high degree a result of low number of sport clubs, organisations, buildings as well as presence of architectural barriers.

  7. Recombinant activated factor VII: 30 years of research and innovation.

    Science.gov (United States)

    Hedner, Ulla

    2015-06-01

    Recombinant activated factor VII (rFVIIa) was initially developed to treat bleeding episodes in patients with congenital haemophilia and inhibitors. The story of its development began in the 1970s, when FVIIa was identified as one of the activated coagulation factors that has minimal potential for inducing thromboembolic side-effects. Extensive research over the last 30 years has greatly increased our knowledge of the characteristics of FVII, its activation, and the mechanisms by which rFVIIa restores haemostasis. In haemophilia, the haemostatic effect of rFVIIa is mediated via binding to thrombin-activated platelets at the site of injury, thereby enhancing thrombin generation also in the absence of factor (F) VIII or FIX. The mechanism of action of rFVIIa has also allowed its successful use in other clinical scenarios characterised by impaired thrombin generation, and its licensed uses have now been extended to acquired haemophilia, congenital FVII deficiency and Glanzmann's thrombasthenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Factors of the active listening of preschool children

    Directory of Open Access Journals (Sweden)

    Purić Daliborka S.

    2016-01-01

    Full Text Available Active listening is a communication skill which is crucial for the development of cooperative relationships in the group, culture of friendship and fellowship, it is also important for the development of literacy skills and talent for speaking. Furthermore, it contributes to the improvement of the level of knowledge, skills and school achievement, as well as to the development of self-confidence of children. Developing of active listening is an important task in the activities with children of preschool age. In this paper, the author, wanting to determine the importance of the factors of active listening of preschool children, examines how preschool teachers (N = 198: (a evaluate the importance of certain elements of active listening that relate to the speaker and the listener, and (b estimate their role in the process of developing active listening skills of preschool children as an essential element of successful interpersonal communication. Results of the survey show that preschool teachers attach greater importance to the factors of active listening related to the listener (attention, listening skill, interest in the subject, than to the factors related to the speaker (motivation for listening, quality of the narrative. More than two-thirds of surveyed preschool teachers (172 or 86.9% define its impact on the stimulation of active listening of children as significant. Work experience and professional qualifications as independent variables significantly influence the attitudes of preschool teachers about the importance of their impact in stimulating active listening. Preschool teacher is a key element of the training of preschool children in the area of the basic communication skills of active listening. In this sense, the results of our survey show that in the context of academic study programs for education of preschool teachers special attention is given to the communication skills and to their role in the development of active listening

  9. Daytime activity and risk factors for late-life insomnia.

    Science.gov (United States)

    Morgan, Kevin

    2003-09-01

    Laboratory evidence linking exercise with improved sleep quality raises the possibility that the lower levels of physical activity characteristic of older age groups may contribute to late-life insomnia. While support for this hypothesis appears to come from epidemiological surveys, few such studies have distinguished satisfactorily between social and physical activities which differ widely in terms of energy cost and theoretical significance. The present analyses were, therefore, designed to assess the independent influence of physical and social activity levels on the prevalence and natural history of late-life insomnia. Survivors from a nationally representative UK sample (n = 1042) of elderly people originally interviewed in 1985 were reassessed in 1989 (n = 690) and 1993 (n = 410). Detailed assessments of physical and social activities, mental and physical health status, and sleep quality were made at each survey wave. Logistic regression models, adjusted for age, sex and health status, were used to assess relationships between activity levels and the prevalence, remission/persistence, and incidence of late-life insomnia. Lower physical health, depressed mood and lower physical (but not social) activity levels consistently emerged as significant risk factors for prevalent, persistent and incident insomnia. Age was unrelated to insomnia variables in all the cross-sectional models, but did emerge as a significant risk for cumulative 4-8-year insomnia incidence. These findings suggest that, independent of those activities more closely associated with social engagement, higher levels of customary physical activity per se appear to be protective against incident and chronic late-life insomnia.

  10. Laterality of Brain Activation for Risk Factors of Addiction.

    Science.gov (United States)

    Gordon, Harold W

    2016-01-01

    Laterality of brain activation is reported for tests of risk factors of addiction- impulsivity and craving-but authors rarely address the potential significance of those asymmetries. The purpose of this study is to demonstrate this laterality and discuss its relevance to cognitive and neurophysiological asymmetries associated with drug abuse vulnerability in order to provide new insights for future research in drug abuse. From published reports, brain areas of activation for two tests of response inhibition or craving for drugs of abuse were compiled from fMRI activation peaks and were tabulated for eight sections (octants) in each hemisphere. Percent asymmetries were calculated (R-L/R+L) across studies for each area. For impulsivity, most activation peaks favored the right hemisphere. Overall, the percent difference was 32% (Χ2 = 16.026; p laterality into consideration is a missed opportunity in designing studies and gaining insight into the etiology of drug abuse and pathways for treatment.

  11. Assembly and activation of neurotrophic factor receptor complexes.

    Science.gov (United States)

    Simi, Anastasia; Ibáñez, Carlos F

    2010-04-01

    Neurotrophic factors play important roles in the development and function of both neuronal and glial elements of the central and peripheral nervous systems. Their functional diversity is in part based on their ability to interact with alternative complexes of receptor molecules. This review focuses on our current understanding of the mechanisms that govern the assembly and activation of neurotrophic factor receptor complexes. The realization that many, if not the majority, of these complexes exist in a preassembled form at the plasma membrane has forced the revision of classical ligand-mediated oligomerization models, and led to the discovery of novel mechanisms of receptor activation and generation of signaling diversity which are likely to be shared by many different classes of receptors.

  12. A study of environmental polluting factors by neutron activation method

    International Nuclear Information System (INIS)

    Paunoiu, C.; Doca, C.

    2004-01-01

    The paper presents: a) some importance factors of the environmental pollution; b) the theoretical aspects of the Neutron Activation Analysis (NAA) used in the study of the environmental pollution; c) the NAA specific hardware and software facilities existing at the Institute for Nuclear Research; d) a direct application of the NAA method in the study of the environmental pollution for Pitesti city by the analysis of some ground and vegetation samples; e) results and conclusions. (authors)

  13. Active Power Factor Correction Using a Sliding Mode Controller

    Directory of Open Access Journals (Sweden)

    Korhan KAYIŞLI

    2008-03-01

    Full Text Available In this paper, a sliding mode controller is designed for active shaping of the input current in the boost converter. Robustness of the designed controller is tested with variable output voltage references, different loads and network voltage variations. For the simulations, MATLAB/Simulink programme is used. From simulation results, the same phase was provided between input current and input voltage and nearly unity power factor was obtained.

  14. TALE factors poise promoters for activation by Hox proteins.

    Science.gov (United States)

    Choe, Seong-Kyu; Ladam, Franck; Sagerström, Charles G

    2014-01-27

    Hox proteins form complexes with TALE cofactors from the Pbx and Prep/Meis families to control transcription, but it remains unclear how Hox:TALE complexes function. Examining a Hoxb1b:TALE complex that regulates zebrafish hoxb1a transcription, we find maternally deposited TALE proteins at the hoxb1a promoter already during blastula stages. These TALE factors recruit histone-modifying enzymes to promote an active chromatin profile at the hoxb1a promoter and also recruit RNA polymerase II (RNAPII) and P-TEFb. However, in the presence of TALE factors, RNAPII remains phosphorylated on serine 5 and hoxb1a transcription is inefficient. By gastrula stages, Hoxb1b binds together with TALE factors to the hoxb1a promoter. This triggers P-TEFb-mediated transitioning of RNAPII to the serine 2-phosphorylated form and efficient hoxb1a transcription. We conclude that TALE factors access promoters during early embryogenesis to poise them for activation but that Hox proteins are required to trigger efficient transcription. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Risk factors for glucose intolerance in active acromegaly

    Directory of Open Access Journals (Sweden)

    Kreze A.

    2001-01-01

    Full Text Available In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19%; 95% CI: 8-33% had diabetes mellitus and 2 (5%; 1-16% impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test. A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors.

  16. Factors affecting perceived change in physical activity in pregnancy.

    Science.gov (United States)

    Merkx, Astrid; Ausems, Marlein; Budé, Luc; de Vries, Raymond; Nieuwenhuijze, Marianne J

    2017-08-01

    reduction of physical activity (PA) during pregnancy is common but undesirable, as it is associated with negative outcomes, including excessive gestational weight gain. Our objective was to explore changes in five types of activity that occurred during pregnancy and the behavioural determinants of the reported changes in PA. we performed a secondary analysis of a cross sectional survey that was constructed using the ASE-Model - an approach to identifying the factors that drive behaviour change that focuses on Attitude, Social influence, and self-Efficacy. 455 healthy pregnant women of all gestational ages, receiving prenatal care from midwifery practices in the Netherlands. more than half of our respondents reported a reduction in their PA during pregnancy. The largest reduction occurred in sports and brief rigorous activities, but other types of PA were reduced as well. Reduction of PA was more likely in women who considered themselves as active before pregnancy, women who experienced pregnancy-related barriers, women who were advised to reduce their PA, and multiparous women. Fewer than 5% increased their PA. Motivation to engage in PA was positively associated with enjoying PA. all pregnant women should be informed about the positive effects of staying active and should be encouraged to engage in, or to continue, moderately intensive activities like walking, biking or swimming. Our findings concerning the predictors of PA reduction can be used to develop an evidence-based intervention aimed at encouraging healthy PA during pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Adolescent Physical Activity: Moderation of Individual Factors by Neighborhood Environment.

    Science.gov (United States)

    D'Angelo, Heather; Fowler, Stephanie L; Nebeling, Linda C; Oh, April Y

    2017-06-01

    Less than a third of U.S. adolescents meet federal physical activity (PA) guidelines. Understanding correlates of PA at multiple levels of the Social Ecological Model could improve PA interventions among youth. This study examines (1) associations between factors across the Social Ecological Model including psychosocial factors, perceived neighborhood physical and social environment characteristics, and adolescent moderate to vigorous PA (MVPA) and (2) whether perceived neighborhood characteristics moderate associations between psychosocial factors and MVPA. A national sample of adolescents (aged 12-17 years) in the 2014 Family Life, Activity, Sun, Health, and Eating Study was used to examine associations between psychosocial characteristics, perceived neighborhood social and physical characteristics, and self-reported weekly minutes of MVPA. Analyses were conducted in 2015. Interaction terms between psychosocial and neighborhood variables were added to multiple linear regression models to examine moderation hypotheses. Significant two-way interactions revealed that neighborhoods with features perceived as supportive of PA strengthened several psychosocial-MVPA associations. The positive associations between MVPA and friend norms, friend support, and attitudes were strengthened for adolescents living in neighborhoods with high versus low PA resource availability (all p<0.05). Furthermore, the association between controlled and autonomous motivation and MVPA was strengthened under conditions of shops/stores near (versus distant from) adolescents' homes (p<0.05). The association between some psychosocial factors and adolescent MVPA may be environment dependent. Neighborhood physical and social environments supportive of PA are important to consider when developing targeted PA interventions and may strengthen the association between psychosocial-level factors and adolescent MVPA. Copyright © 2017 American Journal of Preventive Medicine. All rights reserved.

  18. Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial

    NARCIS (Netherlands)

    de Boer, J. Daan; Berger, Marieke; Majoor, Christof J.; Kager, Liesbeth M.; Meijers, Joost C. M.; Terpstra, Sanne; Nieuwland, Rienk; Boing, Anita N.; Lutter, René; Wouters, Diana; van Mierlo, Gerard J.; Zeerleder, Sacha S.; Bel, Elisabeth H.; van't Veer, Cornelis; de Vos, Alex F.; van der Zee, Jaring S.; van der Poll, Tom

    2015-01-01

    Asthma patients show evidence of a procoagulant state in their airways, accompanied by an impaired function of the anticoagulant protein C system. We aimed to study the effect of recombinant human activated protein C (rhAPC) in allergic asthma patients.We conducted a randomised, double-blind,

  19. Time-activity relationships to VOC personal exposure factors

    Science.gov (United States)

    Edwards, Rufus D.; Schweizer, Christian; Llacqua, Vito; Lai, Hak Kan; Jantunen, Matti; Bayer-Oglesby, Lucy; Künzli, Nino

    Social and demographic factors have been found to play a significant role in differences between time-activity patterns of population subgroups. Since time-activity patterns largely influence personal exposure to compounds as individuals move across microenvironments, exposure subgroups within the population may be defined by factors that influence daily activity patterns. Socio-demographic and environmental factors that define time-activity subgroups also define quantifiable differences in VOC personal exposures to different sources and individual compounds in the Expolis study. Significant differences in exposures to traffic-related compounds ethylbenzene, m- and p-xylene and o-xylene were observed in relation to gender, number of children and living alone. Categorization of exposures further indicated time exposed to traffic at work and time in a car as important determinants. Increased exposures to decane, nonane and undecane were observed for males, housewives and self-employed. Categorization of exposures indicated exposure subgroups related to workshop use and living downtown. Higher exposures to 3-carene and α-pinene commonly found in household cleaning products and fragrances were associated with more children, while exposures to traffic compounds ethylbenzene, m- and p-xylene and o-xylene were reduced with more children. Considerable unexplained variation remained in categorization of exposures associated with home product use and fragrances, due to individual behavior and product choice. More targeted data collection methods in VOC exposure studies for these sources should be used. Living alone was associated with decreased exposures to 2-methyl-1-propanol and 1-butanol, and traffic-related compounds. Identification of these subgroups may help to reduce the large amount of unexplained variation in VOC exposure studies. Further they may help in assessing impacts of urban planning that result in changes in behavior of individuals, resulting in shifts in

  20. Tissue factor activates allosteric networks in factor VIIa through structural and dynamic changes

    DEFF Research Database (Denmark)

    Madsen, Jesper Jonasson; Persson, E.; Olsen, O. H.

    2015-01-01

    that are not likely to be inferred from mutagenesis studies. Furthermore, paths from Met306 to Ile153 (N-terminus) and Trp364, both representing hallmark residues of allostery, are 7% and 37% longer, respectively, in free FVIIa. Thus, there is significantly weaker coupling between the TF contact point and key......Background: Tissue factor (TF) promotes colocalization of enzyme (factorVIIa) and substrate (FX or FIX), and stabilizes the active conformation of FVIIa. Details on how TF induces structural and dynamic changes in the catalytic domain of FVIIa to enhance its efficiency remain elusive. Objective......: To elucidate the activation of allosteric networks in the catalytic domain of the FVIIa protease it is when bound to TF.MethodsLong-timescale molecular dynamics simulations of FVIIa, free and in complex with TF, were executed and analyzed by dynamic network analysis. Results: Allosteric paths of correlated...

  1. Active commuting and sociodemographic factors among university students in Spain.

    Science.gov (United States)

    Molina-García, Javier; Sallis, James F; Castillo, Isabel

    2014-02-01

    Commuting to university represents an opportunity to incorporate physical activity (walking or biking) into students' daily routines. There are few studies that analyze patterns of transport in university populations. This cross-sectional study estimated energy expenditure from active commuting to university (ACU) and examined sociodemographic differences in findings. The sample included 518 students with a mean age of 22.4 years (59.7% female) from 2 urban universities in Valencia, Spain. Time spent in each mode of transport to university and sociodemographic factors was assessed by self-report. Nearly 35% of the students reported walking or biking as their main mode of transport. ACU (min/wk) were highest for walkers (168) and cyclists (137) and lowest for motorbike riders (0.0) and car drivers (16). Public transport users, younger students, low socioeconomic status students, and those living ≤ 2 km from the university had higher energy expenditure from active commuting than comparison groups. Biking was highest among those living 2-5 km from the university. Our findings suggest that active commuting and public transit use generated substantial weekly energy expenditure, contributed to meeting physical activity recommendations, and may aid in obesity prevention.

  2. Expression and characterization of recombinant human factor V and a mutant lacking a major portion of the connecting region

    International Nuclear Information System (INIS)

    Kane, W.H.; Devore-Carter, D.; Ortel, T.L.

    1990-01-01

    Human coagulation factor V is a protein cofactor that is an essential component of the prothrombinase complex. A full-length factor V cDNA has been subcloned into the mammalian expression vector pDX and used to transfect COS cells. Approximately 95 ± 4% of the recombinant human factor V (rHFV) synthesized in COS cells is secreted into the culture medium. Factor V activity determined by fibrometer assay increased approximately 5-fold from 0.027 ± 0.012 to 0.124 ± 0.044 unit/mL following activation by the factor V activating enzyme from Russell's viper venom (RVV-V). A chromogenic assay specific for factor Va indicated that recombinant factor V had 3.8 ± 1.3% of the activity of the activated protein. The estimated specific activity of the recombinant factor Va was approximately 1,800 ± 500 units/mg, which is similar to the specific activity of purified plasma factor Va of 1,700-2,000 units/mg. Immunoprecipitation of [ 35 S]methionine-labeled rHFV revealed a single high molecular mass component. Treatment of rHFV with thrombin or RVV-V resulted in the formation of proteolytic products that were similar to those seen with plasma factor V. The authors have also expressed a mutant, rHFV-des-B 811-1441 , that lacks a large portion of the highly glycosylated connecting region that is present in factor V. This mutant constitutively expressed 38 ± 7% of the activity of the RVV-V-activated protein. These results suggest that one of the functions of the large connecting region in factor V is to inhibit constitutive procoagulant activity

  3. Progress toward inducing immunologic tolerance to factor VIII

    OpenAIRE

    Scott, David W.; Pratt, Kathleen P.; Miao, Carol H.

    2013-01-01

    A major problem in treating hemophilia A patients with therapeutic factor VIII (FVIII) is that 20% to 30% of these patients produce neutralizing anti-FVIII antibodies. These antibodies block (inhibit) the procoagulant function of FVIII and thus are termed “inhibitors.” The currently accepted clinical method to attempt to eliminate inhibitors is immune tolerance induction (ITI) via a protocol requiring intensive FVIII treatment until inhibitor titers drop. Although often successful, ITI is ext...

  4. Influence Factors of Sexual Activity for Internal Migrants in China

    Directory of Open Access Journals (Sweden)

    Junguo Zhang, PhD candidate

    2018-06-01

    Full Text Available Background: Sexual frequency is associated with the quality of life. China’s internal migrants that are sexually active are more likely to participate in sexual behavior. However, less work has been undertaken to assess the sexual frequency and its predictors in migrants. Aim: This study seeks to explore which factors were related to sexual frequency in migrants and how the association varies with different levels of sexual frequency. Methods: A total of 10,834 men and 4,928 women aged 20–49 years from 5 cities in China were enrolled by multi-stage sampling during August 2013–August 2015. Outcomes: Sexual frequency among migrants was determined by asking: How many times have you had sexual intercourse with a man/woman in the past 30 days? Results: In this study, sexual frequency with an average age of 38.28 years was 5.06 (95% CI 5.01–5.11 time per month. Negative binomial showed that male gender, younger age, earlier age of sexual debut, masturbation, more knowledge of sexual and reproductive health, longer time together with a spouse, and higher school education and incomes were predictors of increased sexual frequency in migrants. Communicating with sexual partners frequently had the largest effect on sexual frequency compared with occasional communicating (β = 0.2419, incidence rate ratio = 1.27, 95% CI 1.23–1.31. In the quantile regression, months of cohabitation (β = 0.0999, 95% CI 0.08–0.12, frequent sexual communication (β = 0.4534, 95% CI 0.39–0.52, and masturbation (β = 0.2168, 95% CI 0.14–0.30 were positively related to lower levels of sexual frequency. Interestingly, migrants who had low and high sexual frequency would be affected in opposite directions by the knowledge of sexual and reproductive health. Clinical Translation: Clinicians can more understand the relationship between sexual frequency and its factors that can as the symptom basis of sexually-related diseases. Conclusions: The present findings

  5. Contextual factors influencing leisure physical activity of urbanized indigenous adolescents.

    Science.gov (United States)

    Lo, Feng-En; Tsai, Feng-Chou; Lee, Ming-Been; Tsai, Liang-Ting; Lyu, Shu-Yu; Yang, Chih-Chien

    2015-11-01

    Indigenous populations suffer from disparities in socioeconomic resources and health status. One approach to addressing these disparities is by targeting modifiable risk factors such as leisure physical activity (LPA). This study investigated and compared factors related to LPA among urbanized indigenous and nonindigenous adolescent students. This cross-sectional survey comprised fifth to ninth grade indigenous and nonindigenous students (n = 733). The nonindigenous students were matched with indigenous students on sex and academic achievement and used as a reference group. Data were collected through telephone interviews using structured questionnaires. Major items included: demographic characteristics; average time spent watching television per bout; participation in LPA; and stress and depression experiences. With the exception of the duration of television watching per bout, Chi-square and independent t tests demonstrated that there were no significant differences between indigenous and nonindigenous adolescents in the selected LPA-related factors. Multiple logistic regression analysis including terms investigating interaction between ethnicity and the contextual factors included in this study indicated that the following factors were correlated with LPA participation: age [odds ratio (OR) = 0.82, 95% confidence interval (CI) = 0.71-0.94], male sex (OR = 1.77, 95%CI = 1.19-2.61), total hours spent watching television in the past 2 weeks (OR = 0.79, 95%CI = 0.63-0.99), life satisfaction (OR = 2.25, 95%CI = 1.04-4.90), and exercise enjoyment (OR = 3.40, 95%CI = 1.71-6.74). However, neither indigenous status (OR = 1.03, 95%CI = 0.19-5.79) nor any of the interaction terms reached the significant level. No significant ethnic differences were found in LPA participation. LPA was significantly correlated with age, male sex, total time spent watching television, life satisfaction, and enjoyment of exercise. Copyright © 2014. Published by Elsevier B.V.

  6. Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII.

    Science.gov (United States)

    Ollivier, V; Bentolila, S; Chabbat, J; Hakim, J; de Prost, D

    1998-04-15

    The transmembrane protein tissue factor (TF) is the cell surface receptor for coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has been identified as a regulator of angiogenesis, tumor growth, and metastasis. This study was designed to link the binding of FVII(a) to its receptor, TF, with the subsequent triggering of angiogenesis through vascular endothelial growth factor (VEGF) production by human lung fibroblasts. We report that incubation of fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked immunosorbent assay, was time- and concentration-dependent. VEGF secretion was maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and represented a threefold induction of the basal VEGF level. Reverse transcriptase-polymerase chain reaction analysis of VEGF detected three mRNA species of 180, 312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A 2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12 and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a pool of antibodies against TF, pointing to the involvement of this receptor. On specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production. Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold stimulating effect. Protein tyrosine kinase and protein kinase C are involved in signal transduction leading to VEGF production, as shown by the inhibitory effects of genistein and GF 109203X. The results of this study indicate that TF is essential for VIIa-induced VEGF production by human fibroblasts and that its role is mainly linked to the proteolytic activity of the TF-VIIa complex.

  7. Nuclear factor erythroid 2-related factor-2 activity controls 4-hydroxynonenal metabolism and activity in prostate cancer cells.

    Science.gov (United States)

    Pettazzoni, Piergiorgio; Ciamporcero, Eric; Medana, Claudio; Pizzimenti, Stefania; Dal Bello, Federica; Minero, Valerio Giacomo; Toaldo, Cristina; Minelli, Rosalba; Uchida, Koji; Dianzani, Mario Umberto; Pili, Roberto; Barrera, Giuseppina

    2011-10-15

    4-Hydroxynonenal (HNE) is an end product of lipoperoxidation with antiproliferative and proapoptotic properties in various tumors. Here we report a greater sensitivity to HNE in PC3 and LNCaP cells compared to DU145 cells. In contrast to PC3 and LNCaP cells, HNE-treated DU145 cells showed a smaller reduction in growth and did not undergo apoptosis. In DU145 cells, HNE did not induce ROS production and DNA damage and generated a lower amount of HNE-protein adducts. DU145 cells had a greater GSH and GST A4 content and GSH/GST-mediated HNE detoxification. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a regulator of the antioxidant response. Nrf2 protein content and nuclear accumulation were higher in DU145 cells compared to PC3 and LNCaP cells, whereas the expression of KEAP1, the main negative regulator of Nrf2 activity, was lower. Inhibition of Nrf2 expression with specific siRNA resulted in a reduction in GST A4 expression and GS-HNE formation, indicating that Nrf2 controls HNE metabolism. In addition, Nrf2 knockdown sensitized DU145 cells to HNE-mediated antiproliferative and proapoptotic activity. In conclusion, we demonstrated that increased Nrf2 activity resulted in a reduction in HNE sensitivity in prostate cancer cells, suggesting a potential mechanism of resistance to pro-oxidant therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Is sunspot activity a factor in influenza pandemics?

    Science.gov (United States)

    Qu, Jiangwen

    2016-09-01

    The 2009 AH1N1 pandemic became a global health concern, although fortunately, its worst anticipated effects were not realised. While the origins of such outbreaks remain poorly understood, it is very important to identify the precipitating factors in their emergence so that future pandemics can be detected as quickly as possible. Methords: Descriptive epidemiology was used to analyse the association between influenza pandemics and possible pandemics and relative number of sunspots. Non-conditional logistic regression was performed to analyse the statistical association between sunspot extremes and influenza pandemics to within plus or minus 1 year. Almost all recorded influenza/possible pandemics have occurred in time frames corresponding to sunspot extremes, or +/- 1 year within such extremes. These periods were identified as important risk factors in both possible and confirmed influenza pandemics (odds ratio: 3.87; 95% confidence interval: 1.08 to 13.85). Extremes of sunspot activity to within plus or minus 1 year may precipitate influenza pandemics. Mechanisms of epidemic initiation and early spread are discussed including primary causation by externally derived viral variants (from space via cometary dust). Efforts to construct a comprehensive early warning system for potential influenza and other viral pandemics that include analysis of sunspot activity and stratospheric sampling for viral variants should be supported. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Factors associated with Spanish older people's membership in political organizations: the role of active aging activities.

    Science.gov (United States)

    Serrat, Rodrigo; Villar, Feliciano; Celdrán, Montserrat

    2015-09-01

    This study explores older people's membership in political organizations by using data from the Survey on older people 2010, carried out by Spain's National Institute for older people and social services. The objectives were to describe the extent of this kind of participation among Spaniards aged 65 and over, and to analyze the factors that are associated with it. Results show that only slightly less than 7 % of the sample belonged to a political organization. To analyze the factors related to this membership, a set of models of multivariate analyses were run, including socioeconomic resources and participation in other types of active aging activity (participation in leisure, learning, and productive activities). Educational level, leisure activities, learning activities, and only volunteering in the case of productive activities were found to be associated with membership in political organizations. Results provide partial support for the socioeconomic resources model and suggest that engagement in leisure activities, learning activities, and volunteering might have an enhancing effect on membership in political organizations.

  10. Risk factors of falls in community dwelling active elderly.

    Science.gov (United States)

    Tuunainen, Eeva; Rasku, Jyrki; Jäntti, Pirkko; Pyykkö, Ilmari

    2014-02-01

    To search for measures to describe and relate to accidental falls in community dwelling elderly. A EuroQol EQ-5D questionnaire based on a patient's otoneurological case history provided a general health related quality of life measure, a fall history for the last 3 months and force platform measures for 96 active elderly from a pensioner organization. On average, the elderly experienced 0.3 falls over the preceding three months. A fall was seen to cause a significant deterioration in the quality of life and vertigo and caused fear of falling. The postural instability correlated with falls. Vertigo was present among 42% and was most commonly characterized as episodic and rotatory in factorial analysis items relating to vertigo correlated to falls and balance complaints. Four factors were identified and three of these correlated with falls. Vestibular failure correlated to a fall occurring when a person was rising up; Movement intolerance correlated with falls due to slips and trips, and Near-syncope factor correlated to falls for other reasons. In posturography, the variable measuring critical time describing the memory based "closed loop" control of postural stability carried a risk for accidental fall with an odds ratio of 6. The variable measuring zero crossing velocity showed a high rate of velocity change around the neutral position of stance. Vertigo and poor postural stability were the major reasons for falls in the active elderly. In ageing, postural control is shifted towards open loop control (visual, proprioception, exteroception and vestibular) instead of closed loop control and is a factor that contributes to a fall. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. 78 FR 46418 - Proposed Information Collection (Obligation To Report Factors Affecting Entitlement) Activity...

    Science.gov (United States)

    2013-07-31

    ... (Obligation To Report Factors Affecting Entitlement) Activity; Comment Request AGENCY: Veterans Benefits... use of other forms of information technology. Title: Obligation to Report Factors Affecting... entitlement factors. Individual factors such as income, marital status, and the beneficiary's number of...

  12. Environmental factors associated with physician's engagement in communication activities.

    Science.gov (United States)

    Mazurenko, Olena; Hearld, Larry R

    2015-01-01

    Communication between patients and providers is a crucial component of effective care coordination and is associated with a number of desired patient and provider outcomes. Despite these benefits, physician-patient and physician-physician communication occurs infrequently. The purpose of this study was to examine the relationship between a medical practice's external environment and physician engagement in communication activities. This was a cross-sectional examination of 4,299 U.S. physicians' self-reported engagement in communication activities. Communication was operationalized as physician's time spent on communication with patients and other providers during a typical work day. The explanatory variables were measures of environmental complexity, dynamism, and munificence. Data sources were the Health Tracking Physician Survey, the Area Resource File database, and the Dartmouth Atlas. Binary logistic regression was used to estimate the association between the environmental factors and physician engagement in communication activities. Several environmental factors, including per capita income (odds ratio range, 1.17-1.38), urban location (odds ratio range, 1.08-1.45), fluctuations in Health Maintenance Organization penetration (odds ratio range, 3.47-13.22), poverty (odds ratio range, 0.80-0.97) and population rates (odds ratio range, 1.01-1.02), and the presence of a malpractice crisis (odds ratio range, 0.22-0.43), were significantly associated with communication. Certain aspects of a physician's external environment are associated with different modes of communication with different recipients (patients and providers). This knowledge can be used by health care managers and policy makers who strive to improve communication between different stakeholders within the health care system (e.g., patient and providers).

  13. Associations between Socio-Motivational Factors, Physical Education Activity Levels and Physical Activity Behavior among Youth

    Science.gov (United States)

    Ning, Weihong; Gao, Zan; Lodewyk, Ken

    2012-01-01

    This study examined the relationships between established socio-motivational factors and children's physical activity levels daily and during physical education classes. A total of 307 middle school students (149 boys, 158 girls) from a suburban public school in the Southern United States participated in this study. Participants completed…

  14. Evaluating the Factors that Activate the Development of Public-Private Partnership in Foreign Economic Activity

    Directory of Open Access Journals (Sweden)

    Pyroh Olha V.

    2017-12-01

    Full Text Available The article is concerned with research on public-private partnership in foreign economic activity as process of interaction of the State and business-structures – entities of economic activity of Ukraine along with foreign entities of economic activity, this process includes attraction of investments, acceleration of economic development, etc. The factors determining public-private partnership in the foreign economic sphere (system of the State government bodies, system of economic relations in the State, financial resources of various States, experience in the implementation of public-private partnership projects, trust between partners are researched and generalized. Influence of each of the factors was defined by means of conjunctive analysis, determining that the system of economic relations in the State is most influenced by the formation of conditions, rules and implementation of principles of functioning of public-private partnership in the foreign economic sphere.

  15. Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

    Science.gov (United States)

    van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

    2012-10-01

    The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

  16. Modeling of human factor Va inactivation by activated protein C

    Directory of Open Access Journals (Sweden)

    Bravo Maria

    2012-05-01

    Full Text Available Abstract Background Because understanding of the inventory, connectivity and dynamics of the components characterizing the process of coagulation is relatively mature, it has become an attractive target for physiochemical modeling. Such models can potentially improve the design of therapeutics. The prothrombinase complex (composed of the protease factor (FXa and its cofactor FVa plays a central role in this network as the main producer of thrombin, which catalyses both the activation of platelets and the conversion of fibrinogen to fibrin, the main substances of a clot. A key negative feedback loop that prevents clot propagation beyond the site of injury is the thrombin-dependent generation of activated protein C (APC, an enzyme that inactivates FVa, thus neutralizing the prothrombinase complex. APC inactivation of FVa is complex, involving the production of partially active intermediates and “protection” of FVa from APC by both FXa and prothrombin. An empirically validated mathematical model of this process would be useful in advancing the predictive capacity of comprehensive models of coagulation. Results A model of human APC inactivation of prothrombinase was constructed in a stepwise fashion by analyzing time courses of FVa inactivation in empirical reaction systems with increasing number of interacting components and generating corresponding model constructs of each reaction system. Reaction mechanisms, rate constants and equilibrium constants informing these model constructs were initially derived from various research groups reporting on APC inactivation of FVa in isolation, or in the presence of FXa or prothrombin. Model predictions were assessed against empirical data measuring the appearance and disappearance of multiple FVa degradation intermediates as well as prothrombinase activity changes, with plasma proteins derived from multiple preparations. Our work integrates previously published findings and through the cooperative

  17. hypoxia-inducible factors activate CD133 promoter through ETS family transcription factors.

    Directory of Open Access Journals (Sweden)

    Shunsuke Ohnishi

    Full Text Available CD133 is a cellular surface protein that has been reported to be a cancer stem cell marker, and thus it is considered to be a potential target for cancer treatment. However, the mechanism regulating CD133 expression is not yet understood. In this study, we analyzed the activity of five putative promoters (P1-P5 of CD133 in human embryonic kidney (HEK 293 cells and colon cancer cell line WiDr, and found that the activity of promoters, particularly of P5, is elevated by overexpression of hypoxia-inducible factors (HIF-1α and HIF-2α. Deletion and mutation analysis identified one of the two E-twenty six (ETS binding sites (EBSs in the P5 region as being essential for its promoter activity induced by HIF-1α and HIF-2α. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1α and HIF-2α bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1α physically interacts with Elk1; however, HIF-2α did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1α and HIF-2α resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1α and HIF-2α activate CD133 promoter through ETS proteins.

  18. Activating transcription factor 3 regulates immune and metabolic homeostasis.

    Science.gov (United States)

    Rynes, Jan; Donohoe, Colin D; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek; Uhlirova, Mirka

    2012-10-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins.

  19. Human factors in remote control engineering development activities

    International Nuclear Information System (INIS)

    Clarke, M.M.; Hamel, W.R.; Draper, J.V.

    1983-01-01

    Human factors engineering, which is an integral part of the advanced remote control development activities at the Oak Ridge National Laboratory, is described. First, work at the Remote Systems Development Facility (RSDF) has shown that operators can perform a wide variety of tasks, some of which were not specifically designed for remote systems, with a dextrous electronic force-reflecting servomanipulator and good television remote viewing capabilities. Second, the data collected during mock-up remote maintenance experiments at the RSDF have been analyzed to provide guidelines for the design of human interfaces with an integrated advanced remote maintenance system currently under development. Guidelines have been provided for task allocation between operators, remote viewing systems, and operator controls. 6 references, 5 figures, 2 tables

  20. FACTORS AFFECTED DECARBOXYLATION ACTIVITY OF ENTEROCOCCUS FAECIUM ISOLATED FROM RABBIT

    Directory of Open Access Journals (Sweden)

    František Buňka

    2012-04-01

    Full Text Available Normal 0 21 false false false SK JA X-NONE Biogenic amines (BA are basic nitrogenous compounds formed mainly by decarboxylation of amino acids. There are generated in course of microbial, vegetable and animal metabolisms. The aim of the study was to monitor factors affected production of biogenic amines by Enterococcus faecium, which is found in rabbit meat. Biogenic amines were analyzed by means of UPLC (ultrahigh performance liquid chromatography equipped with a UV/VIS DAD detector. Decarboxylation activity of E. faecium was mainly influenced by the cultivation temperature and the amount of NaCl in this study. E. faecium produced most of the monitored biogenic amines levels: tyramine ˂2500 mg.l-1; putrescine ˂30 mg.l-1; spermidine ˂10 mg.l-1 and cadaverine ˂5 mg.l-1.doi:10.5219/182

  1. Tissue Factor–Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes

    OpenAIRE

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are...

  2. Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Mariko Umemura

    2017-07-01

    Full Text Available Activating transcription factor 5 (ATF5 is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/- mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley’s social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders.

  3. Transcription factor PIF4 controls the thermosensory activation of flowering

    KAUST Repository

    Kumar, S. Vinod; Lucyshyn, Doris; Jaeger, Katja E.; Aló s, Enriqueta; Alvey, Elizabeth; Harberd, Nicholas P.; Wigge, Philip A.

    2012-01-01

    Plant growth and development are strongly affected by small differences in temperature. Current climate change has already altered global plant phenology and distribution, and projected increases in temperature pose a significant challenge to agriculture. Despite the important role of temperature on plant development, the underlying pathways are unknown. It has previously been shown that thermal acceleration of flowering is dependent on the florigen, FLOWERING LOCUS T (FT). How this occurs is, however, not understood, because the major pathway known to upregulate FT, the photoperiod pathway, is not required for thermal acceleration of flowering. Here we demonstrate a direct mechanism by which increasing temperature causes the bHLH transcription factor PHYTOCHROME INTERACTING FACTOR4 (PIF4) to activate FT. Our findings provide a new understanding of how plants control their timing of reproduction in response to temperature. Flowering time is an important trait in crops as well as affecting the life cycles of pollinator species. A molecular understanding of how temperature affects flowering will be important for mitigating the effects of climate change. © 2012 Macmillan Publishers Limited. All rights reserved.

  4. Transcription factor PIF4 controls the thermosensory activation of flowering

    KAUST Repository

    Kumar, S. Vinod

    2012-03-21

    Plant growth and development are strongly affected by small differences in temperature. Current climate change has already altered global plant phenology and distribution, and projected increases in temperature pose a significant challenge to agriculture. Despite the important role of temperature on plant development, the underlying pathways are unknown. It has previously been shown that thermal acceleration of flowering is dependent on the florigen, FLOWERING LOCUS T (FT). How this occurs is, however, not understood, because the major pathway known to upregulate FT, the photoperiod pathway, is not required for thermal acceleration of flowering. Here we demonstrate a direct mechanism by which increasing temperature causes the bHLH transcription factor PHYTOCHROME INTERACTING FACTOR4 (PIF4) to activate FT. Our findings provide a new understanding of how plants control their timing of reproduction in response to temperature. Flowering time is an important trait in crops as well as affecting the life cycles of pollinator species. A molecular understanding of how temperature affects flowering will be important for mitigating the effects of climate change. © 2012 Macmillan Publishers Limited. All rights reserved.

  5. Transcription elongation factor GreA has functional chaperone activity.

    Science.gov (United States)

    Li, Kun; Jiang, Tianyi; Yu, Bo; Wang, Limin; Gao, Chao; Ma, Cuiqing; Xu, Ping; Ma, Yanhe

    2012-01-01

    Bacterial GreA is an indispensable factor in the RNA polymerase elongation complex. It plays multiple roles in transcriptional elongation, and may be implicated in resistance to various stresses. In this study, we show that Escherichia coli GreA inhibits aggregation of several substrate proteins under heat shock condition. GreA can also effectively promote the refolding of denatured proteins. These facts reveal that GreA has chaperone activity. Distinct from many molecular chaperones, GreA does not form stable complexes with unfolded substrates. GreA overexpression confers the host cells with enhanced resistance to heat shock and oxidative stress. Moreover, GreA expression in the greA/greB double mutant could suppress the temperature-sensitive phenotype, and dramatically alleviate the in vivo protein aggregation. The results suggest that bacterial GreA may act as chaperone in vivo. These results suggest that GreA, in addition to its function as a transcription factor, is involved in protection of cellular proteins against aggregation.

  6. PSYCHOLOGICAL FACTORS OF LABOR ACTIVITY OF ELDERLY MAN

    Directory of Open Access Journals (Sweden)

    Lyusova O.V.

    2016-04-01

    Full Text Available In modern Russian society occurred deformation traditions of respect and maintain the credibility of the elderly, and the socio-economic situation has deteriorated. An important condition to characterize the elderly is related to labor activity. expressed doubts surrounding their professionalism and high-quality and modern education. In society there are negative stereotypes about the elderly: Edil accusations of conservatism, the inability to take risks, tolerance for young. Old age pensioners perceived themselves as age losses, shrinking circle of social contacts, there is social exclusion, significant interpersonal contacts become strained. The psychological diagnosis of labor socialization of older employees 40 people participated. Conducted an empirical study it possible to identify the factors of labor activity in old age: the age and state of health; desire to raise the level of material well-being, the need to work, enthusiasm labor process, achievement motivation, the need for communication with the team; desire for samooaktualizatsii, positive self-esteem, internal locus of control. Working pensioners have high situational anxiety, adequate to the achievement of the objectives, an adequate assessment of its internal and external quality, high life satisfaction, motivation tends to focus on the process and result, reflexivity, subjectivity, have no fear of being rejected, is well adapted to society. Workers older people have average values of introversion, neuroticism, psychoticism.

  7. Bivariate Genomic Footprinting Detects Changes in Transcription Factor Activity

    Directory of Open Access Journals (Sweden)

    Songjoon Baek

    2017-05-01

    Full Text Available In response to activating signals, transcription factors (TFs bind DNA and regulate gene expression. TF binding can be measured by protection of the bound sequence from DNase digestion (i.e., footprint. Here, we report that 80% of TF binding motifs do not show a measurable footprint, partly because of a variable cleavage pattern within the motif sequence. To more faithfully portray the effect of TFs on chromatin, we developed an algorithm that captures two TF-dependent effects on chromatin accessibility: footprinting and motif-flanking accessibility. The algorithm, termed bivariate genomic footprinting (BaGFoot, efficiently detects TF activity. BaGFoot is robust to different accessibility assays (DNase-seq, ATAC-seq, all examined peak-calling programs, and a variety of cut bias correction approaches. BaGFoot reliably predicts TF binding and provides valuable information regarding the TFs affecting chromatin accessibility in various biological systems and following various biological events, including in cases where an absolute footprint cannot be determined.

  8. Critical success factors for physical activity promotion through community partnerships.

    Science.gov (United States)

    Lucidarme, Steffie; Marlier, Mathieu; Cardon, Greet; De Bourdeaudhuij, Ilse; Willem, Annick

    2014-02-01

    To define key factors of effective evidence-based policy implementation for physical activity promotion by use of a partnership approach. Using Parent and Harvey's model for sport and physical activity community-based partnerships, we defined determinants of implementation based on 13 face-to-face interviews with network organisations and 39 telephone interviews with partner organisations. Furthermore, two quantitative data-sets (n = 991 and n = 965) were used to measure implementation. In total, nine variables were found to influence implementation. Personal contact was the most powerful variable since its presence contributed to success while its absence led to a negative outcome. Four contributed directly to success: political motive, absence of a metropolis, high commitment and more qualified staff. Four others resulted in a less successful implementation: absence of positive merger effects, exposure motive and governance, and dispersed leadership. Community networks are a promising instrument for the implementation of evidence-based policies. However, determinants of both formation and management of partnerships influence the implementation success. During partnership formation, special attention should be given to partnership motives while social skills are of utmost importance for the management.

  9. The Determining Factors of Entrepreneurial Activity in Broiler Farms

    Directory of Open Access Journals (Sweden)

    Burhanuddin

    2013-12-01

    Full Text Available Indonesia still requires approximately 4 million entrepreneurs to become a developed country. This research aimed at identifying and analyzing the factors forming the broiler farm entrepreneurial activities that contribute on generating new entrepreneurs in Indonesia. Primary data were collected through questionnaire and analyzed by Structural Equation Modeling (SEM. Independent latent variables were innovations (IN, productions (DP, competitiveness (DS, risks (PR, labors (TK, and policies (KP, and then entrepreneurial activities (AK as dependent latent variable. The results showed that the model was built (MODEL1 as measurement model and MODEL2 as structural model had goodness fit and good reliability measurement variables (CR≥0.70, VE≥0.50. Innovation was reflected by the level of willingness to innovate (λ=0.63 and level of technology (λ=0.62. Production was reflected by production efficiency (λ=0.62 and cost control (λ=0.43. Competitiveness was reflected by the internet (λ=0.56, the cost of starting (λ=0.55, and new business formation (λ=0.58. Labor was reflected by the training and development (λ=0.57, and motivation (λ=0.42. Policies was reflected by access to land (λ=0.56, technical assistance (λ=0.60, research and technology (λ=0.66, and copyright protection (λ=0.64. The entrepreneurial activity of broiler farms were formed by innovation (γ=0.91, competitiveness (γ=0.94, and policies (γ=0.98. Broiler farms contributed positively to generate new entrepreneurs. Production and information technology development program, facilitation of the creation of new ventures program, business expansion program, and a program of strengthening intellectual property rights on broiler farms should be a priority of the Indonesian government programs in the future.

  10. Platelet factor 4 impairs the anticoagulant activity of activated protein C.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2012-02-01

    Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

  11. Platelet factor 4 impairs the anticoagulant activity of activated protein C.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2009-02-27

    Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

  12. Coagulation factor XI improves host defence during murine pneumonia-derived sepsis independent of factor XII activation

    NARCIS (Netherlands)

    Stroo, Ingrid; Zeerleder, Sacha; Ding, Chao; Luken, Brenda M.; Roelofs, Joris J. T. H.; de Boer, Onno J.; Meijers, Joost C. M.; Castellino, Francis J.; van 't Veer, Cornelis; van der Poll, Tom

    2017-01-01

    Bacterial pneumonia, the most common cause of sepsis, is associated with activation of coagulation. Factor XI (FXI), the key component of the intrinsic pathway, can be activated via factor XII (FXII), part of the contact system, or via thrombin. To determine whether intrinsic coagulation is involved

  13. Relationship between ABO blood groups and von Willebrand factor, ADAMTS13 and factor VIII in patients undergoing hemodialysis.

    Science.gov (United States)

    Rios, Danyelle R A; Fernandes, Ana Paula; Figueiredo, Roberta C; Guimarães, Daniela A M; Ferreira, Cláudia N; Simões E Silva, Ana C; Carvalho, Maria G; Gomes, Karina B; Dusse, Luci Maria Sant' Ana

    2012-05-01

    Several studies have demonstrated that non-O blood groups subjects present an increased VTE risk as compared to those carrying O blood group. The aim of this study was to investigate the ABO blood groups influence on factor VIII (FVIII) activity, von Willebrand factor (VWF), and ADAMTS13 plasma levels in patients undergoing hemodialysis (HD). Patients undergoing HD (N=195) and 80 healthy subjects (control group) were eligible for this cross-sectional study. The ABO blood group phenotyping was performed by the reverse technique. FVIII activity was measured through coagulometric method, and VWF and ADAMTS13 antigens were assessed by ELISA. FVIII activity and VWF levels were significantly higher and ADAMTS13 levels was decreased in HD patients, as compared to healthy subjects (P blood groups showed a significant increase in FVIII activity (P = 0.001) and VWF levels (P blood group. However, no significant difference was observed in ADAMTS13 levels (P = 0.767). In the control group, increased in FVIII activity (P = 0.001) and VWF levels (P = 0.002) and decreased in ADAMTS13 levels (P = 0.005) were observed in subjects carrying non-O blood groups as compared to carriers of O blood group.Our data confirmed that ABO blood group is an important risk factor for increased procoagulant factors in plasma, as FVIII and VWF. Admitting the possible role of kidneys in ADAMTS13 synthesis or on its metabolism, HD patients were not able to increase ADAMTS13 levels in order to compensate the increase of VWF levels mediated by ABO blood groups. Considering that non-O blood groups constitute a risk factor for thrombosis, it is reasonable to admit that A, B and AB HD patients need a careful and continuous follow-up in order to minimize thrombotic events.

  14. Absolute hypoxic exercise training enhances in vitro thrombin generation by increasing procoagulant platelet-derived microparticles under high shear stress in sedentary men.

    Science.gov (United States)

    Chen, Yu-Wen; Chen, Yi-Ching; Wang, Jong-Shyan

    2013-05-01

    HS (high shear) stress associated with artery stenosis facilitates TG (thrombin generation) by increasing the release of procoagulant PDMPs (platelet-derived microparticles). Physical exercise and hypoxia may paradoxically modulate vascular thrombotic risks. The aim of the present study was to investigate how exercise training with/without hypoxia affected TG mediated by PDMPs under physio-pathological shear flows. A total of 75 sedentary males were randomly divided into five groups (n=15 in each group): 21% O2 [NC (normoxic control)] or 15% O2 [HC (hypoxic control)] at rest or were trained at 50% of peak work rate under 21% O2 [NT (normoxic training)] or 15% O2 [HAT (hypoxic-absolute training)], or 50% of HR (heart rate) reserve under 15% O2 [HRT (hypoxic-relative training)] for 30 min/day, 5 days/week for 4 weeks. The PDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. Before the intervention, strenuous exercise markedly increased the PDMP count (14.8%) and TG rate (19.5%) in PDMP-rich plasma at 100 dynes/cm2 of shear stress (Pexercise. Conversely, HAT notably promoted the PDMP count (37.3%) and TG rate (38.9%) induced by HS (Pexercise. We conclude that both HRT and NT depress similarly HS-mediated TG during exercise, but HAT accelerates the prothrombotic response to vigorous exercise. These findings provide new insights into how exercise training under a hypoxic condition influences the risk of thrombosis associated with stenotic arteries.

  15. Sulindac metabolites inhibit epidermal growth factor receptor activation and expression

    Directory of Open Access Journals (Sweden)

    Ahnen Dennis

    2005-01-01

    Full Text Available Abstract Background Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs is associated with a decreased mortality from colorectal cancer (CRC. NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochemical mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2 signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF receptor (EGFR. Methods HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068, total EGFR, phosphorylated ERK1/2 (pERK1/2, total ERK1/2, activated caspase-3, and α-tubulin. Results EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24 h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12 h following sulindac sulfide treatment and persisted through at least 48 h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation. Conclusion These results suggest that

  16. Factoring - financial instrument supporting the current activity of an enterprise

    Directory of Open Access Journals (Sweden)

    Dorota Czerwińska-Kayzer

    2009-01-01

    Full Text Available Small and medium enterprises have a difficult access to classic financial sources. Therefore the factoring could be a financial instrument supporting effective management of the liabilities. Factoring improves the financial situation of a company, first of all financial liquidity. Moreover, factoring improves structure of financial statement and creates a possibility of risk transfer of debtor insolvency on factor.

  17. Activated protein C ameliorates coagulopathy but does not influence outcome in lethal H1N1 influenza: a controlled laboratory study

    NARCIS (Netherlands)

    Schouten, Marcel; van der Sluijs, Koenraad F.; Gerlitz, Bruce; Grinnell, Brian W.; Roelofs, Joris J. T. H.; Levi, Marcel M.; van 't Veer, Cornelis; van der Poll, Tom

    2010-01-01

    Introduction: Influenza accounts for 5 to 10% of community-acquired pneumonias and is a major cause of mortality. Sterile and bacterial lung injuries are associated with procoagulant and inflammatory derangements in the lungs. Activated protein C (APC) is an anticoagulant with anti-inflammatory

  18. Platelet-activating factor podoplanin: from discovery to drug development.

    Science.gov (United States)

    Takemoto, Ai; Miyata, Kenichi; Fujita, Naoya

    2017-06-01

    Tumor cell-induced platelet aggregation facilitates hematogenous metastasis by promoting tumor embolization, preventing immunological assaults and shear stress, and the platelet-releasing growth factors support tumor growth and invasion. Podoplanin, also known as Aggrus, is a type I transmembrane mucin-like glycoprotein and is expressed on wide range of tumor cells. Podoplanin has a role in platelet aggregation and metastasis formation through the binding to its platelet receptor, C-type lectin-like receptor 2 (CLEC-2). The podoplanin research was originally started from the cloning of highly metastatic NL-17 subclone from mouse colon 26 cancer cell line and from the establishment of 8F11 monoclonal antibody (mAb) that could neutralize NL-17-induced platelet aggregation and hematogenous metastasis. Later on, podoplanin was identified as the antigen of 8F11 mAb, and its ectopic expression brought to cells the platelet-aggregating abilities and hematogenous metastasis phenotypes. From the 8F11 mAb recognition epitopes, podoplanin is found to contain tandemly repeated, highly conserved motifs, designated platelet aggregation-stimulating (PLAG) domains. Series of analyses using the cells expressing the mutants and the established neutralizing anti-podoplanin mAbs uncovered that both PLAG3 and PLAG4 domains are associated with the CLEC-2 binding. The neutralizing mAbs targeting PLAG3 or PLAG4 could suppress podoplanin-induced platelet aggregation and hematogenous metastasis through inhibiting the podoplanin-CLEC-2 binding. Therefore, these domains are certainly functional in podoplanin-mediated metastasis through its platelet-aggregating activity. This review summarizes the platelet functions in metastasis formation, the role of platelet aggregation-inducing factor podoplanin in pathological and physiological situations, and the possibility to develop podoplanin-targeting drugs in the future.

  19. Ruscogenin inhibits lipopolysaccharide-induced acute lung injury in mice: involvement of tissue factor, inducible NO synthase and nuclear factor (NF)-κB.

    Science.gov (United States)

    Sun, Qi; Chen, Ling; Gao, Mengyu; Jiang, Wenwen; Shao, Fangxian; Li, Jingjing; Wang, Jun; Kou, Junping; Yu, Boyang

    2012-01-01

    Acute lung injury is still a significant clinical problem with a high mortality rate and there are few effective therapies in clinic. Here, we studied the inhibitory effect of ruscogenin, an anti-inflammatory and anti-thrombotic natural product, on lipopolysaccharide (LPS)-induced acute lung injury in mice basing on our previous studies. The results showed that a single oral administration of ruscogenin significantly decreased lung wet to dry weight (W/D) ratio at doses of 0.3, 1.0 and 3.0 mg/kg 1 h prior to LPS challenge (30 mg/kg, intravenous injection). Histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells were also attenuated by ruscogenin. In addition, ruscogenin markedly decreased LPS-induced myeloperoxidase (MPO) activity and nitrate/nitrite content, and also downregulated expression of tissue factor (TF), inducible NO synthase (iNOS) and nuclear factor (NF)-κB p-p65 (Ser 536) in the lung tissue at three doses. Furthermore, ruscogenin reduced plasma TF procoagulant activity and nitrate/nitrite content in LPS-induced ALI mice. These findings confirmed that ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-κB p65 activation, indicating it as a potential therapeutic agent for ALI or sepsis. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Hemophilia as a defect of the tissue factor pathway of blood coagulation: Effect of factors VIII and IX on factor X activation in a continuous-flow reactor

    International Nuclear Information System (INIS)

    Repke, D.; Gemmell, C.H.; Guha, A.; Turitto, V.T.; Nemerson, Y.; Broze, G.J. Jr.

    1990-01-01

    The effect of factors VIII and IX on the ability of the tissue factor-factor VIIa complex to activate factor X was studied in a continuous-flow tubular enzyme reactor. Tissue factor immobilized in a phospholipid bilayer on the inner surface of the tube was exposed to a perfusate containing factors VIIa, VIII, IX, and X flowing at a wall shear rate of 57, 300, or 1130 sec -1 . The addition of factors VIII and IX at their respective plasma concentrations resulted in a further 2 endash-to 3 endash fold increase. The direct activation of factor X by tissue factor-factor VIIa could be virtually eliminated by the lipoprotein-associated coagulation inhibitor. These results suggest that the tissue factor pathway, mediated through factors VIII and IX, produces significant levels of factor Xa even in the presence of an inhibitor of the tissue factor-factor VIIa complex; moreover, the activation is dependent on local shear conditions. These findings are consistent both with a model of blood coagulation in which initiation of the system results from tissue factor and with the bleeding observed in hemophilia

  1. Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity

    International Nuclear Information System (INIS)

    Liu Wenjin; Sun Maoyun; Jiang Jianhai; Shen Xiaoyun; Sun Qing; Liu Weicheng; Shen Hailian; Gu Jianxin

    2004-01-01

    The Cyclin D3 protein is a member of the D-type cyclins. Besides serving as cell cycle regulators, D-type cyclins have been reported to be able to interact with several transcription factors and modulate their transcriptional activations. Here we report that human activating transcription factor 5 (hATF5) is a new interacting partner of Cyclin D3. The interaction was confirmed by in vivo coimmunoprecipitation and in vitro binding analysis. Neither interaction between Cyclin D1 and hATF5 nor interaction between Cyclin D2 and hATF5 was observed. Confocal microscopy analysis showed that Cyclin D3 could colocalize with hATF5 in the nuclear region. Cyclin D3 could potentiate hATF5 transcriptional activity independently of its Cdk4 partner. But Cyclin D1 and Cyclin D2 had no effect on hATF5 transcriptional activity. These data provide a new clue to understand the new role of Cyclin D3 as a transcriptional regulator

  2. Plasmin-dependent proteolysis of tissue factor pathway inhibitor in a mouse model of endotoxemia.

    Science.gov (United States)

    Lupu, C; Herlea, O; Tang, H; Lijnen, R H; Lupu, F

    2013-01-01

    The development of a procoagulant state in sepsis, owing to aberrant expression of tissue factor (TF) and a sharp decrease in the level of its major inhibitor, TF pathway inhibitor (TFPI), could lead to microthrombotic organ failure. The mechanism for the decline in TFPI activity in the lung could involve plasmin-mediated cleavage of the inhibitor. To investigate the effect of plasmin generation on lung-associated TFPI activity, in normal conditions and during infusion of endotoxin (lipopolysaccharide [LPS]) in mice. Plasmin generation and TFPI activity were assayed in the lungs of mice deficient in tissue-type plasminogen (Plg) activator (t-PA) or Plg, at 2 h after LPS or saline injection. The sharp loss of lung-associated TFPI activity at 2 h after LPS challenge paralleled the abrupt increase in plasmin generation. TFPI activity was significantly retained in both t-PA(-/-) and Plg(-/-) mice, which are unable to generate plasmin. The increased plasmin generation during the early stages of sepsis could cleave/inactivate TFPI and thus lead to thrombotic complications. © 2012 International Society on Thrombosis and Haemostasis.

  3. Hemophilia B with mutations at glycine-48 of factor IX exhibited delayed activation by the factor VIIa-tissue factor complex.

    Science.gov (United States)

    Wu, P C; Hamaguchi, N; Yu, Y S; Shen, M C; Lin, S W

    2000-10-01

    Gly-48 is in the conserved DGDQC sequence (residues 47-51 of human factor IX) of the first EGF (EGF-1)-like domain of factor IX. The importance of the Gly-48 is manifested by two hemophilia B patients; factor IXTainan and factor IXMalmo27, with Gly-48 replaced by arginine (designated IXG48R) and valine (IXG48V), respectively. Both patients were CRM+ exhibiting mild hemophilic episodes with 25% (former) and 19% (latter) normal clotting activities. We characterize both factor IX variants to show the roles of Gly-48 and the conservation of the DGDQC sequence in factor IX. Purified plasma and recombinant factor IX variants exhibited approximately 26%-27% normal factor IX's clotting activities with G48R or G48V mutation. Both variants depicted normal quenching of the intrinsic fluorescence by increasing concentrations of calcium ions and Tb3+, indicating that arginine and valine substitution for Gly-48 did not perturb the calcium site in the EGF-1 domain. Activation of both mutants by factor XIa appeared normal. The reduced clotting activity of factors IXG48R and IXG48V was attributed to the failure of both mutants to cleavage factor X: in the presence of only phospholipids and calcium ions, both mutants showed a 4 to approximately 7-fold elevation in Km, and by adding factor VIIIa to the system, although factor VIIIa potentiated the activation of factor X by the mutants factor IXaG48R and factor IXaG48V, a 2 to approximately 3-fold decrease in the catalytic function was observed with the mutant factor IXa's, despite that they bound factor VIIIa on the phospholipid vesicles with only slightly reduced affinity when compared to wild-type factor IXa. The apparent Kd for factor VIIIa binding was 0.83 nM for normal factor IXa, 1.74 nM for IXaG48R and 1.4 nM for IXaG48V. Strikingly, when interaction with the factor VIIa-TF complex was examined, both mutations were barely activated by the VIIa-TF complex and they also showed abnormal interaction with VIIa-TF in bovine

  4. Factors influencing quality of life in patients with active tuberculosis.

    Science.gov (United States)

    Marra, Carlo A; Marra, Fawziah; Cox, Victoria C; Palepu, Anita; Fitzgerald, J Mark

    2004-10-20

    With effective treatment strategies, the focus of tuberculosis (TB) management has shifted from the prevention of mortality to the avoidance of morbidity. As such, there should be an increased focus on quality of life (QoL) experienced by individuals being treated for TB. The objective of our study was to identify areas of QoL that are affected by active TB using focus groups and individual interviews. English, Cantonese, and Punjabi-speaking subjects with active TB who were receiving treatment were eligible for recruitment into the study. Gender-based focus group sessions were conducted for the inner city participants but individual interviews were conducted for those who came to the main TB clinic or were hospitalized. Facilitators used open-ended questions and participants were asked to discuss their experiences of being diagnosed with tuberculosis, what impact it had on their lives, issues around adherence to anti-TB medications and information pertaining to their experience with side effects to these medications. All data were audio-recorded, transcribed verbatim, and analyzed using constant comparative analysis. 39 patients with active TB participated. The mean age was 46.2 years (SD 18.4) and 62% were male. Most were Canadian-born being either Caucasian or Aboriginal. Four themes emerged from the focus groups and interviews. The first describes issues related to the diagnosis of tuberculosis and sub-themes were identified as 'symptoms', 'health care provision', and 'emotional impact'. The second theme discusses TB medication factors and the sub-themes identified were 'adverse effects', 'ease of administration', and 'adherence'. The third theme describes social support and functioning issues for the individuals with TB. The fourth theme describes health behavior issues for the individuals with TB and the identified sub-themes were "behavior modification" and "TB knowledge." Despite the ability to cure TB, there remains a significant impact on QOL. Since much

  5. Factors influencing quality of life in patients with active tuberculosis

    Directory of Open Access Journals (Sweden)

    Cox Victoria C

    2004-10-01

    Full Text Available Abstract Background With effective treatment strategies, the focus of tuberculosis (TB management has shifted from the prevention of mortality to the avoidance of morbidity. As such, there should be an increased focus on quality of life (QoL experienced by individuals being treated for TB. The objective of our study was to identify areas of QoL that are affected by active TB using focus groups and individual interviews. Methods English, Cantonese, and Punjabi-speaking subjects with active TB who were receiving treatment were eligible for recruitment into the study. Gender-based focus group sessions were conducted for the inner city participants but individual interviews were conducted for those who came to the main TB clinic or were hospitalized. Facilitators used open-ended questions and participants were asked to discuss their experiences of being diagnosed with tuberculosis, what impact it had on their lives, issues around adherence to anti-TB medications and information pertaining to their experience with side effects to these medications. All data were audio-recorded, transcribed verbatim, and analyzed using constant comparative analysis. Results 39 patients with active TB participated. The mean age was 46.2 years (SD 18.4 and 62% were male. Most were Canadian-born being either Caucasian or Aboriginal. Four themes emerged from the focus groups and interviews. The first describes issues related to the diagnosis of tuberculosis and sub-themes were identified as 'symptoms', 'health care provision', and 'emotional impact'. The second theme discusses TB medication factors and the sub-themes identified were 'adverse effects', 'ease of administration', and 'adherence'. The third theme describes social support and functioning issues for the individuals with TB. The fourth theme describes health behavior issues for the individuals with TB and the identified sub-themes were "behavior modification" and "TB knowledge." Conclusion Despite the ability to

  6. Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis

    Science.gov (United States)

    Rynes, Jan; Donohoe, Colin D.; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek

    2012-01-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins. PMID:22851689

  7. Transcriptional activation of Mina by Sp1/3 factors.

    Science.gov (United States)

    Lian, Shangli; Potula, Hari Hara S K; Pillai, Meenu R; Van Stry, Melanie; Koyanagi, Madoka; Chung, Linda; Watanabe, Makiko; Bix, Mark

    2013-01-01

    Mina is an epigenetic gene regulatory protein known to function in multiple physiological and pathological contexts, including pulmonary inflammation, cell proliferation, cancer and immunity. We showed previously that the level of Mina gene expression is subject to natural genetic variation linked to 21 SNPs occurring in the Mina 5' region. In order to explore the mechanisms regulating Mina gene expression, we set out to molecularly characterize the Mina promoter in the region encompassing these SNPs. We used three kinds of assays--reporter, gel shift and chromatin immunoprecipitation--to analyze a 2 kb genomic fragment spanning the upstream and intron 1 regions flanking exon 1. Here we discovered a pair of Mina promoters (P1 and P2) and a P1-specific enhancer element (E1). Pharmacologic inhibition and siRNA knockdown experiments suggested that Sp1/3 transcription factors trigger Mina expression through additive activity targeted to a cluster of four Sp1/3 binding sites forming the P1 promoter. These results set the stage for comprehensive analysis of Mina gene regulation from the context of tissue specificity, the impact of inherited genetic variation and the nature of upstream signaling pathways.

  8. Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders

    DEFF Research Database (Denmark)

    Johansson, Pär I; Ostrowski, Sisse R

    2010-01-01

    Recombinant activated factor VII (rFVIIa, NovoSeven) was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX.......Recombinant activated factor VII (rFVIIa, NovoSeven) was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX....

  9. Regulation of platelet activating factor receptor coupled phosphoinositide-specific phospholipase C activity

    International Nuclear Information System (INIS)

    Morrison, W.J.

    1988-01-01

    The major objectives of this study were two-fold. The first was to establish whether binding of platelet activating factor (PAF) to its receptor was integral to the stimulation of polyphosphoinositide-specific phospholipase C (PLC) in rabbit platelets. The second was to determine regulatory features of this receptor-coupled mechanism. [ 3 H]PAF binding demonstrated two binding sites, a high affinity site with a inhibitory constant (Ki) of 2.65 nM and a low affinity site with a Ki of 0.80 μM. PAF receptor coupled activation of phosphoinositide-specific PLC was studied in platelets which were made refractory, by short term pretreatments, to either PAF or thrombin. Saponin-permeabilized rabbit platelets continue to regulate the mechanism(s) coupling PAF receptors to PLC stimulation. However, TRPγS and GDPβS, which affect guanine nucleotide regulatory protein functions, were unable to modulate the PLC activity to any appreciable extent as compared to PAF. The possible involvement of protein kinase C (PKC) activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets pretreated with staurosporine followed by pretreatments with PAF or phorbol 12-myristate 13-acetate (PMA)

  10. Isolation of cDNA clones coding for human tissue factor: primary structure of the protein and cDNA

    International Nuclear Information System (INIS)

    Spicer, E.K.; Horton, R.; Bloem, L.

    1987-01-01

    Tissue factor is a membrane-bound procoagulant protein that activates the extrinsic pathway of blood coagulation in the presence of factor VII and calcium. λ Phage containing the tissue factor gene were isolated from a human placental cDNA library. The amino acid sequence deduced from the nucleotide sequence of the cDNAs indicates that tissue factor is synthesized as a higher molecular weight precursor with a leader sequence of 32 amino acids, while the mature protein is a single polypeptide chain composed of 263 residues. The derived primary structure of tissue factor has been confirmed by comparison to protein and peptide sequence data. The sequence of the mature protein suggests that there are three distinct domains: extracellular, residues 1-219; hydrophobic, residues 220-242; and cytoplasmic, residues 243-263. Three potential N-linked carbohydrate attachment sites occur in the extracellular domain. The amino acid sequence of tissue factor shows no significant homology with the vitamin K-dependent serine proteases, coagulation cofactors, or any other protein in the National Biomedical Research Foundation sequence data bank (Washington, DC)

  11. Factors associated with active aging in Finland, Poland, and Spain.

    Science.gov (United States)

    Perales, Jaime; Martin, Steven; Ayuso-Mateos, Jose Luis; Chatterji, Somnath; Garin, Noe; Koskinen, Seppo; Leonardi, Matilde; Miret, Marta; Moneta, Victoria; Olaya, Beatriz; Tobiasz-Adamczyk, Beata; Haro, Josep Maria

    2014-08-01

    Continuous population aging has raised international policy interest in promoting active aging (AA). AA theoretical models have been defined from a biomedical or a psychosocial perspective. These models may be expanded including components suggested by lay individuals. This paper aims to study the correlates of AA in three European countries, namely, Spain, Poland, and Finland using four different definitions of AA. The EU COURAGE in Europe project was a cross-sectional general adult population survey conducted in a representative sample of the noninstitutionalized population of Finland, Poland, and Spain. Participants (10,800) lived in the community. This analysis focuses on individuals aged 50 years old and over (7,987). Four definitions (two biomedical, one psychosocial, and a complete definition including biomedical, psychosocial, and external variables) of AA were analyzed. Differences in AA were found for country, age, education, and occupation. Finland scored consistently the highest in AA followed by Spain and Poland. Younger age was associated with higher AA. Higher education and occupation was associated with AA. Being married or cohabiting was associated with better AA compared to being widowed or separated in most definitions. Gender and urbanicity were not associated with AA, with few exceptions. Men scored higher in AA only in Spain, whereas there was no gender association in the other two countries. Being widowed was only associated with lower AA in Poland and not being married was associated with lower AA in Poland and Finland but not Spain. Associations with education, marital status, and occupation suggest that these factors are the most important components of AA. These association patterns, however, seem to vary across the three countries. Actions to promote AA in these countries may be addressed at reducing inequalities in occupation and education or directly tackling the components of AA lacking in each country.

  12. Production of biologically active recombinant human factor H in Physcomitrella.

    Science.gov (United States)

    Büttner-Mainik, Annette; Parsons, Juliana; Jérôme, Hanna; Hartmann, Andrea; Lamer, Stephanie; Schaaf, Andreas; Schlosser, Andreas; Zipfel, Peter F; Reski, Ralf; Decker, Eva L

    2011-04-01

    The human complement regulatory serum protein factor H (FH) is a promising future biopharmaceutical. Defects in the gene encoding FH are associated with human diseases like severe kidney and retinal disorders in the form of atypical haemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis II (MPGN II) or age-related macular degeneration (AMD). There is a current need to apply intact full-length FH for the therapy of patients with congenital or acquired defects of this protein. Application of purified or recombinant FH (rFH) to these patients is an important and promising approach for the treatment of these diseases. However, neither protein purified from plasma of healthy individuals nor recombinant protein is currently available on the market. Here, we report the first stable expression of the full-length human FH cDNA and the subsequent production of this glycoprotein in a plant system. The moss Physcomitrella patens perfectly suits the requirements for the production of complex biopharmaceuticals as this eukaryotic system not only offers an outstanding genetical accessibility, but moreover, proteins can be produced safely in scalable photobioreactors without the need for animal-derived medium compounds. Transgenic moss lines were created, which express the human FH cDNA and target the recombinant protein to the culture supernatant via a moss-derived secretion signal. Correct processing of the signal peptide and integrity of the moss-produced rFH were verified via peptide mapping by mass spectrometry. Ultimately, we show that the rFH displays complement regulatory activity comparable to FH purified from plasma. © 2010 The Authors. Plant Biotechnology Journal © 2010 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  13. Platelet-activating factor (PAF) receptor-binding antagonist activity of Malaysian medicinal plants.

    Science.gov (United States)

    Jantan, I; Rafi, I A A; Jalil, J

    2005-01-01

    Forty-nine methanol extracts of 37 species of Malaysian medicinal plants were investigated for their inhibitory effects on platelet-activating factor (PAF) binding to rabbit platelets, using 3H-PAF as a ligand. Among them, the extracts of six Zingiberaceae species (Alpinia galanga Swartz., Boesenbergia pandurata Roxb., Curcuma ochorrhiza Val., C. aeruginosa Roxb., Zingiber officinale Rosc. and Z. zerumbet Koenig.), two Cinnamomum species (C. altissimum Kosterm. and C. pubescens Kochummen.), Goniothalamus malayanus Hook. f. Momordica charantia Linn. and Piper aduncum L. are potential sources of new PAF antagonists, as they showed significant inhibitory effects with IC50 values ranging from 1.2 to 18.4 microg ml(-1).

  14. Physical activity and cardiovascular risk factors in children

    DEFF Research Database (Denmark)

    Andersen, Lars Bo; Riddoch, Chris; Kriemler, Susi

    2011-01-01

    A number of recent systematic reviews have resulted in changes in international recommendations for children's participation in physical activity (PA) for health. The World Health Authority (WHO) has recently released new recommendations. The WHO still recommends 60 min of moderate to vigorous...... physical activity (MVPA), but also emphasises that these minutes should be on top of everyday physical activities. Everyday physical activities total around 30 min of MVPA in the quintile of the least active children, which means that the new recommendations constitute more activity in total compared...

  15. Procoagulant reactivity to laboratory acute mental stress in Africans and Caucasians, and its relation to depressive symptoms: the SABPA study.

    Science.gov (United States)

    von Känel, R; Hamer, M; Malan, N T; Scheepers, K; Meiring, M; Malan, L

    2013-11-01

    The risk of cardiovascular disease is dramatically increasing in Africans (black). The prothrombotic stress response contributes to atherothrombotic disease and is modulated by depressive symptoms. We examined coagulation reactivity to acute mental stress and its relation to psychological well-being in Africans relative to Caucasians (white). A total of 102 African and 165 Caucasian school teachers underwent the Stroop Color-Word Conflict test. Circulating levels of von Willebrand factor (VWF) antigen, fibrinogen, and D-dimer were measured before and after the Stroop. Cardiovascular reactivity measures were also obtained. All participants completed the Patient Health Questionnaire-9 and the General Health Questionnaire-28 for the assessment of depressive symptoms and total psychological distress, respectively. After controlling for covariates, resting levels of VWF, fibrinogen, and D-dimer were higher in Africans than in Caucasians (all p-values ≤0.006). Depressive symptoms and psychological distress were not significantly associated with resting coagulation measures. Stress reactivity in VWF (pstress when compared with Caucasians. Ethnic differences in the vascular adrenergic stress response might partially explain this finding. Depressive symptoms were associated with exaggerated VWF reactivity in Africans relative to Caucasians. The clinical implications of these findings for Africans need further study.

  16. Symbiotic Activity of Pea (Pisum sativum) after Application of Nod Factors under Field Conditions

    OpenAIRE

    Siczek, Anna; Lipiec, Jerzy; Wielbo, Jerzy; Kidaj, Dominika; Szarlip, Paweł

    2014-01-01

    Growth and symbiotic activity of legumes are mediated by Nod factors (LCO, lipo-chitooligosaccharides). To assess the effects of application of Nod factors on symbiotic activity and yield of pea, a two-year field experiment was conducted on a Haplic Luvisol developed from loess. Nod factors were isolated from Rhizobium leguminosarum bv. viciae strain GR09. Pea seeds were treated with the Nod factors (10−11 M) or water (control) before planting. Symbiotic activity was evaluated by measurement...

  17. Gc protein-derived macrophage activating factor (GcMAF): isoelectric focusing pattern and tumoricidal activity.

    Science.gov (United States)

    Mohamad, Saharuddin Bin; Nagasawa, Hideko; Sasaki, Hideyuki; Uto, Yoshihiro; Nakagawa, Yoshinori; Kawashima, Ken; Hori, Hitoshi

    2003-01-01

    Gc protein is the precursor for Gc protein-derived macrophage activating factor (GcMAF), with three phenotypes: Gc1f, Gc1s and Gc2, based on its electrophoretic mobility. The difference in electrophoretic mobility is because of the difference in its posttranslational sugar moiety composition. We compared the difference between Gc protein and GcMAF electrophoretic mobility using the isoelectric focusing (IEF) method. The tumoricidal activity of GcMAF-treated macrophage was evaluated after coculture with L-929 cell. The tumoricidal mechanism was investigated using TNF bioassay and nitric oxide (NO) release. The difference in Gc protein and GcMAF electrophoretic mobility was detected. The tumoricidal activity of GcMAF-treated macrophage was detected, but no release of TNF and NO was detected. The difference of isoelectric focusing mobility in Gc protein and GcMAF would be useful to develop a GcMAF detection method. GcMAF increased macrophage tumoricidal activity but TNF and NO release were not involved in the mechanism.

  18. Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR)

    DEFF Research Database (Denmark)

    Christensen, Anders; Kiss, Katalin; Lelkaitis, Giedrius

    2017-01-01

    Background: Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhib...... with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer....

  19. Giving Children a Voice: Exploring Qualitative Perspectives on Factors Influencing Recess Physical Activity

    Science.gov (United States)

    Pawlowski, Charlotte Skau; Schipperijn, Jasper; Tjørnhøj-Thomsen, Tine; Troelsen, Jens

    2018-01-01

    Facilitators and barriers to recess physical activity are not well understood. To date, research on recess physical activity has predominantly focused on quantitative measures typically focusing on a narrow set of predefined factors, often constructed by adults. To really understand the factors affecting recess physical activity it is crucial to…

  20. Effect of montelukast on platelet activating factor- and tachykinin induced mucus secretion in the rat

    Directory of Open Access Journals (Sweden)

    Groneberg David A

    2008-02-01

    Full Text Available Abstract Background Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity. Methods The effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique. Results Platelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity. Conclusion Cys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.

  1. Factors affecting implementation of practical activities in science ...

    African Journals Online (AJOL)

    Absence of separate and well equipped laboratory for each science, absence of efforts made by science teacher to use local material for practice of basic activities and less attention of local government and school administrative to existing problem results in less student motivation to practical activity which have influence ...

  2. Are intestinal helminths risk factors for developing active tuberculosis?

    DEFF Research Database (Denmark)

    Elias, Daniel; Mengistu, Getahun; Akuffo, Hannah

    2006-01-01

    OBJECTIVES: To determine the prevalence of intestinal helminth infections in active tuberculosis patients and their healthy household contacts and to assess its association with active TB in an area endemic for both types of infections. METHODS: Smear-positive pulmonary TB patients and healthy...

  3. Factors affecting perceived change in physical activity in pregnancy

    NARCIS (Netherlands)

    Astrid Merkx; Marlein Ausems; Luc Budé; Raymond de Vries; Marianne J. Nieuwenhuijze

    2017-01-01

    Objective reduction of physical activity (PA) during pregnancy is common but undesirable, as it is associated with negative outcomes, including excessive gestational weight gain. Our objective was to explore changes in five types of activity that occurred during pregnancy and the behavioural

  4. Awareness and habit: important factors in physical activity in children

    NARCIS (Netherlands)

    Kremers, S.P.J.; Dijkman, M.A.M.; de Meij, J.S.B.; Jurg, M.E.; Brug, J.

    2008-01-01

    Purpose - The purpose of this paper is to gain insight into the extent to which Dutch children are aware of their own physical activity level, and to what extent children's physical activity is habitual. Special attention was paid to the potential moderating effect of "awareness" and "habit

  5. Metabolic Vascular Syndrome: New Insights into a Multidimensional Network of Risk Factors and Diseases.

    Science.gov (United States)

    Scholz, Gerhard H; Hanefeld, Markolf

    2016-10-01

    Since 1981, we have used the term metabolic syndrome to describe an association of a dysregulation in lipid metabolism (high triglycerides, low high-density lipoprotein cholesterol, disturbed glucose homeostasis (enhanced fasting and/or prandial glucose), gout, and hypertension), with android obesity being based on a common soil (overnutrition, reduced physical activity, sociocultural factors, and genetic predisposition). We hypothesized that main traits of the syndrome occur early and are tightly connected with hyperinsulinemia/insulin resistance, procoagulation, and cardiovascular diseases. To establish a close link between the traits of the metabolic vascular syndrome, we focused our literature search on recent original work and comprehensive reviews dealing with the topics metabolic syndrome, visceral obesity, fatty liver, fat tissue inflammation, insulin resistance, atherogenic dyslipidemia, arterial hypertension, and type 2 diabetes mellitus. Recent research supports the concept that the metabolic vascular syndrome is a multidimensional and interactive network of risk factors and diseases based on individual genetic susceptibility and epigenetic changes where metabolic dysregulation/metabolic inflexibility in different organs and vascular dysfunction are early interconnected. The metabolic vascular syndrome is not only a risk factor constellation but rather a life-long abnormality of a closely connected interactive cluster of developing diseases which escalate each other and should continuously attract the attention of every clinician.

  6. Factors Affecting Number of Diabetes Management Activities Provided by Pharmacists.

    Science.gov (United States)

    Lo, Annie; Lorenz, Kathleen; Cor, Ken; Simpson, Scot H

    2016-12-01

    Legislative changes since 2007 have given Alberta pharmacists additional authorizations and new practice settings, which should enhance provision of clinical services to patients. This study examined whether these changes are related to the number of diabetes management activities provided by pharmacists. Cross-sectional surveys of Alberta pharmacists were conducted in 2006 and 2015. Both questionnaires contained 63 diabetes management activities, with response options to indicate how frequently the activity was provided. Respondents were grouped by survey year, practice setting, diabetes-specific training and additional authorizations. The number of diabetes management activities provided often or always were compared among groups by using analysis of variance. Data from 128 pharmacists participating in the 2006 survey were compared with 256 pharmacists participating in the 2015 survey; overall mean age was 41.6 (±10.9) years, 245 (64%) were women, mean duration of practice was 16.1 (±11.8) years, 280 (73%) were community pharmacists, 75 (20%) were certified diabetes educators (CDEs), and 100 (26%) had additional prescribing authorization (APA). Pharmacists provided a mean of 28.7 (95% CI 26.3 to 31.2) diabetes management activities in 2006 and 35.2 (95% CI 33.4-37.0) activities in 2015 (p<0.001). Pharmacists who were CDEs provided significantly more activities compared to other pharmacists (p<0.001). In 2015, working in a primary care network and having APA were also associated with provision of more activities (p<0.05 for both comparisons). Pharmacists provided more diabetes management activities in 2015 than in 2006. The number of diabetes management activities was also associated with being a CDE, working in a primary care network or having APA. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  7. Alternative pathways of thromboplastin-dependent activation of human factor X in plasma

    International Nuclear Information System (INIS)

    Marlar, R.A.; Griffin, J.H.

    1981-01-01

    To determine the interrelationships of the major coagulation pathways, the activation of 3H-labeled factor X in normal and various deficient human plasmas was evaluated when clotting was triggered by dilute rabbit or human thromboplastin. Various dilutions of thromboplastin and calcium were added to plasma samples containing 3H-factor X, and the time course of factor X activation was determined. At a 1/250 dilution of rabbit brain thromboplastin, the rate of factor X activation in plasmas deficient in factor VIII or factor IX was 10% of the activation rate of normal plasma or of factor XI deficient plasma. Reconstitution of the deficient plasmas with factors VIII or IX, respectively, reconstituted normal factor X activation. Similar results were obtained when various dilutions of human thromboplastin replaced the rabbit thromboplastin. From these plasma experiments, it is inferred that the dilute thromboplastin-dependent activation of factor X requires factors VII, IX, and VIII. An alternative extrinsic pathway that involves factors IX and VIII may be the physiologic extrinsic pathway and hence help to explain the consistent clinical observations of bleeding diatheses in patients deficient in factors IX or VIII

  8. Mucorales species activation of a serum leukotactic factor.

    Science.gov (United States)

    Marx, R S; Forsyth, K R; Hentz, S K

    1982-01-01

    Previous studies have suggested that the focal accumulation of phagocytic leukocytes is an important feature of the host response in mucormycosis. To ascertain the basis for this influx of inflammatory cells, we evaluated the effect of members of the order Mucorales, including species from the genera Rhizopus, Absidia, and Mucor, on the chemotactic activity of normal human serum for neutrophils and monocytes. Both hyphae and spores produced concentration-dependent chemotaxigenesis in serum to a maximum level equivalent to that produced by zymosan activation of serum. Chemotactic activity was similar for live and heat-killed hyphae. No leukotactic activity was demonstrated in the absence of serum. The pretreatment of serum with anti-C3 antibody, heating at 56 degrees C, or 0.01 M EDTA abolished the activity. The pretreatment of serum with 0.01 M ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid did not abolish the activity. These data provide evidence that the leukotactic activity of Mucorales species is generated through the alternative complement pathway. PMID:6759409

  9. Increased tissue factor, MMP-8, and D-dimer expression in diabetic patients with unstable advanced carotid atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jerzy Krupinski

    2007-09-01

    Full Text Available Jerzy Krupinski1,2, Marta M Turu1,2, M Angels Font1, Nesser Ahmed3, Matthew Sullivan3, Ana Luque1,2, Francisco Rubio1, Lina Badimon2, Mark Slevin31Department of Neurology, Stroke Unit, University Hospital of Bellvitge (HUB, Fundacio IDIBELL, Barcelona, Spain; 2Cardiovascular Research Centre, IIBB/CSIC-HSCSP-UAB, Barcelona, Spain; 3School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester, United KingdomAbstract: Advanced atherogenesis is characterized by the presence of markers of enhanced prothrombotic capacity, attenuated fibrinolysis, and by clinical conditions associated with defective coagulation. Diabetes may be associated with enhanced lesion instability and atherosclerotic plaque rupture. Plaques obtained from 206 patients undergoing carotid endarterectomy were divided into diabetic (type 2 and nondiabetic and analyzed by Western blotting and immunohistochemistry to detect tissue factor (TF, metalloproteinases (MMP-2, -8, -9, and fibrin/fibrinogen related antigens, and in situ zymography to detect MMP activity. Plasma samples were quantified for TF procoagulant activity, C-reactive protein, fibrinogen and D-dimer. Diabetic and symptomatic patients with hypoechogenic plaques had increased plasma TF activity and D-dimer, compared with those with hyperechogenic plaques (p = 0.03, p = 0.007, respectively. Diabetic, symptomatic patients had higher plasma D-dimer levels than asymptomatic patients (p = 0.03. There was a significant correlation between intramural TF levels and D-dimer in diabetic patients with symptomatic disease (p = 0.001, r2 = 0.4. In diabetic patients, plasma fibrinogen levels were higher in patients with hypoechogenic plaques (p = 0.007. Diabetic patients with ulcerated plaques had higher plasma D-dimer and MMP-8 levels than those with fibrous plaques (p = 0.02, p = 0.01, respectively. This data suggests that currently available circulating markers may be clinically useful to select

  10. Activating transcription factor 3 regulates immune and metabolic homeostasis

    Czech Academy of Sciences Publication Activity Database

    Ryneš, J.; Donohoe, C. D.; Frommolt, P.; Brodesser, S.; Jindra, Marek; Uhlířová, M.

    2012-01-01

    Roč. 32, č. 19 (2012), s. 3949-3962 ISSN 0270-7306 R&D Projects: GA ČR(CZ) GD204/09/H058 Institutional support: RVO:60077344 Keywords : metabolic homeostasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.372, year: 2012

  11. A MATHEMATICAL MODEL FOR ASSESSING THE FACTORING ACTIVITY

    Directory of Open Access Journals (Sweden)

    Madalina Radoi

    2013-11-01

    Full Text Available Originally–being over 4,000 years old–factoring was first used in the fertile territory of old Mesopotamia at a time when the famous Code of Hammurabi was drawn up. However, many years passed until the British colonists started to use it on a large scale at a time when the metropolis would pay them sums of money for the merchandise that colonists sent to the old continent until they collected the invoices.In Romania factoring started to play a major role in financial operations for it led to the increase of liquidities on the market.According to the Romanian legislation, factoring is a contract concluded between a party known as “the client”, which supplies merchandise or provides services, and a banking institution or specialized financial institution known as “the factor”, whereby the latter ensures the financing source, collects the receivables and protects credit risks, while the client assigns to the factor the receivables resulting from the sale of goods or the provision of services to third parties.

  12. Activity limitations and factors influencing functional outcome of ...

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... life and satisfaction with life1,22. A recent study conducted among community dwelling stroke survivors found functional ability and independence to be the strongest predictor of, and were responsible for the greatest variance on participation22. For determining the factors influencing outcome with the use ...

  13. Factors influencing nurse participation in continuing professional development activities : Survey results from the Netherlands

    NARCIS (Netherlands)

    Brekelmans, G.A.; Maassen, S.; Poell, R.F.; Weststrate, J.; Geurdes, E.

    2016-01-01

    Background Professionals are individually responsible for planning and carrying out continuing professional development (CPD) activities, ensuring their relevance to current practice and career development. The key factors that encourage nurses to undertake CPD activities are not yet clear. Several

  14. Thrombin like activity of Asclepias curassavica L. latex: action of cysteine proteases.

    Science.gov (United States)

    Shivaprasad, H V; Rajesh, R; Nanda, B L; Dharmappa, K K; Vishwanath, B S

    2009-05-04

    To validate the scientific basis of plant latex to stop bleeding on fresh cuts. Cysteine protease(s) from Asclepias curassavica (Asclepiadaceae) plant latex was assessed for pro-coagulant and thrombin like activities. A waxy material from the latex of Asclepias curassavica latex was removed by freezing and thawing. The resulted latex enzyme fraction was assayed for proteolytic activity using denatured casein as substrate. Its coagulant activity and thrombin like activity were determined using citrated plasma and pure fibrinogen, respectively. Inhibition studies were performed using specific protease inhibitors to know the type of protease. The latex enzyme fraction exhibited strong proteolytic activity when compared to trypsin and exerted pro-coagulant action by reducing plasma clotting time from 195 to 58 s whereas trypsin reduced clotting time marginally from 195 to 155 s. The pro-coagulant activity of this enzyme fraction was exerted by selectively hydrolyzing A alpha and B beta subunits of fibrinogen to form fibrin clot when pure fibrinogen was used as substrate as assessed by fibrinogen-agarose plate method and fibrinogen polymerization assay. Trypsin failed to induce any fibrin clot under similar conditions. The electrophoretic pattern of latex enzyme fraction-induced fibrin clot was very much similar to that of thrombin-induced fibrin clot and mimic thrombin like action. The proteolytic activity including thrombin like activity of Asclepias curassavica latex enzyme fraction was completely inhibited by iodoaceticacid (IAA). Cysteine proteases from Asclepias curassavica latex exhibited strong pro-coagulant action and were found to be specific in its action (Thrombin like). This could be the basis for the use of plant latex in pharmacological applications that justify their use as folk medicine.

  15. Activation measurements for thermal neutrons. Part J. Evaluation of thermal neutron transmission factors

    International Nuclear Information System (INIS)

    Egbert, Stephen D.

    2005-01-01

    In order to relate thermal neutron activation measurements in samples to the calculated free-in-air thermal neutron activation levels given in Chapter 3, use is made of sample transmission factors. Transmission factors account for the modification of the fluence and activation at each sample's in situ location. For the purposes of this discussion, the transmission factor (TF) is defined as the ratio of the in situ sample activation divided by the free-in-air (FIA) activation at a height of 1 m above ground at the same ground range. The procedures for calculation of TF's and example results are presented in this section. (author)

  16. Contact activation of blood-plasma coagulation

    Science.gov (United States)

    Golas, Avantika

    Surface engineering of biomaterials with improved hemocompatibility is an imperative, given the widespread global need for cardiovascular devices. Research summarized in this dissertation focuses on contact activation of FXII in buffer and blood plasma frequently referred to as autoactivation. The extant theory of contact activation imparts FXII autoactivation ability to negatively charged, hydrophilic surfaces. According to this theory, contact activation of plasma involves assembly of proteins comprising an "activation complex" on activating surfaces mediated by specific chemical interactions between complex proteins and the surface. This work has made key discoveries that significantly improve our core understanding of contact activation and unravel the existing paradigm of plasma coagulation. It is shown herein that contact activation of blood factor XII (FXII, Hageman factor) in neat-buffer solution exhibits a parabolic profile when scaled as a function of silanized-glass-particle activator surface energy (measured as advancing water adhesion tension t°a=g° Iv costheta in dyne/cm, where g°Iv is water interfacial tension in dyne/cm and theta is the advancing contact angle). Nearly equal activation is observed at the extremes of activator water-wetting properties --36 moderated by adsorption of plasma proteins unrelated to coagulation through an "adsorption-dilution" effect that blocks FXII contact with hydrophobic activator surfaces. The adsorption-dilution effect explains the apparent specificity for hydrophilic activators pursued by earlier investigators. Finally a comparison of FXII autoactivation in buffer, serum, protein cocktail, and plasma solutions is shown herein. Activation of blood plasma coagulation in vitro by contact with material surfaces is demonstrably dependent on plasma-volume-to-activator-surface-area ratio. However, activation of factor XII dissolved in buffer, protein cocktail, heat-denatured serum, and FXI deficient plasma does not

  17. WRKY transcription factors involved in activation of SA biosynthesis genes

    NARCIS (Netherlands)

    van Verk, Marcel C; Bol, John F; Linthorst, Huub J M

    2011-01-01

    Increased defense against a variety of pathogens in plants is achieved through activation of a mechanism known as systemic acquired resistance (SAR). The broad-spectrum resistance brought about by SAR is mediated through salicylic acid (SA). An important step in SA biosynthesis in Arabidopsis is the

  18. Food choices, physical activity levels and other factors associated ...

    African Journals Online (AJOL)

    The aim of the study was to evaluate educators' health behaviours regarding dietary intake and physical activity (PA). A survey was undertaken in 517 educators at 83 primary schools in the Western Cape. Food choices (healthy vs. unhealthy), PA levels, and health knowledge were measured by questionnaire. The six most ...

  19. Factors influencing beta-amylase activity in sorghum malt

    CSIR Research Space (South Africa)

    Taylor, JRN

    1993-09-01

    Full Text Available isozyme of pI approximately 4.4-4.5, unlike the many isozymes all of higher pI in barley. However, like barley, sorghum beta-amylase was more temperature-labile than its alpha-amylase. Beta-amylase activity in sorghum malt was increased by germination time...

  20. Factors Influencing Physical Activity among Postpartum Iranian Women

    Science.gov (United States)

    Roozbahani, Nasrin; Ghofranipour, Fazlollah; Eftekhar Ardabili, Hassan; Hajizadeh, Ebrahim

    2014-01-01

    Background: Postpartum women are a population at risk for sedentary living. Physical activity (PA) prior to pregnancy may be effective in predicting similar behaviour in the postpartum period. Objective: To test a composite version of the extended transtheoretical model (TTM) by adding "past behaviour" in order to predict PA behaviour…

  1. On factors controlling activity of submonolayer bimetallic catalysts: Nitrogen desorption

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Wei; Vlachos, Dionisios G., E-mail: vlachos@udel.edu [Center for Catalytic Science and Technology, Catalysis Center for Energy Innovation, Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware 19716 (United States)

    2014-01-07

    We model N{sub 2} desorption on submonolayer bimetallic surfaces consisting of Co clusters on Pt(111) via first-principles density functional theory-based kinetic Monte Carlo simulations. We find that submonolayer structures are essential to rationalize the high activity of these bimetallics in ammonia decomposition. We show that the N{sub 2} desorption temperature on Co/Pt(111) is about 100 K higher than that on Ni/Pt(111), despite Co/Pt(111) binding N weaker at low N coverages. Co/Pt(111) has substantially different lateral interactions than single metals and Ni/Pt. The lateral interactions are rationalized with the d-band center theory. The activity of bimetallic catalysts is the result of heterogeneity of binding energies and reaction barriers among sites, and the most active site can differ on various bimetallics. Our results are in excellent agreement with experimental data and demonstrate for the first time that the zero-coverage descriptor, used until now, for catalyst activity is inadequate due not only to lacking lateral interactions but importantly to presence of multiple sites and a complex interplay of thermodynamics (binding energies, occupation) and kinetics (association barriers) on those sites.

  2. Factors influencing activity of triazole fungicides towards Botrytis cinerea.

    NARCIS (Netherlands)

    Stehmann, C.; Waard, de M.A.

    1996-01-01

    The activity of triazole fungicides towards Botrytis cinerea was investigated in vitro (radial growth on fungicide-amended agar) and in vivo (foliar-sprayed tomato plants and dip-treated grapes). In both tests the benzimidazoles, benomyl and thiabendazole, and the dicarboximides, iprodione and

  3. Expression and Activation of STAT Transcription Factors in Breast Cancer

    Science.gov (United States)

    1998-05-08

    clinicians. J~, 273: 577-585, 1995. 183 Hundertmark 5, Buhler H, Rudolf M, Weitzel HK, Ragosch V: Inhibition of 11 beta-hydroxysteroid dehydrogenase...activated protein kinase through a Jakl-dependent pathway. Mol. Cell. Bioi., 17:3833-40, 1997. Stewart JF, Rubens RO, King RJ, Minton MJ, Steiner R

  4. Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

    Energy Technology Data Exchange (ETDEWEB)

    Bitencourt, C.S. [Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I. [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-02

    Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

  5. Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

    International Nuclear Information System (INIS)

    Bitencourt, C.S.; Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I.

    2012-01-01

    Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production

  6. B16-BL6 melanoma cells release inhibitory factor(s) of active pump activity in isolated lymph vessels.

    Science.gov (United States)

    Nakaya, K; Mizuno, R; Ohhashi, T

    2001-12-01

    We investigated whether supernatant cultured with melanoma cell lines B16-BL6 and K1735 or the Lewis lung carcinoma cell line (LLC) can regulate lymphatic pump activity with bioassay preparations isolated from murine iliac lymph vessels. B16-BL6 and LLC supernatants caused significant dilation of lymph microvessels with cessation of pump activity. B16-BL6 supernatant produced dose-related cessation of lymphatic pump activity. There was no significant tachyphylaxis in the supernatant-mediated inhibitory response of lymphatic pump activity. Pretreatment with 3 x 10(-5) M N(omega)-nitro-L-arginine methyl ester (L-NAME) or 10(-7) M or 10(-6) M glibenclamide and 5 x 10(-4) M 5-hydroxydecanoic acid caused significant reduction of supernatant-mediated inhibitory responses. Simultaneous treatment with 10(-3) M L-arginine and 3 x 10(-5) M L-NAME significantly lessened L-NAME-induced inhibition of the supernatant-mediated response, suggesting that endogenous nitric oxide (NO) plays important roles in supernatant-mediated inhibitory responses. Chemical treatment dialyzed substances of B16-BL6 cells may release nonpeptide substance(s) of <1,000 MW, resulting in significant cessation of lymphatic pump activity via production and release of endogenous NO and activation of mitochondrial ATP-sensitive K(+) channels.

  7. Demographic factors, workplace factors and active transportation use in the USA: a secondary analysis of 2009 NHTS data.

    Science.gov (United States)

    Quinn, Tyler D; Jakicic, John M; Fertman, Carl I; Barone Gibbs, Bethany

    2017-05-01

    While active transportation has health, economic and environmental benefits, participation within the USA is low. The purpose of this study is to examine relationships of demographic and workplace factors with health-enhancing active transportation and commuting. Participants in the 2009 National Household Travel Survey reported demographics, workplace factors (time/distance to work, flextime availability, option to work from home and work start time) and active transportation (for any purpose) or commuting (to and from work, workers only) as walking or biking (≥10 min bouts only). Multiple logistic regression examined cross-sectional relationships between demographics and workplace factors with active transportation and commuting. Among 152 573 participants, active transportation was reported by 1.11% by biking and 11.74% by walking. Among 111 808 working participants, active commuting was reported by 0.80% by biking and 2.76% by walking. Increased odds (pbike but decreased odds of walk transporting. Inconsistent patterns were observed by race, but whites had greater odds of any biking (p<0.05). Odds of active commuting were higher with a flexible schedule (p<0.001), the option to work from home (p<0.05), shorter time and distance to work (both p<0.001), and work arrival time between 11:00 and 15:59 (walking only, p=0.001). Active transportation differed across demographic and workplace factors. These relationships could inform infrastructure policy decisions and workplace wellness programming targeting increased active transportation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. THE TIME FACTOR IN MARITIME TRANSPORT AND PORT LOGISTICS ACTIVITIES

    Directory of Open Access Journals (Sweden)

    Florin NICOLAE

    2016-06-01

    Full Text Available Execution of the carriage contract requires compliance to all the conditions in it, by all those involved in the transport. Main obligations incumbent upon the vessel, and obviously, to other transporters, who must provide transportation according to deadlines and safety. Contract compliance is certifying transport participants about their seriousness and an appropriate market quotation. Therefore, present work pragmatically sets schematics reference time associated implementation of the carriage contract. Also, are demonstrated relationships established between maritime transport “players” and sequence of activities related to the operation of the vessel in port. The authors propose a set of concepts and terms whose utility is established to solve practical problems in this area of activity.

  9. Factors affecting the adsorption of chromium (VI) on activated carbon

    Energy Technology Data Exchange (ETDEWEB)

    Yavuz, R.; Orbak, I.; Karatepe, N. [Istanbul Technical University, Istanbul (Turkey)

    2006-09-15

    The aim of this investigation was to determine the adsorption behavior of chromium (VI) on two different activated carbon samples produced from Tuncbilek lignite. The effects of the initial chromium (VI) concentration (250-1000 mg/L), temperature (297-323 K) and pH (2.0-9.5) on adsorption were investigated systematically. The effectiveness of the parameters on chromium adsorption was found to be in the order of pH, the initial Cr(VI) concentration and the temperature. Increasing the pH from 2.0 to 9.5 caused a decrease in adsorption. However, the adsorption was increased by increasing the initial Cr(VI) concentration and temperature. The multilinear mathematical model was also developed to predict the Cr(VI) adsorption on activated carbon samples within the experimental conditions.

  10. Dynamic factors and electromyographic activity in a sprint start

    Directory of Open Access Journals (Sweden)

    M Čoh

    2009-07-01

    Full Text Available The aim of the study was to establish the major dynamic parameters as well as the EMG activation of muscles in a sprint start as the first derivative of sprint velocity. The subject of the analysis was block velocity, the production of force in the front and rear starting blocks, the block acceleration in the first two steps and the electromyographic activity (EMG of the following muscles: the erector spinae muscle, gluteus maximus muscle, rectus femoris muscle, vastus medialis muscle, vastus lateralis muscle, biceps femoris muscle and gastrocnemius–medialis muscle. One international-class female sprinter participated in the experiment. She performed eight starts in constant laboratory conditions. The 3-D kinematic analysis was made using a system of nine Smart-e 600 cameras operating at a frame rate of 60 Hz. Dynamic parameters were established by means of two separate force platforms to which the starting blocks were fixed. A 16-channel electromyograph was used to analyse electromyographic activity (EMG. It was established that the block velocity depended on the absolute force produced in the front and rear starting blocks and that it was 2.84±0.21 m.s-1. The maximal force on the rear and front blocks was 628±34 N and 1023±30 N, respectively. In view of the total impulse (210±11 Ns the force production/time ratio in the rear and front blocks was 34%:66%. The erector spinae muscle, vastus lateralis muscle and gastrocnemius–medialis muscle generate the efficiency of the start. The block acceleration in the first two steps primarily depends on the activation of the gluteus maximus muscle, rectus femoris muscle, biceps femoris muscle and gastrocnemius–medialis muscle. A sprint start is a complex motor stereotype requiring a high degree of integration of the processes of central movement regulation and an optimal level of biomotor abilities.

  11. Price sensitivity to tourism activities: looking for determinant factors

    OpenAIRE

    Lorenzo Masiero; Juan L. Nicolau

    2011-01-01

    The literature contains evidence that there is a marked heterogeneity in price responses to tourism products, leading to a great variety of tourist sensitivities to price. Thus the role price plays is complex, and a particularly challenging aspect of this complexity is that its effect is not unambiguous, thereby negating the idea that the demand for tourism products and tourist activities can always be regarded as demand for ordinary goods. This article identifies and explains, as a novelty f...

  12. High Income Inequality as a Structural Factor in Entrepreneurial Activity

    Directory of Open Access Journals (Sweden)

    Antonio Lecuna

    2014-04-01

    Full Text Available Statistical tests on a panel of data from 54 countries over the 2004–2009 period support the proposition that high income inequality and entrepreneurial activity share a positive linear relationship. In a novel approach, the dependent variable is defined from two independent and uncorrelated perspectives: (1 the World Bank Group Entrepreneurship Snapshot, which measures new business entry density based on secondary official sources; and (2 the Total Early Stage Entrepreneurial Activity of the Global Entrepreneurship Monitor project, which is a survey-based measure of formal and informal entrepreneurial participation rates. The empirical strategy is based on the logic that economies with increasing concentrations of wealth tend to encourage entrepreneurial activity because entrepreneurs accumulate more income than workers. Following the disequalizing model, once this inequality appears, it is reinforced in successive generations. The intuition behind this outcome is that a certain level of initial capital is required to establish a new enterprise, which implies that the probability of becoming an entrepreneur increases if an individual has inherited wealth.

  13. A transcription factor active on the epidermal growth factor receptor gene

    International Nuclear Information System (INIS)

    Kageyama, R.; Merlino, G.T.; Pastan, I.

    1988-01-01

    The authors have developed an in vitro transcription system for the epidermal growth factor receptor (EGFR) oncogene by using nuclear extracts of A431 human epidermoid carcinoma cells, which overproduce EGFR. They found that a nuclear factor, termed EGFR-specific transcription factor (ETF), specifically stimulated EGFR transcription by 5- to 10-fold. In this report, ETF, purified by using sequence-specific oligonucleotide affinity chromatography, is shown by renaturing material eluted from a NaDodSO 4 /polyacrylamide gel to be a protein with a molecular mass of 120 kDa. ETF binds to the promoter region, as measured by DNase I footprinting and gel-mobility-shift assays, and specifically stimulates the transcription of the EGFR gene in a reconstituted in vitro transcription system. These results suggest that ETF could play a role in the overexpression of the cellular oncogene EGFR

  14. Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography.

    Science.gov (United States)

    Mousavi Hosseini, Kamran; Nasiri, Saleh

    2015-01-01

    Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). RESULTS of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII.

  15. Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect.

    Science.gov (United States)

    Mathijssen, Natascha C J; Masereeuw, Rosalinde; Holme, Pal Andre; van Kraaij, Marian G J; Laros-van Gorkom, Britta A P; Peyvandi, Flora; van Heerde, Waander L

    2013-08-01

    Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. Ten factor VII deficient patients were treated with either recombinant activated (20 μg/kg) or plasma-derived (25 IU/kg) factor VII in a cross-over design. Pharmacokinetic parameters were analyzed through activated factor VII activity, factor VII clotting activity, and factor VII antigen levels on depicted time points. Factor VII activity half-lifes, determined by non-compartmental and one-compartmental analysis (results in brackets), were shorter for recombinant activated (1.4h; 0.7h) than for plasma-derived factor VII (6.8h; 3.2h); both recombinant activated (5.1h; 2.1h and plasma-derived factor VII (5.8h; 3.2h) resulted in longer half-lives of factor VII antigen. Activated factor VII half-lives (based on activated factor VII activity levels) were significantly higher compared to factor VII clotting activity (1.6h; 0.9h). Volumes of distribution were significantly higher for activated factor VII (236 ml/kg; 175 ml/kg, measured by activated factor VII) as compared to plasma-derived factor VII (206 ml/kg; 64 ml/kg, measured by factor FVII activity), suggesting a plasma- and extracellular fluid distribution for recombinant activated factor VII. Recombinant activated factor VII showed significantly shorter half-lifes than plasma-derived factor VII. Volumes of distribution were significantly higher for treatment with recombinant activated factor VII. The longer half-life for plasma-derived factor VII, compared to recombinant activated factor VII, and the increased volume of distribution for recombinant activated factor VII, compared to plasma-derived factor VII may further elucidate the beneficial effect of prophylactic treatment of both products. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Recombinant activated factor VII in cardiac surgery: single-center experience.

    Science.gov (United States)

    Singh, Sarvesh Pal; Chauhan, Sandeep; Choudhury, Minati; Malik, Vishwas; Choudhary, Shiv Kumar

    2014-02-01

    The widespread off-label use of recombinant activated factor VII for the control of refractory postoperative hemorrhage continues despite a warning from the Food and Drug Administration. Although effective in reducing the need for transfusion of blood and blood products, safety concerns still prevail. To compare the dosing and efficacy of recombinant activated factor VII between pediatric and adult patients, and in the operating room and intensive care unit. The records of 69 patients (33 children and 36 adults) who underwent cardiovascular surgery and received recombinant activated factor VII were reviewed retrospectively. The dose of recombinant activated factor VII, mediastinal drainage, use of blood and blood products, incidence of thrombosis, and 28-day mortality were studied. the efficacy of recombinant activated factor VII was comparable in adults and children, despite the lower dose in adults. Prophylactic use of recombinant activated factor VII decreased the incidence of mediastinal exploration and the duration of intensive care unit stay. A 4.3% incidence of thrombotic complications was observed in this study. The efficacious dose of recombinant activated factor VII is much less in adults compared to children. Prophylactic use of recombinant activated factor VII decreases the dose required, the incidence of mediastinal exploration, and intensive care unit stay, with no survival benefit.

  17. Determination of calibration factors for field measurements of liquid and gaseous activities

    International Nuclear Information System (INIS)

    Jose, M.T.; Ravi, T.; Raghunath, V.M.

    1994-01-01

    While working out the procedures for calibration and activity estimation of 41 Ar gaseous effluent earlier, it was felt necessary to obtain similar factors for liquid and gas activity measurements for other energies also. The paper describes the work done towards this and the conversion factors and minimum detectable levels established. (author). 3 tabs., 1 ref

  18. Predictive factors of unfavorable prostate cancer in patients who underwent prostatectomy but eligible for active surveillance

    Directory of Open Access Journals (Sweden)

    Seol Ho Choo

    2014-06-01

    Conclusions: A significant proportion of patients who were candidates for active surveillance had unfavorable prostate cancer. Age, PSA density, and two positive cores were independent significant predictive factors for unfavorable prostate cancer. These factors should be considered when performing active surveillance.

  19. WRKY Transcription Factors Involved in Activation of SA Biosynthesis Genes

    Directory of Open Access Journals (Sweden)

    Bol John F

    2011-05-01

    Full Text Available Abstract Background Increased defense against a variety of pathogens in plants is achieved through activation of a mechanism known as systemic acquired resistance (SAR. The broad-spectrum resistance brought about by SAR is mediated through salicylic acid (SA. An important step in SA biosynthesis in Arabidopsis is the conversion of chorismate to isochorismate through the action of isochorismate synthase, encoded by the ICS1 gene. Also AVRPPHB SUSCEPTIBLE 3 (PBS3 plays an important role in SA metabolism, as pbs3 mutants accumulate drastically reduced levels of SA-glucoside, a putative storage form of SA. Bioinformatics analysis previously performed by us identified WRKY28 and WRKY46 as possible regulators of ICS1 and PBS3. Results Expression studies with ICS1 promoter::β-glucuronidase (GUS genes in Arabidopsis thaliana protoplasts cotransfected with 35S::WRKY28 showed that over expression of WRKY28 resulted in a strong increase in GUS expression. Moreover, qRT-PCR analyses indicated that the endogenous ICS1 and PBS3 genes were highly expressed in protoplasts overexpressing WRKY28 or WRKY46, respectively. Electrophoretic mobility shift assays indentified potential WRKY28 binding sites in the ICS1 promoter, positioned -445 and -460 base pairs upstream of the transcription start site. Mutation of these sites in protoplast transactivation assays showed that these binding sites are functionally important for activation of the ICS1 promoter. Chromatin immunoprecipitation assays with haemagglutinin-epitope-tagged WRKY28 showed that the region of the ICS1 promoter containing the binding sites at -445 and -460 was highly enriched in the immunoprecipitated DNA. Conclusions The results obtained here confirm results from our multiple microarray co-expression analyses indicating that WRKY28 and WRKY46 are transcriptional activators of ICS1 and PBS3, respectively, and support this in silico screening as a powerful tool for identifying new components of stress

  20. Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI.

    Directory of Open Access Journals (Sweden)

    Cristina Puy

    Full Text Available Factor (F XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα, in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin.Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma.Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP.

  1. THE FACTORS THAT INFLUENCE THE ACTIVITY OF ECONOMIC ENTITIES

    Directory of Open Access Journals (Sweden)

    SINTEA(ANGHEL LUCICA

    2014-02-01

    Full Text Available In the current situation many experts and ordinary people are asking themselves: Where is the economy heading? How can we counteract the disruptive factors? Which strategies must be employed? How should the risks be properly assessed in order to diminish them to the lowest level? What measures should be taken to improve the situation? This requires a necessary economic and financial analysis, based on the data from the financial statements, the discovery and application of risk assessment methods and the detection of procedures to mitigate this risk. It is also necessary to draw a comparison between the expected results of a rational and scientific research, and those obtained through empirical processes by means of marketing.

  2. Risk factors for active trachoma among children aged 1-9 years in ...

    African Journals Online (AJOL)

    Background: Trachoma is a public health problem in sub-Saharan Africa. Data on risk factors for active trachoma are limited. There is a need for understanding the factors affecting trachoma in order to plan for targeted interventions. The aim of the study was to examine the relationship between potential risk factors and ...

  3. Symbiotic Activity of Pea (Pisum sativum after Application of Nod Factors under Field Conditions

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    Anna Siczek

    2014-04-01

    Full Text Available Growth and symbiotic activity of legumes are mediated by Nod factors (LCO, lipo-chitooligosaccharides. To assess the effects of application of Nod factors on symbiotic activity and yield of pea, a two-year field experiment was conducted on a Haplic Luvisol developed from loess. Nod factors were isolated from Rhizobium leguminosarum bv. viciae strain GR09. Pea seeds were treated with the Nod factors (10−11 M or water (control before planting. Symbiotic activity was evaluated by measurements of nitrogenase activity (acetylene reduction assay, nodule number and mass, and top growth by shoot mass, leaf area, and seed and protein yield. Nod factors generally improved pea yield and nitrogenase activity in the relatively dry growing season 2012, but not in the wet growing season in 2013 due to different weather conditions.

  4. Activation measurements for fast neutrons. Part E. Evaluation of fast neutron 63Ni transmission factors

    International Nuclear Information System (INIS)

    Egbert, Stephen D.

    2005-01-01

    The 63 Ni measurements for fast neutrons in copper samples are compared to the calculated free-in-air 63 Ni neutron activation given in Chapter 3 by use of transmission factors. Transmission factors were calculated to account for the modification of the fluence and activation at each sample's in situ location. For the purposes of this discussion, the transmission factor (TF) is defined as the ratio of the in situ sample activation divided by the untilted free-in-air (FIA) activation at a height of 1 m above ground at the same ground range. Examples of the application of TF's will be provided in this section. (author)

  5. Glioma-secreted soluble factors stimulate microglial activation: The role of interleukin-1β and tumor necrosis factor-α.

    Science.gov (United States)

    Hwang, Ji-Sun; Jung, Eun-Hye; Kwon, Mi-Youn; Han, Inn-Oc

    2016-09-15

    We aimed to elucidate the effect of soluble factors secreted by glioma on microglial activation. Conditioned medium (CM) from glioma cells, CRT-MG and C6, significantly induced nitric oxide (NO) production and stimulated the mRNA expression of inducible NO synthase (iNOS), interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-α) and cyclooxygenase 2 (COX-2) in BV2 cells. Glioma CM stimulated p38 mitogen-activated protein kinase (MAPK) phosphorylation, and a p38 MAPK inhibitor, SB203580, suppressed CM-induced NO production in BV2 cells. In addition, CM stimulated nuclear factor-kappaB (NF-κB) DNA binding and transcriptional activity, which was repressed by SB203580. Gliomas displayed higher mRNA expression and release of TNF-α and IL-1β than primary astrocyte cells. Neutralization of TNF-α and IL-1β in C6-CM using a neutralizing antibody inhibited NO/iNOS expression in BV-2 cells. These results indicate potential contribution of diffusible tumor-derived factors to regulate microglial activation and subsequent tumor microenvironment. Copyright © 2016. Published by Elsevier B.V.

  6. Prebiotic Factors Influencing the Activity of a Ligase Ribozyme

    Directory of Open Access Journals (Sweden)

    Fabrizio Anella

    2017-04-01

    Full Text Available An RNA-lipid origin of life scenario provides a plausible route for compartmentalized replication of an informational polymer and subsequent division of the container. However, a full narrative to form such RNA protocells implies that catalytic RNA molecules, called ribozymes, can operate in the presence of self-assembled vesicles composed of prebiotically relevant constituents, such as fatty acids. Hereby, we subjected a newly engineered truncated variant of the L1 ligase ribozyme, named tL1, to various environmental conditions that may have prevailed on the early Earth with the objective to find a set of control parameters enabling both tL1-catalyzed ligation and formation of stable myristoleic acid (MA vesicles. The separate and concurrent effects of temperature, concentrations of Mg2+, MA, polyethylene glycol and various solutes were investigated. The most favorable condition tested consists of 100 mM NaCl, 1 mM Mg2+, 5 mM MA, and 4 °C temperature, whereas the addition of Mg2+-chelating solutes, such as citrate, tRNAs, aspartic acid, and nucleoside triphosphates severely inhibits the reaction. These results further solidify the RNA-lipid world hypothesis and stress the importance of using a systems chemistry approach whereby a wide range of prebiotic factors interfacing with ribozymes are considered.

  7. Are school factors and urbanization supportive for being physically active and engaging in less screen-based activities?

    NARCIS (Netherlands)

    Kopcakova, Jaroslava; Dankulincova Veselska, Zuzana; Madarasova Geckova, Andrea; Klein, Daniel; van Dijk, Jitse P; Reijneveld, Sijmen A

    The aim was to assess the association between physical activity and screen-based activities in adolescents and selected school factors and urbanization and whether these associations were modified by degree of urbanization. We obtained data regarding the fifth-ninth grade students from 130 schools

  8. Pseudomonas aeruginosa toxin ExoU induces a PAF-dependent impairment of alveolar fibrin turnover secondary to enhanced activation of coagulation and increased expression of plasminogen activator inhibitor-1 in the course of mice pneumosepsis

    Directory of Open Access Journals (Sweden)

    Suassuna José HR

    2011-08-01

    Full Text Available Abstract Background ExoU, a Pseudomonas aeruginosa cytotoxin with phospholipase A2 activity, was shown to induce vascular hyperpermeability and thrombus formation in a murine model of pneumosepsis. In this study, we investigated the toxin ability to induce alterations in pulmonary fibrinolysis and the contribution of the platelet activating factor (PAF in the ExoU-induced overexpression of plasminogen activator inhibitor-1 (PAI-1. Methods Mice were intratracheally instilled with the ExoU producing PA103 P. aeruginosa or its mutant with deletion of the exoU gene. After 24 h, animal bronchoalveolar lavage fluids (BALF were analyzed and lung sections were submitted to fibrin and PAI-1 immunohistochemical localization. Supernatants from A549 airway epithelial cells and THP-1 macrophage cultures infected with both bacterial strains were also analyzed at 24 h post-infection. Results In PA103-infected mice, but not in control animals or in mice infected with the bacterial mutant, extensive fibrin deposition was detected in lung parenchyma and microvasculature whereas mice BALF exhibited elevated tissue factor-dependent procoagulant activity and PAI-1 concentration. ExoU-triggered PAI-1 overexpression was confirmed by immunohistochemistry. In in vitro assays, PA103-infected A549 cells exhibited overexpression of PAI-1 mRNA. Increased concentration of PAI-1 protein was detected in both A549 and THP-1 culture supernatants. Mice treatment with a PAF antagonist prior to PA103 infection reduced significantly PAI-1 concentrations in mice BALF. Similarly, A549 cell treatment with an antibody against PAF receptor significantly reduced PAI-1 mRNA expression and PAI-1 concentrations in cell supernatants, respectively. Conclusion ExoU was shown to induce disturbed fibrin turnover, secondary to enhanced procoagulant and antifibrinolytic activity during P. aeruginosa pneumosepsis, by a PAF-dependent mechanism. Besides its possible pathophysiological relevance, in

  9. Factors influencing suspended solids concentrations in activated sludge settling tanks.

    Science.gov (United States)

    Kim, Y; Pipes, W O

    1999-05-31

    A significant fraction of the total mass of sludge in an activated sludge process may be in the settling tanks if the sludge has a high sludge volume index (SVI) or when a hydraulic overload occurs during a rainstorm. Under those conditions, an accurate estimate of the amount of sludge in the settling tanks is needed in order to calculate the mean cell residence time or to determine the capacity of the settling tanks to store sludge. Determination of the amount of sludge in the settling tanks requires estimation of the average concentration of suspended solids in the layer of sludge (XSB) in the bottom of the settling tanks. A widely used reference recommends averaging the concentrations of suspended solids in the mixed liquor (X) and in the underflow (Xu) from the settling tanks (XSB=0. 5{X+Xu}). This method does not take into consideration other pertinent information available to an operator. This is a report of a field study which had the objective of developing a more accurate method for estimation of the XSB in the bottom of the settling tanks. By correlation analysis, it was found that only 44% of the variation in the measured XSB is related to sum of X and Xu. XSB is also influenced by the SVI, the zone settling velocity at X and the overflow and underflow rates of the settling tanks. The method of averaging X and Xu tends to overestimate the XSB. A new empirical estimation technique for XSB was developed. The estimation technique uses dimensionless ratios; i.e., the ratio of XSB to Xu, the ratio of the overflow rate to the sum of the underflow rate and the initial settling velocity of the mixed liquor and sludge compaction expressed as a ratio (dimensionless SVI). The empirical model is compared with the method of averaging X and Xu for the entire range of sludge depths in the settling tanks and for SVI values between 100 and 300 ml/g. Since the empirical model uses dimensionless ratios, the regression parameters are also dimensionless and the model can be

  10. 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 Goeijenbier

    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.

  11. Metabolic factors affecting enhanced phosphorus uptake by activated sludge.

    Science.gov (United States)

    Boughton, W H; Gottfried, R J; Sinclair, N A; Yall, I

    1971-10-01

    Activated sludges obtained from the Rilling Road plant located at San Antonio, Tex., and from the Hyperion treatment plant located at Los Angeles, Calif., have the ability to remove all of the orthophosphate normally present in Tucson sewage within 3 hr after being added to the waste water. Phosphorus removal was independent of externally supplied sources of energy and ions, since orthophosphate and (32)P radioactivity were readily removed from tap water, glass-distilled water, and deionized water. Phosphorus uptake by Rilling sludge in the laboratory appears to be wholly biological, as it has an optimum pH range (7.7 to 9.7) and an optimum temperature range (24 to 37 C). It was inhibited by HgCl(2), iodoacetic acid, p-chloromercuribenzoic acid, NaN(3), and 2, 4-dinitrophenol (compounds that affect bacterial membrane permeability, sulfhydryl enzymes, and adenosine triphosphate synthesis). Uptake was inhibited by 1% NaCl but was not affected by 10(-3)m ethylenediaminetetraacetic acid disodium salt (a chelating agent for many metallic ions).

  12. The glycoprotein Ib-IX-V complex contributes to tissue factor-independent thrombin generation by recombinant factor VIIa on the activated platelet surface

    NARCIS (Netherlands)

    Weeterings, Cees; de Groot, Philip G.; Adelmeijer, Jelle; Lisman, Ton

    2008-01-01

    Several lines of evidence suggest that recombinant factor VIIa (rFVIIa) is able to activate factor X on an activated platelet, in a tissue factor-independent manner. We hypothesized that, besides the anionic surface, a receptor on the activated platelet surface is involved in this process. Here, we

  13. Cisplatin Induces Cytotoxicity through the Mitogen-Activated Protein Kinase Pathways ana Activating Transcription Factor 3

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    Carly St. Germain

    2010-07-01

    Full Text Available The mechanisms underlying the proapoptotic effect of the chemotherapeutic agent, cisplatin, are largely undefined. Understanding the mechanisms regulating cisplatin cytotoxicity may uncover strategies to enhance the efficacy of this important therapeutic agent. This study evaluates the role of activating transcription factor 3 (ATF3 as a mediator of cisplatin-induced cytotoxicity. Cytotoxic doses of cisplatin and carboplatin treatments consistently induced ATF3 expression in five tumor-derived cell lines. Characterization of this induction revealed a p53, BRCA1, and integrated stress response-independent mechanism, all previously implicated in stress-mediated ATF3 induction. Analysis of mitogenactivated protein kinase (MAPK pathway involvement in ATF3 induction by cisplatin revealed a MAPK-dependent mechanism. Cisplatin treatment combined with specific inhibitors to each MAPK pathway (c-Jun N-terminal kinase, extracellularsignal-regulated kinase, and p38 resulted in decreasedATF3 induction at the protein level. MAPK pathway inhibition led to decreased ATF3 messenger RNA expression and reduced cytotoxic effects of cisplatin as measured by the 3-(4,5-dimethylthiazol-2-ylF2,5-diphenyltetrazolium bromide cell viability assay. In A549 lung carcinoma cells, targeting ATF3 with specific small hairpin RNA also attenuated the cytotoxic effects of cisplatin. Similarly, ATF3-/murine embryonic fibroblasts (MEFs were shown to be less sensitive to cisplatin-induced cytotoxicity compared with ATF3+/+ MEFs. This study identifies cisplatin as a MAPK pathway-dependent inducer of ATF3, whose expression influences cisplatin’s cytotoxic effects.

  14. Specific features of domestic banks activity in the factoring services market

    Directory of Open Access Journals (Sweden)

    Trygub Olena V.

    2014-01-01

    Full Text Available The article analyses specific features of formation and development of the domestic factoring market. In the result of the study the article establishes that development of factoring in Ukraine took place due to active participation of banking institutions in this process and nowadays they are leaders in the domestic factoring services market due to possessing significant competitive advantages if compared with non-banking companies that specialise in factoring. The article detects that nowadays the banks are not only offerers of factoring services and finance factoring operations of other market participants, but also take an active part in establishment of factoring branches and are consumers of factoring services. In order to accelerate development of international factoring in Ukraine, the article offers such forms of state support of banks, which render factoring services to domestic exporters. The article recommends to focus banks’ attention, under modern conditions that are characterised with volatility of financial markets, on factoring servicing of those clients, whom they have long business relations with, without jeopardising themselves through provision of factoring services to a big number of small debtors. The article provides schemes of banks’ co-operation in the sphere of “non-classic” factoring with accredited factoring companies.

  15. ANALYSIS OF THE EXTERNAL FACTORS OF INFLUENCE ON INNOVATION ACTIVITY OF AN INDUSTRIAL ENTERPRISE

    Directory of Open Access Journals (Sweden)

    I. A. Salikov

    2014-01-01

    Full Text Available Summary. For successful functioning and development of the enterprise is a need to strive as possible deeper and more dynamic influence on parameters and objects OK-environmental management, primarily due to increase their innovation activity. Innovative activity of enterprises influenced by many factors. They can be classified on the factors of direct influence (micro and factors of indirect impacts (macro. Factors of direct impact of the influence on the pace and scale of development of the enterprise, on its effectiveness, because the whole spectrum of these factors acts as a limiter. Macro factors create the General conditions of existence of the enterprise in the external environment. To analyses these factors approach was used to SNW-analysis. As a result of analysis, factors of micro and macro-were classified on: stimulating, it minesweepers and dissuasive. Also studied were the degree of influence of these factors on the innovative activity of the enterprise. Reviewed rating factors hindering the development of innovation activity of industrial enterprise in Russia. In the result of which identified factors that hinder the development of innovative activity, and justified in the direction of overcoming them. It should be noted that the distinction between enabling and constraining factors is rather thin and conditional. So, the factors initially restraining innovation, at a certain point can be transformed into a stimulus for its development. Accounting for these factors, creation of necessary conditions and introduction of innovations in various aspects of the functioning of industrial enterprises will allow them to provide competitor-term benefits and sustainable development in a rapidly changing environment and the external environment.

  16. A new automated method for continuous registration of factor VII activation in vitro. Activation is accelerated by the concentration of factor VII and the activity state of the protein

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, J; Gram, J

    1994-01-01

    When a plasma sample is exposed to tissue factor, single-chain factor VII (FVII) is gradually converted to the active two-chain form (FVIIa). In the present study, we have constructed a measurement system, which allows continuous registration of the activation of FVII to FVIIa in vitro....... In this system, FVII activation follows parabolic kinetic after an initial lag-phase. The slope of the linear phase is a measure of the protein concentration of factor VII (FVIItotal), while the length of the non-linear phase represents the velocity of FVII activation. The time required for complete activation...

  17. Influences of lifestyle factors on cardiac autonomic nervous system activity over time

    NARCIS (Netherlands)

    Hu, Mandy Xian; Lamers, Femke; de Geus, Eco J C; Penninx, Brenda W J H

    Physical activity, alcohol use and smoking might affect cardiovascular disease through modifying autonomic nervous system (ANS) activity. We investigated: 1) whether there are consistent relationships between lifestyle factors and cardiac ANS activity over time, and 2) whether 2-year changes in

  18. Immobilisation of homogeneous olefin polymerisation catalysts. Factors influencing activity and stability

    NARCIS (Netherlands)

    Severn, J.R.; Chadwick, J.C.

    2013-01-01

    The activity and stability of homogeneous olefin polymerisation catalysts, when immobilised on a support, are dependent on both chemical and physical effects. Chemical factors affecting catalyst activity include the ease of formation of the active species, which is strongly dependent on the

  19. Platelet-, monocyte-derived and tissue factor-carrying circulating microparticles are related to acute myocardial infarction severity.

    Directory of Open Access Journals (Sweden)

    Gemma Chiva-Blanch

    Full Text Available Circulating microparticles (cMPs are phospholipid-rich vesicles released from cells when activated or injured, and contribute to the formation of intracoronary thrombi. Tissue factor (TF, CD142 is the main trigger of fibrin formation and TF-carrying cMPs are considered one of the most procoagulant cMPs. Similar types of atherosclerotic lesions may lead to different types of AMI, although the mechanisms behind are unresolved. Therefore, we aimed to investigate the phenotype of cMPs found in plasma of ACS patients and its relation to AMI severity and thrombotic burden.In a cross-sectional study, two hundred patients aged 75±4 years were included in the study 2-8 weeks after suffering an AMI. Annexin V positive (AV+-cMPs derived from blood and vascular cells were measured by flow cytometry. Plasma procoagulant activity (TF-PCA was measured through a chromogenic assay.STEMI patients (n = 75 showed higher levels of platelet-derived cMPs [CD61+/AV+, CD31+/AV+, CD42b+/AV+ and CD31+/CD42b+/AV+, P = 0.048, 0.038, 0.009 and 0.006, respectively], compared to NSTEMI patients (n = 125. Patients who suffered a heart failure during AMI (n = 17 had increased levels of platelet (CD61+-and monocyte (CD14+-derived cMPs carrying TF (CD142+ (P<0.0001 and 0.004, respectively. Additionally, NYHA class III (n = 23 patients showed higher levels of CD142+/AV+, CD14+/AV+ and CD14+/CD142+/AV+ cMPs than those in class I/II (P = 0.001, 0.015 and 0.014, respectively. The levels of these cMPs positively correlated with TF-PCA (r≥0.166, P≤0.027, all.Platelets and monocytes remain activated in AMI patients treated as per guidelines and release cMPs that discriminate AMI severity. Therefore, TF-MPs, and platelet- and monocyte-MPs may reflect thrombotic burden in AMI patients.

  20. Factor Xa stimulates fibroblast procollagen production, proliferation, and calcium signaling via PAR1 activation

    International Nuclear Information System (INIS)

    Blanc-Brude, Olivier P.; Archer, Fabienne; Leoni, Patricia; Derian, Claudia; Bolsover, Steven; Laurent, Geoffrey J.; Chambers, Rachel C.

    2005-01-01

    Fibroblast proliferation and procollagen production are central features of tissue repair and fibrosis. In addition to its role in blood clotting, the coagulation cascade proteinase thrombin can contribute to tissue repair by stimulating fibroblasts via proteolytic activation of proteinase-activated receptor-1 (PAR 1 ). During hemostasis, the coagulation cascade proteinase factor X is converted into factor Xa. We have previously shown that factor Xa upregulates fibroblast proliferation via production of autocrine PDGF. In this study, we further examined the effects of factor Xa on fibroblast function and aimed to identify its signaling receptor. We showed that factor Xa stimulates procollagen promoter activity and protein production by human and mouse fibroblasts. This effect was independent of PDGF and thrombin production, but dependent on factor Xa proteolytic activity. We also showed that PAR 1 -deficient mouse fibroblasts did not upregulate procollagen production, mobilize cytosolic calcium, or proliferate in response to factor Xa. Desensitization techniques and PAR 1 -specific agonists and inhibitors were used to demonstrate that PAR 1 mediates factor Xa signaling in human fibroblasts. This is the first report that factor Xa stimulates extracellular matrix production. In contrast with endothelial cells and vascular smooth muscle cells, fibroblasts appear to be the only cell type in which the effects of factor Xa are mediated mainly via PAR 1 and not PAR 2 . These findings are critical for our understanding of tissue repair and fibrotic mechanisms, and for the design of novel approaches to inhibit the profibrotic effects of the coagulation cascade without compromising blood hemostasis

  1. Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-1

    Directory of Open Access Journals (Sweden)

    Shin-ichi Kawaguchi

    2018-04-01

    Full Text Available Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase domain-containing protein have been developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1 has also been shown to have the potential to activate HIF-α. However, few small-molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a series of furan- and thiophene-2-carbonyl amino acid derivatives having the potential to inhibit FIH-1. The inhibitory activities of these compounds were evaluated in SK-N-BE(2c cells by measuring HIF response element (HRE promoter activity. Several furan- and thiophene-2-carbonyl amino acid derivatives inhibited FIH-1 based on correlations among the docking score of the FIH-1 active site, the chemical structure of the compounds, and biological HIF-α/HRE transcriptional activity.

  2. Factor analysis shows association between family activity environment and children's health behaviour.

    Science.gov (United States)

    Hendrie, Gilly A; Coveney, John; Cox, David N

    2011-12-01

    To characterise the family activity environment in a questionnaire format, assess the questionnaire's reliability and describe its predictive ability by examining the relationships between the family activity environment and children's health behaviours - physical activity, screen time and fruit and vegetable intake. This paper describes the creation of a tool, based on previously validated scales, adapted from the food domain. Data are from 106 children and their parents (Adelaide, South Australia). Factor analysis was used to characterise factors within the family activity environment. Pearson-Product Moment correlations between the family environment and child outcomes, controlling for demographic variation, were examined. Three factors described the family activity environment - parental activity involvement, opportunity for role modelling and parental support for physical activity - and explained 37.6% of the variance. Controlling for demographic factors, the scale was significantly correlated with children's health behaviour - physical activity (r=0.27), screen time (r=-0.24) and fruit and vegetable intake (r=0.34). The family activity environment questionnaire shows high internal consistency and moderate predictive ability. This study has built on previous research by taking a more comprehensive approach to measuring the family activity environment. This research suggests the family activity environment should be considered in family-based health promotion interventions. © 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.

  3. Newly diagnosed congenital factor VII deficiency and utilization of recombinant activated factor VII (NovoSeven(®)).

    Science.gov (United States)

    Bartosh, Nicole S; Tomlin, Tara; Cable, Christian; Halka, Kathleen

    2013-01-01

    This case report presents a newly diagnosed congenital factor VII deficiency treated with recombinant activated factor VII (rFVIIa). Congenital factor VII deficiency is a rare autosomal-recessive bleeding disorder that occurs in fewer than 1/500,000 persons. Its presentation can vary from epistaxis to hemarthroses and severe central nervous system bleeding, and correlates poorly with factor VII levels. Our patient had not had a significant hemostatic challenge prior to his presentation and therefore never had any symptomatology suggestive of this disease. He was treated with rFVIIa, and was able to undergo repair of his fractures without bleeding. A 19-year-old African-American male presented to the emergency room after an altercation that resulted in significant trauma. He sustained bilateral mandibular angle fractures and orbital floor fractures, requiring urgent surgical correction. On initial evaluation, he was noted to have a prolonged prothrombin time of 40.1 seconds, with an International Normalized Ratio of 4.0, a normal activated partial thromboplastin time of 29.9 seconds, and a platelet count of 241. After receiving vitamin K and fresh frozen plasma, he was taken to the operating room for a temporary rigid maxillomandibular fixation. A 1:1 mixing study with normal plasma corrected the prothrombin time (decreasing from 40.7 to 14.7 seconds) and a factor VII assay revealed 5% of the normal factor VII level. The patient was diagnosed with congenital factor VII deficiency. Due to his coagulopathy and the extensive surgical correction needed, rFVIIa was administered and surgery was accomplished without hemorrhagic sequelae. This case report and review describes a rare congenital disease, the history of rFVIIa use, and its mechanism. rFVIIA use in our patient provided a treatment option that allowed the necessary surgical correction, but further prospective studies on dose optimization would ensure adequate dosing with minimal risk of severe side effects.

  4. Newly diagnosed congenital factor VII deficiency and utilization of recombinant activated factor VII (NovoSeven®)

    Science.gov (United States)

    Bartosh, Nicole S; Tomlin, Tara; Cable, Christian; Halka, Kathleen

    2013-01-01

    This case report presents a newly diagnosed congenital factor VII deficiency treated with recombinant activated factor VII (rFVIIa). Congenital factor VII deficiency is a rare autosomal-recessive bleeding disorder that occurs in fewer than 1/500,000 persons. Its presentation can vary from epistaxis to hemarthroses and severe central nervous system bleeding, and correlates poorly with factor VII levels. Our patient had not had a significant hemostatic challenge prior to his presentation and therefore never had any symptomatology suggestive of this disease. He was treated with rFVIIa, and was able to undergo repair of his fractures without bleeding. Case report A 19-year-old African-American male presented to the emergency room after an altercation that resulted in significant trauma. He sustained bilateral mandibular angle fractures and orbital floor fractures, requiring urgent surgical correction. On initial evaluation, he was noted to have a prolonged prothrombin time of 40.1 seconds, with an International Normalized Ratio of 4.0, a normal activated partial thromboplastin time of 29.9 seconds, and a platelet count of 241. After receiving vitamin K and fresh frozen plasma, he was taken to the operating room for a temporary rigid maxillomandibular fixation. A 1:1 mixing study with normal plasma corrected the prothrombin time (decreasing from 40.7 to 14.7 seconds) and a factor VII assay revealed 5% of the normal factor VII level. The patient was diagnosed with congenital factor VII deficiency. Due to his coagulopathy and the extensive surgical correction needed, rFVIIa was administered and surgery was accomplished without hemorrhagic sequelae. Conclusion This case report and review describes a rare congenital disease, the history of rFVIIa use, and its mechanism. rFVIIA use in our patient provided a treatment option that allowed the necessary surgical correction, but further prospective studies on dose optimization would ensure adequate dosing with minimal risk of

  5. Intrapersonal, behavioral, and environmental factors associated with meeting recommended physical activity among rural Latino youth.

    Science.gov (United States)

    Perry, Cynthia K; Saelens, Brian E; Thompson, Beti

    2011-11-01

    This study aimed to identify intrapersonal, behavioral, and environmental factors associated with engaging in recommended levels of physical activity among rural Latino middle school youth. Data were from an anonymous survey of 773 Latino youth (51% female) about level of and barriers and motivators to physical activity, risk behaviors, and park use. Logistic regression models identified factors correlated with meeting recommended levels of physical activity (5 days or more 3 60 min/day). Thirty-four percent of girls and 41% of boys reported meeting this physical activity recommendation. Participation in an organized after school activity (p < .001) and in physical education (PE) classes 5 days a week (p < .001) were strongly associated with meeting recommended physical activity level. Making PE available 5 days a week and creating opportunities for organized after school physical activity programs may increase the number of rural Latino middle school youth who meet recommended physical activity level.

  6. Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes

    Science.gov (United States)

    Das, Hiranmoy; Kumar, Ajay; Lin, Zhiyong; Patino, Willmar D.; Hwang, Paul M.; Feinberg, Mark W.; Majumder, Pradip K.; Jain, Mukesh K.

    2006-01-01

    The mechanisms regulating activation of monocytes remain incompletely understood. Herein we provide evidence that Kruppel-like factor 2 (KLF2) inhibits proinflammatory activation of monocytes. In vitro, KLF2 expression in monocytes is reduced by cytokine activation or differentiation. Consistent with this observation, KLF2 expression in circulating monocytes is reduced in patients with chronic inflammatory conditions such as coronary artery disease. Adenoviral overexpression of KLF2 inhibits the LPS-mediated induction of proinflammatory factors, cytokines, and chemokines and reduces phagocytosis. Conversely, short interfering RNA-mediated reduction in KLF2 increased inflammatory gene expression. Reconstitution of immunodeficient mice with KLF2-overexpressing monocytes significantly reduced carrageenan-induced acute paw edema formation. Mechanistically, KLF2 inhibits the transcriptional activity of both NF-κB and activator protein 1, in part by means of recruitment of transcriptional coactivator p300/CBP-associated factor. These observations identify KLF2 as a novel negative regulator of monocytic activation. PMID:16617118

  7. An integrative review: work environment factors associated with physical activity among white-collar workers.

    Science.gov (United States)

    Lin, Yun-Ping; McCullagh, Marjorie C; Kao, Tsui-Sui; Larson, Janet L

    2014-02-01

    The purpose of this review is to synthesize the research evidence for the role of the work environment-workplace physical activity policies and resources and job strain factors-in explaining physical activity in white-collar workers. White-collar workers are at risk for developing a sedentary lifestyle, which contributes to all-cause mortality. Understanding how work environment can influence worker physical activity is important for the development of effective interventions. We reviewed 15 research articles that describe the relationship between work environment factors and physical activity in predominantly white-collar workers. Relatively consistent evidence was found for the effects of supportive workplace policies and resources. Weak evidence was found for the effects of job strain. Both work environment factors have the potential to influence physical activity but require further exploration to fully understand their contribution to physical activity in white-collar workers. Limitations and implications are discussed.

  8. Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

    Science.gov (United States)

    Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

    2017-06-01

    During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation

  9. An increase in circulating B cell-activating factor in childhood-onset ocular myasthenia gravis.

    Science.gov (United States)

    Motobayashi, Mitsuo; Inaba, Yuji; Nishimura, Takafumi; Kobayashi, Norimoto; Nakazawa, Yozo; Koike, Kenichi

    2015-04-01

    Myasthenia gravis is a B cell-mediated autoimmune disorder. The pathophysiology of childhood-onset ocular myasthenia gravis remains unclear. We investigated serum B cell-activating factor levels and other immunological parameters in child patients with ocular myasthenia gravis. Blood samples were obtained from 9 children with ocular myasthenia gravis and 20 age-matched controls. We assayed serum concentrations of B cell-activating factor, anti-acetylcholine receptor antibody titers, 7 types of cytokines (interleukins-2, -4, -6, -10, and -17A; interferon-γ; tumor necrosis factor-α) as well as the percentages of peripheral blood CD4+, CD8+, and CD19+ cells. Serum B cell-activating factor levels were significantly higher before immunosuppressive therapy in patients with childhood-onset ocular myasthenia gravis than in controls and decreased after immunosuppressive therapy. A significant positive correlation was observed between serum B cell-activating factor levels and anti-acetylcholine receptor antibody titers in patients with myasthenia gravis. Serum B cell-activating factor concentrations did not correlate with the percentages of CD4+, CD8+, and CD19+ cells or the CD4+/CD8+ ratio. No significant differences were observed in the levels of the 7 different types of cytokines examined, including interleukin-17A, between preimmunosuppressive therapy myasthenia gravis patients and controls. Circulating B cell-activating factor may play a key role in the pathophysiology of childhood-onset ocular myasthenia gravis. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Regulation of the Incorporation of Tissue Factor into Microparticles by Serine Phosphorylation of the Cytoplasmic Domain of Tissue Factor*

    Science.gov (United States)

    Collier, Mary E. W.; Ettelaie, Camille

    2011-01-01

    The mechanisms that regulate the incorporation and release of tissue factors (TFs) into cell-derived microparticles are as yet unidentified. In this study, we have explored the regulation of TF release into microparticles by the phosphorylation of serine residues within the cytoplasmic domain of TF. Wild-type and mutant forms of TF, containing alanine and aspartate substitutions at Ser253 and Ser258, were overexpressed in coronary artery and dermal microvascular endothelial cells and microparticle release stimulated with PAR2 agonist peptide (PAR2-AP). The release of TF antigen and activity was then monitored. In addition, the phosphorylation state of the two serine residues within the released microparticles and the cells was monitored for 150 min. The release of wild-type TF as procoagulant microparticles peaked at 90 min and declined thereafter in both cell types. The TF within these microparticles was phosphorylated at Ser253 but not at Ser258. Aspartate substitution of Ser253 resulted in rapid release of TF antigen but not activity, whereas TF release was reduced and delayed by alanine substitution of Ser253 or aspartate substitution of Ser258. Alanine substitution of Ser258 prolonged the release of TF following PAR2-AP activation. The release of TF was concurrent with phosphorylation of Ser253 and was followed by dephosphorylation at 120 min and phosphorylation of Ser258. We propose a sequential mechanism in which the phosphorylation of Ser253 through PAR2 activation results in the incorporation of TF into microparticles, simultaneously inducing Ser258 phosphorylation. Phosphorylation of Ser258 in turn promotes the dephosphorylation of Ser253 and suppresses the release of TF. PMID:21310953

  11. Sex differences in social cognitive factors and physical activity in Korean college students

    OpenAIRE

    Choi, Jin Yi; Chang, Ae Kyung; Choi, Eun-Ju

    2015-01-01

    [Purpose] This study examined sex differences in physical activity and social cognitive theory factors in Korean college students. [Subjects and Methods] A cross-sectional survey of 688 college students (285 men and 403 women) in Korea was conducted using a self-reported questionnaire. [Results] There was a significant difference in the level of physical activity between male and female students. The significant predictors of physical activity for male students were physical activity goals, p...

  12. Substance P enhances tissue factor release from granulocyte-macrophage colony-stimulating factor-dependent macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway.

    Science.gov (United States)

    Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

    2016-03-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) induces procoagulant activity of macrophages. Tissue factor (TF) is a membrane-bound glycoprotein and substance P (SP) is a pro-inflammatory neuropeptide involved in the formation of membrane blebs. This study investigated the role of SP in TF release by GM-CSF-dependent macrophages. SP significantly decreased TF levels in whole-cell lysates of GM-CSF-dependent macrophages. TF was detected in the culture supernatant by enzyme-linked immunosorbent assay after stimulation of macrophages by SP. Aprepitant (an SP/neurokinin 1 receptor antagonist) reduced TF release from macrophages stimulated with SP. Pretreatment of macrophages with a radical scavenger(pyrrolidinedithiocarbamate) also limited the decrease of TF in whole-cell lysates after stimulation with SP. A protein kinase C inhibitor (rottlerin) partially blocked this macrophage response to SP, while it was significantly inhibited by a ROCK inhibitor (Y-27632) or a dynamin inhibitor (dinasore). An Akt inhibitor (perifosine) also partially blocked this response. Furthermore, siRNA targeting p22phox, β-arrestin 2, or Rho A, blunted the release of TF from macrophages stimulated with SP. In other experiments, visceral adipocytes derived from cryopreserved preadipocytes were found to produce SP. In conclusion, SP enhances the release of TF from macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Quantitative PET Imaging of Tissue Factor Expression Using 18F-labled Active Site Inhibited Factor VII

    DEFF Research Database (Denmark)

    Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E

    2016-01-01

    Tissue factor (TF) is up regulated in many solid tumors and its expression is linked to tumor angiogenesis, invasion, metastasis and prognosis. A non-invasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII (FVII) is the natural ligand to TF. Here we...... report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of FVII. METHODS: Active site inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4......-[(18)F]-fluorobenzoate ([(18)F]SFB) and purified. The corresponding product, [(18)F]FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small animal PET/CT imaging 1, 2 and 4 hours after injection. Ex vivo biodistribution was performed...

  14. Giving children a voice: Exploring qualitative perspectives on factors influencing recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Schipperijn, Jasper; Tjørnhøj-Thomsen, Tine

    2018-01-01

    Facilitators and barriers to recess physical activity are not well understood. To date, research on recess physical activity has predominantly focused on quantitative measures typically focusing on a narrow set of predefined factors, often constructed by adults. To really understand the factors...... 11–12-year-old children. The socio-ecological model was used as the overall theoretical framework. Twelve factors were identified as influencing the children’s recess physical activity: bodily self-esteem and ability; gender; gendered school culture; peer influence; conflicts and exclusion; space...... and place experiences; lack of play facilities; outdoor play policy; use of electronic devices; recess duration; organised activities; and weather. These factors were located within different layers of the socio-ecological model, but were interdependent. The findings speak for implementing a combination...

  15. risk factors of active tuberculosis in people living with hiv/aids

    African Journals Online (AJOL)

    Abrham

    2011-07-02

    Jul 2, 2011 ... The objective of this study was to assess distal ... KEYWORDS: Active TB, HIV, risk factors, case control study, Southwest Ethiopia ... and Khat (stimulant plant from Chata Edulis), .... to live in a house made of a cement floor.

  16. The Contribution of Home, Neighbourhood and School Environmental Factors in Explaining Physical Activity among Adolescents

    International Nuclear Information System (INIS)

    Haerens, L.; Deforche, B.; Cardon, G.; Bourdeaudhuij, I.D.; Craeynest, M.; Maes, L.

    2010-01-01

    The present study aimed at investigating the influence of home, neighbourhood and school environmental factors on adolescents' engagement in self-reported extracurricular physical activity and leisure time sports and on MVPA objectively measured by accelerometers. Environmental factors were assessed using questionnaires. Gender specific hierarchical regression analyses were conducted, with demographic variables entered in the first block, and environmental, psychosocial factors and interactions terms entered in the second block. Participation in extracurricular activities at school was positively related to the number of organized activities and the provision of supervision. Perceived accessibility of neighborhood facilities was not related to engagement in leisure time sports, whereas the availability of sedentary and physical activity equipment was. Findings were generally supportive of ecological theories stating that behaviors are influenced by personal and environmental factors that are constantly interacting.

  17. Hypoxia-Inducible Factor 1 Is an Inductor of Transcription Factor Activating Protein 2 Epsilon Expression during Chondrogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Stephan Niebler

    2015-01-01

    Full Text Available The transcription factor AP-2ε (activating enhancer-binding protein epsilon is expressed in cartilage of humans and mice. However, knowledge about regulatory mechanisms influencing AP-2ε expression is limited. Using quantitative real time PCR, we detected a significant increase in AP-2ε mRNA expression comparing initial and late stages of chondrogenic differentiation processes in vitro and in vivo. Interestingly, in these samples the expression pattern of the prominent hypoxia marker gene angiopoietin-like 4 (Angptl4 strongly correlated with that of AP-2ε suggesting that hypoxia might represent an external regulator of AP-2ε expression in mammals. In order to show this, experiments directly targeting the activity of hypoxia-inducible factor-1 (HIF1, the complex mediating responses to oxygen deprivation, were performed. While the HIF1-activating compounds 2,2′-dipyridyl and desferrioxamine resulted in significantly enhanced mRNA concentration of AP-2ε, siRNA against HIF1α led to a significantly reduced expression rate of AP-2ε. Additionally, we detected a significant upregulation of the AP-2ε mRNA level after oxygen deprivation. In sum, these different experimental approaches revealed a novel role for the HIF1 complex in the regulation of the AP-2ε gene in cartilaginous cells and underlined the important role of hypoxia as an important external regulatory stimulus during chondrogenic differentiation modulating the expression of downstream transcription factors.

  18. In vivo bioimaging with tissue-specific transcription factor activated luciferase reporters.

    OpenAIRE

    Buckley, SM; Delhove, JM; Perocheau, DP; Karda, R; Rahim, AA; Howe, SJ; Ward, NJ; Birrell, MA; Belvisi, MG; Arbuthnot, P; Johnson, MR; Waddington, SN; McKay, TR

    2015-01-01

    The application of transcription factor activated luciferase reporter cassettes in vitro is widespread but potential for in vivo application has not yet been realized. Bioluminescence imaging enables non-invasive tracking of gene expression in transfected tissues of living rodents. However the mature immune response limits luciferase expression when delivered in adulthood. We present a novel approach of tissue-targeted delivery of transcription factor activated luciferase reporter lentiviruse...

  19. Nuclear safety regulation on nuclear safety equipment activities in relation to human and organizational factors

    International Nuclear Information System (INIS)

    Li Tianshu

    2013-01-01

    Based on years of knowledge in nuclear safety supervision and experience of investigating and dealing with violation events in repair welding of DFHM, this paper analyzes major faults in manufacturing and maintaining activities of nuclear safety equipment in relation to human and organizational factors. It could be deducted that human and organizational factors has definitely become key features in the development of nuclear energy and technology. Some feasible measures to reinforce supervision on nuclear safety equipment activities have also been proposed. (author)

  20. Increased active von Willebrand factor during disease development in the aging diabetic patient population.

    Science.gov (United States)

    Chen, Shuang Feng; Xia, Zuo Li; Han, Ji Ju; Wang, Yi Ting; Wang, Ji Yue; Pan, Shao Dong; Wu, Ya Ping; Zhang, Bin; Li, Guang Yao; Du, Jing Wei; Gao, Hen Qiang; de Groot, Philip G; de Laat, Bas; Hollestelle, Martine J

    2013-02-01

    Type 2 diabetes is known to cause endothelial activation resulting in the secretion of von Willebrand factor (VWF). We have shown that levels of VWF in a glycoprotein Ib-binding conformation are increased in specific clinical settings. The aim of the current study is to investigate whether active VWF levels increase during aging and the development of diabetes within the population of patients suffering from type 2 diabetes. Patients and controls were divided into two groups based on age: older and younger than 60 years of age. VWF antigen, VWF propeptide, VWF activation factor and total active VWF were measured. Patients older than 60 years of age had increased levels of total active VWF, VWF activation factor and VWF propeptide compared to younger patients and controls. All measured VWF parameters were associated with age in diabetic patients. Total active VWF and VWF propeptide correlated with the period of being diagnosed with diabetes. Regression analyses showed that especially the VWF activation factor was strongly associated with diabetes in patients older than 60 years of age. In conclusion, we found that the conformation of VWF could be involved in the disease process of diabetes and that the VWF in a glycoprotein Ib-binding conformation could play a role as risk marker during the development of diabetes in combination with an increase in age. Our study shows that the active quality of VWF was more important than the quantity.

  1. Factor VII-activating protease in patients with acute deep venous thrombosis

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Vitzthum, Frank; Funding, Eva

    2008-01-01

    Factor VII-activating protease (FSAP) is involved in haemostasis and inflammation. FSAP cleaves single chain urokinase-type plasminogen activator (scu-PA). The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene leads to the expression of a FSAP variant with reduced ability to activate scu......-PA, without affecting the ability to activate coagulation Factor VII (FVII). Previous studies have investigated the association of the 1601GA genotype with incidence and progression of carotid stenosis and deep venous thrombosis (DVT). The present study is the first to evaluate the potential association...... between the FSAP phenotype and DVT. We studied the association between the 1601G/A polymorphism, FSAP activity, FSAP antigen, Factor VIIa (FVIIa), prothrombin fragment 1+2 (F1+2), and C-reactive protein (CRP) in plasmas of 170 patients suspected for DVT. FSAP genotypes were equally distributed in patients...

  2. Social and Health Factors Associated with Physical Activity among Kuwaiti College Students.

    Science.gov (United States)

    Al-Isa, Abdulwahab Naser; Campbell, Jennifer; Desapriya, Ediriweera; Wijesinghe, Namal

    2011-01-01

    Our aim was to explore the social and health factors that are associated with the level of physical activity among Kuwaiti college students. A random sample of 787 students (48% males and 52% females) was chosen and weight and height were measured to obtain body mass index (BMI, kg/m(2)). Associated social and health factors were obtained using a questionnaire. Those reporting being physically inactive numbered 354 and the remaining 433 were active. Obesity among males was 13% and was 10.5% among females. The social and health factors that were found to be significantly associated with physical activity among the students were gender (P degree (P benefits of being physically active should be instituted to increase the practice of sports and other physical activities in order to control and decrease obesity-related morbidity and mortality.

  3. Motivating and Demotivating Factors for Students with Low Emotional Intelligence to Participate in Speaking Activities

    Science.gov (United States)

    Méndez López, Mariza G.; Bautista Tun, Moisés

    2017-01-01

    The study aims to understand what factors may motivate and demotivate students with low emotional intelligence to participate in speaking activities during English class. Participants wrote an emotions journal to identify factors affecting student participation and were then interviewed at the end of the study period in order to elaborate on their…

  4. Sun protection factor persistence on human skin during a day without physical activity or ultraviolet exposure

    DEFF Research Database (Denmark)

    Beyer, Ditte Maria; Faurschou, Annesofie; Philipsen, Peter Alshede

    2010-01-01

    Recently, we showed that the sun protection factor (SPF) decreases by a constant factor to reach 55% during a day with activities. Organic sunscreens but not inorganic ones are absorbed through the skin. We wished to determine the SPF decrease caused by absorption by investigating the difference...

  5. SOME IMPORTANT FACTORS AFFECTING EVOLUTION OF ACTIVITY BASED COSTING (ABC) SYSTEM IN EGYPTIAN MANUFACTURING FIRMS

    OpenAIRE

    Karim MAMDOUH ABBAS

    2014-01-01

    The present investigation aims to determine the factors affecting evolution of Activity Based Costing (ABC) system in Egyptian case. The study used the survey method to describe and analyze these factors in some Egyptian firms. The population of the study is Egyptian manufacturing firms. Accordingly, the number of received questionnaires was 392 (23 Egyptian manufacturing firms) in the first half of 2013. Finally, the study stated some influencing factors for evolution this system (ABC) in Eg...

  6. SOME IMPORTANT FACTORS AFFECTING EVOLUTION OF ACTIVITY BASED COSTING (ABC SYSTEM IN EGYPTIAN MANUFACTURING FIRMS

    Directory of Open Access Journals (Sweden)

    Karim MAMDOUH ABBAS

    2014-04-01

    Full Text Available The present investigation aims to determine the factors affecting evolution of Activity Based Costing (ABC system in Egyptian case. The study used the survey method to describe and analyze these factors in some Egyptian firms. The population of the study is Egyptian manufacturing firms. Accordingly, the number of received questionnaires was 392 (23 Egyptian manufacturing firms in the first half of 2013. Finally, the study stated some influencing factors for evolution this system (ABC in Egyptian manufacturing firms.

  7. Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling.

    Science.gov (United States)

    Mutoh, Shingo; Sobhany, Mack; Moore, Rick; Perera, Lalith; Pedersen, Lee; Sueyoshi, Tatsuya; Negishi, Masahiko

    2013-05-07

    Phenobarbital is a central nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism, as well as cell growth (and death), in the liver. We found that phenobarbital activated CAR by inhibiting epidermal growth factor receptor (EGFR) signaling. Phenobarbital bound to EGFR and potently inhibited the binding of EGF, which prevented the activation of EGFR. This abrogation of EGFR signaling induced the dephosphorylation of receptor for activated C kinase 1 (RACK1) at Tyr(52), which then promoted the dephosphorylation of CAR at Thr(38) by the catalytic core subunit of protein phosphatase 2A. The findings demonstrated that the phenobarbital-induced mechanism of CAR dephosphorylation and activation is mediated through its direct interaction with and inhibition of EGFR.

  8. Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis

    Directory of Open Access Journals (Sweden)

    Herrera Maria

    2006-04-01

    Full Text Available Abstract Background Platelet activation is crucial in normal hemostasis. Using a clotting system free of external tissue factor, we investigated whether activated Factor VII in combination with platelet agonists increased thrombin generation (TG in vitro. Methods and results TG was quantified by time parameters: lag time (LT and time to peak (TTP, and by amount of TG: peak of TG (PTG and area under thrombin formation curve after 35 minutes (AUC→35min in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA, ADP, and collagen (Col. In addition, the effects of recombinant activated FVII (rFVIIa alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p 35min were significantly increased (p 35min (but not PTG when compared to platelet rich plasma activated with agonists in the absence of rFVIIa. Conclusion Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis.

  9. Pharmacodynamics of recombinant activated factor VII and plasma-derived factor VII in a cohort of severe FVII deficient patients.

    Science.gov (United States)

    van Geffen, Mark; Mathijssen, Natascha C J; Holme, Pål A; Laros-van Gorkom, Britta A P; van Kraaij, Marian G J; Masereeuw, Roselinde; Peyvandi, Flora; van Heerde, Waander L

    2013-07-01

    Recombinant activated factor VII (rFVIIa) and plasma-derived factor VII (pdFVII) are used to prevent bleedings in severe FVII deficient patients, despite their short half-lifes. It is suggested that FVII levels of 15-20 IU/dL are sufficient to maintain hemostasis. We analyzed the pharmacodynamic effects of FVII substitution therapy in the Nijmegen Hemostasis Assay (NHA) that simultaneously measures thrombin and plasmin generation. Ten severe FVII deficient patients were treated with 20 μg/kg rFVIIa or 25 IU/kg pdFVII in a cross-over design. Thrombin generation lag-time (TG-LT) was identified as an effect-response parameter. Pharmacodynamic analysis using a maximum effect model showed 50% reduction of the TG-LT effect at ~2 IU/dL FVII activity for both rFVIIa and pdFVII. The FVII activity to obtain TG-LT comparable to the upper limit of normal range in healthy controls (4 min) was given by the effective concentration (ECnormal), showing sufficient hemostasis at 3-4 IU/dL FVII activity. No association was seen between FVII activity and other thrombin or plasmin generation parameters as measured by NHA. In conclusion, 3-4 IU/dL FVII activity seems sufficient to maintain hemostasis in patients with severe FVII deficiency during prophylaxis. These data may suggest a potential value for measurement of TG-LT in the monitoring of FVII(a) therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Comparison of Some Cardiovascular Risk Factors between Active and Sedentary Elderly Men

    Directory of Open Access Journals (Sweden)

    H. Najafgholizadeh

    2017-04-01

    Full Text Available Background: One of the major problems threatening the world’s people are cardiovascular diseases, accounting for 30% of the deaths. The factors exposing people to this danger are called risk factors. Objective: This study aimed to compare the cardiovascular risk factors and C-reactive protein between active and sedentary elderly men. Methods: The study was a descriptive comparison of two groups that were conducted in Rasht city in 2015. The subjects of this study consist of 30 active elderly men and 30 sedentary elderly men who were selected non-randomly and purposefully. Inclusion criteria of research for active subjects were have regular physical activity at least six months and don’t use cigarette and pills that affect profile lipids and inclusion criteria for sedentary subjects were don’t have regular physical activity and also don’t use cigarette and pills that affect profile lipids. The measured cardiovascular risk factors of subjects include fasting blood sugar (FBS, triglyceride (TG, total cholesterol (TC, highdensity lipoprotein (HDL, low-density lipoprotein (LDL, very low-density lipoprotein (VLDL, glycated haemoglobinA1c (HbA1c, and C-reactive protein (CRP. The statistical methods used for data analysis are Kolmogorov-Smirnov test, t-student, and U Mann-Whitney with significance level less than 0.05. Findings: The t-student exam shows that cardiovascular risk factors, including FBS, TG, TC, HDL, VLDL, HbA1c, and CRP, in active elderly men are lower than sedentary elderly men. This difference is also statistically significant (P≤0/01. Conclusion: The study showed that cardiovascular risk factors in active elderly men are less than sedentary ones. However, 80% of active elderly men had still at least one or several cardiovascular risk factors.

  11. Physical Activity, a Critical Exposure Factor of Environmental Pollution in Children and Adolescents Health Risk Assessment.

    Science.gov (United States)

    Dong, Jingmei; Zhang, Su; Xia, Li; Yu, Yi; Hu, Shuangshuang; Sun, Jingyu; Zhou, Ping; Chen, Peijie

    2018-01-23

    It is an extremely urgent problem that physical fitness promotion must face not only the increasing air pollution but also the decline of physical activity level of children and adolescents worldwide at present, which is the major reason that forms an inactive lifestyle and does harm to adolescents' health. Thus, it is necessary to focus on the exposure factor in environmental health risk assessment (EHRA) which conducts supervision of environmental pollution and survey of adolescents' activity patterns according to the harmful characteristics of air pollutant and relationship between dose and response. Some countries, such as USA, Canada and Australia, regard both respiratory rate and physical activity pattern as main exposure factors for adolescents in both air pollution health risk assessment and exercise risk assessment to forecast a safe exposing condition of pollutant for adolescents while they are doing exercise outdoors. In addition, it suggests that the testing indexes and testing methods of these two exposure factors, such as investigating the time of daily physical activity, strength, and characteristic of frequency, help to set up the quantitative relationship between environmental pollution index and the time, strength, frequency of daily activities, and formulate children's and adolescents' activity instructions under different levels of environmental pollutions. As smog becomes increasingly serious at present, it is meaningful to take physical activity as a critical composition of exposure factor and establish physical activity guideline, so as to reduce the risk of air pollution, and promote physical health of children and adolescents effectively.

  12. Physical and Psychosocial Factors Associated With Physical Activity in Patients With Chronic Obstructive Pulmonary Disease

    NARCIS (Netherlands)

    Hartman, Jorine E.; Boezen, H. Marike; de Greef, Mathieu H.; ten Hacken, Nick H.

    2013-01-01

    Objectives: To assess physical activity and sitting time in patients with chronic obstructive pulmonary disease (COPD) and to investigate which physical and psychosocial factors are associated with physical activity and sitting time. Design: Cross-sectional study. Setting: Patients were recruited at

  13. A ¤high-fat meal does not activate blood coagulation factor vii in minipigs

    DEFF Research Database (Denmark)

    Olsen, A. K.; Larsen, L. F.; Bladbjerg, E.-M.

    2001-01-01

    It is a matter of debate whether postprandial activation of blood coagulation factor VII (FVII) is associated with an increased risk of thrombosis. To clarify this question, an animal model in which consequences of dietary FVII activation can be studied in a more detailed way would be an important...

  14. Associations of Weight Status, Social Factors, and Active Travel among College Students

    Science.gov (United States)

    Bopp, Melissa; Behrens, Timothy K.; Velecina, Rachel

    2014-01-01

    Background: Active travel (AT) is associated with various health benefits and may help prevent the decline in physical activity during college years. Purpose: The purpose of this study was to examine the relationship of several factors with AT to campus by weight status. Methods: Students at a large northeastern US campus completed an online…

  15. Interpersonal and Intrapersonal Factors Associated with Autonomous Motivation in Adolescents' After-School Activities

    Science.gov (United States)

    Beiswenger, Krista L.; Grolnick, Wendy S.

    2010-01-01

    This study explored interpersonal and intrapersonal factors associated with the level of autonomous motivation adolescents experience for their after-school activities. A total of 142 seventh-grade adolescents completed measures of peer relatedness, autonomy within friendships, mother and father autonomy support, perceived activity competence,…

  16. Physical Activity, a Critical Exposure Factor of Environmental Pollution in Children and Adolescents Health Risk Assessment

    Science.gov (United States)

    Zhang, Su; Xia, Li; Yu, Yi; Hu, Shuangshuang; Sun, Jingyu; Zhou, Ping; Chen, Peijie

    2018-01-01

    It is an extremely urgent problem that physical fitness promotion must face not only the increasing air pollution but also the decline of physical activity level of children and adolescents worldwide at present, which is the major reason that forms an inactive lifestyle and does harm to adolescents’ health. Thus, it is necessary to focus on the exposure factor in environmental health risk assessment (EHRA) which conducts supervision of environmental pollution and survey of adolescents’ activity patterns according to the harmful characteristics of air pollutant and relationship between dose and response. Some countries, such as USA, Canada and Australia, regard both respiratory rate and physical activity pattern as main exposure factors for adolescents in both air pollution health risk assessment and exercise risk assessment to forecast a safe exposing condition of pollutant for adolescents while they are doing exercise outdoors. In addition, it suggests that the testing indexes and testing methods of these two exposure factors, such as investigating the time of daily physical activity, strength, and characteristic of frequency, help to set up the quantitative relationship between environmental pollution index and the time, strength, frequency of daily activities, and formulate children’s and adolescents’ activity instructions under different levels of environmental pollutions. As smog becomes increasingly serious at present, it is meaningful to take physical activity as a critical composition of exposure factor and establish physical activity guideline, so as to reduce the risk of air pollution, and promote physical health of children and adolescents effectively. PMID:29360730

  17. Factor VII-activating protease : Unraveling the release and regulation of dead cell nuclear damps

    NARCIS (Netherlands)

    Marsman, G.

    2017-01-01

    Upon inflammation, uncleared dying cells are an important source of pro-inflammatory damage-associated molecular patterns (DAMPs). Major DAMPs are histones and double-stranded DNA, which together form chromatin. Factor VII-activating protease (FSAP) is activated upon contact with dead cells, and its

  18. Physical Activity, a Critical Exposure Factor of Environmental Pollution in Children and Adolescents Health Risk Assessment

    Directory of Open Access Journals (Sweden)

    Jingmei Dong

    2018-01-01

    Full Text Available It is an extremely urgent problem that physical fitness promotion must face not only the increasing air pollution but also the decline of physical activity level of children and adolescents worldwide at present, which is the major reason that forms an inactive lifestyle and does harm to adolescents’ health. Thus, it is necessary to focus on the exposure factor in environmental health risk assessment (EHRA which conducts supervision of environmental pollution and survey of adolescents’ activity patterns according to the harmful characteristics of air pollutant and relationship between dose and response. Some countries, such as USA, Canada and Australia, regard both respiratory rate and physical activity pattern as main exposure factors for adolescents in both air pollution health risk assessment and exercise risk assessment to forecast a safe exposing condition of pollutant for adolescents while they are doing exercise outdoors. In addition, it suggests that the testing indexes and testing methods of these two exposure factors, such as investigating the time of daily physical activity, strength, and characteristic of frequency, help to set up the quantitative relationship between environmental pollution index and the time, strength, frequency of daily activities, and formulate children’s and adolescents’ activity instructions under different levels of environmental pollutions. As smog becomes increasingly serious at present, it is meaningful to take physical activity as a critical composition of exposure factor and establish physical activity guideline, so as to reduce the risk of air pollution, and promote physical health of children and adolescents effectively.

  19. Factors of physical activity among Chinese children and adolescents : A systematic review

    NARCIS (Netherlands)

    Lu, Congchao; Stolk, Ronald P.; Sauer, Pieter J. J.; Sijtsma, Anna; Wiersma, Rikstje; Huang, Guowei; Corpeleijn, Eva

    2017-01-01

    Background: Lack of physical activity is a growing problem in China, due to the fast economic development and changing living environment over the past two decades. The aim of this review is to summarize the factors related to physical activity in Chinese children and adolescents during this

  20. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men

    Directory of Open Access Journals (Sweden)

    A. Zembron-Lacny

    2016-01-01

    Full Text Available Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF and its relationship to oxidative damage and conventional cardiovascular disease (CVD biomarkers, such as atherogenic index, C-reactive protein (hsCRP and oxidized LDL (oxLDL, in active and inactive men. Seventeen elderly males (61-80 years and 17 young males (20-24 years participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001. In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL, hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men.

  1. Activities concerning a re-evaluation of gamma-ray buildup factors in Japan

    International Nuclear Information System (INIS)

    Hirayama, Hideo

    2000-01-01

    Research related to gamma-ray buildup factors in Japan are continuing to improve in accuracy and usefulness after the publication of new standard buildup factors as NUREG/CR-5740. Buildup factors for homogeneous materials were studied by three different calculation methods. Several improvements were made to calculate buildup factors up to 40 mfp for various materials for a wide energy range at each code. Systematic data production of buildup factors for multilayer materials were performed by using the EGS4 Monte Carlo code, and were used to improve the fitting formula. These research activities related to gamma-ray buildup factors performed in Japan are presented together with discussions concerning re-evaluation of buildup factors. (author)

  2. Motivational factors and stages of change for physical activity among college students in Amman, Jordan.

    Science.gov (United States)

    Madanat, Hala; Merrill, Ray M

    2006-01-01

    The purpose of this study was to investigate physical activity levels across the five stages of change for physical activity and to identify motivational factors for physical activity according to these stages of change among college students in Amman, Jordan. Analyses were based on a cross-sectional survey of 431 students, with a mean age of 21.1 (SD=0.16) and 67.5% female. Based on the recommendation that physical activity requires at least 30 minutes of physical activity 3 or more days per week, men were more likely than women to classify themselves in later stages: 7.3% vs. 9.5% in the precontemplation stage, 17.4% vs. 14.7% in the contemplation stage, 50.0% vs. 63.5% in the preparation stage, 9.4% vs. 5.6% in the action stage, and 15.9% vs. 6.7% in the maintenance stage [X2(4) = 14.04, p = 0.0072]. Seven potential motivational items for physical activity were assessed using factor analysis: experience better self-worth, prevent chronic disease, relieve stress, stay in shape, longevity, recreation/fun, and social benefits. Two factor groupings were identified from these items. The first factor included the first five items, labeled as "Physical and Mental". The second factor included the last two items, labeled as "Social and Recreational." "Physical and Mental" items compared with "Social and Recreational" items were most likely to motivate physical activity across the stages of change for physical activity. The strongest motivator of physical activity was to stay in shape. The weakest motivator of physical activity was for social reasons. The influence of the intermediate motivational factors was slightly affected by the students' stage of change for physical activity. Motivators for physical activity did not differ according to sex. These results provide important information about the motivational factors for physical activity for college-aged students in Jordan that can be useful in developing effective physical activity intervention programs.

  3. Gender Similarities and Differences in Factors Associated with Adolescent Moderate-Vigorous Physical Activity

    Science.gov (United States)

    Wenthe, Phyllis J.; Janz, Kathleen F; Levy, Stephen M.

    2010-01-01

    This study investigated the relationship between predisposing, reinforcing, and enabling factors conceptualized within the Youth Physical Activity Promotion Model (YPAP) and moderate to vigorous physical activity (MVPA) of adolescent males and females. Specifically, self-efficacy to overcome barriers, enjoyment of physical activity; family support, peer support, perceived school climate, neighborhood safety and access to physical activity were examined. The Physical Activity Questionnaire for Adolescents (PAQ-A) and the Actigraph 7164 were used to obtain three different measures of MVPA in 205 adolescents (102 males, 103 females). Family support emerged as the most significant and consistent factor associated with the MVPA of both adolescent males and females. This relationship was noted even when different methods of measuring MVPA were employed. These findings should increase the confidence of public health officials that family support has the potential to positively alter the physical activity behavior of adolescents. PMID:19827453

  4. Modulation of protein C activation by histones, platelet factor 4, and heparinoids: new insights into activated protein C formation.

    Science.gov (United States)

    Kowalska, M Anna; Zhao, Guohua; Zhai, Li; David, George; Marcus, Stephen; Krishnaswamy, Sriram; Poncz, Mortimer

    2014-01-01

    Histones are detrimental in late sepsis. Both activated protein C (aPC) and heparin can reverse their effect. Here, we investigated whether histones can modulate aPC generation in a manner similar to another positively charged molecule, platelet factor 4, and how heparinoids (unfractionated heparin or oxygen-desulfated unfractionated heparin with marked decrease anticoagulant activity) may modulate this effect. We measured in vitro and in vivo effects of histones, platelet factor 4, and heparinoids on aPC formation, activated partial thromboplastin time, and murine survival. In vitro, histones and platelet factor 4 both affect thrombin/thrombomodulin aPC generation following a bell-shaped curve, with a peak of >5-fold enhancement. Heparinoids shift these curves rightward. Murine aPC generation studies after infusions of histones, platelet factor 4, and heparinoids supported the in vitro data. Importantly, although unfractionated heparin and 2-O, 3-O desulfated heparin both reversed the lethality of high-dose histone infusions, only mice treated with 2-O, 3-O desulfated heparin demonstrated corrected activated partial thromboplastin times and had significant levels of aPC. Our data provide a new contextual model of how histones affect aPC generation, and how heparinoid therapy may be beneficial in sepsis. These studies provide new insights into the complex interactions controlling aPC formation and suggest a novel therapeutic interventional strategy.

  5. Platelet-derived growth factor inhibits platelet activation in heparinized whole blood.

    Science.gov (United States)

    Selheim, F; Holmsen, H; Vassbotn, F S

    1999-08-15

    We previously have demonstrated that human platelets have functionally active platelet-derived growth factor alpha-receptors. Studies with gel-filtered platelets showed that an autocrine inhibition pathway is transduced through this tyrosine kinase receptor during platelet activation. The physiological significance of this inhibitory effect of platelet-derived growth factor on gel-filtered platelets activation is, however, not known. In the present study, we investigated whether platelet-derived growth factor inhibits platelet activation under more physiological conditions in heparinized whole blood, which represents a more physiological condition than gel-filtered platelets. Using flow cytometric assays, we demonstrate here that platelet-derived growth factor inhibits thrombin-, thrombin receptor agonist peptide SFLLRN-, and collagen-induced platelet aggregation and shedding of platelet-derived microparticles from the platelet plasma membrane during platelet aggregation in stirred heparinized whole blood. The inhibitory effect of platelet-derived growth factor was dose dependent. However, under nonaggregating conditions (no stirring), we could not demonstrate any significant effect of platelet-derived growth factor on thrombin- and thrombin receptor agonist peptide-induced platelet surface expression of P-selectin. Our results demonstrate that platelet-derived growth factor appears to be a true antithrombotic agent only under aggregating conditions in heparinized whole blood.

  6. Krüppel-like factor 4, a novel transcription factor regulates microglial activation and subsequent neuroinflammation

    Directory of Open Access Journals (Sweden)

    Das Sulagna

    2010-10-01

    Full Text Available Abstract Background Activation of microglia, the resident macrophages of the central nervous system (CNS, is the hallmark of neuroinflammation in neurodegenerative diseases and other pathological conditions associated with CNS infection. The activation of microglia is often associated with bystander neuronal death. Nuclear factor-κB (NF-κB is one of the important transcription factors known to be associated with microglial activation which upregulates the expression of inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (Cox-2 and other pro-inflammatory cytokines. Recent studies have focused on the role of Krüppel-like factor 4 (Klf4, one of the zinc-finger transcription factors, in mediating inflammation. However, these studies were limited to peripheral system and its role in CNS is not understood. Our studies focused on the possible role of Klf4 in mediating CNS inflammation. Methods For in vitro studies, mouse microglial BV-2 cell lines were treated with 500 ng/ml Salmonella enterica lipopolysacchride (LPS. Brain tissues were isolated from BALB/c mice administered with 5 mg/kg body weight of LPS. Expressions of Klf4, Cox-2, iNOS and pNF-κB were evaluated using western blotting, quantitative real time PCR, and reverse transcriptase polymerase chain reactions (RT-PCRs. Klf4 knockdown was carried out using SiRNA specific for Klf4 mRNA and luciferase assays and electromobility shift assay (EMSA were performed to study the interaction of Klf4 to iNOS promoter elements in vitro. Co-immunoprecipitation of Klf4 and pNF-κB was done in order to study a possible interaction between the two transcription factors. Results LPS stimulation increased Klf4 expression in microglial cells in a time- and dose-dependent manner. Knockdown of Klf4 resulted in decreased levels of the pro-inflammatory cytokines TNF-α, MCP-1 and IL-6, along with a significant decrease in iNOS and Cox-2 expression. NO production also decreased as a result of Klf4 knockdown

  7. Hybrid Active-Passive Microwave Photonic Filter with High Quality Factor

    International Nuclear Information System (INIS)

    En-Ming, Xu; Xin-Liang, Zhang; Li-Na, Zhou; Yu, Zhang; De-Xiu, Huang

    2009-01-01

    A hybrid high quality factor (Q-factor) microwave photonic filter with a cascaded active filter and a passive filter is presented and experimentally demonstrated. The active infinite impulse response filter is realized by a recirculating delay line loop with a semiconductor optical amplifier, and a much narrower 3 dB bandwidth of response peaks can be achieved. A passive finite impulse response filter is realized by an unbalance Mach–Zehnder interferometer, and it is cascaded to select the desired filter frequencies and to suppress the intermediate peaks. Compared with the purely active filter scheme, the free spectrum range and the Q-factor of the hybrid structure can be doubled. Stable operation and a high Q-factor of 362 are experimentally demonstrated

  8. Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha.

    Science.gov (United States)

    Montrucchio, G.; Lupia, E.; de Martino, A.; Battaglia, E.; Arese, M.; Tizzani, A.; Bussolino, F.; Camussi, G.

    1997-01-01

    We evaluated the role of an endogenous production of nitric oxide (NO) in the in vitro migration of endothelial cells and in the in vivo angiogenic response elicited by platelet-activating factor (PAF), tumor necrosis factor-alpha (TNF), and basic fibroblast growth factor (bFGF). The NO synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME), but not its enantiomer D-NAME, prevented chemotaxis of endothelial cells induced in vitro by PAF and by TNF. The motogenic activity of TNF was also inhibited by WEB 2170, a specific PAF-receptor antagonist. In contrast, chemotaxis induced by bFGF was not prevented by L-NAME or by WEB 2170. Angiogenesis was studied in vivo in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model, the angiogenesis induced by PAF and TNF was inhibited by WEB 2170 and L-NAME but not by D-NAME. In contrast, angiogenesis induced by bFGF was not affected by L-NAME or by WEB 2170. TNF, but not bFGF, induced PAF synthesis within Matrigel. These results suggest that NO mediates the angiogenesis induced by PAF as well as that induced by TNF, which is dependent on the production of PAF. In contrast, the angiogenic effect of bFGF appears to be both PAF and NO independent. Images Figure 3 Figure 4 PMID:9250168

  9. A specific colorimetric assay for measuring transglutaminase 1 and factor XIII activities.

    Science.gov (United States)

    Hitomi, Kiyotaka; Kitamura, Miyako; Alea, Mileidys Perez; Ceylan, Ismail; Thomas, Vincent; El Alaoui, Saïd

    2009-11-15

    Transglutaminase (TGase) is an enzyme that catalyzes both isopeptide cross-linking and incorporation of primary amines into proteins. Eight TGases have been identified in humans, and each of these TGases has a unique tissue distribution and physiological significance. Although several assays for TGase enzymatic activity have been reported, it has been difficult to establish an assay for discriminating each of these different TGase activities. Using a random peptide library, we recently identified the preferred substrate sequences for three major TGases: TGase 1, TGase 2, and factor XIII. In this study, we use these substrates in specific tests for measuring the activities of TGase 1 and factor XIII.

  10. Factor XII-independent activation of the bradykinin-forming cascade

    DEFF Research Database (Denmark)

    Joseph, Kusumam; Tholanikunnel, Baby G; Bygum, Anette

    2013-01-01

    and assayed for kallikrein formation. C1-INH was removed from factor XII-deficient plasma by means of immunoadsorption. RESULTS: We demonstrate that prekallikrein-HK will activate to kallikrein in phosphate-containing buffers and that the rate is further accelerated on addition of heat shock protein 90...... the prekallikrein-HK complex to prevent HK cleavage either by prekallikrein or by prekallikrein-HK autoactivation to generate kallikrein. In patients with hereditary angioedema, kallikrein and bradykinin formation can occur without invoking factor XII activation, although the kallikrein formed can rapidly activate...

  11. Activation of Rho GTPases by Cytotoxic Necrotizing Factor 1 Induces Macropinocytosis and Scavenging Activity in Epithelial Cells

    Science.gov (United States)

    Fiorentini, Carla; Falzano, Loredana; Fabbri, Alessia; Stringaro, Annarita; Logozzi, Mariaantonia; Travaglione, Sara; Contamin, Stéphanette; Arancia, Giuseppe; Malorni, Walter; Fais, Stefano

    2001-01-01

    Macropinocytosis, a ruffling-driven process that allows the capture of large material, is an essential aspect of normal cell function. It can be either constitutive, as in professional phagocytes where it ends with the digestion of captured material, or induced, as in epithelial cells stimulated by growth factors. In this case, the internalized material recycles back to the cell surface. We herein show that activation of Rho GTPases by a bacterial protein toxin, the Escherichia coli cytotoxic necrotizing factor 1 (CNF1), allowed epithelial cells to engulf and digest apoptotic cells in a manner similar to that of professional phagocytes. In particular, we have demonstrated that 1) the activation of all Rho, Rac, and Cdc42 by CNF1 was essential for the capture and internalization of apoptotic cells; and 2) such activation allowed the discharge of macropinosomal content into Rab7 and lysosomal associated membrane protein-1 acidic lysosomal vesicles where the ingested particles underwent degradation. Taken together, these findings indicate that CNF1-induced “switching on” of Rho GTPases may induce in epithelial cells a scavenging activity, comparable to that exerted by professional phagocytes. The activation of such activity in epithelial cells may be relevant, in mucosal tissues, in supporting or integrating the scavenging activity of resident macrophages. PMID:11452003

  12. Perceived influence of intrinsic/extrinsic factors on participation in life activities after spinal cord injury.

    Science.gov (United States)

    Cobb, John E; Leblond, Jean; Dumont, Frédéric S; Noreau, Luc

    2018-04-03

    Various types of limitations on community participation are experienced by people with spinal cord injury (SCI). To determine: 1) the perceived influence of six intrinsic/extrinsic factors (i.e. physical impairment, emotional condition, thinking skills, environment, lack of assistance, discrimination) on participation in 26 life activities, 2) if this influence varied based on extent of participation, and 3) if personal or environmental characteristics influenced perceptions. Secondary analysis of a cohort (SCI Community Survey, n = 1508) using the SCI Person-Perceived Participation in Daily Activities Questionnaire. Frequency tables, Fisher's exact tests and correspondence analyses. Respectively, 79.6% and 38.5% of respondents perceived that their physical impairment and the natural and/or built environment were the main factors that limited participation across all activities. Considering participation between three groups (no participation; less than wanted; as much as wanted), significant differences (p intrinsic/extrinsic factors on participation was not significantly influenced by other personal or environmental characteristics. A majority of people with SCI perceived that their participation is limited by one or more of intrinsic/extrinsic factors. Perceptions regarding which factors influence participation differ between activities and these perceptions appear related to the extent of participation suggesting that those who actively participate could be the most sensitive to limitations in certain activities. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation.

    LENUS (Irish Health Repository)

    Ni Ainle, Fionnuala

    2009-08-20

    Protamine sulfate is a positively charged polypeptide widely used to reverse heparin-induced anticoagulation. Paradoxically, prospective randomized trials have shown that protamine administration for heparin neutralization is associated with increased bleeding, particularly after cardiothoracic surgery with cardiopulmonary bypass. The molecular mechanism(s) through which protamine mediates this anticoagulant effect has not been defined. In vivo administration of pharmacologic doses of protamine to BALB\\/c mice significantly reduced plasma thrombin generation and prolonged tail-bleeding time (from 120 to 199 seconds). Similarly, in pooled normal human plasma, protamine caused significant dose-dependent prolongations of both prothrombin time and activated partial thromboplastin time. Protamine also markedly attenuated tissue factor-initiated thrombin generation in human plasma, causing a significant decrease in endogenous thrombin potential (41% +\\/- 7%). As expected, low-dose protamine effectively reversed the anticoagulant activity of unfractionated heparin in plasma. However, elevated protamine concentrations were associated with progressive dose-dependent reduction in thrombin generation. To assess the mechanism by which protamine mediates down-regulation of thrombin generation, the effect of protamine on factor V activation was assessed. Protamine was found to significantly reduce the rate of factor V activation by both thrombin and factor Xa. Protamine mediates its anticoagulant activity in plasma by down-regulation of thrombin generation via a novel mechanism, specifically inhibition of factor V activation.

  14. Studies on levels and interactions of contact activation factors in plasma

    International Nuclear Information System (INIS)

    Hoem, N.O.

    1992-01-01

    Summary of findings and conclusions of relevance: A part of the thesis concerns the effects of intravenous contrast media on the blood pressure and on factors of the contact activation system in the rat. The intravenous injection of dextran induced a profound and lasting fall in blood pressure, preceded by significant lowering in prekallikrein and activation factor 12. The non-ionic radiographic contrast media iohexol caused no significant alterations, neither in blood pressure, nor in levels of contact factors, whereas the ionic radiographic contrast media iodipamide had effects. It induced a rapid, but short-lived, fall in blood pressure and a small, but statistically significant reduction in the measurable amount of activation factor 12a. An observation of significance was that pretreatment of the rats with iodipamide almost blocked the dextran-induced blood pressure fall, and abolished the reduction in prekallikrein and activation factor 12a. It is concluded that the ionic radiographic contrast media used was capable of blocking dextran shock in the rat by preventing an activation of contact activation system. 130 refs., 5 figs

  15. A comparison between recombinant activated factor VII (Aryoseven) and Novoseven in patients with congenital factor VII deficiency.

    Science.gov (United States)

    Faranoush, M; Abolghasemi, Hassan; Toogeh, Gh; Karimi, M; Eshghi, P; Managhchi, M; Hoorfar, H; Dehdezi, B Keikhaei; Mehrvar, A; Khoeiny, B; Kamyar, K; Heshmat, R; Baghaeipour, M R; Mirbehbahani, N B; Fayazfar, R; Ahmadinejad, M; Naderi, M

    2015-11-01

    In order to establish the efficacy and biosimilar nature of AryoSeven to NovoSeven in the treatment of congenital factor VII (FVII) deficiency, patients received either agent at 30 μg/kg, intravenously per week for 4 weeks, in a randomized fashion. The primary aim was to compare FVII:coagulation activity (FVII:C), 20 minutes after recombinant activated FVII (rFVIIa) injection, in the 2 groups. A secondary measure was self-reported bleeding. The median interquartile baseline range of the plasma level of activated FVII (FVIIa) activity in the 2 groups was 1.6 (1.1-14.0) IU/dL and 5.0 (1.1-25.5) IU/dL. All patients achieved levels of FVIIa (FVII:C) >30 IU/dL, 20 minutes after the injection of rFVIIa. Bleeding was similar between the 2 groups, with a comparable decrease in severity and frequency compared to the last month prior to treatment. AryoSeven is similar to NovoSeven in increasing postinjection FVIIa activity as well as in clinical safety and efficacy. © The Author(s) 2014.

  16. THE EXTERNAL FACTORS OF STUDENTS’ INVOLVEMENT IN SPEAKING ACTIVITY AT SMP PROGRESIF BUMI SHALAWAT

    Directory of Open Access Journals (Sweden)

    M.A. Nurul Haikal

    2016-07-01

    Full Text Available This research is conducted to know what factors that influence the students’ involvement in speaking activity in order to practice their speaking skill and what strategies that the teacher used to encourage those external factors. This research uses descriptive qualitative method. There are two instruments used for this research, namely, class observation and interview. Based on the results of class observation and interview, the researcher concludes that teacher factor gives the greatest impact on students’ involvement and the appropriate strategies can support those external factors.

  17. Female reproductive factors are associated with objectively measured physical activity in middle-aged women

    Science.gov (United States)

    Kulmala, Janne; Aukee, Pauliina; Hakonen, Harto; Kujala, Urho M.; Lowe, Dawn A.; Kovanen, Vuokko; Tammelin, Tuija; Sipilä, Sarianna

    2017-01-01

    Physical activity improves health and may delay the onset of several chronic diseases. For women in particular, the rate of these diseases accelerates at middle age; therefore it is important to identify the determinants of health-enhancing physical activity during midlife in this population. In this study, we focused on determinants that are unique to the female sex, such as childbearing and menopause. The main objective was to characterize the level of physical activity and differences between active and inactive middle-aged Finnish women. In addition, we examined the association of physical activity with female reproductive factors at midlife. The study population consisted of 647 women aged 48 to 55 years who participated in our Estrogenic Regulation of Muscle Apoptosis (ERMA) study during the period from 2015 to 2016. Physical activity was measured objectively using hip-worn accelerometers for seven consecutive days. The outcome measures included the amounts of light intensity physical activity and moderate to vigorous intensity physical activity accumulated in bouts of at least 10 minutes (MVPA10). MVPA10 was used to determine whether women were placed in the active (≥150 min/week) or inactive (physical activity measures as dependent variables and cumulative reproductive history index, menopausal symptoms, and pelvic floor dysfunction as independent variables. We found that a large portion (61%) of Finnish middle-aged women did not meet the physical activity recommendations of 150 minutes of MVPA10 per week. In the studied cohort, 78% of women experienced menopausal symptoms, and 54% exhibited pelvic floor dysfunction. Perceived menopausal symptoms were associated with greater light physical activity. Perceived pelvic floor dysfunction was associated with lower MVPA10. According to the fully adjusted multiple linear regression models, reproductive factors explained 6.0% of the variation of MVPA10 and 7.5% of the variation of light physical activity. The

  18. Vitamin D inhibits the growth of and virulence factor gene expression by Porphyromonas gingivalis and blocks activation of the nuclear factor kappa B transcription factor in monocytes.

    Science.gov (United States)

    Grenier, D; Morin, M-P; Fournier-Larente, J; Chen, H

    2016-06-01

    Increasing evidence suggests that 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), a fat-soluble secosteroid hormone, has a positive impact on periodontal health through diverse mechanisms. The present study was aimed at investigating the effect of 1,25(OH)2 D3 on the growth of and virulence factor gene expression by the periodontopathogenic bacterium Porphyromonas gingivalis. The effect of 1,25(OH)2 D3 on P. gingivalis-mediated activation of nuclear factor kappa B (NF-κB) transcription factor in monocytes was also assessed. A broth microdilution assay was used to determine the antibacterial activity of 1,25(OH)2 D3 . The modulation of virulence factor gene expression in P. gingivalis was assessed by quantitative reverse transcription-polymerase chain reaction. NF-κB activation was assessed using a human monocytic cell line stably transfected with a luciferase reporter containing NF-κB binding sites. Minimal inhibitory concentrations of 1,25(OH)2 D3 against P. gingivalis ranged from 3.125 to 6.25 μg/mL. Moreover, a partial synergistic effect was observed when 1,25(OH)2 D3 was used in association with metronidazole. 1,25(OH)2 D3 attenuated the virulence of P. gingivalis by reducing the expression of genes coding for important virulence factors, including adhesins (fimA, hagA and hagB) and proteinases (rgpA, rgpB and kgp). 1,25(OH)2 D3 dose-dependently prevented P. gingivalis-induced NF-κB activation in a monocyte model. Our study suggested that 1,25(OH)2 D3 selectively inhibits the growth of and virulence factor gene expression by P. gingivalis, in addition to attenuating NF-κB activation by this periodontopathogen. This dual action on P. gingivalis and the inflammatory response of host cells may be of particular interest with a view to developing a novel and inexpensive preventive/therapeutic strategy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. DMPD: Nuclear factor-kappaB: activation and regulation during toll-like receptorsignaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17349209 Nuclear factor-kappaB: activation and regulation during toll-like receptorsignaling. Carmody...uclear factor-kappaB: activation and regulation during toll-like receptorsignaling. Authors Carmody

  20. Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Jinah Han

    2015-02-01

    Full Text Available Neural stem cells (NSCs continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs, VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

  1. The Nuclear Factor of Activated T Cells (Nfat) Transcription Factor Nfatp (Nfatc2) Is a Repressor of Chondrogenesis

    Science.gov (United States)

    Ranger, Ann M.; Gerstenfeld, Louis C.; Wang, Jinxi; Kon, Tamiyo; Bae, Hyunsu; Gravallese, Ellen M.; Glimcher, Melvin J.; Glimcher, Laurie H.

    2000-01-01

    Nuclear factor of activated T cells (NFAT) transcription factors regulate gene expression in lymphocytes and control cardiac valve formation. Here, we report that NFATp regulates chondrogenesis in the adult animal. In mice lacking NFATp, resident cells in the extraarticular connective tissues spontaneously differentiate to cartilage. These cartilage cells progressively differentiate and the tissue undergoes endochondral ossification, recapitulating the development of endochondral bone. Proliferation of already existing articular cartilage cells also occurs in some older animals. At both sites, neoplastic changes in the cartilage cells occur. Consistent with these data, NFATp expression is regulated in mesenchymal stem cells induced to differentiate along a chondrogenic pathway. Lack of NFATp in articular cartilage cells results in increased expression of cartilage markers, whereas overexpression of NFATp in cartilage cell lines extinguishes the cartilage phenotype. Thus, NFATp is a repressor of cartilage cell growth and differentiation and also has the properties of a tumor suppressor. PMID:10620601

  2. Effect of some factors used to the chicken meat preservation and processing on the protease activity

    International Nuclear Information System (INIS)

    Przysiezna, E.; Skrabka-Blotnicka, T.

    1996-01-01

    The obtained results indicated that the cathepsin activity was higher by about 60% in the extract from thigh than from breast muscles. Freezing and defrosting (not stored) of chicken meat did not influence the breast muscle cathepsin activity while they caused a decrease of activity of about 20% in the case of thigh muscles. The increase in cathepsin activity was noticed in both kinds of muscles during storage at -20 °C up to 4 months (45.6% and 19.4% for thigh and breast muscles respectively). The activity of cathepsin in extract from 5 months stored meat reached 80% in case of breast muscles and 83% in case of thigh muscles in relation to control sample respectively. The cathepsin activity significantly increased during heating of breast muscles up to 60 °C, but in case of thigh muscles it was slightly higher than at 50°C. The heating of cured chicken breast muscles up to 60°C caused a non significant growth in cathepsin activity opposite to raw muscles. The cathepsin activity from all cured samples heated up to 70°C were several times lower in relation to control samples. The cathepsin activity of both thigh and breast muscles were resistant to gamma radiation. The investigated factors caused changes in the activity of cathepsin but none of them caused its total inactivation. The changes of cathepsin activity depended on the kind of muscles and the kind and the value of acting factors

  3. Nimesulide inhibits platelet-activating factor synthesis in activated human neutrophils

    NARCIS (Netherlands)

    Verhoeven, A. J.; Tool, A. T.; Kuijpers, T. W.; Roos, D.

    1993-01-01

    In an inflammatory locus, products of activated neutrophils may be toxic both to the micro-organisms to be eliminated and to the surrounding tissue. In several models of inflammation, nimesulide possesses marked anti-inflammatory properties. The present study was undertaken to further investigate

  4. Factors Related to Meeting Physical Activity Guidelines in Active College Students: A Social Cognitive Perspective

    Science.gov (United States)

    Farren, G. L.; Zhang, T.; Martin, S. B.; Thomas, K. T.

    2017-01-01

    Objective: To examine the relations of sex, exercise self-efficacy, outcome expectations, and social support with meeting physical activity guidelines (PAGs). Participants: Three hundred ninety-six college students participated in this study in the summer 2013. Methods: Students completed online questionnaires that assessed physical activity…

  5. Continuous infusion of recombinant activated factor VII for bleeding control after lobectomy in a patient with inherited factor VII deficiency.

    Science.gov (United States)

    Miyata, Naoko; Isaka, Mitsuhiro; Kojima, Hideaki; Maniwa, Tomohiro; Takahashi, Shoji; Takamiya, Osamu; Ohde, Yasuhisa

    2016-03-01

    Inherited factor VII (FVII) deficiency is a rare recessive inherited coagulation disorder with limited available information, especially in patients undergoing major thoracic surgery. In addition, an optimal management strategy for the disease has not been defined. We herein report a case involving a 61-year-old man with asymptomatic FVII deficiency who underwent a right middle and lower lobectomy to treat lung cancer. To the best of our knowledge, the present report is the first to describe the use of recombinant activated FVII continuous infusion for bleeding control after a major thoracic surgery in a patient with inherited FVII deficiency.

  6. Athlete and Coach Relationship as a Factor of the Success in Sports Activities

    Directory of Open Access Journals (Sweden)

    Svetlova A.A.,

    2014-11-01

    Full Text Available We present the results of a theoretical analysis of the psychological bases of success of athletes. We provide an overview of studies of the factors influencing the success of the activities in the sport. Sports activities are considered as a joint activity of athlete and coach, the success of which is affected by the personal qualities and characteristics of the relationship of its members. We summarize the main approaches to the study of personality and social psychological aspects of successful athletes and coaches. As the main factors in the success of sports activities, we considered individual psychological characteristics of athletes (motives, attitudes, modes of behavior and response, and socio-psychological characteristics of the interaction of coach and athlete (leadership style, the nature of interpersonal relationships and role expectations. We emphasize the importance of mutual role expectations of athlete and coach to achieve high results of sports activity.

  7. Barriers and motivational factors towards physical activity in COPD - an interview based pilot study

    DEFF Research Database (Denmark)

    Østergaard, Elisabeth Bomholt; Sritharan, Sophia Sajitha; Thomsen, Pernille Maja

    2018-01-01

    Title Barriers and motivational factors towards physical activity in COPD - an interview based pilot study Authors Elisabeth Bomholt Østergaard, Sophia Sajitha Sritharan, Pernille Maja Thomsen, Anne Dal Kristiansen, Anders Løkke Background: Surprisingly few people in Denmark with Chronic...... Obstructive Pulmonary Disease (COPD) engage in physical activity even though it is evident that pulmonary rehabilitation has positive effects on activity level, dyspnea, anxiety, fatigue and quality of life. Aims: To explore why people with COPD do not engage in physical activity and their motivational...... factors for being physically active. Methods: Fieldwork among five people with COPD in Jutland, Denmark 2013-2016 using qualitative semi-structured interviews. Supplementary short semistructured interviews with three general practitioners, and participation in a closed Facebook-group for people with COPD...

  8. Workplace victimization risk and protective factors for suicidal behavior among active duty military personnel.

    Science.gov (United States)

    Hourani, Laurel L; Williams, Jason; Lattimore, Pamela K; Morgan, Jessica K; Hopkinson, Susan G; Jenkins, Linda; Cartwright, Joel

    2018-04-22

    Workplace victimization is a potential risk factor for suicidal behaviors (SB) among military personnel that has been largely overlooked. This paper examines both the impact of workplace victimization on reported SB and several potential protective factors associated with such suicidal behaviors in a large sample of active duty soldiers. A case-control study was conducted with 71 soldiers who reported SB in the past 12 months, each matched on sociodemographic characteristics to two others without reported suicidal behaviors. A multiple regression model was estimated to assess the effects of risk and protective factors while controlling for other variables. SB was associated with several aspects of victimization, mental health and substance abuse conditions, pain, impulsivity, stressors, negative life events, work-family conflict, active coping behaviors and positive military-related factors. Controlling for other variables, those with SB were more likely to have sought mental health or substance abuse services, to be depressed, anxious, impulsive, and less resilient than non-SB personnel. Study limitations included the use of retrospective self-report data, absence of some known SB predictors, and a population restricted to active duty Army personnel. SB among active duty personnel is associated with victimization since joining the military and is protected by resiliency. These findings suggest that in addition to the usual mental health factors, these additional predictors should be accounted for in SB intervention and prevention planning for active duty personnel. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. [Physical activity and cardiovascular risk factors among Chilean young men and women].

    Science.gov (United States)

    Arteaga, Antonio; Bustos, Patricia; Soto, Rodrigo; Velasco, Nicolás; Amigo, Hugo

    2010-10-01

    Physical activity (PA) has a protective role in cardiovascular diseases. To quantify PA in young adults and to correlate it with cardiovascular risk factors. A cross-sectional study was performed employing the international physical activity questionnaire (IPAQ), to measure the PA of 983 randomly selected young adults from Valparaiso region born between 1974 and 1978. Its results were associated with levels of obesity, insulin resistance and cardiovascular risk factors defined by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP- ATP III) RESULTS: Mean physical activity among men and women was 3731 ± 3923 and 1360 ± 2303 METs-minutes/week, respectively (p women and 21.5% of men had an insufficient level of physical activity (p men and 23.4% of women had an intense level of physical activity (p physical activity and insulin resistance. A high physical activity was protective, specially among men, against a low HDL cholesterol level and high triglyceride levels with Odds Ratios of 0.59 (confidence interval (CI): 0,35-0.98) and 0.49 (CI: 0,27-0,87) respectively, after adjusting for body mass index and age. In this sample, men had higher levels of physical activity, that was protective against insulin resistance and the presence of cardiovascular risk factors.

  10. Scaling factors for the activity determination of radioactive waste from nuclear power reactors

    International Nuclear Information System (INIS)

    Medici, Marcela A.; Piumetti, Elsa H.

    2007-01-01

    Specific information of the total activity and activity concentration of the radionuclides contained is required for conditioning, transporting and final disposal of radioactive waste. Due to the complexity associated to alpha and beta measurements for these emitters it is worldwide used, particularly in the case of heterogeneous radioactive waste, the Scaling Factor Method. As in other cases, inputs of the results of the analysis of waste samples taking from waste streams are necessary. The Scaling Factor Method is based on the determination of averaged correlations between the activity concentrations of Difficult to Measure (DTM) nuclides (i.e. alpha and beta emitters) and the activity concentration of easy to measure nuclides (i.e. strong gamma emitters) called Key Nuclides (KN). In the application of this method two phases may be identified: in the first one the degree of correlation between averaged activities of DTM and a given KN is verified, and specific Scaling Factors are derived for every DTM radionuclide. In the second stage the total activity and the activity concentration of the selected KN is determined in each waste item and, by applying the SFs obtained previously, the activities of DTM nuclides are calculated. It is concluded that this method is appropriate and cost-effective and it is stressed that it is only applicable while the Nuclear Power Reactor is in operation. (author)

  11. Muscle atrophy reversed by growth factor activation of satellite cells in a mouse muscle atrophy model.

    Directory of Open Access Journals (Sweden)

    Simon Hauerslev

    Full Text Available Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we demonstrated that myostatin regulates satellite cell activation and myogenesis in vivo following treatment, consistent with previous findings in vitro. Our results suggest, not only a novel in vivo pharmacological treatment directed specifically at activating the satellite cells, but also a myostatin dependent mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.

  12. Diagnostics of the Factors Influencing the Export Activity of an Enterprise

    Directory of Open Access Journals (Sweden)

    Skrynkovskyy Ruslan M.

    2017-09-01

    Full Text Available The modern practice of doing business proves that a successful entrance of any enterprise to external (international markets depends on the level of its readiness for carrying out foreign economic activity. Under such circumstances, the process of targeted analysis and assessment of factors influencing the export activity of the enterprise is relevant, expedient and important. The aim of the article is the formation and development of theoretical and methodological bases for diagnosing factors influencing the export activity of an enterprise on the basis of theory and practice in the field of management and administration. It is found that the diagnostics should be understood as the process of identification, analysis and evaluation of influence (functional, dysfunctional of the factors (circumstances, conditions, etc. on the export activity of an enterprise in order to identify and solve problems (current, possible ones in the sphere of supply and implementation of specific actions (steps related to its entrance to external (international markets. It is determined that the key business indicators of the system for diagnosing the factors influencing the export activity of an enterprise are indicators reflecting the influence of the main factors on its export activity: level of fulfillment of obligations in terms of cost; level of conclusion of “expensive contracts”; share of renewed business contracts in the total number of contracts; level of satisfaction of claims; level of delivery variability. The prospect for further research in this scientific direction is developing a system of partial diagnostic goals of the integrated system of goals for conducting economic diagnostics of enterprises taking into account the diagnostics of factors influencing the export activity of an enterprise as a partial diagnostic goal.

  13. Adherence to physical activity recommendations and its associated factors: an interregional population-based study

    Directory of Open Access Journals (Sweden)

    Ala'a Alkerwi

    2015-03-01

    Full Text Available Background. Though the influence of physical activity in preventing cardiovascular diseases is well documented, only a few comparative studies have determined the degree of adherence to physical activity recommendations among populations and identified the demographic, socioeconomic, behavioural and health-related factors associated with good compliance. Design and methods. Cross-sectional interregional NESCaV survey of 3133 subjects compared three populations, Luxembourg, Lorraine (France and Wallonia (Belgium, by using the International Physical Activity Questionnaire. Age and gender prevalence rates of physical activity were standardized to the European population. Results. The likelihood to meet the recommendations was higher in Luxembourg, after adjustment for age, gender, education, employment, weight status, morbidity score, health perception and level of importance attributed to the practice of physical activity (P<0.0001. The odds for meeting the recommendations were significantly higher among those with secondary than tertiary education. Compared to good self-health perception, subjects with poor or fair self-perceived health were less likely to meet the recommendations; this also applied to those attributing little or enough importance to physical activity compared with great importance. Conclusions. Region, education, self-perceived health and perception of importance of physical activity were emerged as independent determinants of meeting the recommendations. Awareness of the positive health effects of physical activity might thus be crucial for motivating the people to become more active. Further research is needed to explore potential region-specific factors which might explain the difference in population behaviours with respect to physical activity.

  14. Factors Associated with Nursing Activities in Humanitarian Aid and Disaster Relief

    Science.gov (United States)

    Noguchi, Norihito; Inoue, Satoshi; Shimanoe, Chisato; Shibayama, Kaoru; Shinchi, Koichi

    2016-01-01

    Background Although nurses play an important role in humanitarian aid and disaster relief (HA/DR), little is known about the nursing activities that are performed in HA/DR. We aimed to clarify the nursing activities performed by Japanese nurses in HA/DR and to examine the factors associated with the frequency of nursing activities. Methods A self-administered questionnaire survey was completed by 147 nurses with HA/DR experience. The survey extracted information on demographic characteristics, past experience (e.g., disaster medical training experience, HA/DR experience), circumstances surrounding their dispatched to HA/DR (e.g., team size, disaster type, post-disaster phase, mission term), and the frequency of nursing activities performed under HA/DR. The frequency of nursing activities was rated on a 5-point Likert scale. Evaluation of nursing activities was conducted based on the “nursing activity score”, which represents the frequency of each nursing activity. Factors related to the nursing activity score were evaluated by multiple logistic regression analysis. Results Nurses were involved in 27 nursing activities in HA/DR, 10 of which were performed frequently. On analysis, factors significantly associated with nursing activity score were nursing license as a registered nurse (OR 7.79, 95% CI 2.95–20.57), two or more experiences with disaster medical training (OR 2.90 95%, CI 1.12–7.49) and a post-disaster phase of three weeks or longer (OR 8.77, 95% CI 2.59–29.67). Conclusions These results will contribute to the design of evidence-based disaster medical training that improves the quality of nursing activities. PMID:26959351

  15. Risk factors for negative impacts on sexual activity and function in younger breast cancer survivors.

    Science.gov (United States)

    Lee, Maria; Kim, Yun Hwan; Jeon, Myung Jae

    2015-09-01

    We aim to examine changes in sexual activity and function among younger breast cancer survivors who were sexually active before diagnosis and to investigate risk factors for negative impacts on them. An observational cohort study enrolled 304 premenopausal and sexually active women diagnosed with early stage breast cancer. Questionnaires were completed, and sexual activity was measured at two time points: after surgery, to assess sexual activity and function before diagnosis, and then at least 12 months after the completion of chemotherapy or endocrine therapy. For each domain of the Female Sexual Function Index, a score below 3 was classified as indicative of a sexual problem. Each sexual problem was considered to be dysfunctional if it was associated with distress. The median age at the last survey was 46.0 years (range: 23-57). Of the participants, 35 (11.5%) became sexually inactive after treatment. Among the 269 women who remained sexually active, 31.6% were currently experiencing sexual dysfunction, which was significantly higher compared with the frequency before diagnosis. In the multivariate logistic regression model, chemo-related menopause, thyroid dysfunction, and depression were independent risk factors for sexual inactivity. Chemo-related menopause was a significant risk factor for sexual dysfunction. Chemo-related menopause was significantly associated with both sexual inactivity and dysfunction after treatment. Thyroid dysfunction and depression were risk factors for sexual inactivity in younger breast cancer survivors. Copyright © 2015 John Wiley & Sons, Ltd.

  16. Transforming growth factor-β1 induces expression of human coagulation factor XII via Smad3 and JNK signaling pathways in human lung fibroblasts.

    Science.gov (United States)

    Jablonska, Ewa; Markart, Philipp; Zakrzewicz, Dariusz; Preissner, Klaus T; Wygrecka, Malgorzata

    2010-04-09

    Coagulation factor XII (FXII) is a liver-derived serine protease involved in fibrinolysis, coagulation, and inflammation. The regulation of FXII expression is largely unknown. Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that has been linked to several pathological processes, including tissue fibrosis by modulating procoagulant and fibrinolytic activities. This study investigated whether TGF-beta1 may regulate FXII expression in human lung fibroblasts. Treatment of human lung fibroblasts with TGF-beta1 resulted in a time-dependent increase in FXII production, activation of p44/42, p38, JNK, and Akt, and phosphorylation and translocation into the nucleus of Smad3. However, TGF-beta1-induced FXII expression was repressed only by the JNK inhibitor and JNK and Smad3 antisense oligonucleotides but not by MEK, p38, or phosphoinositide 3-kinase blockers. JNK inhibition had no effect on TGF-beta1-induced Smad3 phosphorylation, association with Smad4, and its translocation into the nucleus but strongly suppressed Smad3-DNA complex formation. FXII promoter analysis revealed that the -299/+1 region was sufficient for TGF-beta1 to induce FXII expression. Sequence analysis of this region detected a potential Smad-binding element at position -272/-269 (SBE-(-272/-269)). Chromatin immunoprecipitation and streptavidin pulldown assays demonstrated TGF-beta1-dependent Smad3 binding to SBE-(-272/-269). Mutation or deletion of SBE-(-272/-269) substantially reduced TGF-beta1-mediated activation of the FXII promoter. Clinical relevance was demonstrated by elevated FXII levels and its co-localization with fibroblasts in the lungs of patients with acute respiratory distress syndrome. Our results show that JNK/Smad3 pathway plays a critical role in TGF-beta1-induced FXII expression in human lung fibroblasts and implicate its possible involvement in pathological conditions characterized by elevated TGF-beta1 levels.

  17. Prevalence of factors related to active reproductive health behavior: a cross-sectional study Indonesian adolescent

    Directory of Open Access Journals (Sweden)

    Tantut Susanto

    2016-09-01

    Full Text Available OBJECTIVES Complex and diverse factors are related to reproductive health (RH behavior among adolescents according to the social and cultural context of each countries. This study examined the prevalence of active RH and factors related to active RH behavior among Indonesian adolescents. METHODS A cross-sectional study was conducted among 1,040 of students who were selected through a multi-stage random sampling technique. A self-administered questionnaire was developed, including the World Health Organization Illustrative Questionnaire for Interview-Surveys with Young People, pubertal development scale, and sexual activity scale, modified in accordance to the Indonesian context. The data were analyzed using descriptive and comparative statistics, as well as logistic regression analyses. RESULTS The prevalence of active RH behavior were more higher in boys (56.6%; 95% confidence interval [CI], 50.6% to 62.6% than in girls (43.7%; 95% CI, 37.6% to 49.8%. Negative attitudes towards RH were a factor related to active RH behavior in both boys and girls. Smoking and kind relationship envisioned before marriage (pacaran [courtship] and nikah siri [non-registered marriage] were factors related to active RH behavior in boys; whereas the absence of access to information on substance abuse was an additional factor in girls. Moreover, an interaction was found between access to information on development and smoking (boys and attitudes on RH (girls as independent variables associated with active RH behavior. CONCLUSIONS Sex education for adolescents in Indonesia, particularly in the context of a health promotion program, should be developed based on prevalent social, cultural, and religious values to prevent active RH behavior. Such programs should focus on the kind of relationship envisioned before marriage and smoking for boys and access to information on subtance abuse for girls.

  18. A novel assay system for macrophage-activating factor activity using a human U937 cell line.

    Science.gov (United States)

    Ishikawa, Mami; Inoue, Takahiro; Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Uto, Yoshihiro; Nishikata, Takahito

    2014-08-01

    Macrophages play important roles in antitumor immunity, and immunotherapy with the group-specific component protein-derived macrophage-activating factor (GcMAF) has been reported to be effective in patients with various types of cancers. However, in macrophage research, it is important to properly evaluate macrophage activity. U937 macrophages were induced by 12-O-tetradecanoyl-13-phorbolacetate (TPA). The phagocytic activity of macrophages was evaluated as the internalized beads ratio. The MAF activity was assessed at 30 min after MAF addition as the activation ratio. We established a novel assay for phagocytic activities using differentiated U937 macrophages. The novel protocol was simple and rapid and was sensitive for GcMAF. This protocol should be useful not only for basic studies, such as those on molecular mechanisms underlying macrophage activation, but also for clinical studies, such as assessment of GcMAF activity prior to clinical use. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. Impact of detector-element active-area shape and fill factor on super-resolution

    Directory of Open Access Journals (Sweden)

    Russell Craig Hardie

    2015-05-01

    Full Text Available In many undersampled imaging systems, spatial integration from the individual detector elements is the dominant component of the system point spread function (PSF. Conventional focal plane arrays (FPAs utilize square detector elements with a nearly 100% fill factor, where fill factor is defined as the fraction of the detector element area that is active in light detection. A large fill factor is generally considered to be desirable because more photons are collected for a given pitch, and this leads to a higher signal-to-noise-ratio (SNR. However, the large active area works against super-resolution (SR image restoration by acting as an additional low pass filter in the overall PSF when modeled on the SR sampling grid. A high fill factor also tends to increase blurring from pixel cross-talk. In this paper, we study the impact of FPA detector-element shape and fill factor on SR. A detailed modulation transfer function analysis is provided along with a number of experimental results with both simulated data and real data acquired with a midwave infrared (MWIR imaging system. We demonstrate the potential advantage of low fill factor detector elements when combined with SR image restoration. Our results suggest that low fill factor circular detector elements may be the best choice. New video results are presented using robust adaptive Wiener filter SR processing applied to data from a commercial MWIR imaging system with both high and low detector element fill factors.

  20. Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from LPS-stimulated myeloid cells.

    LENUS (Irish Health Repository)

    Gleeson, Eimear M

    2013-07-19

    Vitamin K-dependent proteases generated in response to vascular injury and infection enable fibrin clot formation, but also trigger distinct immuno-regulatory signaling pathways on myeloid cells. Factor Xa, a protease crucial for blood coagulation, also induces protease-activated receptor-dependent cell signaling. Factor Xa can bind both monocytes and macrophages, but whether factor Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production in response to Toll-like receptor activation is not known. In this study, exposure to factor Xa significantly impaired pro-inflammatory cytokine production from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1 monocytic cells and murine macrophages. Furthermore, factor Xa inhibited nuclear factor-kappa B activation in THP-1 reporter cells, requiring phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. Active-site blockade, γ-carboxyglutamic acid domain truncation and a peptide mimic of the factor Xa inter-epidermal growth factor-like region prevented factor Xa inhibition of lipopolysaccharide-induced tumour necrosis factor-α release. In addition, factor Xa anti-inflammatory activity was markedly attenuated by the presence of an antagonist of protease-activated receptor 2, but not protease-activated receptor 1. The key role of protease-activated receptor 2 in eliciting factor Xa-dependent anti-inflammatory signaling on macrophages was further underscored by the inability of factor Xa to mediate inhibition of tumour necrosis factor-α and interleukin-6 release from murine bone marrow-derived protease-activated receptor 2-deficient macrophages. We also show for the first time that, in addition to protease-activated receptor 2, factor Xa requires a receptor-associated protein-sensitive low-density lipoprotein receptor to inhibit lipopolysaccharide-induced cytokine production. Collectively, this study supports a novel function for factor Xa as an endogenous, receptor

  1. Isotypic analysis of antibodies against activated Factor VII in patients with Factor VII deficiency using the x-MAP technology.

    Science.gov (United States)

    Pfeiffer, Caroline; Mathieu-Dupas, Eve; Logghe, Pauline; Lissalde-Lavigne, Géraldine; Balicchi, Julien; Caliskan, Umran; Valentin, Thomas; Laune, Daniel; Molina, Franck; Schved, Jean François; Giansily-Blaizot, Muriel

    2016-05-01

    While the immune response to hemophilic factors in hemophilia has been widely studied, little is known about the development of anti-Factor VII (FVII) antibodies in FVII deficiency. We developed a robust technique based on the x-MAP technology to detect the presence of antibodies against FVII and characterize their isotype and validated this method using blood samples from 100 patients with FVII deficiency (median FVII clotting activity [FVII:C]: 6%) and 95 healthy controls. Anti-FVII antibodies were detected in patients but also in some controls, although the concentration of total immunoglobulin G (IgGt) and IgG1 and IgG4 subclasses was significantly different between groups. The IgG1 subclass concentrations remained significantly different also when only untreated patients were compared with controls. This difference could partially be related to the F7 genotype, particularly in patients harboring the p.Arg139Gln mutation. This x-MAP-based method might be useful for assessing the immunogenicity of novel FVII compounds and of activated FVII (FVIIa) concentrates. Further prospective studies are needed to better understand the clinical relevance of these antibodies in the management of patients with FVII deficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Evidence from intrinsic activity that asymmetry of the human brain is controlled by multiple factors.

    Science.gov (United States)

    Liu, Hesheng; Stufflebeam, Steven M; Sepulcre, Jorge; Hedden, Trey; Buckner, Randy L

    2009-12-01

    Cerebral lateralization is a fundamental property of the human brain and a marker of successful development. Here we provide evidence that multiple mechanisms control asymmetry for distinct brain systems. Using intrinsic activity to measure asymmetry in 300 adults, we mapped the most strongly lateralized brain regions. Both men and women showed strong asymmetries with a significant, but small, group difference. Factor analysis on the asymmetric regions revealed 4 separate factors that each accounted for significant variation across subjects. The factors were associated with brain systems involved in vision, internal thought (the default network), attention, and language. An independent sample of right- and left-handed individuals showed that hand dominance affects brain asymmetry but differentially across the 4 factors supporting their independence. These findings show the feasibility of measuring brain asymmetry using intrinsic activity fluctuations and suggest that multiple genetic or environmental mechanisms control cerebral lateralization.

  3. Tissue Factor-Expressing Tumor-Derived Extracellular Vesicles Activate Quiescent Endothelial Cells via Protease-Activated Receptor-1

    Directory of Open Access Journals (Sweden)

    Sara P. Y. Che

    2017-11-01

    Full Text Available Tissue factor (TF-expressing tumor-derived extracellular vesicles (EVs can promote metastasis and pre-metastatic niche formation, but the mechanisms by which this occurs remain largely unknown. We hypothesized that generation of activated factor X (FXa by TF expressed on tumor-derived EV could activate protease-activated receptors (PARs on non-activated endothelial cells to induce a pro-adhesive and pro-inflammatory phenotype. We obtained EV from TF-expressing breast (MDA-MB-231 and pancreatic (BxPC3 and Capan-1 tumor cell lines. We measured expression of E-selectin and secretion of interleukin-8 (IL-8 in human umbilical vein endothelial cells after exposure to EV and various immunologic and chemical inhibitors of TF, FXa, PAR-1, and PAR-2. After 6 h of exposure to tumor-derived EV (pretreated with factor VIIa and FX in vitro, endothelial cells upregulated E-selectin expression and secreted IL-8. These changes were decreased with an anti-TF antibody, FXa inhibitors (FPRCK and EGRCK, and PAR-1 antagonist (E5555, demonstrating that FXa generated by TF-expressing tumor-derived EV was signaling through endothelial PAR-1. Due to weak constitutive PAR-2 expression, these endothelial responses were not induced by a PAR-2 agonist peptide (SLIGKV and were not inhibited by a PAR-2 antagonist (FSLLRY after exposure to tumor-derived EV. In conclusion, we found that TF-expressing cancer-derived EVs activate quiescent endothelial cells, upregulating E-selectin and inducing IL-8 secretion through generation of FXa and cleavage of PAR-1. Conversion of resting endothelial cells to an activated phenotype by TF-expressing cancer-derived EV could promote cancer metastases.

  4. Staurosporine potentiates platelet activating factor stimulated phospholipase C activity in rabbit platelets but does not block desensitization by platelet activating factor

    International Nuclear Information System (INIS)

    Morrison, W.J.; Dhar, A.; Shukla, S.D.

    1989-01-01

    The possible involvement of protein kinase C activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets. PAF stimulated incorporation of 32 P into proteins and caused [ 3 H]InsP 3 levels to increase about 260% of control. These responses were compared after platelets were pretreated with either PAF, phorbol 12-myristate 13-acetate (PMA) or staurosporine and also after pretreatments with staurosporine followed by PAF or PMA. Pretreating platelets with staurosporine potentiated PAF-stimulated [ 3 H]InsP 3 levels by 54% and blocked protein phosphorylation. Pretreatments with PAF and PMA caused PAF-stimulated [ 3 H]InsP 3 levels to decrease to 115 and 136%, respectively. Staurosporine pretreatment blocked the decrease caused by the PMA pretreatment but not that by PAF. This study demonstrates that PAF-stimulated PLC activity is negatively affected by protein kinase C (PKC) activation and that inhibition of PKC activity did not prevent desensitization of PLC by PAF

  5. Nuclear factor-kappaB activation correlates with better prognosis and Akt activation in human gastric cancer.

    Science.gov (United States)

    Lee, Byung Lan; Lee, Hye Seung; Jung, Jieun; Cho, Sung Jin; Chung, Hee-Yong; Kim, Woo Ho; Jin, Young-Woo; Kim, Chong Soon; Nam, Seon Young

    2005-04-01

    Because the biological significance of constitutive nuclear factor-kappaB (NF-kappaB) activation in human gastric cancer is unclear, we undertook this study to clarify the regulatory mechanism of NF-kappaB activation and its clinical significance. Immunohistochemistry for NF-kappaB/RelA was done on 290 human gastric carcinoma specimens placed on tissue array slides. The correlations between NF-kappaB activation and clinicopathologic features, prognosis, Akt activation, tumor suppressor gene expression, or Bcl-2 expression were analyzed. We also did luciferase reporter assay, Western blot analysis, and reverse transcription-PCR using the SNU-216 human gastric cancer cell line transduced with retroviral vectors containing constitutively active Akt or the NF-kappaB repressor mutant of IkappaBalpha. Nuclear expression of RelA was found in 18% of the gastric carcinomas and was higher in early-stage pathologic tumor-node-metastasis (P = 0.019). A negative correlation was observed between NF-kappaB activation and lymphatic invasion (P = 0.034) and a positive correlation between NF-kappaB activation and overall survival rate of gastric cancer patients (P = 0.0228). In addition, NF-kappaB activation was positively correlated with pAkt (P = 0.047), p16 (P = 0.004), adenomatous polyposis coli (P Smad4 (P = 0.002), and kangai 1 (P Akt. NF-kappaB activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis and Akt activation. These findings suggest that NF-kappaB activation is a valuable prognostic variable in gastric carcinoma.

  6. Outcomes Following Three-Factor Inactive Prothrombin Complex Concentrate Versus Recombinant Activated Factor VII Administration During Cardiac Surgery.

    Science.gov (United States)

    Harper, Patrick C; Smith, Mark M; Brinkman, Nathan J; Passe, Melissa A; Schroeder, Darrell R; Said, Sameh M; Nuttall, Gregory A; Oliver, William C; Barbara, David W

    2018-02-01

    To compare outcomes following inactive prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa) administration during cardiac surgery. Retrospective propensity-matched analysis. Academic tertiary-care center. Patients undergoing cardiac surgery requiring cardiopulmonary bypass who received either rFVIIa or the inactive 3-factor PCC. Outcomes following intraoperative administration of rFVIIa (263) or factor IX complex (72) as rescue therapy to treat bleeding. In the 24 hours after surgery, propensity-matched patients receiving PCC versus rFVIIa had significantly less chest tube outputs (median difference -464 mL, 95% confidence interval [CI] -819 mL to -110 mL), fresh frozen plasma transfusion rates (17% v 38%, p = 0.028), and platelet transfusion rates (26% v 49%, p = 0.027). There were no significant differences between propensity-matched groups in postoperative stroke, deep venous thrombosis, pulmonary embolism, myocardial infarction, or intracardiac thrombus. Postoperative dialysis was significantly less likely in patients administered PCC versus rFVIIa following propensity matching (odds ratio = 0.3, 95% CI 0.1-0.7). No significant difference in 30-day mortality in patients receiving PCC versus rFVIIa was present following propensity matching. Use of rFVIIa versus inactive PCCs was significantly associated with renal failure requiring dialysis and increased postoperative bleeding and transfusions. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Radon variations in active volcanoes and in regions with high seismicity: internal and external factors

    International Nuclear Information System (INIS)

    Segovia, N.; Cruz-Reyna, S. De la; Mena, M.

    1986-01-01

    The results of 4 years of observations of radon concentrations in soils of active volcanoes of Costa Rica and a highly seismic region in Mexico are discussed. A distinction is made between the influences of external (mostly meteorological) and internal (magmatic or tectonic) factors on the variation in radon levels. The geological meaning of the radon data can be thus enhanced if the external factors are excluded. (author)

  8. Human factors activities in teleoperator development at the Oak Ridge National Laboratory

    International Nuclear Information System (INIS)

    Draper, J.V.; Herndon, J.N.

    1986-01-01

    The Consolidated Fuel Reprocessing Program (CFRP) at the Oak Ridge National Laboratory is developing advanced teleoperator systems for maintenance of future nuclear reprocessing facilities. Remote maintenance systems developed by the CFRP emphasize man-in-the-loop teleoperation. Consequently, human factors issues which affect teleoperator performance must be addressed. This papers surveys research and development activities carried out by the human factors group within the Remote Control Engineering Task of the CFRP

  9. Growth factors related to the activation of primordial follicles in cattle

    Directory of Open Access Journals (Sweden)

    Lidy Viviana Castillo Barón

    2011-10-01

    Full Text Available This article analyzes the presence and expression of molecules, called growth factors that act to control follicular dynamics in early stages; It also describes the nature and mechanism of action of the major growth factors involved in the activation of the paramount follicles in cattle. This is to show the importance of these molecules in developing follicle and oocyte quality, which can become fertilized on the way to increase the reproductive potential of domestic animals.

  10. Erectile Dysfunction Among HIV Patients Undergoing Highly Active Antiretroviral Therapy: Dyslipidemia as a Main Risk Factor

    Directory of Open Access Journals (Sweden)

    Gustavo Romero‐Velez, MD

    2014-04-01

    Conclusions: ED is highly prevalent in HIV patients. Dyslipidemia should be considered as a risk factor for ED in HIV patients. Romero‐Velez G, Lisker‐Cervantes A, Villeda‐Sandoval CI, Sotomayor de Zavaleta M, Olvera‐Posada D, Sierra‐Madero JG, Arreguin‐Camacho LO, and Castillejos‐Molina RA. Erectile dysfunction among HIV patients undergoing highly active antiretroviral therapy: Dyslipidemia as a main risk factor. Sex Med 2014;2:24–30.

  11. Production of active pigment epithelium-derived factor inE. coli.

    Science.gov (United States)

    Zhang, Tao; Guan, Ming; Lu, Yuan

    2005-03-01

    Human pigment epithelium-derived factor (PEDF), a neurotrophic factor, is the most potent natural inhibitor of angiogenesis. To produce the active PEDF, the gene coding for the human PEDF protein was expressed in E. coli. The rPEDF protein was expressed at 457 mg l-1 as a soluble protein. The yield of purified GST fusion protein was 14 mg l-1. Purified rPEDF inhibited tube formation in endothelial cells.

  12. Sun protection factor persistence on human skin during a day without physical activity or ultraviolet exposure

    DEFF Research Database (Denmark)

    Beyer, Ditte Maria; Faurschou, Annesofie; Philipsen, Peter Alshede

    2010-01-01

    Recently, we showed that the sun protection factor (SPF) decreases by a constant factor to reach 55% during a day with activities. Organic sunscreens but not inorganic ones are absorbed through the skin. We wished to determine the SPF decrease caused by absorption by investigating the difference...... in SPF decreases between an organic and an inorganic sunscreen, assuming that the sunscreens are stable, and that the SPF decrease is time dependent if caused by absorption....

  13. Evidence from intrinsic activity that asymmetry of the human brain is controlled by multiple factors

    OpenAIRE

    Liu, Hesheng; Stufflebeam, Steven M.; Sepulcre, Jorge; Hedden, Trey; Buckner, Randy L.

    2009-01-01

    Cerebral lateralization is a fundamental property of the human brain and a marker of successful development. Here we provide evidence that multiple mechanisms control asymmetry for distinct brain systems. Using intrinsic activity to measure asymmetry in 300 adults, we mapped the most strongly lateralized brain regions. Both men and women showed strong asymmetries with a significant, but small, group difference. Factor analysis on the asymmetric regions revealed 4 separate factors that each ac...

  14. Combined influence of healthy diet and active lifestyle on cardiovascular disease risk factors in adolescents.

    Science.gov (United States)

    Cuenca-García, M; Ortega, F B; Ruiz, J R; González-Gross, M; Labayen, I; Jago, R; Martínez-Gómez, D; Dallongeville, J; Bel-Serrat, S; Marcos, A; Manios, Y; Breidenassel, C; Widhalm, K; Gottrand, F; Ferrari, M; Kafatos, A; Molnár, D; Moreno, L A; De Henauw, S; Castillo, M J; Sjöström, M

    2014-06-01

    To investigate the combined influence of diet quality and physical activity on cardiovascular disease (CVD) risk factors in adolescents, adolescents (n = 1513; 12.5-17.5 years) participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence study were studied. Dietary intake was registered using a 24-h recall and a diet quality index was calculated. Physical activity was assessed by accelerometry. Lifestyle groups were computed as: healthy diet and active, unhealthy diet but active, healthy diet but inactive, and unhealthy diet and inactive. CVD risk factor measurements included cardiorespiratory fitness, adiposity indicators, blood lipid profile, blood pressure, and insulin resistance. A CVD risk score was computed. The healthy diet and active group had a healthier cardiorespiratory profile, fat mass index (FMI), triglycerides, and high-density lipoprotein cholesterol (HDL-C) levels and total cholesterol (TC)/HDL-C ratio (all P ≤ 0.05). Overall, active adolescents showed higher cardiorespiratory fitness, lower FMI, TC/HDL-C ratio, and homeostasis model assessment index and healthier blood pressure than their inactive peers with either healthy or unhealthy diet (all P ≤ 0.05). Healthy diet and active group had healthier CVD risk score compared with the inactive groups (all P ≤ 0.02). Thus, a combination of healthy diet and active lifestyle is associated with decreased CVD risk in adolescents. Moreover, an active lifestyle may reduce the adverse consequences of an unhealthy diet. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)

    DEFF Research Database (Denmark)

    Erlandsson, Maria; Nielsen, Carsten Haagen; Jeppesen, Troels Elmer

    2015-01-01

    Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example......, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an 18F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[18F]fluorobenzoate, and the [18F]ASIS was purified on a PD-10 desalting...... column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [18F]ASIS to TF and to a specific anti-factor VII...

  16. Mechanisms of integrin-vascular endothelial growth factor receptor cross-activation in angiogenesis.

    Science.gov (United States)

    Mahabeleshwar, Ganapati H; Feng, Weiyi; Reddy, Kumar; Plow, Edward F; Byzova, Tatiana V

    2007-09-14

    The functional responses of endothelial cells are dependent on signaling from peptide growth factors and the cellular adhesion receptors, integrins. These include cell adhesion, migration, and proliferation, which, in turn, are essential for more complex processes such as formation of the endothelial tube network during angiogenesis. This study identifies the molecular requirements for the cross-activation between beta3 integrin and tyrosine kinase receptor 2 for vascular endothelial growth factor (VEGF) receptor (VEGFR-2) on endothelium. The relationship between VEGFR-2 and beta3 integrin appears to be synergistic, because VEGFR-2 activation induces beta3 integrin tyrosine phosphorylation, which, in turn, is crucial for VEGF-induced tyrosine phosphorylation of VEGFR-2. We demonstrate here that adhesion- and growth factor-induced beta3 integrin tyrosine phosphorylation are directly mediated by c-Src. VEGF-stimulated recruitment and activation of c-Src and subsequent beta3 integrin tyrosine phosphorylation are critical for interaction between VEGFR-2 and beta3 integrin. Moreover, c-Src mediates growth factor-induced beta3 integrin activation, ligand binding, beta3 integrin-dependent cell adhesion, directional migration of endothelial cells, and initiation of angiogenic programming in endothelial cells. Thus, the present study determines the molecular mechanisms and consequences of the synergism between 2 cell surface receptor systems, growth factor receptor and integrins, and opens new avenues for the development of pro- and antiangiogenic strategies.

  17. Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis

    DEFF Research Database (Denmark)

    Iankova, Irena; Petersen, Rasmus K; Annicotte, Jean-Sébastien

    2006-01-01

    Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c......-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9...... with and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master regulator of this process, on the promoter of PPARgamma target genes. PPARgamma-cdk9 interaction results in increased transcriptional activity of PPARgamma and therefore increased adipogenesis....

  18. Diclofenac inhibits tumor necrosis factor-α-induced nuclear factor-κB activation causing synergistic hepatocyte apoptosis.

    Science.gov (United States)

    Fredriksson, Lisa; Herpers, Bram; Benedetti, Giulia; Matadin, Quraisha; Puigvert, Jordi C; de Bont, Hans; Dragovic, Sanja; Vermeulen, Nico P E; Commandeur, Jan N M; Danen, Erik; de Graauw, Marjo; van de Water, Bob

    2011-06-01

    Drug-induced liver injury (DILI) is an important clinical problem. It involves crosstalk between drug toxicity and the immune system, but the exact mechanism at the cellular hepatocyte level is not well understood. Here we studied the mechanism of crosstalk in hepatocyte apoptosis caused by diclofenac and the proinflammatory cytokine tumor necrosis factor α (TNF-α). HepG2 cells were treated with diclofenac followed by TNF-α challenge and subsequent evaluation of necrosis and apoptosis. Diclofenac caused a mild apoptosis of HepG2 cells, which was strongly potentiated by TNF-α. A focused apoptosis machinery short interference RNA (siRNA) library screen identified that this TNF-α-mediated enhancement involved activation of caspase-3 through a caspase-8/Bid/APAF1 pathway. Diclofenac itself induced sustained activation of c-Jun N-terminal kinase (JNK) and inhibition of JNK decreased both diclofenac and diclofenac/TNF-α-induced apoptosis. Live cell imaging of GFPp65/RelA showed that diclofenac dampened the TNF-α-mediated nuclear factor kappaB (NF-κB) translocation oscillation in association with reduced NF-κB transcriptional activity. This was associated with inhibition by diclofenac of the TNF-α-induced phosphorylation of the inhibitor of NF-κB alpha (IκBα). Finally, inhibition of IκB kinase β (IKKβ) with BMS-345541 as well as stable lentiviral short hairpin RNA (shRNA)-based knockdown of p65/RelA sensitized hepatocytes towards diclofenac/TNF-α-induced cytotoxicity. Together, our data suggest a model whereby diclofenac-mediated stress signaling suppresses TNF-α-induced survival signaling routes and sensitizes cells to apoptosis. Copyright © 2011 American Association for the Study of Liver Diseases.

  19. Motivational factors associated with physical activity and quality of life in people with severe mental illness.

    Science.gov (United States)

    Farholm, Anders; Sørensen, Marit; Halvari, Hallgeir

    2017-12-01

    There has been increasing interest for investigating the role of motivation in physical activity among people with severe mental illness (SMI). Autonomous motivation has been suggested to have a potentially important role in adoption and maintenance of physical activity. However, the knowledge about factors that facilitate autonomous motivation among people with SMI is scarce. The aim of this study was to examine factors associated with motivation for physical activity as well as the relationships between motivation, physical activity and health-related quality of life in individuals with SMI that were currently physically active. A cross-sectional design was used, and 88 participants were recruited from a public health network promoting physical activity for people with SMI. They answered a questionnaire package consisting of scales measuring psychological need support - psychological need satisfaction - and motivation for physical activity, physical activity and health-related quality of life. The majority of participants reported to be in regular physical activity. Associations between variables were tested according to the self-determination theory process model. Structural equation modelling yielded good fit of the process model to the data. Specifically, a need-supportive environment was positively associated with psychological need satisfaction, while psychological need satisfaction was positively associated with autonomous motivation and mental health-related quality of life, and negatively associated with controlled motivation and amotivation. Physical activity was positively associated with autonomous motivation and physical health-related quality of life, and negatively associated with amotivation. This study indicates that individuals with SMI can be regularly physically active when provided with suitable opportunities. Furthermore, the present results suggest that it is vital for health-care practitioners to emphasise creating a need

  20. [Sedentary lifestyle is associated with metabolic and cardiovascular risk factors independent of physical activity].

    Science.gov (United States)

    Leiva, Ana María; Martínez, María Adela; Cristi-Montero, Carlos; Salas, Carlos; Ramírez-Campillo, Rodrigo; Díaz Martínez, Ximena; Aguilar-Farías, Nicolás; Celis-Morales, Carlos

    2017-04-01

    Sedentary behavior is a main risk factor for cardiovascular disease and mortality. To investigate the association between sedentary behavior and metabolic and cardiovascular risk factors. We assessed 322 participants aged between 18 to 65 years. Physical activity and sedentary behavior were measured with accelerometers (Actigraph®). Body mass index (BMI), waist circumference, percentage of body fat, diet and blood markers (glucose, lipid profile, insulin and HOMA-IR) were measured with standardized protocols. Thirty four percent of participants were physically inactive and spent on average 8.7 h/day on sedentary activities. Per one hour increase in sedentary behavior there were significant adverse changes in glucose (4.79 mg/dl), insulin (2.73 pmol/l), HOMA-IR (0.75), BMI (0.69 kg/m²), waist circumference (1.95 cm), fat mass (1.03%), total cholesterol (9.73 mg/dl), HDL-cholesterol (-3.50 mg/dl), LDL-cholesterol (10.7 mg/dl) and triglycerides (12.4 mg/dl). These findings were independent of main confounding factors including total physical activity, dietary factors, BMI and socio-demographics. The detrimental effect of sedentary behaviors on cardiometabolic and obesity-related traits is independent of physical activity levels. Therefore, reducing sedentary time should be targeted in the population apart from increasing their physical activity levels.

  1. MOTIVATIONAL FACTORS RELATED TO THE PRACTICE OF PHYSICAL ACTIVITIES OF THE ELDERLY

    Directory of Open Access Journals (Sweden)

    Agnes Navarro Cabral da Silva

    2017-01-01

    Full Text Available The aim of this study was to investigate the motivational factors for older adults to practice physical activities regularly. The sample consisted of 77 elderly of both genders, aged 55 to 90 years and who were practicing physical activities for at least a month in centers of sports and leisure in the city of Indaiatuba. The inventory IMPRAF-54 (Motivation for the Regular Practice of Physical Activity Inventory was used for data collection. This instrument covers 6 dimensions of motivation for the practice of physical activities: stress control, health, sociability, competitiveness, aesthetic and pleasure. The results showed that the main motivational factor for the elderly is health. After health, sociability, pleasure and control of stress appear tied and, finally, aesthetics and competitiveness. With these results, it is possible to know what encourages older adults to attend classes and to plan for them properly, including their interests and considering them holistically.

  2. Oral Colostrum Macrophage-activating Factor for Serious Infection and Chronic Fatigue Syndrome: Three Case Reports.

    Science.gov (United States)

    Inui, Toshio; Kubo, Kentaro; Kuchiike, Daisuke; Uto, Yoshihiro; Nishikata, Takahito; Sakamoto, Norihiro; Mette, Martin

    2015-08-01

    Gc protein-derived macrophage-activating factor (GcMAF) immunotherapy has been steadily advancing over the last two decades. Oral colostrum macrophage-activating factor (MAF) produced from bovine colostrum has shown high macrophage phagocytic activity. GcMAF-based immunotherapy has a wide application for use in treating many diseases via macrophage activation or for use as supportive therapy. Three case studies demonstrate that oral colostrum MAF can be used for serious infection and chronic fatigue syndrome (CFS) without adverse effects. We demonstrate that colostrum MAF shows promising clinical results in patients with infectious diseases and for symptoms of fatigue, which is common in many chronic diseases. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. Shielding factors for vehicles to gamma radiation from activity deposited on structures and ground surfaces

    International Nuclear Information System (INIS)

    Lauridsen, B.; Hedemann Jensen, P.

    1982-04-01

    This report describes a measuring procedure for the determination of shielding factors for vehicles passing through areas that have been contaminated by activity released to the atmosphere from a reactor accident. A simulated radiation field from fallout has been approximated by a point source that has been placed in a matrix around and above the vehicle. Modifying factors are discussed such as mutual shielding by nearby buildings and passengers. From measurements on different vehicles with and without passengers shielding factors are recommended for ordinary cars and busses in both urban and open areas, and areas with single family houses. (author)

  4. Snoring, sympathetic activity and cardiovascular risk factors in a 70 year old population

    DEFF Research Database (Denmark)

    Jennum, P; Schultz-Larsen, K; Christensen, Niels Juel

    1993-01-01

    ), plasma lipids (triglycerides, cholesterol, high density lipoprotein), plasma catecholamines (epinephrine, norepinephrine), fasting blood glucose and glucose tolerance test (1 gram glucose per kg body weight given and blood glucose was measured 1 and 2 hours thereafter) were evaluated in all participants......In order to describe the relation between snoring, cardiovascular risk factors, metabolic factors and sympathetitic activity, 804 70-year-old males and females were classified according to snoring habits and life-style factors (alcohol and tobacco consumption), blood pressure, body mass index (BMI....... Self-reported snoring was associated with gender (males showed higher prevalence than females, p glucose tolerance test (p

  5. FACTORES FINANCIEROS LOCALES INFLUYEN LAS ACTIVIDADES DE LOS BANCOS COOPERATIVOS GRIEGOS / LOCAL FINANCIAL FACTORS INFLUENCING ACTIVITIES OF GREEK COOPERATIVE BANKS

    Directory of Open Access Journals (Sweden)

    GEORGE KONTEOS

    2010-09-01

    Full Text Available Este artículo examina la influencia de las condiciones locales en las actividades bancarias centrandose en el caso de los 14 bancos cooperativos en Grecia durante el período 1999-2007. Estos bancos han sido seleccionados por su carácter local y en consecuencia, están más influenciadas por las condiciones locales, en comparación con los bancos con red nacional e incluso internacional. Las condiciones locales pueden ser endógenas y exógenas al banco. Las endógenas al banco es la red bancaria que se desarrolla a nivel local o regional asi como a los miembros de los bancos que son la parte principal de la clientela de estas. Una macroeconómica y exógena condición del banco es la cantidad de ahorros en la localidad donde opera. Las actividades bancarias que han sido examinadas incluyen los depósitos y los préstamos que constituyen la parte principal de las actividades bancarias de los bancos cooperativos en Grecia. El crecimiento de la red bancaria es el principal factor de aumento de las actividades del banco; el crecimiento de los miembros de las cooperativas y el aumento de las economías locales tienen una influencia positiva, pero menos importante en las actividades de los bancos cooperativos./This paper examines the influence of local conditions on banking activities focusing on the case of 14 cooperative banks in Greece for the period 1999-2007. These banks have been chosen because of their local character and consequently they are more influenced by local conditions in comparison to banks having a national and even international network. Local conditions could be endogenous and exogenous to the bank. The endogenous to the bank are the banking network developed locally or regionally, and the members of the banks who are the main part of the banks’ clientele. A macroeconomic and exogenous to the bank condition is the amount of savings in the prefecture in which the cooperative bank operates. The banking activities which have

  6. Scintigraphic measurement of the contractile activity of the gastric antrum using factor analysis

    International Nuclear Information System (INIS)

    Bergmann, H.; Hoebart, J.; Kugi, A.; Stacher, G.; Granser, G.V.

    1990-01-01

    The motor activity of the gastric antrum is difficult to record by manometric means and scintigraphic methods have proved unsatisfactory so far as no consistent relationship between antral contractile activity and gastric emptying rate could be detected. We investigated, using data recorded in 16 healthy human subjects after the ingestion of a semisolid standard meal, whether a newly developed method employing factor analysis would yield more meaningful and reproducible results. Factor analysis was applied to sequential scintigraphic images (3-s frame time) of gastric antrum. The computed factor images and the respective factor curves are representative of distinct dynamic structures of the antrum. From the more or less sinusoidal excursions of the factor curves, which exhibited the 3 cycles per minute frequency characteristic for the stomach, amplitude, frequency and propagation velocity of antral contractions can be calculated. The amplitudes of the factor curves were used to calculate a contraction index. This contraction index was found to be correlated significantly negatively with the gastric half-emptying time of the ingested meal. The employed factor analytical approach thus seems a promising tool to further investigate the role of antral contractility in the process of gastric emptying. (Authors)

  7. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans

    DEFF Research Database (Denmark)

    Huang, T; Larsen, K T; Ried-Larsen, M

    2014-01-01

    The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain-derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles...... studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness. More research is needed to confirm the findings from the observational studies....

  8. Post-Materialism as a Cultural Factor Influencing Entrepreneurial Activity across Nations

    OpenAIRE

    Uhlaner, L.M.; Thurik, A.R.; Hutjes, J.

    2002-01-01

    textabstractThe study of the determinants of entrepreneurship at the country level has been dominated by economic influences. The relative stability of differences in levels of entrepreneurship across coun-tries suggests that other forces such as certain institutional and/or cultural factors are at play. The objective of this paper is to explore how post-materialism explains differences in entrepreneurial activity across countries. Entrepreneurial activity is defined as the percent of a count...

  9. Single-chain vascular endothelial growth factor variant with antagonist activity

    DEFF Research Database (Denmark)

    Boesen, Thomas P; Soni, Bobby; Schwartz, Thue W

    2002-01-01

    receptor molecules and inducing dimerization. By mixing two vascular endothelial growth factor monomers, each with different substitutions, heterodimers with only one active receptor binding site have previously been prepared. These heterodimers bind the receptor molecule but are unable to induce...... dimerization and activation. However, preparation of heterodimers is cumbersome, involving separate expression of different monomers, refolding the mixture, and separating heterodimers from homodimers. Here we show that a fully functional ligand can efficiently be expressed as a single protein chain containing...

  10. Factors Associated with Physical Activity among Macedonian Adolescents in Albanian Ethnic Community

    OpenAIRE

    GONTAREV, Seryozha; KALAC, Ruzdija; AMETI, Vullnet; REDJEPI, Agim

    2016-01-01

    Background: The purpose of this study was to determine the relationship of demographic, psychological, social and environmental factors with physical activity and to determine whether indicators of physical activity differ by gender among Macedonian adolescents from Albanian ethnic community from 11 to 14 yr (N = 886). Methods: Research were conducted in 2014 in several primary schools randomly selected from Tetovo and Gostivar region of the R. Macedonia. Students completed a questionnaire wh...

  11. Changes in antagonistic activity of lactic acid bacteria induced by their response to technological factors

    Directory of Open Access Journals (Sweden)

    Dovile Jonkuviene

    2015-12-01

    Full Text Available This study examined the changes in antagonistic activity of selected lactic acid bacteria (LAB in response to technological factors used in food production. The antimicrobial activity of 12 selected LAB strains was assessed against the bacterial and fungal strains using the agar well diffusion method. Sodium chloride (NaCl 6.5–8.0%, glucose 20-30% and pH 4.0, pH 8.0 and higher were the most crucial factors in reducing the spectra of the microorganisms antagonized. Heating at 80 °C or 100 °C had a greater negative impact than 63 °C on the antifungal activity of LAB. Freezing at –72 °C eliminated the antifungal activity, or it changed from fungicidal to fungistatic. Although each LAB demonstrated the ability to retain antimicrobial activity induced by various technological factors, Lactococcus lactis 768/5 was superior in retaining high antimicrobial activity against tested indicator strains.

  12. The environment and physical activity: The influence of psychosocial, perceived and built environmental factors

    Directory of Open Access Journals (Sweden)

    Bullen Chris

    2009-03-01

    Full Text Available Abstract This study sought to integrate perceived and built environmental and individual factors into the Theory of Planned Behavior (TPB model to better understand adolescents' physical activity. Methods Participants (n = 110 aged 12 to 17 years (M = 14.6 ± 1.55 were recruited from two large metropolitan high schools in Auckland, New Zealand, were included in the analysis. Participants completed measures of the revised TPB and the perceived environment. Individual factors such as ethnicity and level of deprivation were also collected. Geographical Information Systems (GIS software was used to measure the physical environment (walkability, access to physical activity facilities. Physical activity was assessed using the ActiGraph accelerometer and the Physical Activity Questionnaire for Adolescents (PAQ-A. Data from the various sources were combined to develop an integrated model integrated for statistical analysis using structural equation modeling. Results The TPB model variables (intention and perceived behavioral control explained 43% of the variance of PAQ-A. Unique and individual contributions were made by intention and PBC and home ownership of home equipment. The model explained 13% of time spent in moderate and vigorous physical activity (Actigraph. Unique and individual contribution was made by intention. Conclusion Social cognitive variables were better predictors of both subjective and objective physical activity compared to perceived environmental and built environment factors. Implications of these findings are discussed.

  13. Social and Health Factors Associated with Physical Activity among Kuwaiti College Students

    Directory of Open Access Journals (Sweden)

    Abdulwahab Naser Al-Isa

    2011-01-01

    Full Text Available Our aim was to explore the social and health factors that are associated with the level of physical activity among Kuwaiti college students. A random sample of 787 students (48% males and 52% females was chosen and weight and height were measured to obtain body mass index (BMI, kg/m2. Associated social and health factors were obtained using a questionnaire. Those reporting being physically inactive numbered 354 and the remaining 433 were active. Obesity among males was 13% and was 10.5% among females. The social and health factors that were found to be significantly associated with physical activity among the students were gender (P<.001, marital status (P<.05, BMI category (obese or nonobese (P<.05, last dental and health checkup (P<.01, desiring a higher degree (P<.001, and countries preferred for visiting (P<.01. Males significantly exceeded females in the practice of physical activity. In conclusion, behavioural modifications, intervention studies, and health education touting the benefits of being physically active should be instituted to increase the practice of sports and other physical activities in order to control and decrease obesity-related morbidity and mortality.

  14. Trajectories of physical activity and risk factors among Taiwanese older adults.

    Science.gov (United States)

    Pan, Ling-Yen; Hsu, Hui-Chuan; Chang, Wen-Chiung; Luh, Dih-Ling

    2015-02-01

    The significance of physical activity has been noticed. However, the dynamic change and the heterogeneity of physical activity patterns among older people are little explored. This study aimed to identify the trajectory patterns of engaging in physical activity over time and its related factors. Nationally representative four-wave panel data from Taiwanese older adults, gathered between 1996 and 2007, were used (n = 4,018). The participants ranged in age from 50 to 96 years old. "Being physically active" was defined as performing physical activity in sports or exercises at least three times per week and lasting for at least 30 min each time. Group-based trajectory analysis was performed for analyzing the data. Four trajectory patterns were identified: inactive (47.83%), decreasing (12.21%), increasing (23.36%), and active (16.60%). Older respondents and those with more education were more likely to be active. Those respondents having more depressive symptoms, having more physical functional limitations, and having jobs were less likely to be physically active in the decreasing, increasing, and active patterns. There is heterogeneity among the trajectory patterns of physical activity across time in the older adults. Different strategies of physical activity promotion for the older people should be developed by the group characteristics.

  15. Assessing Physical Activity and its Relationship to Cardiovascular Risk Factors: NHANES 2003-2006

    Directory of Open Access Journals (Sweden)

    Cao Guichan

    2011-05-01

    Full Text Available Abstract Background Levels of physical activity (PA in the general population are difficult to characterize. Historically measurement has been based on self-report, which can be subject to bias. PA monitor use has created opportunities to improve surveillance and analytic research on activity and health. The aims of the current study were to investigate the associations between objectively measured PA and cardiovascular disease risk factors and obesity. Methods Data on PA from accelerometers, demographics, blood pressure, plasma glucose and lipids, self-reported hypertension and diabetes were obtained for adults, ages 20-65, in the NHANES surveys, 2003-2006. Outcomes were assessed as levels of moderate and vigorous activity, percentage of participants meeting recommended guidelines, and the correlations between activity and cardiovascular risk factors. Accelerometry data were available on 3,370 adults. Based on standard algorithms, activity levels were extremely low in all age-gender-race/ethnic groups, with an average of only 1 bout of vigorous activity lasting longer than 1 minute/day. Results Men spent 35 minutes in moderate activity/day, women 21 minutes; >75% of this activity was accumulated in 1-minute bouts. Levels of activity declined sharply after age 50 in all groups. Negative associations were observed between minutes of combined moderate and vigorous activity and systolic blood pressure, blood glucose, diabetes, hypertension, body mass index and obesity, and a positive association was seen with HDL-cholesterol (all P ≤ 0.03, suggesting valid rank ordering of participants by activity level. Conclusion The magnitude of the gap between self-report and accelerometry activity must be a result of either a vast social acceptability bias in reporting or inaccurate measurement with accelerometry. Therefore, due to the low validity of self reported PA data for epidemiologic research, it is pertinent to encourage the use of valid, objective

  16. Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect

    NARCIS (Netherlands)

    Mathijssen, N.C.J.; Masereeuw, R.; Holme, P.A.; Kraaij, M.G.J. van; Laros, B.A.P.; Peyvandi, F.; Heerde, W.L. van

    2013-01-01

    INTRODUCTION: Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. MATERIALS AND METHODS: Ten factor VII deficient patients

  17. Predicting Factors Associated with Regular Physical Activity among College Students: Applying BASNEF Model

    Directory of Open Access Journals (Sweden)

    B. Moeini

    2011-10-01

    Full Text Available Introduction & Objective: One of the important problems in modern society is people's sedentary life style. The aim of this study was to determine factors associated with regular physical activity among college students based on BASNEF model.Materials & Methods: This study was a cross-sectional study carried out on 400 students in Hamadan University of Medical Sciences. Based on the assignment among different schools, classified sampling method was chosen for data gathering using a questionnaire in three parts including: demographic information, constructs of BASNEF model, and standard international physical activity questionnaire (IPAQ. Data were analyzed by SPSS-13, and using appropriate statistical tests (Chi-square, T-test and regression. Results: Based on the results, 271 students(67.8 % had low, 124 (31% moderate ,and 5 (1.2% vigorous physical activity. There was a significant relationship (c2=6.739, df= 1, P= 0.034 between their residence and physical activity and students living in dormitory were reported to have higher level of physical activity. Behavioral intention and enabling factors from the constructs of BASNEF model were the best predictors for having physical activity in students (OR=1.215, P = 0.000 and (OR=1.119, P= 0.000 respectively.Conclusion: With regard to the fact that majority of the students did not engage in enough physical activity and enabling factors were the most effective predictors for having regular physical activity in them, it seems that providing sports facilities can promote physical activity among the students.(Sci J Hamadan Univ Med Sci 2011;18(3:70-76

  18. Physical activity and associated factors among young adults in Malaysia: an online exploratory survey.

    Science.gov (United States)

    Sreeramareddy, C T; Majeed Kutty, N A; Razzaq Jabbar, M A; Boo, N Y

    2012-06-01

    The burden of non-communicable diseases is increasing in Malaysia. Insufficient Physical Activity, which is an important risk factor for non-communicable diseases, is less researched in Malaysia. We aimed to assess the level of physical activity and identify its correlates. An online survey was carried out during October, 2011 in the University Tunku Abdul Rahman by the opinion poll research committee. Young adults answered the Short International Physical Activity Questionnaire and a questionnaire about factors according to a socio-ecological model which was adapted from published studies. Metabolic equivalent (MET)-hours and MET-minutes were calculated. Physical activity was classified as sufficient when MET-minutes were > 840. The mean age of the 474 participants was 22.4 years (S.D. = 4.7), and 253 (53.4%) were females. Their mean and median of MET-hours of PA done during the previous seven days were 31.36 (S.D., 52.19) and 14.7 (IQR, 5.77-32.07), respectively. Physical activity done was sufficient among 242 (51.1%) participants. Using univariate analysis, being male, good self-rated health, positive intention, self-efficacy, perceived benefits, social support, and availability of facilities were associated with sufficient physical activity. Using multivariate analysis sufficient physical activity was associated with participants' intention (OR 0.75, 95% CIs 0.64, 0.88), self-efficacy (OR 0.91, 95% CIs 0.85, 0.97) and facility availability (OR 0.81, 95% CIs 0.73, 0.91). The proportion of participants with sufficient physical activity was low. Positive intention and self-efficacy associated with sufficient physical activity should be supported by availability of facilities and a safely-built environment. A nationwide survey about physical and associated socialecological factors is needed to design rational health promotion strategies.

  19. Factors associated with delay in trauma team activation and impact on patient outcomes.

    Science.gov (United States)

    Connolly, Rory; Woo, Michael Y; Lampron, Jacinthe; Perry, Jeffrey J

    2017-09-05

    Trauma code activation is initiated by emergency physicians using physiological and anatomical criteria, mechanism of injury, and patient demographic factors. Our objective was to identify factors associated with delayed trauma team activation. We assessed consecutive cases from a regional trauma database from January 2008 to March 2014. We defined a delay in trauma code activation as a time greater than 30 minutes from the time of arrival. We conducted univariate analysis for factors potentially influencing trauma team activation, and we subsequently used multiple logistic regression analysis models for delayed activation in relation to mortality, length of stay, and time to operative management. Patients totalling 846 were included for our analysis; 4.1% (35/846) of trauma codes were activated after 30 minutes. Mean age was 40.8 years in the early group versus 49.2 in the delayed group (p=0.01). Patients were over age 70 years in 7.6% in the early activation group versus 17.1% in the delayed group (p=0.04). There was no significant difference in sex, type of injury, injury severity, or time from injury between the two groups. There was no significant difference in mortality, median length of stay, or median time to operative management. Delayed activation is linked with increasing age with no clear link to increased mortality. Given the severe injuries in the delayed cohort that required activation of the trauma team, further emphasis on the older trauma patient and interventions to recognize this vulnerable population should be made.

  20. Dissociation of activated protein C functions by elimination of protein S cofactor enhancement.

    LENUS (Irish Health Repository)

    Harmon, Shona

    2008-11-07

    Activated protein C (APC) plays a critical anticoagulant role in vivo by inactivating procoagulant factor Va and factor VIIIa and thus down-regulating thrombin generation. In addition, APC bound to the endothelial cell protein C receptor can initiate protease-activated receptor-1 (PAR-1)-mediated cytoprotective signaling. Protein S constitutes a critical cofactor for the anticoagulant function of APC but is not known to be involved in regulating APC-mediated protective PAR-1 signaling. In this study we utilized a site-directed mutagenesis strategy to characterize a putative protein S binding region within the APC Gla domain. Three single amino acid substitutions within the APC Gla domain (D35T, D36A, and A39V) were found to mildly impair protein S-dependent anticoagulant activity (<2-fold) but retained entirely normal cytoprotective activity. However, a single amino acid substitution (L38D) ablated the ability of protein S to function as a cofactor for this APC variant. Consequently, in assays of protein S-dependent factor Va proteolysis using purified proteins or in the plasma milieu, APC-L38D variant exhibited minimal residual anticoagulant activity compared with wild type APC. Despite the location of Leu-38 in the Gla domain, APC-L38D interacted normally with endothelial cell protein C receptor and retained its ability to trigger PAR-1 mediated cytoprotective signaling in a manner indistinguishable from that of wild type APC. Consequently, elimination of protein S cofactor enhancement of APC anticoagulant function represents a novel and effective strategy by which to separate the anticoagulant and cytoprotective functions of APC for potential therapeutic gain.

  1. Shielding factors for gamma radiation from activity deposited on structures and ground surfaces

    International Nuclear Information System (INIS)

    Hedemann Jensen, P.

    1982-11-01

    This report describes a computer model that calculates shielding factors for indoor residence in multistorey and single-family houses for gamma radiation from activity despoited on roofs, outer walls, and ground surfaces. The dimensions of the buildings including window areas and the nearby surroundings has to be speficied in the calculations. Shielding factors can be calculated for different photon energies and for a uniform surface activity distribution as well as for separate activity on roof, outer wall, and ground surface achieved from decontamination or different deposition velocities. For a given area with a known distribution of different houses a weighted shielding factor can be calculated as well as a time-averaged one based on a given residence time distribution for work/school, home, outdoors, and transportation. Calculated shielding factors are shown for typical Danish houses. To give an impression of the sensitivity of the shielding factor on the parameters used in the model, variations were made in some of the most important parameters: wall thickness, road and ground width, percentage of outer wall covered by windows, photon energy, and decontamination percentage for outer walls, ground and roofs. The uncertainity of the calculations is discussed. (author)

  2. Physical activity and dark skin tone: protective factors against low bone mass in Mexican men.

    Science.gov (United States)

    Vivanco-Muñoz, Nalleli; Jo, Talavera; Gerardo, Huitron-Bravo; Juan, Tamayo; Clark, Patricia

    2012-01-01

    A cross-sectional study was conducted on 268 Mexican men between the ages of 13 and 80 yr to evaluate the association of clinical factors related with bone mass. Men from high schools, universities, and retirement homes were invited to participate. Body mass index (BMI) was measured, and bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry for L1-L4 and total hip. Factors related to bone mass were assessed by questionnaire and analyzed using a logistic regression model. Demographic factors (age, education, and occupation), clinical data (BMI, skin tone, previous fracture, history of osteoporosis [OP], and history of fractures), and lifestyle variables (diet, physical activity, sun exposure, and smoking) were evaluated. Physical activity (≥ 60 min/5 times a week) reduced the risk for low BMD for age, osteopenia, and OP at the spine and total hip (odds ratio [OR]: 0.276; 95% confidence interval [CI]: 0.099-0.769; p=0.014; and OR: 0.184; 95% CI: 0.04-0.849; p=0.03, respectively). Dark skin tone was a protective factor, decreasing the risk by up to 70%. In this population of healthy Mexican men (aged 13-80 yr), dark skin and physical activity were protective factors against low bone mass. Copyright © 2012 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  3. Hormone therapy affects plasma measures of factor VII-activating protease in younger postmenopausal women

    DEFF Research Database (Denmark)

    Mathiasen, Jørn Sidelmann; Skouby, S.O.; Vitzthum, F.

    2010-01-01

    Objectives Current reviews indicate that hormone therapy (HT) has a protective role in coronary heart disease (CHD) in younger postmenopausal women, whereas HT contributes to CHD in older women Factor VII-activating protease (FSAP) is a serine protease that accumulates in unstable atherosclerotic...

  4. Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven)

    DEFF Research Database (Denmark)

    Viuff, D.; Lauritzen, B.; Pusateri, A.E.

    2008-01-01

    BACKGROUND: A range of plasma volume expanders is used clinically, often in settings where haemostasis may already be impaired. The haemostatic agent, recombinant activated factor VII (rFVIIa, NovoSeven), may be used to improve haemostasis but potential interactions with different volume expanders...

  5. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Mayer, Stephan A; Brun, Nikolai C; Begtrup, Kamilla

    2008-01-01

    BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke. We performed this phase 3 trial to confirm a previous study in which recombinant activated factor VII (rFVIIa) reduced growth of the hematoma and improved survival and functional outcomes. METHODS: We randomly assigned 841...

  6. Safety update on the use of recombinant activated factor VII in approved indications.

    Science.gov (United States)

    Neufeld, Ellis J; Négrier, Claude; Arkhammar, Per; Benchikh el Fegoun, Soraya; Simonsen, Mette Duelund; Rosholm, Anders; Seremetis, Stephanie

    2015-06-01

    This updated safety review summarises the large body of safety data available on the use of recombinant activated factor VII (rFVIIa) in approved indications: haemophilia with inhibitors, congenital factor VII (FVII) deficiency, acquired haemophilia and Glanzmann's thrombasthenia. Accumulated data up to 31 December 2013 from clinical trials as well as post-marketing data (registries, literature reports and spontaneous reports) were included. Overall, rFVIIa has shown a consistently favourable safety profile, with no unexpected safety concerns, in all approved indications. No confirmed cases of neutralising antibodies against rFVIIa have been reported in patients with congenital haemophilia, acquired haemophilia or Glanzmann's thrombasthenia. The favourable safety profile of rFVIIa can be attributed to the recombinant nature of rFVIIa and its localised mechanism of action at the site of vascular injury. Recombinant FVIIa activates factor X directly on the surface of activated platelets, which are present only at the site of injury, meaning that systemic activation of coagulation is avoided and the risk of thrombotic events (TEs) thus reduced. Nonetheless, close monitoring for signs and symptoms of TE is warranted in all patients treated with any pro-haemostatic agent, including rFVIIa, especially the elderly and any other patients with concomitant conditions and/or predisposing risk factors to thrombosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. School Administrators' Perceptions of Factors that Influence Children's Active Travel to School

    Science.gov (United States)

    Price, Anna E.; Pluto, Delores M.; Ogoussan, Olga; Banda, Jorge A.

    2011-01-01

    Background: Increasing children's active travel to school may be 1 strategy for addressing the growing prevalence of obesity among school age children. Using the School Travel Survey, we examined South Carolina school district leaders' perceptions of factors that influence elementary and middle school students walking to school. Methods: Frequency…

  8. Soluble receptors for tumor necrosis factor as markers of disease activity in visceral leishmaniasis

    NARCIS (Netherlands)

    Zijlstra, E. E.; van der Poll, T.; Mevissen, M.

    1995-01-01

    Serum concentrations of soluble receptors for tumor necrosis factor (sTNFRs) were measured before and after antimony therapy in 25 Sudanese patients with active visceral leishmaniasis (VL). Both sTNFR types I and II were significantly elevated in patients with VL compared with healthy controls from

  9. Cross activity of orthologous WRKY transcription factors in wheat and Arabidopsis

    NARCIS (Netherlands)

    Poietti, S.; Bertini, L.; Ent, S. van der; Leon Reyes, H.A.; Pieterse, C.M.J.; Tucci, M.; Caporale, C.; Caruso, C.

    2011-01-01

    WRKY proteins are transcription factors involved in many plant processes including plant responses to pathogens. Here, the cross activity of TaWRKY78 from the monocot wheat and AtWRKY20 from the dicot Arabidopsis on the cognate promoters of the orthologous PR4-type genes wPR4e and AtHEL of wheat and

  10. Ergonomic and macro ergonomic factors of the 'Ukrytie' shelter personnel safe activity

    International Nuclear Information System (INIS)

    Zhuravlev, G.E.; Kupnyj, V.I.; Danilov, V.M.; Vtornikov, V.E.

    1999-01-01

    Four actions are planned based upon this preliminary analysis of Human Factors technology applied to the Chernobyl Shelter activities, namely: 1. Provide expertise to and participate in all projects regarding the Shelter's future. 2. Conduct a detailed on-site survey of the current Shelter's situation. 3. Organize a business game (brain-storming) to shape the system of the Shelter's HF problems

  11. Do family environment factors play a role in adolescents' involvement in organized activities?

    NARCIS (Netherlands)

    Badura, Petr; Madarasova Geckova, Andrea; Sigmundova, Dagmar; Sigmund, Erik; van Dijk, Jitse P; Reijneveld, Sijmen A

    The study assessed the association of family environment factors with adolescents' participation in organized leisure-time activities (OLTA). We used data on 10,472 Czech adolescents aged 11-15 years (49.2% boys) from the 2013/2014 Health Behaviour in School-aged Children study. The associations of

  12. Are There Gender-Specific Risk Factors for Suicidal Activity among Patients with Schizophrenia and Depression?

    Science.gov (United States)

    Kaplan, Kalman J.; Harrow, Martin; Faull, Robert N.

    2012-01-01

    Are there gender-specific risk factors for suicidal activity among patients with schizophrenia and depression? A total of 74 schizophrenia patients (51 men, 23 women) and 77 unipolar nonpsychotic depressed patients (26 men, 51 women) from the Chicago Follow-up Study were studied prospectively at 2 years posthospitalization and again at 7.5 years.…

  13. A Comparison of Motivational Factors and Barriers to Physical Activity among Traditional versus Nontraditional College Students

    Science.gov (United States)

    Kulavic, Kimberly; Hultquist, Cherilyn N.; McLester, John R.

    2013-01-01

    Objective: To investigate the motivational factors and the barriers to physical activity (PA) in traditional college students (TS) and nontraditional college students (NTS) and determine if differences exist between these 2 groups. Participants: A total of 746 college students; 628 were TS (19.1 [plus-minus] 1.2 years), and 118 were NTS (31.2…

  14. Zyxin regulates migration of renal epithelial cells through activation of hepatocyte nuclear factor-1β.

    Science.gov (United States)

    Choi, Yun-Hee; McNally, Brian T; Igarashi, Peter

    2013-07-01

    Hepatocyte nuclear factor-1β (HNF-1β) is an epithelial tissue-specific transcription factor that regulates gene expression in the kidney, liver, pancreas, intestine, and other organs. Mutations of HNF-1β in humans produce renal cysts and congenital kidney anomalies. Here, we identify the LIM-domain protein zyxin as a novel binding partner of HNF-1β in renal epithelial cells. Zyxin shuttles to the nucleus where it colocalizes with HNF-1β. Immunoprecipitation of zyxin in leptomycin B-treated cells results in coprecipitation of HNF-1β. The protein interaction requires the second LIM domain of zyxin and two distinct domains of HNF-1β. Overexpression of zyxin stimulates the transcriptional activity of HNF-1β, whereas small interfering RNA silencing of zyxin inhibits HNF-1β-dependent transcription. Epidermal growth factor (EGF) induces translocation of zyxin into the nucleus and stimulates HNF-1β-dependent promoter activity. The EGF-mediated nuclear translocation of zyxin requires activation of Akt. Expression of dominant-negative mutant HNF-1β, knockdown of zyxin, or inhibition of Akt inhibits EGF-stimulated cell migration. These findings reveal a novel pathway by which extracellular signals are transmitted to the nucleus to regulate the activity of a transcription factor that is essential for renal epithelial differentiation.

  15. Factors associated with physical therapists’ implementation of physical activity interventions in the Netherlands

    NARCIS (Netherlands)

    Huijg, J.M.; Dusseldorp, E.; Gebhardt, W.A.; Verheijden, M.W.; Zouwe, N. van der; Middelkoop, B.J.C.; Duijzer, G.; Crone, M.R.

    2015-01-01

    Background. Physical therapists play an important role in the promotion of physical activity (PA) and the effectiveness of PA interventions. However, little is known about the extent to which they implement PA interventions following the intervention protocol and about the factors influencing their

  16. Giving children a voice: Exploring qualitative perspectives on factors influencing recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Schipperijn, Jasper; Tjørnhøj-Thomsen, Tine

    2018-01-01

    and place experiences; lack of play facilities; outdoor play policy; use of electronic devices; recess duration; organised activities; and weather. These factors were located within different layers of the socio-ecological model, but were interdependent. The findings speak for implementing a combination...

  17. Antibody-induced dimerization activates the epidermal growth factor receptor tyrosine kinase

    NARCIS (Netherlands)

    Spaargaren, M.; Defize, L. H.; Boonstra, J.; de Laat, S. W.

    1991-01-01

    The relationship between epidermal growth factor receptor (EGF-R) protein tyrosine kinase activation and ligand-induced receptor dimerization was investigated using several bivalent anti-EGF-R antibodies directed against various receptor epitopes. In A431 membrane preparations and permeabilized

  18. Effects of Light Intensity Activity on CVD Risk Factors: A Systematic Review of Intervention Studies

    Directory of Open Access Journals (Sweden)

    Romeo B. Batacan

    2015-01-01

    Full Text Available The effects of light intensity physical activity (LIPA on cardiovascular disease (CVD risk factors remain to be established. This review summarizes the effects of LIPA on CVD risk factors and CVD-related markers in adults. A systematic search of four electronic databases (PubMed, Academic Search Complete, SPORTDiscus, and CINAHL examining LIPA and CVD risk factors (body composition, blood pressure, glucose, insulin, glycosylated hemoglobin, and lipid profile and CVD-related markers (maximal oxygen uptake, heart rate, C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and tumor necrosis factor receptors 1 and 2 published between 1970 and 2015 was performed on 15 March 2015. A total of 33 intervention studies examining the effect of LIPA on CVD risk factors and markers were included in this review. Results indicated that LIPA did not improve CVD risk factors and CVD-related markers in healthy individuals. LIPA was found to improve systolic and diastolic blood pressure in physically inactive populations with a medical condition. Reviewed studies show little support for the role of LIPA to reduce CVD risk factors. Many of the included studies were of low to fair study quality and used low doses of LIPA. Further studies are needed to establish the value of LIPA in reducing CVD risk.

  19. Moringa oleifera Lam.: Protease activity against blood coagulation cascade.

    Science.gov (United States)

    Satish, A; Sairam, Sudha; Ahmed, Faiyaz; Urooj, Asna

    2012-01-01

    The present study evaluated the protease activity of aqueous extracts of Moringa oleifera (Moringaceae) leaf (MOL) and root (MOR). Protease activity was assayed using casein, human plasma clot and human fibrinogen as substrates. Caseinolytic activity of MOL was significantly higher (P ≤ 0.05) than that of MOR. Similar observations were found in case of human plasma clot hydrolyzing activity, wherein MOL caused significantly higher (P ≤ 0.05) plasma clot hydrolysis than MOR. Zymographic techniques were used to detect proteolytic enzymes following electrophoretic separation in gels. Further, both the extracts exhibited significant procoagulant activity as reflected by a significant decrease (P ≤ 0.05) in recalcification time, accompanied by fibrinogenolytic and fibrinolytic activities; clotting time was decreased from 180 ± 10 sec to 119 ± 8 sec and 143 ± 10 sec by MOL and MOR, respectively, at a concentration of 2.5 mg/mL. Fibrinogenolytic (human fibrinogen) and fibrinolytic activity (human plasma clot) was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), plate method and colorimetric method. Zymographic profile indicated that both the extracts exerted their procoagulant activity by selectively hydrolyzing Aα and Bβ subunits of fibrinogen to form fibrin clot, thereby exhibiting fibrinogenolytic activity. However, prolonged incubation resulted in degradation of the formed fibrin clot, suggesting fibrinolytic like activity. These findings support the traditional usage of M. oleifera extracts for wound healing.

  20. Large enhancement of functional activity of active site-inhibited factor VIIa due to protein dimerization: insights into mechanism of assembly/disassembly from tissue factor.

    Science.gov (United States)

    Stone, Matthew D; Harvey, Stephen B; Martinez, Michael B; Bach, Ronald R; Nelsestuen, Gary L

    2005-04-26

    Active site-inhibited blood clotting factor VIIa (fVIIai) binds to tissue factor (TF), a cell surface receptor that is exposed upon injury and initiates the blood clotting cascade. FVIIai blocks binding of the corresponding enzyme (fVIIa) or zymogen (fVII) forms of factor VII and inhibits coagulation. Although several studies have suggested that fVIIai may have superior anticoagulation effects in vivo, a challenge for use of fVIIai is cost of production. This study reports the properties of dimeric forms of fVIIai that are cross-linked through their active sites. Dimeric wild-type fVIIai was at least 75-fold more effective than monomeric fVIIai in blocking fVIIa association with TF. The dimer of a mutant fVIIai with higher membrane affinity was 1600-fold more effective. Anticoagulation by any form of fVIIai differed substantially from agents such as heparin and showed a delayed mode of action. Coagulation proceeded normally for the first minutes, and inhibition increased as equilibrium binding was established. It is suggested that association of fVIIa(i) with TF in a collision-dependent reaction gives equal access of inhibitor and enzyme to TF. Assembly was not influenced by the higher affinity and slower dissociation of the dimer. As a result, anticoagulation was delayed until the reaction reached equilibrium. Properties of different dissociation experiments suggested that dissociation of fVIIai from TF occurred by a two-step mechanism. The first step was separation of TF-fVIIa(i) while both proteins remained bound to the membrane, and the second step was dissociation of the fVIIa(i) from the membrane. These results suggest novel actions of fVIIai that distinguish it from most of the anticoagulants that block later steps of the coagulation cascade.

  1. Factors of physical activity among Chinese children and adolescents: a systematic review.

    Science.gov (United States)

    Lu, Congchao; Stolk, Ronald P; Sauer, Pieter J J; Sijtsma, Anna; Wiersma, Rikstje; Huang, Guowei; Corpeleijn, Eva

    2017-03-21

    Lack of physical activity is a growing problem in China, due to the fast economic development and changing living environment over the past two decades. The aim of this review is to summarize the factors related to physical activity in Chinese children and adolescents during this distinct period of development. A systematic search was finished on Jan 10 th , 2017, and identified 2200 hits through PubMed and Web of Science. English-language published studies were included if they reported statistical associations between factors and physical activity. Adapted criteria from the Strengthening The Reporting of OBservational studies in Epidemiology (STROBE) statement and evaluation of the quality of prognosis studies in systematic reviews (QUIPS) were used to assess the risk of bias of the included studies. Related factors that were reported in at least three studies were summarized separately for children and adolescents using a semi-quantitative method. Forty two papers (published 2002-2016) were included. Most designs were cross-sectional (79%), and most studies used questionnaires to assess physical activity. Sample size was above 1000 in 18 papers (43%). Thirty seven studies (88%) showed acceptable quality by methodological quality assessment. Most studies reported a low level of physical activity. Boys were consistently more active than girls, the parental physical activity was positively associated with children and adolescents' physical activity, children in suburban/rural regions showed less activity than in urban regions, and, specifically in adolescents, self-efficacy was positively associated with physical activity. Family socioeconomic status and parental education were not associated with physical activity in children and adolescents. The studies included in this review were large but mostly of low quality in terms of study design (cross-sectional) and methods (questionnaires). Parental physical activity and self-efficacy are promising targets for future

  2. Platelet-derived growth factor (PDGF) stimulates glycogen synthase activity in 3T3 cells

    International Nuclear Information System (INIS)

    Chan, C.P.; Bowen-Pope, D.F.; Ross, R.; Krebs, E.G.

    1986-01-01

    Hormonal regulation of glycogen synthase, an enzyme that can be phosphorylated on multiple sites, is often associated with changes in its phosphorylation state. Enzyme activation is conventionally monitored by determining the synthase activity ratio [(activity in the absence of glucose 6-P)/(activity in the presence of glucose 6-P)]. Insulin causes an activation of glycogen synthase with a concomitant decrease in its phosphate content. In a previous report, the authors showed that epidermal growth factor (EGF) increases the glycogen synthase activity ratio in Swiss 3T3 cells. The time and dose-dependency of this response was similar to that of insulin. Their recent results indicate that PDGF also stimulates glycogen synthase activity. Enzyme activation was maximal after 30 min. of incubation with PDGF; the time course observed was very similar to that with insulin and EGF. At 1 ng/ml (0.03nM), PDGF caused a maximal stimulation of 4-fold in synthase activity ratio. Half-maximal stimulation was observed at 0.2 ng/ml (6 pM). The time course of changes in enzyme activity ratio closely followed that of 125 I-PDGF binding. The authors data suggest that PDGF, as well as EFG and insulin, may be important in regulating glycogen synthesis through phosphorylation/dephosphorylation mechanisms

  3. Regulation of the yeast metabolic cycle by transcription factors with periodic activities

    Directory of Open Access Journals (Sweden)

    Pellegrini Matteo

    2011-10-01

    Full Text Available Abstract Background When growing budding yeast under continuous, nutrient-limited conditions, over half of yeast genes exhibit periodic expression patterns. Periodicity can also be observed in respiration, in the timing of cell division, as well as in various metabolite levels. Knowing the transcription factors involved in the yeast metabolic cycle is helpful for determining the cascade of regulatory events that cause these patterns. Results Transcription factor activities were estimated by linear regression using time series and genome-wide transcription factor binding data. Time-translation matrices were estimated using least squares and were used to model the interactions between the most significant transcription factors. The top transcription factors have functions involving respiration, cell cycle events, amino acid metabolism and glycolysis. Key regulators of transitions between phases of the yeast metabolic cycle appear to be Hap1, Hap4, Gcn4, Msn4, Swi6 and Adr1. Conclusions Analysis of the phases at which transcription factor activities peak supports previous findings suggesting that the various cellular functions occur during specific phases of the yeast metabolic cycle.

  4. Factors influencing primary health care professionals' physical activity promotion behaviors: a systematic review.

    Science.gov (United States)

    Huijg, Johanna M; Gebhardt, Winifred A; Verheijden, Marieke W; van der Zouwe, Nicolette; de Vries, Juriena D; Middelkoop, Barend J C; Crone, Mathilde R

    2015-02-01

    Despite the promising findings related to the efficacy of interventions aimed at promoting physical activity (PA) in primary health care (PHC), the translation of these interventions to PHC practice does not always happen as desired. To help understand why efficacious PHC-based PA interventions are not effectively translated to practice, this study systematically reviewed the literature on factors influencing PHC professionals' PA promotion practices. Literature searches were conducted in Web of Science, PubMed, and PsycINFO for peer-reviewed articles published in English from 1990 onwards. Studies were included that met the following criteria: (1) involving PHC-based PA interventions, and (2) reporting factors influencing PHC professionals' PA promotion behaviors. Two researchers independently screened studies and extracted data. A narrative synthesis using thematic analysis was conducted to identify factors. Of the 4,469 identified articles, 59 were included in the review. Factors were identified by qualitative methods, barrier/facilitator ratings, and the examination of the relationship between factors and PA promotion, and the effectiveness of introduction strategies. Many factors related to the development, delivery, and effects of the innovation, the sociopolitical and organizational culture, resources, and support, patient and PHC professional characteristics, and innovation strategies were identified as potential influences on PHC professionals' PA promotion practices. However, the lack of evidence on the relationship between factors and PA promotion indicated insufficient evidence on PA promotion determinants. This extensive overview of potential factors can inform intervention developers and implementers on which factors may play a role when introducing PA interventions in PHC. Future research should further investigate relationships between factors and PA promotion, which should be guided by qualitative in-depth knowledge on influencing factors.

  5. Seasonal distribution of active systemic lupus erythematosus and its correlation with meteorological factors

    Directory of Open Access Journals (Sweden)

    Zhang Hua-Li

    2011-01-01

    Full Text Available OBJECTIVE: To explore the characteristics of seasonal distribution of active systemic lupus erythematosus (SLE and the influences of meteorological factors including temperature and humidity on active systemic lupus erythematosus. METHODS: The characteristics of seasonal distribution of active SLE and its correlation with meteorological factors were retrospectively analyzed in 640 patients living in the city of Zhanjiang, China and had active SLE between January 1997 and December 2006. RESULTS: In winter, when there are weaker ultraviolet (UV rays, the ratio of patients with active SLE to total inpatients was 3.89 %o, which is significantly higher than in other seasons with stronger UV rays, including 2.17 %o in spring, 1.87 0 in summer and 2.12 0 in autumn. The number of patients with active SLE had significant negative correlation with mean temperature and was not significantly related to mean humidity. CONCLUSION: Active SLE has the characteristics of seasonal distribution and is associated with temperature. The mechanism remains to be further studied.

  6. Psychosocial factors and physical activity as predictors of fruit and vegetable intake in college students

    Directory of Open Access Journals (Sweden)

    Rafael Miranda TASSITANO

    2016-04-01

    Full Text Available Objective: To analyze whether psychosocial factors and physical activity are predictors of fruit and vegetable intake in young adults attending college. Methods: This cross-sectional study included a representative sample of students from a public university in the Brazilian Northeast (n=717. Fruit and vegetable intake was measured by a Food Frequency Questionnaire containing 21 items. The psychosocial factors for behavior change, measured by a questionnaire, were: behavior change strategy, self-efficacy, perceived barriers and facilitators in decision making, and social support. The level of physical activity was measured by the International Physical Activity Questionnaire. Multiple linear regression was the intake prediction model using a significance level of 5% (p<0.05. Results: The median fruit and vegetable intake was 2.0 servings/day. In adjusted analysis, behavior change strategy (R²=0.31, self-efficacy (R²=0.03, friends' support (R²=0.02, and physical activity (R²=0.03 explained 39% of the fruit and vegetable intake variance in men. Behavior change strategy (R²=0.03, self-efficacy (R²=0.13, perceived barriers (R²=0.08, and physical activity (R²=0.02 explained 26% of the fruit and vegetable intake variance in women. Fruit and vegetable intake would increase by one serving for every extra 35 and 47 minutes of physical activity men and women, respectively, practice a day. Conclusion: The main predictors of fruit and vegetable intake are behavior change strategies, self-efficacy, and physical activity.

  7. MiT/TFE transcription factors are activated during mitophagy downstream of Parkin and Atg5.

    Science.gov (United States)

    Nezich, Catherine L; Wang, Chunxin; Fogel, Adam I; Youle, Richard J

    2015-08-03

    The kinase PINK1 and ubiquitin ligase Parkin can regulate the selective elimination of damaged mitochondria through autophagy (mitophagy). Because of the demand on lysosomal function by mitophagy, we investigated a role for the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, in this process. We show that during mitophagy TFEB translocates to the nucleus and displays transcriptional activity in a PINK1- and Parkin-dependent manner. MITF and TFE3, homologues of TFEB belonging to the same microphthalmia/transcription factor E (MiT/TFE) family, are similarly regulated during mitophagy. Unlike TFEB translocation after starvation-induced mammalian target of rapamycin complex 1 inhibition, Parkin-mediated TFEB relocalization required Atg9A and Atg5 activity. However, constitutively active Rag guanosine triphosphatases prevented TFEB translocation during mitophagy, suggesting cross talk between these two MiT/TFE activation pathways. Analysis of clustered regularly interspaced short palindromic repeats-generated TFEB/MITF/TFE3/TFEC single, double, and triple knockout cell lines revealed that these proteins partly facilitate Parkin-mediated mitochondrial clearance. These results illuminate a pathway leading to MiT/TFE transcription factor activation, distinct from starvation-induced autophagy, which occurs during mitophagy.

  8. Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3.

    Science.gov (United States)

    Chen, M; Hieng, S; Qian, X; Costa, R; Ou, J H

    1994-11-15

    Hepatitis B virus (HBV) ENI enhancer can activate the expression of HBV and non-HBV genes in a liver-specific manner. By performing the electrophoretic mobility-shift assays, we demonstrated that the three related, liver-enriched, transcription factors, HNF3 alpha, HNF3 beta, and HNF3 gamma could all bind to the 2c site of HBV ENI enhancer. Mutations introduced in the 2c site to abolish the binding by HNF3 reduced the enhancer activity approximately 15-fold. Moreover, expression of HNF3 antisense sequences to suppress the expression of HNF3 in Huh-7 hepatoma cells led to reduction of the ENI enhancer activity. These results indicate that HNF3 positively regulates the ENI enhancer activity and this regulation is most likely mediated through the 2c site. The requirement of HNF3 for the ENI enhancer activity could explain the liver specificity of this enhancer element.

  9. Murine inflammatory factor co-chromatographs with murine interleukin-2 activity

    International Nuclear Information System (INIS)

    Freitas, C.S.; Shinzato, T.O.; Maciel, C.M.M.; Rumjanek, V.M.

    1986-01-01

    In a study of the in vivo effects of semi-purified mouse interleukin-2 (IL-2), inflammatory activity indicated by edema and plasma protein extravasation (PPE) was detected in those fractions having IL-2 activity. The molecular weight of the inflammatory factor activity from conditioned medium was 30 to 48 kDal on the basis of gel filtration on Sephadex G75. The edema, characterized as maximum paw thickness, occurred at 4 h, whereas the PPE peak (measured with 125 I-albumin) occurred 1.5 to 3 h after injection. Both edema and PPE were inhibited by dexamethasone or indomethacin, suggesting the involvement of prostaglandins in the process. This inflammatory activity may be partly responsible for some of the in vivo activities ascribed to IL-2. (author) [pt

  10. Apple, Cherry, and Blackcurrant Increases Nuclear Factor Kappa B Activation in Liver of Transgenic Mice

    DEFF Research Database (Denmark)

    Balstad, Trude; Paur, Ingvild; Poulsen, Morten

    2010-01-01

    Nuclear factor kappa B (NF-B) is essential in normal physiology, and several human disorders involve inappropriate regulation of NF-B. Diets dominated by plant-based foods protect against chronic diseases, and several food derived compounds have been identified as promising NF-B modulators. We...... investigated the effects of diets supplemented with apple, blackcurrant, or cherries on lipopolysaccharide (LPS)-induced NF-B activation in transgenic NF-B-luciferase mice. Whole body and organ specific NF-B activities were determined. The mice had ad libitum access to the respective experimental diets for 7...... slightly higher whole-body NF-B activation at 4 h, and all 3 experimental groups had higher NF-B activation at 6 h. LPS-induced NF-B activation in liver was increased with all 3 experimental diets, but no effects were observed in other organs. Our findings indicate that high intakes of lyophilized fruits...

  11. Urban-rural differences in physical activity in Belgian adults and the importance of psychosocial factors.

    Science.gov (United States)

    Dyck, Delfien Van; Cardon, Greet; Deforche, Benedicte; De Bourdeaudhuij, Ilse

    2011-02-01

    Recent research in urban planning and public health has drawn attention to the associations between urban form and physical activity in adults. Because little is known on the urban-rural differences in physical activity, the main aims of the present study were to examine differences in physical activity between urban and rural adults and to investigate the moderating effects of the physical environment on the relationship between psychosocial factors and physical activity. In Flanders, Belgium, five rural and five urban neighborhoods were selected. A sample of 350 adults (20-65 years of age; 35 adults per neighborhood) participated in the study. Participants wore a pedometer for 7 days, and self-reported physical activity and psychosocial data were also collected. Results showed that urban adults took more steps/day and reported more walking and cycling for transport in the neighborhood, more recreational walking in the neighborhood, and more walking for transportation outside the neighborhood than rural adults. Rural adults reported more recreational cycling in the neighborhoods. The physical environment was a significant moderator of the associations between several psychosocial factors (modeling from family, self-efficacy, and perceived barriers) and physical activity. In rural participants, adults with psychosocial scores above average were more physically active, whereas there were no differences in physical activity according to psychosocial factors in urban participants. These results are promising and plead for the development of multidimensional interventions, targeting specific population subgroups. In rural environments, where changing the environment would be a very challenging task, interventions focusing on modifiable psychosocial constructs could possibly be effective.

  12. [Placental gene activity of significant angiogenetic factors in the background of intrauterine growth restriction].

    Science.gov (United States)

    Kovács, Péter; Rab, Attila; Szentpéteri, Imre; Joó, József Gábor; Kornya, László

    2017-04-01

    Placental vascular endothelial growth factor A (VEGF-A) gene and endoglin gene are both overexpressed in placental samples obtained from pregnancies with intrauterine growth restriction compared to normal pregnancies. In the background of these changes a mechanism can be supposed, in which the increased endoglin activity in intrauterine growth restriction (IUGR) leads to impaired placental circulation through an antioangiogenetic effect. This results in the development of placental vascular dysfunction and chronic fetal hypoxia. It is chronic hypoxia that turns on VEGF-A as a compensatory mechanism to improve fetal vascular blood supply by promoting placental blood vessel formation. Although the maternal serum placental growth factor (PlGF) level is a potential predictor for both IUGR and praeeclampsia, placental PlGF gene activity may be less of an active in the regulation of placental circulation in IUGR pregnancies during the later stages of gestation. Orv. Hetil., 2017, 158(16), 612-617.

  13. The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43.

    OpenAIRE

    Hurst, H C; Masson, N; Jones, N C; Lee, K A

    1990-01-01

    Promoter elements containing the sequence motif CGTCA are important for a variety of inducible responses at the transcriptional level. Multiple cellular factors specifically bind to these elements and are encoded by a multigene family. Among these factors, polypeptides termed activating transcription factor 43 (ATF-43) and ATF-47 have been purified from HeLa cells and a factor referred to as cyclic AMP response element-binding protein (CREB) has been isolated from PC12 cells and rat brain. We...

  14. Hemistepsin A ameliorates acute inflammation in macrophages via inhibition of nuclear factor-κB and activation of nuclear factor erythroid 2-related factor 2.

    Science.gov (United States)

    Kim, Jae Kwang; Lee, Ji Eun; Jung, Eun Hye; Jung, Ji Yun; Jung, Dae Hwa; Ku, Sae Kwang; Cho, Il Je; Kim, Sang Chan

    2018-01-01

    Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata (Bunge) Bunge. We investigated the anti-inflammatory effects of HsA and sought to determine its mechanisms of action in macrophages. HsA pretreatment inhibited nitric oxide production, and reduced the expression of iNOS and COX-2 in Toll-like receptor ligand-stimulated RAW 264.7 cells. Additionally, HsA decreased the secretion of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated Kupffer cells as well as in RAW 264.7 cells. HsA inhibited phosphorylation of IKKα/β and degradation of IκBα, resulting in decreased nuclear translocation of nuclear factor-κB (NF-κB) and its transcriptional activity. Moreover, HsA phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2), increased expression levels of antioxidant genes, and attenuated LPS-stimulated H 2 O 2 production. Phosphorylation of p38 and c-Jun N-terminal kinase was required for HsA-mediated Nrf2 phosphorylation. In a D-galactosamine/LPS-induced liver injury model, HsA ameliorated D-galactosamine/LPS-induced hepatocyte degeneration and inflammatory cells infiltration. Moreover, immunohistochemical analyses using nitrotyrosine, 4-hydroxynonenal, and cleaved poly (ADP-ribose) polymerase antibodies revealed that HsA protected the liver from oxidative stress. Furthermore, HsA reduced the numbers of proinflammatory cytokine-positive cells in hepatic tissues. Thus, these results suggest HsA may be a promising natural product to manage inflammation-mediated tissue injuries through inhibition of NF-κB and activation of Nrf2. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. A new protein inhibitor of trypsin and activated Hageman factor from pumpkin (Cucurbita maxima) seeds.

    Science.gov (United States)

    Krishnamoorthi, R; Gong, Y X; Richardson, M

    1990-10-29

    A protein inhibitor (CMTI-V; Mr 7106) of trypsin and activated Hageman factor (Factor XIIa), a serine protease involved in blood coagulation, has been isolated for the first time from pumpkin (Cucurbita maxima) seeds by means of trypsin-affinity chromatography and reverse phase high performance liquid chromatography (HPLC). The dissociation constants of the inhibitor complexes with trypsin and Factor XIIa have been determined to be 1.6 x 10(-8) and 4.1 x 10(-8) M, respectively. The primary structure of CMTI-V is reported. The protein has 68 amino acid residues and one disulfide bridge and shows a high level of sequence homology to the Potato I inhibitor family. Furthermore, its amino terminus consists of an N-acetylates Ser. The reactive site has been established to be the peptide bond between Lys44-Asp45. The modified inhibitor which has the reactive site peptide bond hydrolyzed inhibits trypsin but not the Hageman factor.

  16. The Psychosocial Risk Factors in the Activity of the Advanced Technicians on Occupational Health

    Directory of Open Access Journals (Sweden)

    Joana F. Ramalho

    2017-12-01

    Full Text Available Social and organisational changes are causing deep transformations, which can generate quite concerning psychosocial dynamics in the work places. The “psychosocial risks” result from a set of conditions and factors inherent to the organisation of the work and it is important to identify them. This study's main purpose was to verify whether the Advanced Technicians on Occupational Health (ATOH who perform their activity in Portugal are exposed, or not, to psychosocial risk factors and whether, consequently, their health condition is deteriorating. The findings show they are exposed to psychosocial risk factors related to the work conditions and characteristics. Their health is perceived as good and not entirely work-related, though some of their health problems are made worse by the work. The less the ATOH are affected by the psychosocial risk factors, the better do they perceive their health.

  17. Muscle Atrophy Reversed by Growth Factor Activation of Satellite Cells in a Mouse Muscle Atrophy Model

    DEFF Research Database (Denmark)

    Hauerslev, Simon; Vissing, John; Krag, Thomas O

    2014-01-01

    mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.......Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory...... factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth...

  18. The relationship between postnatal depression, sociodemographic factors, levels of partner support, and levels of physical activity

    Directory of Open Access Journals (Sweden)

    Maryam eSaligeh

    2014-07-01

    Full Text Available Background: postnatal depression (PND is defined as a psychological mood disorder that occurs in a mother within six weeks of her giving birth. It refers to an episode that causes mood disturbance and it could begin in, or extend into, the postpartum period. It is thought to have a high impact upon the mother’s health as well as the family’s functioning and the child’s development. Socio-demographic, psych-social, and physical activity factors may all contribute to postpartum mood and ability to cope with responsibilities. The primary aim of this study was to determine which of these factors predicted PND in postpartum women. A secondary aim was to identify the socio-demographic and psycho-social predictors of physical activity in postpartum women . Methods: The study used a cross-sectional correlational design. A sample of 150 postpartum women was sent a package of six standardised questionnaires. Results: There was no association between physical activity and PND; however, older mothers, mothers of younger children, mothers who are less reluctant to ask for help, and mothers who are more satisfied with the help they get experience lower levels of PND. Mothers of older babies, mothers with more children, and less educated mothers are more likely to engage in caregiving activities, whereas mothers with fewer children and higher levels of partner support are more likely to engage in occupational activities. None of the socio-demographic factors or any of the parenting factors predicted levels of sporting activity.

  19. Stimulation of LDL receptor activity in Hep-G2 cells by a serum factor(s)

    International Nuclear Information System (INIS)

    Ellsworth, J.L.; Brown, C.; Cooper, A.D.

    1988-01-01

    The regulation of low-density lipoprotein (LDL) receptor activity in the human hepatoma cell line Hep-G2 by serum components was examined. Incubation of dense monolayers of Hep-G2 cells with fresh medium containing 10% fetal calf serum (FM) produced a time-dependent increase in LDL receptor activity. Uptake and degradation of 125I-LDL was stimulated two- to four-fold, as compared with that of Hep-G2 cells cultured in the same media in which they had been grown to confluence (CM); the maximal 125I-LDL uptake plus degradation increased from 0.2 microgram/mg cell protein/4 h to 0.8 microgram/mg cell protein/4 h. In addition, a two-fold increase in cell surface binding of 125I-LDL to Hep-G2 cells was observed when binding was measured at 4 degrees C. There was no change in the apparent Kd. The stimulation of LDL receptor activity was suppressed in a concentration-dependent manner by the addition of cholesterol, as LDL, to the cell medium. In contrast to the stimulation of LDL receptor activity, FM did not affect the uptake or degradation of 125I-asialoorosomucoid. Addition of FM increased the protein content per dish, and DNA synthesis was stimulated approximately five-fold, as measured by [3H]thymidine incorporation into DNA; however, the cell number did not change. Cellular cholesterol biosynthesis was also stimulated by FM; [14C]acetate incorporation into unesterified and esterified cholesterol was increased approximately five-fold. Incubation of Hep-G2 cells with high-density lipoproteins (200 micrograms protein/ml) or albumin (8.0 mg/ml) in the absence of the serum factor did not significantly increase the total processed 125I-LDL. Stimulation of LDL receptor activity was dependent on a heat-stable, nondialyzable serum component that eluted in the inclusion volume of a Sephadex G-75 column

  20. Effect of Robola and Cabernet Sauvignon extracts on platelet activating factor enzymes activity on U937 cells.

    Science.gov (United States)

    Xanthopoulou, M N; Asimakopoulos, D; Antonopoulou, S; Demopoulos, C A; Fragopoulou, E

    2014-12-15

    A number of studies support the anti-atherogenic effect of wine compounds. The scope of this study was to examine the effect of a red (Cabernet Sauvignon-CS) and a white (Robola-R) wine, as well as resveratrol and quercetin, on the platelet activating factor (PAF) biosynthetic enzymes, acetyl-CoA:lyso-PAF acetyltransferase (lyso-PAF-AT) and DTT-insensitive CDP-choline 1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT), and its main catabolic enzyme (PAF acetylhydrolase; PAF-AH), on U937 cells, in cell free and in intact cell experiments. In cell free experiments, phenolic compounds and wine extracts inhibited PAF biosynthetic enzymes, however in higher concentrations than intact cell experiments. In the latter cases, polar lipids of both wines inhibited in the same order of magnitude the action of lyso-PAF-AT and of PAF-CPT. The water fractions possessed a dual action, in lower concentrations they activated both enzymes, while in higher concentrations only inhibited PAF-CPT. All fractions either did not affect or slightly activated PAF-AH activity. In conclusion, wine compounds may exert their anti-inflammatory activity by reducing PAF levels through modulation of the PAF metabolic enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Preparation of Gc protein-derived macrophage activating factor (GcMAF) and its structural characterization and biological activities.

    Science.gov (United States)

    Mohamad, Saharuddin Bin; Nagasawa, Hideko; Uto, Yoshihiro; Hori, Hitoshi

    2002-01-01

    Gc protein has been reported to be a precursor of Gc protein-derived macrophage activation factor (GcMAF) in the inflammation-primed macrophage activation cascade. An inducible beta-galactosidase of B cells and neuraminidase of T cells convert Gc protein to GcMAF. Gc protein from human serum was purified using 25(OH)D3 affinity column chromatography and modified to GcMAF using immobilized glycosidases (beta-galactosidase and neuraminidase) The sugar moiety structure of GcMAF was characterized by lectin blotting by Helix pomatia agglutinin. The biological activities of GcMAF were evaluated by a superoxide generation assay and a phagocytosis assay. We successfully purified Gc protein from human serum. GcMAF was detected by lectin blotting and showed a high biological activity. Our results support the importance of the terminal N-acetylgalactosamine moiety in the GcMAF-mediated macrophage activation cascade, and the existence of constitutive GcMAF in human serum. These preliminary data are important for designing small molecular GcMAF mimics.

  2. Macroenvironmental factors including GDP per capita and physical activity in Europe.

    Science.gov (United States)

    Cameron, Adrian J; Van Stralen, Maartje M; Kunst, Anton E; Te Velde, Saskia J; Van Lenthe, Frank J; Salmon, Jo; Brug, Johannes

    2013-02-01

    Socioeconomic inequalities in physical activity at the individual level are well reported. Whether inequalities in economic development and other macroenvironmental variables between countries are also related to physical activity at the country level is comparatively unstudied. We examined the relationship between country-level data on macroenvironmental factors (gross domestic product (GDP) per capita, public sector expenditure on health, percentage living in urban areas, and cars per 1000 population) with country-level physical activity prevalence obtained from previous pan-European studies. Studies that assessed leisuretime physical activity (n = 3 studies including 27 countries in adults, n = 2 studies including 28 countries in children) and total physical activity (n = 3 studies in adults including 16 countries) were analyzed separately as were studies among adults and children. Strong and consistent positive correlations were observed between country prevalence of leisure-time physical activity and country GDP per capita in adults (average r = 0.70; all studies, P G 0.05). In multivariate analysis, country prevalence of leisure-time physical activity among adults remained associated with country GDP per capita (two of three studies) but not urbanization or educational attainment. Among school-age populations, no association was found between country GDP per capita and country prevalence of leisure-time physical activity. In those studies that assessed total physical activity (which also includes occupational and transport physical activity), no association with country GDP per capita was observed. Clear differences in national leisure-time physical activity levels throughout Europe may be a consequence of economic development. Lack of economic development of some countries in Europe may make increasing leisure-time physical activity more difficult. Further examination of the link between country GDP per capita and national physical activity levels (across

  3. Practice of walking, moderate and vigorous physical activity and associated factors in first year undergraduate students

    Directory of Open Access Journals (Sweden)

    Gaia Salvador Claumann

    2014-12-01

    Full Text Available The changes that occur with the beginning of university life may interfere with the practice of physical activities by students. The aim was to investigate the association between the practice of walking, moderate and vigorous physical activities with sociodemographic factors and weight status in freshman students in the first semester of the first year of a public university in Florianopolis/SC. This study assessed198 students (86 men and 112 women. The practice of physical activities was collected with the International Physical Activity Questionnaire – IPAQ, short version. Students of human and educational sciences reported higher amounts of moderate physical activity when compared to health and exact science counterparts (p< 0.05. It was verified that male students, from higher economic status, from the health sciences, and full-time students showed higher time of practice of vigorous physical activity (p< 0.05. Significant associations were also observed between study period and walking, and between gender, scientific field and vigorous physical activity. It was concluded that the variables associated with the practice of physical activity differ according to the type and intensity of physical activity.

  4. Leisure-time physical activity and associated factors in fitness zones

    Directory of Open Access Journals (Sweden)

    Marcelo Cozzensa da Silva

    2017-05-01

    Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2017v19n2p185   Fitness zones (FZ are a great alternative to physical activity practice. The aim of this study was verify physical activity practice and associated factors among FZ users of Pelotas. Participants answered a questionnaire containing demographic, socioeconomic, behavioral, health and on the use of FZs. A long version of the International Physical Activity Questionnaire was used to determine the level of physical activity and those who reported at least 150 minutes / week of PA in the leisure time were considered sufficiently active. The study included 323 subjects (65.3% women, mean age 52.5 years, 83.6% white skin color and 61.9% married. Almost half of respondents were overweight (48.0%, 45.8% had high blood pressure, 10.5% had diabetes and 64.4% used medications. About 77.7% of respondents were classified as sufficiently active. Health perception was associated to leisure physical activity, and the better the health perception, the higher the prevalence of sufficient physical activity. Collective programs with participation of Physical Education teacher can contribute to interaction of practitione with the use of fitness zones and increase the level of physical activity of individuals.

  5. Factors related to rural young adolescents' participation in outdoor, noncompetitive physical activity.

    Science.gov (United States)

    Christiana, Richard W; Davis, Marsha; Wilson, Mark G; McCarty, Frances A; Green, Gary T

    2014-12-01

    Young adolescents who have little interest in participating in competitive team sports are at an increased risk for physical inactivity. Noncompetitive outdoor physical activity can provide young adolescents with increased opportunities to participate in physical activities that appeal to them and have positive health effects. The purpose of this study was to examine factors related to rural young adolescents' participation in noncompetitive outdoor physical activity to inform intervention design. Young adolescents aged 10 to 14 years old (N = 1,032) from 1 rural county completed a self-administered questionnaire assessing constructs from self-determination theory (SDT) and the theory of planned behavior (TPB) related to noncompetitive outdoor physical activity. Structural equation modeling was used to examine an integrated conceptual model of hypothesized relationships among constructs. The hypothesized conceptual model provided a good fit to the data with greater perceptions of autonomy support and self-determined motivation having statistically significant positive indirect effects on participation in noncompetitive outdoor physical activity mediated by the constructs of the TPB. All direct paths in the model were statistically significant; however, the direct effect of attitudes on intention was weak (.08) and self-determined motivation had no indirect effect on intention through attitudes (.03). Constructs of SDT and TPB should be accounted for by interventions targeting noncompetitive outdoor physical activity among young adolescents. More research is needed to determine young adolescents' preferences for noncompetitive and competitive physical activity and the potential influence that noncompetitive outdoor physical activity may have on total daily physical activity.

  6. Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site-Inhibited Factor VII.

    Science.gov (United States)

    Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E; Jensen, Mette M; Kristensen, Lotte K; Madsen, Jacob; Petersen, Lars C; Kjaer, Andreas

    2016-01-01

    Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of factor VII. Active site-inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-(18)F-fluorobenzoate and purified. The corresponding product, (18)F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of (18)F-FVIIai in the tumors measured in vivo by PET imaging. The PET images showed high uptake of (18)F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3-9.3 MBq of (18)F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of (18)F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P < 0.001). The uptake of (18)F-FVIIai measured in vivo by PET imaging correlated (r = 0.72, P < 0.02) with TF protein level measured ex vivo. (18)F-FVIIai is a promising PET tracer for

  7. CORRELATION BETWEEN PREEXPONENTIAL FACTOR AND ACTIVATION ENERGY OF ISOAMYLALCOHOL HYDROGENOLYSIS ON PLATINUM CATALYSTS

    Directory of Open Access Journals (Sweden)

    Triyono Triyono

    2010-06-01

    Full Text Available Arrhenius equation stated that reaction will proceed faster at higher temperature and with lower activation energy (Ea. Many literatures reported that preexponential factor (A is constant for certain reaction and there is no relation between A and Ea. Experiment on the reaction of isoamylalcohol hydrogenolysis showed that logarithm of A increased linearly with Ea. The result of this investigation suggests that the rate of a process is affected by the number of active centers on the surface of a catalysts, which influences the value of the pre-exponential term in the expression for the rate constant of a reaction. An increase in the number of active centers corresponds to a higher value of A, the active centers would be less effective and is attended by a growth in the value of Ea. Therefore, reaction with lower activation energy will not always has higher reaction rate due to decreasing of Ea.   Keywords: isoamylalcohol hydrogenolysis, preexponential factor, activation  energy.

  8. [Adsorbent effect of activated carbon on small molecular uremic toxin and its influence factors].

    Science.gov (United States)

    Yang, Bo; Jiang, Yun-sheng; Li, Jun

    2003-06-01

    To analyze the adsorbent effect of activated carbon on uremic toxin and its influence factors. Uremic toxins (urea, creatinine and uric acid) were dissolved in the distilled water to obtain uremic toxic solution. Activated carbon was added to the solution, and the concentrations of uremic toxins were measured at different time spots. To determine the influence factors, some possible related materials, such as bile, amino acid, Ringer's, solution of glucose, HCl or NaOH respectively were added simultaneously. The concentrations of toxins in uremic toxic solution decreased 5 min after adding the activated carbon. The concentration of urea was the lowest at 30 min, but it increased after 50 min; while the concentrations of creatinine and uric acid reached the lowest level from 10 to 30 min after adding the activated carbon, and maintained at the same level after that. The bile, amino acid, electrolyte, glucose and pH value did not influence the adsorption of uric acid significantly, but they influenced the adsorption of urea and creatinine. Bile and amino acid influenced the concentration of urea remarkably, following glucose, NaOH and HCl. The effect of pH 2.0 solution on the creatinine concentration was the most significant, following glucose. Activated carbon has adsorptive effect on uremic toxins, but its adsorptive effect decreases as time goes on. Bile, glucose, amino acid, NaOH and HCl can affect the adsorptive effect of activated carbon on uremic toxins to some extent.

  9. Factors associated with non-reimbursable activity on an inpatient pediatric consultation-liaison service.

    Science.gov (United States)

    Bierenbaum, Melanie L; Katsikas, Steven; Furr, Allen; Carter, Bryan D

    2013-12-01

    The aim of this study was to identify factors contributing to clinician time spent in non-reimbursable activity on an inpatient pediatric consultation-liaison (C-L) service. A retrospective study was conducted using inpatient C-L service data on 1,246 consecutive referrals. For this patient population, the strongest predictor of level of non-reimbursable clinical activity was illness chronicity and the number of contacts with C-L service clinicians during their hospital stay. Patients with acute life-threatening illnesses required the highest mean amount of non-reimbursable service activity. On average, 28 % of total clinician time in completing a hospital consultation was spent in non-reimbursable activity. Effective C-L services require a proportion of time spent in non-reimbursable clinical activity, such as liaison and coordinating care with other providers. Identifying referral and systemic factors contributing to non-reimbursable activity can provide insight into budgeting/negotiating for institutional support for essential clinical and non-clinical functions in providing competent quality patient care.

  10. Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells

    International Nuclear Information System (INIS)

    Nakajima, Hideaki; Shibata, Fumi; Fukuchi, Yumi; Goto-Koshino, Yuko; Ito, Miyuki; Urano, Atsushi; Nakahata, Tatsutoshi; Aburatani, Hiroyuki; Kitamura, Toshio

    2006-01-01

    Immune suppressor factor (ISF) is a subunit of the vacuolar ATPase proton pump. We earlier identified a short form of ISF (ShIF) as a stroma-derived factor that supports cytokine-independent growth of mutant Ba/F3 cells. Here, we report that ISF/ShIF supports self-renewal and expansion of primary hematopoietic stem cells (HSCs). Co-culture of murine bone marrow cells with a stromal cell line overexpressing ISF or ShIF (MS10/ISF or MS10/ShIF) not only enhanced their colony-forming activity and the numbers of long-term culture initiating cells, but also maintained the competitive repopulating activity of HSC. This stem cell supporting activity depended on the proton-transfer function of ISF/ShIF. Gene expression analysis of ISF/ShIF-transfected cell lines revealed down-regulation of secreted frizzled-related protein-1 and tissue inhibitor of metalloproteinase-3, and the restoration of their expressions in MS10/ISF cells partially reversed its enhanced LTC-IC supporting activity to a normal level. These results suggest that ISF/ShIF confers stromal cells with enhanced supporting activities for HSCs by modulating Wnt-activity and the extracellular matrix

  11. [Determinants of the elevated factor VIII activity in patients following venous thromboembolism].

    Science.gov (United States)

    Lech, Monika; Kościelniak, Barbara; Bryk, Agata; Undas, Anetta

    2016-01-01

    Activity of factor VIII (FVIII) increased above 150% of reference range predisposes to venous thromboembolism (VTE). The aim of this study was to identify predictors of increased FVIII activity in patients following VTE. 241 (38% men) patients presented due to objectively documented VTE episode at least 3 months ago were included in this study. FVIII activity was measured using a clotting assay on the analyzer BCS XP. Among 241 patients with VTE, activity of FVIII above 150% (FVIII ≥ 150%) was observed in 96 (40%). These patients were older (p = 0.035) and their concentrations of fibrinogen and C-reactive protein (CRP) were higher by 12% and 88% (p 200%) and this group was also older (p = 0.015), more patients in that group had obesity (p = 0.015), idiopathic VTE (p = 0.043), less of them had positive family history (p = 0.010) and they were characterized by fibrinogen and CRP increased by 28% (p 200% (p = 0.016). The activity of FVIII in patients after VTE episode is influenced by age, concentration of fibrinogen, bilirubin, hemoglobin, glucose, CRP and homocysteine. Our results suggest the role of environmental factors, mainly inflammatory response in maintaining elevated FVIII activity following VTE.

  12. New Insights into Butyrylcholinesterase Activity Assay: Serum Dilution Factor as a Crucial Parameter.

    Directory of Open Access Journals (Sweden)

    Joanna Jońca

    Full Text Available Butyrylcholinesterase (BChE activity assay and inhibitor phenotyping can help to identify patients at risk of prolonged paralysis following the administration of neuromuscular blocking agents. The assay plays an important role in clinical chemistry as a good diagnostic marker for intoxication with pesticides and nerve agents. Furthermore, the assay is also commonly used for in vitro characterization of cholinesterases, their toxins and drugs. There is still lack of standardized procedure for measurement of BChE activity and many laboratories use different substrates at various concentrations. The purpose of this study was to validate the BChE activity assay to determine the best dilution of human serum and the most optimal concentration of substrates and inhibitors. Serum BChE activity was measured using modified Ellman's method applicable for a microplate reader. We present our experience and new insights into the protocol for high-throughput routine assays of human plasma cholinesterase activities adapted to a microplate reader. During our routine assays used for the determination of BChE activity, we have observed that serum dilution factor influences the results obtained. We show that a 400-fold dilution of serum and 5mM S-butyrylthiocholine iodide can be successfully used for the accurate measurement of BChE activity in human serum. We also discuss usage of various concentrations of dibucaine and fluoride in BChE phenotyping. This study indicates that some factors of such a multicomponent clinical material like serum can influence kinetic parameters of the BChE. The observed inhibitory effect is dependent on serum dilution factor used in the assay.

  13. Recombinant activated factor VII: its mechanism of action and role in the control of hemorrhage.

    Science.gov (United States)

    Allen, Geoffrey A; Hoffman, Maureane; Roberts, Harold R; Monroe, Dougald M

    2002-12-01

    Recombinant activated factor VII (rFVIIa) has proven both safe and efficacious in the treatment of bleeding episodes in patients with hemophilia A or B who have developed inhibitors. More recently, a growing number of reports suggests that rFVIIa may also have indications for the treatment of bleeding in patients with other hemostatic disorders, including qualitative and quantitative platelet defects, factor deficiencies other than hemophilia, and in otherwise healthy patients with uncontrollable hemorrhage following surgery or trauma. We have attempted to reconcile the various proposed mechanisms of action of rFVIIa with its apparent efficacy in such diverse clinical settings. A review of the literature was performed to determine those clinical scenarios in which rFVIIa appears to have been effective in controlling associated hemorrhage. Findings from our group and others have demonstrated that rFVIIa is able to directly activate factor X and increase thrombin production on the surface of activated platelets in the absence of factor VIII or IX, as well as to improve thrombin generation in thrombocytopenia, and to yield a fibrin dot more resistant to fibrinolysis in vitro. Through these primary mechanisms, we believe that rFVIIa may be able to compensate for a variety of defects in hemostasis and merits further investigation as a general therapeutic for uncontrollable hemorrhage.

  14. Characterization of emission factors related to source activity for trichloroethylene degreasing and chrome plating processes.

    Science.gov (United States)

    Wadden, R A; Hawkins, J L; Scheff, P A; Franke, J E

    1991-09-01

    A study at an automotive parts fabrication plant evaluated four metal surface treatment processes during production conditions. The evaluation provides examples of how to estimate process emission factors from activity and air concentration data. The processes were open tank and enclosed tank degreasing with trichloroethylene (TCE), chromium conversion coating, and chromium electroplating. Area concentrations of TCE and chromium (Cr) were monitored for 1-hr periods at three distances from each process. Source activities at each process were recorded during each sampling interval. Emission rates were determined by applying appropriate mass balance models to the concentration patterns around each source. The emission factors obtained from regression analysis of the emission rate and activity data were 16.9 g TCE/basket of parts for the open-top degreaser; 1.0 g TCE/1000 parts for the enclosed degreaser; 1.48-1.64 mg Cr/1000 parts processed in the hot CrO3/HNO3 tank for the chrome conversion coating; and 5.35-9.17 mg Cr/rack of parts for chrome electroplating. The factors were also used to determine the efficiency of collection for the local exhaust systems serving each process. Although the number of observations were limited, these factors may be useful for providing initial estimates of emissions from similar processes in other settings.

  15. Synthesis and characterization of (18)F-labeled active site inhibited factor VII (ASIS).

    Science.gov (United States)

    Erlandsson, Maria; Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Jesper B; Petersen, Lars C; Madsen, Jacob; Kjaer, Andreas

    2015-05-15

    Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an (18)F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[(18)F]fluorobenzoate, and the [(18)F]ASIS was purified on a PD-10 desalting column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [(18)F]ASIS to TF and to a specific anti-factor VII antibody (F1A2-mAb). No significant difference in binding efficacy between [(18)F]ASIS and ASIS could be detected. Furthermore, [(18)F]ASIS was relatively stable in vitro and in vivo in mice. In conclusion, [(18)F]ASIS has for the first time been successfully synthesized as a possible positron emission tomography tracer to image TF expression levels. In vivo positron emission tomography studies to evaluate the full potential of [(18)F]ASIS are in progress. Copyright © 2015 John Wiley & Sons, Ltd.

  16. [Musical Inactivity - A Risk Factor? A Short Questionnaire to Assess Musical Activity (MusA)].

    Science.gov (United States)

    Fernholz, Isabel; Menzel, Juliane; Jabusch, Hans-Christian; Gembris, Heiner; Fischer, Felix; Kendel, Friederike; Kreutz, Gunter; Schmidt, Alexander; Willich, Stefan N; Weikert, Cornelia

    2018-02-27

    There is only a limited number of studies on associations between musical activity and health issues. It seems that musical activity has physiological and psychological benefits, as well as effects on the mental capacity, but this has been studied only in a few clinical and epidemiological studies. One reason might be that no appropriate survey instrument assessing musical activity is available. Here we provide an overview of survey instruments that assess musicality and musical activity. One focus is the presentation of a newly developed German questionnaire (MusA), which assesses musical activity (active music making and music reception) and was specifically developed for the "German National Cohort", a German health study. Through literature research, questionnaires were identified that assess musicality and / or musical activity. A new German questionnaire was developed from a panel of experts and tested in a small study (n=121, women and men age 18-70 years). In the literature research, 3 questionnaires were identified which focus on musicality and musical activity with different aspects (Gold-MSI, MUSE, MEQ). All 3 instruments may be characterized as large psychometric scales, which especially assess aspects of musicality in the English language. The Gold-MSI is additionally available in German. None of the existing questionnaires covers musical activities in detail. A new short German questionnaire consisting of 9 questions with a maximum filling time of 3-5 min has been developed. There are few questionnaires available for assessing musicality and musical activity with different aspects. The newly developed MusA in the German language focuses on the assessment of musical activity and is intended to be used in larger, population-based as well as clinical studies, to examine music activities and listening to music as independent factors in connection with prevention and therapy of chronic diseases. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Effect of water quality and confounding factors on digestive enzyme activities in Gammarus fossarum.

    Science.gov (United States)

    Charron, L; Geffard, O; Chaumot, A; Coulaud, R; Queau, H; Geffard, A; Dedourge-Geffard, O

    2013-12-01

    The feeding activity and subsequent assimilation of the products resulting from food digestion allow organisms to obtain energy for growth, maintenance and reproduction. Among these biological parameters, we studied digestive enzymes (amylase, cellulase and trypsin) in Gammarus fossarum to assess the impact of contaminants on their access to energy resources. However, to enable objective assessment of a toxic effect of decreased water quality on an organisms' digestive capacity, it is necessary to establish reference values based on its natural variability as a function of changing biotic and abiotic factors. To limit the confounding influence of biotic factors, a caging approach with calibrated male organisms from the same population was used. This study applied an in situ deployment at 23 sites of the Rhone basin rivers, complemented by a laboratory experiment assessing the influence of two abiotic factors (temperature and conductivity). The results showed a small effect of conductivity on cellulase activity and a significant effect of temperature on digestive enzyme activity but only at the lowest temperature (7 °C). The experimental conditions allowed us to define an environmental reference value for digestive enzyme activities to select sites where the quality of the water impacted the digestive capacity of the organisms. In addition to the feeding rate, this study showed the relevance of digestive enzymes as biomarkers to be used as an early warning tool to reflect organisms' health and the chemical quality of aquatic ecosystems.

  18. Risk and Protective Factors for Sudden Cardiac Death During Leisure Activities in the Mountains: An Update.

    Science.gov (United States)

    Burtscher, Martin

    2017-08-01

    Annually, more than 100 million tourists with widely varying health and fitness status are attracted by the mountainous areas around the world. Whereas mountaineering activities may contribute to the well established beneficial effects of regular exercise, for certain individuals these activities are also associated with a relatively high risk of death. This manuscript presents an updated overview of risk and protective factors for sudden cardiac death during leisure activities in the mountains. Sudden cardiac death (SCD) has been proven to be the most frequent cause of non traumatic death in males aged over 34 years, e.g. during mountain hiking, cross country skiing or downhill skiing. Risk factors for cardiovascular diseases and, in particular, prior myocardial infarction, are the most important risk factors for SCD, predominantly relevant in downhill skiers. The unusual physical exertion on the first day at altitude, the late morning hours and the prolonged abstinence from food and fluid intake during exercise at altitude are most important triggers. Acute hypoxia may represent a trigger for SCD on the one hand but might also evoke beneficial effects by preconditioning on the other hand. The identification of high-risk subjects and SCD triggers, evidence-based therapy of treatable risk factors, the appropriate individual preparation by physical training, and considering behavioural aspects, especially at the beginning of the physically active altitude sojourn will help to prevent SCD and increase the health benefits generated by mountaineering activities. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  19. The impact of physical activity on cumulative cardiovascular disease risk factors among Malaysian adults.

    Science.gov (United States)

    Rasiah, Rajah; Thangiah, Govindamal; Yusoff, Khalid; Manikam, Rishya; Chandrasekaran, Sankara Kumar; Mustafa, Rujhan; Bakar, Najmin Binti Abu

    2015-12-16

    Numerous studies have shown the importance of physical activity in reducing the morbidity and mortality rates caused by cardiovascular disease (CVD). However, most of these studies emphasise little on the cumulative effect of CVD risk factors. Hence, this study investigates the association between physical exercise and cumulative CVD risk factors among adults in three different age groups. Using a sample of 7276 respondents drawn from community centers, the REDISCOVER team gathered information on physical activity, CVD risk factors (obesity, diabetes, hypertension, hypercholesterolemia, tobacco use) and socioeconomic and demographic variables in Malaysia. Because the study required medical examination, a convenience sampling frame was preferred in which all volunteers were included in the study. Fasting blood samples and anthropometric (height, weight and more) measurements were collected by trained staffs. Socio-demographic and physical activity variables were recorded through questionnaires. A Chi-square test was performed to identify the bivariate association between the covariates (socioeconomic variables, demographic variables and physical activity) and outcome variable. The association between the main exposure, physical activity, and the outcome variable, cumulative CVD risk factors, was assessed using an ordinal logistic regression model, controlling for socioeconomic status and demographic influences in three different age groups, 35-49, 50-64 and 65 and above. The mean age of participants is 51.8 (SD = 9.4). Respondents in the age groups of 35-49 (aORmoderate = 0.12; 95 % CI: 0.02 - 0.53 ) and 65 and above (aORhigh = 0.58; 95 % CI: 0.24, 0.78) showed a statistically significant inverse relationship between physical activity and cumulative CVD risk factors. However, this relationship was not significant among respondents in the 50-64 age group suggesting the possible influence of other variables, such as stress and environment. The

  20. Factors That Influence Park Use and Physical Activity in Predominantly Hispanic and Low-Income Neighborhoods.

    Science.gov (United States)

    Dolash, Karry; He, Meizi; Yin, Zenong; Sosa, Erica T

    2015-04-01

    Park features' association with physical activity among predominantly Hispanic communities is not extensively researched. The purpose of this study was to assess factors associated with park use and physical activity among park users in predominantly Hispanic neighborhoods. Data were collected across 6 parks and included park environmental assessments to evaluate park features, physical activity observations to estimate physical activity energy expenditure as kcal/kg/ minute per person, and park user interviews to assess motivators for park use. Quantitative data analysis included independent t tests and ANOVA. Thematic analysis of park user interviews was conducted collectively and by parks. Parks that were renovated had higher physical activity energy expenditure scores (mean = .086 ± .027) than nonrenovated parks (mean = .077 ± .028; t = -3.804; P motivation to be physically active, using the play spaces in the park, parks as the main place for physical activity, and social support for using parks. Renovations to park amenities, such as increasing basketball courts and trail availability, could potentially increase physical activity among low-socioeconomic-status populations.

  1. Factors Predicting the Physical Activity Behavior of Female Adolescents: A Test of the Health Promotion Model

    Directory of Open Access Journals (Sweden)

    Hashem Mohamadian

    2014-01-01

    Full Text Available ObjectivesPhysical activity behavior begins to decline during adolescence and continues to decrease throughout young adulthood. This study aims to explain factors that influence physical activity behavior in a sample of female adolescents using a health promotion model framework.MethodsThis cross-sectional survey was used to explore physical activity behavior among a sample of female adolescents. Participants completed measures of physical activity, perceived self-efficacy, self-esteem, social support, perceived barriers, and perceived affect. Interactions among the variables were examined using path analysis within a covariance modeling framework.ResultsThe final model accounted for an R2 value of 0.52 for physical activity and offered a good model-data fit. The results indicated that physical activity was predicted by self-esteem (β=0.46, p<0.001, perceived self-efficacy (β=0.40, p<0.001, social support (β=0.24, p<0.001, perceived barriers (β=-0.19, p<0.001, and perceived affect (β=0.17, p<0.001.ConclusionsThe findings of this study showed that the health promotion model was useful to predict physical activity behavior among the Iranian female adolescents. Information related to the predictors of physical activity behavior will help researchers plan more tailored culturally relevant health promotion interventions for this population.

  2. Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF.

    Science.gov (United States)

    Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki

    2008-07-01

    Serum Gc protein (known as vitamin D(3)-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years.

  3. Epidemiology of leisure, transportation, occupational, and household physical activity: prevalence and associated factors.

    Science.gov (United States)

    Florindo, Alex Antonio; Guimarães, Vanessa Valente; Cesar, Chester Luiz Galvão; Barros, Marilisa Berti de Azevedo; Alves, Maria Cecília Goi Porto; Goldbaum, Moisés

    2009-09-01

    To estimate the prevalence of and identify factors associated with physical activity in leisure, transportation, occupational, and household settings. This was a cross-sectional study aimed at investigating living and health conditions among the population of São Paulo, Brazil. Data on 1318 adults aged 18 to 65 years were used. To assess physical activity, the long version of the International Physical Activity Questionnaire was applied. Multivariate analysis was conducted using a hierarchical model. The greatest prevalence of insufficient activity related to transportation (91.7%), followed by leisure (77.5%), occupational (68.9%), and household settings (56.7%). The variables associated with insufficient levels of physical activity in leisure were female sex, older age, low education level, nonwhite skin color, smoking, and self-reported poor health; in occupational settings were female sex, white skin color, high education level, self-reported poor health, nonsmoking, and obesity; in transportation settings were female sex; and in household settings, with male sex, separated, or widowed status and high education level. Physical activity in transportation and leisure settings should be encouraged. This study will serve as a reference point in monitoring different types of physical activities and implementing public physical activity policies in developing countries.

  4. CSK negatively regulates nerve growth factor induced neural differentiation and augments AKT kinase activity

    International Nuclear Information System (INIS)

    Dey, Nandini; Howell, Brian W.; De, Pradip K.; Durden, Donald L.

    2005-01-01

    Src family kinases are involved in transducing growth factor signals for cellular differentiation and proliferation in a variety of cell types. The activity of all Src family kinases (SFKs) is controlled by phosphorylation at their C-terminal 527-tyrosine residue by C-terminal SRC kinase, CSK. There is a paucity of information regarding the role of CSK and/or specific Src family kinases in neuronal differentiation. Pretreatment of PC12 cells with the Src family kinase inhibitor, PP1, blocked NGF-induced activation of SFKs and obliterated neurite outgrowth. To confirm a role for CSK and specific isoforms of SFKs in neuronal differentiation, we overexpressed active and catalytically dead CSK in the rat pheochromocytoma cell line, PC12. CSK overexpression caused a profound inhibition of NGF-induced activation of FYN, YES, RAS, and ERK and inhibited neurite outgrowth, NGF-stimulated integrin-directed migration and blocked the NGF-induced conversion of GDP-RAC to its GTP-bound active state. CSK overexpression markedly augmented the activation state of AKT following NGF stimulation. In contrast, kinase-dead CSK augmented the activation of FYN, RAS, and ERK and increased neurite outgrowth. These data suggest a distinct requirement for CSK in the regulation of NGF/TrkA activation of RAS, RAC, ERK, and AKT via the differential control of SFKs in the orchestration of neuronal differentiation

  5. Factors influencing the adoption, implementation, and continuation of physical activity interventions in primary health care: A Delphi study

    NARCIS (Netherlands)

    Huijg, J.M.; Crone, M.R.; Verheijden, M.W.; Zouwe, N. van der; Middelkoop, B.J.; Gebhardt, W.A.

    2013-01-01

    Background: The introduction of efficacious physical activity interventions in primary health care is a complex process. Understanding factors influencing the process can enhance the development of effective introduction strategies. This Delphi study aimed to identify factors most relevant for the

  6. HELLP Syndrome and Cerebral Venous Sinus Thrombosis Associated with Factor V Leiden Mutation during Pregnancy

    Directory of Open Access Journals (Sweden)

    Zeynep Ozcan Dag

    2014-01-01

    Full Text Available Preeclampsia is a leading cause of maternal mortality and morbidity worldwide. The neurological complications of preeclampsia and eclampsia are responsible for a major proportion of the morbidity and mortality for women and their infants alike. Hormonal changes during pregnancy and the puerperium carry an increased risk of venous thromboembolism including cerebral venous sinus thrombosis (CVST. Factor 5 leiden (FVL is a procoagulant mutation associated primarily with venous thrombosis and pregnancy complications. We report a patient with FVL mutation who presented with CVST at 24th week of pregnancy and was diagnosed as HELLP syndrome at 34th week of pregnancy.

  7. Factors affecting release of ethanol vapour in active modified atmosphere packaging systems for horticultural products

    Directory of Open Access Journals (Sweden)

    Weerawate Utto

    2014-04-01

    Full Text Available The active modified atmosphere packaging (active MAP system , which provides interactive postharvest control , using ethanol vapour controlled release, is one of the current interests in the development of active packaging for horticultural products. A number of published research work have discussed the relationship between the effectiveness of ethanol vapour and its concentration in the package headspace, including its effect on postharvest decay and physiological controls. This is of importance because a controlled release system should release and maintain ethanol vapour at effective concentrations during the desired storage period. A balance among the mass transfer processes of ethanol vapour in the package results in ethanol vapour accumulation in the package headspace. Key factors affecting these processes include ethanol loading, packaging material, packaged product and storage environment (temperature and relative h umidity. This article reviews their influences and discusses future work required to better understand their influences on ethanol vapour release and accumulations in active MAP.

  8. Resveratrol Reactivates Latent HIV through Increasing Histone Acetylation and Activating Heat Shock Factor 1.

    Science.gov (United States)

    Zeng, Xiaoyun; Pan, Xiaoyan; Xu, Xinfeng; Lin, Jian; Que, Fuchang; Tian, Yuanxin; Li, Lin; Liu, Shuwen

    2017-06-07

    The persistence of latent HIV reservoirs presents a significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural phytoalexin resveratrol has been demonstrated to enhance HIV gene expression, although its mechanism remains unclear. In this study, we demonstrated that resveratrol was able to reactivate latent HIV without global T cell activation in vitro. Mode of action studies showed resveratrol-mediated reactivation from latency did not involve the activation of silent mating type information regulation 2 homologue 1 (SIRT1), which belonged to class-3 histone deacetylase (HDAC). However, latent HIV was reactivated by resveratrol mediated through increasing histone acetylation and activation of heat shock factor 1 (HSF1). Additionally, synergistic activation of the latent HIV reservoirs was observed under cotreatment with resveratrol and conventional LRAs. Collectively, this research reveals that resveratrol is a natural LRA and shows promise for HIV therapy.

  9. Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells.

    Science.gov (United States)

    Takito, Jiro; Kimura, Junko; Kajima, Koji; Uozumi, Nobuyuki; Watanabe, Makoto; Yokosuka, Akihito; Mimaki, Yoshihiro; Nakamura, Masanori; Ohizumi, Yasushi

    2016-07-01

    Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells.

  10. Association of the macrophage activating factor (MAF) precursor activity with polymorphism in vitamin D-binding protein.

    Science.gov (United States)

    Nagasawa, Hideko; Sasaki, Hideyuki; Uto, Yoshihiro; Kubo, Shinichi; Hori, Hitoshi

    2004-01-01

    Serum vitamin D-binding protein (Gc protein or DBP) is a highly expressed polymorphic protein, which is a precursor of the inflammation-primed macrophage activating factor, GcMAF, by a cascade of carbohydrate processing reactions. In order to elucidate the relationship between Gc polymorphism and GcMAF precursor activity, we estimated the phagocytic ability of three homotypes of Gc protein, Gc1F-1F, Gc1S-1S and Gc2-2, through processing of their carbohydrate moiety. We performed Gc typing of human serum samples by isoelectric focusing (IEF). Gc protein from human serum was purified by affinity chromatography with 25-hydroxyvitamin D3-sepharose. A phagocytosis assay of Gc proteins, modified using beta-glycosidase and sialidase, was carried out. The Gc1F-1F phenotype was revealed to possess Galbeta1-4GalNAc linkage by the analysis of GcMAF precursor activity using beta1-4 linkage-specific galactosidase from jack bean. The GcMAF precursor activity of the Gc1F-1F phenotype was highest among three Gc homotypes. The Gc polymorphism and carbohydrate diversity of Gc protein are significant for its pleiotropic effects.

  11. Design of Recombinant Stem Cell Factor macrophage Colony Stimulating Factor Fusion Proteins and their Biological Activity In Vitro

    Science.gov (United States)

    Chen, Tao; Yang, Jie; Wang, Yuelang; Zhan, Chenyang; Zang, Yuhui; Qin, Junchuan

    2005-05-01

    Stem cell factor (SCF) and macrophage colony stimulating factor (M-CSF) can act in synergistic way to promote the growth of mononuclear phagocytes. SCF-M-CSF fusion proteins were designed on the computer using the Homology and Biopolymer modules of the software packages InsightII. Several existing crystal structures were used as templates to generate models of the complexes of receptor with fusion protein. The structure rationality of the fusion protein incorporated a series of flexible linker peptide was analyzed on InsightII system. Then, a suitable peptide GGGGSGGGGSGG was chosen for the fusion protein. Two recombinant SCF-M-CSF fusion proteins were generated by construction of a plasmid in which the coding regions of human SCF (1-165aa) and M-CSF (1-149aa) cDNA were connected by this linker peptide coding sequence followed by subsequent expression in insect cell. The results of Western blot and activity analysis showed that these two recombinant fusion proteins existed as a dimer with a molecular weight of 84 KD under non-reducing conditions and a monomer of 42 KD at reducing condition. The results of cell proliferation assays showed that each fusion protein induced a dose-dependent proliferative response. At equimolar concentration, SCF/M-CSF was about 20 times more potent than the standard monomeric SCF in stimulating TF-1 cell line growth, while M-CSF/SCF was 10 times of monomeric SCF. No activity difference of M-CSF/SCF or SCF/M-CSF to M-CSF (at same molar) was found in stimulating the HL-60 cell linear growth. The synergistic effect of SCF and M-CSF moieties in the fusion proteins was demonstrated by the result of clonogenic assay performed with human bone mononuclear, in which both SCF/M-CSF and M-CSF/SCF induced much higher number of CFU-M than equimolar amount of SCF or M-CSF or that of two cytokines mixture.

  12. Role of bioavailable iron in coal dust-induced activation of activator protein-1 and nuclear factor of activated T cells: difference between Pennsylvania and Utah coal dusts.

    Science.gov (United States)

    Huang, Chuanshu; Li, Jingxia; Zhang, Qi; Huang, Xi

    2002-11-01

    Activator protein-1 (AP-1) and nuclear factor of activated T cells (NFAT) are two important transcription factors responsible for the regulation of cytokines, which are involved in cell proliferation and inflammation. Coal workers' pneumoconiosis (CWP) is an occupational lung disease that may be related to chronic inflammation caused by coal dust exposure. In the present study, we demonstrate that coal from the Pennsylvania (PA) coalmine region, which has a high prevalence of CWP, can activate both AP-1 and NFAT in JB6 mouse epidermal cells. In contrast, coal from the Utah (UT) coalmine region, which has a low prevalence of CWP, has no such effects. The PA coal stimulates mitogen-activated protein kinase (MAPK) family members of extracellular signal-regulated kinases (ERKs) and p38 MAPK but not c-Jun-NH(2)-terminal kinases, as determined by the phosphorylation assay. The increase in AP-1 by the PA coal was completely eliminated by the pretreatment of cells with PD98059, a specific MAPK kinase inhibitor, and SB202190, a p38 kinase inhibitor, further confirming that the PA coal-induced AP-1 activation is mediated through ERKs and p38 MAPK pathways. Deferoxamine (DFO), an iron chelator, synergistically enhanced the PA coal-induced AP-1 activity, but inhibited NFAT activity. For comparison, cells were treated with ferrous sulfate and/or DFO. We have found that iron transactivated both AP-1 and NFAT, and DFO further enhanced iron-induced AP-1 activation but inhibited NFAT. These results indicate that activation of AP-1 and NFAT by the PA coal is through bioavailable iron present in the coal. These data are in agreement with our previous findings that the prevalence of CWP correlates well with levels of bioavailable iron in coals from various mining regions.

  13. Role of Bioavailable Iron in Coal Dust-Induced Activation of Activator Protein-1 and Nuclear Factor of Activated T Cells

    Science.gov (United States)

    Huang, Chuanshu; Li, Jingxia; Zhang, Qi; Huang, Xi

    2010-01-01

    Activator protein-1 (AP-1) and nuclear factor of activated T cells (NFAT) are two important transcription factors responsible for the regulation of cytokines, which are involved in cell proliferation and inflammation. Coal workers’ pneumoconiosis (CWP) is an occupational lung disease that may be related to chronic inflammation caused by coal dust exposure. In the present study, we demonstrate that coal from the Pennsylvania (PA) coalmine region, which has a high prevalence of CWP, can activate both AP-1 and NFAT in JB6 mouse epidermal cells. In contrast, coal from the Utah (UT) coalmine region, which has a low prevalence of CWP, has no such effects. The PA coal stimulates mitogen-activated protein kinase (MAPK) family members of extracellular signal-regulated kinases (ERKs) and p38 MAPK but not c-Jun-NH2-terminal kinases, as determined by the phosphorylation assay. The increase in AP-1 by the PA coal was completely eliminated by the pretreatment of cells with PD98059, a specific MAPK kinase inhibitor, and SB202190, a p38 kinase inhibitor, further confirming that the PA coal-induced AP-1 activation is mediated through ERKs and p38 MAPK pathways. Deferoxamine (DFO), an iron chelator, synergistically enhanced the PA coal-induced AP-1 activity, but inhibited NFAT activity. For comparison, cells were treated with ferrous sulfate and/or DFO. We have found that iron transactivated both AP-1 and NFAT, and DFO further enhanced iron-induced AP-1 activation but inhibited NFAT. These results indicate that activation of AP-1 and NFAT by the PA coal is through bioavailable iron present in the coal. These data are in agreement with our previous findings that the prevalence of CWP correlates well with levels of bioavailable iron in coals from various mining regions. PMID:12397016

  14. Effect of peroxisome proliferator-activated receptor alpha activators on tumor necrosis factor expression in mice during endotoxemia.

    Science.gov (United States)

    Hill, M R; Clarke, S; Rodgers, K; Thornhill, B; Peters, J M; Gonzalez, F J; Gimble, J M

    1999-07-01

    Inflammatory mediators orchestrate the host immune and metabolic response to acute bacterial infections and mediate the events leading to septic shock. Tumor necrosis factor (TNF) has long been identified as one of the proximal mediators of endotoxin action. Recent studies have implicated peroxisome proliferator-activated receptor alpha (PPARalpha) as a potential target to modulate regulation of the immune response. Since PPARalpha activators, which are hypolipidemic drugs, are being prescribed for a significant population of older patients, it is important to determine the impact of these drugs on the host response to acute inflammation. Therefore, we examined the role of PPARalpha activators on the regulation of TNF expression in a mouse model of endotoxemia. CD-1 mice treated with dietary fenofibrate or Wy-14,643 had fivefold-higher lipopolysaccharide (LPS)-induced TNF plasma levels than LPS-treated control-fed animals. Higher LPS-induced TNF levels in drug-fed animals were reflected physiologically in significantly lower glucose levels in plasma and a significantly lower 50% lethal dose than those in LPS-treated control-fed animals. Utilizing PPARalpha wild-type (WT) and knockout (KO) mice, we showed that the effect of fenofibrate on LPS-induced TNF expression was indeed mediated by PPARalpha. PPARalpha WT mice fed fenofibrate also had a fivefold increase in LPS-induced TNF levels in plasma compared to control-fed animals. However, LPS-induced TNF levels were significantly decreased and glucose levels in plasma were significantly increased in PPARalpha KO mice fed fenofibrate compared to those in control-fed animals. Data from peritoneal macrophage studies indicate that Wy-14,643 modestly decreased TNF expression in vitro. Similarly, overexpression of PPARalpha in 293T cells decreased activity of a human TNF promoter-luciferase construct. The results from these studies suggest that any anti-inflammatory activity of PPARalpha in vivo can be masked by other

  15. Sphingosine-1-phosphate mediates epidermal growth factor-induced muscle satellite cell activation

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Yosuke, E-mail: cynagata@mail.ecc.u-tokyo.ac.jp; Ohashi, Kazuya; Wada, Eiji; Yuasa, Yuki; Shiozuka, Masataka; Nonomura, Yoshiaki; Matsuda, Ryoichi

    2014-08-01

    Skeletal muscle can regenerate repeatedly due to the presence of resident stem cells, called satellite cells. Because satellite cells are usually quiescent, they must be activated before participating in muscle regeneration in response to stimuli such as injury, overloading, and stretch. Although satellite cell activation is a crucial step in muscle regeneration, little is known of the molecular mechanisms controlling this process. Recent work showed that the bioactive lipid sphingosine-1-phosphate (S1P) plays crucial roles in the activation, proliferation, and differentiation of muscle satellite cells. We investigated the role of growth factors in S1P-mediated satellite cell activation. We found that epidermal growth factor (EGF) in combination with insulin induced proliferation of quiescent undifferentiated mouse myoblast C2C12 cells, which are also known as reserve cells, in serum-free conditions. Sphingosine kinase activity increased when reserve cells were stimulated with EGF. Treatment of reserve cells with the D-erythro-N,N-dimethylsphingosine, Sphingosine Kinase Inhibitor, or siRNA duplexes specific for sphingosine kinase 1, suppressed EGF-induced C2C12 activation. We also present the evidence showing the S1P receptor S1P2 is involved in EGF-induced reserve cell activation. Moreover, we demonstrated a combination of insulin and EGF promoted activation of satellite cells on single myofibers in a manner dependent on SPHK and S1P2. Taken together, our observations show that EGF-induced satellite cell activation is mediated by S1P and its receptor. - Highlights: • EGF in combination with insulin induces proliferation of quiescent C2C12 cells. • Sphingosine kinase activity increases when reserve cells are stimulated with EGF. • EGF-induced activation of reserve cells is dependent on sphingosine kinase and ERK. • The S1P receptor S1P2 is involved in EGF-induced reserve cell activation. • EGF-induced reserve cell activation is mediated by S1P and its

  16. Sphingosine-1-phosphate mediates epidermal growth factor-induced muscle satellite cell activation

    International Nuclear Information System (INIS)

    Nagata, Yosuke; Ohashi, Kazuya; Wada, Eiji; Yuasa, Yuki; Shiozuka, Masataka; Nonomura, Yoshiaki; Matsuda, Ryoichi

    2014-01-01

    Skeletal muscle can regenerate repeatedly due to the presence of resident stem cells, called satellite cells. Because satellite cells are usually quiescent, they must be activated before participating in muscle regeneration in response to stimuli such as injury, overloading, and stretch. Although satellite cell activation is a crucial step in muscle regeneration, little is known of the molecular mechanisms controlling this process. Recent work showed that the bioactive lipid sphingosine-1-phosphate (S1P) plays crucial roles in the activation, proliferation, and differentiation of muscle satellite cells. We investigated the role of growth factors in S1P-mediated satellite cell activation. We found that epidermal growth factor (EGF) in combination with insulin induced proliferation of quiescent undifferentiated mouse myoblast C2C12 cells, which are also known as reserve cells, in serum-free conditions. Sphingosine kinase activity increased when reserve cells were stimulated with EGF. Treatment of reserve cells with the D-erythro-N,N-dimethylsphingosine, Sphingosine Kinase Inhibitor, or siRNA duplexes specific for sphingosine kinase 1, suppressed EGF-induced C2C12 activation. We also present the evidence showing the S1P receptor S1P2 is involved in EGF-induced reserve cell activation. Moreover, we demonstrated a combination of insulin and EGF promoted activation of satellite cells on single myofibers in a manner dependent on SPHK and S1P2. Taken together, our observations show that EGF-induced satellite cell activation is mediated by S1P and its receptor. - Highlights: • EGF in combination with insulin induces proliferation of quiescent C2C12 cells. • Sphingosine kinase activity increases when reserve cells are stimulated with EGF. • EGF-induced activation of reserve cells is dependent on sphingosine kinase and ERK. • The S1P receptor S1P2 is involved in EGF-induced reserve cell activation. • EGF-induced reserve cell activation is mediated by S1P and its

  17. Activation of MAPK/ERK signaling by Burkholderia pseudomallei cycle inhibiting factor (Cif.

    Directory of Open Access Journals (Sweden)

    Mei Ying Ng

    Full Text Available Cycle inhibiting factors (Cifs are virulence proteins secreted by the type III secretion system of some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Cif is known to function to deamidate Nedd8, leading to inhibition of Cullin E3 ubiquitin ligases (CRL and consequently induction of cell cycle arrest. Here we show that Cif can function as a potent activator of MAPK/ERK signaling without significant activation of other signaling pathways downstream of receptor tyrosine kinases. Importantly, we found that the ability of Cif to activate ERK is dependent on its deamidase activity, but independent of Cullin E3 ligase inhibition. This suggests that apart from Nedd8, other cellular targets of Cif-dependent deamidation exist. We provide evidence that the mechanism involved in Cif-mediated ERK activation is dependent on recruitment of the Grb2-SOS1 complex to the plasma membrane. Further investigation revealed that Cif appears to modify the phosphorylation status of SOS1 in a region containing the CDC25-H and proline-rich domains. It is known that prolonged Cullin E3 ligase inhibition leads to cellular apoptosis. Therefore, we hypothesize that ERK activation is an important mechanism to counter the pro-apoptotic effects of Cif. Indeed, we show that Cif dependent ERK activation promotes phosphorylation of the proapoptotic protein Bim, thereby potentially conferring a pro-survival signal. In summary, we identified a novel deamidation-dependent mechanism of action of the B. pseudomallei virulence factor Cif/CHBP to activate MAPK/ERK signaling. Our study demonstrates that bacterial proteins such as Cif can serve as useful molecular tools to uncover novel aspects of mammalian signaling pathways.

  18. Innovation activity of scientists as a factor in the development of academic entrepreneurship in Russia

    Directory of Open Access Journals (Sweden)

    L. N. Babak

    2016-01-01

    Full Text Available The development of academic entrepreneurship as a way of transfer of innovation is an urgent task. One of the main factors in the development of academic entrepreneurship is innovation-oriented staff of higher education institutions. Insufficient attention of the scientific literature to importance of this factor is thwarting progress of various forms of academic entrepreneurship. In connection with this proposed study is aimed at determining the degree of scientific innovation activity influence on the development of academic entrepreneurship in Russia. Academic entrepreneurship in Russia has been chosen as the object of study. Analysis of the basic research in the field of academic entrepreneurship for the period of 2011-2016 years was used to achieve this goal. Analysis of publications was revealed that the innovative activity of the teaching staff of universities is a critical factor in the development of academic entrepreneurship. However, Russian scientists are characterized by low innovation activity, resulting in academic entrepreneurship in Russia is weak. The researchers suggest the following solutions to eliminate or minimize the effects of this problem: full awareness and moral training of the scientists involved in the innovation process of higher education institutions; profit payment; creating a psychological climate that will affect the scientific process of self-realization; continuous training of employees involved in the innovation process of higher education institutions; the creation of conditions that will contribute to the manifestation of creative activity of scientists; provide greater confidence to young scientists, graduate students and undergraduates; providing moral and material encouragement of initiatives, experimentation and creativity of scientific and pedagogical staff; the allocation of free time for scientists to research and search activities and others. The data obtained can be used by the guidance of

  19. The role of demographic and motivational factors on mobile commerce usage activities in South Africa

    Directory of Open Access Journals (Sweden)

    Malcolm Cullen

    2018-03-01

    Full Text Available Background: Many studies have examined the mobile commerce phenomenon and most of these have focused on understanding the organisational and environmental factors that affect its adoption. Few have examined how an individual’s characteristics and their perceived motivational appetite affect their mobile commerce usage and specifically the activities they engage in.   Objectives: This study examines the role of demographics (individuals’ characteristics and motivational factors on mobile commerce usage activities from the South African perspective.   Method: An objective approach and a positivistic stance were followed. The research model and instrument from earlier studies by Chong (2013a were contextualised to suit this study. Data collection was done through an online questionnaire, 88 responses were received and 81 used for data analysis.   Results: The findings show that age is significantly related to mobile commerce transactions, and one’s education status influences the following mobile commerce usage activities: transactions and location-based services. One’s gender influences how one uses mobile commerce. A significant relationship between all three motivational variables and mobile commerce usage activities is evident.   Conclusion: The findings provide the financial services industry and providers of mobile commerce offerings with a better understanding of the relationships between customer demographics and the mobile commerce activities they engage in. An additional variable of customer income has been identified for future studies to better understand the relationship.

  20. Chronic intermittent hypoxia activates nuclear factor-κB in cardiovascular tissues in vivo

    International Nuclear Information System (INIS)

    Greenberg, Harly; Ye Xiaobing; Wilson, David; Htoo, Aung K.; Hendersen, Todd; Liu Shufang

    2006-01-01

    Obstructive sleep apnea (OSA) is an important risk factor for cardiovascular morbidity and mortality. The mechanisms through which OSA promotes the development of cardiovascular disease are poorly understood. In this study, we tested the hypotheses that chronic exposure to intermittent hypoxia and reoxygenation (CIH) is a major pathologic factor causing cardiovascular inflammation, and that CIH-induces cardiovascular inflammation and pathology by activating the NF-κB pathway. We demonstrated that exposure of mice to CIH activated NF-κB in cardiovascular tissues, and that OSA patients had markedly elevated monocyte NF-κB activity, which was significantly decreased when obstructive apneas and their resultant CIH were eliminated by nocturnal CPAP therapy. The elevated NF-κB activity induced by CIH is accompanied by and temporally correlated to the increased expression of iNOS protein, a putative and important NF-κB-dependent gene product. Thus, CIH-mediated NF-κB activation may be a molecular mechanism linking OSA and cardiovascular pathologies seen in OSA patients

  1. Test-retest reliability of a questionnaire to assess physical environmental factors pertaining to physical activity

    Directory of Open Access Journals (Sweden)

    McGinn Aileen P

    2005-06-01

    Full Text Available Abstract Background Despite the documented benefits of physical activity, many adults do not obtain the recommended amounts. Barriers to physical activity occur at multiple levels, including at the individual, interpersonal, and environmental levels. Only until more recently has there been a concerted focus on how the physical environment might affect physical activity behavior. With this new area of study, self-report measures should be psychometrically tested before use in research studies. Therefore the objective of this study was to document the test-retest reliability of a questionnaire designed to assess physical environmental factors that might be associated with physical activity in a diverse adult population. Methods Test and retest surveys were conducted over the telephone with 106 African American and White women and men living in either Forsyth County, North Carolina or Jackson, Mississippi. Reliability of self-reported environmental factors across four domains (e.g., access to facilities and destinations, functionality and safety, aesthetics, natural environment was determined using intraclass correlation coefficients (ICC overall and separately by gender and race. Results Generally items displayed moderate and sometimes substantial reliability (ICC between 0.4 to 0.8, with a few differences by gender or race, across each of the domains. Conclusion This study provides some psychometric evidence for the use of many of these questions in studies examining the effect of self-reported physical environmental measures on physical activity behaviors, among African American and White women and men.

  2. Regulation of the ligand-dependent activation of the epidermal growth factor receptor by calmodulin

    DEFF Research Database (Denmark)

    Li, Hongbing; Panina, Svetlana; Kaur, Amandeep

    2012-01-01

    Calmodulin (CaM) is the major component of calcium signaling pathways mediating the action of various effectors. Transient increases in the intracellular calcium level triggered by a variety of stimuli lead to the formation of Ca2+/CaM complexes, which interact with and activate target proteins....... In the present study the role of Ca2+/CaM in the regulation of the ligand-dependent activation of the epidermal growth factor receptor (EGFR) has been examined in living cells. We show that addition of different cell permeable CaM antagonists to cultured cells or loading cells with a Ca2+ chelator inhibited...

  3. Studies on thermal neutron perturbation factor needed for bulk sample activation analysis

    CERN Document Server

    Csikai, J; Sanami, T; Michikawa, T

    2002-01-01

    The spatial distribution of thermal neutrons produced by an Am-Be source in a graphite pile was measured via the activation foil method. The results obtained agree well with calculated data using the MCNP-4B code. A previous method used for the determination of the average neutron flux within thin absorbing samples has been improved and extended for a graphite moderator. A procedure developed for the determination of the flux perturbation factor renders the thermal neutron activation analysis of bulky samples of unknown composition possible both in hydrogenous and graphite moderators.

  4. A high fat meal activates blood coagulation factor vii in rats

    DEFF Research Database (Denmark)

    Olsen, A. K.; Bladbjerg, E. M.; Kornerup Hansen, A.

    2002-01-01

    In humans, high fat meals cause postprandial activation of blood coagulation factor VII (FVII), but human studies have not provided definite evidence for a prothrombotic effect of dietary FVII activation. An animal model would be an attractive way to pursue this question and therefore we tested...... the LEW/Mol rat. We gavaged 3 mL of a fat emulsion (n = 42) or 3 mL isotonic glucose (n = 42). Blood was sampled by heart puncture 2, 4 and 6 h (n = 14/group at each time) after the fat/glucose load. Furthermore, blood was sampled from 16 untreated rats to determine the baseline levels. Triglyceride...

  5. Factors predicting health behaviors among Army Reserve, active duty Army, and civilian hospital employees.

    Science.gov (United States)

    Wynd, Christine A; Ryan-Wenger, Nancy A

    2004-12-01

    This study identified health-risk and health-promoting behaviors in military and civilian personnel employed in hospitals. Intrinsic self-motivation and extrinsic organizational workplace factors were examined as predictors of health behaviors. Because reservists represent a blend of military and civilian lifestyles, descriptive analyses focused on comparing Army Reserve personnel (n = 199) with active duty Army (n = 218) and civilian employees (n = 193), for a total sample of 610. Self-motivation and social support were significant factors contributing to the adoption of health-promoting behaviors; however, organizational workplace cultures were inconsistent predictors of health among the three groups. Only the active Army subgroup identified a hierarchical culture as having an influence on health promotion, possibly because of the Army's mandatory physical fitness and weight control standards. Social support and self-motivation are essential to promoting health among employees, thus hospital commanders and chief executive officers should encourage strategies that enhance and reward these behaviors.

  6. Low Capacitive Inductors for Fast Switching Devices in Active Power Factor Correction Applications

    DEFF Research Database (Denmark)

    Hernandez Botella, Juan Carlos; Petersen, Lars Press; Andersen, Michael A. E.

    2014-01-01

    This paper examines different winding strategies for reduced capacitance inductors in active power factor correction circuits (PFC). The effect of the parasitic capacitance is analyzed from an electro magnetic compatibility (EMI) and efficiency point of views. The purpose of this work is to inves......This paper examines different winding strategies for reduced capacitance inductors in active power factor correction circuits (PFC). The effect of the parasitic capacitance is analyzed from an electro magnetic compatibility (EMI) and efficiency point of views. The purpose of this work...... is to investigate different winding approaches and identify suitable solutions for high switching frequency/high speed transition PFC designs. A low parasitic capacitance PCB based inductor design is proposed to address the challenges imposed by high switching frequency PFC Boost converters....

  7. The moderating effect of psychosocial factors in the relation between neighborhood walkability and children's physical activity.

    Science.gov (United States)

    D'Haese, Sara; Gheysen, Freja; De Bourdeaudhuij, Ilse; Deforche, Benedicte; Van Dyck, Delfien; Cardon, Greet

    2016-12-09

    The study aimed to investigate if psychosocial factors moderate the association between objective walkability and different domains of children's physical activity (PA). A second aim of the study was to investigate the direct associations between psychosocial factors and children's PA. Based on previous literature, it was hypothesized that walkability would be more strongly related to PA among children with negative psychosocial profiles. Data were collected between December 2011 and May 2013 as part of the Belgian Environmental Physical Activity Study in children (BEPAS-child). In total, data from 494 children and one of their parents were included in the study. Children wore an accelerometer for 7 consecutive days and together with one of their parents, they completed the Flemish Physical Activity Questionnaire. Parents filled out a questionnaire concerning their child's psychosocial factors toward PA (i.e. parental attitude toward their child's PA, parental social norm toward their child's PA, parental support, friend support, children's self-efficacy, and perceived benefits and barriers toward sports and PA). Neighborhood walkability was calculated using geographical information systems (GIS). Multilevel cross-classified analyses were conducted. Of the 42 investigated interactions between neighborhood walkability and psychosocial factors in relation to PA among children, only 7 significant interactions were found of which 3 were only significant among children from low-income neighborhoods. Parental support and self-efficacy were positive correlates of children's PA in high- and low-income neighborhoods independent of the level of walkability, but effect sizes were small. The hypothesis that walkability would be more strongly related to PA among children with negative psychosocial profiles could not be confirmed and in general, psychosocial factors and objective walkability did not interact in relation to children's PA. Focusing on parental support and self

  8. Interactions of psychosocial factors with built environments in explaining adolescents' active transportation.

    Science.gov (United States)

    Wang, Xiaobo; Conway, Terry L; Cain, Kelli L; Frank, Lawrence D; Saelens, Brian E; Geremia, Carrie; Kerr, Jacqueline; Glanz, Karen; Carlson, Jordan A; Sallis, James F

    2017-07-01

    The present study examined independent and interacting associations of psychosocial and neighborhood built environment variables with adolescents' reported active transportation. Moderating effects of adolescent sex were explored. Mixed-effects regression models were conducted on data from the Teen Environment and Neighborhood observational study (N=928) in the Seattle, WA and Baltimore regions 2009-2011. Frequency index of active transportation to neighborhood destinations (dependent variable) and 7 psychosocial measures were reported by adolescents. Built environment measures included home walkability and count of nearby parks and recreation facilities using GIS procedures and streetscape quality from environmental audits. Results indicated all 3 environmental variables and 3 psychosocial variables (self-efficacy, social support from peers, and enjoyment of physical activity) had significant positive main effects with active transportation (Pstransportation (Pstransportation was found among adolescents with the combination of activity-supportive built environment and positive psychosocial characteristics. Three-way interactions with sex indicated similar associations for girls and boys, with one exception. Results provided modest support for the ecological model principle of interactions across levels, highlight the importance of both built environment and psychosocial factors in shaping adolescents' active transportation, demonstrated the possibility of sex-specific findings, and suggested strategies for improving adolescents' active transportation may be most effective when targeting multiple levels of influence. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. RESEARCHING FACTORS OF INNOVATIVE ACTIVITIES OF AGRARIAN BUSINESS OF UKRAINE UNDER GLOBALIZATION OF THE WORLD ECONOMY

    Directory of Open Access Journals (Sweden)

    Vadim Sidorov

    2017-11-01

    Full Text Available Modern processes of reforming the agroindustrial complex of Ukraine, a large part of which belongs to the agrarian sector, under the globalization of world economic processes in the agricultural market require that domestic agroindustrial enterprises improve and rationally manage innovative activities (IА. The effective solution of problems that arise in this context in the rapidly changing economic and social and political environment requires that analytical methods in the management of the enterprises of the agroindustrial complex (AIC be used on the basis of the tools of economic and mathematical modelling, taking into account characteristics of agrarian production. The main approaches to modelling systems related to IА management are either descriptive or insufficiently formalized, and suggest virtual experimenting with IA management, avoiding the possibility of assessing the impact and consequences of different management options in the long view, minimizing IA risks when making managerial decisions. The subject matter of the article is the tools of economic and mathematical simulation of the development of innovative activities of the domestic agroindustrial complex. The goal is to develop tools for modelling innovative activities of enterprises of the agroindustrial complex of Ukraine in the form of analytical dependencies of impact factors. The objective is to research the dynamics of innovative activities of enterprises of the agroindustrial complex of Ukraine in terms of its components under the globalization of world economic processes in the market of agricultural products. General scientific methods are used, such as system analysis – to determine the peculiarities of development of IА of agroindustrial production in Ukraine, factor analysis – to formalize the cause-and-effect relationships of the investigated factors of AIC enterprises impact on IA. The following results were obtained: on the basis of the analysis of the

  10. Association of Geographical Factors With Administration of Tissue Plasminogen Activator for Acute Ischemic Stroke

    OpenAIRE

    Kunisawa, Susumu; Morishima, Toshitaka; Ukawa, Naoto; Ikai, Hiroshi; Otsubo, Tetsuya; Ishikawa, Koichi B.; Yokota, Chiaki; Minematsu, Kazuo; Fushimi, Kiyohide; Imanaka, Yuichi

    2013-01-01

    Background Intravenous tissue plasminogen activator (tPA) is an effective treatment for acute ischemic stroke if administered within a few hours of stroke onset. Because of this time restriction, tPA administration remains infrequent. Ambulance use is an effective strategy for increasing tPA administration but may be influenced by geographical factors. The objectives of this study are to investigate the relationship between tPA administration and ambulance use and to examine how patient trave...

  11. Influence of socioeconomic factors on daily life activities and quality of life of Thai elderly

    Directory of Open Access Journals (Sweden)

    Ratana Somrongthong

    2017-06-01

    Full Text Available Background: The increasing number of older people is a significant issue in Thailand, resulted in growing demands of health and social welfare services. The study aim was to explore the influence of socioeconomic factors on activities of daily living and quality of life of Thai seniors. Design and methods: Using randomised cluster sampling, one province was sampled from each of the Central, North, Northeast and South regions, then one subdistrict sampled in each province, and a household survey used to identify the sample of 1678 seniors aged 60 years and over. The Mann-Whitney U-test and binary logistic regression were used to compare and determine the association of socioeconomic variables on quality of life and activities of daily living. Results: The findings showed that sociodemographic and socioeconomic factors were significantly related to functional capacity of daily living. Education levels were strongly associated with daily life activities, with 3.55 adjusted ORs for respondents with secondary school education. Gender was important, with females comprising 61% of dependent respondents but only 47% of independent respondents. Seniors with low incomes were more likely to be anxious in the past, present and future and less likely to accept death in the late stage, with 1.40 Adjusted ORs (95%CI: 1.02-1.92, and 0.72 (95%CI: 0.53-0.98, respectively. However, they were more likely to engage in social activities. Conclusions: While socioeconomic factors strongly indicated the functional capacity to live independently, a good quality of life also required other factors leading to happiness and life satisfaction.

  12. Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models

    OpenAIRE

    Siner, Joshua I.; Samelson-Jones, Benjamin J.; Crudele, Julie M.; French, Robert A.; Lee, Benjamin J.; Zhou, Shanzhen; Merricks, Elizabeth; Raymer, Robin; Nichols, Timothy C.; Camire, Rodney M.; Arruda, Valder R.

    2016-01-01

    Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645–1648) in the design of B-domain–deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by fu...

  13. Reduced Transforming Growth FactorActivity in the Endometrium of Women With Heavy Menstrual Bleeding

    OpenAIRE

    Maybin, Jacqueline A.; Boswell, Lyndsey; Young, Vicky J.; Duncan, William C.; Critchley, Hilary O. D.

    2017-01-01

    Context: Heavy menstrual bleeding (HMB) is common and incapacitating. Aberrant menstrual endometrial repair may result in HMB. The transforming growth factor (TGF)-β superfamily contributes to tissue repair, but its role in HMB is unknown. Objective: We hypothesized that TGF-β1 is important for endometrial repair, and women with HMB have aberrant TGF-β1 activity at menses. Participants/Setting: Endometrial biopsies were collected from women, and menstrual blood loss objectively measured [HMB ...

  14. Analysis of Factors Influencing Activity-Based Costing Applications in the Hospitality Industry in Yenagoa, Nigeria

    OpenAIRE

    Appah, Ebimobowei; Bariweni Binaebi

    2013-01-01

    This research examines the factors influencing activity-based costing application in the hospitality industry in Yenagoa, Nigeria. To achieve this objective, primary and secondary data were used. The secondary data include books, journals, periodicals, unpublished research materials and the internet and the primary data include interview and a well structured questionnaire administered to one hundred and 165 respondents in the 50 hotels sampled from the population. The data collected from the...

  15. Internalization mechanisms of the epidermal growth factor receptor after activation with different ligands

    DEFF Research Database (Denmark)

    Henriksen, Lasse; Grandal, Michael Vibo; Knudsen, Stine Louise Jeppe

    2013-01-01

    after ligand activation focuses on the effect of epidermal growth factor (EGF) and transforming growth factor-α (TGF-α). For a long time it was believed that clathrin-mediated endocytosis was the major pathway for internalization of the receptor, but recent work suggests that different pathways exist....... Here we show that clathrin ablation completely inhibits internalization of EGF- and TGF-α-stimulated receptor, however the inhibition of receptor internalization in cells treated with heparin-binding EGF-like growth factor (HB-EGF) or betacellulin (BTC) was only partial. In contrast, clathrin knockdown...... fully inhibits EGFR degradation after all ligands tested. Furthermore, inhibition of dynamin function blocked EGFR internalization after stimulation with all ligands. Knocking out a number of clathrin-independent dynamin-dependent pathways of internalization had no effect on the ligand...

  16. Methodology for Selection of Economic Performance Factors in the Area of Information and Communication Activities

    Directory of Open Access Journals (Sweden)

    Jana Hornungová

    2015-01-01

    Full Text Available The article presents one part of the research work of the author that is focused on the business performance. The aim of this paper is to find and introduce economic factors of corporate performance system that are important part of the performance, because can help to organization define and measure progress toward organizational goals. The aim also included the determination of Key Performance Indicators (KPIs. The first step for the evaluation of performance is the projective access. This approach is meant, that the performance in terms of the future development of the company it is possible to conclude on the basis of, and ongoing activities. In relation to this idea are as fundamental the economic indicators of the performance scale. To find these factors were used the theoretical information from the area of KPIs and data from primary research. This data were tested through mathematical-statistical analysis, in this case, directly on the basis of factor analysis.

  17. Mesenchymal Stem/Multipotent Stromal Cells from Human Decidua Basalis Reduce Endothelial Cell Activation.

    Science.gov (United States)

    Alshabibi, Manal A; Al Huqail, Al Joharah; Khatlani, Tanvir; Abomaray, Fawaz M; Alaskar, Ahmed S; Alawad, Abdullah O; Kalionis, Bill; Abumaree, Mohamed Hassan

    2017-09-15

    Recently, we reported the isolation and characterization of mesenchymal stem cells from the decidua basalis of human placenta (DBMSCs). These cells express a unique combination of molecules involved in many important cellular functions, which make them good candidates for cell-based therapies. The endothelium is a highly specialized, metabolically active interface between blood and the underlying tissues. Inflammatory factors stimulate the