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Sample records for activated factor vii

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

    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...

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

    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 125I-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

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

    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

  4. Monoclonal antibodies to human factor VII: a one step immunoradiometric assay for VII:Ag.

    Takase, T.; Tuddenham, E G; Chand, S; Goodall, A H

    1988-01-01

    Three mouse monoclonal antibodies (RFF-VII/1, RFF-VII/2, and RFF-VII/3) which bind specifically to different epitopes on human factor VII antigen were raised. Two of the antibodies, RFF-VII/1 and RFF-VII/2, bound strongly to factor VII antigen (VII:Ag), but only RFF-VII/1 and RFF-VII/3 were potent inhibitors of factor VII coagulation activity (VII:C). RFF-VII/1 and RFF-VII/2 were used in a one step, double monoclonal immunoradiometric assay for VII:Ag. This was highly reproducible and detecte...

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

    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....

  6. Factor VII deficiency

    ... page: //medlineplus.gov/ency/article/000548.htm Factor VII deficiency To use the sharing features on this page, please enable JavaScript. Factor VII (seven) deficiency is a disorder caused by a ...

  7. Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)

    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...

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

    Sidelmann, Johannes Jakobsen; 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...

  9. A high-fat meal does not activate blood coagulation factor VII in minipigs

    Olsen, A K; Larsen, L F; Bladbjerg, E-M; Hansen, A K; Jespersen, J; Marckmann, P

    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...

  10. The use of recombinant activated coagulation factor VII for spine surgery

    Weiskopf, Richard B.

    2004-01-01

    This article focuses on our current understanding of the role of activated coagulation factor VII (FVIIa) in coagulation, the current evidence regarding the efficacy and safety of recombinant FVIIa (rFVIIa), and thoughts regarding the use of rFVIIa in spine surgery. rFVIIa is approved in many countries (including the European Union and the USA) for patients with hemophilia and inhibitors (antibodies) to coagulation factors VIII or IX. High circulating concentrations of FVIIa, achieved by exog...

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

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

    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. Obj...

  12. Synthesis and characterization of (18)F-labeled active site inhibited factor VII (ASIS).

    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. PMID:25820758

  13. Constitutively expressed ERF-VII transcription factors redundantly activate the core anaerobic response in Arabidopsis thaliana.

    Bui, Liem T; Giuntoli, Beatrice; Kosmacz, Monika; Parlanti, Sandro; Licausi, Francesco

    2015-07-01

    Plant adaptation to hypoxic conditions is mediated by the transcriptional activation of genes involved in the metabolic reprogramming of plant cells to cope with reduced oxygen availability. Recent studies indicated that members of the group VII of the Ethylene Responsive Transcription Factor (ERFs) family act as positive regulators of this molecular response. In the current study, the five ERF-VII transcription factors of Arabidopsis thaliana were compared to infer a hierarchy in their role with respect to the anaerobic response. When the activity of each transcription factor was tested on a set of hypoxia-responsive promoters, RAP2.2, RAP2.3 and RAP2.12 appeared to be the most powerful activators. RAP2.12 was further dissected in transactivation assays in Arabidopsis protoplasts to identify responsible regions for transcriptional activation. An ultimate C-terminal motif was identified as sufficient to drive gene transcription. Finally, using realtime RT-PCR in single and double mutants for the corresponding genes, we confirmed that RAP2.2 and RAP2.12 exert major control upon the anaerobic response. PMID:26025519

  14. Failure of Recombinant Activated Factor VII in Treatment of Diffuse Alveolar Hemorrhage due to Cryoglobulinemic Vasculitis

    Dania Khoulani

    2014-01-01

    Full Text Available Diffuse alveolar hemorrhage (DAH is a serious complication of the small vessel vasculitis syndromes and carries a high mortality. Recombinant activated factor VII (rFVIIa is used to treat bleeding in patients with hemophilia and antibodies to factor VIII or IX. It is increasingly being used in life-threatening hemorrhage in a variety of other settings in which conventional therapy is unsuccessful. Randomized controlled trials of rFVIIa in DAH are lacking. However, several case reports have described a complete or sustained control of DAH using rFVIIa after patients failed to respond to medical treatment. There are no case reports in the literature describing the use or the failure of rFVIIa in DAH associated with cryoglobulinemic vasculitis. We here report the failure of rFVIIa to control DAH in a patient with CD5+ B-cell non-Hodgkin’s lymphoma and cryoglobulinemic vasculitis.

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

    Pär I Johansson

    2010-06-01

    Full Text Available Pär I Johansson, Sisse R OstrowskiCapital Region Blood Bank, Section for Transfusion Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkBackground: Recombinant activated factor VII (rFVIIa, NovoSeven® was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX.Objective: To review the evidence supporting the use of rFVIIa for the treatment of patients with congenital bleeding disorders.Patients and methods: English-language databases were searched in September 2009 for reports of randomized controlled trials (RCTs evaluating the ability of rFVIIa to restore hemostasis in patients with congenital bleeding disorders.Results: Eight RCTs involving 256 hemophilic patients with antibodies against coagulation factors, also known as inhibitors, were identified. The evidence supporting the use of rFVIIa in these patients was weak with regard to dose, clinical setting, mode of administration, efficacy, and adverse events, given the limited sample size of each RCT and the heterogeneity of the studies.Conclusion: The authors suggest that rFVIIa therapy in hemophilic patients with inhibitors should be based on the individual’s ability to generate thrombin and form a clot, and not on the patient’s weight alone. Therefore, assays for thrombin generation, such as whole-blood thromboelastography, have the potential to significantly improve the treatment of these patients.Keywords: hemophilia, inhibitors, coagulation factor VIII, coagulation factor IX, rFVIIa, NovoSeven, FEIBA, hemostasis, RCT

  16. Treatment of massive gastrointestinal bleeding occurred during autologous stem cell transplantation with recombinant activated factor VII and octreotide

    Erman Atas

    2015-01-01

    Full Text Available After hematopoietic stem cell transplantation (HSCT, patients may suffer from bleeding. One of the bleeding type is gastrointestinal (GI which has serious morbidity and mortality in children with limited treatment options. Herein, we presented a child with upper GI bleeding post autologous HSCT controlled successfully by using recombinant activated factor VII (rFVIIa and octreotide infusion.

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

    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 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...... 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. CONCLUSION: [(18)F]FVIIai is a promising PET tracer for specific and non-invasive imaging of tumor TF expression. The tracer merits further development and clinical translation...

  18. Uso de fator VII recombinante ativado para tratamento e profilaxia de grandes sangramentos Use of recombinant activated factor VII for treatment and prophylaxis of major bleeding

    Flávio Augusto Henriques Vince

    2009-09-01

    pacientes. Dessa forma, o recente aumento do uso de rFVIIa em situações ainda não aprovadas levou ao crescente questionamento sobre eficácia e segurança desta específica medicação em tais situações.INTRODUCTION: Recombinant activated factor VII (rFVIIa is a protein produced by genetic engineering, the structure is very similar to the structure of intrinsic activated factor VII (FVII. Its action is based on knowledge of the coagulation mechanism in vivo by acting in direct activation of factor X independent resulting in formation of thrombin at the injury site and thereby contributing to the formation of stable fibrin clots without the action of factor VIII and factor IX. METHODS: Was conducted extensive review of the literature in order to determine the new findings related to the use of recombinant activated factor VII in patients with severe bleeding. RESULTS: It was found that the use of rFVIIa started in the 80's for prophylaxis and treatment of bleeding in patients with a history of hemophilia A or B with inhibitors to factor VIII and IX, factor VII deficiency and Glanzmann's thrombasthenia refractory to replacement platelet. In 1999 its use was expanded to other clinical situations and thus began to be published several studies showing the efficacy of rFVIIa as a pro-hemostatic agent in patients with bleeding disorders or other previously healthy patients with a history of acute bleeding of major consequence. Trauma is the leading cause of mortality worldwide and uncontrolled bleeding the main challenge in caring for these patients. It is common for the association of trauma with coagulopathy, requiring in some cases specific therapy to treat it. At this point in adjuvant therapy with rFVIIa should be considered. Other common causes of bleeding are the heart, gynecologic/obstetric surgeries and diseases involving the liver. The coagulopathy in these cases is deficiency of factors dependent on vitamin K, and the FVII factor with smaller half life. CONCLUSION

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

    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.

  20. The importance of residues 195-206 of human blood clotting factor VII in the interaction of factor VII with tissue factor

    Previous studies indicated that human and bovine factor VII exhibit 71% amino acid sequence identity. In the present study, competition binding experiments revealed that the interaction of human factor VII with cell-surface human tissue factor was not inhibited by 100-fold molar excess of bovine factor VII. This finding indicated that bovine and human factor VII are not structurally homologous in the region(s) where human factor VII interacts with human tissue factor. On this premise, the authors synthesized three peptides corresponding to regions of human factor VII that exhibited marked structural dissimilarity to bovine factor VII; these regions of dissimilarity included residues 195-206, 263-274, and 314-326. Peptide 195-206 inhibited the interaction of factor VII with cell-surface tissue factor and the activation of factor X by a complex of factor VIIa and tissue factor half-maximally at concentrations of 1-2 mM. A structurally rearranged form of peptide 195-206 containing an aspartimide residue inhibited these reactions half-maximally at concentrations of 250-300 μM. In contrast, neither peptide 263-274 nor peptide 314-326, at 2 mM concentration, significantly affected either factor VIIa interaction with tissue factor or factor VIIa-mediated activation of factor X. The data provide presumptive evidence that residues 195-206 of human factor VII are involved in the interaction of human factor VII with the extracellular domain of human tissue factor apoprotein

  1. The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

    Larsen, L F; Marckmann, P; Bladbjerg, Else-Marie;

    2000-01-01

    Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples......-rich lipoproteins activate prokallikrein postprandially, which might form an important initial event in FVII activation after consumption of high-fat meals....... were collected. The high-fat test was associated with an increase in plasma triglyceride and kallikrein concentrations and postprandial FVII activation (p<0.001). Plasma kallikrein was strongly associated with triglycerides in fasting and non-fasting samples (r2=0.74-0.87, p<0.0001), suggesting that...

  2. Hydatid cyst surgery complicated by hemorrhage resistant to activated recombinant factor VII, in a hemophiliac A patient with an inhibitor.

    Nabil, Saad; Bentalha, Aziza; Jaiteh, Lamine; El Khorassani, Mohammed; El Koraichi, Alae; El Kettani, Salma E-C

    2016-09-01

    Factor VII is a new coagulation factor replacement therapy. It has permitted the practice of invasive procedures which were up until recently associated with a huge risk of bleeding in patients with hemophilia with inhibitors. Our case illustrates factor replacement therapy failure in a 13-year-old child operated on for hepatic cysts associated with a pelvic cyst. Major bleeding occurred postoperatively requiring several transfusions, an increase in dosage of factor VII, and administration of a heavy dose of factor VIII as a last resort. This case highlights the possibility of failure of factor replacement therapies constituting a life-threatening situation in which alternatives are few. PMID:26761579

  3. Canine specific ELISA for coagulation factor VII

    Knudsen, Tom; Kjelgaard-Hansen, Mads; Tranholm, Mikael; Wiinberg, Bo; Clausen, Jes T.; Hansen, Jens Jacob; Nichols, Timothy C.; Kjalke, Marianne; Jensen, Asger Lundorff; Kristensen, Annemarie Thuri

    2011-01-01

    Canine coagulation factor VII (FVII) deficiency can be hereditary or acquired and may cause life threatening bleeding episodes if untreated. FVII procoagulant activity can be measured by FVII activity (FVII:C), but assays for measurement of canine specific FVII antigen (FVII:Ag) have not been...... available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable...... in the diagnosis of hereditary canine FVII deficiency....

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

    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....... Objective: We tested the hypothesis that FVII activation would be less after consumption of saturated fatty acids than after other fatty acids. Design: The effects of 6 matching dietary test fats, rich in stearic (S), palmitic (P), palmitic + myristic (M), oleic (O), trans 18:1 (T), and linoleic (L) acid......, respectively, on the postprandial lipid and hemostatic profile (after 2, 4, 6, and 8 h) were investigated in 16 young men. High-fat meals (1 g fat/kg body wt; 43% from the test fatty acid) were served in the morning on 6 separate days. Results: All fats increased FVII activation. The S fat resulted in a lower...

  5. Production and properties of monoclonal antibodies to human blood coagulation factor VII and factor VIIa

    Human factor VII is a trace vitamin K-dependent protein that circulates in blood as a single-chain precursor to a serine protease. Upon activation, two-chain factor VIIa activates factor x in the presence of tissue factor and calcium. Purified preparations of single-chain (SC) human factor VII and two-chain (TC) factor VIIa were utilized to immunize Balb/c mice. Spleen cells from these immunized mice were fused to a non-secreting NS-1 derivative of X63-Ag8 myeloma cells and grown in selective medium. Analysis of culture supernatants by EIA revealed several hybridomas that were secreting IgG specific for Sc-factor VII and TC-factor VIIa. In addition, several hybridomas secreted IgG that reacted equally well with factor VII and factor VIIa. One of the latter McAb (A-29) reacted with the heavy chain of factor VIIa and the intact factor VII molecule equally as judged by Western blotting. A-29 was produced in ascites fluid, purified and coupled to activated CH-Sepharose. Application of one liter of normal human plasma to 10 ml of this immunoadsorbent column, elution of factor VII and subsequent Western blot using 125I-rabbit anti-human factor VII indicated a single species of factor VII(M/sub r/ = 50 KDa) in normal plasma. These specific factor VII/VIIa McAbs may prove useful in the analysis of these factors, and in the separation of SC-factor VII from TC-factor VIIa

  6. Recombinant activated factor VII in the treatment of intractable non-surgical bleeding following major vascular procedures

    Končar Igor B.

    2008-01-01

    Full Text Available INTRODUCTION A recombinant form of activated factor VII (rFVIIa is a haemostatic drug that is approved for use in haemophiliacs with antibodies to factor VIII or factor IX. Most recent studies and clinical experience have shown that rFVIIa (NovoSeven ®, Novo Nordisk A/S, Denmark gives extreme haemostatic effect in patients with severe "non-haemophilic" bleeding produced after trauma and major surgery. OBJECTIVE We present our preliminary experience of the use of rFVIIa in vascular surgery when conventional haemostatic measures are inadequate. METHOD There were 32 patients divided into five groups: Group I - 14 patients with ruptured abdominal aortic aneurysms; Group II - 10 patients with thoracoabdominal aortic aneurysms; Group III - 5 patients with retroperitoneal tumors involving great abdominal vessels; Group IV - 2 patients with portal hypertension and Group V - one patient with iatrogenic injury of brachial artery and vein during fibrinolytic treatment, because of myocardial infarction. RESULTS Clinical improvement was detected following treatment in 29 patients. Bleeding was successfully controlled as evidenced by improved haemodynamic parameters and decreased inotropic and transfusion requirements. CONCLUSION In vascular patients more liberal use of rFVIIa is limited, because no randomized controlled trial has proved its efficacy and safety in such patients; while also keeping in mind that the price of a 4.8 mg of rFVIIa is $4,080. We recommend the use of rFVIIa in vascular surgery only during and after operative treatment of thoracoabdominal aortic aneurysms, ruptured abdominal aortic aneurysms, retroperitoneal tumors involving the aorta and/or inferior vena cava, as well as portal hypertension, when non-surgical massive uncontrolled bleeding are present.

  7. Hormone therapy affects plasma measures of factor VII-activating protease in younger postmenopausal women

    Mathiasen, Jørn Sidelmann; Skouby, S.O.; Vitzthum, F.; Schwarz, H.; Jespersen, J.

    2010-01-01

    for the determination of FSAP antigen and FSAP activity. Results The FSAP measures were comparable at baseline. No significant changes were observed in the control group after 12 months. HT in general induced a significant increase in FSAP antigen (7.7 mu g/ml at baseline and 8.0 mu g/ml after 12...... induced by HT in younger postmenopausal women...

  8. Use of activated recombinant factor VII for severe coagulopathy post ventricular assist device or orthotopic heart transplant

    Despotis George J

    2007-07-01

    Full Text Available Abstract Background Ventricular assist devices(VAD implantation/removal is a complex surgical procedure with perioperative bleeding complications occurring in nearly half of the cases. Recombinant activated factor VII (rFVIIa has been used off-label to control severe hemorrhage in surgery and trauma. We report here our experience with rFVIIa as a rescue therapy to achieve hemostasis in patients undergoing orthotopic heart transplant (OHT and/or VAD implantation. Methods A retrospective review was conducted from Jan 03 to Aug 05 for patients who received rFVIIa for the management of intractable bleeding unresponsive to standard hemostatic blood component therapy. Blood loss and the quantity of blood products, prior to, and for at least 12 hours after, administration of rFVIIa were recorded. Results Mean patient age was 53, (38–64 yrs, mean dose of rFVIIa administered was 78.3 μg/kg (24–189 μg/kg in 1–3 doses. All patients received the drug either intraoperatively or within 6 hours of arrival in ICU. Mean transfusion requirements and blood loss were significantly reduced after rFVIIa administration (PRBC's; 16.9 ± 13.3 to 7.1 ± 6.9 units, FFP; 13.1 ± 8.2 to 4.1 ± 4.9 units, platelets; 4.0 ± 2.8 to 2.1 ± 2.2 units, p Conclusion In this review, there was a significant decrease in transfusion requirement and blood loss after rFVIIa administration. Although, 5/17 developed thromboembolic complications, these patients may have been at higher risk based on the multiple modality therapy used to manage intractable bleeding. Nevertheless, the exact role of rFVIIa with respect to development of thromboembolic complications cannot be clearly determined. Further investigation is needed to determine rFVIIa's safety and its effectiveness in improving postoperative morbidity and mortality.

  9. Use of recombinant activated factor VII for reduction of perioperative blood loss during elective surgical correction of spine deformity in a Jehovah's Witness. Case report.

    Kącka, Katarzyna; Kącki, Wojciech; Merak, Joanna; Błęka, Adam

    2010-01-01

    Planned surgical procedures at patients who refuse allogenic blood transfusion because of religious convictions are important problem, not only medical but also ethical and juristical. At the study authors report the successful use of activated recombinant factor VII (rFVIIa) for the reduction of perioperative blood loss in four years old child - Jehovah's Witness, who had planned Torode kyphectomy. Applied perioperative management together with preparing to surgery with erythropoietin allowed for reduction of blood loss and avoiding of blood transfusion. Authors state, that appropriate perioperative proceeding makes a possibility of safe surgical procedures also at patients who refuse the transfusion. PMID:21057153

  10. Synthesis, purification, and characterization of an Arg152 → Glu site-directed mutant of recombinant human blood clotting factor VII

    Coagulation factor VII circulates in blood as a single-chain zymogen of a serine protease and is converted to its activated two-chain form, factor VIIa, by cleavage of an internal peptide bond located at Arg152-Ile153. Previous studies using serine protease active-site inhibitors suggest that zymogen factor VII may possess sufficient proteolytic activity to initiate the extrinsic pathway of blood coagulation. In order to assess the putative intrinsic proteolytic activity of single-chain factor VII, the authors have constructed a site-specific mutant of recombinant human factor VII in which arginine-152 has been replaced with a glutamic acid residue. Mutant factor VII was purified in a single step from culture supernatants of baby hamster kidney cells transfected with a plasmid containing the sequence for Arg152 → Glu factor VII using a calcium-dependent, murine anti-factor VII monoclonal antibody column. The clotting activity of mutant factor VII was completely inhibited following incubation with dansyl-Glu-Gly-Arg chloromethyl ketone, suggesting that the apparent clotting activity of mutant factor VII was due to a contaminating serine protease. Immunoblots of mutant factor VII with human factor IXa revealed no cleavage, whereas incubation of mutant factor VII with human factor Xa resulted in cleavage of mutant factor VII and the formation of a lower molecular weight degradation product migrating at Mr∼40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX

  11. Monoclonal anti-human factor VII antibodies. Detection in plasma of a second protein antigenically and genetically related to factor VII.

    Broze, G J; S. Hickman; Miletich, J P

    1985-01-01

    Several murine monoclonal anti-human Factor VII antibodies were produced using hybridoma technology. Two noncompetitive monoclonal antibodies were used to examine by Western blotting the Factor VII cross-reactive material (CRM) in normal human plasma and three commercially available congenitally Factor VII-deficient plasmas, and to construct a facile "sandwich" immunoassay for plasma Factor VII. A second, previously undescribed, form of Factor VII CRM was detected in human plasma, which on We...

  12. Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II+VII+X activity in subjects infused with the drug. Influence of time and temperature

    Thorsen, Sixtus; Teisner, Ane; Jensen, Søren Astrup; Philips, Malou; Dalhoff, Kim; Bendtsen, Flemming

    2009-01-01

    OBJECTIVES: The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influence...

  13. Successful use of N-acetyl cysteine and activated recombinant factor VII in fulminant hepatic failure and massive bleeding secondary to dengue hemorrhagic fever

    Edirisooriya Maddumage Manoj

    2014-01-01

    Full Text Available Consensus on management of complicated cases of dengue infection is evolving. Dengue hemorrhagic fever (DHF occasionally progress to fulminant liver failure with high fatality rate. Inadvertent use of blood products to control massive bleeding in dengue shock syndrome may worsen fluid overload and subsequently the multi-organ dysfunction. We report a case of 37-years-old Sri Lankan man who developed fulminant liver failure and massive bleeding associated with DHF, subsequently recovered completely with supportive measures including administration of N-acetyl cysteine and activated recombinant factor VII. In conclusion, prevention of ischemic injury to liver and adoption of early aggressive supportive measures in complicated cases of dengue hemorrhagic fever is crucial for a favorable outcome. Indications for rFVIIa to arrest uncontrolled internal bleeding and use of NAC in non-acetaminophen-induced acute liver failure in complicated DHF are a platform for discussion.

  14. Genotype–phenotype relationship of F7 R353Q polymorphism and plasma factor VII coagulant activity in Asian Indian families predisposed to coronary artery disease

    Jayashree Shanker; Ganapathy Perumal; Arindam Maitra; Veena S. Rao; B. K. Natesha; Shibu John; Sridhar Hebbagodi; Vijay V. Kakkar

    2009-12-01

    Elevated factor VII (FVII) level is a risk factor for coronary artery disease (CAD). We investigated the role of R353Q polymorphism in the F7 gene in 139 Indian families with CAD, comprising of 222 affected subjects, 105 unaffected subjects and 126 affected sibling pairs. Plasma per cent FVIIc activity (FVII.c activity) differed significantly across R353Q genotype ($P \\lt 0.0001$). Frequency of subjects with RR and QQ genotypes were higher in 4th quartile and 1st quartile of FVII.c activity, respectively ($P \\lt 0.0001$). F7 R353Q SNP was able to explain up to 7% of variation in FVII.c activity by regression analysis and an additive genetic component of variance of 28.04% by heritability analysis. Quantitative trait loci analysis showed suggestive linkage evidence of F7 SNP with per cent FVII.c activity (LOD score $-1.82$; $P = 0.002$). Individuals with RR and RQ genotypes carried an OR of 2.071 (95% c.i. = 1.506–2.850) and 2.472 (95% c.i. = 1.679–3.641), respectively, towards CAD risk. There was significant correlation of FVII.c activity with lipid markers, particularly among those with RR and RQ genotype after covariate adjustment. In conclusion, the F7 R353Q SNP appears to moderately influence plasma FVII.c activity and risk of CAD in Indians.

  15. Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery

    Gill, Ravi; Herbertson, Mike; Vuylsteke, Alain;

    2009-01-01

    BACKGROUND: Blood loss is a common complication of cardiac surgery. Evidence suggests that recombinant activated factor VII (rFVIIa) can decrease intractable bleeding in patients after cardiac surgery. Our objective was to investigate the safety and possible benefits of rFVIIa in patients who bleed...... after cardiac surgery. METHODS AND RESULTS: In this phase II dose-escalation study, patients who had undergone cardiac surgery and were bleeding were randomized to receive placebo (n=68), 40 microg/kg rFVIIa (n=35), or 80 microg/kg rFVIIa (n=69). The primary end points were the number of patients....../kg, 14%; P=0.25; 80 microg/kg, 12%; P=0.43). After randomization, significantly fewer patients in the rFVIIa group underwent a reoperation as a result of bleeding (P=0.03) or required allogeneic transfusions (P=0.01). CONCLUSIONS: On the basis of this preliminary evidence, rFVIIa may be beneficial for...

  16. Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

    Bladbjerg, E-M; Skouby, S O.; Andersen, L F;

    2002-01-01

    BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor pat...

  17. Successful management of maternal factor VII deficiency in a cesarean section.

    Lee, Young-Jae; Ju, Da-Hye; Yi, Sang-Wook; Lee, Sang-Soo; Sohn, Woo-Seok

    2014-07-01

    Factor VII (FVII) deficiency is an infrequent hereditary bleeding disorder that can make excessive bleeding in surgical interventions, such as a postpartum hemorrhage in a cesarean section. Although a recombinant form of activated FVII has been applied for bleeding control in FVII-deficient patients, its applications in the field of obstetrics are still limited, especially in Korea. Replacement of blood products is still preferred as first-line therapy, with antifibrinolytic agents used as adjunctive therapy. We report herein the case of a successful cesarean section in an 18-year-old woman with FVII deficiency. PMID:25105106

  18. In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. possible implications for measurements in vivo after heparin therapy

    Bladbjerg, E-M; Larsen, L F; Ostergaard, P;

    2000-01-01

    The coagulant activity of blood coagulation factor VII (FVII:C) can be lowered by changes in lifestyle and by therapeutic intervention, e.g. heparin infusion. The question is, however, whether FVII:C determined ex vivo is a valid measure of the FVII activity in vivo. We measured plasma FVII:C, ac...

  19. Are olive oil diets antithrombotic? Diets enriched with olive, rapeseed, or sunflower oil affect postprandial factor VII differently

    Larsen, L.F.; Jespersen, J; Marckmann, P.

    1999-01-01

    compared the effects of virgin olive oil with those of rapeseed and sunflower oils on blood coagulation factor VII (FVII), a key factor in thrombogenesis. DESIGN: In a randomized and strictly controlled crossover study, 18 healthy young men consumed diets enriched with 5 g/MJ (19% of total energy) olive...... oil, sunflower oil, or rapeseed oil for periods of 3 wk. On the final day of each period, participants consumed standardized high-fat meals (42% of energy as fat). Fasting and nonfasting blood samples were collected after each period. RESULTS: Mean (+/-SEM) nonfasting peak concentrations of activated...... with respect to nonfasting factor VII coagulant activity (FVII:c), prothrombin fragment 1+2 (F1+2), and tissue factor pathway inhibitor (TFPI) concentrations, or with respect to fasting plasma values of FVII protein, FVII:c, FVIIa, F1+2, or TFPI. CONCLUSION: A background diet rich in olive oil may...

  20. Polymorphisms in the genes for coagulation factor II,V,VII in patients undergoing coronary angiography

    徐耕; 金国栋; 傅国胜; 马骥; 单江; 王建安

    2003-01-01

    Objective: To determine whether polymorphisms in the genes for coagulation factor II,V, VII could predispose an individual to increase risk for coronary artery disease (CAD) and/or myocardial infarction (MI) in Chinese. Methods: We screened coagulation factor II(G20210A),V(G1691A),VII (R353Q and HVR4) genotype in 374 patients undergoing coronary angiography by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay. Results: The R353Q and HVR4 genotype of the factor VII distribution was in accordance with Hardy-Weinberg equilibrium. The frequencies of FVII genotype or allele did not show statistically significant differences between CAD group and controls or between male and female. The frequencies of the Q allele and (RQ+QQ) genotype were significantly higher among the CAD patients without myocardial infarction (MI) history than among those with MI history (P<0.05). However, HVR4 polymorphism was not significantly different within groups. We only find one normal control of factorII(G20210A) mutation. No coagulation factor V(G1691A) mutation was found in the CAD patients and controls. Conclusion: The factor II(G20210A),V(G1691A) mutation is absent and may not be a major genetic factor for CAD and/or MI; the Q allele of the R353Q polymorphism of the factor VII gene may be a protective genetic factor against myocardial infarction in Chinese.

  1. Targeting tissue factor on tumour cells and angiogenic vascular endothelial cells by factor VII-targeted verteporfin photodynamic therapy for breast cancer in vitro and in vivo in mice

    The objective of this study was to develop a ligand-targeted photodynamic therapy (tPDT) by conjugating factor VII (fVII) protein with photosensitiser verteporfin in order to overcome the poor selectivity and enhance the effect of non-targeted PDT (ntPDT) for cancer. fVII is a natural ligand for receptor tissue factor (TF) with high affinity and specificity. The reason for targeting receptor TF for the development of tPDT is that TF is a common but specific target on angiogenic tumour vascular endothelial cells (VEC) and many types of tumour cells, including solid tumours and leukaemia. Murine factor VII protein (mfVII) containing a mutation (Lys341Ala) was covalently conjugated via a cross linker EDC with Veterporfin (VP) that was extracted from liposomal Visudyne, and then free VP was separated by Sephadex G50 spin columns. fVII-tPDT using mfVII-VP conjugate, compared to ntPDT, was tested in vitro for the killing of breast cancer cells and VEGF-stimulated VEC and in vivo for inhibiting the tumour growth of breast tumours in a mouse xenograft model. We showed that: (i) fVII protein could be conjugated with VP without affecting its binding activity; (ii) fVII-tPDT could selectively kill TF-expressing breast cancer cells and VEGF-stimulated angiogenic HUVECs but had no side effects on non-TF expressing unstimulated HUVEC, CHO-K1 and 293 cells; (iii) fVII targeting enhanced the effect of VP PDT by three to four fold; (iii) fVII-tPDT induced significantly stronger levels of apoptosis and necrosis than ntPDT; and (iv) fVII-tPDT had a significantly stronger effect on inhibiting breast tumour growth in mice than ntPDT. We conclude that the fVII-targeted VP PDT that we report here is a novel and effective therapeutic with improved selectivity for the treatment of breast cancer. Since TF is expressed on many types of cancer cells including leukaemic cells and selectively on angiogenic tumour VECs, fVII-tPDT could have broad therapeutic applications for other solid cancers

  2. Linkage and evolutionary relationships of the genes for human clotting factors VII and X

    Polumbo, P.A.; Dierwechter, L.M.; Whitesides, L.D. [Vanderbilt Univ. School of Medicine, Nashville, TN (United States)] [and others

    1994-09-01

    Factors VII and X are structurally similar serine proteases which are involved in blood coagulation. The gene for factor X (F10) has been previously mapped to human chromosome 13q34 by in situ hybridization and DNA linkage analysis, and both F10 and the gene for factor VII (F7) have been mapped to this region by dosage studies in patients with chromosomal aneuploidies. We have determined the genetic distance between F7 and F10 using PCR-based polymorphisms and DNA linkage analysis. The F7 locus lies 6 centiMorgans proximal to F10, and the most likely locus order is D13S123-[D13S107/D13S52]-F7-D13S49-D13S54-F10. F7 and F10 share 52% sequence homology in their coding regions, and their exonic organization is identical to the genes for factor IX and protein C. DNA sequence analysis using the neighbor-joining method confirms the evolution of F7 and F10 from a common ancestral gene, but the analysis suggests that one did not arise directly from the other by tandem duplication on chromosome 13. These data contribute to our knowledge of the evolution of the family of vitamin K-dependent serine proteases, and should prove useful in studying families with inherited deficiencies in factor VII or X.

  3. Plasma concentrations of blood coagulation factor VII measured by immunochemical and amidolytic methods

    Bladbjerg, E-M; Gram, J; Jespersen, J

    2000-01-01

    Ever since the coagulant activity of blood coagulation factor VII (FVII:C) was identified as a risk indicator of cardiac death, a large number of studies have measured FVII protein concentrations in plasma. FVII protein concentrations are either measured immunologically with an ELISA method (FVII......:Ag) or estimated with an amidolytic method (FVII:Am). We have investigated whether FVII:Am is a valuable alternative to FVII:Ag. FVII:Ag and FVII:Am were measured in 147 plasma samples from blood donors, patients on oral anticoagulant therapy, postmenopausal women on hormone replacement therapy, in...... after omitting the data from patients on oral anticoagulant therapy, with mean values of 113 U/ml for FVII:Ag and 110 U/ml for FVII:Am (p < 0.01). In a linear regression analysis, the intercept (alpha=-21.50) was different from zero (p < 0.0001) and the slope (beta=1.16) was different from 1.0 (p < 0...

  4. Prevention of bleeding and hemorrhagic complications in surgical patients with inherited factor VII deficiency.

    Wiszniewski, Adam; Szczepanik, Andrzej; Misiak, Andrzej; Bykowska, Ksenia; Szopiński, Piotr

    2015-04-01

    Inherited factor VII (FVII) deficiency is a rare autosomal recessive hemorrhagic disorder. The major clinical symptoms include: bleeding from the oral cavity, epistaxis, menorrhagia, spontaneous hemarthros, bleeding to the gastrointestinal tract and central nervous system, and perioperative bleeding. The aim of this study was to present our experience in preventing bleeding and hemorrhagic disorders in surgical patients with inherited FVII deficiency by using recombinant activated FVIIa (rFVIIa), and with prothrombin complex concentrates (PCCs). In 2002-2011, 17 patients with inherited FVII deficiency underwent surgery. Thirteen patients had isolated FVII deficiency below 10%, and four patients 10-25. To prevent bleeding and hemorrhagic complications, we administered small single doses of rFVIIa (Novo-Seven) at 12-h intervals to 15 patients on surgery day and on day 1 following surgery, then every 24 h; PCCs were administered (Prothromplex, Beriplex) to two patients. No symptoms of bleeding, hemorrhagic or thromboembolic complications were observed in the perioperative and 1-month observation period in surgical patients treated with rFVIIa. One patient treated with PCC (Prothromplex) developed distal deep vein thrombosis on postoperative day 7. The results suggest that small, single, every 12-h doses of rFVIIa (NovoSeven) and in next days after surgery one time every 24 h are well tolerated and effective for prevention of thromboembolic, bleeding and hemorrhagic complications in FVII-deficient patients. Antithrombotic prophylaxis with low-molecular-weight heparin should be applied in patients using PCCs. PMID:25688458

  5. Mutagenesis in sequence encoding of human factor VII for gene therapy of hemophilia

    B Kazemi

    2009-12-01

    Full Text Available "nBackground: Current treatment of hemophilia which is one of the most common bleeding disorders, involves replacement therapy using concentrates of FVIII and FIX .However, these concentrates have been associated with viral infections and thromboembolic complications and development of antibodies. "nThe use of recombinant human factor VII (rhFVII is effective  for the treatment of patients with  hemophilia A or B, who develop antibodies ( referred as inhibitors against  replacement therapy , because it induces coagulation independent of FVIII and FIX. However, its short half-life and high cost have limited its use. One potential solution to this problem may be the use of FVIIa gene transfer, which would attain continuing therapeutic levels of expression from a single injection. The aim of this study was to engineer a novel hFVII (human FVII gene containing a cleavage site for the intracellular protease and furin, by PCR mutagenesis "nMethods: The sequence encoding light and heavy chains of hFVII, were amplified by using hFVII/pTZ57R and specific primers, separately. The PCR products were cloned in pTZ57R vector. "nResults and discussion: Cloning was confirmed by restriction analysis or PCR amplification using specific primers and plasmid universal primers. Mutagenesis of sequence encoding light and heavy chain was confirmed by restriction enzyme. "nConclusion: In the present study, it was provided recombinant plasmids based on mutant form of DNA encoding light and heavy chains.  Joining mutant form of DNA encoding light chain with mutant heavy chain led to a new variant of hFVII. This variant can be activated by furin and an increase in the proportion of activated form of FVII. This mutant form of hFVII may be used for gene therapy of hemophilia.

  6. Severe coagulation factor VII deficiency caused by a novel homozygous mutation (p. Trp284Gly) in loop 140s.

    Hao, Xiuping; Cheng, XiaoLi; Ye, Jiajia; Wang, Yingyu; Yang, LiHong; Wang, Mingshan; Jin, Yanhui

    2016-06-01

    Congenital coagulation factor VII (FVII) deficiency is a rare disorder caused by mutation in F7 gene. Herein, we reported a patient who had unexplained hematuria and vertigo with consanguineous parents. He has been diagnosed as having FVII deficiency based on the results of reduced FVII activity (2.0%) and antigen (12.8%). The thrombin generation tests verified that the proband has obstacles in producing thrombin. Direct sequencing analysis revealed a novel homozygous missense mutation p.Trp284Gly. Also noteworthy is the fact that the mutational residue belongs to structurally conserved loop 140s, which majorly undergo rearrangement after FVII activation. Model analysis indicated that the substitution disrupts these native hydrophobic interactions, which are of great importance to the conformation in the activation domain of FVIIa. PMID:26761581

  7. 凝血因子VII基因突变的检测%The detection of factor VII gene mutation

    吴玉水; 朱晓辉; 程烽; 何菊英; 朱忠勇; 方国安; 林青

    2001-01-01

    To identify mutation in the factor VII gene of a patient with hereditary factor VII deficiency from Fuzhou city of Fujian province,we analyzed the factor VII gene of the patient and her mother by using polymerase chain reaction combined with restricted endonuclease enzyme HgiC I digestion,The results showed a homozygous C329G mutation in the patient,and a heterozygous one in her mother.This is the second pedigree of hereditary factor VII deficiency in chinese with factor VII gene C329G mutation.%目的为检测福建省福州市一个遗传性凝血因子VII缺乏症先证者的因子VII基因突变类型。方法采有PCR结合限制性内切酶HgiCI,以先证者及其母亲的FVII基因片进行分析。结果表明先证者的FVII基因为C329G纯合子,其母亲为杂合子。结论该家系为FVII基因存在C329G突变的第2个遗传性因子VII缺乏症家系。

  8. A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

    Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

    2012-12-01

    Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII. PMID:23244324

  9. Management of Pregnancy in a Chilean Patient with Congenital Deficiency of Factor VII and Glanzmann's Thrombasthenia Variant

    Murray, Nigel P.; Garcia, Claudio; Ilabaca, Javier; Lagos, Nestor

    2014-01-01

    Patients with inherited bleeding disorders are rare in obstetric practice but present with prolonged bleeding even after minor invasive procedures. They require a combined approach with obstetric and hematological management of each case, including the neonatal management of a possibly affected fetus. We present the case of a pregnancy in a patient with combined Factor VII deficiency and Glanzmann's thrombasthenia, the successful obstetric and hematological management of the case, and a review of the literature. PMID:25525535

  10. Management of Pregnancy in a Chilean Patient with Congenital Deficiency of Factor VII and Glanzmann’s Thrombasthenia Variant

    Nigel P. Murray

    2014-01-01

    Full Text Available Patients with inherited bleeding disorders are rare in obstetric practice but present with prolonged bleeding even after minor invasive procedures. They require a combined approach with obstetric and hematological management of each case, including the neonatal management of a possibly affected fetus. We present the case of a pregnancy in a patient with combined Factor VII deficiency and Glanzmann’s thrombasthenia, the successful obstetric and hematological management of the case, and a review of the literature.

  11. Recombinant factor VII (NovoSeven) in intraoperative blood saving during neurosurgical treatment of the brain arteriovenous malformation

    Novak Vesna; Petrović Budimir; Čalija Branko; Mitov Ljiljana; Rančić Zoran

    2007-01-01

    Background. Cerebral arteriovenous (AV) malformation causes, due to the increased blood flow through a malformation, a massive intraoperative bleeding complicating, so, surgical treatment. The use of intraoperative blood saving apparatus during surgery and a recombinant factor VII-a (NovoSeven) significantly reduce complications during surgical treatment. Case report. We reported a case of surgical treatment of the patient with AV malformation of IV stage according to the Spetzler-Martin scal...

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

    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...... activity in plasma. Significant effects of pH were observed for clotting time, clot formation time, maximum clot firmness, and factor VII coagulant activity in the direction of longer clot formation times and less firm clots with decreasing pH. Temperature had significant effects on clotting time, clot...

  13. Uso del FVII activado recombinante en la enfermedad de Rendú-Osler-Weber o telangiectasia hemorrágica hereditaria y sangramiento digestivo: Primer caso comunicado en Cuba Use of recombinat activated factor VII in Rendú-Osler-Weber's disease or hereditary hemorrhagic talangiectasia and digestive bleeding: First case reported in Cuba

    Olga M Agramonte Llanes; Delfina Almagro Vázquez; Heydi Garrote Santana; Sandra Sarduy Sáez; Yaneth Zamora González

    2008-01-01

    El Factor VII activado recombinante (rFVIIa Novoseven, Novonordisk, Dinamarca) ha sido usado con éxito en el tratamiento de las hemorragias en pacientes hemofílicos con inhibidores, en la deficiencia congénita del FVII y en la tromboastenia de Glanzmann. Además, se ha planteado su uso en pacientes no hemofílicos con anticuerpos adquiridos contra el FVIII (hemofilia adquirida) y otros trastornos de la función plaquetaria como el síndrome de Bernard Soulier (SBS). Administrado en dosis farmacol...

  14. In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. possible implications for measurements in vivo after heparin therapy.

    Bladbjerg, E M; Larsen, L F; Ostergaard, P; Jespersen, J

    2000-12-01

    The coagulant activity of blood coagulation factor VII (FVII:C) can be lowered by changes in lifestyle and by therapeutic intervention, e.g. heparin infusion. The question is, however, whether FVII:C determined ex vivo is a valid measure of the FVII activity in vivo. We measured plasma FVII:C, activated FVII (FVIIa), FVII protein (FVII:Ag), tissue factor pathway inhibitor (TFPI), triglycerides, and free fatty acids (FFA) before and 15 min after infusion of a bolus of unfractionated heparin (50 IU/kg body weight) in 12 healthy subjects. Additionally, we conducted in vitro experiments to investigate the effect of unfractionated heparin and TFPI, which is released from the endothelium by heparin, on FVII:C, FVIIa, and FVII:Ag. Heparin infusion decreased triglycerides and increased FFA and TFPI. This was accompanied by significant reductions in FVIIa, FVII:C and FVII:Ag. In vitro, anti-TFPI antibodies increased FVIIa and FVII:C, and heparin reduced FVIIa. The heparinase Hepzyme was unable to abolish the effect of heparin. There were no in vitro effects on FVII:Ag. We conclude that, due to interference by TFPI and heparin in post-heparin plasma, it is impossible to measure the in vivo FVII activity by means of FVII clotting assays. These assays should therefore not be used to measure the coagulation status of patients in heparin therapy, unless extraordinary precautions are taken to eliminate TFPI and heparin effects ex vivo. The observed effect of heparin on FVII:Ag should be investigated further. PMID:11132652

  15. R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study

    Pérez-Jiménez Francisco

    2011-04-01

    Full Text Available Abstract Background Heterozygous Familial Hypercholesterolemia (FH is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. Results This case-control study comprised 720 patients (546 with FH and 174 controls. We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag and whether they could be predictive factors for cardiovascular risk. 75% (410 of the patients with FH were RR, 23% (127 RQ and 1.6% (9 QQ; in the control group 75.3% (131 were RR, 21.3% (37 RQ and 3.4% (6 QQ (p = 0.32. No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease, either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96. In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97. Conclusions Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.

  16. Recombinant factor VII (NovoSeven in intraoperative blood saving during neurosurgical treatment of the brain arteriovenous malformation

    Novak Vesna

    2007-01-01

    Full Text Available Background. Cerebral arteriovenous (AV malformation causes, due to the increased blood flow through a malformation, a massive intraoperative bleeding complicating, so, surgical treatment. The use of intraoperative blood saving apparatus during surgery and a recombinant factor VII-a (NovoSeven significantly reduce complications during surgical treatment. Case report. We reported a case of surgical treatment of the patient with AV malformation of IV stage according to the Spetzler-Martin scale, in the brain. Due to a possible heavy bleeding we used a apparatus for intrasurgical blood recovery, Cell Saver, Sequestra 1 000, Medtronic, U.S.A., and recombinant human factor VIIa (rFVIIa - NovoSeven, NovoNordisk, Denmark to control bleeding and restore an adequate hemostasis. Conclusion. The use of an apparatus for intraoperative blood saving, as well as the NovoSeven preparation in the management of AV malformation of IV stage, showed to be successful.

  17. Therapeutic neonatal hepatic gene therapy in mucopolysaccharidosis VII dogs

    Ponder, Katherine Parker; Melniczek, John R.; Xu, Lingfei; Weil, Margaret A.; O'Malley, Thomas M; O'Donnell, Patricia A.; Knox, Van W.; Aguirre, Gustavo D.; Mazrier, Hamutal; Ellinwood, N. Matthew; Sleeper, Meg; Maguire, Albert M.; Volk, Susan W.; Mango, Robert L.; Zweigle, Jean

    2002-01-01

    Dogs with mucopolysaccharidosis VII (MPS VII) were injected intravenously at 2–3 days of age with a retroviral vector (RV) expressing canine β-glucuronidase (cGUSB). Five animals received RV alone, and two dogs received hepatocyte growth factor (HGF) before RV in an attempt to increase transduction efficiency. Transduced hepatocytes expanded clonally during normal liver growth and secreted enzyme with mannose 6-phosphate. Serum GUSB activity was stable for up to 14 months at normal levels for...

  18. XMM-Newton Survey of Local O VII Absorption Lines in the Spectra of Active Galactic Nuclei

    Fang, Taotao; Bullock, James S; Ma, Renyi

    2015-01-01

    Highly ionized, z=0 metal absorption lines detected in the X-ray spectra of background active galactic nuclei (AGNs) provide an effective method to probe the hot ($T\\sim10^6$ K) gas and its metal content in and around the Milky Way. We present an all-sky survey of the $K_{\\alpha}$ transition of the local O VII absorption lines obtained by Voigt-profile fitting archival XMM-Newton observations. A total of 43 AGNs were selected, among which 12 are BL Lac-type AGNs, and the rest are Seyfert 1 galaxies. At above the $3\\sigma$ level the local O VII absorption lines were detected in 21 AGNs, among which 7 were newly discovered in this work. The sky covering fraction, defined as the ratio between the number of detections and the sample size, increases from at about 40% for all targets to 100% for the brightest targets, suggesting a uniform distribution of the O VII absorbers. We correlate the line equivalent width with the Galactic coordinates and do not find any strong correlations between these quantities. Some AG...

  19. Rat Prostate Tumors Express Cancer Procoagulant, an Activator of Coagulation Factor X

    Kamocka, Malgorzata; Pollard, Morris; Suckow, Mark; Wojciech P. Mielicki; Rosen, Elliot D.

    2008-01-01

    Two common procoagulant activities associated with tumors are tissue factor and cancer procoagulant (CP), an activator of coagulation factor X. We have identified a convenient source of CP in transplanted Lobund–Wistar rat PA3 prostate tumors. CP activity was purified from 5 independent transplanted prostate tumors by column chromatography. The protein activated factor X in the absence of TF and factor VII. An antihuman CP antibody recognized rat CP in an ELISA and inactivated CP activity in ...

  20. Population genetic and phylogenetic evidence for positive selection on regulatory mutations at the factor VII locus in humans.

    Hahn, Matthew W; Rockman, Matthew V; Soranzo, Nicole; Goldstein, David B; Wray, Gregory A

    2004-06-01

    The abundance of cis-regulatory polymorphisms in humans suggests that many may have been important in human evolution, but evidence for their role is relatively rare. Four common polymorphisms in the 5' promoter region of factor VII (F7), a coagulation factor, have been shown to affect its transcription and protein abundance both in vitro and in vivo. Three of these polymorphisms have low-frequency alleles that decrease expression of F7 and may provide protection against myocardial infarction (heart attacks). The fourth polymorphism has a minor allele that increases the level of transcription. To look for evidence of natural selection on the cis-regulatory variants flanking F7, we genotyped three of the polymorphisms in six Old World populations for which we also have data from a group of putatively neutral SNPs. Our population genetic analysis shows evidence for selection within humans; surprisingly, the strongest evidence is due to a large increase in frequency of the high-expression variant in Singaporean Chinese. Further characterization of a Japanese population shows that at least part of the increase in frequency of the high-expression allele is found in other East Asian populations. In addition, to examine interspecific patterns of selection we sequenced the homologous 5' noncoding region in chimpanzees, bonobos, a gorilla, an orangutan, and a baboon. Analysis of these data reveals an excess of fixed differences within transcription factor binding sites along the human lineage. Our results thus further support the hypothesis that regulatory mutations have been important in human evolution. PMID:15238535

  1. Influence of a treatment by PPSB (concentrate of II, VII, X and IX factors) on the hemorrhagic syndrome in the baboon irradiated in mixed neutron-gamma fluence

    The daily administration of PPSB (concentrate of II, VII, X, IX factors) to baboons submitted to a whole-body irradiation in mixed neutron-gamma fluence at doses of 5 and 6 Gy, corrected the alterations of the prothrombin time, the APTT and the chronometric dosage of Vitamin K dependent hepatic factors. The treatment had a positive effect in the survey at 5 Gy (LD50) but did not modify it at 6 Gy (LD90). At this dose, it was observed a dramatic increase in the thrombin time. It developed on the three days preceding the death and may be related to a fibrinolysis

  2. Pathogenesis of Mitral Valve Disease in Mucopolysaccharidosis VII Dogs

    Bigg, Paul W.; Baldo, Guilherme; Sleeper, Meg M.; O'Donnell, Patricia A.; Bai, Hanqing; Rokkam, Venkata R.P.; Liu, Yuli; Wu, Susan; Giugliani, Roberto; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

    2013-01-01

    Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs) in lysosomes and multisystemic disease with cardiavascular manifestations. The goal here was to determine the pathogenesis of mitral valve (MV) disease in MPS VII dogs. Untreated MPS VII dogs had a marked reduction in the histochemical signal for structurally-intact collagen in the MV at 6 months of age, when mitral regurgitation had developed...

  3. Pathogenesis of lumbar spine disease in mucopolysaccharidosis VII

    Smith, Lachlan J.; Baldo, Guilherme; Wu, Susan; Liu, Yuli; Whyte, Michael P.; Giugliani, Roberto; Elliott, Dawn M; Haskins, Mark E.; Ponder, Katherine P.

    2012-01-01

    Mucopolysaccharidosis type VII (MPS VII) is characterized by deficient β-glucuronidase (GUSB) activity, which leads to accumulation of chondroitin, heparan and dermatan sulfate glycosaminoglycans (GAGs), and multisystemic disease. MPS VII patients can develop kypho-scoliotic deformity and spinal cord compression due to disease of intervertebral discs, vertebral bodies, and associated tissues. We have previously demonstrated in MPS VII dogs that intervertebral discs degenerate, vertebral bodie...

  4. Blood flow controls coagulation onset via the positive feedback of factor VII activation by factor Xa

    Panteleev Mikhail A; Lobanova Ekaterina S; Shibeko Alexey M; Ataullakhanov Fazoil I

    2010-01-01

    Abstract Background Blood coagulation is a complex network of biochemical reactions, which is peculiar in that it is time- and space-dependent, and has to function in the presence of rapid flow. Recent experimental reports suggest that flow plays a significant role in its regulation. The objective of this study was to use systems biology techniques to investigate this regulation and to identify mechanisms creating a flow-dependent switch in the coagulation onset. Results Using a detailed mech...

  5. Study of FK Comae Berenices: VII. Correlating photospheric and chromospheric activity

    Vida, K.; Korhonen, H.; Ilyin, I. V.; Oláh, K.; Andersen, M. I.; Hackman, T.

    2015-01-01

    We study the connection between the chromospheric and photospheric behaviour of the active late-type star FK Comae. We use spot temperature modelling, light curve inversion based on narrow- and wide-band photometric measurements, Halpha observations from 1997-2010, and Doppler maps from 2004-2010 to compare the behaviour of chromospheric and photospheric features. Investigating low-resolution Halpha spectra we find that the changes in the chromosphere seem to happen mainly on a time scale lon...

  6. Study of FK Comae Berenices. VII. Correlating photospheric and chromospheric activity

    Vida, K.; Korhonen, H.; Ilyin, I. V.; Oláh, K.; Andersen, M. I.; Hackman, T.

    2015-08-01

    Aims: We study the connection between the chromospheric and photospheric behaviour of the active late-type star FK Comae. Methods: We use spot temperature modelling, light curve inversion based on narrow- and wide-band photometric measurements, Hα observations from 1997-2010, and Doppler maps from 2004-2010 to compare the behaviour of chromospheric and photospheric features. Results: Investigating low-resolution Hα spectra, we find that the changes in the chromosphere seem to happen mainly on a time scale longer than a few hours, but shorter variations are also observed. According to the Hα measurements, prominences are often found in the chromosphere that reach to more than a stellar radius and are stable for weeks, and they seem to be often, but not always connected to dark photospheric spots. The rotational modulation of the Hα emission typically seems to be anticorrelated with the light curve, but we did not find convincing evidence of a clear connection in the long-term trends of the Hα emission and the brightness of the star. In addition, FK Com seems to be in an unusually quiet state in 2009-2010 with very little chromospheric activity and low spot contrast, which might indicate the long-term decrease in activity. Based on the observations obtained at the Nordic Optical Telescope, Observatorio Roque de los Muchachos, La Palma, Canary Islands, Spain; Kitt Peak National Observatory, USA.Figures 12, 13, and Appendix A are available in electronic form at http://www.aanda.orgNew data are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/580/A64

  7. Roche tomography of cataclysmic variables - VII. The long-term magnetic activity of AE Aqr

    Hill, C. A.; Watson, C. A.; Steeghs, D.; Dhillon, V. S.; Shahbaz, T.

    2016-06-01

    We present a long-term study of the secondary star in the cataclysmic variable AE Aqr, using Roche tomography to indirectly image starspots on the stellar surface spanning 8 years of observations. The seven maps show an abundance of spot features at both high and low latitudes. We find that all maps have at least one large high-latitude spot region, and we discuss its complex evolution between maps, as well as its compatibility with current dynamo theories. Furthermore, we see the apparent growth in fractional spot coverage, fs, around 45° latitude over the duration of observations, with a persistently high fs near latitudes of 20°. These bands of spots may form as part of a magnetic activity cycle, with magnetic flux tubes emerging at different latitudes, similar to the `butterfly' diagram for the Sun. We discuss the nature of flux tube emergence in close binaries, as well as the activity of AE Aqr in the context of other stars.

  8. Roche tomography of cataclysmic variables - VII. The long-term magnetic activity of AE Aqr

    Hill, C A; Steeghs, D; Dhillon, V S; Shahbaz, T

    2016-01-01

    We present a long-term study of the secondary star in the cataclysmic variable AE~Aqr, using Roche tomography to indirectly image starspots on the stellar surface spanning 8~years of observations. The 7 maps show an abundance of spot features at both high and low latitudes. We find that all maps have at least one large high-latitude spot region, and we discuss its complex evolution between maps, as well as its compatibility with current dynamo theories. Furthermore, we see the apparent growth in fractional spot coverage, $f_{\\mathrm{s}}$, around $45^{\\circ}$~latitude over the duration of observations, with a persistently high $f_{\\mathrm{s}}$ near latitudes of $20^{\\circ}$. These bands of spots may form as part of a magnetic activity cycle, with magnetic flux tubes emerging at different latitudes, similar to the `butterfly' diagram for the Sun. We discuss the nature of flux tube emergence in close binaries, as well as the activity of AE~Aqr in the context of other stars.

  9. MOJAVE: MONITORING OF JETS IN ACTIVE GALACTIC NUCLEI WITH VLBA EXPERIMENTS. VII. BLAZAR JET ACCELERATION

    We discuss acceleration measurements for a large sample of extragalactic radio jets from the Monitoring Of Jets in Active Galactic Nuclei with VLBA Experiments (MOJAVE) program, which studies the parsec-scale jet structure and kinematics of a complete, flux-density-limited sample of active galactic nuclei (AGNs). Accelerations are measured from the apparent motion of individual jet features or 'components' which may represent patterns in the jet flow. We find that significant accelerations are common both parallel and perpendicular to the observed component velocities. Parallel accelerations, representing changes in apparent speed, are generally larger than perpendicular acceleration that represent changes in apparent direction. The trend for larger parallel accelerations indicates that a significant fraction of these changes in apparent speed are due to changes in intrinsic speed of the component rather than changes in direction to the line of sight. We find an overall tendency for components with increasing apparent speed to be closer to the base of their jets than components with decreasing apparent speed. This suggests a link between the observed pattern motions and the underlying flow which, in some cases, may increase in speed close to the base and decrease in speed further out; however, common hydrodynamical processes for propagating shocks may also play a role. About half of the components show 'non-radial' motion, or a misalignment between the component's structural position angle and its velocity direction, and these misalignments generally better align the component motion with the downstream emission. Perpendicular accelerations are closely linked with non-radial motion. When observed together, perpendicular accelerations are usually in the correct direction to have caused the observed misalignment.

  10. Study of FK Comae Berenices: VII. Correlating photospheric and chromospheric activity

    Vida, K; Ilyin, I V; Oláh, K; Andersen, M I; Hackman, T

    2015-01-01

    We study the connection between the chromospheric and photospheric behaviour of the active late-type star FK Comae. We use spot temperature modelling, light curve inversion based on narrow- and wide-band photometric measurements, Halpha observations from 1997-2010, and Doppler maps from 2004-2010 to compare the behaviour of chromospheric and photospheric features. Investigating low-resolution Halpha spectra we find that the changes in the chromosphere seem to happen mainly on a time scale longer than a few hours, but shorter variations were also observed. According to the Halpha measurements prominences are often found in the chromosphere that reach to more than a stellar radius and are stable for weeks, and which seem to be often, but not every time connected with dark photospheric spots. The rotational modulation of the Halpha emission seems to typically be anticorrelated with the light curve, but we did not find convincing evidence of a clear connection in the long-term trends of the Halpha emission and th...

  11. Tissue factor expression in ovarian cancer: implications for immunotherapy with hI-con1, a factor VII-IgGF(c) chimeric protein targeting tissue factor.

    Cocco, Emiliano; Varughese, Joyce; Buza, Natalia; Bellone, Stefania; Lin, Ken-Yu; Bellone, Marta; Todeschini, Paola; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Carrara, Luisa; Tassi, Renata; Pecorelli, Sergio; Lockwood, Charles J; Santin, Alessandro D

    2011-10-01

    We evaluated the expression of tissue factor (TF) in ovarian cancer (EOC) and the potential of hI-con1, an antibody-like molecule targeting TF, as a novel form of therapy against chemotherapy-resistant ovarian disease. We studied the expression of TF in 88 EOC by immunohistochemistry (IHC) and real-time-PCR (qRT-PCR) and the levels of membrane-bound-complement-regulatory-proteins CD46, CD55 and CD59 in primary EOC cell lines by flow-cytometry. Sensitivity to hI-con1-dependent-cell-mediated-cytotoxicity (IDCC), complement-dependent-cell-cytotoxicity and inhibition of IDCC by γ-immunoglobulin were evaluated in 5-h (51)chromium-release-assays. Cytoplasmic and/or membrane TF expression was observed in 24 out of 25 (96%) of the EOC samples tested by IHC, but not in normal ovarian-tissue. EOC with clear cell histology significantly overexpress TF when compared to serous, endometrioid, or undifferentiated tumors by qRT-PCR. With a single exception, all primary EOC that overexpressed TF demonstrated high levels of CD46, CD55 and CD59 and regardless of their histology or resistance to chemotherapy, were highly sensitive to IDCC. The effect of complement and physiologic doses of γ-immunoglobulin on IDCC in ovarian cancer cell lines overexpressing TF was tumor specific and related to the overexpression of CD59 on tumor cells. Small-interfering-RNA-mediated knockdown of CD59 expression in ovarian tumors significantly increased hI-con1-mediated cytotoxic activity in vitro. Finally, low doses of interleukin-2 further increased the cytotoxic effect induced by hI-con1 (P < 0.01). hI-con1 molecule induces strong cytotoxicity against primary chemotherapy-resistant ovarian cancer cell lines overexpressing TF and may represent a novel therapeutic agent for the treatment of ovarian tumors refractory to standard treatment modalities. PMID:21725665

  12. Tissue factor expression in ovarian cancer: implications for immunotherapy with hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor

    Cocco, Emiliano; Varughese, Joyce; Buza, Natalia; Bellone, Stefania; Lin, Ken-Yu; Bellone, Marta; Todeschini, Paola; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E.; Rutherford, Thomas J.; Carrara, Luisa; Tassi, Renata; Pecorelli, Sergio; Lockwood, Charles J.

    2013-01-01

    We evaluated the expression of tissue factor (TF) in ovarian cancer (EOC) and the potential of hI-con1, an antibody-like molecule targeting TF, as a novel form of therapy against chemotherapy-resistant ovarian disease. We studied the expression of TF in 88 EOC by immunohistochemistry (IHC) and real-time-PCR (qRT-PCR) and the levels of membrane-bound-complement-regulatory-proteins CD46, CD55 and CD59 in primary EOC cell lines by flow-cytometry. Sensitivity to hI-con1-dependent-cell-mediated-cytotoxicity (IDCC), complement-dependent-cell-cytotoxicity and inhibition of IDCC by γ-immunoglobulin were evaluated in 5-h 51chromium-release-assays. Cytoplasmic and/or membrane TF expression was observed in 24 out of 25 (96%) of the EOC samples tested by IHC, but not in normal ovarian-tissue. EOC with clear cell histology significantly overexpress TF when compared to serous, endometrioid, or undifferentiated tumors by qRT-PCR. With a single exception, all primary EOC that overexpressed TF demonstrated high levels of CD46, CD55 and CD59 and regardless of their histology or resistance to chemotherapy, were highly sensitive to IDCC. The effect of complement and physiologic doses of γ-immunoglobulin on IDCC in ovarian cancer cell lines overexpressing TF was tumor specific and related to the overexpression of CD59 on tumor cells. Small-interfering-RNA-mediated knockdown of CD59 expression in ovarian tumors significantly increased hI-con1-mediated cytotoxic activity in vitro. Finally, low doses of interleukin-2 further increased the cytotoxic effect induced by hI-con1 (P < 0.01). hI-con1 molecule induces strong cytotoxicity against primary chemotherapy-resistant ovarian cancer cell lines overexpressing TF and may represent a novel therapeutic agent for the treatment of ovarian tumors refractory to standard treatment modalities. PMID:21725665

  13. Proceedings of simulators VII

    In the last three years the simulators conference has each year increased in attendance, number and quality of papers. Particularly impressive is the roll of the nuclear simulators group that increased form just a few sessions in 1987 to 24 sessions in 1990. It is now the largest and main conference on simulators and applied simulation sponsored by the Society of Computer Simulation, International. This increase has been made possible due to strong contributions from the session chairmen at all levels, and the activity of the Utility Simulator Users Group (USUG) that its annual meeting became part of the conference. Simulators VII concentrates on simulation, modeling and simulators mainly in the nuclear industry. A special plenary session (organized by Ariel Sharon) is dedicated to the simulators market place as viewed by the management of three major simulator vendors: CAE, Singer-Link and Westinghouse. This session demonstrates the large role that power plant simulators have in the nuclear power industry present and future activities. The excellent operating record of the commercial nuclear power plants in the U.S. and abroad is to a large extent due to the extensive use of simulators. The nuclear simulators program has four large groups: Mathematic Modeling, New Frontiers in simulators, Applied Simulator Technology, Simulation of Complex Transients and Accidents

  14. Deoxyribonucleic acid repair in Escherichia coli mutants deficient in the 5'----3' exonuclease activity of deoxyribonucleic acid polymerase I and exonuclease VII

    A series of Escherichia coli strains deficient in the 5'----3' exonuclease activity associated with deoxyribonucleic acid (DNA) polymerase I (exonuclease VI) and exonuclease VII has been constructed. Both of these enzymes are capable of pyrimidine dimer excision in vitro. These strains were examined for conditional lethality, sensitivity to ultraviolet (UV) and X-irradiation, postirradiation DNA degradation, and ability to excise pyrimidine dimers. It was found that strains deficient in both exonuclease VI (polAex-) and exonuclease VII (xseA-) are significantly reduced in their ability to survive incubation at elevated temperature (43 degrees C) beyond the reduction previously observed for the polAex single mutants. The UV and X-ray sensitivity of the exonuclease VI-deficient strains was not increased by the addition of the xseA7 mutation. Mutants deficient in both enzymes are about as efficient as wild-type strains at excising dimers produced by up to 40 J/m2 UV. At higher doses strains containing only polAex- mutations show reduced ability to excise dimers; however, the interpretation of dimer excision data at these doses is complicated by extreme postirradiation DNA degradation in these strains. The additional deficiency in the polAex xseA7 double-mutant strains has no significant effect on either postirradiation DNA degradation or the apparent deficiency in dimer excision at high UV doses observed in polAex single mutants

  15. Basic fibroblast growth factor: a missing link between collagen VII, increased collagenase, and squamous cell carcinoma in recessive dystrophic epidermolysis bullosa.

    Arbiser, J. L.; Fine, J D; Murrell, D.; Paller, A; Connors, S.; Keough, K.; Marsh, E.; Folkman, J

    1998-01-01

    BACKGROUND: Patients with recessive dystrophic epidermolysis bullosa (RDEB) have deficiencies of collagen type VII and have elevated levels of fibroblast collagenase, and a greatly increased risk of cutaneous squamous cell carcinoma. Patients with other genetic blistering disorders do not have elevated collagenase or an increased risk of squamous cell carcinoma, despite chronic wounding. The connection between collagen type VII deficiency, increased collagenase, and squamous cell carcinoma is...

  16. Expression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor

    Rutherford Thomas J

    2011-06-01

    Full Text Available Abstract Background Cervical cancer continues to be an important worldwide health problem for women. Up to 35% of patients who are diagnosed with and appropriately treated for cervical cancer will recur and treatment results are poor for recurrent disease. Given these sobering statistics, development of novel therapies for cervical cancer remains a high priority. We evaluated the expression of Tissue Factor (TF in cervical cancer and the potential of hI-con1, an antibody-like-molecule targeted against TF, as a novel form of immunotherapy against multiple primary cervical carcinoma cell lines with squamous- and adenocarcinoma histology. Methods Because TF is a transmembrane receptor for coagulation factor VII/VIIa (fVII, in this study we evaluated the in vitro expression of TF in cervical carcinoma cell lines by immunohistochemistry (IHC, real time-PCR (qRT-PCR and flow cytometry. Sensitivity to hI-con1-dependent cell-mediated-cytotoxicity (IDCC was evaluated in 5-hrs-51chromium-release-assays against cervical cancer cell lines in vitro. Results Cytoplasmic and/or membrane TF expression was observed in 8 out of 8 (100% of the tumor tissues tested by IHC and in 100% (11 out of 11 of the cervical carcinoma cell lines tested by real-time-PCR and flow cytometry but not in normal cervical keratinocytes (p = 0.0023 qRT-PCR; p = 0.0042 flow cytometry. All primary cervical cancer cell lines tested overexpressing TF, regardless of their histology, were highly sensitive to IDCC (mean killing ± SD, 56.2% ± 15.9%, range, 32.4%-76.9%, p p = 0.025 while human serum did not significantly decrease IDCC against cervical cancer cell lines (p = 0.597. Conclusions TF is highly expressed in squamous and adenocarcinoma of the uterine cervix. hI-con1 induces strong cytotoxicity against primary cervical cancer cell lines overexpressing TF and may represent a novel therapeutic agent for the treatment of cervical cancer refractory to standard treatment modalities.

  17. Expression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor

    Cervical cancer continues to be an important worldwide health problem for women. Up to 35% of patients who are diagnosed with and appropriately treated for cervical cancer will recur and treatment results are poor for recurrent disease. Given these sobering statistics, development of novel therapies for cervical cancer remains a high priority. We evaluated the expression of Tissue Factor (TF) in cervical cancer and the potential of hI-con1, an antibody-like-molecule targeted against TF, as a novel form of immunotherapy against multiple primary cervical carcinoma cell lines with squamous- and adenocarcinoma histology. Because TF is a transmembrane receptor for coagulation factor VII/VIIa (fVII), in this study we evaluated the in vitro expression of TF in cervical carcinoma cell lines by immunohistochemistry (IHC), real time-PCR (qRT-PCR) and flow cytometry. Sensitivity to hI-con1-dependent cell-mediated-cytotoxicity (IDCC) was evaluated in 5-hrs-51chromium-release-assays against cervical cancer cell lines in vitro. Cytoplasmic and/or membrane TF expression was observed in 8 out of 8 (100%) of the tumor tissues tested by IHC and in 100% (11 out of 11) of the cervical carcinoma cell lines tested by real-time-PCR and flow cytometry but not in normal cervical keratinocytes (p = 0.0023 qRT-PCR; p = 0.0042 flow cytometry). All primary cervical cancer cell lines tested overexpressing TF, regardless of their histology, were highly sensitive to IDCC (mean killing ± SD, 56.2% ± 15.9%, range, 32.4%-76.9%, p < 0.001), while negligible cytotoxicity was seen in the absence of hI-con1 or in the presence of rituximab-control-antibody. Low doses of interleukin-2 further increased the cytotoxic effect induced by hI-con1 (p = 0.025) while human serum did not significantly decrease IDCC against cervical cancer cell lines (p = 0.597). TF is highly expressed in squamous and adenocarcinoma of the uterine cervix. hI-con1 induces strong cytotoxicity against primary cervical cancer cell

  18. Genetics Home Reference: mucopolysaccharidosis type VII

    ... Home Health Conditions mucopolysaccharidosis type VII mucopolysaccharidosis type VII Enable Javascript to view the expand/collapse boxes. ... All Open All Close All Description Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, is ...

  19. A high fat meal activates blood coagulation factor VII in rats

    Olsen, Aage K; Bladbjerg, Else M; Hansen, Axel K;

    2002-01-01

    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....../L), and FVIIa was significantly raised at 4 h (54 U/L) and 6 h (58 U/L) compared with baseline (29 U/L). No postprandial changes in FVIIc, FVIIam and TAT were observed. Glucose administration did not affect any variable. We conclude that the LEW/Mol rat is a promising model for use in future studies of...

  20. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage

    Mayer, Stephan A; Brun, Nikolai C; Begtrup, Kamilla;

    2008-01-01

    patients with intracerebral hemorrhage to receive placebo (268 patients), 20 microg of rFVIIa per kilogram of body weight (276 patients), or 80 microg of rFVIIa per kilogram (297 patients) within 4 hours after the onset of stroke. The primary end point was poor outcome, defined as severe disability or...... microg of rFVIIa per kilogram and by 3.8 ml (95% CI, 0.9 to 6.7; P=0.009) in the group receiving 80 microg, as compared with the placebo group. Despite this reduction in bleeding, there was no significant difference among the three groups in the proportion of patients with poor clinical outcome (24% in...

  1. SUPPORT FOR BEIR VII

    The office is supporting the continued funding of National Academy of Sciences Study to update our understanding of the effects of low-level radiation. In particular, this study, entitled the Biological Effects of Ionizing Radiation VII, will draw upon the most recent data avail...

  2. Antituberculosis agents. VII. Synthesis and in vitro evaluation of antimycobacterial activity and cytotoxicity of some N-piperazinyl quinolone derivatives.

    Foroumadi, A; Soltani, F; Asadipour, A

    2003-04-01

    A series of N-[2-(2,4-dichlorophenyl)-2-oxoethyl] and N-[2-aryl-2-benzyloxyimino ethyl]piperazinyl quinolones (5-13) have been prepared as part of a study to examine the relationship between structural modification at 7-position and activity against Mycobacterium tuberculosis. Primary screening was conducted at concentration of 6.25 micrograms/ml against M. tuberculosis H37Rv using BACTEC 460 radiometric system and BACTEC 12B medium. The actual minimum inhibitory concentrations (MIC) were determined for compounds demonstrating at least 90% inhibition in the primary screening. The results demonstrate that substitution of phenyl ring with 4- fluoro, 2, 4-difluoro and 2,4-dichloro groups resulted in variable inhibition percentage (Inh% = 7-101). Despite the significant antituberculosis activity of ciprofloxacin and norfloxacin derivatives containing 2-(2,4-dichlorophenyl)-2-oxoethyl moiety (MIC = 0.39 & 6.25 micrograms/ml), compounds with 2-aryl-2-(hydroxyimino)ethyl, 2-aryl-2-(benzyloxyimino)ethyl and 2-aryl-2-(4-chlorobenzyloxyimino)ethyl did not show any activity (MIC > 6.25 micrograms/ml, Inh% = -7 to 75). Active compounds were also screened by serial dilution to assess toxicity to a VERO cell line. While the most active compound 5a was not soluble in tissue culture media, compound 5b showed IC50 = 5.3 micrograms/ml. PMID:12806833

  3. 重组凝血因子Ⅶ表达和合成机制的研究进展%Research advances of recombinant coagulation factor VII expression and synthesizing mechanism

    彭林; 于笑; 蔡燕飞; 金坚; 李华钟

    2015-01-01

    Haemophilia is caused by lack of coagulation factor VIII or IX in patients′blood with inadequate hemostasis.Currently recombinant coagulation factor VII(rFVII)produced in different cells is used against clini-cal bleeding of haemophilia patients.To enhance the production and activity of rFVII;some eukaryotic cells such as baby hamster kidney(BHK);Chinese hamster ovary(CHO);insect cell and fish embryo;were used to express rFVII.Meanwhile;the effect of functional gene on the activity of rFVII and the limitation of rFVII production caused by post-translational modification were investigated by different methods.The role of rFVII in hemostasis;synthesis of rFVII in different eukaryotic cells and impact on production of post-translational modification are reviewed in this article.%血友病是由于人体内缺乏相应凝血因子造成的凝血障碍,目前主要利用基因重组技术在不同细胞中表达重组凝血因子Ⅶ(Ⅶ因子)从而对血友患者出血进行治疗。为有效提高重组Ⅶ因子的产量及活性,已有研究者尝试利用不同真核表达系统合成重组Ⅶ因子,如BHK细胞、CHO细胞、昆虫细胞和鱼胚胎等。同时,不同外源功能性基因对重组Ⅶ因子活性和翻译后修饰对表达产量的影响也通过不同方法进行探究。本文从Ⅶ因子在凝血途径中的作用、重组表达重组Ⅶ因子和翻译后修饰对合成的影响3个方面对重组Ⅶ因子表达和合成机制研究进行了综述。

  4. Ethylene bis-imidazoles are highly potent and selective activators for isozymes VA and VII of carbonic anhydrase, with a potential nootropic effect

    Draghici, Bogdan; Vullo, Daniela; Akocak, Suleyman; Walker, Ellen A; Supuran, Claudiu T.; Ilies, Marc A.

    2014-01-01

    A series of ethylene bis-imidazoles was synthesized via a novel microwave-mediated synthesis. Biological testing on eight isozymes of carbonic anhydrase (CA) present in the human brain revealed compounds with nanomolar potency against CA VA and CA VII, also displaying excellent selectivity against other CA isozymes present in this organ.

  5. International Normalized Ratio (INR), coagulation factor activities and calibrated automated thrombin generation - influence of 24 h storage at ambient temperature

    Christensen, T D; Jensen, C; Larsen, T B;

    2010-01-01

    clotting activity of coagulation factors II, VII, IX, and X as well as CAT generation was recorded after 0 and 24 h respectively. Statistical analyses included Bland-Altman plot, 95% limits of agreement, and a variability test using a mixed effect model. The level of INR remained statistically unchanged......International Normalized Ratio (INR) measurements are used to monitor oral anticoagulation therapy with coumarins. Single coagulation factor activities and calibrated automated thrombin (CAT) generation are considered as more advanced methods for evaluating overall haemostatic capacity. The aims...

  6. Psychosocial factors underlying physical activity

    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.

  7. Canine lymphocyte activating factor (LAF)

    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

  8. Mechanism of Shortened Bones in Mucopolysaccharidosis VII

    Jason A. Metcalf; Zhang, Yanming(Institute of Theoretical Physics, Henan Normal University, Xinxiang, 453007, China); Matthew J. Hilton; Long, Fanxin; Ponder, Katherine P.

    2009-01-01

    Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease in which deficiency in β-glucuronidase results in glycosaminoglycan (GAG) accumulation in and around cells, causing shortened long bones through mechanisms that remain largely unclear. We demonstrate here that MPS VII mice accumulate massive amounts of the GAG chondroitin-4-sulfate (C4S) in their growth plates, the cartilaginous region near the ends of long bones responsible for growth. MPS VII mice also have only 60% of the n...

  9. Psychosocial factors underlying physical activity

    Ji Cheng-Ye; Middlestadt Susan E; Zhang Juan

    2007-01-01

    Abstract Background Given the increasing importance of obesity in China, prevention interventions encouraging physical activity by middle school students are needed. The purpose of this study is to illustrate how a rapid elicitation method can be used to identify salient consequences, referents, and circumstances about physical activity as perceived by middle school students and to provide suggestions for interventions and quantitative research. Method A theory-based qualitative study using a...

  10. Phenotypic expression in mucopolysaccharidosis VII.

    Bernsen, P L; Wevers, R. A.; Gabreëls, F J; Lamers, K J; Sonnen, A E; Stekhoven, J H

    1987-01-01

    beta-glucuronidase deficiency is an extremely rare disorder which is known to have a considerable phenotypic variation. A survey of the clinical findings in 19 previously reported patients with mucopolysaccharidosis VII is presented together with the results of clinical and biochemical studies in two further patients. Because a similar clinical picture is present in a heterozygotic sister it is doubted whether all signs and symptoms can be attributed to the beta-glucuronidase deficiency. The ...

  11. Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

    Larsen, Ole H; Stentoft, Jesper; Radia, Deepti;

    2013-01-01

    Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole b...

  12. Anaphylactic actions of platelet-activating factor.

    Stimler, N. P.; Bloor, C. M.; Hugli, T E; Wykle, R. L.; McCall, C E; O'Flaherty, J. T.

    1981-01-01

    Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) is a potent inducer of systemic anaphylactoid reactions in animals. It was found to be similarly potent in contracting smooth muscle of guinea pig ileum and lung and in enhancing vascular permeability when injected subcutaneously into these animals. This factor, therefore, possesses in vitro and in vivo bioactions that resemble those of C3a and C5a anaphylatoxins. However, platelet-activating factor induces a slowl...

  13. Association of protein Z and factor VII gene polymorphisms with risk of cerebral hemorrhage: a case–control and a family-based association study in a Chinese Han pulation

    YI ZENG; LE ZHANG; ZHIPING HU; QIDONG YANG; MINGMING MA; BAOQIONG LIU; JIAN XIA; HONGWEI XU; YUNHA I LIU; XIAOPING DU

    2016-06-01

    Protein Z (PZ) and factor (F) VII are two important factors in the clotting pathway which have similar structure, linkedfunction and nearby gene sites. The aims of this study were to investigate whether the common variants of PZ and FVII genesare associated with the risk of cerebral hemorrhage (CH) and to explore the combined effects of PZ and FVII polymorphismsfor CH risk. We performed genotyping analysis for two single-nucleotide polymorphisms (SNPs) of FVII (rs510317 andrs6046) and three SNPs of PZ (rs2273971, rs3024718 and rs3024731) both in a population-based case–control study andin a family-based association study. Case–control analysis found no evidence of significant association. But family-basedassociation study revealed that the G allele of PZ rs2273971, and three haplotypes carrying the ‘G’ allele of PZ rs2273971:haplotype GA, CG and CGA of PZ and FVII genes, all had a significant effect on CH susceptibility (Z =1.882,P =0.049;Z =1.922,P =0.044; Z =1.826,P =0.047; Z =1.977,P =0.048, respectively). While, the A allele of PZ rs2273971, andfour haplotypes carrying or crossing the ‘A’ allele of PZ rs2273971: haplotypes CA, ACAA, ACAT and ACAAT of PZ andFVII genes, may confer protection against CH (Z =−1.882,P =0.049; Z =−2.000,P =0.045; Z =−2.319,P =0.020;Z =−2.002,P =0.045; Z =−2.015,P =0.043, respectively). This is a first family-based association study providing geneticevidences that PZ and FVII genes, especially PZ rs2273971 are involved in the development of CH in Han-Chinese families.

  14. Physical Activity: Economic and Policy Factors

    Melayne M. McInnes; Shinogle, Judith A.

    2009-01-01

    While much research has focused on the costs of obesity and economic factors that drive obesity growth, little economic research has examined the factors that contribute to obesity -- physical inactivity and poor nutrition. This paper will examine correlates and predictors of physical activity over time with emphasis on economic factors. We use data for adults from the 2000-2005 Behavioral Risk Factor Surveillance System (BRFSS) survey that includes state and county codes for each individual ...

  15. Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs.

    Peck, Sun H; O'Donnell, Philip J M; Kang, Jennifer L; Malhotra, Neil R; Dodge, George R; Pacifici, Maurizio; Shore, Eileen M; Haskins, Mark E; Smith, Lachlan J

    2015-11-01

    Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein

  16. Genetics Home Reference: glycogen storage disease type VII

    ... storage disease type VII glycogen storage disease type VII Enable Javascript to view the expand/collapse boxes. ... All Close All Description Glycogen storage disease type VII (GSDVII) is an inherited disorder caused by an ...

  17. Corrective GUSB Transfer to the Canine Mucopolysaccharidosis VII Brain

    Cubizolle, Aurelie; Serratrice, Nicolas; Skander, Nadia; Colle, Marie-Anne; Ibanes, Sandy; Gennetier, Aurelie; Bayo-Puxan, Neus; Mazouni, Khalil; Mennechet, Franck; Joussemet, Beatrice; Cherel, Yan; Lajat, Yaouen; Vite, Charles; Bernex, Florence; Kalatzis, Vasiliki

    2014-01-01

    Severe deficiency in lysosomal β-glucuronidase (β-glu) enzymatic activity results in mucopolysaccharidosis (MPS) VII, an orphan disease with symptoms often appearing in early childhood. Symptoms are variable, but many patients have multiple organ disorders including neurological defects. At the cellular level, deficiency in β-glu activity leads to abnormal accumulation of glycosaminoglycans (GAGs), and secondary accumulation of GM2 and GM3 gangliosides, which have been linked to neuroinflamma...

  18. Tumour necrosis factor and endotoxin synergistically activate intestinal phospholipase A2 in mice. Role of endogenous platelet activating factor and effect of exogenous platelet activating factor.

    Sun, X.; Caplan, M S; Hsueh, W

    1994-01-01

    Previous studies have shown that: (a) platelet activating factor induces shock and intestinal injury, (b) exogenous platelet activating factor stimulates synthesis of endogenous platelet activating factor, and (c) tumour necrosis factor alpha and endotoxin synergise to induce shock and bowel injury in animals. These last two effects are largely mediated by platelet activating factor forming phospholipase A2 A2, a key enzyme for platelet activating factor synthesis, was examined in mouse intes...

  19. Line ratios for O VII

    New theoretical rates for electron excitation of the transitions 11S-23P and 11S-23P in O VII are used to calculate the line ratios R0 (forbidden line to intercombination line) and G0 (forbidden plus intercombination lines to resonance line). Our theoretical values of R0 are slightly larger than earlier calculations but our values of G0 are significantly lower than the earlier calculations. With our results the value of G0 1.0, from the solar observations of McKenzie and Landecker, would predict an electron temperature of 2.0 x 106 K, which is in good agreement with the temperature of 1.8 x 106 K predicted by recombination-ionization equilibrium calculations. (author)

  20. Silence of Synaptotagmin VII inhibits release of dense core vesicles in PC12 cells

    2009-01-01

    Synaptotagmin VII (Syt VII), which has a higher Ca2+ affinity and slower disassembly kinetics with lipid than Syt I and Syt IX, was regarded as being uninvolved in synaptic vesicle (SV) exocytosis but instead possibly as a calcium sensor for the slower kinetic phase of dense core vesicles (DCVs) release. By using high temporal resolution capacitance and amperometry measurements, it was demonstrated that the knockdown of endogenous Syt VII attenuated the fusion of DCV with the plasma membrane, reduced the amplitude of the exocytotic burst of the Ca2+-triggered DCV release without affecting the slope of the sustained component, and blocked the fusion pore expansion. This suggests that Syt VII is the Ca2+ sensor of DCV fusion machinery and is an essential factor for the establishment and maintenance of the pool size of releasable DCVs in PC12 cells.

  1. Mucopolysaccharidosis type VII: Characterization of mutations and molecular heterogeneity

    Tomatsu, Shunji; Fukuda, Seiji; Sukegawa, Kazuko; Ikedo, Yuko; Yamada, Shinji; Yamada, Yukiji; Sasaki, Toshiya; Okamoto, Hiroyuki; Kuwahara, Takashi; Yamaguchi, Seiji; Kiman, Tadashi; Shintaku, Haruo; Isshiki, Gen; Orii, Tadao

    1991-01-01

    We identified two different exonic point mutations causing β-glucuronidase (βGl) deficiency in two Japanese patients with mucopolysaccharidosis type VII (MPSVII). Enzyme assay of lysates of the lymphocytes and cultured fibroblasts showed little residual activity. The βGl-specific mRNA levels were normal, as determined by northern blot analysis. Mutated cDNA clones, including the entire coding sequence, were isolated using the polymerase chain reaction (PCR) products derived from βGl-deficient...

  2. Unemployment as a factor of entrepreneurial activity

    Sebastian Șipoș-Gug

    2012-12-01

    Full Text Available We aim to investigate the nature and direction of the relationship between unemployment and entrepreneurial activity. Our research, using monthly data from Romania (1991-2012, brings evidence to the hypothesis that the relationship is non-linear in regard to the temporal delay factor. From our data it would seem that unemployment and entrepreneurial activity are negatively related on the short term, and positively related on the long term. Based on these results, we propose that the two effects be treated separately, and we propose two predictive models of entrepreneurial activity based on unemployment that follow this distinction.

  3. 19 CFR Annex Vii to Part 351 - Antidumping Investigations Timeline

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Antidumping Investigations Timeline VII Annex VII to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VII Annex VII to Part 351—Antidumping Investigations Timeline ER19MY97.001...

  4. 29 CFR 1606.2 - Scope of title VII protection.

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Scope of title VII protection. 1606.2 Section 1606.2 Labor... BECAUSE OF NATIONAL ORIGIN § 1606.2 Scope of title VII protection. Title VII of the Civil Rights Act of..., religion, sex or national origin. The title VII principles of disparate treatment and adverse...

  5. Re(VII) oxide on mesoporous alumina of different types - Activity in the metathesis of olefins and their oxygen-containing derivatives

    Balcar, Hynek; Hamtil, Roman; Žilková, Naděžda; Zhang, Z.; Pinnavaia, T. J.; Čejka, Jiří

    2007-01-01

    Roč. 320, - (2007), s. 56-63. ISSN 0926-860X R&D Projects: GA AV ČR IAA4040411; GA MPO FT-TA/042 Grant ostatní: NSF(US) CHE-0211029 Institutional research plan: CEZ:AV0Z40400503 Source of funding: V - iné verejné zdroje Keywords : organized mesoporous alumina * metathesis * olefin functional derivatives * rhenium oxide Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.166, year: 2007

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

    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.

  7. Comments on the DDREF estimate of the BEIR VII Committee.

    Hoel, David G

    2015-03-01

    Radiation cancer risk estimates have been based primarily on the atomic bomb survivor cohorts, which involve an acute exposure. To adjust for lower dose and continuous exposures, a dose and dose rate effectiveness factor (DDREF) is applied to the acute risk estimates. The commonly accepted value for the DDREF at 1 Gy by the ICRP and the NCRP has been 2. BEIR VII changed this by estimating the value to be 1.5 including an uncertainty distribution. The BEIR VII committee used the atomic bomb solid cancer incidence data to make this estimation, and they chose to truncate the data at 1.5 Gy. The Committee also used the Oak Ridge mouse studies and estimated a DDREF based on these data. Finally they used the animal data-derived DDREF distribution as a Bayesian prior distribution for the atomic bomb survivor DDREF distribution and used the posterior distribution as their DDREF result. The resulting distribution had a maximum likelihood estimate of 1.4, and the Committee chose 1.5 as their best estimate. The purpose of this paper is to reexamine the BEIR VII analysis of both the atomic bomb survivor data and the mouse data. Based upon this analysis, the author concludes that changing the DDREF from 2 to 1.5 is not justified. PMID:25627947

  8. CNAPS VII - CIRCULATING NUCLEIC ACIDS IN PLASMA AND SERUM

    Guest Editor: Damián García-Olmo, Spain

    2011-10-01

    Full Text Available On behalf of The 7th International Conference on Circulating Nucleic Acids in Plasma and Serum (CNAPS VII Organizing Committee, it is my great pleasure to extend a warm invitation to you to participate in the CNAPS VII, scheduled to be held the first time in Madrid, Spain, 24th and 25th October 2011, at the La Paz University Hospital. After the great success of the CNAPS VI at Hong Kong, we are honored with the opportunity to host the CNAPS VII in our city of  Madrid. To keep up with our bourgeoning field of science, an outstanding array of international experts on this field have agreed to share their latest results and experiences with us during this meeting, with elating debates, lectures and networking sessions. As in previous conferences, poster and oral presentation sessions will provide all participants with the opportunity to discuss their results with other experts in the field. Aside from the opportunities afforded by the conference´s working sessions, you will also have the chance to experience a myriad of Spanish tourist and cultural attractions. From classic visits to our famous museums, historical buildings and monuments, to a great variety of cultural activities and tours; from our delicious gastronomy to fabulous shopping bargains, there is plenty that will leave you with fond memories of Madrid and its warm and welcoming people.

  9. The GAPS Programme with HARPS-N at TNG. VII. Putting exoplanets in the stellar context: magnetic activity and asteroseismology of $\\tau$ Bootis A

    Borsa, F; Rainer, M; Bignamini, A; Maggio, A; Poretti, E; Lanza, A F; Di Mauro, M P; Benatti, S; Biazzo, K; Bonomo, A S; Damasso, M; Esposito, M; Gratton, R; Affer, L; Barbieri, M; Boccato, C; Claudi, R U; Cosentino, R; Covino, E; Desidera, S; Fiorenzano, A F M; Gandolfi, D; Harutyunyan, A; Maldonado, J; Micela, G; Molaro, P; Molinari, E; Pagano, I; Pillitteri, I; Piotto, G; Shkolnik, E; Silvotti, R; Smareglia, R; Southworth, J; Sozzetti, A; Stelzer, B

    2015-01-01

    Aims. We observed the $\\tau$ Boo system with the HARPS-N spectrograph to test a new observational strategy aimed at jointly studying asteroseismology, the planetary orbit, and star-planet magnetic interaction. Methods. We collected high-cadence observations on 11 nearly consecutive nights and for each night averaged the raw FITS files using a dedicated software. In this way we obtained spectra with a high signal-to-noise ratio, used to study the variation of the CaII H&K lines and to have radial velocity values free from stellar oscillations, without losing the oscillations information. We developed a dedicated software to build a new custom mask that we used to refine the radial velocity determination with the HARPS-N pipeline and perform the spectroscopic analysis. Results. We updated the planetary ephemeris and showed the acceleration caused by the stellar binary companion. Our results on the stellar activity variation suggest the presence of a high-latitude plage during the time span of our observatio...

  10. European Energy Law. Report VII

    The European Energy Law Report VII presents in four parts an overview of the most important legal developments in the field of EU and national energy and climate change law as discussed at the 2009 European Energy Law Seminar. The first part examines recent developments in EU climate change regulation. It includes an overview of the revision of the EU Directive governing CO2 emissions trading and a more detailed analysis of the new allocation regime, including the auctioning of emission rights. This is followed by an analysis of the competitiveness of the new EU emissions trading Directive and recent developments in the US regarding emissions trading. The second part focuses on the energy liberalisation process and the Third Energy Package. Following an overview of recent developments in EU competition law and the impact of the Sector Inquiry on the energy sector, this part concentrates particularly on the new Internal Energy Market Directives and most particularly on the legality of the unbundling provisions. Subsequently, the focus is on the role of the TSOs. After an analysis of the need for an increased cooperation of the German TSOs, another chapter discusses the need for more consolidation in the European gas transmission market and the role of regulation therein. Is there a new role for nuclear energy? In order to secure long term energy supply, the focus turns again to nuclear energy. The third part of this report discusses two elements of nuclear liability. First, it analyses the issue of the possible privatisation of the nuclear sector and its impact on long term liability. Although the focus is on the UK nuclear sector, a comparison is made with some other regulatory regimes. Next, the role of nuclear energy is discussed as an instrument to reduce CO2 emissions and, more particularly as a means to reach the 20-20-20 targets. The question is raised whether the international rules on civil liability provide sufficient protection to victims of nuclear

  11. Creactive protein and interleukin-6 as markers of systemic inflammatory response and as prognostic factors for metastatic colorectal cancer. Data from the randomized phase III NORDIC-VII study

    Thomsen, M.; Kersten, C.; Sorbye, H.;

    2015-01-01

    Background: A systemic inflammatory response (SIR) affects prognosis and treatment outcome in metastatic colorectal cancer (mCRC). The aim of the study was to explore the prognostic significance of several SIR-derived markers and the correlation between the best marker of SIR and plasma interleukin......-6 (IL-6). Methods: The study was based on data from the randomized phase III NORDIC-VII study (Nordic FLOX +/cetuximab as first line treatment of mCRC). The effect of different markers of SIR, including modified Glasgow Prognostic Score (mGPS), derived Neutrophil Lymphocyte Ratio (dNLR), levels of...... SIR and 393 were eligible for the final analysis related to CRP, IL-6 and RAF and BRAF mutation status. The prognostic significance of CRP was at least as good as the other markers of SIR. CRP together with IL-6 were selected for further investigation. Logtrans-formed CRP and IL-6 were highly...

  12. Tissue factor-independent effects of recombinant factor VIIa on hemostasis

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

    2008-01-01

    The molecular mechanisms responsible for the hemostatic efficacy of recombinant activated factor VII (rFVIIa; NovoSeven (R), Novo Nordisk, Bagsvaerd, Denmark) in platelet-related bleeding disorders remain unclear. The general concept is that rFVIIa locally enhances thrombin generation at the site of

  13. 29 CFR 1601.93 - Opinions-title VII.

    2010-07-01

    ... § 1608.10 (a) or (b) of the Commission's Guidelines on Affirmative Action, 29 CFR part 1608, when such... 29 Labor 4 2010-07-01 2010-07-01 false Opinions-title VII. 1601.93 Section 1601.93 Labor... VII Interpretations and Opinions by the Commission § 1601.93 Opinions—title VII. Only the...

  14. VII rahvusvaheline turismikonverents : Eesti - Unistuste sihtkoht

    2012-01-01

    Tallinnas Mustpeade majas 27. septembril toimunud VII rahvusvahelisest turismikonverentsist, mille moderaator oli Tallinna Lennujaama juhatuse liige Erik Sakkov ning ettekannetega esinesid Tarmo Mutso, Laszlo Puzcko, Andres Arrak, Marje Josing, Tanel Pandre. Konverentsil kuulutati välja ka Turismiuuendaja 2012 nominendid. Pikemalt EASi turismiarenduskeskuse turundusdirektori Tarmo Mutso ettekandest "Eesti turismi arengukava 2014-2020"

  15. Active suppression of host-vs-graft reaction in pregnant mice. VII. Spontaneous abortion of allogeneic CBA/J x DBA/2 fetuses in the uterus of CBA/J mice correlates with deficient non-T suppressor cell activity

    The mammalian fetus has been viewed as an unusually successful type of allograft and unexplained spontaneous abortion as a possible example of maternal rejection. Previous studies have shown the presence of small lymphocytic suppressor cells in the murine decidua which block the generation and reactivation of anti-paternal cytotoxic T lymphocytes (CTL) and lymphokine-activated killer cells (LAK) by elaborating a factor that inhibits the response to interleukin 2 (IL 2). A deficiency of these suppressor cells was associated with implants of xenogeneic Mus caroli embryos in the Mus musculus uterus which are infiltrated by maternal lymphoid cells and aborted. A deficiency of such suppressor cells in the lymph nodes draining the uterus of CBA/J females in the process of aborting their semi-allogeneic CBA x DBA/2 F1 progeny has also been shown. CBA/J females possess significantly lower levels of decidua-associated non-T suppressor cells on day 8.5 to 10.5 of allopregnancy than do mothers that will produce large litters of live babies. The F1 embryos are infiltrated by maternal lymphocytes prior to abortion, and the infiltration and abortion rate appears to be augmented by pre-immunization with paternal DBA/2 spleen cells. The CBA/J x DBA/2J mating combination provides a model of spontaneous abortion in which immunologic factors play an important role and demonstrates that the association between deficiency of decidua-associated suppressor cells and xenopregnancy failure also holds true for the failure of allopregnancies resulting from natural within-species mating

  16. Intelsat VII communications capabilities and performance

    Abdel-Nabi, T.; Koh, E.; Kennedy, D.

    This paper describes the general characteristics of the Intelsat VII communications payload and analyzes the suitability of its design for digital transmission, for efficient incorporation of small earth stations into the Intelsat network, and for a relatively straightforward transition from the current Intelsat VA/VI configuration. An overview is presented of the comunications performance of the Intelsat VII satellite for the more important Intelsat digital and analog services, and earth stations standards. Specifically, the advantages, in terms of performance and capabilities, of the improved transponder linearity characteristics associated with the C-Band SSPA's and the K(u)-Band linearized TWTA's are addressed. The enhanced ability of this spacecraft to provide bandwidth where required from several possible orbital locations is discussed.

  17. Evaluation of AAV-mediated Gene Therapy for Central Nervous System Disease in Canine Mucopolysaccharidosis VII.

    Gurda, Brittney L; De Guilhem De Lataillade, Adrien; Bell, Peter; Zhu, Yanqing; Yu, Hongwei; Wang, Ping; Bagel, Jessica; Vite, Charles H; Sikora, Tracey; Hinderer, Christian; Calcedo, Roberto; Yox, Alexander D; Steet, Richard A; Ruane, Therese; O'Donnell, Patricia; Gao, Guangping; Wilson, James M; Casal, Margret; Ponder, Katherine P; Haskins, Mark E

    2016-02-01

    Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease arising from mutations in β-d-glucuronidase (GUSB), which results in glycosaminoglycan (GAG) accumulation and a variety of clinical manifestations including neurological disease. Herein, MPS VII dogs were injected intravenously (i.v.) and/or intrathecally (i.t.) via the cisterna magna with AAV9 or AAVrh10 vectors carrying the canine GUSB cDNA. Although i.v. injection alone at 3 days of age resulted in normal cerebrospinal fluid (CSF) GUSB activity, brain tissue homogenates had only ~1 to 6% normal GUSB activity and continued to have elevated GAG storage. In contrast, i.t. injection at 3 weeks of age resulted in CSF GUSB activity 44-fold normal while brain tissue homogenates had >100% normal GUSB activity and reduced GAGs compared with untreated dogs. Markers for secondary storage and inflammation were eliminated in i.t.-treated dogs and reduced in i.v.-treated dogs compared with untreated dogs. Given that i.t.-treated dogs expressed higher levels of GUSB in the CNS tissues compared to those treated i.v., we conclude that i.t. injection of AAV9 or AAVrh10 vectors is more effective than i.v. injection alone in the large animal model of MPS VII. PMID:26447927

  18. Evaluated Nuclear Data Covariances: The Journey From ENDF/B-VII.0 to ENDF/B-VII.1

    detail various aspects of the data producer community's efforts to improve the evaluation methods and to add covariance content to the ENDF/B library. The present paper offers just a brief glimpse of these activities by drawing material from covariance papers presented at meetings, workshops and international conferences during the past five years. Highlighted are: advances in methods for producing and processing covariance data, recently developed covariance visualization capabilities, and the development and implementation of quality assurance (QA) requirements that should be satisfied for covariance data to be included in ENDF/B-VII.1.

  19. VII International Congress of Engineering Physics

    2015-01-01

    In the frame of the fortieth anniversary celebration of the Universidad Autónoma Metropolitana and the Physics Engineering career, the Division of Basic Science and Engineering and its Departments organized the "VII International Congress of Physics Engineering". The Congress was held from 24 to 28 November 2014 in Mexico City, Mexico. This congress is the first of its type in Latin America, and because of its international character, it gathers experts on physics engineering from Mexico and all over the globe. Since 1999, this event has shown research, articles, projects, technological developments and vanguard scientists. These activities aim to spread, promote, and share the knowledge of Physics Engineering. The topics of the Congress were: • Renewable energies engineering • Materials technology • Nanotechnology • Medical physics • Educational physics engineering • Nuclear engineering • High precision instrumentation • Atmospheric physics • Optical engineering • Physics history • Acoustics This event integrates lectures on top trending topics with pre-congress workshops, which are given by recognized scientists with an outstanding academic record. The lectures and workshops allow the exchange of experiences, and create and strengthen research networks. The Congress also encourages professional mobility among all universities and research centres from all countries. CIIF2014 Organizing and Editorial Committee Dr. Ernesto Rodrigo Vázquez Cerón Universidad Autónoma Metropolitana - Azcapotzalco ervc@correo.azc.uam.mx Dr. Luis Enrique Noreña Franco Universidad Autónoma Metropolitana - Azcapotzalco lnf@correo.azc.uam.mx Dr. Alberto Rubio Ponce Universidad Autónoma Metropolitana - Azcapotzalco arp@correo.azc.uam.mx Dr. Óscar Olvera Neria Universidad Autónoma Metropolitana - Azcapotzalco oon@correo.azc.uam.mx Professor Jaime Granados Samaniego Universidad Autónoma Metropolitana - Azcapotzalco jgs@correo.azc.uam.mx Dr. Roberto Tito Hern

  20. Tissue factor/FVIIa activates Bcl-2 and prevents doxorubicin-induced apoptosis in neuroblastoma cells

    Tissue factor (TF) is a transmembrane protein that acts as a receptor for activated coagulation factor VII (FVIIa), initiating the coagulation cascade. Recent studies demonstrate that expression of tumor-derived TF also mediates intracellular signaling relevant to tumor growth and apoptosis. Our present study investigates the possible mechanism by which the interaction between TF and FVIIa regulates chemotherapy resistance in neuroblastoma cell lines. Gene and siRNA transfection was used to enforce TF expression in a TF-negative neuroblastoma cell line and to silence endogenous TF expression in a TF-overexpressing neuroblastoma line, respectively. The expression of TF, Bcl-2, STAT5, and Akt as well as the phosphorylation of STAT5 and Akt in gene transfected cells or cells treated with JAK inhibitor and LY294002 were determined by Western blot assay. Tumor cell growth was determined by a clonogenic assay. Cytotoxic and apoptotic effect of doxorubicin on neuroblastoma cell lines was analyzed by WST assay and annexin-V staining (by flow cytometry) respectively. Enforced expression of TF in a TF-negative neuroblastoma cell line in the presence of FVIIa induced upregulation of Bcl-2, leading to resistance to doxorubicin. Conversely, inhibition of endogenous TF expression in a TF-overexpressing neuroblastoma cell line using siRNA resulted in down-regulation of Bcl-2 and sensitization to doxorubicin-induced apoptosis. Additionally, neuroblastoma cells expressing high levels of either endogenous or transfected TF treated with FVIIa readily phosphorylated STAT5 and Akt. Using selective pharmacologic inhibitors, we demonstrated that JAK inhibitor I, but not the PI3K inhibitor LY294002, blocked the TF/FVIIa-induced upregulation of Bcl-2. This study shows that in neuroblastoma cell lines overexpressed TF ligated with FVIIa produced upregulation of Bcl-2 expression through the JAK/STAT5 signaling pathway, resulting in resistance to apoptosis. We surmise that this TF

  1. Ukraine Country Report. Annex VII

    The objectives of the Research Contract UKR 13374: 'Forecast of radionuclides migration from geological repository at early stages of siting geological repository (as applied to granitoid formations of Korostensky pluton and Chernobyl exclusion zone, Ukraine)' were to: - Reform radionuclide transport simulation in support of a site suitability analysis for a geological repository within the Chernobyl exclusion zone and adjacent territories; - Determinate of additional data for model updating, assessment of granite formations' suitability and identification of hydrogeological factors influencing to the repository safety; and - Study advanced international experience of applying of numerical simulation in support of site characterization and safety assessment of geological disposal

  2. Ecological Factors Improving Efficiency of Business Activities

    Kononova G. A.

    2015-01-01

    Full Text Available The economic importance of optimizing the environmental situation from the perspective of an entrepreneur are assessed in the article. The classification of administrative decisions taken in the course of the business activities is proposed. The authors identified a group of solutions directly providing optimization of environment external to the enterprise, solutions that have an indirect positive impact on the environment and solutions that improve ecology of industrial premises. The nature of economic effect of resulting solutions of various types is taken into account. Vectors of influence of working conditions on the economic results of business activities are described. The nature and strength of the impact of model management decisions results of business activities are defined. Key performance indicators of entrepreneurial activity are identified: employee productivity, the amount of revenue and profitability, solvency, staff stability, the competitiveness of enterprises. Grouping the costs of ecological parameters optimization of the production environment is proposed. Relationship between level of working conditions and socio-psychological climate in the collective enterprise is disclosed. The methods of motivation of entrepreneurs in solving of environmental, production problems are considered. The role of training entrepreneurs engaged of medium and small businesses are underlined especially. Thus, in the article the relationship between environmental and economic problems of entrepreneurial activity is investigated. Role and opportunities of entrepreneurs in solving these problems are defined and structured.

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

    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 by a modification of a method described for bovine Factor IX activation by Zur and Nemerson (Zur, M., and Y. Nemerson, 1980, J. Biol. Chem., 255:5703-5707). Initial rates of trichloroacetic acid-soluble 3H-release were linear over 10-30 min of incubation of Factor IX (88 nM) with CaCl2 (5 mM) and with pure (g...

  4. Successful use of N-acetyl cysteine and activated recombinant factor VII in fulminant hepatic failure and massive bleeding secondary to dengue hemorrhagic fever

    Edirisooriya Maddumage Manoj; Gayan Ranasinghe; Ragunathan MK

    2014-01-01

    Consensus on management of complicated cases of dengue infection is evolving. Dengue hemorrhagic fever (DHF) occasionally progress to fulminant liver failure with high fatality rate. Inadvertent use of blood products to control massive bleeding in dengue shock syndrome may worsen fluid overload and subsequently the multi-organ dysfunction. We report a case of 37-years-old Sri Lankan man who developed fulminant liver failure and massive bleeding associated with DHF, subsequently recovered comp...

  5. Dietary factor VII activation does not increase plasma concentrations of prothrombin fragment 1+2 in patients with stable angina pectoris and coronary atherosclerosis

    Bladbjerg, E-M; Münster, A M; Marckmann, P; Keller, N; Jespersen, J

    2000-01-01

    angiographically verified coronary atherosclerosis. They were served a low-fat (5% of energy from fat) breakfast and lunch and a high-fat (40% of energy from fat) breakfast and lunch on 2 different days. Venous blood samples were collected at 8:15 AM (fasting), 12:30 PM, 2:00 PM, 3:30 PM, and 4:45 PM and analyzed...

  6. Influencing Factors of Thermogenic Adipose Tissue Activity.

    Zhang, Guoqing; Sun, Qinghua; Liu, Cuiqing

    2016-01-01

    Obesity is an escalating public health challenge and contributes tremendously to the disease burden globally. New therapeutic strategies are required to alleviate the health impact of obesity-related metabolic dysfunction. Brown adipose tissue (BAT) is specialized for dissipating chemical energy for thermogenesis as a defense against cold environment. Intriguingly, the brown-fat like adipocytes that dispersed throughout white adipose tissue (WAT) in rodents and humans, called "brite" or "beige" adipocytes, share similar thermogenic characteristics to brown adipocytes. Recently, researchers have focused on cognition of these thermogenic adipose tissues. Some factors have been identified to regulate the development and function of thermogenic adipose tissues. Cold exposure, pharmacological conditions, and lifestyle can enhance non-shivering thermogenesis and metabolism via some mechanisms. However, environmental pollutants, such as ambient fine particulates and ozone, may impair the function of these thermogenic adipose tissues and thereby induce metabolic dysfunction. In this review, the origin, function and influencing factors of thermogenic adipose tissues were summarized and it will provide insights into identifying new therapeutic strategies for the treatment of obesity and obesity-related diseases. PMID:26903879

  7. Factors of activation and wage system of business

    Jansová, Ivana

    2011-01-01

    The aim of this thesis was to evaluate the factors motivating the company and the payroll system. This work deals with wages, describes the creation and application of company payroll system, activating factors and their impact on employees. Businesses pay as variable influencing the cost and performance tool for inciting people. The theoretical part is focused on explaining the basic concepts and approaches used to compile salary and wage system, as described activating factors and their use...

  8. Positive activities as protective factors against mental health conditions

    Layous, K; Chancellor, J; Lyubomirsky, S

    2014-01-01

    Applying Nolen-Hoeksema and Watkins's (2011) transdiagnostic risk factor heuristic to our work on positive activities (i.e., practices that characterize naturally happy people, like expressing gratitude and practicing generosity), we propose that such activities may serve as protective factors that mitigate proximal risk factors both directly and by intervening with the mechanisms that give rise to them. First, we discuss theoretical and empirical support for the importance of well-being and ...

  9. Ecological Factors Improving Efficiency of Business Activities

    Kononova G. A.; Tsiganov V. V.

    2015-01-01

    The economic importance of optimizing the environmental situation from the perspective of an entrepreneur are assessed in the article. The classification of administrative decisions taken in the course of the business activities is proposed. The authors identified a group of solutions directly providing optimization of environment external to the enterprise, solutions that have an indirect positive impact on the environment and solutions that improve ecology of industrial premises. The nature...

  10. Recombinant Factor VIIa (Eptacog Alfa): A Pharmacoeconomic Review of its Use in Haemophilia in Patients with Inhibitors to Clotting Factors VIII or IX

    Katherine A. Lyseng-Williamson; Plosker, Greg L.

    2007-01-01

    Recombinant factor VIIa (NovoSeven(R); also known as recombinant activated factor VII or eptacog alfa) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In noncomparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of succe...

  11. Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

    Kyle, J.W.; Vogler, C.; Hoffmann, J.W.; Sly, W.S. (St. Louis Univ. School of Medicine, MO (USA)); Birkenmeier, E.H.; Gwynn, B. (Jackson Laboratory, Bar Harbor, ME (USA))

    1990-05-01

    The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.

  12. 77 FR 64400 - Order of Succession for HUD Region VII

    2012-10-19

    ... URBAN DEVELOPMENT Order of Succession for HUD Region VII AGENCY: Office of Field Policy and Management, HUD. ACTION: Notice of Order of Succession. SUMMARY: In this notice, the Assistant Deputy Secretary... Succession for the Kansas City Regional Office and its Field Offices (Region VII). This Order of...

  13. 40 CFR Appendixes I-Vii to Part 85 - [Reserved

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false I Appendixes I-VII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Appendixes I-VII to Part 85...

  14. Frederik VII og folkets kærlighed

    Perlt, Michael; Vinding, Niels Valdemar

    2013-01-01

    I den turbulente tid mellem de to slesvigske krige drog kong Frederik VII under en rejse til Jylland i 1857 i procession op på højene i Jelling for at modtage folkets hyldest. På det historiske sted lod Frederik VII sig fejre som danskernes konge under en stor folkefest med bønder og deres familier...

  15. 40 CFR Appendixes Vi-Vii to Part 600 - [Reserved

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false VI Appendixes VI-VII to Part 600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Appendixes VI-VII to Part 600...

  16. 40 CFR Appendixes Vii-Viii to Part... - [Reserved

    2010-07-01

    ... 40 Protection of Environment 25 2010-07-01 2010-07-01 false VII Appendixes VII-VIII to Part 264 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Appendixes...

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

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

    2015-01-01

    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...... domain that are activated by TF and help to make FVIIa an efficient catalyst of FIX and FX activation....

  18. Human cytomegalovirus IE2 protein interacts with transcription activating factors

    徐进平; 叶林柏

    2002-01-01

    The human cytomegalovirus (HCMV) IE86 Cdna was cloned into Pgex-2T and fusion protein GST-IE86 was expressed in E. Coli. SDS-PAGE and Western blot assay indicated that fusion protein GST-IE86 with molecular weight of 92 ku is soluble in the supernatant of cell lysate. Protein GST and fusion protein GST-IE86 were purified by affinity chromatography. The technology of co-separation and specific affinity chromatography was used to study the interactions of HCMV IE86 protein with some transcriptional regulatory proteins and transcriptional factors. The results indicated that IE86 interacts separately with transcriptional factor TFIIB and promoter DNA binding transcription trans-activating factors SP1, AP1 and AP2 to form a heterogenous protein complex. These transcriptional trans-activating factors, transcriptional factor and IE86 protein were adsorbed and retained in the affinity chromatography simultaneously. But IE86 protein could not interact with NF-Кb, suggesting that the function of IE86 protein that can interact with transcriptional factor and transcriptional trans-activating factors has no relevance to protein glycosylation. IE86 protein probably has two domains responsible for binding transcriptional trans-activating regulatory proteins and transcriptional factors respectively, thus activating the transcription of many genes. The interactions accelerated the assembly of the transcriptional initiation complexes.

  19. Mechanism of the anticoagulant effect of warfarin as evaluated in rabbits by selective depression of individual procoagulant vitamin K-dependent clotting factors.

    Zivelin, A; Rao, L V; Rapaport, S I

    1993-01-01

    We have evaluated the contribution of depression of individual procoagulant vitamin K-dependent clotting factors to the ability of warfarin to protect rabbits against tissue factor-induced coagulation. Mean activities of individual procoagulant factors were determined, in assays with rabbit substrates, for a group of rabbits achieving a protective degree of anticoagulation with warfarin. Values were: factor VII, 12%; factor IX, 7%; factor X, 14%, and prothrombin, 13%. The effect upon tissue f...

  20. Crystallographic B factor of critical residues at enzyme active site

    张海龙; 宋时英; 林政炯

    1999-01-01

    Thirty-seven sets of crystallographic enzyme data were selected from Protein Data Bank (PDB, 1995). The average temperature factors (B) of the critical residues at the active site and the whole molecule of those enzymes were calculated respectively. The statistical results showed that the critical residues at the active site of most of the enzymes had lower B factors than did the whole molecules, indicating that in the crystalline state the critical residues at the active site of the natural enzymes possess more stable conformation than do the whole molecules. The flexibility of the active site during the unfolding by denaturing was also discussed.

  1. Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange

    Rand, Kasper Dyrberg; Jørgensen, Thomas; Olsen, Ole H; Persson, Egon; Jensen, Ole; Stennicke, Henning R; Andersen, Mette

    2006-01-01

    Coagulation factor VIIa (FVIIa) is a serine protease that, after binding to tissue factor (TF), plays a pivotal role in the initiation of blood coagulation. We used hydrogen exchange monitored by mass spectrometry to visualize the details of FVIIa activation by comparing the exchange kinetics of ...... provide novel insights into the cofactor-induced activation of this important protease and reveal the potential for allosteric regulation in the trypsin family of proteases....

  2. Factors Influencing Trade Area Activity in the Great Basin Area

    George Ebai; Thomas R. Harris

    1997-01-01

    Proper assessment of rural retail sector activity would yield effective and targeted retail extension/outreach programs. Pull factors assess a local retail sector's ability to meet local retail demands and to capture outside trade. If the local retail sector's pull factor vaiue is above the threshold value of one, the local retail sector is capturing local and non-local retail demands. Tobit estimation procedures were used for eight retail sectors to determine factors which influence the capt...

  3. Attributes, Environment Factors and Women Entrepreneurial Activity: A Literature Review

    Isidore Ekpe

    2011-08-01

    Full Text Available Purpose: The purpose of this study is to examine the effect of individual attributes and business environment factors on the entrepreneurial activity of women entrepreneurs. Individual attributes such as education, working experience, attitude towards risk-taking, affect women entrepreneurial activity. Economic constraints such as lack of credit due to lack of asset collaterals and socio-cultural barriers, lack of savings due to low household income, and lack of labour skills due to low educational level also affect women entrepreneurial activity. The effect of these factors on entrepreneurial activity is worth studying because entrepreneurship development is considered a vital link to an overall economic growth of a nation through its positive impact on economic development especially at the grassroots. However, limited studies have reviewed literatures on individual attributes and business environment factors on the entrepreneurial activity of women entrepreneurs. This is the focus of this study.Methodology: The paper is a descriptive study that reviews literature on individual attributes and environment factors on women entrepreneurial activity.Conclusion: The paper concludes that environment factors exert much more influence on women entrepreneurial activity than individual attributes.Research limitation: The paper is limited to a literature review that may need further research by using a framework to investigate the factors on entrepreneurial activity.Practical implication: It shows the need for the government to support entrepreneurs through adequate provision of micro-finance.Originality: The study is a new way to look at crucial factors affecting entrepreneurial activity in a country. Paper type: This is a research paper.

  4. Positive activities as protective factors against mental health conditions.

    Layous, Kristin; Chancellor, Joseph; Lyubomirsky, Sonja

    2014-02-01

    Applying Nolen-Hoeksema and Watkins's (2011) transdiagnostic risk factor heuristic to our work on positive activities (i.e., practices that characterize naturally happy people, like expressing gratitude and practicing generosity), we propose that such activities may serve as protective factors that mitigate proximal risk factors both directly and by intervening with the mechanisms that give rise to them. First, we discuss theoretical and empirical support for the importance of well-being and the mechanisms that explain how positive activities promote well-being (by boosting positive emotions, positive thoughts, positive behaviors, and need satisfaction; Lyubomirsky & Layous, 2013). Second, we outline examples of how positive activities can mitigate two particular proximal risk factors (rumination and loneliness) and counteract environmental triggers (i.e., moderators) that might amplify them (e.g., through adaptive coping). Third, we argue that positive activities can be taught to youth to instill positive patterns of emotions, thoughts, and behaviors that may serve as protective factors over the course of their lifetimes. Lastly, we propose that certain positive activities might be particularly well-suited to certain individuals and to specific risk factors. PMID:24661154

  5. Comparison of automated von Willebrand factor activity assays

    Timm, Annette; Hillarp, Andreas; Philips, Malou;

    2015-01-01

    INTRODUCTION: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. Measurement of von Willebrand factor (VWF) activity in plasma is often based on platelet agglutination stimulated by the ristocetin cofactor activity. Novel assays, based on latex beads with recombinant...

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

    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 NaDodSO4/PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated 125I-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

  7. Potential Role of Activating Transcription Factor 5 during Osteogenesis

    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. MOTIVATIONAL FACTORS FOR PHYSICAL ACTIVITY IN THE ELDERS

    J. Parreira

    2015-04-01

    Full Text Available Nowadays the elderly population is well aware of the benefits of the practice of physical activity, which leads to an increasing demand for specialized physical activity programs in urban centers or recreational self-practice. However, people easily quit those programs or recreational self-practice and return to a sedentary lifestyle. A key factor to avoid this quittance is to keep them motivated to practice and stay in the programs.Objectives: This study aims to understand the motivational factors that lead older people to physical activity in order to improve existing programs so to better meet the needs of this population.

  9. Inhibition of hepatocyte nuclear factor 4 transcriptional activity by the nuclear factor {kappa}B pathway

    Nikolaidou-Neokosmidou, Varvara; Zannis, Vassilis I.; Kardassis, Dimitris

    2006-01-01

    Abstract Hepatocyte Nuclear Factor 4 (HNF-4) is a key regulator of liver specific gene expression in mammals. We have shown previously that the activity of the human apolipoprotein C-III (APOC3) promoter is positively regulated by the anti-inflammatory cytokine Transforming Growth Factor {beta} (TGF{beta}) and its effectors Smad3 and Smad4 proteins via physical and functional interactions between Smads and HNF-4. We now show that the pro-inflammatory cytokine Tumor Necrosis Factor ...

  10. Enzyme replacement therapy for murine mucopolysaccharidosis type VII.

    Sands, M S; C. Vogler; Kyle, J W; Grubb, J H; Levy, B; Galvin, N; W. S. Sly; Birkenmeier, E H

    1994-01-01

    Recombinant mouse beta-glucuronidase administered intravenously to newborn mice with mucopolysaccharidosis type VII (MPS VII) is rapidly cleared from the circulation and localized in many tissues. Here we determine the tissue distribution of injected enzyme and describe its effects on the histopathology in 6-wk-old MPS VII mice that received either one injection of 28,000 U recombinant beta-glucuronidase at 5 wk of age or received six injections of 28,000 U given at weekly intervals beginning...

  11. Tissue factor/FVIIa activates Bcl-2 and prevents doxorubicin-induced apoptosis in neuroblastoma cells

    Alvarado Carlos S

    2008-03-01

    Full Text Available Abstract Background Tissue factor (TF is a transmembrane protein that acts as a receptor for activated coagulation factor VII (FVIIa, initiating the coagulation cascade. Recent studies demonstrate that expression of tumor-derived TF also mediates intracellular signaling relevant to tumor growth and apoptosis. Our present study investigates the possible mechanism by which the interaction between TF and FVIIa regulates chemotherapy resistance in neuroblastoma cell lines. Methods Gene and siRNA transfection was used to enforce TF expression in a TF-negative neuroblastoma cell line and to silence endogenous TF expression in a TF-overexpressing neuroblastoma line, respectively. The expression of TF, Bcl-2, STAT5, and Akt as well as the phosphorylation of STAT5 and Akt in gene transfected cells or cells treated with JAK inhibitor and LY294002 were determined by Western blot assay. Tumor cell growth was determined by a clonogenic assay. Cytotoxic and apoptotic effect of doxorubicin on neuroblastoma cell lines was analyzed by WST assay and annexin-V staining (by flow cytometry respectively. Results Enforced expression of TF in a TF-negative neuroblastoma cell line in the presence of FVIIa induced upregulation of Bcl-2, leading to resistance to doxorubicin. Conversely, inhibition of endogenous TF expression in a TF-overexpressing neuroblastoma cell line using siRNA resulted in down-regulation of Bcl-2 and sensitization to doxorubicin-induced apoptosis. Additionally, neuroblastoma cells expressing high levels of either endogenous or transfected TF treated with FVIIa readily phosphorylated STAT5 and Akt. Using selective pharmacologic inhibitors, we demonstrated that JAK inhibitor I, but not the PI3K inhibitor LY294002, blocked the TF/FVIIa-induced upregulation of Bcl-2. Conclusion This study shows that in neuroblastoma cell lines overexpressed TF ligated with FVIIa produced upregulation of Bcl-2 expression through the JAK/STAT5 signaling pathway, resulting

  12. 15 CFR Appendix Vii to Subpart P... - Areas To Be Avoided Boundary Coordinates

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Areas To Be Avoided Boundary Coordinates VII Appendix VII to Subpart P of Part 922 Commerce and Foreign Trade Regulations Relating to... National Marine Sanctuary Pt. 922, Subpt. P, App. VII Appendix VII to Subpart P of Part 922—Areas To...

  13. 40 CFR Appendix Vii to Part 86 - Standard Bench Cycle (SBC)

    2010-07-01

    ... 40 Protection of Environment 19 2010-07-01 2010-07-01 false Standard Bench Cycle (SBC) VII Appendix VII to Part 86 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS.... VII Appendix VII to Part 86—Standard Bench Cycle (SBC) 1. The standard bench aging...

  14. Localization of blood coagulation factors in the germinal centers of human Peyer's patches

    Kudo, S.; Yamakawa, Mitsunori; Imai, Yutaka; Tsukamoto, M.

    1992-01-01

    The immunohistochemical distribution of 15 blood coagulation factors in the germinal centers (GCs) of human Peyer's patches (PPs) was studied. Although factor VIII, active alpha-thrombin, and fibrinogen were hardly evident in the GCs, the majority of coagulation factors, such as kallikrein, high-molecular-weight kininogen, factos XII, X, IX, VII, V, XIIIa and XIIIb, prothrombin, anti-thrombin 111 and inactive alpha-thrombin were found, showing a lace-like s...

  15. Settling Title VII Disputes: A Role for the Arbitrator

    Owens, Stephen D.

    1976-01-01

    Selected arbitration cases illustrate the dilemma facing the arbitrator when employment practices that violate both the collective bargaining agreement and Title VII must be resolved. Problems in dealing with race and sex discrimination are discussed. (LBH)

  16. Theoretical emission line ratios for O VII in low-density plasmas

    New electron excitation rates for O VII calculated by Tayal and Kingston using the R-matrix method are used to determine theoretical emission line strengths. Values of the electron density sensitive ratio R (forbidden line to intercombination line) are found to be very similar to those deduced by other authors. However the temperature sensitive ratios G (intercombination plus forbidden lines to resonance line) are approximately 20% lower than the best previous estimates. The observed value of G for solar active regions (G=1.0 +- 0.1) predicts an electron temperature in the range 1.1 x 106 K 6 K, which overlaps that of maximum O VII emissivity, Tsub(M) = 1.8 x 106 K. In addition, the theoretical G versus Tsub(e) curve is an excellent agreement with the observed for a Tokamak plasma. (orig.)

  17. Physical activity and associated factors among students attending evening classes

    Fabio Luis Ceschini

    2015-03-01

    Full Text Available The aim of this study was to describe the physical activity level and associated factors among students attending evening classes in public and private schools in a region of the city of São Paulo. The sample was composed of 1,844 adolescents of both sexes aged 15-20 years. Three public and private schools in the city of São Paulo were visited. Daily physical activity level was assessed through International Physical Activity Questionnaire that classifies physical activity level. Physical activity level was divided into insufficiently active (when subject reported less than 300 minutes of moderate to vigorous physical activities per week and physically active (when subject reported more than 300 minutes of moderate to vigorous physical activities per week. Information related to risk behavior such as smoking and alcohol consumption was collected. Data were analyzed using logistic regression with three levels of data input and p<.05 as significance level. The prevalence of physically active adolescents was 36.1%. Most active subjects were: A younger boys with low socioeconomic levels; B adolescents from private schools; C adolescents that do not smoke or drink alcoholic beverages; D those who do not attend formal exercise program; E those who go to school to perform physical activities on weekends. Adolescents attending evening classes tended to be insufficiently active. We believe that school structure, working hours, and distance from home and workplace to school and risk factor should explain these data. Intervention programs could significantly contribute to increase the physical activity level among adolescents.

  18. Reduced serum inhibition of platelet-activating factor activity in preeclampsia.

    Benedetto, C; Massobrio, M; Bertini, E; Abbondanza, M; Enrieu, N; Tetta, C

    1989-01-01

    We determined in normal nonpregnant (group 1) women, normal pregnant (group 2) women, and patients with preeclampsia (group 3) the serum inhibition of platelet-activating factor activity, the presence of detectable amounts of platelet-activating factor in the blood, and platelet responsiveness in vitro to platelet-activating factor, and to other agonists (adenosine diphosphate, collagen, and ristocetin), and prostacyclin (prostaglandin I2). In patients with preeclampsia (group 3) the serum inhibition of platelet-activating factor activity was significantly lower than that in groups 1 and 2. However, no detectable amounts of platelet-activating factor were observed. The mean values of platelet aggregation induced by platelet-activating factor, adenosine diphosphate, collagen and ristocetin, and the prostaglandin I2-inhibitory concentration of 50% which is inversely correlated with platelet sensitivity to prostaglandin I2, were not significantly different between groups 2 and 3. It is suggested that in preeclampsia the defect in serum inhibitory potential of platelet-activating factor--induced platelet aggregation may contribute to the disturbance in the homeostatic balance between proaggregant and antiaggregant substances. PMID:2912073

  19. Presentation of mucopolysaccharidosis VII (beta-glucuronidase deficiency) in infancy.

    Hoyme, H E; Jones, K L; Higginbottom, M C; O'Brien, J S

    1981-01-01

    A child is presented with mucopolysaccharidosis VII (beta-glucuronidase deficiency), bringing to six the number of reported patients with the infantile onset form of this disorder. This patient exhibited the following features, previously unrecognised as part of this syndrome: presentation in the neonatal period, progressive joint contractures, and hydrocephalus. This child's course and data from published reports indicate that mucopolysaccharidosis VII, unlike the other known mucopolysacchar...

  20. Factors limiting microbial activity in volcanic tuff at Yucca Mountain

    Samples of tuff aseptically collected from 10 locations in the Exploratory Shaft Facility at the site of the proposed high-level nuclear waste repository at Yucca Mountain, Nevada Test Site were analyzed for microbiological populations, activities, and factors limiting microbial activity. Radiotracer assays (14C-labeled organic substrate mineralization), direct microscopic counts, and plate counts were used. Radiolabeled substrates were glucose, acetate, and glutamate. Radiotracer experiments were carried out with and without moisture and inorganic nutrient amendments to determine factors limiting to microbial activities. Nearly all samples showed the presence of microorganisms with the potential to mineralize organic substrates. Addition of inorganic nutrients stimulated activities in a small number of samples. The presence of viable microbial communities within the tuff has implications for transport of contaminants

  1. Attributes, Environment Factors and Women Entrepreneurial Activity: A Literature Review

    Isidore Ekpe; Norsiah Mat; Razli Che Razak

    2011-01-01

    Purpose: The purpose of this study is to examine the effect of individual attributes and business environment factors on the entrepreneurial activity of women entrepreneurs. Individual attributes such as education, working experience, attitude towards risk-taking, affect women entrepreneurial activity. Economic constraints such as lack of credit due to lack of asset collaterals and socio-cultural barriers, lack of savings due to low household income, and lack of labour skills due to low educa...

  2. Bayesian analysis of anisotropic cosmologies: Bianchi VII_h and WMAP

    McEwen, J D; Feeney, S M; Peiris, H V; Lasenby, A N

    2013-01-01

    We perform a definitive analysis of Bianchi VII_h cosmologies with WMAP observations of the cosmic microwave background (CMB) temperature anisotropies. Bayesian analysis techniques are developed to study anisotropic cosmologies using full-sky and partial-sky, masked CMB temperature data. We apply these techniques to analyse the full-sky internal linear combination (ILC) map and a partial-sky, masked W-band map of WMAP 9-year observations. In addition to the physically motivated Bianchi VII_h model, we examine phenomenological models considered in previous studies, in which the Bianchi VII_h parameters are decoupled from the standard cosmological parameters. In the two phenomenological models considered, Bayes factors of 1.7 and 1.1 units of log-evidence favouring a Bianchi component are found in full-sky ILC data. The corresponding best-fit Bianchi maps recovered are similar for both phenomenological models and are very close to those found in previous studies using earlier WMAP data releases. However, no evi...

  3. Molecular analysis of patients with {Beta}-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII

    Vervoort, R.; Liebaers, I.; Lissens, W. [Univ. Hospital, Brussels (Belgium)] [and others

    1996-03-01

    Although not all mucopolysaccharidosis type VII (MPS VII) neonates present with hydrops fetalis or with related symptoms, hydrops fetalis is a common form of presentation of this mucopolysaccharidosis. We used reverse-transcription-PCR-SSCP and direct sequencing to screen for mutations in the human {beta}-glucuronidase cDNA of 17 MPS VII patients with severe presentation of the disease. Mutations resulting in an unstable mRNA were detected in genomic DNA with direct sequencing of the PCR-amplified {beta}-glucuronidase exons. We found extensive genetic heterogeneity in MPS VII alleles: in addition to 6 of 12 previously reported mutations (L176F, R216W, R357X, R382C, W507X, and W627C), we detected 14 undescribed mutations in the {beta}-glucuronidase coding region that produce MPS VII alleles (G136R, E150K, S312X, Y320S, Y320C, H351Y, R382H, R374C, R435P, R477W, G572D, Y508C, K606N, and 1900{Delta}GA). The mutations in hydropic fetuses were widely scattered in the {beta}-glucuronidase gene. Analysis of three polymorphic sites of the mutant alleles (1766T/C, 1972C/T, and a new 1091+27C/G polymorphism) allowed exclusion of identity by descent for some recurrent mutations. Three of four mutations introducing a premature translation stop codon were found to affect mRNA abundance and/or structure. Expression studies provided evidence for the causal relationship between each of the mutations found in MPS VII alleles and the enzyme deficiency, in that all mutations identified exhibited markedly reduced enzyme activity expressed in COS7 cells following transfection with the mutant cDNA. 52 refs., 4 figs., 5 tabs.

  4. Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues

    Kawaguchi, Makiko; Kataoka, Hiroaki, E-mail: mejina@med.miyazaki-u.ac.jp [Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

    2014-09-29

    Hepatocyte growth factor/scatter factor (HGF/SF) plays critical roles in cancer progression through its specific receptor, MET. HGF/SF is usually synthesized and secreted as an inactive proform (pro-HGF/SF) by stromal cells, such as fibroblasts. Several serine proteases are reported to convert pro-HGF/SF to mature HGF/SF and among these, HGF activator (HGFA) and matriptase are the most potent activators. Increased activities of both proteases have been observed in various cancers. HGFA is synthesized mainly by the liver and secreted as an inactive pro-form. In cancer tissues, pro-HGFA is likely activated by thrombin and/or human kallikrein 1-related peptidase (KLK)-4 and KLK-5. Matriptase is a type II transmembrane serine protease that is expressed by most epithelial cells and is also synthesized as an inactive zymogen. Matriptase activation is likely to be mediated by autoactivation or by other trypsin-like proteases. Recent studies revealed that matriptase autoactivation is promoted by an acidic environment. Given the mildly acidic extracellular environment of solid tumors, matriptase activation may, thus, be accelerated in the tumor microenvironment. HGFA and matriptase activities are regulated by HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment. HAIs may have an important role in cancer cell biology by regulating HGF/SF-activating proteases.

  5. Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues

    Hepatocyte growth factor/scatter factor (HGF/SF) plays critical roles in cancer progression through its specific receptor, MET. HGF/SF is usually synthesized and secreted as an inactive proform (pro-HGF/SF) by stromal cells, such as fibroblasts. Several serine proteases are reported to convert pro-HGF/SF to mature HGF/SF and among these, HGF activator (HGFA) and matriptase are the most potent activators. Increased activities of both proteases have been observed in various cancers. HGFA is synthesized mainly by the liver and secreted as an inactive pro-form. In cancer tissues, pro-HGFA is likely activated by thrombin and/or human kallikrein 1-related peptidase (KLK)-4 and KLK-5. Matriptase is a type II transmembrane serine protease that is expressed by most epithelial cells and is also synthesized as an inactive zymogen. Matriptase activation is likely to be mediated by autoactivation or by other trypsin-like proteases. Recent studies revealed that matriptase autoactivation is promoted by an acidic environment. Given the mildly acidic extracellular environment of solid tumors, matriptase activation may, thus, be accelerated in the tumor microenvironment. HGFA and matriptase activities are regulated by HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment. HAIs may have an important role in cancer cell biology by regulating HGF/SF-activating proteases

  6. Murine eosinophil differentiation factor. An eosinophil-specific colony- stimulating factor with activity for human cells

    1986-01-01

    A purified murine lymphokine, eosinophil differentiation factor (EDF), was found to be a selective stimulus for the clonal proliferation and differentiation of murine eosinophil progenitor cells, establishing it as the murine eosinophil colony-stimulating factor (Eo-CSF). EDF was also active on human eosinophil progenitors and mature blood eosinophils, but had no effect on neutrophil or macrophage precursor cells, nor on blood neutrophils. In culture of human bone marrow cells, EDF stimulated...

  7. Planning as a factor of locating production activities in Slovenia

    Simon Kušar

    2010-12-01

    Full Text Available Institutional approach in economic geography highlights the role of institutions at economic development and locating enterprises. Formal planning is an institutional factor as well, while it includes a system of rules, laws and norms. The article presents the role of planning at locating production activities in Slovenia after 1990 by analysing literature and development documents, together with a case study.

  8. Desain Pembelajaran Materi Belah Ketupat Menggunakan Kain Jumputan Palembang untuk Siswa Kelas VII

    Fauziyah Fauziyah

    2016-06-01

    Full Text Available Desain pembelajaran materi belah ketupat menggunakan kain Jumputan Palembang untuk siswa kelas VII. Penelitian ini bertujuan untuk melihat bagaimana penggunaan kain Jumputan Palembang dalam membangun pemahaman siswa mengenai belah ketupat. Siswa akan membandingkan luas daerah dua buah kain Jumputan, merancang dan membuat belah ketupat kemudian menggunting serta menyusunnya kembali menjadi suatu bentuk baru, menentukan luas daerah belah ketupat, membandingkan keliling dua buah kain Jumputan dan menentukan keliling belah ketupat. Subjek penelitian ini adalah 30 siswa kelas VII SMP Pusri Palembang. Penelitian ini menggunakan design research yang terdiri dari tiga tahap : preparing for the experiment, experiment in the classroom (pilot experiment dan  teaching experiment, dan retrospective analysis. Pada tahap preparing for the experiment, beberapa aktifitas dibuat menggunakan pendekatan Pendidikan Matematika Realistik Indonesia (PMRI. Hasil dari penelitian menunjukkan kain Jumputan Palembang dapat digunakan sebagai starting point dalam pembelajaran belah ketupat untuk siswa kelas VII SMP.The design learning rhombus using kain Jumputan Palembang for VII grade students. This research aims to investigate how to use Kain Jumputan Palembang to build student’s understanding on rhombus. Students were required to comparing the area of two cloths, designing and making rhombus then reshaping to new shapes, determining the area of rhombus, comparing the perimeter of two cloths and determining the perimeter of rhombus. Subjects were 30 first grade students of SMP Pusri Palembang. The study used a design research method consisting of three stages : preparing for the experiment, experiment in the classroom (pilot experiment and teaching experiment, and retrospective analysis. During the preparing for the experiment stage, instructional activities was designing utilizing of Indonesian Realistic Mathematics Education (PMRI approach. The result of experiments

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

    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

  10. Factors Predicting Physical Activity Among Children With Special Needs

    Shahram Yazdani, MD

    2013-07-01

    Full Text Available Introduction 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. Methods 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. Results 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. Conclusion 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.

  11. Supported liquid membrane extraction of 99mTc(VII) in a hollow fibre contactor

    Supported liquid membrane (SLM) extraction of 99mTc(VII) in a hollow fiber contactor was investigated in this study. Technetium in a form of pertechnetate was extracted in the three phase system, from the acidic donor solution through the organic phase placed in the membrane pores and then to the alkaline acceptor solution. Tri-n-octylamine as a well known selective extractant for the separation of technetium from molybdenum was applied for this purpose. The aim of this work was to characterize SLM extraction of 99mTc in order to investigate the applicability of this technique for the alternative, cyclotron production of 99mTc and other positron emitting isotopes of Tc. SLM extraction of 99mTc (VII) was performed in a membrane contactor consisting of a glass housing in a form of U-shaped glass tube and a single hollow fiber. The microporous hydrophobic polypropylene hollow fiber membrane (Hoechst-Celanese, USA) was used in this study. The inner diameter of the hollow fiber was 280 μm, the thickness of the wall was 190 μm, and the length of the hollow fiber was 120 mm. The donor solution was initially containing 13 kBq 99mTc (VII) in 1 dm3 0.9 % NaCl at pH=3-4 and fed along the lumen of the hollow fiber, either in continuous or recirculated mode of operation, by a peristaltic pump. The membrane was impregnated by soaking in the organic phase (50% tri-n-octylamine in hexane) for 1h, which was followed by washing in a water-bath in order to remove the excess of the solvent. The acceptor solution containing 0.1 mol·dm-3 NaOH was fed along the shell side in continuous mode of operation. The activity concentration of 99mTc in the donor and acceptor solution was determined using an automated γ-counter. The transport of 99mTc(VII) across the tri-n-octylamine-hexane based SLM as a function of the donor flow rate under continuous and recirculation mode of operation was investigated. The obtained results are discussed in terms of extraction efficiency, mass transfer

  12. Vena porta thrombosis in patient with inherited factor VII deficiency

    Klovaite, Jolanta; Friis-Hansen, Lennart Jan; Larsen, Fin S; Toffner-Clausen, Nielsaage; Bjerrum, Ole W

    2010-01-01

    inherited FVII deficiency and chronic vena porta thrombosis. She presented at 32 weeks of gestation with spontaneously increased international normalized ratio, severe thrombocytopenia and very few unspecific symptoms. The extensive examination of the patient revealed cavernous transformation of the portal...

  13. Activating transcription factor 4 regulates osteoclast differentiation in mice

    Cao, Huiling; Yu, Shibing; Yao, Zhi; Galson, Deborah L; Jiang, Yu; Zhang, Xiaoyan; Fan, Jie; Lu, Binfeng; Guan, Youfei; Luo, Min; Lai, Yumei; Zhu, Yibei; Kurihara, Noriyoshi; Patrene, Kenneth; Roodman, G. David

    2010-01-01

    Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Atf4 in mice. OCL differentiation was drastically decreased in Atf4–/– bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4–/– BMMs with WT OBLs or a high concentration of RANKL failed ...

  14. Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner.

    Seiko Oda

    Full Text Available BACKGROUND: Macrophage migration inhibitory factor (MIF is not only a cytokine which has a critical role in several inflammatory conditions but also has endocrine and enzymatic functions. MIF is identified as an intracellular signaling molecule and is implicated in the process of tumor progression, and also strongly enhances neovascularization. Overexpression of MIF has been observed in tumors from various organs. MIF is one of the genes induced by hypoxia in an hypoxia-inducible factor 1 (HIF-1-dependent manner. METHODS/PRINCIPAL FINDINGS: The effect of MIF on HIF-1 activity was investigated in human breast cancer MCF-7 and MDA-MB-231 cells, and osteosarcoma Saos-2 cells. We demonstrate that intracellular overexpression or extracellular administration of MIF enhances activation of HIF-1 under hypoxic conditions in MCF-7 cells. Mutagenesis analysis of MIF and knockdown of 53 demonstrates that the activation is not dependent on redox activity of MIF but on wild-type p53. We also indicate that the MIF receptor CD74 is involved in HIF-1 activation by MIF at least when MIF is administrated extracellularly. CONCLUSION/SIGNIFICANCE: MIF regulates HIF-1 activity in a p53-dependent manner. In addition to MIF's potent effects on the immune system, MIF is linked to fundamental processes conferring cell proliferation, cell survival, angiogenesis, and tumor invasiveness. This functional interdependence between MIF and HIF-1alpha protein stabilization and transactivation activity provide a molecular mechanism for promotion of tumorigenesis by MIF.

  15. Keefektivan PMRI Berbantuan Alat Peraga Terhadap Kemampuan Pemecahan Masalah Serupa PISA Pada Kelas VII

    Riyanto Riyanto

    2014-06-01

    Full Text Available AbstrakTujuan penelitian ini untuk mengetahui keefektivan pembelajaran dengan metode Pendidi-kan Matematika Realistik Indonesia (PMRI berbantuan alat peraga terhadap kemampuan pemecahan masalah serupa PISA siswa pada materi segiempat. Populasi dalam penelitian ini adalah siswa kelas VII SMP Negeri 3 Ungaran tahun pelajaran 2012/2013. Pemilihan sampel dengan cara random sampling, diperoleh siswa kelas VII-I dan siswa kelas VII-J se-bagai kelas eksperimen dan kelas kontrol. Kelas eksperimen diajar dengan metode PMRI berbantuan alat peraga, sedangkan kelas kontrol diajar dengan metode ekspositori. Data di-peroleh dengan metode observasi untuk mengamati aktivitas belajar guru dan metode tes untuk menentukan hasil belajar siswa yang kemudian dianalisis dengan uji ketuntasan dan uji perbedaan rata-rata: uji satu pihak (pihak kanan. Hasil penelitian adalah (1 hasil be-lajar siswa kelas eksperimen belum mencapai kriteria ketuntasan klasikal, (2 rata-rata ke-mampuan pemecahan masalah serupa PISA kelas eksperimen lebih baik dari kelas kontrol, dan (3 skor rata-rata aktivitas guru kelas ekperimen dan kelas kontrol memiliki kategori baik. Kata kunci:       Kualitas Pembelajaran; PISA; PMRI.  AbstractThe purpose of this research was to determine the effectiveness of learning by Teams Pendidikan Matematika Realistik Indonesia (PMRI assisted on figure tools to the problem solving skills PISA student on quadrilateral material. The population in this study is student of VIIth grade class of 3 Ungaran junior high school on period 2012/2013. The selection of the sample is done by random sampling which is gotten students class VII-I and students class VII-J as the experimental class and the controlling class. Experimental class was taught by PMRI assisted on figure tools, while the controlling class was taught with the expository method. Data obtained by the observation method to observe the activities of teacher learning and test methods for determining

  16. PENGARUH KETERAMPILAN MENGELOLA KELAS DAN GAYA MENGAJAR GURU TERHADAP KEAKTIFAN BELAJAR SISWA KELAS VII MATA PELAJARAN IPS TERPADU DI SMP NEGERI SE-KECAMATAN WEDUNG KABUPATEN DEMAK

    Rifanah

    2014-06-01

    Full Text Available Tujuan Penelitian ini adalah mengetahui pengaruh keterampilan mengelola kelas, dan gaya mengajar guru terhadap keaktifan belajar siswa kelas VII SMP Negeri se-Kecamatan Wedung. Dalam penelitian ini populasi yang digunakan adalah seluruh siswa kelas VII SMP Negeri se-Kecamatan Wedung yang berjumlah 296 siswa. Penelitian ini menggunakan sampel yang berjumlah 81 sampel. Teknik pengambilan sampel menggunakan proportional random sampling. Variabel dalam penelitian ini adalah variabel bebas yaitu keterampilan mengelola kelas (XI, gaya mengajar guru (X2, dan keaktifan belajar siswa (Y sebagai variabel terikat. Metode pengumpulan data: dokumentasi dan angket. Metode analisis yaitu analisi deskriptif persentase. Hasil penelitian diperoleh persamaan regresi Y = 1,873+ 0,260 X1 + 0,670 X2. Secara deskriptif penelitian menunjukkan bahwa keterampilan mengelola kelas, dan gaya mengajar guru adalah baik. Pengaruh keterampilan mengelola kelas terhadap keaktifan belajar siswa sebesar 84,5%, gaya mengajar guru terhadap keaktifan belajar siswa sebesar 92,8%, pengarunya positif dan signifikan. Sedangkan pengaruh keterampilan mengelola kelas dan gaya mengajar guru secara bersama berpengaruh terhadap keaktifan belajar siswa sebesar 89,7% dan sisanya sebesar 10,3% dipengaruhi oleh faktor lain yang tidak diteliti. The purpose of this study was to determine the effect of classroom management skills, and the teaching style of teachers to students of class VII activity of SMP Wedung throughout the District. In this study population used is the entire Junior High School seventh grade students throughout the District Wedung totaling 296 students. This study used a sample of 81 samples. Sampling technique using proportional random sampling. The variable in this study is the independent variable classroom management skills (XI, the teacher's teaching style (X2, and the activity of student learning (Y as the dependent variable. Methods of data collection: documentation and

  17. The dust covering factor in active galactic nuclei

    Stalevski, Marko; Ricci, Claudio; Ueda, Yoshihiro; Lira, Paulina; Fritz, Jacopo; Baes, Maarten

    2016-05-01

    The primary source of emission of active galactic nuclei (AGNs), the accretion disc, is surrounded by an optically and geometrically thick dusty structure (`the so-called dusty torus'). The infrared radiation emitted by the dust is nothing but a reprocessed fraction of the accretion disc emission, so the ratio of the torus to the AGN luminosity (Ltorus/LAGN) should corresponds to the fraction of the sky obscured by dust, i.e. the covering factor. We undertook a critical investigation of the Ltorus/LAGN as the dust covering factor proxy. Using state-of-the-art 3D Monte Carlo radiative transfer code, we calculated a grid of spectral energy distributions (SEDs) emitted by the clumpy two-phase dusty structure. With this grid of SEDs, we studied the relation between Ltorus/LAGN and the dust covering factor for different parameters of the torus. We found that in the case of type 1 AGNs the torus anisotropy makes Ltorus/LAGN underestimate low covering factors and overestimate high covering factors. In type 2 AGNs Ltorus/LAGN always underestimates covering factors. Our results provide a novel easy-to-use method to account for anisotropy and obtain correct covering factors. Using two samples from the literature, we demonstrated the importance of our result for inferring the obscured AGN fraction. We found that after the anisotropy is properly accounted for, the dust covering factors show very weak dependence on LAGN, with values in the range of ≈0.6-0.7. Our results also suggest a higher fraction of obscured AGNs at high luminosities than those found by X-ray surveys, in part owing to the presence of a Compton-thick AGN population predicted by population synthesis models.

  18. Design and analysis of an active power factor correction circuit

    Zhou, Zhen

    1989-01-01

    The design of an active-unity power factor correction circuit with variable-hysteresis control for off-line dc-to-dc switching power supplies is described. Design equations relating the boost inductor current ripple to the circuit components selection and circuit performance arc discussed. A computer-aided design program (CADO) is developed to give the optimal circuit components selection. A 500 watt, 300 volt experimental circuit is built to verify the simulation and analysis ...

  19. 凝血因子ⅦR353Q基因多态性与中国汉族儿童脑性瘫痪的相关性研究%Relationship between Gene Polymorphism of Factor VII R353Q and Cerebral Palsy for Han Chinese Children

    李晓捷; 徐磊; 康贝贝

    2013-01-01

    Objective To investigate the relationship between gene polymorphism of factor VII R353Q (FVII R353Q) and cerebral pal-sy for Han Chinese children. Methods Polymerase chain reaction-restricted fragment length polymorphism were used to determine geno-type and allele of R353Q gene in 160 children with cerebral palsy and 137 normal children. Results The genotype of FVII R353Q is close to Hardy-Weinberg equilibrium in both CP group and control group (P>0.05). There was not significant difference in the distribution of the al-lelic frequency and genotype of FVII R353Q between the both groups (P=0.436, P=0.182, respectively). Conclusion The gene polymor-phism of FVII R353Q is not significantly related with cerebral palsy for Han Chinese children.%目的探讨凝血因子ⅦR353Q基因多态性与中国汉族儿童脑瘫的关系。方法应用聚合酶链反应与限制性片断长度多态性分析方法对160例脑瘫患儿和137名正常儿童的凝血因子ⅦR353Q基因型和等位基因进行测定。结果脑瘫组和对照组人群凝血因子ⅦR353Q基因型分布符合Hardy-weinberg平衡定律(P>0.05),两组凝血因子ⅦR353Q基因型(P=0.436)和等位基因分布无显著性差异(P=0.182)。结论凝血因子ⅦR353Q基因多态性不是中国汉族儿童脑瘫发病的遗传易感因子。

  20. Search for novel genetic risk factors for venous thrombosis: a dual approach

    van Minkelen, Rick

    2008-01-01

    Venous thrombosis (VT) is a multicausal disease that is caused by the interaction of both genetic and acquired risk factors. The aim of the studies described in this thesis was to identify novel genes or genomic regions that contribute to the susceptibility of VT. We used two different approaches to achieve this goal: the hypothesis-based candidate gene approach and the discovery-based genome-wide approach. The candidate genes investigated are factor VII-activating protease, coagulation facto...

  1. Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation

    Hauge, Camilla; Antal, Torben L; Hirschberg, Daniel; Doehn, Ulrik; Thorup, Katrine; Idrissova, Leila; Hansen, Klaus; Jensen, Ole N; Jørgensen, Thomas J; Biondi, Ricardo M; Frödin, Morten

    2007-01-01

    The growth factor/insulin-stimulated AGC kinases share an activation mechanism based on three phosphorylation sites. Of these, only the role of the activation loop phosphate in the kinase domain and the hydrophobic motif (HM) phosphate in a C-terminal tail region are well characterized. We invest...

  2. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.

    Naranjo, José R; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C; Arrabal, María D; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-02-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD. PMID:26752648

  3. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease

    Naranjo, José R.; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M.; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C.; Arrabal, María D.; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-01-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD. PMID:26752648

  4. Bianchi VII_h models and the cold spot texture

    Bridges, M; Cruz, M; Hobson, M P; Lasenby, A N; Vielva, P; Martínez-González, E

    2007-01-01

    We have returned to our previous Bianchi VII_h analysis in light of the Cruz et al. 2007 suggestion that the cold spot observed near the southern Galactic pole may be a remnant temperature perturbation of a cosmic texture. In Bridges et al. 2006b we found two favoured left handed Bianchi VII_h templates with restricted prior probabilities so that the template was centred close to the cold spot. Using WMAP data `corrected' for the texture fit we have now reexamined both models to assess any changes to these conclusions. We find that both models are left almost entirely unconstrained by the data and consequently exhibit significantly reduced Bayesian evidences. Both models are now disfavoured by the data. This result reinforces our previous suggestion that the cold spot was likely to be driving any Bianchi VII_h detection.

  5. Mutational analysis of a patient with mucopolysaccharidosis type VII, and identification of pseudogenes

    Shipley, J.M.; Klinkenberg, M.; Wu, B.M.; Bachinsky, D.R.; Grubb, J.H.; Sly, W.S. (St. Louis Univ. School of Medicine, MO (United States))

    1993-03-01

    PCR of cDNA produced from patient fibroblasts allowed the authors to determine the paternal mutation in the first patient reported with [beta]-glucuronidase-deficiency mucopolysaccharidosis type VII (MPS VII). The G[r arrow]T transversion 1,881 bp downstream of the ATG translation initiation codon destroys an MboII restriction site and converts Trp627 to Cys (W627C). Digestion of genomic DNA PCR fragments with MboII indicated that the patient and the father were heterozygous for this missense mutation in exon 12. Failure to find cDNAs from patient RNA which did not contain this mutation suggested that the maternal mutation leads to greatly reduced synthesis or reduced stability of mRNA from the mutant allele. In order to identify the maternal mutation, it was necessary to analyze genomic sequences. This approach was complicated by the finding of multiple unprocessed pseudogenes and/or closely related genes. Using PCR with a panel of human/rodent hybrid cell lines, the authors found that these pseudogenes were present over chromosomes 5-7, 20, and 22 and the Y chromosome. Conditions were defined which allowed them to amplify and characterize genomic sequences for the true [beta]-glucuronidase gene despite this background of related sequences. The patient proved to be heterozygous for a second mutation, in which a C[r arrow]T transition introduces a termination codon (R356STOP) in exon 7. The mother was also heterozygous for this mutation. Expression of a cDNA containing the maternal mutation produced no enzyme activity, as expected. Expression of the paternal mutation in COS-7 cells produced a surprisingly high (65% of control) level of activity. However, activity was 13% of control in transiently transfected murine MPS VII cells. The level of activity of this mutant allele appears to correlate with the level of overexpression. 39 refs., 5 figs., 1 tab.

  6. Time-activity relationships to VOC personal exposure factors

    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

  7. Apollonius de Perge, Coniques tome 4, livres VI et VII

    Rashed, Roshdi

    2009-01-01

    Book VI of the Konika is essentially devoted to the question of the identity and similarity of two conic sections, or two parts of conic sections. In Book VII Apollonius deals with the various relationships between the lengths of diameters and conjugate diameters. The results are applied to the exposition of a number of problems, as well as to some problems which Apollonius indicates will be demonstrated and solved in Book VIII, which was lost in Antiquity. Books VI and VII have only survived in an Arabic translation, and are presented here in a critical edition, together with a faithful trans

  8. Transcription Factor Arabidopsis Activating Factor1 Integrates Carbon Starvation Responses with Trehalose Metabolism.

    Garapati, Prashanth; Feil, Regina; Lunn, John Edward; Van Dijck, Patrick; Balazadeh, Salma; Mueller-Roeber, Bernd

    2015-09-01

    Plants respond to low carbon supply by massive reprogramming of the transcriptome and metabolome. We show here that the carbon starvation-induced NAC (for NO APICAL MERISTEM/ARABIDOPSIS TRANSCRIPTION ACTIVATION FACTOR/CUP-SHAPED COTYLEDON) transcription factor Arabidopsis (Arabidopsis thaliana) Transcription Activation Factor1 (ATAF1) plays an important role in this physiological process. We identified TREHALASE1, the only trehalase-encoding gene in Arabidopsis, as a direct downstream target of ATAF1. Overexpression of ATAF1 activates TREHALASE1 expression and leads to reduced trehalose-6-phosphate levels and a sugar starvation metabolome. In accordance with changes in expression of starch biosynthesis- and breakdown-related genes, starch levels are generally reduced in ATAF1 overexpressors but elevated in ataf1 knockout plants. At the global transcriptome level, genes affected by ATAF1 are broadly associated with energy and carbon starvation responses. Furthermore, transcriptional responses triggered by ATAF1 largely overlap with expression patterns observed in plants starved for carbon or energy supply. Collectively, our data highlight the existence of a positively acting feedforward loop between ATAF1 expression, which is induced by carbon starvation, and the depletion of cellular carbon/energy pools that is triggered by the transcriptional regulation of downstream gene regulatory networks by ATAF1. PMID:26149570

  9. Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity

    Sorensen, Anders B.; Madsen, Jesper Jonasson; Svensson, L. Anders; Pedersen, Anette A.; Østergaard, Henrik; Overgaard, Michael T.; Olsen, Ole H.; Gandhi, Prafull S

    2016-01-01

    The complex of coagulation factor VIIa (FVIIa), a trypsin-like serine protease, and membrane-bound tissue factor (TF) initiates blood coagulation upon vascular injury. Binding of TF to FVIIa promotes allosteric conformational changes in the FVIIa protease domain and improves its catalytic...... properties. Extensive studies have revealed two putative pathways for this allosteric communication. Here we provide further details of this allosteric communication by investigating FVIIa loop swap variants containing the 170 loop of trypsin that display TF-independent enhanced activity. Using x......-ray crystallography, we show that the introduced 170 loop from trypsin directly interacts with the FVIIa active site, stabilizing segment 215-217 and activation loop 3, leading to enhanced activity. Molecular dynamics simulations and novel fluorescence quenching studies support that segment 215-217 conformation is...

  10. The dust covering factor in active galactic nuclei

    Stalevski, Marko; Ueda, Yoshihiro; Lira, Paulina; Fritz, Jacopo; Baes, Maarten

    2016-01-01

    The primary source of emission of active galactic nuclei (AGN), the accretion disk, is surrounded by an optically and geometrically thick dusty structure ("the so-called dusty torus"). The infrared radiation emitted by the dust is nothing but a reprocessed fraction of the accretion disk emission, so the ratio of the torus to the AGN luminosity ($L_{\\text{torus}}/L_{\\text{AGN}}$) should correspond to the fraction of the sky obscured by dust, i.e. the covering factor. We undertook a critical investigation of the $L_{\\text{torus}}/L_{\\text{AGN}}$ as the dust covering factor proxy. Using state-of-the-art 3D Monte Carlo radiative transfer code, we calculated a grid of SEDs emitted by the clumpy two-phase dusty structure. With this grid of SEDs, we studied the relation between $L_{\\text{torus}}/L_{\\text{AGN}}$ and the dust covering factor for different parameters of the torus. We found that in case of type 1 AGNs the torus anisotropy makes $L_{\\text{torus}}/L_{\\text{AGN}}$ underestimate low covering factors and ove...

  11. Protein kinase A binds and activates heat shock factor 1.

    Ayesha Murshid

    Full Text Available BACKGROUND: Many inducible transcription factors are regulated through batteries of posttranslational modifications that couple their activity to inducing stimuli. We have studied such regulation of Heat Shock Factor 1 (HSF1, a key protein in control of the heat shock response, and a participant in carcinogenisis, neurological health and aging. As the mechanisms involved in the intracellular regulation of HSF1 in good health and its dysregulation in disease are still incomplete we are investigating the role of posttranslational modifications in such regulation. METHODOLOGY/PRINCIPAL FINDINGS: In a proteomic study of HSF1 binding partners, we have discovered its association with the pleiotropic protein kinase A (PKA. HSF1 binds avidly to the catalytic subunit of PKA, (PKAcα and becomes phosphorylated on a novel serine phosphorylation site within its central regulatory domain (serine 320 or S320, both in vitro and in vivo. Intracellular PKAcα levels and phosphorylation of HSF1 at S320 were both required for HSF1 to be localized to the nucleus, bind to response elements in the promoter of an HSF1 target gene (hsp70.1 and activate hsp70.1 after stress. Reduction in PKAcα levels by small hairpin RNA led to HSF1 exclusion from the nucleus, its exodus from the hsp70.1 promoter and decreased hsp70.1 transcription. Likewise, null mutation of HSF1 at S320 by alanine substitution for serine led to an HSF1 species excluded from the nucleus and deficient in hsp70.1 activation. CONCLUSIONS: These findings of PKA regulation of HSF1 through S320 phosphorylation add to our knowledge of the signaling networks converging on this factor and may contribute to elucidating its complex roles in the stress response and understanding HSF1 dysregulation in disease.

  12. 76 FR 79065 - Recordkeeping and Reporting Requirements Under Title VII, the ADA and GINA

    2011-12-21

    ... Employment Opportunity Commission 29 CFR Part 1602 Recordkeeping and Reporting Requirements Under Title VII..., revised as of July 1, 2011, in Part 1602, remove the words ``section 709(c) of title VII or section 107 of the ADA'' and add in their place the words ``section 709(c) of title VII, section 107 of the ADA,...

  13. 20 CFR 211.12 - Compensation credited for title VII benefits.

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Compensation credited for title VII benefits... RETIREMENT ACT CREDITABLE RAILROAD COMPENSATION § 211.12 Compensation credited for title VII benefits. Payments made to an employee under title VII of the Regional Rail Reorganization Act of 1973 are...

  14. 78 FR 36011 - Region VII Regulatory Fairness Board; Federal Regulatory Enforcement Fairness Hearing

    2013-06-14

    ... ADMINISTRATION Region VII Regulatory Fairness Board; Federal Regulatory Enforcement Fairness Hearing AGENCY: U.S. Small Business Administration (SBA). ACTION: Notice of open meeting of the Regional (Region VII) Small... Region VII Regulatory Fairness Board must contact Jeanna Trenkamp by June 17, 2013 in writing, by fax...

  15. 29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Relationship of title VII to the Equal Pay Act. 1604.8... GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The employee coverage of the prohibitions against discrimination based on sex contained in title VII...

  16. Underground Test Area Subproject Phase I Data Analysis Task. Volume VII - Tritium Transport Model Documentation Package

    None

    1996-12-01

    Volume VII of the documentation for the Phase I Data Analysis Task performed in support of the current Regional Flow Model, Transport Model, and Risk Assessment for the Nevada Test Site Underground Test Area Subproject contains the tritium transport model documentation. Because of the size and complexity of the model area, a considerable quantity of data was collected and analyzed in support of the modeling efforts. The data analysis task was consequently broken into eight subtasks, and descriptions of each subtask's activities are contained in one of the eight volumes that comprise the Phase I Data Analysis Documentation.

  17. Factors influencing dust exposure: finishing activities in drywall construction.

    Simmons, Catherine E; Jones, Rachael M; Boelter, Fred W

    2011-05-01

    Sanding drywall joint compound is a dusty construction activity. We studied potential factors influencing exposure to respirable and total dust for sanders and bystanders in the area of drywall joint compound finishing in 17 test events within a room-scale isolation chamber. We found the air change rate to be negatively correlated with dust C(twa) both in the sander's personal breathing zone and surrounding area. We could not conclude that sanding tool type systematically influences dust C(twa), but the use of 80-grit abrasive was associated with the highest dust C(twa). We found respirable dusts were uniformly dispersed 1-8.2 m from sanding activities at a fixed location. As anticipated, both respirable and total dust C(twa) in the sander's personal breathing zone are higher than in the surrounding area. The respirable fraction of the total dust mass C(twa) was greater in the surrounding area than in the sander's personal breathing zone. Respirable dust concentrations measured in real time increased over the duration of sanding, exhibiting a temporal trend that is similar to that predicted by the well-mixed box model with contaminant removal by mechanical ventilation only, and continuous emission. Dust concentrations returned to pre-activity (background) levels 2-4 hr after cessation of the sanding activity. PMID:21491324

  18. Viis armastuslugu suurel ekraanil / Tristan Priimägi

    Priimägi, Tristan, 1976-

    2008-01-01

    Viis näidet filmiajaloost, kus režissööri ja staari vahel on tunded : Roger Vadim ja Tema Naised, Werner Herzog ja Klaus Kinski, Federico Fellini ja Anita Ekberg, Quentin Tarantino ja Uma Thurman, Rainer Werner Fassbinder ja Mr/Mrs X

  19. Use of the Tactaid II and Tactaid VII with Children.

    Weisenberger, Janet M.; Percy, Mary E.

    1994-01-01

    This paper discusses basic strategies in providing speech information to deaf individuals via the tactile modality and describes the Tactaid II and Tactaid VII vibrotactile aids employed in the Central Institute for the Deaf Sensory Aids Study. Coding, display, and operation are described for each device. Results from previous studies with both…

  20. Photosynthetic pigments of oceanic Chlorophyta belonging to prasinophytes clade VII.

    Lopes Dos Santos, Adriana; Gourvil, Priscillia; Rodríguez, Francisco; Garrido, José Luis; Vaulot, Daniel

    2016-02-01

    The ecological importance and diversity of pico/nanoplanktonic algae remains poorly studied in marine waters, in part because many are tiny and without distinctive morphological features. Amongst green algae, Mamiellophyceae such as Micromonas or Bathycoccus are dominant in coastal waters while prasinophytes clade VII, yet not formerly described, appear to be major players in open oceanic waters. The pigment composition of 14 strains representative of different subclades of clade VII was analyzed using a method that improves the separation of loroxanthin and neoxanthin. All the prasinophytes clade VII analyzed here showed a pigment composition similar to that previously reported for RCC287 corresponding to pigment group prasino-2A. However, we detected in addition astaxanthin for which it is the first report in prasinophytes. Among the strains analyzed, the pigment signature is qualitatively similar within subclades A and B. By contrast, RCC3402 from subclade C (Picocystis) lacks loroxanthin, astaxanthin, and antheraxanthin but contains alloxanthin, diatoxanthin, and monadoxanthin that are usually found in diatoms or cryptophytes. For subclades A and B, loroxanthin was lowest at highest light irradiance suggesting a light-harvesting role of this pigment in clade VII as in Tetraselmis. PMID:26987097

  1. Viis aastakümmet raamatukogunduse radadel / Anne Veinberg

    Veinberg, Anne

    2008-01-01

    Arvustus: Kikas, Konrad. Verba volant, scripta manent : viis aastakümmet raamatukogunduse ja infoteaduse radadel = Verba volant, scripta manent : five decades on the field of librarianship and information science. - Tallinn : Tallinna Tehnikaülikooli Kirjastus, 2008. - 366 lk. : ill. portr. - (Tallinna Tehnikaülikooli Raamatukogu töid. A ; 5)

  2. Statistics and Title VII Proof: Prima Facie Case and Rebuttal.

    Whitten, David

    1978-01-01

    The method and means by which statistics can raise a prima facie case of Title VII violation are analyzed. A standard is identified that can be applied to determine whether a statistical disparity is sufficient to shift the burden to the employer to rebut a prima facie case of discrimination. (LBH)

  3. Enrico VII e l’Italia. Un primo bilancio

    Gian Maria Varanini

    2014-06-01

    Full Text Available Il testo introduce i saggi pubblicati nel fasc. 1 (2014 di “Reti Medievali - Rivista”, traccia un sintetico bilancio delle ricerche recenti sulla spedizione di Enrico VII di Lussemburgo in Italia (1310-1313 e propone alcune questioni interpretative.

  4. Kasuperest viidi viis last ja algatati kriminaalmenetlus piinamises / Rasmus Rekand

    Rekand, Rasmus

    2011-01-01

    Lugu asenduskodu teenust pakkuvast perekonnast, kelle hoole all oli lisaks pere enda 3 lapsele 6 võõrast last ning kuidas lastega mittehakkama saamine viis olukorrani, kus lapsed viidi kasupere juurest ära ja lisaks algatati uurimine keelatud võtete kasutamise kohta kasvatamistegevuses

  5. Thyroid Transcription Factor 1 Reprograms Angiogenic Activities of Secretome.

    Wood, Lauren W; Cox, Nicole I; Phelps, Cody A; Lai, Shao-Chiang; Poddar, Arjun; Talbot, Conover; Mu, David

    2016-01-01

    Through both gain- and loss-of-TTF-1 expression strategies, we show that TTF-1 positively regulates vascular endothelial growth factor (VEGF) and that the VEGF promoter element contains multiple TTF-1-responsive sequences. The major signaling receptor for VEGF, i.e VEGFR2, also appears to be under a direct and positive regulation of TTF-1. The TTF-1-dependent upregulation of VEGF was moderately sensitive to rapamycin, implicating a partial involvement of mammalian target of rapamycin (mTOR). However, hypoxia did not further increase the secreted VEGF level of the TTF-1(+) lung cancer cells. The TTF-1-induced VEGF upregulation occurs in both compartments (exosomes and exosome-depleted media (EDM)) of the conditioned media. Surprisingly, the EDM of TTF-1(+) lung cancer cells (designated EDM-TTF-1(+)) displayed an anti-angiogenic activity in the endothelial cell tube formation assay. Mechanistic studies suggest that the increased granulocyte-macrophage colony-stimulating factor (GM-CSF) level in the EDM-TTF-1(+) conferred the antiangiogenic activities. In human lung cancer, the expression of TTF-1 and GM-CSF exhibits a statistically significant and positive correlation. In summary, this study provides evidence that TTF-1 may reprogram lung cancer secreted proteome into an antiangiogenic state, offering a novel basis to account for the long-standing observation of favorable prognosis associated with TTF-1(+) lung adenocarcinomas. PMID:26912193

  6. IDENTIFICATION OF CRITICAL SSCM ACTIVITIES THROUGH CONFIRMATORY FACTOR ANALYSIS

    V. Narasimham

    2013-06-01

    Full Text Available As a developing country, economic and environmental performance has to be balanced in India. Green supply chain management (GSCM is emerging as an important proactive approach for Indian enterprises for improving environmental performance of processes and products in accordance with the requirements of environmental regulations. This study examines the consistency approaches by confirmatory factor analysis that determines the construct validity, convergent validity,construct reliability and internal consistency of the items of Sustainable supply chain management (SSCM requirements. This study examines the consistency approaches by Confirmatory factor analysis that determines the adoption and implementation of Sustainable supply chain management activities in small & medium scale industries. The requirements include Management commitment, customer coordination, sustainable design & production, green procurement and eco logistics for sustainable supply chains. This study suggested that the five factor model with eighteen items of the sustainable supply chain design had a good fit. Further, the study showed a valid and reliable measurement to identify critical items among the requirements of sustainable supply chains.

  7. Purification of human plasma platelet-activating factor acetylhydrolase

    Platelet-activating factor (PAF;1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine is synthesized by a variety of cells. It induces hypotension, and activates platelets, neutrophils, and macrophages at nanomolar concentrations. Removal of the acetate abolishes biological activity, and is catalyzed by a specific PAF acetylhydrolase present in plasma and tissues. The authors developed a rapid assay, based on separation of [3H]acetate from [3H-acetyl]PAF by reversed-phase chromatography. In human plasma the enzyme exhibits an apparent Km of 5.7μM, with a Vmax of 0.027μmol/h/mg. Ultracentrifugation in density gradients showed that 30% of the activity is associated with high density lipoproteins (HDL) and 70% with low density lipoproteins (LDL). The enzyme was purified from LDL by precipitation with Na phosphotungstate and MgCl2, solubilization with Tween 20, column chromatography and electrophoresis. This procedure resulted in a preparation that was 21,000-fold purified from plasma (spec. act. 575μmol/h/mg) with a recovery of 10%. The purified enzyme has a molecular weight of about 43,000, a broad pH optimum (peak 7.5-8.0), and a pl of 4.6. It has greater activity when PAF is in a micellar, as compared to monomeric, and exhibits surface dilution kinetics, which may be important in vivo. The purification and characterization of this enzyme will allow detailed studies of its role in PAF metabolism

  8. Determining the Oral Health Status of Disabled Patients of the Area VII in Cienfuegos

    Ana Belkys Hernández Millán

    2014-10-01

    Full Text Available Background: disability is a social concern; however, there are few studies on the oral health status of disabled patients. Objective: to determine the oral health status of disabled patients of the Area VII in Cienfuegos province. Methods: a case series study was conducted in the Area VII of the municipality of Cienfuegos from January through December 2013. A total of 192 disabled patients who attended the dental clinic or received home visits were included. The variables analyzed were: age, sex, educational level, type of disability, epidemiological classification by oral health status, systemic diseases, risk factors for oral diseases, oral health, periodontal disease (gingivitis, periodontitis, malocclusions, premalignant lesions, need for total or partial denture and need for treatment in primary or secondary care. The information was collected from the medical records and the disability rating sheets. Results are expressed as numbers and percentages. Results: women and patients aged 35-59 years were the most affected. Chronic degenerative diseases predominated, as well as patients in the epidemiological classification by oral health status and hypertension among systemic diseases. Having a history of cavities was the most significant risk factor; chronic edematous gingivitis was the most common, with a higher percentage. Conclusions: the oral health in the study group was poor and it is difficult for the Comprehensive General Dentist to treat these patients despite the existence of care programs for the disabled.

  9. Calidad de las actividades de la asignatura medicina general integral VII en los diferentes escenarios docentes

    Maricel Felicia Castellanos González

    2012-06-01

    Full Text Available Fundamento: en el proceso de enseñanza-aprendizaje que se desarrolla en los diferentes escenarios docentes, se deben tener en cuenta los contenidos ya impartidos, para logar una integración entre los conocimientos teóricos con la práctica médica. Objetivo: evaluar los escenarios docentes según la calidad de las actividades desarrolladas en la asignatura medicina general integral VII, en el contexto del policlínico universitario. Método: se realizó una investigación cuanti-cualitativa según el cumplimiento de indicadores de calidad mediante la aplicación de una guía de observación en los escenarios docentes de la asignatura medicina general integral VII, en el policlínico universitario. Los escenarios docentes evaluados fueron: consultorios, vacunatorios, círculos infantiles, hogares maternos y consulta de planificación familiar. Resultados: el consultorio, el vacunatorio, la consulta de planificación familiar, la escuela y círculo infantil fueron evaluados de regular, solo obtuvieron categoría de bien el hogar materno y el escenario cuerpo de guardia. Las actividades docentes con mayores dificultades fueron: la vigilancia epidemiológica para la pesquisa de factores de riesgo, el control de foco para enfermedades transmisibles y la presentación del análisis de la situación de salud a la comunidad. Conclusiones: el nivel escenario docente en la asignatura medicina general integral VII, de forma general fue evaluado de regular, por tener: el escenario consultorio, el vacunatorio, consulta de planificación familiar, la escuela y círculo infantil evaluados de regular, el hogar materno y el escenario cuerpo de guardia evaluados de bien.

  10. Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Véronique Truffinet; Francois Labrousse; Yves Denizot

    2006-01-01

    AIM: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF (the PAF precursor),phospholipase A2 (PLA2, the enzymatic activity generating lyso-PAF), acetylhydrolase activity (AHA, the PAF degrading enzyme) and PAF receptor (PAF-R) transcripts in cirrhotic liver and hepatocellular carcinoma (HCC).METHODS: Twenty-nine patients with HCC were ehrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. LysoPAF was assessed after its chemical acetylation into PAF.AHA was determined by degradation of [3H]-PAF. PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR.RESULTS: Elevated amounts of PAF and PAF-R transcripts 1 (leukocyte-type) were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 (tissue-type) were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC.CONCLUSION: While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.

  11. Solvent extraction of Tc(VII) and Re(VII) from nitric acid solution with the mixture of CMPO and TBP

    The distribution mechanism of Tc(VII) and Re(VII) between nitric acid solution and n-octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO) / tributyl phosphate (TBP) in n-dodecane or decalin was studied. By using distribution coefficients of Tc(VII) and Re(VII), acid concentration dependence and CMPO concentration dependence were confirmed. The distribution coefficient from a mixed CMPO-TBP system was found to be larger than the sum of those obtained from a CMPO system and a TBP system. This enhancement of Tc extraction was discussed in terms of formation of mixed Tc-CMPO-TBP complexes. (orig.)

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

    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.

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

    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

  14. Phylogenomics of caspase-activated DNA fragmentation factor

    The degradation of nuclear DNA by DNA fragmentation factor (DFF) is a key step in apoptosis of mammalian cells. Using comparative genomics, we have here determined the evolutionary history of the genes encoding the two DFF subunits, DFFA (also known as ICAD) and DFFB (CAD). Orthologs of DFFA and DFFB were identified in Nematostella vectensis, a representative of the primitive metazoan clade cnidarians, and in various vertebrates and insects, but not in representatives of urochordates, echinoderms, and nematodes. The domains mediating the interaction of DFFA and DFFB, a caspase cleavage site in DFFA, and the amino acid residues critical for endonuclease activity of DFFB were conserved in Nematostella. These findings suggest that DFF has been a part of the primordial apoptosis system of the eumetazoan common ancestor and that the ancient cell death machinery has degenerated in several evolutionary lineages, including the one leading to the prototypical apoptosis model, Caenorhabditis elegans

  15. Human factors in remote control engineering development activities

    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

  16. Cooperative Regulation of the Activity of Factor Xa within Prothrombinase by Discrete Amino Acid Regions from Factor Va Heavy Chain†

    2008-01-01

    The prothrombinase complex catalyzes the activation of prothrombin to α-thrombin. We have repetitively shown that amino acid region 695DYDY698 from the COOH terminus of the heavy chain of factor Va regulates the rate of cleavage of prothrombin at Arg271 by prothrombinase. We have also recently demonstrated that amino acid region 334DY335 is required for the optimal activity of prothrombinase. To assess the effect of these six amino acid residues on cofactor activity, we created recombinant factor Va molecules combining mutations at amino acid regions 334–335 and 695−698 as follows: factor V3K (334DY335 → KF and 695DYDY698 → KFKF), factor VKF/4A (334DY335 → KF and 695DYDY698 → AAAA), and factor V6A (334DY335 → AA and 695DYDY698 → AAAA). The recombinant factor V molecules were expressed and purified to homogeneity. Factor Va3K, factor VaK4/4A, and factor Va6A had reduced affinity for factor Xa, when compared to the affinity of the wild-type molecule (factor VaWt) for the enzyme. Prothrombinase assembled with saturating concentrations of factor Va3K had a 6-fold reduced second-order rate constant for prothrombin activation compared to the value obtained with prothrombinase assembled with factor VaWt, while prothrombinase assembled with saturating concentrations of factor VaKF/4A and factor Va6A had approximately 1.5-fold reduced second-order rate constants. Overall, the data demonstrate that amino acid region 334–335 together with amino acid region 695−698 from factor Va heavy chain are part of a cooperative mechanism within prothrombinase regulating cleavage and activation of prothrombin by factor Xa. PMID:18991406

  17. 40 CFR Appendix Vii to Part 266 - Health-Based Limits for Exclusion of Waste-Derived Residues*

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Health-Based Limits for Exclusion of Waste-Derived Residues* VII Appendix VII to Part 266 Protection of Environment ENVIRONMENTAL PROTECTION... SPECIFIC TYPES OF HAZARDOUS WASTE MANAGEMENT FACILITIES Pt. 266, App. VII Appendix VII to Part...

  18. 75 FR 51429 - Definitions Contained in Title VII of Dodd-Frank Wall Street Reform and Consumer Protection Act

    2010-08-20

    ... Definitions Contained in Title VII of Dodd-Frank Wall Street Reform and Consumer Protection Act AGENCY... VII of the Dodd-Frank Act (``Title VII''), provides that the Securities and Exchange Commission (``SEC... ``mixed swaps,'' as that term is used in Title VII of the Dodd-Frank Act. To assist the SEC and CFTC...

  19. Transcription factor PIF4 controls the thermosensory activation of flowering

    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.

  20. Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III.

    Cichon, Sven; Martin, Ludovic; Hennies, Hans Christian; Müller, Felicitas; Van Driessche, Karen; Karpushova, Anna; Stevens, Wim; Colombo, Roberto; Renné, Thomas; Drouet, Christian; Bork, Konrad; Nöthen, Markus M

    2006-12-01

    Hereditary angioedema (HAE) is characterized clinically by recurrent acute skin swelling, abdominal pain, and potentially life-threatening laryngeal edema. Three forms of HAE have been described. The classic forms, HAE types I and II, occur as a consequence of mutations in the C1-inhibitor gene. In contrast to HAE types I and II, HAE type III has been observed exclusively in women, where it appears to be correlated with conditions of high estrogen levels--for example, pregnancy or the use of oral contraceptives. A recent report proposed two missense mutations (c.1032C-->A and c.1032C-->G) in F12, the gene encoding human coagulation factor XII (FXII, or Hageman factor) as a possible cause of HAE type III. Here, we report the occurrence of the c.1032C-->A (p.Thr328Lys) mutation in an HAE type III-affected family of French origin. Investigation of the F12 gene in a large German family did not reveal a coding mutation. Haplotype analysis with use of microsatellite markers is compatible with locus heterogeneity in HAE type III. To shed more light on the pathogenic relevance of the HAE type III-associated p.Thr328Lys mutation, we compared FXII activity and plasma levels in patients carrying the mutation with that of healthy control individuals. Our data strongly suggest that p.Thr328Lys is a gain-of-function mutation that markedly increases FXII amidolytic activity but that does not alter FXII plasma levels. We conclude that enhanced FXII enzymatic plasma activity in female mutation carriers leads to enhanced kinin production, which results in angioedema. Transcription of F12 is positively regulated by estrogens, which may explain why only women are affected with HAE type III. The results of our study represent an important step toward an understanding of the molecular processes involved in HAE type III and provide diagnostic and possibly new therapeutic opportunities. PMID:17186468

  1. 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

    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

  2. Grazing by protozoa as selection factor for activated sludge bacteria.

    Güde, H

    1979-09-01

    In continuous culture enrichments that were inoculated with activated sludge and were fed with polymeric substrates, freely dispersed single-celled bacteria belonging to theCytophaga group dominated among the initial populations, irrespective of the activated sludge source. These populations were grazed by flagellated protozoa which after several days reached high cell densities. Other morphologic bacterial groups such as spiral-shaped or filamentous bacteria then became dominant. In defined mixed culture experiments with bacterial isolates from the enrichment cultures, it was shown that a "grazing-resistant"Microcyclus strain outgrew aCytophaga strain in the presence of grazing protozoa. In contrast, theCytophaga strain competed successfully with theMicrocyclus strain and with other "grazing-resistant" strains under protozoa-free conditions. Furthermore, it was demonstrated that assumed grazing resistance factors such as floccing or filamentous growth were lost by some of the strains when they were grown for several generations in continuous culture under the same conditions, but in the absence of protozoa. PMID:24232496

  3. The Determining Factors of Entrepreneurial Activity in Broiler Farms

    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.

  4. A role of transcriptional activators as antirepressors for the autoinhibitory activity of TATA box binding of transcription factor IID

    Kotani, Tomohiro; Banno, Ken-ichi; Ikura, Mitsuhiko; Hinnebusch, Alan G.; Nakatani, Yoshihiro; Kawaichi, Masashi; Kokubo, Tetsuro

    2000-01-01

    The TATA box-binding activity of transcription factor IID (TFIID) is autoinhibited by the N-terminal domain of the Drosophila TATA box-binding protein- (TBP) associated factor 230/yeast TBP-associated factor 145 subunit, which binds to the TATA box-binding domain of TBP by mimicking the TATA box structure. Here, we propose a mechanism of transcriptional activation that involves antirepression of this autoinhibitory activity by transcriptional activators. Like the autoinhibitory domain of TFII...

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

    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.

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

    Dorota Czerwińska-Kayzer; Anna Bieniasz

    2009-01-01

    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.

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

    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.

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

    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.

  9. ZPPR-21 critical benchmark analyses with ENDF/B-V and -VII data

    The six benchmark problems for the ZPPR-21 critical experiments phases A through F were analyzed using the ENDF/B-V2 and ENDF/B-VII.0 data. For reference calculations, Monte Carlo simulations were performed using the VIM code with the continuous energy cross sections. For deterministic calculations, composition and region dependent multi-group cross sections were generated using the ETOE2-2/MC2-2/SDX code system and core calculations were performed with the TWODANT discrete ordinate transport code. Based on sensitivity studies, deterministic core calculations were carried out with 230 energy groups, ∼1 cm spatial mesh size, S24 angular approximation, and P5 anisotropic scattering order Comparisons showed that the core multiplication factor determined with TWODANT agreed well with the VIM Monte Carlo solution within 0.20 %Δk for the ENDF/B-V2 data and 0.27 %Δk for the ENDF/B-VII.0 data. Detailed comparisons of reaction rates were also made between VIM and TWODANT solutions. The results showed that the multigroup cross sections generated with MC2-2 accurately reproduced the isotopic reaction rates of VIM calculations. (authors)

  10. Determination of factor X activator in the venom of the saw-scaled viper (Echis carinatus).

    Stocker, K; Fischer, H; Brogli, M

    1986-01-01

    Factor X activator in Echis carinatus venom was determined by incubating the zymogen 'factor X' with venom, interrupting the activation process by ethylenediaminetetraacetic acid and measuring the generated proteinase 'factor Xa' by means of a synthetic chromogenic substrate. A comparison of factor X- and prothrombin-activating potencies in E. carinatus venoms of five different geographic origins revealed no correlation between these two procoagulant activities. PMID:3715901

  11. The Geometrical Structure of the Tolman VII solution

    Raghoonundun, Ambrish M

    2016-01-01

    The Tolman~VII solution, an exact analytic solution to the spherically symmetric, static Einstein equations with a perfect fluid source, has many characteristics that make it interesting for modelling high density physical astronomical objects. Here we supplement those characteristics with the geometrical tensors that this solution possess, and find that the Weyl, Riemann, and Ricci tensor components show unexpected mathematical behaviour that change depending on physically motivated parameters, even though the mass of the modelled objects is fixed. We show these features firstly through tensor components, and then through the scalars in the null tetrad formalism of Newmann and Penrose. The salient conclusion of this analysis is the intimate relationship between the Tolman~VII solution and the constant density Schwarzschild interior solution: the former being a straight forward generalization of the latter while eschewing the unphysical constant density.

  12. The Tolman VII solution, trapped null orbits and w - modes

    Neary, N J; Lake, K; Neary, Nicholas; Ishak, Mustapha; Lake, Kayll

    2001-01-01

    The Tolman VII solution is an exact static spherically symmetric perfect fluid solution of Einstein's equations that exhibits a surprisingly good approximation to a neutron star. We show that this solution exhibits trapped null orbits in a causal region even for a tenuity (total radius to mass ratio) $> 3$. In this region the dynamical part of the potential for axial w - modes dominates over the centrifugal part.

  13. 举重若轻 NIKE AIR MAX LEBRON VII

    PITT

    2009-01-01

    2009年8月8日,耐克公司在俄亥俄州阿克化城举行举行全球媒体峰会,隆重推出AIR MAX LEBRON VII,这款球鞋是勒布朗·詹姆斯签名鞋系列之中最具创新性的新款篮球鞋。

  14. CROSS SECTION EVALUATIONS FOR ENDF/B-VII.

    HERMAN, M.; ROCHMAN, D.; OBLOZINSKY, P.

    2006-06-05

    This is the final report of the work performed under the LANL contract on neutron cross section evaluations for ENDF/B-VII (April 2005-May 2006). The purpose of the contract was to ensure seamless integration of the LANL neutron cross section evaluations in the new ENDF/B-VII library. The following work was performed: (1) LANL evaluated data files submitted for inclusion in ENDF/B-VII were checked and, when necessary, formal formatting errors were corrected. As a consequence, ENDF checking codes, run on all LANL files, do not report any errors that would rise concern. (2) LANL dosimetry evaluations for {sup 191}Ir and {sup 193}Ir were completed to match ENDF requirements for the general purpose library suitable for transport calculations. A set of covariances for both isotopes is included in the ENDF files. (3) Library of fission products was assembled and successfully tested with ENDF checking codes, processed with NJOY-99.125 and simple MCNP calculations. (4) KALMAN code has been integrated with the EMPIRE system to allow estimation of covariances based on the combination of measurements and model calculations. Covariances were produced for 155,157-Gd and also for 6 remaining isotopes of Gd.

  15. The Education Innovator. Volume VII, No. 2

    Schweitzer, Sherry, Ed.

    2009-01-01

    The purpose of the U.S. Department of Education's online newsletter "The Education Innovator" is to promote innovative practices in education; to offer features on promising programs and practices; to provide information on innovative research, schools, policies, and trends; and to keep readers informed of key Department priorities and activities.…

  16. The Education Innovator. Volume VII, No. 8

    Herbert, Doug, Ed.

    2009-01-01

    The purpose of the U.S. Department of Education's online newsletter "The Education Innovator" is to promote innovative practices in education; to offer features on promising programs and practices; to provide information on innovative research, schools, policies, and trends; and to keep readers informed of key Department priorities and activities.…

  17. The Education Innovator. Volume VII, No. 5

    Schweitzer, Sherry, Ed.

    2009-01-01

    The purpose of the U.S. Department of Education's online newsletter "The Education Innovator" is to promote innovative practices in education; to offer features on promising programs and practices; to provide information on innovative research, schools, policies, and trends; and to keep readers informed of key Department priorities and activities.…

  18. The Education Innovator. Volume VII, No. 7

    Herbert, Doug, Ed.

    2009-01-01

    The purpose of the U.S. Department of Education's online newsletter "The Education Innovator" is to promote innovative practices in education; to offer features on promising programs and practices; to provide information on innovative research, schools, policies, and trends; and to keep readers informed of key Department priorities and activities.…

  19. The Education Innovator. Volume VII, No. 3

    Schweitzer, Sherry, Ed.

    2009-01-01

    The purpose of the U.S. Department of Education's online newsletter "The Education Innovator" is to promote innovative practices in education; to offer features on promising programs and practices; to provide information on innovative research, schools, policies, and trends; and to keep readers informed of key Department priorities and activities.…

  20. The Education Innovator. Volume VII, No. 4

    Schweitzer, Sherry, Ed.

    2009-01-01

    The purpose of the U.S. Department of Education's online newsletter "The Education Innovator" is to promote innovative practices in education; to offer features on promising programs and practices; to provide information on innovative research, schools, policies, and trends; and to keep readers informed of key Department priorities and activities.…

  1. Regulating the regulators: modulators of transcription factor activity.

    Everett, Logan; Hansen, Matthew; Hannenhalli, Sridhar

    2010-01-01

    Gene transcription is largely regulated by DNA-binding transcription factors (TFs). However, the TF activity itself is modulated via, among other things, post-translational modifications (PTMs) by specific modification enzymes in response to cellular stimuli. TF-PTMs thus serve as "molecular switchboards" that map upstream signaling events to the downstream transcriptional events. An important long-term goal is to obtain a genome-wide map of "regulatory triplets" consisting of a TF, target gene, and a modulator gene that specifically modulates the regulation of the target gene by the TF. A variety of genome-wide data sets can be exploited by computational methods to obtain a rough map of regulatory triplets, which can guide directed experiments. However, a prerequisite to developing such computational tools is a systematic catalog of known instances of regulatory triplets. We first describe PTM-Switchboard, a recent database that stores triplets of genes such that the ability of one gene (the TF) to regulate a target gene is dependent on one or more PTMs catalyzed by a third gene, the modifying enzyme. We also review current computational approaches to infer regulatory triplets from genome-wide data sets and conclude with a discussion of potential future research. PTM-Switchboard is accessible at http://cagr.pcbi.upenn.edu/PTMswitchboard / PMID:20827600

  2. [Chemical tests with Marrubium species. Official data on Marubii herba in Pharmacopoeia Hungarica VII].

    Telek, E; Tõth, L; Botz, L; Máthé, I

    1997-01-01

    About 40 species of the Marrubium genus (Lamiaceae) are known of which 2 species (M. vulgare L. and M. peregrinum L.) and one hybrid (M. x paniculatum Desr.) can be found as native plants in Hungary. The above-ground parts of M. vulgare L. are official in Hungarian Pharmacopoeia VII. Active substances in Marrubii herba are labdane-structured bitter materials. Although the presence of furanic labdane diterpenes in the plant is known, the pharmacopoeia gives only microscopic tests, qualitative tests (for other parts of the plant and foreign organic matter) for the bitter value of Marrubii herba. We have examined the main terpenoid substances isolated with column, gel and preparative layer chromatography. Structure elucidations were performed by means of UV, mass and NMR spectroscopy. We have compared the changes in terpenoid-type compounds (premarrubiin and marrubiin) in plants during the vegetation period; in different Marrubium species and in the different extractions of horehound by means of thin layer chromatography and densitometry. By reason of our results we propose qualitative and quantitative chemical tests for the paragraph of Marrubii herba in Pharmacopoeia Hungarica VII. PMID:9163258

  3. Potassium chloride-bearing ice VII and ice planet dynamics

    Frank, Mark R.; Scott, Henry P.; Aarestad, Elizabeth; Prakapenka, Vitali B.

    2016-02-01

    Accurate modeling of planetary interiors requires that the pressure-volume-temperature (PVT) properties of phases present within the body be well understood. The high-pressure polymorphs of H2O have been studied extensively due to the abundance of ice phases in icy moons and, likely, vast number of extra-solar planetary bodies, with only select studies evaluating impurity-laden ices. In this study, ice formed from a 1.6 mol percent KCl-bearing aqueous solution was studied up to 32.89 ± 0.19 GPa and 625 K, and the incorporation of K+ and Cl- ionic impurities into the ice VII structure was documented. The compression data at 295 K were fit with a third order Birch-Murnaghan equation of state and yielded a bulk modulus (KT0), its pressure derivative (KT0‧), and zero pressure volume (V0) of 24.7 ± 0.9 GPa, 4.44 ± 0.09, and 39.2 ± 0.2 Å3, respectively. The impurity-laden ice was found to be 6-8% denser than ice VII formed from pure H2O. Thermal expansion coefficients were also determined for several isothermal compression curves at elevated temperatures, and a PVT equation of state was obtained. The melting curve of ice VII with incorporated K+ and Cl- was estimated by fitting experimental data up to 10.2 ± 0.4 GPa, where melting occurred at 625 K, to the Simon-Glatzel equation. The melting curve of this impurity-laden ice is systematically depressed relative to that of pure H2O by approximately 45 K and 80 K at 4 and 11 GPa, respectively. A portion of the K+ and Cl- contained within the ice VII structure was observed to exsolve with increasing temperature. This suggests that an internal differentiating process could concentrate a K-rich phase deep within H2O-rich planets, and we speculate that this could supply an additional source of heat through the radioactive decay of 40K. Our data illustrate ice VII can incorporate significant concentrations of K+ and Cl- and increasing the possibility of deep-sourced and solute-rich plumes in moderate to large sized H2O

  4. Tissue factor pathway inhibitor levels in patients with homocystinuria.

    Cella, G; Burlina, A; Sbarai, A; Motta, G; Girolami, A; Berrettini, M; Strauss, W

    2000-06-01

    Thrombotic events are a well-recognized complication of homocystinuria. However, the mechanisms involved in the atherogenic and thrombotic effects of homocyst(e)ine remain incompletely understood. The objective of this study was to determine the role of endothelial cell activation/damage as indicated by levels of thrombomodulin, tissue factor and tissue factor pathway inhibitor, and factor VII activity in patients with homocystinuria. Six patients with homocystinuria, nonresponsive to pyridoxine, treated only with trimethylglycine (betaine) were injected with a bolus of 20 IU/kg body weight of unfractionated commercial heparin to induce the release of tissue factor pathway inhibitor from the vascular endothelium. Tissue factor, thrombomodulin, and factor VII activity were measured by enzyme-linked immunosorbent assay and clotting assay before heparin administration. Tissue factor pathway inhibitor antigen and activity were measured before and 5 minutes after the bolus of heparin. Levels of homocyst(e)ine were elevated (patients: 144.2+/-19.2 micromol/L; controls: 10.2+/-0.9 micromol/L); however, levels of thrombomodulin, tissue factor, and tissue factor pathway inhibitor antigen were not statistically different from the control group. In contrast, tissue factor pathway inhibitor activity showed a significantly increased level (patients: 2.09+/-0.34 U/L; controls: 1.14+/-0.20 U/L; p<0.05) that was correlated with homocyst(e)ine. Factor VII activity was significantly decreased (patients: 64.7+/-5.1%; controls: 91.4+/-4.7%; p<0.05) and inversely correlated with homocyst(e)ine. After heparin the patients released higher amounts of tissue factor pathway inhibitor antigen and activity compared with the control group; however, the difference was not statistically significant. Although not treated with antithrombotic drugs, none of the patients had any thromboembolic complications after starting betaine. In addition to betaine treatment, the enhanced factor pathway

  5. A Stellar Population Gradient in VII Zw 403 Implications for the Formation of Blue Compact Dwarf Galaxies

    Schulte-Ladbeck, R E; Crone, M M; Greggio, L; Schulte-Ladbeck, Regina E.; Hopp, Ulrich; Crone, Mary M.; Greggio, Laura

    1999-01-01

    We present evidence for the existence of an old stellar halo in the Blue Compact Dwarf galaxy VII Zw 403. VII Zw 403 is the first Blue Compact Dwarf galaxy for which a clear spatial segregation of the resolved stellar content into a "core-halo" structure is detected. Multicolor HST/WFPC2 observations indicate that active star formation occurs in the central region, but is strikingly absent at large radii. Instead, a globular-cluster-like red giant branch suggests the presence of an old (> 10 Gyr) and metal poor (=-1.92) stellar population in the halo. While the vast majority of Blue Compact Dwarf galaxies has been recognized to possess halos of red color in ground-based surface photometry, our observations of VII Zw 403 establish for the first time a direct correspondence between a red halo color and the presence of old, red giant stars. If the halos of Blue Compact Dwarf galaxies are all home to such ancient stellar populations, then the fossil record conflicts with delayed-formation scenarios for dwarfs.

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

    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. ({sup 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 {mu}M. 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, TRP{gamma}S and GDP{beta}S, 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).

  7. Assessing the Subject General Medicine VII in the University Polyclinic Evaluación de la asignatura Medicina General Integral VII en el policlínico universitario

    Cynthia Olivia Morales Pérez

    2012-06-01

    Full Text Available Background: the subject General Medicine VII is part of the guiding discipline in Medicine studies. It ensures that when Medicine Doctors obtain their degrees they have acquired all the knowledge that allows them to perform multiple tasks in health care services. Objective: to assess the subject General Medicine VII, in the university polyclinic as part of the educational process. Methods: we conducted a mixed research using quantitative and qualitative methods through a methodology that included the level of satisfaction of students, teachers, managers, and knowledge levels obtained by students. This methodology was applied in the fourth year of Medicine studies and in the four university polyclinics in the municipality of Cienfuegos, inserted into the new training model. Results: managers referred insufficient chances for exchanging with subordinates as well as for the profits of methodological activities, teachers were dissatisfied because of insufficient educational preparation and high work load and students reported difficulties with the availability and on-time delivery of textbooks, in addition to not having the necessary instrumentation for skills appropriation. Conclusions: we found that managers were dissatisfied with organizational and functional aspects, teachers with planning and implementation of the teaching process and students with the literature and the necessary tools while in teaching practice.Fundamento: la asignatura Medicina General Integral VII es parte de la disciplina rectora de la carrera de Medicina, que garantiza que una vez graduado el Médico General, posea conocimientos que le permitan desempeñar múltiples tareas en los servicios de atención médica. Objetivo: evaluar la asignatura Medicina General Integral VII en el policlínico universitario como parte del proceso docente educativo.

  8. The Positive Transcription Elongation Factor b Is an Essential Cofactor for the Activation of Transcription by Myocyte Enhancer Factor 2

    Nojima, Masanori; Huang, Yehong; Tyagi, Mudit; Kao, Hung-Ying; Fujinaga, Koh

    2008-01-01

    The positive transcription elongation factor b (P-TEFb), composed of cyclin-dependent kinase 9 and cyclin T1, stimulates the elongation of transcription by hyperphosphorylating the C-terminal region of RNA polymerase II. Aberrant activation of P-TEFb results in manifestations of cardiac hypertrophy in mice, suggesting that P-TEFb is an essential factor for cardiac myocyte function and development. Here, we present evidence that P-TEFb selectively activates transcription mediated by the myocyt...

  9. The stress signalling pathway nuclear factor E2-related factor 2 is activated in the liver of sows during lactation

    Rosenbaum Susann; Ringseis Robert; Hillen Sonja; Becker Sabrina; Erhardt Georg; Reiner Gerald; Eder Klaus

    2012-01-01

    Abstract Background It has recently been shown that the lactation-induced inflammatory state in the liver of dairy cows is accompanied by activation of the nuclear factor E2-related factor 2 (Nrf2) pathway, which regulates the expression of antioxidant and cytoprotective genes and thereby protects tissues from inflammatory mediators and reactive oxygen species (ROS). The present study aimed to study whether the Nrf2 pathway is activated also in the liver of lactating sows. Findings Transcript...

  10. Physical activity and cardiovascular risk factors in children

    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 with...