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Sample records for tissue factor electronic

  1. Tissue-electronics interfaces: from implantable devices to engineered tissues

    Science.gov (United States)

    Feiner, Ron; Dvir, Tal

    2018-01-01

    Biomedical electronic devices are interfaced with the human body to extract precise medical data and to interfere with tissue function by providing electrical stimuli. In this Review, we outline physiologically and pathologically relevant tissue properties and processes that are important for designing implantable electronic devices. We summarize design principles for flexible and stretchable electronics that adapt to the mechanics of soft tissues, such as those including conducting polymers, liquid metal alloys, metallic buckling and meandering architectures. We further discuss technologies for inserting devices into the body in a minimally invasive manner and for eliminating them without further intervention. Finally, we introduce the concept of integrating electronic devices with biomaterials and cells, and we envision how such technologies may lead to the development of bionic organs for regenerative medicine.

  2. Imaging of tissue sections with very slow electrons

    Czech Academy of Sciences Publication Activity Database

    Frank, Luděk; Nebesářová, Jana; Vancová, Marie; Paták, Aleš; Müllerová, Ilona

    2015-01-01

    Roč. 148, JAN 2015 (2015), s. 146-150 ISSN 0304-3991 R&D Projects: GA TA ČR TE01020118; GA MŠk(CZ) LO1212 Institutional support: RVO:68081731 ; RVO:60077344 Keywords : Biological STEM * Ultralow energy STEM * Tissue sections * Cathode lens * Depolymerisation Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 2.874, year: 2015

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

    OpenAIRE

    Rao, L V; Rapaport, S I

    1988-01-01

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

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  5. Tissue regenerating functions of coagulation factor XIII

    DEFF Research Database (Denmark)

    Soendergaard, C; Kvist, P H; Seidelin, J B

    2013-01-01

    The protransglutaminase factor XIII (FXIII) has recently gained interest within the field of tissue regeneration, as it has been found that FXIII significantly influences wound healing by exerting a multitude of functions. It supports haemostasis by enhancing platelet adhesion to damaged......-receptor 2 and the αVβ3 integrin is important for angiogenesis supporting formation of granulation tissue. Chronic inflammatory conditions involving bleeding and activation of the coagulation cascade have been shown to lead to reduced FXIII levels in plasma. Of particular importance for this review...

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

    International Nuclear Information System (INIS)

    Sakai, T.; Kisiel, W.

    1990-01-01

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

  7. Imaging of tissue sections with very slow electrons

    Energy Technology Data Exchange (ETDEWEB)

    Frank, L., E-mail: ludek@isibrno.cz [Institute of Scientific Instruments AS CR, v.v.i., Královopolská 147, 61264 Brno (Czech Republic); Nebesářová, J.; Vancová, M. [Biology Centre AS CR, v.v.i., Branišovská 31, 37005 České Budějovice (Czech Republic); Paták, A.; Müllerová, I. [Institute of Scientific Instruments AS CR, v.v.i., Královopolská 147, 61264 Brno (Czech Republic)

    2015-01-15

    The examination of thin sections of tissues with electron microscopes is an indispensable tool. Being composed of light elements, samples of living matter illuminated with electrons at the usual high energies of tens or even hundreds of kiloelectronvolts provide very low image contrasts in transmission or scanning transmission electron microscopes. Therefore, heavy metal salts are added to the specimen during preparation procedures (post-fixation with osmium tetroxide or staining). However, these procedures can modify or obscure the ultrastructural details of cells. Here we show that the energy of electrons used for the scanned transmission imaging of tissue sections can be reduced to mere hundreds or even tens of electronvolts and can produce extremely high contrast even for samples free of any metal salts. We found that when biasing a sufficiently thin tissue section sample to a high negative potential in a scanning transmission electron microscope, thereby reducing the energy of the electrons landing on the sample, and collecting the transmitted electrons with a grounded detector, we obtain a high contrast revealing structure details not enhanced by heavy atoms. Moreover, bombardment with slow electrons sensitively depolymerises the resin in which the tissue is embedded, thereby enhancing the transmitted signal with no observable loss of structure details. The use of low-energy electrons requires ultrathin sections of a thickness of less than 10 nm, but their preparation is now possible. Ultralow energy STEM provides a tool enabling the observation of very thin biological samples without any staining. This method should also be advantageous for examination of 2D crystals, thin films of polymers, polymer blends, etc. - Highlights: • Sections of a thickness below 10 nm were imaged in STEM at hundreds and tens of eV. • Image contrast grows steeply with decreasing electron energy in the STEM. • Very slow electrons provide high contrast for samples free of

  8. Mesh Nanoelectronics: Seamless Integration of Electronics with Tissues.

    Science.gov (United States)

    Dai, Xiaochuan; Hong, Guosong; Gao, Teng; Lieber, Charles M

    2018-02-20

    Nanobioelectronics represents a rapidly developing field with broad-ranging opportunities in fundamental biological sciences, biotechnology, and medicine. Despite this potential, seamless integration of electronics has been difficult due to fundamental mismatches, including size and mechanical properties, between the elements of the electronic and living biological systems. In this Account, we discuss the concept, development, key demonstrations, and future opportunities of mesh nanoelectronics as a general paradigm for seamless integration of electronics within synthetic tissues and live animals. We first describe the design and realization of hybrid synthetic tissues that are innervated in three dimensions (3D) with mesh nanoelectronics where the mesh serves as both as a tissue scaffold and as a platform of addressable electronic devices for monitoring and manipulating tissue behavior. Specific examples of tissue/nanoelectronic mesh hybrids highlighted include 3D neural tissue, cardiac patches, and vascular constructs, where the nanoelectronic devices have been used to carry out real-time 3D recording of electrophysiological and chemical signals in the tissues. This novel platform was also exploited for time-dependent 3D spatiotemporal mapping of cardiac tissue action potentials during cell culture and tissue maturation as well as in response to injection of pharmacological agents. The extension to simultaneous real-time monitoring and active control of tissue behavior is further discussed for multifunctional mesh nanoelectronics incorporating both recording and stimulation devices, providing the unique capability of bidirectional interfaces to cardiac tissue. In the case of live animals, new challenges must be addressed, including minimally invasive implantation, absence of deleterious chronic tissue response, and long-term capability for monitoring and modulating tissue activity. We discuss each of these topics in the context of implantation of mesh

  9. [Scanning electron microscopy of heat-damaged bone tissue].

    Science.gov (United States)

    Harsanyl, L

    1977-02-01

    Parts of diaphyses of bones were exposed to high temperature of 200-1300 degrees C. Damage to the bone tissue caused by the heat was investigated. The scanning electron microscopic picture seems to be characteristic of the temperature applied. When the bones heated to the high temperature of 700 degrees C characteristic changes appear on the periostal surface, higher temperatura on the other hand causes damage to the compact bone tissue and can be observed on the fracture-surface. Author stresses the importance of this technique in the legal medicine and anthropology.

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

    Science.gov (United States)

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

    2002-07-01

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

  11. Tissue Factor and Tissue Factor Pathway Inhibitor in the Wound-Healing Process After Neurosurgery.

    Science.gov (United States)

    Ślusarz, Robert; Głowacka, Mariola; Biercewicz, Monika; Barczykowska, Ewa; Haor, Beata; Rość, Danuta; Gadomska, Grażyna

    2016-03-01

    The aim of the study was to assess the concentrations of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the blood of patients with a postoperative wound after neurosurgery. Participants included 20 adult patients who underwent neurosurgery because of degenerative spine changes. The concentration of TF and TFPI in the patients' blood serum was measured 3 times: before surgery, during the first 24 hr after surgery, and between the 5th and 7th days after surgery. The control group comprised 20 healthy volunteers similar to the patient group with respect to gender and age. A statistically significant difference was observed between TF concentration at all three measurement time points in the research group and TF concentration in the control group (p = .018, p = .010, p = .001). A statistically significant difference was found between TFPI concentration at the second time point in the research group and TFPI concentration in the control group (p = .041). No statistically significant within-subject difference was found between TF concentrations before and after surgery. A statistically significant within-subject difference was found between TFPI concentrations within 24 hr after surgery and 5-7 days after surgery (p = .004). High perioperative concentrations of TF indicate not only the presence of thrombophilia but also the importance of TF in the wound-healing process. Perioperative changes in TFPI concentrations are related to its compensatory influence on hemostasis in thrombophilic conditions. © The Author(s) 2015.

  12. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor beta induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  13. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  14. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    Science.gov (United States)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-06-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

  15. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    Science.gov (United States)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-01-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, free-standing electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on-demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function. PMID:26974408

  16. Growth factor effects on costal chondrocytes for tissue engineering fibrocartilage

    Science.gov (United States)

    Johns, D.E.; Athanasiou, K.A.

    2010-01-01

    Tissue engineered fibrocartilage could become a feasible option for replacing tissues like the knee meniscus or temporomandibular joint disc. This study employed five growth factors insulin-like growth factor-I, transforming growth factor-β1, epidermal growth factor, platelet-derived growth factor-BB, and basic fibroblast growth factor in a scaffoldless approach with costal chondrocytes, attempting to improve biochemical and mechanical properties of engineered constructs. Samples were quantitatively assessed for total collagen, glycosaminoglycans, collagen type I, collagen type II, cells, compressive properties, and tensile properties at two time points. Most treated constructs were worse than the no growth factor control, suggesting a detrimental effect, but the IGF treatment tended to improve the constructs. Additionally, the 6wk time point was consistently better than 3wks, with total collagen, glycosaminoglycans, and aggregate modulus doubling during this time. Further optimization of the time in culture and exogenous stimuli will be important in making a more functional replacement tissue. PMID:18597118

  17. Electron form factors of deformable nuclei

    International Nuclear Information System (INIS)

    Tartakovskii, V.K.; Isupov, V.Yu.

    1988-01-01

    Using the smallness of the deformation parameter of the nucleus, we obtain simple explicit expressions for the form factors of electroexcitation of the low-lying rotation-vibration states of light, deformable, even-even nuclei. The expressions satisfactorily describe the experimental data on the excitation of collective nuclear states by the inelastic scattering of fast electrons

  18. Electron Microscopy Observation of Biomineralization within Wood Tissues of Kurogaki

    Directory of Open Access Journals (Sweden)

    Kazue Tazaki

    2017-07-01

    Full Text Available Interactions between minerals and microorganisms play a crucial role in living wood tissues. However, living wood tissues have never been studied in the field. Fortunately, we found several kurogaki (black persimmon; Diospyros kaki trees at Tawara in Kanazawa, Ishikawa, Japan. Here, we report the characterization of kurogaki based on scanning electron microscopy equipped with energy-dispersive spectroscopy (SEM-EDS and transmission electron microscopy (TEM, associated with inductively coupled plasma-mass spectrometry (ICP-MS analyses, X-ray fluorescence analyses (XRF and X-ray powder diffraction (XRD analyses. This study aims to illustrate the ability of various microorganisms associated with biominerals within wood tissues of kurogaki, as shown by SEM-EDS elemental content maps and TEM images. Kurogaki grows very slowly and has extremely hard wood, known for its striking black and beige coloration, referred to as a “peacock pattern”. However, the scientific data for kurogaki are very limited. The black “peacock pattern” of the wood mainly comprises cellulose and high levels of crystal cristobalite. As per the XRD results, the black taproot contains mineralized 7 Å clays (kaolinite, cellulose, apatite and cristobalite associated with many microorganisms. The chemical compositions of the black and beige portions of the black persimmon tree were obtained by ICP-MS analyses. Particular elements such as abundant Ca, Mg, K, P, Mn, Ba, S, Cl, Fe, Na, and Al were concentrated in the black region, associated with Pb and Sr elements. SEM-EDS semi-qualitative analyses of kurogaki indicated an abundance of P and Ca in microorganisms in the black region, associated with Pb, Sr, S, Mn, and Mg elements. On the other hand, XRF and XRD mineralogical data showed that fresh andesite, weathered andesite, and the soils around the roots of kurogaki correlate with biomineralization of the black region in kurogaki roots, showing clay minerals (kaolinite and

  19. Tissue Engineering Using Transfected Growth-Factor Genes

    Science.gov (United States)

    Madry, Henning; Langer, Robert S.; Freed, Lisa E.; Trippel, Stephen; Vunjak-Novakovic, Gordana

    2005-01-01

    A method of growing bioengineered tissues includes, as a major component, the use of mammalian cells that have been transfected with genes for secretion of regulator and growth-factor substances. In a typical application, one either seeds the cells onto an artificial matrix made of a synthetic or natural biocompatible material, or else one cultures the cells until they secrete a desired amount of an extracellular matrix. If such a bioengineered tissue construct is to be used for surgical replacement of injured tissue, then the cells should preferably be the patient s own cells or, if not, at least cells matched to the patient s cells according to a human-leucocyteantigen (HLA) test. The bioengineered tissue construct is typically implanted in the patient's injured natural tissue, wherein the growth-factor genes enhance metabolic functions that promote the in vitro development of functional tissue constructs and their integration with native tissues. If the matrix is biodegradable, then one of the results of metabolism could be absorption of the matrix and replacement of the matrix with tissue formed at least partly by the transfected cells. The method was developed for articular chondrocytes but can (at least in principle) be extended to a variety of cell types and biocompatible matrix materials, including ones that have been exploited in prior tissue-engineering methods. Examples of cell types include chondrocytes, hepatocytes, islet cells, nerve cells, muscle cells, other organ cells, bone- and cartilage-forming cells, epithelial and endothelial cells, connective- tissue stem cells, mesodermal stem cells, and cells of the liver and the pancreas. Cells can be obtained from cell-line cultures, biopsies, and tissue banks. Genes, molecules, or nucleic acids that secrete factors that influence the growth of cells, the production of extracellular matrix material, and other cell functions can be inserted in cells by any of a variety of standard transfection techniques.

  20. Paramagnetic form factors from itinerant electron theory

    International Nuclear Information System (INIS)

    Cooke, J.F.; Liu, S.H.; Liu, A.J.

    1985-01-01

    Elastic neutron scattering experiments performed over the past two decades have provided accurate information about the magnetic form factors of paramagnetic transition metals. These measurements have traditionally been analyzed in terms of an atomic-like theory. There are, however, some cases where this procedure does not work, and there remains the overall conceptual problem of using an atomistic theory for systems where the unpaired-spin electrons are itinerant. We have recently developed computer codes for efficiently evaluating the induced magnetic form factors of fcc and bcc itinerant electron paramagnets. Results for the orbital and spin contributions have been obtained for Cr, Nb, V, Mo, Pd, and Rh based on local density bands. By using calculated spin enhancement parameters, we find reasonable agreement between theory and neutron form factor data. In addition, these zero parameter calculations yield predictions for the bulk susceptibility on an absolute scale which are in reasonable agreement with experiment in all treated cases except palladium

  1. Neutron kerma factors, and water equivalence of some tissue substitutes

    International Nuclear Information System (INIS)

    Singh, V. P.; Badiger, N. M.; Vega C, H. R.

    2014-08-01

    The kerma factors and kerma relative to air and water of 24 compounds used as tissue substitutes were calculated for neutron energy from 2.53 x 10 -8 up to 29 MeV. The kerma ratio of the tissue substitutes relative to air and water were calculated by the ratio of kerma factors of the tissue substitute to air and water respectively. The water equivalence of the selected tissue substitutes was observed above neutron energies 100 eV. Kerma ratio relative to the air for Poly-vinylidene fluoride and Teflon are found to be nearest to unity in very low energy (up to 1 eV) and above 63 eV respectively. It was found that the natural rubber as a water equivalent tissue substitute compound. The results of the kerma factors in our investigation shows a very good agreement with those published in ICRU-44. We found that at higher neutron energies, the kerma factors and kerma ratios of the selected tissue substitute compounds are approximately same, but differences are large for energies below 100 eV. (Author)

  2. Tissue localization of human trefoil factors 1, 2, and 3

    DEFF Research Database (Denmark)

    Madsen, Jens; Nielsen, Ole; Tornøe, Ida

    2007-01-01

    Trefoil factors (TTFs) are small, compact proteins coexpressed with mucins in the gastrointestinal tract. Three trefoil factors are known in mammals: TFF1, TFF2, and TFF3. They are implicated to play diverse roles in maintenance and repair of the gastrointestinal channel. We compared the expression...... pattern of the three trefoil factors analyzing mRNA from a panel of 20 human tissues by conventional reverse transcriptase (RT) PCR and, in addition, by real-time PCR. These findings were supported by immunohistochemical analysis of paraffin-embedded human tissues using rabbit polyclonal antibodies raised...... against these factors. TFF1 showed highest expression in the stomach and colon, whereas TFF2 and TFF3 showed highest expression in stomach and colon, respectively. All three TFFs were found in the ducts of pancreas. Whereas TFF2 was found to be restricted to these two tissues, the structurally more...

  3. Computer modeling the boron compound factor in normal brain tissue

    International Nuclear Information System (INIS)

    Gavin, P.R.; Huiskamp, R.; Wheeler, F.J.; Griebenow, M.L.

    1993-01-01

    The macroscopic distribution of borocaptate sodium (Na 2 B 12 H 11 SH or BSH) in normal tissues has been determined and can be accurately predicted from the blood concentration. The compound para-borono-phenylalanine (p-BPA) has also been studied in dogs and normal tissue distribution has been determined. The total physical dose required to reach a biological isoeffect appears to increase directly as the proportion of boron capture dose increases. This effect, together with knowledge of the macrodistribution, led to estimates of the influence of the microdistribution of the BSH compound. This paper reports a computer model that was used to predict the compound factor for BSH and p-BPA and, hence, the equivalent radiation in normal tissues. The compound factor would need to be calculated for other compounds with different distributions. This information is needed to design appropriate normal tissue tolerance studies for different organ systems and/or different boron compounds

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

    National Research Council Canada - National Science Library

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

    2003-01-01

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

  5. Combinatorial regulation of tissue specification by GATA and FOG factors

    Science.gov (United States)

    Chlon, Timothy M.; Crispino, John D.

    2012-01-01

    The development of complex organisms requires the formation of diverse cell types from common stem and progenitor cells. GATA family transcriptional regulators and their dedicated co-factors, termed Friend of GATA (FOG) proteins, control cell fate and differentiation in multiple tissue types from Drosophila to man. FOGs can both facilitate and antagonize GATA factor transcriptional regulation depending on the factor, cell, and even the specific gene target. In this review, we highlight recent studies that have elucidated mechanisms by which FOGs regulate GATA factor function and discuss how these factors use these diverse modes of gene regulation to control cell lineage specification throughout metazoans. PMID:23048181

  6. Immunolocalization of transforming growth factor alpha in normal human tissues

    DEFF Research Database (Denmark)

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

  7. Monte Carlo study of voxel S factor dependence on tissue density and atomic composition

    Energy Technology Data Exchange (ETDEWEB)

    Amato, Ernesto, E-mail: eamato@unime.it [University of Messina, Department of Biomedical Sciences and of Morphologic and Functional Imaging, Section of Radiological Sciences, via Consolare Valeria, 1, I-98125 Messina (Italy); Italiano, Antonio [INFN – Istituto Nazionale di Fisica Nucleare, Gruppo Collegato di Messina (Italy); Baldari, Sergio [University of Messina, Department of Biomedical Sciences and of Morphologic and Functional Imaging, Section of Radiological Sciences, via Consolare Valeria, 1, I-98125 Messina (Italy)

    2013-11-21

    Voxel dosimetry is a common approach to the internal dosimetry of non-uniform activity distributions in nuclear medicine therapies with radiopharmaceuticals and in the estimation of the radiation hazard due to internal contamination of radionuclides. Aim of the present work is to extend our analytical approach for the calculation of voxel S factors to materials different from the soft tissue. We used a Monte Carlo simulation in GEANT4 of a voxelized region of each material in which the source of monoenergetic electrons or photons was uniformly distributed within the central voxel, and the energy deposition was scored over the surrounding 11×11×11 voxels. Voxel S factors were obtained for the following standard ICRP materials: Adipose tissue, Bone cortical, Brain, Lung, Muscle skeletal and Tissue soft with 1 g cm{sup −3} density. Moreover, we considered the standard ICRU materials: Bone compact and Muscle striated. Voxel S factors were represented as a function of the “normalized radius”, defined as the ratio between the source–target voxel distance and the voxel side. We found that voxel S factors and related analytical fit functions are mainly affected by the tissue density, while the material composition gives only a slight contribution to the difference between data series, which is negligible for practical purposes. Our results can help in broadening the dosimetric three-dimensional approach based on voxel S factors to other tissues where diagnostic and therapeutic radionuclides can be taken up and radiation can propagate.

  8. Monte Carlo study of voxel S factor dependence on tissue density and atomic composition

    International Nuclear Information System (INIS)

    Amato, Ernesto; Italiano, Antonio; Baldari, Sergio

    2013-01-01

    Voxel dosimetry is a common approach to the internal dosimetry of non-uniform activity distributions in nuclear medicine therapies with radiopharmaceuticals and in the estimation of the radiation hazard due to internal contamination of radionuclides. Aim of the present work is to extend our analytical approach for the calculation of voxel S factors to materials different from the soft tissue. We used a Monte Carlo simulation in GEANT4 of a voxelized region of each material in which the source of monoenergetic electrons or photons was uniformly distributed within the central voxel, and the energy deposition was scored over the surrounding 11×11×11 voxels. Voxel S factors were obtained for the following standard ICRP materials: Adipose tissue, Bone cortical, Brain, Lung, Muscle skeletal and Tissue soft with 1 g cm −3 density. Moreover, we considered the standard ICRU materials: Bone compact and Muscle striated. Voxel S factors were represented as a function of the “normalized radius”, defined as the ratio between the source–target voxel distance and the voxel side. We found that voxel S factors and related analytical fit functions are mainly affected by the tissue density, while the material composition gives only a slight contribution to the difference between data series, which is negligible for practical purposes. Our results can help in broadening the dosimetric three-dimensional approach based on voxel S factors to other tissues where diagnostic and therapeutic radionuclides can be taken up and radiation can propagate

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

    International Nuclear Information System (INIS)

    Oesterud, B.; Rapaport, S.I.

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

  10. Fibroblast Growth Factors: Biology, Function, and Application for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Ye-Rang Yun

    2010-01-01

    Full Text Available Fibroblast growth factors (FGFs that signal through FGF receptors (FGFRs regulate a broad spectrum of biological functions, including cellular proliferation, survival, migration, and differentiation. The FGF signal pathways are the RAS/MAP kinase pathway, PI3 kinase/AKT pathway, and PLCγ pathway, among which the RAS/MAP kinase pathway is known to be predominant. Several studies have recently implicated the in vitro biological functions of FGFs for tissue regeneration. However, to obtain optimal outcomes in vivo, it is important to enhance the half-life of FGFs and their biological stability. Future applications of FGFs are expected when the biological functions of FGFs are potentiated through the appropriate use of delivery systems and scaffolds. This review will introduce the biology and cellular functions of FGFs and deal with the biomaterials based delivery systems and their current applications for the regeneration of tissues, including skin, blood vessel, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve tissues.

  11. Effect of tissue inhomogeneity on dose distribution of point sources of low-energy electrons

    International Nuclear Information System (INIS)

    Kwok, C.S.; Bialobzyski, P.J.; Yu, S.K.; Prestwich, W.V.

    1990-01-01

    Perturbation in dose distributions of point sources of low-energy electrons at planar interfaces of cortical bone (CB) and red marrow (RM) was investigated experimentally and by Monte Carlo codes EGS and the TIGER series. Ultrathin LiF thermoluminescent dosimeters were used to measure the dose distributions of point sources of 204 Tl and 147 Pm in RM. When the point sources were at 12 mg/cm 2 from a planar interface of CB and RM equivalent plastics, dose enhancement ratios in RM averaged over the region 0--12 mg/cm 2 from the interface were measured to be 1.08±0.03 (SE) and 1.03±0.03 (SE) for 204 Tl and 147 Pm, respectively. The Monte Carlo codes predicted 1.05±0.02 and 1.01±0.02 for the two nuclides, respectively. However, EGS gave consistently 3% higher dose in the dose scoring region than the TIGER series when point sources of monoenergetic electrons up to 0.75 MeV energy were considered in the homogeneous RM situation or in the CB and RM heterogeneous situation. By means of the TIGER series, it was demonstrated that aluminum, which is normally assumed to be equivalent to CB in radiation dosimetry, leads to an overestimation of backscattering of low-energy electrons in soft tissue at a CB--soft-tissue interface by as much as a factor of 2

  12. Factors affecting the tissues composition of pork belly.

    Science.gov (United States)

    Duziński, K; Knecht, D; Lisiak, D; Janiszewski, P

    2015-11-01

    Bellies derived from the commercial population of pig carcasses are diverse in terms of tissue composition. Knowledge of the factors influencing it and the expected results, permits quick and easy evaluation of raw material. The study was designed to determine the factors affecting the tissues composition of pork bellies and to estimate their lean meat content. The research population (n=140 pig carcasses) was divided into groups according to sex (gilts, barrows), half-carcass mass (meat content class: S (⩾60%), E (55% to 60%), U (50% to 55%), R (meat content affected the growth of the fat and skin mass in a linear way. No differences were observed between class S and E in terms of belly muscle mass. A 0.37% higher share of belly in the half-carcass was found for barrows (Pmeat content in bellies, suggesting they may be used directly in the production line.

  13. Modern concepts for basic radiobiological factors characterizing tumor tissue radiosensitivity

    International Nuclear Information System (INIS)

    Gocheva, L.; Sergieva, K.

    2002-01-01

    Traditionally radiotherapy is prescribed at doses consistent with the expected therapeutic response and tolerance of tumor and normal tissues without consideration to individual differences in radiosensitivity. However, the basic radiobiological knowledge and clinical experience along this line point to significant variations in the observed therapeutic results. It has been established that cells and tissues under experimental and clinical conditions manifest a wide spectrum of individual radiosensitivity. The aim of this survey is to outline the current concepts for the basic radiobiological factors influencing tumor radiosensitivity. A thorough discussion is done of the essence, mechanisms of action, methods of determination and measurement, and effect on the prognosis in patients with malignant diseases of a number of radiobiological factors, such as: tumor-cell proliferation, apoptosis, tumor hypoxia and neovascularization. Although the knowledge of the mechanisms of radiosensitivity is constantly expanding, its clinical implementation is still rather limited. The true role of radiosensitivity in predicting the therapeutic response should be more accurately defined. (authors)

  14. The analysis for energy distribution and biological effects of the clusters from electrons in the tissue equivalent material

    International Nuclear Information System (INIS)

    Zhang Wenzhong; Guo Yong; Luo Yisheng; Wang Yong

    2004-01-01

    Objective: To study energy distribution of the clusters from electrons in the tissue equivalent material, and discuss the important aspects of these clusters on inducing biological effects. Methods: Based on the physical mechanism for electrons interacting with tissue equivalent material, the Monte Carlo (MC) method was used. The electron tracks were lively simulated on an event-by-event (ionization, excitation, elastic scattering, Auger electron emission) basis in the material. The relevant conclusions were drawn from the statistic analysis of these events. Results: The electrons will deposit their energy in the form (30%) of cluster in passing through tissue equivalent material, and most clusters (80%) have the energy amount of more than 50 eV. The cluster density depends on its diameter and energy of electrons, and the deposited energy in the cluster depends on the type and energy of radiation. Conclusion: The deposited energy in cluster is the most important factor in inducing all sort of lesions on DNA molecules in tissue cells

  15. Tissue Factor and Thrombin in Sickle Cell Anemia

    OpenAIRE

    Chantrathammachart, Pichika; Pawlinski, Rafal

    2012-01-01

    Sickle cell anemia is an inherited hematologic disorder associated with hemolytic and vaso-occlusive complications. An activation of coagulation is also a prominent feature of sickle cell anemia. Growing evidence indicates that coagulation may contribute to the inflammation and vascular injury in sickle cell anemia. This review focuses on tissue factor expression and its contribution to the activation of coagulation, thrombosis and vascular inflammation in sickle cell anemia.

  16. Chord-based versus voxel-based methods of electron transport in the skeletal tissues

    International Nuclear Information System (INIS)

    Shah, Amish P.; Jokisch, Derek W.; Rajon, Didier A.; Watchman, Christopher J.; Patton, Phillip W.; Bolch, Wesley E.

    2005-01-01

    energy deposition than given by voxel-based transport (average factor of about 1.6). The study supports future use of voxel-based skeletal models which (1) permit nonlinear electron trajectories across the skeletal tissues (2) do not rely on mathematical algorithms for treating the endosteal tissue layer, and (3) do not implicitly assume independence of marrow and bone trajectories as is the case for chord-based skeletal models

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

    OpenAIRE

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

    2009-01-01

    Background: Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian ca...

  18. Indian values of tissue weighting factors for internal dosimetry

    International Nuclear Information System (INIS)

    Mehta, S.K.

    1995-01-01

    In the present work the induced cancer component of detriment by the relative risk (RR) as well as US National Institute of Health (NIH) models using Indian organ based baseline cancer data and the all-causes mortality of the Indian population has been estimated. The Indian values of tissue weighting factors (W T ) have been worked out by the ICRP-60 methodology. The Indian values of detriment from the exposure of principal organs stomach, lung, colon and bone marrow are factors of 1.5 to 2.5 lower than the corresponding ICRP values. The Indian values of W T differ significantly from the ICRP five population average values. A tissue weighting factor of 0.08 for breast, colon, lung and stomach for the Indian population is more appropriate than the ICRP assigned factors of 0.05, 0.12, 0.12 and 0.12 respectively for these organs. For gonads, the appropriate Indian factor is 0.29 instead of the ICRP value of 0.20. The use of appropriate Indian values of W T is advocated for the Indian population in special investigation cases requiring regulatory intervention. (author). 11 refs., 11 figs., 4 tabs

  19. Determination of electron depth-dose curves for water, ICRU tissue, and PMMA and their application to radiation protection dosimetry

    International Nuclear Information System (INIS)

    Grosswendt, B.

    1994-01-01

    For monoenergetic electrons in the energy range between 60 keV and 10 MeV, normally incident on water, 4-element ICRU tissue and PMMA phantoms, depth-dose curves have been calculated using the Monte Carlo method. The phantoms' shape was that of a rectangular solid with a square front face of 30 cm x 30 cm and a thickness of 15 cm; it corresponds to that recommended by the ICRU for use in the procedure of calibrating radiation protection dosemeters. The depth-dose curves have been used to determine practical ranges, half-value depths, electron fluence to maximum absorbed dose conversion factors, and conversion factors between electron fluence and absorbed dose at depths d corresponding to 0.007 g.cm -2 , 0.3 g.cm -2 , and 1.0 g.cm -2 . The latter data can be used as fluence to dose equivalent conversion factors for extended parallel electron beams. (Author)

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

    Science.gov (United States)

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

    2010-11-01

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

  1. The influence of environmental factors on bone tissue engineering.

    Science.gov (United States)

    Szpalski, Caroline; Sagebin, Fabio; Barbaro, Marissa; Warren, Stephen M

    2013-05-01

    Bone repair and regeneration are dynamic processes that involve a complex interplay between the substrate, local and systemic cells, and the milieu. Although each constituent plays an integral role in faithfully recreating the skeleton, investigators have long focused their efforts on scaffold materials and design, cytokine and hormone administration, and cell-based therapies. Only recently have the intangible aspects of the milieu received their due attention. In this review, we highlight the important influence of environmental factors on bone tissue engineering. Copyright © 2012 Wiley Periodicals, Inc.

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

    International Nuclear Information System (INIS)

    Morrison, S.A.; Jesty, J.

    1984-01-01

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

  3. Estimation of anisotropy factor spectrum for determination of optical properties in biological tissues

    Science.gov (United States)

    Iwamoto, Misako; Honda, Norihiro; Ishii, Katsunori; Awazu, Kunio

    2017-07-01

    Spectroscopic setup for measuring anisotropy factor g spectrum of biological tissues was constructed. g of chicken liver tissue was lower than chicken breast tissue. High absorption of hemoglobin can have an influence on g spectrum.

  4. Staining plastic blocks with triiodide to image cells and soft tissues in backscattered electron SEM of skeletal and dental tissues

    Directory of Open Access Journals (Sweden)

    A Boyde

    2012-07-01

    Full Text Available Backscattered electron scanning electron microscopy (BSE SEM is an invaluable method for studying the histology of the hard, mineralised components of poly-methyl methacrylate (PMMA or other resin embedded skeletal and dental tissues. Intact tissues are studied in micro-milled or polished block faces with an electron-optical section thickness of the order of a half to one micron and with the area of the section as big as a whole – large or small – bone organ. However, BSE SEM does not give information concerning the distribution of uncalcified, ‘soft’, cellular and extracellular matrix components. This can be obtained by confocal microscopy of the same block and the two sorts of images merged but the blocks have to be studied in two microscope systems. The present work shows a new, simple and economic approach to visualising both components by using the triiodide ion in Lugol's iodine solution to stain the block surface prior to the application of any conductive coating – and the latter can be omitted if charging is suppressed by use of poor vacuum conditions in the SEM sample chamber. The method permits the use of archival tissue, and it will be valuable in studies of both normal growth and development and pathological changes in bones and joints, including osteoporosis and osteoarthritis, and tissue adaptation to implants.

  5. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function.

    Science.gov (United States)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-06-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

  6. Electron probe microanalysis for clinical investigations: Microdrop and soft tissue analysis

    International Nuclear Information System (INIS)

    Ingram, M.J.; Ingram, F.D.

    1984-01-01

    The most important advantage offered by electron probe microanalysis (EPA) for clinical investigations is the ability to analyze smaller volumes of tissue than is possible with conventional techniques. The sample can be a biological soft tissue specimen, which involves subcellular localization, or a picoliter fluid droplet. In either case, the analysis can be nondestructive and permit multiple analyses for a number of elements in a given sample. The most highly developed electron microprobe analytical technique is fluid drop analysis, popularly referred to as microdrop analysis. This method provides the investigator with an analytic capability that has an accuracy of measurement often 1% or better on 20 to 30 picoliter fluid droplets. Electron microprobe techniques have been used for studies of animal hard tissue and for studies that involve insoluble inclusions. However, the development of techniques for studies of labile constituents in animal soft tissue has been much slower. It has been necessary not only to develop appropriate methods of tissue preparation, but also to establish sound techniques for tissue collection. Although there are adequate methods for collection of most types of tissue from laboratory animals, many of these methods are not suitable for human subjects. In order to provide the reader with a better understanding of the capabilities and potential for the application of electron microprobe methodology to problems in clinical medicine, the authors discuss some of their experiences with liquid droplet analysis and quantitative electrolyte distribution measurements in animal soft tissue

  7. Connective tissue growth factor is a substrate of ADAM28

    International Nuclear Information System (INIS)

    Mochizuki, Satsuki; Tanaka, Rena; Shimoda, Masayuki; Onuma, Junko; Fujii, Yutaka; Jinno, Hiromitsu; Okada, Yasunori

    2010-01-01

    Research highlights: → The hyper-variable region in the cysteine-rich domain of ADAM28 binds to C-terminal domain of CTGF. → ADAM28 cleaves CTGF alone and CTGF in the CTGF/VEGF 165 complex. → CTGF digestion by ADAM28 releases biologically active VEGF 165 from the complex. → ADAM28, CTGF and VEGF 165 are commonly co-expressed by carcinoma cells in human breast carcinoma tissues. → These suggest that ADAM28 promotes VEGF 165 -induced angiogenesis in the breast carcinomas by selective CTGF digestion in the CTGF/VEGF 165 complex. -- Abstract: ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, is over-expressed by carcinoma cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala 181 -Tyr 182 and Asp 191 -Pro 192 bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor 165 (VEGF 165 ), releasing biologically active VEGF 165 from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF 165 -induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF 165 complex.

  8. Association of intraoperative tissue oxygenation with suspected risk factors for tissue hypoxia.

    Science.gov (United States)

    Spruit, R J; Schwarte, L A; Hakenberg, O W; Scheeren, T W L

    2013-10-01

    Tissue hypoxia may cause organ dysfunction, but not much is known about tissue oxygenation in the intraoperative setting. We studied microcirculatory tissue oxygen saturation (StO₂) to determine representative values for anesthetized patients undergoing urological surgery and to test the hypothesis that StO₂ is associated with known perioperative risk factors for morbidity and mortality, conventionally monitored variables, and hypotension requiring norepinephrine. Using near-infrared spectroscopy, we measured StO₂ on the thenar eminence in 160 patients undergoing open urological surgery under general anesthesia (FiO2 0.35-0.4), and calculated its correlations with age, risk level for general perioperative complications and mortality (high if age ≥70 and procedure is radical cystectomy), mean arterial pressure (MAP), hemoglobin concentration (Hb), central venous oxygen saturation (ScvO₂), and norepinephrine use. The time averaged StO₂ was 86 ± 6 % (mean ± SD). In the multivariate analysis, Hb [standardized coefficient (SC) 0.21, p = 0.003], ScvO₂ (SC 0.53, p SStO₂ was partly dependent on MAP only when this was below 65 mmHg (lowest MAP SC 0.20, p = 0.006, MAP area under the curve <65 mmHg SC 0.03, p = 0.02). Finally, StO₂ was slightly lower in patients requiring norepinephrine (85 ± 6 vs. 89 ± 6 %, p = 0.001). Intraoperative StO₂ in urological patients was comparable to that of healthy volunteers breathing room air as reported in the literature and correlated with known perioperative risk factors. Further research should investigate its association with outcome and the effect of interventions aimed at optimizing StO₂.

  9. Correction factors to convert microdosimetry measurements in silicon to tissue in 12C ion therapy.

    Science.gov (United States)

    Bolst, David; Guatelli, Susanna; Tran, Linh T; Chartier, Lachlan; Lerch, Michael L F; Matsufuji, Naruhiro; Rosenfeld, Anatoly B

    2017-03-21

    Silicon microdosimetry is a promising technology for heavy ion therapy (HIT) quality assurance, because of its sub-mm spatial resolution and capability to determine radiation effects at a cellular level in a mixed radiation field. A drawback of silicon is not being tissue-equivalent, thus the need to convert the detector response obtained in silicon to tissue. This paper presents a method for converting silicon microdosimetric spectra to tissue for a therapeutic 12 C beam, based on Monte Carlo simulations. The energy deposition spectra in a 10 μm sized silicon cylindrical sensitive volume (SV) were found to be equivalent to those measured in a tissue SV, with the same shape, but with dimensions scaled by a factor κ equal to 0.57 and 0.54 for muscle and water, respectively. A low energy correction factor was determined to account for the enhanced response in silicon at low energy depositions, produced by electrons. The concept of the mean path length [Formula: see text] to calculate the lineal energy was introduced as an alternative to the mean chord length [Formula: see text] because it was found that adopting Cauchy's formula for the [Formula: see text] was not appropriate for the radiation field typical of HIT as it is very directional. [Formula: see text] can be determined based on the peak of the lineal energy distribution produced by the incident carbon beam. Furthermore it was demonstrated that the thickness of the SV along the direction of the incident 12 C ion beam can be adopted as [Formula: see text]. The tissue equivalence conversion method and [Formula: see text] were adopted to determine the RBE 10 , calculated using a modified microdosimetric kinetic model, applied to the microdosimetric spectra resulting from the simulation study. Comparison of the RBE 10 along the Bragg peak to experimental TEPC measurements at HIMAC, NIRS, showed good agreement. Such agreement demonstrates the validity of the developed tissue equivalence correction factors and of

  10. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  11. Electron density values of various human tissues: in vitro Compton scatter measurements and calculated ranges

    International Nuclear Information System (INIS)

    Shrimpton, P.C.

    1981-01-01

    Accurate direct measurements of electron density have been performed on specimens from 10 different tissue types of the human body, representing the major organs, using a Compton scatter technique. As a supplement to these experimental values, calculations have been carried out to determine the electron densities expected for these tissue types. The densities observed are in good agreement with the broad ranges deduced from the basic data previously published. The results of both the in vitro sample measurements and the approximate calculations indicate that the electron density of most normal healthy soft tissue can be expected to fall within the fairly restricted range of +- 5% around 3.4 X 10 23 electrons per cm 3 . The obvious exception to this generalisation is the result for lung tissue, which falls considerably below this range owing to the high air content inherent in its construction. In view of such an overall limited variation with little difference between tissues, it would appear that electron density alone is likely to be a rather poor clinical parameter for tissue analysis, with high accuracy and precision being essential in any in vivo Compton measurements for imaging or diagnosis on specific organs. (author)

  12. Electron holography study of the charging effect in microfibrils of sciatic nerve tissues.

    Science.gov (United States)

    Kim, Ki Hyun; Akase, Zentaro; Shindo, Daisuke; Ohno, Nobuhiko; Fujii, Yasuhisa; Terada, Nobuo; Ohno, Shinichi

    2013-08-01

    The charging effects of microfibrils of sciatic nerve tissues due to electron irradiation are investigated using electron holography. The phenomenon that the charging effects are enhanced with an increase of electron intensity is visualized through direct observations of the electric potential distribution around the specimen. The electric potential at the surface of the specimen could be quantitatively evaluated by simulation, which takes into account the reference wave modulation due to the long-range electric field.

  13. Proteolytic processing of connective tissue growth factor in normal ocular tissues and during corneal wound healing.

    Science.gov (United States)

    Robinson, Paulette M; Smith, Tyler S; Patel, Dilan; Dave, Meera; Lewin, Alfred S; Pi, Liya; Scott, Edward W; Tuli, Sonal S; Schultz, Gregory S

    2012-12-13

    Connective tissue growth factor (CTGF) is a fibrogenic cytokine that is up-regulated by TGF-β and mediates most key fibrotic actions of TGF-β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. This study addresses the role of proteolytic processing of CTGF in human corneal fibroblasts (HCF) stimulated with TGF-β, normal ocular tissues and wounded corneas. Proteolytic processing of CTGF in HCF cultures, normal animal eyes, and excimer laser wounded rat corneas were examined by Western blot. The identity of a 21-kDa band was determined by tandem mass spectrometry, and possible alternative splice variants of CTGF were assessed by 5' Rapid Amplification of cDNA Ends (RACE). HCF stimulated by TGF-β contained full length 38-kDa CTGF and fragments of 25, 21, 18, and 13 kDa, while conditioned medium contained full length 38- and a 21-kDa fragment of CTGF that contained the middle "hinge" region of CTGF. Fragmentation of recombinant CTGF incubated in HCF extracts was blocked by the aspartate protease inhibitor, pepstatin. Normal mouse, rat, and rabbit whole eyes and rabbit ocular tissues contained abundant amounts of C-terminal 25- and 21-kDa fragments and trace amounts of 38-kDa CTGF, although no alternative transcripts were detected. All forms of CTGF (38, 25, and 21 kDa) were detected during healing of excimer ablated rat corneas, peaking on day 11. Proteolytic processing of 38-kDa CTGF occurs during corneal wound healing, which may have important implications in regulation of corneal scar formation.

  14. Fibroblast growth factors as tissue repair and regeneration therapeutics

    Directory of Open Access Journals (Sweden)

    Quentin M. Nunes

    2016-01-01

    Full Text Available Cell communication is central to the integration of cell function required for the development and homeostasis of multicellular animals. Proteins are an important currency of cell communication, acting locally (auto-, juxta-, or paracrine or systemically (endocrine. The fibroblast growth factor (FGF family contributes to the regulation of virtually all aspects of development and organogenesis, and after birth to tissue maintenance, as well as particular aspects of organism physiology. In the West, oncology has been the focus of translation of FGF research, whereas in China and to an extent Japan a major focus has been to use FGFs in repair and regeneration settings. These differences have their roots in research history and aims. The Chinese drive into biotechnology and the delivery of engineered clinical grade FGFs by a major Chinese research group were important enablers in this respect. The Chinese language clinical literature is not widely accessible. To put this into context, we provide the essential molecular and functional background to the FGF communication system covering FGF ligands, the heparan sulfate and Klotho co-receptors and FGF receptor (FGFR tyrosine kinases. We then summarise a selection of clinical reports that demonstrate the efficacy of engineered recombinant FGF ligands in treating a wide range of conditions that require tissue repair/regeneration. Alongside, the functional reasons why application of exogenous FGF ligands does not lead to cancers are described. Together, this highlights that the FGF ligands represent a major opportunity for clinical translation that has been largely overlooked in the West.

  15. Connective tissue growth factor (CTGF) and cancer progression.

    Science.gov (United States)

    Chu, Chia-Yu; Chang, Cheng-Chi; Prakash, Ekambaranellore; Kuo, Min-Liang

    2008-11-01

    Connective tissue growth factor (CTGF) is a member of the CCN family of secreted, matrix-associated proteins encoded by immediate early genes that play various roles in angiogenesis and tumor growth. CCN family proteins share uniform modular structure which mediates various cellular functions such as regulation of cell division, chemotaxis, apoptosis, adhesion, motility, angiogenesis, neoplastic transformation, and ion transport. Recently, CTGF expression has been shown to be associated with tumor development and progression. There is growing body of evidence that CTGF may regulate cancer cell migration, invasion, angiogenesis, and anoikis. In this review, we will highlight the influence of CTGF expression on the biological behavior and progression of various cancer cells, as well as its regulation on various types of protein signals and their mechanisms.

  16. Single-stage unity power factor based electronic ballast

    Indian Academy of Sciences (India)

    This paper deals with the design, modeling, analysis and implementation of unity power factor (UPF) based electronic ballast for a fluorescent lamp (FL). The proposed electronic ballast uses a boost AC–DC converter as a power factor corrector (PFC) to improve the power quality at the input ac mains. In this singlestage ...

  17. p27{sup Kip1} inhibits tissue factor expression

    Energy Technology Data Exchange (ETDEWEB)

    Breitenstein, Alexander, E-mail: alexander.breitenstein@usz.ch [Cardiology, University Heart Center, University Hospital Zurich (Switzerland); Cardiovascular Research, Physiology Institute, University of Zurich (Switzerland); Center for Integrative Human Physiology (ZHIP), University of Zurich (Switzerland); Akhmedov, Alexander; Camici, Giovanni G.; Lüscher, Thomas F.; Tanner, Felix C. [Cardiology, University Heart Center, University Hospital Zurich (Switzerland); Cardiovascular Research, Physiology Institute, University of Zurich (Switzerland); Center for Integrative Human Physiology (ZHIP), University of Zurich (Switzerland)

    2013-10-04

    Highlights: •p27{sup Kip1}regulates the expression of tissue factor at the transcriptional level. •This inhibitory effect of p27{sup Kip1} is independently of its cell regulatory action. •The current study provides new insights into a pleiotrophic function of p27{sup Kip1}. -- Abstract: Background: The cyclin-dependent kinase inhibitor (CDKI) p27{sup Kip1} regulates cell proliferation and thus inhibits atherosclerosis and vascular remodeling. Expression of tissue factor (TF), the key initator of the coagulation cascade, is associated with atherosclerosis. Yet, it has not been studied whether p27{sup Kip1} influences the expression of TF. Methods and results: p27{sup Kip1} overexpression in human aortic endothelial cells was achieved by adenoviral transfection. Cells were rendered quiescent for 24 h in 0.5% fetal-calf serum. After stimulation with TNF-α (5 ng/ml), TF protein expression and activity was significantly reduced (n = 4; P < 0.001) in cells transfected with p27{sup Kip1}. In line with this, p27{sup Kip1} overexpression reduced cytokine-induced TF mRNA expression (n = 4; P < 0.01) and TF promotor activity (n = 4; P < 0.05). In contrast, activation of the MAP kinases p38, ERK and JNK was not affected by p27{sup Kip1} overexpression. Conclusion: This in vitro study suggests that p27{sup Kip1} inhibits TF expression at the transcriptional level. These data indicate an interaction between p27{sup Kip1} and TF in important pathological alterations such as atherosclerosis and vascular remodeling.

  18. Modification of PLGA Nanofibrous Mats by Electron Beam Irradiation for Soft Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Jae Baek Lee

    2015-01-01

    Full Text Available Biodegradable poly(lactide-co-glycolide (PLGA has found widespread use in modern medical practice. However, the degradation rate of PLGA should be adjusted for specific biomedical applications such as tissue engineering, drug delivery, and surgical implantation. This study focused on the effect of electron beam radiation on nanofibrous PLGA mats in terms of physical properties and degradation behavior with cell proliferation. PLGA nanofiber mats were prepared by electrospinning, and electron beam was irradiated at doses of 50, 100, 150, 200, 250, and 300 kGy. PLGA mats showed dimensional integrity after electron beam irradiation without change of fiber diameter. The degradation behavior of a control PLGA nanofiber (0 kGy and electron beam-irradiated PLGA nanofibers was analyzed by measuring the molecular weight, weight loss, change of chemical structure, and fibrous morphology. The molecular weight of the PLGA nanofibers decreased with increasing electron beam radiation dose. The mechanical properties of the PLGA nanofibrous mats were decreased with increasing electron beam irradiation dose. Cell proliferation behavior on all electron beam irradiated PLGA mats was similar to the control PLGA mats. Electron beam irradiation of PLGA nanofibrous mats is a potentially useful approach for modulating the biodegradation rate of tissue-specific nonwoven nanofibrous scaffolds, specifically for soft tissue engineering applications.

  19. Electronic equilibrium as a function of depth in tissue from cobalt-60 point source exposures

    International Nuclear Information System (INIS)

    Myrick, J.A.

    1994-08-01

    The Nuclear Regulatory Commission has set the basic criteria for assessing skin dose stemming from hot particle contaminations. Compliance with 10 CFR 20.101 requires that exposure to the skin be evaluated over a 1 cm 2 area at a depth of 0.007 cm. Skin exposure can arise from both the beta and gamma components of radioactive particles and gamma radiation can contribute significantly to skin doses. The gamma component of dose increases dramatically when layers of protective clothing are interposed between the hot particle source and the skin, and in cases where the hot particle is large in comparison to the range of beta particles. Once the protective clothing layer is thicker than the maximum range of the beta particles, skin dose is due solely to gamma radiation. Charged particle equilibrium is not established at shallow depths. The degree of electronic equilibrium establishment must be assessed for shallow doses to prevent the over-assessment of skin dose because conventional fluence-to-dose conversion factors are not applicable. To assess the effect of electronic equilibrium, selected thicknesses of tissue equivalent material were interposed between radiochromic dye film and a 60 Co hot particle source and dose was measured as a function of depth. These measured values were then compared to models which are used to calculate charged particle equilibrium. The Miller-Reece model was found to agree closely with the experimental data while the Lantz-Lambert model overestimated dose at shallow depths

  20. Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

    Science.gov (United States)

    Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

    2013-07-01

    Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

  1. Adhesion-governed buckling of thin-film electronics on soft tissues

    Directory of Open Access Journals (Sweden)

    Bo Wang

    2016-01-01

    Full Text Available Stretchable/flexible electronics has attracted great interest and attention due to its potentially broad applications in bio-compatible systems. One class of these ultra-thin electronic systems has found promising and important utilities in bio-integrated monitoring and therapeutic devices. These devices can conform to the surfaces of soft bio-tissues such as the epidermis, the epicardium, and the brain to provide portable healthcare functionalities. Upon contractions of the soft tissues, the electronics undergoes compression and buckles into various modes, depending on the stiffness of the tissue and the strength of the interfacial adhesion. These buckling modes result in different kinds of interfacial delamination and shapes of the deformed electronics, which are very important to the proper functioning of the bio-electronic devices. In this paper, detailed buckling mechanics of these thin-film electronics on elastomeric substrates is studied. The analytical results, validated by experiments, provide a very convenient tool for predicting peak strain in the electronics and the intactness of the interface under various conditions.

  2. Effective atomic numbers, electron densities, and tissue equivalence of some gases and mixtures for dosimetry of radiation detectors

    Directory of Open Access Journals (Sweden)

    Singh Vishwanath P.

    2012-01-01

    Full Text Available Total mass attenuation coefficients, µm, effective atomic number, Zeff, and effective electron density, Neff, of different gases - carbon dioxide, methane, acetylene, propane, butane, and pentane used in radiation detectors, have been calculated for the photon energy of 1 keV to 100 GeV. Each gas has constant Zeff values between 0.10 to 10 MeV photon energies; however, these values are way far away from ICRU tissue. Carbon dioxide gas shows the closest tissue equivalence in the entire photon energy spectrum. Relative tissue equivalences of the mixtures of gases with respect to ICRU tissue are in the range of 0.998-1.041 for air, argon (4.5% + methane (95.5%, argon (0.5% + carbon dioxide (99.5%, and nitrogen (5% + methane (7% + carbon dioxide (88%. The gas composition of xenon (0.5% + carbon dioxide (99.5% shows 1.605 times higher tissue equivalence compared to the ICRU tissue. The investigated photon interaction parameters are useful for exposure and energy absorption buildup factors calculation and design, and fabrication of gaseous detectors for ambient radiation measurement by the Geiger-Muller detector, ionization chambers and proportional counters.

  3. Expression and localization of tissue factor pathway inhibitor-2 in normal and atherosclerotic human vessels

    NARCIS (Netherlands)

    Crawley, James T. B.; Goulding, David A.; Ferreira, Valérie; Severs, Nicholas J.; Lupu, Florea

    2002-01-01

    Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type, serine protease inhibitor with inhibitory activity toward activated factor XI, plasma kallikrein, plasmin, certain matrix metalloproteinases, and the tissue factor:activated factor VII complex. In this study, we investigated TFPI-2

  4. Effect of tissue and plasma factors on kidney proliferation.

    Science.gov (United States)

    Inda, A M; García, A L; Errecalde, A L; Badrán, A F

    1997-04-01

    Liver extract, plasma from intact mice, ES2 tumour extract and plasma from tumour bearing mice has an inhibiting effect on the mitotic activity of hepatocytes and duodenal enterocytes. In the present experiments, the effect of these treatments on the mitotic activity of renal tubular cells was studied. C3HS 28 day-old male mice, standardized for periodicity analysis were used. The determination of normal mitotic circadian curve of the renocytes was done. A second batch of mice were injected with 0.01 ml/gr of either liver extract, plasma from intact mice, ES2 tumour extract or plasma from tumour bearing mice, at 16:00 hours and controlled at 08:00, 12:00 and 16:00 hs during 2 consecutive days post treatment. Colchicine (2 micrograms/gr) was injected 4 hours before killing. Kidneys were processed for histology and mitotic index determinations. Results were expressed as colchicine metaphases per 1000 nuclei, and showed that mitotic activity values of treated animals were significantly lower than those of controls. In conclusion, mitotic activity inhibition of renocytes may be due to some non specific plasmatic and/or tissue factors.

  5. Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

    International Nuclear Information System (INIS)

    Antoniassi, M.; Conceição, A.L.C.; Poletti, M.E.

    2012-01-01

    Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: ► Electron density of normal and neoplastic breast tissues was measured using Compton scattering. ► Monochromatic synchrotron radiation was used to obtain the Compton scattering data. ► The area of Compton peaks was used to determine the electron densities of samples. ► Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. ► Comparison with previous results showed differences smaller than 4%.

  6. Monte Carlo based electron treatment planning and cutout output factor calculations

    Science.gov (United States)

    Mitrou, Ellis

    Electron radiotherapy (RT) offers a number of advantages over photons. The high surface dose, combined with a rapid dose fall-off beyond the target volume presents a net increase in tumor control probability and decreases the normal tissue complication for superficial tumors. Electron treatments are normally delivered clinically without previously calculated dose distributions due to the complexity of the electron transport involved and greater error in planning accuracy. This research uses Monte Carlo (MC) methods to model clinical electron beams in order to accurately calculate electron beam dose distributions in patients as well as calculate cutout output factors, reducing the need for a clinical measurement. The present work is incorporated into a research MC calculation system: McGill Monte Carlo Treatment Planning (MMCTP) system. Measurements of PDDs, profiles and output factors in addition to 2D GAFCHROMICRTM EBT2 film measurements in heterogeneous phantoms were obtained to commission the electron beam model. The use of MC for electron TP will provide more accurate treatments and yield greater knowledge of the electron dose distribution within the patient. The calculation of output factors could invoke a clinical time saving of up to 1 hour per patient.

  7. Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

    Science.gov (United States)

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

  8. Ocular Safety of Intravitreal Connective Tissue Growth Factor Neutralizing Antibody.

    Science.gov (United States)

    Motevasseli, Tahmineh; Daftarian, Narsis; Kanavi, Mozhgan Rezaei; Ahmadieh, Hamid; Bagheri, Abouzar; Hosseini, Seyed Bagher; Ansari, Shabnam; Soheili, Zahra-Soheila

    2017-08-01

    To detect the safety of intravitreal injection of anti-connective tissue growth factor (CTGF) (IVAC) in rat eyes in order to apply this neutralizing antibody for experimental animal studies. Forty-five Lister Hooded male pigmented rats were divided into five groups that received IVAC (2 μl) corresponding to the doses of 10 (B), 20 (C), 50 (D), and 100 μg/ml (E), equal to 1.25, 2.5, 6.25, and 12.5 µg/ml of antibody concentration in rat vitreous, respectively. The sham group (A) received 2 μl of normal saline. Full field electroretinography (ERG) was performed at baseline and on days 7 and 28 after IVAC. The animals were euthanized and the corresponding eyes were subjected to routine histopathology, immunohistochemistry for glial fibrillary acidic protein (GFAP), and terminal transferase dUTP nick end-labeling (TUNEL) assay. Scotopic rod b-wave amplitude and maximal combined b-wave amplitude were 111.89 ± 71.2 and 178.57 ± 55.58 μV, respectively, at baseline which significantly reduced to 79.31 ± 52.59 and 128.73 ± 41.61 μV, respectively, after 28 days in group E (p < 0.05). There was no significant reduction of amplitudes in other groups with lower doses of anti-CTGF antibody. Retinal ganglion cells were significantly decreased in group E as compared to other groups. GFAP immune reactivity was not significant in any of the groups. TUNEL test showed inner retinal neural cell apoptosis only in group E. ERG, histopathologic, and apoptotic assays revealed no toxic effects of 10-50 μg/ml of IVAC in rat eyes. Using 100 μg/ml IVAC led to a significant toxic effect in terms of functional, histopathologic, and TUNEL findings.

  9. Application of principal component and factor analyses in electron spectroscopy

    International Nuclear Information System (INIS)

    Siuda, R.; Balcerowska, G.

    1998-01-01

    Fundamentals of two methods, taken from multivariate analysis and known as principal component analysis (PCA) and factor analysis (FA), are presented. Both methods are well known in chemometrics. Since 1979, when application of the methods to electron spectroscopy was reported for the first time, they became to be more and more popular in different branches of electron spectroscopy. The paper presents examples of standard applications of the method of Auger electron spectroscopy (AES), X-ray photoelectron spectroscopy (XPS), and electron energy loss spectroscopy (EELS). Advantages one can take from application of the methods, their potentialities as well as their limitations are pointed out. (author)

  10. Tissue engineering of bladder using vascular endothelial growth factor gene-modified endothelial progenitor cells.

    Science.gov (United States)

    Chen, Bai-Song; Xie, Hua; Zhang, Sheng-Li; Geng, Hong-Quan; Zhou, Jun-Mei; Pan, Jun; Chen, Fang

    2011-12-01

    This study assessed the use of vascular endothelial growth factor (VEGF) gene-modified endothelial progenitor cells (EPCs) seeded onto bladder acellular matrix grafts (BAMGs), to enhance the blood supply in tissue-engineered bladders in a porcine model. Autologous porcine peripheral EPCs were isolated, cultured, expanded, characterized, and modified with the VEGF gene using an adenovirus vector. The expression of VEGF was examined using reverse transcriptase polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). VEGF gene modified EPCs were seeded onto BAMG and cultured for 3 days before implantation into pigs for bladder tissue engineering. A partial bladder cystectomy was performed in 12 pigs. The experimental group (6 pigs) received VEGF gene-modified EPC-seeded BAMG. The control group (6 pigs) received BAMG without seeded EPCs. The resulting tissue-engineered bladders were subject to a general and histological analysis. Microvessel density (MVD) was assessed using immunohistochemistry. The ex vivo transfection efficiency of EPCs was greater than 60%-70% when concentrated adenovirus was used. The genetically modified cells expressed both VEGF and green fluorescent protein (GFP). Scanning electron microscopy (SEM) and Masson's trichrome staining of cross sections of the cultured cells seeded to BAMG showed cell attachment and proliferation on the surface of the BAMG. Histological examination revealed bladder regeneration in a time-dependent fashion. Significant increases in MVD were observed in the experimental group, in comparison with the control group. VEGF-modified EPCs significantly enhanced neovascularization, compared with BAMG alone. These results indicate that EPCs, combined with VEGF gene therapy, may be a suitable approach for increasing blood supply in the tissue engineering of bladders. Thus, a useful strategy to achieve a tissue-engineered bladder is indicated.

  11. Localization of xanthine oxidoreductase activity using the tissue protectant polyvinyl alcohol and final electron acceptor Tetranitro BT

    NARCIS (Netherlands)

    Kooij, A.; Frederiks, W. M.; Gossrau, R.; van Noorden, C. J.

    1991-01-01

    We have detected xanthine oxidoreductase activity in unfixed cryostat sections of rat and chicken liver, rat duodenum, and bovine mammary gland using the tissue protectant polyvinyl alcohol, the electron carrier 1-methoxyphenazine methosulfate, the final electron acceptor Tetranitro BT, and

  12. Electron tomography of HIV-1 infection in gut-associated lymphoid tissue.

    Science.gov (United States)

    Ladinsky, Mark S; Kieffer, Collin; Olson, Gregory; Deruaz, Maud; Vrbanac, Vladimir; Tager, Andrew M; Kwon, Douglas S; Bjorkman, Pamela J

    2014-01-01

    Critical aspects of HIV-1 infection occur in mucosal tissues, particularly in the gut, which contains large numbers of HIV-1 target cells that are depleted early in infection. We used electron tomography (ET) to image HIV-1 in gut-associated lymphoid tissue (GALT) of HIV-1-infected humanized mice, the first three-dimensional ultrastructural examination of HIV-1 infection in vivo. Human immune cells were successfully engrafted in the mice, and following infection with HIV-1, human T cells were reduced in GALT. Virions were found by ET at all stages of egress, including budding immature virions and free mature and immature viruses. Immuno-electron microscopy verified the virions were HIV-1 and showed CD4 sequestration in the endoplasmic reticulum of infected cells. Observation of HIV-1 in infected GALT tissue revealed that most HIV-1-infected cells, identified by immunolabeling and/or the presence of budding virions, were localized to intestinal crypts with pools of free virions concentrated in spaces between cells. Fewer infected cells were found in mucosal regions and the lamina propria. The preservation quality of reconstructed tissue volumes allowed details of budding virions, including structures interpreted as host-encoded scission machinery, to be resolved. Although HIV-1 virions released from infected cultured cells have been described as exclusively mature, we found pools of both immature and mature free virions within infected tissue. The pools could be classified as containing either mostly mature or mostly immature particles, and analyses of their proximities to the cell of origin supported a model of semi-synchronous waves of virion release. In addition to HIV-1 transmission by pools of free virus, we found evidence of transmission via virological synapses. Three-dimensional EM imaging of an active infection within tissue revealed important differences between cultured cell and tissue infection models and furthered the ultrastructural understanding of

  13. Electron tomography of HIV-1 infection in gut-associated lymphoid tissue.

    Directory of Open Access Journals (Sweden)

    Mark S Ladinsky

    2014-01-01

    Full Text Available Critical aspects of HIV-1 infection occur in mucosal tissues, particularly in the gut, which contains large numbers of HIV-1 target cells that are depleted early in infection. We used electron tomography (ET to image HIV-1 in gut-associated lymphoid tissue (GALT of HIV-1-infected humanized mice, the first three-dimensional ultrastructural examination of HIV-1 infection in vivo. Human immune cells were successfully engrafted in the mice, and following infection with HIV-1, human T cells were reduced in GALT. Virions were found by ET at all stages of egress, including budding immature virions and free mature and immature viruses. Immuno-electron microscopy verified the virions were HIV-1 and showed CD4 sequestration in the endoplasmic reticulum of infected cells. Observation of HIV-1 in infected GALT tissue revealed that most HIV-1-infected cells, identified by immunolabeling and/or the presence of budding virions, were localized to intestinal crypts with pools of free virions concentrated in spaces between cells. Fewer infected cells were found in mucosal regions and the lamina propria. The preservation quality of reconstructed tissue volumes allowed details of budding virions, including structures interpreted as host-encoded scission machinery, to be resolved. Although HIV-1 virions released from infected cultured cells have been described as exclusively mature, we found pools of both immature and mature free virions within infected tissue. The pools could be classified as containing either mostly mature or mostly immature particles, and analyses of their proximities to the cell of origin supported a model of semi-synchronous waves of virion release. In addition to HIV-1 transmission by pools of free virus, we found evidence of transmission via virological synapses. Three-dimensional EM imaging of an active infection within tissue revealed important differences between cultured cell and tissue infection models and furthered the ultrastructural

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

    Science.gov (United States)

    Collier, Mary E. W.; Ettelaie, Camille

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    International Nuclear Information System (INIS)

    Wildgoose, P.; Kisiel, W.; Kazim, A.L.

    1990-01-01

    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

  17. Establishing the impact of temporary tissue expanders on electron and photon beam dose distributions.

    Science.gov (United States)

    Asena, A; Kairn, T; Crowe, S B; Trapp, J V

    2015-05-01

    This study investigates the effects of temporary tissue expanders (TTEs) on the dose distributions in breast cancer radiotherapy treatments under a variety of conditions. Using EBT2 radiochromic film, both electron and photon beam dose distribution measurements were made for different phantoms, and beam geometries. This was done to establish a more comprehensive understanding of the implant's perturbation effects under a wider variety of conditions. The magnetic disk present in a tissue expander causes a dose reduction of approximately 20% in a photon tangent treatment and 56% in electron boost fields immediately downstream of the implant. The effects of the silicon elastomer are also much more apparent in an electron beam than a photon beam. Evidently, each component of the TTE attenuates the radiation beam to different degrees. This study has demonstrated that the accuracy of photon and electron treatments of post-mastectomy patients is influenced by the presence of a tissue expander for various beam orientations. The impact of TTEs on dose distributions establishes the importance of an accurately modelled high-density implant in the treatment planning system for post-mastectomy patients. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  19. Atmospheric scanning electron microscope observes cells and tissues in open medium through silicon nitride film.

    Science.gov (United States)

    Nishiyama, Hidetoshi; Suga, Mitsuo; Ogura, Toshihiko; Maruyama, Yuusuke; Koizumi, Mitsuru; Mio, Kazuhiro; Kitamura, Shinichi; Sato, Chikara

    2010-03-01

    Direct observation of subcellular structures and their characterization is essential for understanding their physiological functions. To observe them in open environment, we have developed an inverted scanning electron microscope with a detachable, open-culture dish, capable of 8 nm resolution, and combined with a fluorescence microscope quasi-simultaneously observing the same area from the top. For scanning electron microscopy from the bottom, a silicon nitride film window in the base of the dish maintains a vacuum between electron gun and open sample dish while allowing electrons to pass through. Electrons are backscattered from the sample and captured by a detector under the dish. Cells cultured on the open dish can be externally manipulated under optical microscopy, fixed, and observed using scanning electron microscopy. Once fine structures have been revealed by scanning electron microscopy, their component proteins may be identified by comparison with separately prepared fluorescence-labeled optical microscopic images of the candidate proteins, with their heavy-metal-labeled or stained ASEM images. Furthermore, cell nuclei in a tissue block stained with platinum-blue were successfully observed without thin-sectioning, which suggests the applicability of this inverted scanning electron microscope to cancer diagnosis. This microscope visualizes mesoscopic-scale structures, and is also applicable to non-bioscience fields including polymer chemistry. (c) 2010 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2009-12-15

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

  1. Measurement of electron blockage factors for mamma scars

    International Nuclear Information System (INIS)

    Marques Fraguela, E.; Suero Rodrigo, M. A.

    2011-01-01

    Pencil Beam algorithm XiO CMS scheduler uses the applicator factor, instead of blocking factor in the calculation of monitor units (MU) shaped electron fields. This feature makes the algorithm for calculating an input field the same dose in the beam axis than it would if it were not blocked. It should, therefore, to correct the UM that provides the planner by a factor. The blocks used in electron treatment of the surgical mamma cancers often have a narrow elongated shape following the contour of the scar. Such openings have difficulty measuring the blocking factor with plane-parallel chambers recommended by national and international protocols (eg PTW Roos 34 001) as being so narrow that sometimes the camera is not completely irradiated. In this paper, we study the possibility of using a PTW 30010 Farmer cylindrical chamber for measuring the blocking factor of such openings.

  2. Critical Success Factors for Electronic Commerce in Chinese Electronic Information Industry

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Critical success factors (CSF) for electronic commerce (EC) are important for enterprises.This research discusses both assessment indicators and impact factors for EC success to help Chinese enterprises to achieve successful EC implementations. On the basis of literature review and experts survey, the research suggests some assessment indicators and impact factors for EC success. A hypothesis is proposed that leadership, strategy, management, organization, technology, customers,and suppliers factors would affect EC success. Furthermore, the research conducts an empirical study on the Chinese Electronic Information Industry to verify the hypothesis. Using factor analysis and regression analysis, the research finds out several critical factors--leadership, strategy, and organization--and critical sub-factors, such as leadership belief and organization management. These findings indicate the usefulness of this research model, especially for Chinese enterprises.

  3. Robust parameterization of elastic and absorptive electron atomic scattering factors

    International Nuclear Information System (INIS)

    Peng, L.M.; Ren, G.; Dudarev, S.L.; Whelan, M.J.

    1996-01-01

    A robust algorithm and computer program have been developed for the parameterization of elastic and absorptive electron atomic scattering factors. The algorithm is based on a combined modified simulated-annealing and least-squares method, and the computer program works well for fitting both elastic and absorptive atomic scattering factors with five Gaussians. As an application of this program, the elastic electron atomic scattering factors have been parameterized for all neutral atoms and for s up to 6 A -1 . Error analysis shows that the present results are considerably more accurate than the previous analytical fits in terms of the mean square value of the deviation between the numerical and fitted scattering factors. Parameterization for absorptive atomic scattering factors has been made for 17 important materials with the zinc blende structure over the temperature range 1 to 1000 K, where appropriate, and for temperature ranges for which accurate Debye-Waller factors are available. For other materials, the parameterization of the absorptive electron atomic scattering factors can be made using the program by supplying the atomic number of the element, the Debye-Waller factor and the acceleration voltage. For ions or when more accurate numerical results for neutral atoms are available, the program can read in the numerical values of the elastic scattering factors and return the parameters for both the elastic and absorptive scattering factors. The computer routines developed have been tested both on computer workstations and desktop PC computers, and will be made freely available via electronic mail or on floppy disk upon request. (orig.)

  4. Generalized Fokker-Planck theory for electron and photon transport in biological tissues: application to radiotherapy.

    Science.gov (United States)

    Olbrant, Edgar; Frank, Martin

    2010-12-01

    In this paper, we study a deterministic method for particle transport in biological tissues. The method is specifically developed for dose calculations in cancer therapy and for radiological imaging. Generalized Fokker-Planck (GFP) theory [Leakeas and Larsen, Nucl. Sci. Eng. 137 (2001), pp. 236-250] has been developed to improve the Fokker-Planck (FP) equation in cases where scattering is forward-peaked and where there is a sufficient amount of large-angle scattering. We compare grid-based numerical solutions to FP and GFP in realistic medical applications. First, electron dose calculations in heterogeneous parts of the human body are performed. Therefore, accurate electron scattering cross sections are included and their incorporation into our model is extensively described. Second, we solve GFP approximations of the radiative transport equation to investigate reflectance and transmittance of light in biological tissues. All results are compared with either Monte Carlo or discrete-ordinates transport solutions.

  5. The irradiation action on human dental tissue by X-rays and electrons. A nanoindenter study

    Energy Technology Data Exchange (ETDEWEB)

    Fraenzel, Wolfgang [Halle-Wittenberg Univ., Halle (Germany). Dept. of Physics; Gerlach, Reinhard [Halle-Wittenberg Univ., Halle (Germany). Clinic of Radiation Therapy

    2009-07-01

    It is known that ionizing radiation is used in medicine for Roentgen diagnostics and for radiation therapy. The radiation interacts with matter, in particular with biological one, essentially by scattering, photoelectric effect, Compton effect and pair production. To what extent the biological material is changed thereby, depends on the type and the amount of radiation energy, on the dose and on the tissue constitution. In modern radiation therapy two different kinds of radiation are used: high energy X-rays and electron radiation. In the case of head-neck tumors the general practice is an irradiation with high energy X-rays with absorbed dose to water up to 70 Gy. Teeth destruction has been identified as a side effect during irradiation. In addition, damage to the salivary glands is often observed which leads to a decrease or even the complete loss of the salivary secretion (xerostomia). This study shows how the different energy and radiation types damage the tooth tissue. The effects of both, high X-ray energy and high energy electrons, on the mechanical properties hardness and elasticity of the human dental tissue are measured by the nanoindentation technique. We compare these results with the effect of the irradiation of low X-ray energy on the dental tissue. (orig.)

  6. The irradiation action on human dental tissue by X-rays and electrons. A nanoindenter study

    International Nuclear Information System (INIS)

    Fraenzel, Wolfgang; Gerlach, Reinhard

    2009-01-01

    It is known that ionizing radiation is used in medicine for Roentgen diagnostics and for radiation therapy. The radiation interacts with matter, in particular with biological one, essentially by scattering, photoelectric effect, Compton effect and pair production. To what extent the biological material is changed thereby, depends on the type and the amount of radiation energy, on the dose and on the tissue constitution. In modern radiation therapy two different kinds of radiation are used: high energy X-rays and electron radiation. In the case of head-neck tumors the general practice is an irradiation with high energy X-rays with absorbed dose to water up to 70 Gy. Teeth destruction has been identified as a side effect during irradiation. In addition, damage to the salivary glands is often observed which leads to a decrease or even the complete loss of the salivary secretion (xerostomia). This study shows how the different energy and radiation types damage the tooth tissue. The effects of both, high X-ray energy and high energy electrons, on the mechanical properties hardness and elasticity of the human dental tissue are measured by the nanoindentation technique. We compare these results with the effect of the irradiation of low X-ray energy on the dental tissue. (orig.)

  7. Endocrine factors influencing radiation injury to central nervous tissue

    International Nuclear Information System (INIS)

    Aristizabal, S.A.; Boone, M.L.; Laguna, J.F.

    1979-01-01

    Corticosteroids have been shown experimentally to lower the tolerance of various normal tissues (lung, kidney, intestine) to irradiation. Pre-existing hypertension also modified the effect of irradiation on the rat spinal cord and brain. Hypercorticism and hypertension co-exist in patients with Cushing's disease. Although these patients are often approached therapeutically by irradiation, no reports concerning differences in the radiation sensitivity of nervous tissue between normal subjects (non-functioning pituitary adenomas) and those with hormonal imbalance and/or hypertension appear to be available. A comprehensive review of the literature revealed 14 patients with radiation damage to brain or to optic pathways following moderate doses for pituitary adenomas. Seven of the 14 patients (50%) had Cushing's disease. This apparent higher incidence of radiation injury is significant if we consider that less than 5% of all patients receiving irradiation for pituitary adenomas have Cushing's disease

  8. Measurement of electron blockage factors for mamma scars; Medida de los factores de bloque de electrones para cicatrices de mama

    Energy Technology Data Exchange (ETDEWEB)

    Marques Fraguela, E; Suero Rodrigo, M A

    2011-07-01

    Pencil Beam algorithm XiO CMS scheduler uses the applicator factor, instead of blocking factor in the calculation of monitor units (MU) shaped electron fields. This feature makes the algorithm for calculating an input field the same dose in the beam axis than it would if it were not blocked. It should, therefore, to correct the UM that provides the planner by a factor. The blocks used in electron treatment of the surgical mamma cancers often have a narrow elongated shape following the contour of the scar. Such openings have difficulty measuring the blocking factor with plane-parallel chambers recommended by national and international protocols (eg PTW Roos 34 001) as being so narrow that sometimes the camera is not completely irradiated. In this paper, we study the possibility of using a PTW 30010 Farmer cylindrical chamber for measuring the blocking factor of such openings.

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  10. Examining the factors affecting willingness to use electronic banking ...

    African Journals Online (AJOL)

    Examining the factors affecting willingness to use electronic banking: the ... which information technologies are accepted are of the research studies. ... Customers' understanding of the ease of use of e-banking systems has a significant impact on perceived usefulness and their attitude had. ... AJOL African Journals Online.

  11. Factors affecting the utilisation of electronic medical records system ...

    African Journals Online (AJOL)

    Malawi Medical Journal 29 (3): September 2017. Electronic medical ... care, as they enable storage of large amounts of data and ... EMRs. This study assessed factors that affect the use of EMRs in Malawi, particularly at Queen Elizabeth and Kamuzu Central ..... paperless hospitals in Norway : A socio-technical perspective.

  12. SU-F-T-67: Correction Factors for Monitor Unit Verification of Clinical Electron Beams

    Energy Technology Data Exchange (ETDEWEB)

    Haywood, J [Mercy Health Partners, Muskegon, MI (United States)

    2016-06-15

    Purpose: Monitor units calculated by electron Monte Carlo treatment planning systems are often higher than TG-71 hand calculations for a majority of patients. Here I’ve calculated tables of geometry and heterogeneity correction factors for correcting electron hand calculations. Method: A flat water phantom with spherical volumes having radii ranging from 3 to 15 cm was created. The spheres were centered with respect to the flat water phantom, and all shapes shared a surface at 100 cm SSD. D{sub max} dose at 100 cm SSD was calculated for each cone and energy on the flat phantom and for the spherical volumes in the absence of the flat phantom. The ratio of dose in the sphere to dose in the flat phantom defined the geometrical correction factor. The heterogeneity factors were then calculated from the unrestricted collisional stopping power for tissues encountered in electron beam treatments. These factors were then used in patient second check calculations. Patient curvature was estimated by the largest sphere that aligns to the patient contour, and appropriate tissue density was read from the physical properties provided by the CT. The resulting MU were compared to those calculated by the treatment planning system and TG-71 hand calculations. Results: The geometry and heterogeneity correction factors range from ∼(0.8–1.0) and ∼(0.9–1.01) respectively for the energies and cones presented. Percent differences for TG-71 hand calculations drop from ∼(3–14)% to ∼(0–2)%. Conclusion: Monitor units calculated with the correction factors typically decrease the percent difference to under actionable levels, < 5%. While these correction factors work for a majority of patients, there are some patient anatomies that do not fit the assumptions made. Using these factors in hand calculations is a first step in bringing the verification monitor units into agreement with the treatment planning system MU.

  13. Calculation of W for low energy electrons in tissue-equivalent gas. [<10 keV

    Energy Technology Data Exchange (ETDEWEB)

    Dayashankar, [Bhabha Atomic Research Centre, Bombay (India). Div. of Radiation Protection

    1977-11-01

    The mean energy expended per ion pair formed (W-value) in the tissue-equivalent gas for incident electrons of energy up to 10 keV has been calculated in the continuous slowing-down approximation. The effect of secondary and tertiary electrons has been considered by utilizing recent measurements of Opal et al., (1971, J. Chem. Phys., 55,4100) on the energy spectra of low-energy secondary electrons and the Mott formula for the spectra of high-energy secondaries. The results, which are provisional in nature due to the limitations on the accuracy of the input cross-section data and the neglect of the discrete nature of energy loss process, are compared with the available measurements.

  14. Connective tissue growth factor in renal development and injury

    NARCIS (Netherlands)

    Ito, Y.

    2011-01-01

    Langdurige weefselbeschadiging leidt vaak tot functieverlies van het betreffende orgaan door het ontstaan van veel littekens (fibrose). Yasuhiko Ito ontdekte dat genexpressie van de factor CTGF sterk is verhoogd bij veelvoorkomende nierziekten waarbij fibrose optreedt. De hoeveelheid CTGF in de

  15. Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

    Science.gov (United States)

    Chen, Guobao; Lv, Yonggang

    2015-01-01

    Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

  16. Radiation induced low-energy electron transport in a tissue environment

    International Nuclear Information System (INIS)

    Toburen, L.H.; Dingfelder, M.; Ozturk, N.; Christou, C.; Shinpaugh, J.L.; Friedland, W.; Wilson, W.E.; Paretzke, H.G.

    2003-01-01

    Monte Carlo (MC) track simulation codes are used extensively in radiobiology to quantify the spatial distributions of interactions initiated by the absorption of ionizing radiation. The spatial patterns of ionization and excitation are instrumental for assessing the formation of damage clusters in DNA and chromosomes leading to such biologic endpoints as cellular transformation and mutation. The MC codes rely on an extensive database of elastic and inelastic scattering cross sections to follow the production and slowing of secondary electrons. Because of inherent uncertainties in this database we are exploring the sensitivity of MC results to the details of the cross sections used with emphasis on low-energy electrons, i.e., track ends, that are anticipated to play a dominant role in damage cluster formation. Simulations of electron transport using gas or liquid based interaction cross sections illustrate substantial difference in the spectra of electrons with energies less than about 50 eV. In addition, the electron yields from MC simulations appear to be nearly a factor of five larger than our recent measurements of electron transport spectra in water (ice) at electron energies of about 10 eV. Examples of the changes in electron transport spectra for variations in the electron scattering cross sections used for the MC calculations will be illustrated and compared with an evolving database of measured spectra of electrons from ion induced secondary electron transport in thin foils. These measurements provide guidance for assessment of elastic and elastic cross sections appropriate to condensed phase transport. This work is supported in part by the U.S. Department of Energy, Grant No. DE-FG02-01ER-63233; the National Cancer Institute, Grant No. 1R01CA93351-01A1; and the European Community under Contract No. FIGH-CT-1999-00005

  17. Absorptive form factors for high-energy electron diffraction

    International Nuclear Information System (INIS)

    Bird, D.M.; King, Q.A.

    1990-01-01

    The thermal diffuse scattering contribution to the absorptive potential in high-energy electron diffraction is calculated in the form of an absorptive contribution to the atomic form factor. To do this, the Einstein model of lattice vibrations is used, with isotropic Debye-Waller factors. The absorptive form factors are calculated as a function of scattering vector s and temperature factor M on a grid which enables polynomial interpolation of the results to be accurate to better than 2% for much of the ranges 0≤Ms 2 ≤6 and 0≤M≤2 A 2 . The computed values, together with an interpolation routine, have been incorporated into a Fortran subroutine which calculates both the real and absorptive form factors for 54 atomic species. (orig.)

  18. Correlative light and immuno-electron microscopy of retinal tissue cryostat sections

    Science.gov (United States)

    Burgoyne, Thomas; Lane, Amelia; Laughlin, William E.; Cheetham, Michael E.

    2018-01-01

    Correlative light-electron microscopy (CLEM) is a powerful technique allowing localisation of specific macromolecules within fluorescence microscopy (FM) images to be mapped onto corresponding high-resolution electron microscopy (EM) images. Existing methods are applicable to limited sample types and are technically challenging. Here we describe novel methods to perform CLEM and immuno-electron microscopy (iEM) on cryostat sections utilising the popular FM embedding solution, optimal cutting temperature (OCT) compound. Utilising these approaches, we have (i) identified the same phagosomes by FM and EM in the retinal pigment epithelium (RPE) of retinal tissue (ii) shown the correct localisation of rhodopsin on photoreceptor outer segment disc like-structures in iPSC derived optic cups and (iii) identified a novel interaction between peroxisomes and melanosomes as well as phagosomes in the RPE. These data show that cryostat sections allow easy characterisation of target macromolecule localisation within tissue samples, thus providing a substantial improvement over many conventional methods that are limited to cultured cells. As OCT embedding is routinely used for FM this provides an easily accessible and robust method for further analysis of existing samples by high resolution EM. PMID:29315318

  19. Use of fibroblast growth factor 2 for expansion of chondrocytes and tissue engineering

    Science.gov (United States)

    Vunjak-Novakovic, Gordana (Inventor); Martin, Ivan (Inventor); Freed, Lisa E. (Inventor); Langer, Robert (Inventor)

    2003-01-01

    The present invention provides an improved method for expanding cells for use in tissue engineering. In particular the method provides specific biochemical factors to supplement cell culture medium during the expansion process in order to reproduce events occurring during embryonic development with the goal of regenerating tissue equivalents that resemble natural tissues both structurally and functionally. These specific biochemical factors improve proliferation of the cells and are capable of de-differentiation mature cells isolated from tissue so that the differentiation potential of the cells is preserved. The bioactive molecules also maintain the responsiveness of the cells to other bioactive molecules. Specifically, the invention provides methods for expanding chondrocytes in the presence of fibroblast growth factor 2 for use in regeneration of cartilage tissue.

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

    DEFF Research Database (Denmark)

    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...... pathway inhibitor (TFPI) may be deleterious. METHODS: We measured factor VII clotting activity, activated factor VII, and concentrations of factor VII and TFPI during 12 months in healthy post-menopausal women randomized to: (i). cyclic oral estrogen/progestin (n = 25); (ii). long-cycle oral estrogen......: No variations were observed in the reference group. There was a substantial decrease in TFPI concentrations in the HRT groups irrespective of the type of progestin. In women receiving long-cycle treatment, all factor VII measures increased during the unopposed estrogen periods, and the increase was reversed...

  1. Detection of free radicals in γ-irradiated seasnail hard tissues by electron paramagnetic resonance

    International Nuclear Information System (INIS)

    Koeseoglu, Rahmi; Koeksal, Fevzi

    2003-01-01

    Gamma-irradiated seasnail (from family of Helix lukortium) hard tissues (CaCO 3 ) were investigated by electron paramagnetic resonance (EPR) at room temperature. The radicals produced by γ-irradiation in seasnail were attributed to orthorhombic C · O 2 - , freely rotating C · O 2 - , orthorhombic C · O 3 - , axial C · O 3 - , and axial C · O 3 3- free radicals. Unirradiated seasnail hard tissues also feature Mn 2+ ions in their EPR spectra. The hyperfine values were determined for the 13 C nucleus in the orthorhombic C · O 2 - and axial C · O 3 3- free radicals and for the manganese impurity ions. The g values of all the free radicals have been measured. The results were compared with the literature data for similar defects

  2. Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification

    Science.gov (United States)

    Bertazzo, Sergio; Gentleman, Eileen; Cloyd, Kristy L.; Chester, Adrian H.; Yacoub, Magdi H.; Stevens, Molly M.

    2013-06-01

    The accumulation of calcified material in cardiovascular tissue is thought to involve cytochemical, extracellular matrix and systemic signals; however, its precise composition and nanoscale architecture remain largely unexplored. Using nano-analytical electron microscopy techniques, we examined valves, aortae and coronary arteries from patients with and without calcific cardiovascular disease and detected spherical calcium phosphate particles, regardless of the presence of calcific lesions. We also examined lesions after sectioning with a focused ion beam and found that the spherical particles are composed of highly crystalline hydroxyapatite that crystallographically and structurally differs from bone mineral. Taken together, these data suggest that mineralized spherical particles may play a fundamental role in calcific lesion formation. Their ubiquitous presence in varied cardiovascular tissues and from patients with a spectrum of diseases further suggests that lesion formation may follow a common process. Indeed, applying materials science techniques to ectopic and orthotopic calcification has great potential to lend critical insights into pathophysiological processes underlying calcific cardiovascular disease.

  3. Gas electron multiplier (GEM) operation with tissue-equivalent gases at various pressures

    International Nuclear Information System (INIS)

    Farahmand, M.; Bos, A.J.J.; Eijk, C.W.E. van

    2003-01-01

    We have studied the operation of two different Gas Electron Multiplier (GEM) structures in both methane and propane based Tissue-Equivalent (TE) gases at different pressures varying from 0.1 to 1 atm. This work was motivated to explore the possibility of using a GEM for a new type of Tissue Equivalent Proportional Counter. In methane based TE gas, a maximum safe GEM gain of 1.5x10 3 has been reached while in propane based TE gas this is 6x10 3 . These maxima have been reached at different gas pressures depending on GEM structure and TE gas. Furthermore, we observed a decrease of the GEM gain in time before it becomes stable. Charge up/polarisation effects can explain this

  4. Angiogenesis is not impaired in connective tissue growth factor (CTGF) knock-out mice

    NARCIS (Netherlands)

    Kuiper, Esther J.; Roestenberg, Peggy; Ehlken, Christoph; Lambert, Vincent; van Treslong-de Groot, Henny Bloys; Lyons, Karen M.; Agostini, Hans-Jürgen T.; Rakic, Jean-Marie; Klaassen, Ingeborg; van Noorden, Cornelis J. F.; Goldschmeding, Roel; Schlingemann, Reinier O.

    2007-01-01

    Connective tissue growth factor (CTGF) is a member of the CCN family of growth factors. CTGF is important in scarring, wound healing, and fibrosis. It has also been implicated to play a role in angiogenesis, in addition to vascular endothelial growth factor (VEGF). In the eye, angiogenesis and

  5. Imaging of early conifer embryogenic tissues with the environmental scanning electron microscope

    Czech Academy of Sciences Publication Activity Database

    Neděla, Vilém; Hřib, J.; Vooková, B.

    2012-01-01

    Roč. 56, č. 3 (2012), s. 595-598 ISSN 0006-3134 R&D Projects: GA ČR GAP102/10/1410 Institutional support: RVO:68081731 Keywords : Abies alba * A. numidica * extracellular matrix Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 1.692, year: 2012

  6. Factors Influencing Acceptance of Electronic Health Records in Hospitals

    OpenAIRE

    Wilkins, Melinda A

    2009-01-01

    The study's aim was to examine factors that may influence health information managers in the adoption of electronic health records. The Technology Acceptance Model (TAM) served as theoretical foundation for this quantitative study. Hospital health information managers in Arkansas were queried as to the constructs of perceived usefulness, perceived ease of use, and behavior intention. The study population comprised 94 health information managers with a return rate of 74.5 percent. One manager ...

  7. Electronic cigarettes: incorporating human factors engineering into risk assessments

    OpenAIRE

    Yang, Ling; Rudy, Susan F; Cheng, James M; Durmowicz, Elizabeth L

    2014-01-01

    Objective A systematic review was conducted to evaluate the impact of human factors (HF) on the risks associated with electronic cigarettes (e-cigarettes) and to identify research gaps. HF is the evaluation of human interactions with products and includes the analysis of user, environment and product complexity. Consideration of HF may mitigate known and potential hazards from the use and misuse of a consumer product, including e-cigarettes. Methods Five databases were searched through Januar...

  8. Market Makers' Recognition of Key Success Factors in Electronic Marketplaces

    Directory of Open Access Journals (Sweden)

    Rosemary Stockdale

    2003-05-01

    Full Text Available This study examines the recognition and use of critical success factors by market makers in electronic marketplaces. A content analysis of e-marketplace websites enabled an examination of how these factors have been incorporated into marketplace sites. Evidence of market makers’ awareness of the success factors was found in all the sites although there remain questions and issues to be addressed. Awareness of the need for critical mass and privacy were very evident, but the key factors of security, technological infrastructure and neutrality were identified as areas of concern. Evidence of an awareness of the importance of trust by market makers was found, but more effective signalling of trust to buyers and sellers within the marketplaces is required.

  9. Electron fluence correction factors for various materials in clinical electron beams

    International Nuclear Information System (INIS)

    Olivares, M.; Blois, F. de; Podgorsak, E.B.; Seuntjens, J.P.

    2001-01-01

    Relative to solid water, electron fluence correction factors at the depth of dose maximum in bone, lung, aluminum, and copper for nominal electron beam energies of 9 MeV and 15 MeV of the Clinac 18 accelerator have been determined experimentally and by Monte Carlo calculation. Thermoluminescent dosimeters were used to measure depth doses in these materials. The measured relative dose at d max in the various materials versus that of solid water, when irradiated with the same number of monitor units, has been used to calculate the ratio of electron fluence for the various materials to that of solid water. The beams of the Clinac 18 were fully characterized using the EGS4/BEAM system. EGSnrc with the relativistic spin option turned on was used to optimize the primary electron energy at the exit window, and to calculate depth doses in the five phantom materials using the optimized phase-space data. Normalizing all depth doses to the dose maximum in solid water stopping power ratio corrected, measured depth doses and calculated depth doses differ by less than ±1% at the depth of dose maximum and by less than 4% elsewhere. Monte Carlo calculated ratios of doses in each material to dose in LiF were used to convert the TLD measurements at the dose maximum into dose at the center of the TLD in the phantom material. Fluence perturbation correction factors for a LiF TLD at the depth of dose maximum deduced from these calculations amount to less than 1% for 0.15 mm thick TLDs in low Z materials and are between 1% and 3% for TLDs in Al and Cu phantoms. Electron fluence ratios of the studied materials relative to solid water vary between 0.83±0.01 and 1.55±0.02 for materials varying in density from 0.27 g/cm3 (lung) to 8.96 g/cm3 (Cu). The difference in electron fluence ratios derived from measurements and calculations ranges from -1.6% to +0.2% at 9 MeV and from -1.9% to +0.2% at 15 MeV and is not significant at the 1σ level. Excluding the data for Cu, electron fluence

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

    OpenAIRE

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  12. The influence of tethered epidermal growth factor on connective tissue progenitor colony formation

    OpenAIRE

    Marcantonio, Nicholas A.; Boehm, Cynthia A.; Rozic, Richard J.; Au, Ada; Wells, Alan; Muschler, George F.; Griffith, Linda G.

    2009-01-01

    Strategies to combine aspirated marrow cells with scaffolds to treat connective tissue defects are gaining increasing clinical attention and use. In situations such as large defects where initial survival and proliferation of transplanted connective tissue progenitors (CTPs) are limiting, therapeutic outcomes might be improved by using the scaffold to deliver growth factors that promote the early stages of cell function in the graft. Signaling by the epidermal growth factor receptor (EGFR) pl...

  13. Trefoil factors in saliva and gingival tissues of patients with chronic periodontitis

    DEFF Research Database (Denmark)

    Chaiyarit, Ponlatham; Chayasadom, Anek; Wara-Aswapati, Nawarat

    2012-01-01

    BACKGROUND: Trefoil factors (TFFs) are secreted molecules that are involved in cytoprotection against tissue damage and the immune response. TFFs have been detected in saliva and oral tissues, but their clinical significance has never been investigated in patients with chronic periodontitis....... The objective of this study is to determine whether TFF expression in saliva and gingival tissues is associated with periodontal pathology. METHODS: Saliva and gingival tissue samples were collected from 25 non-periodontitis individuals and 25 patients with chronic periodontitis (CP). Enzyme...... observed in patients with CP (P = 0.003 and P periodontal pathology and number of Porphyromonas gingivalis...

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

    DEFF Research Database (Denmark)

    Christensen, Anders; Kiss, Katalin; Lelkaitis, Giedrius

    2017-01-01

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

  15. A First Step in De Novo Synthesis of a Living Pulp Tissue Replacement Using Dental Pulp MSCs and Tissue Growth Factors, Encapsulated within a Bioinspired Alginate Hydrogel.

    Science.gov (United States)

    Bhoj, Manasi; Zhang, Chengfei; Green, David W

    2015-07-01

    A living, self-supporting pulp tissue replacement in vitro and for transplantation is an attractive yet unmet bioengineering challenge. Our aim is to create 3-dimensional alginate-based microenvironments that replicate the shape of gutta-percha and comprise key elements for the proliferation of progenitor cells and the release of growth factors. An RGD-bearing alginate framework was used to encapsulate dental pulp stem cells and human umbilical vein endothelial cells in a ratio of 1:1. The alginate hydrogel also retained and delivered 2 key growth factors, vascular endothelial growth factor-121 and fibroblast growth factor, in a sufficient amount to induce proliferation. A method was then devised to replicate the shape of gutta-percha using RGD alginate within a custom-made mold of thermoresponsive N-isopropylacrylamide. Plugs of alginate containing different permutations of growth factor-based encapsulates were tested and evaluated for viability, proliferation, and release kinetics between 1 and 14 days. According to scanning electron microscopic and confocal microscopic observations, the encapsulated human endothelial cells and dental pulp stem cell distribution were frequent and extensive throughout the length of the construct. There were also high levels of viability in all test environments. Furthermore, cell proliferation was higher in the growth factor-based groups. Growth factor release kinetics also showed significant differences between them. Interestingly, the combination of vascular endothelial growth factor and fibroblast growth factor synergize to significantly up-regulate cell proliferation. RGD-alginate scaffolds can be fabricated into shapes to fill the pulp space by simple templating. The addition of dual growth factors to cocultures of stem cells within RGD-alginate scaffolds led to the creation of microenvironments that significantly enhance the proliferation of dental pulp stem cell/human umbilical vein endothelial cell combinations. Copyright

  16. Increased and correlated expression of connective tissue growth factor and transforming growth factor beta 1 in surgically removed periodontal tissues with chronic periodontitis.

    Science.gov (United States)

    Mize, T W; Sundararaj, K P; Leite, R S; Huang, Y

    2015-06-01

    Both gingival tissue destruction and regeneration are associated with chronic periodontitis, although the former overwhelms the latter. Studies have shown that transforming growth factor beta 1 (TGF-β1), a growth factor largely involved in tissue regeneration and remodeling, is upregulated in chronic periodontitis. However, the gingival expression of connective tissue growth factor (CTGF or CCN2), a TGF-β1-upregulated gene, in patients with periodontitis remains undetermined. Although both CTGF/CCN2 and TGF-b1 increase the production of extracellular matrix, they have many different biological functions. Therefore, it is important to delineate the impact of periodontitis on gingival CTGF/CCN2 expression. Periodontal tissue specimens were collected from seven individuals without periodontitis (group 1) and from 14 with periodontitis (group 2). The expression of CTGF and TGFβ1 mRNAs were quantified using real-time PCR. Analysis using the nonparametric Mann-Whitney U-test showed that the levels of expression of both CTGF/CCN2 and TGFβ1 mRNAs were significantly increased in individuals with periodontitis compared with individuals without periodontitis. Furthermore, analysis using a nonparametric correlation (Spearman r) test showed a positive correlation between TGFβ1 and CTGF/CCN2 mRNAs. The gingival expression levels of CTGF/CCN2 and TGFβ1 mRNAs in individuals with periodontitis are upregulated and correlated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. A probable risk factor of female breast cancer: study on benign and malignant breast tissue samples.

    Science.gov (United States)

    Rehman, Sohaila; Husnain, Syed M

    2014-01-01

    The study reports enhanced Fe, Cu, and Zn contents in breast tissues, a probable risk factor of breast cancer in females. Forty-one formalin-fixed breast tissues were analyzed using atomic absorption spectrophotometry. Twenty malignant, six adjacent to malignant and 15 benign tissues samples were investigated. The malignant tissues samples were of grade 11 and type invasive ductal carcinoma. The quantitative comparison between the elemental levels measured in the two types of specimen (benign and malignant) tissues (removed after surgery) suggests significant elevation of these metals (Fe, Cu, and Zn) in the malignant tissue. The specimens were collected just after mastectomy of women aged 19 to 59 years from the hospitals of Islamabad and Rawalpindi, Pakistan. Most of the patients belong to urban areas of Pakistan. Findings of study depict that these elements have a promising role in the initiation and development of carcinoma as consistent pattern of elevation for Fe, Cu, and Zn was observed. The results showed the excessive accumulation of Fe (229 ± 121 mg/L) in malignant breast tissue samples of patients (p factor of breast cancer. In order to validate our method of analysis, certified reference material muscle tissue lyophilized (IAEA) MA-M-2/TM was analyzed for metal studied. Determined concentrations were quite in good agreement with certified levels. Asymmetric concentration distribution for Fe, Cu, and Zn was observed in both malignant and benign tissue samples.

  18. Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil)

    2012-07-15

    Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: Black-Right-Pointing-Pointer Electron density of normal and neoplastic breast tissues was measured using Compton scattering. Black-Right-Pointing-Pointer Monochromatic synchrotron radiation was used to obtain the Compton scattering data. Black-Right-Pointing-Pointer The area of Compton peaks was used to determine the electron densities of samples. Black-Right-Pointing-Pointer Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. Black-Right-Pointing-Pointer Comparison with previous results showed differences smaller than 4%.

  19. Tissue-engineered cartilage: the crossroads of biomaterials, cells and stimulating factors.

    Science.gov (United States)

    Bhardwaj, Nandana; Devi, Dipali; Mandal, Biman B

    2015-02-01

    Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Gene therapy with growth factors for periodontal tissue engineering–A review

    Science.gov (United States)

    Gupta, Shipra; Mahendra, Aneet

    2012-01-01

    The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. A challenge faced by periodontal therapy is the predictable regeneration of periodontal tissues lost as a consequence of disease. Growth factors are critical to the development, maturation, maintenance and repair of oral tissues as they establish an extra-cellular environment that is conducive to cell and tissue growth. Tissue engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. The aim of this paper is to review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Various such materials have been formulated into devices that can be used as vehicles for delivery of cells, growth factors and DNA. Different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral and tooth supporting structure. Key words: Periodontal disease, gene therapy, regeneration, tissue repair, growth factors, tissue engineering. PMID:22143705

  1. Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors.

    Science.gov (United States)

    Orgeur, Mickael; Martens, Marvin; Leonte, Georgeta; Nassari, Sonya; Bonnin, Marie-Ange; Börno, Stefan T; Timmermann, Bernd; Hecht, Jochen; Duprez, Delphine; Stricker, Sigmar

    2018-03-29

    Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling of chick limb micromass cultures revealed a set of common genes regulated by all five transcription factors, which we describe as a connective tissue core expression set. This common core was enriched with genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created by the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development. © 2018. Published by The Company of Biologists Ltd.

  2. Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

    Science.gov (United States)

    Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

    2016-03-01

    Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

  3. Tissue Banking, Bioinformatics, and Electronic Medical Records: The Front-End Requirements for Personalized Medicine

    Science.gov (United States)

    Suh, K. Stephen; Sarojini, Sreeja; Youssif, Maher; Nalley, Kip; Milinovikj, Natasha; Elloumi, Fathi; Russell, Steven; Pecora, Andrew; Schecter, Elyssa; Goy, Andre

    2013-01-01

    Personalized medicine promises patient-tailored treatments that enhance patient care and decrease overall treatment costs by focusing on genetics and “-omics” data obtained from patient biospecimens and records to guide therapy choices that generate good clinical outcomes. The approach relies on diagnostic and prognostic use of novel biomarkers discovered through combinations of tissue banking, bioinformatics, and electronic medical records (EMRs). The analytical power of bioinformatic platforms combined with patient clinical data from EMRs can reveal potential biomarkers and clinical phenotypes that allow researchers to develop experimental strategies using selected patient biospecimens stored in tissue banks. For cancer, high-quality biospecimens collected at diagnosis, first relapse, and various treatment stages provide crucial resources for study designs. To enlarge biospecimen collections, patient education regarding the value of specimen donation is vital. One approach for increasing consent is to offer publically available illustrations and game-like engagements demonstrating how wider sample availability facilitates development of novel therapies. The critical value of tissue bank samples, bioinformatics, and EMR in the early stages of the biomarker discovery process for personalized medicine is often overlooked. The data obtained also require cross-disciplinary collaborations to translate experimental results into clinical practice and diagnostic and prognostic use in personalized medicine. PMID:23818899

  4. Calculation of dose-rate conversion factors for external exposure to photons and electrons

    International Nuclear Information System (INIS)

    Kocher, D.C.

    1978-01-01

    Methods are presented for the calculation of dose-rate conversion factors for external exposure to photon and electron radiation from radioactive decay. A dose-rate conversion factor is defined as the dose-equivalent rate per unit radionuclide concentration. Exposure modes considered are immersion in contaminated air, immersion in contaminated water, and irradiation from a contaminated ground surface. For each radiation type and exposure mode, dose-rate conversion factors are derived for tissue-equivalent material at the body surface of an exposed individual. In addition, photon dose-rate conversion factors are estimated for 22 body organs. The calculations are based on the assumption that the exposure medium is infinite in extent and that the radionuclide concentration is uniform. The dose-rate conversion factors for immersion in contaminated air and water then follow from the requirement that all of the energy emitted in the radioactive decay is absorbed in the infinite medium. Dose-rate conversion factors for ground-surface exposure are calculated at a reference location above a smooth, infinite plane using the point-kernel integration method and known specific absorbed fractions for photons and electrons in air

  5. A hypothesis: factor VII governs clot formation, tissue repair and apoptosis.

    Science.gov (United States)

    Coleman, Lewis S

    2007-01-01

    A hypothesis: thrombin is a "Universal Enzyme of Energy Transduction" that employs ATP energy in flowing blood to activate biochemical reactions and cell effects in both hemostasis and tissue repair. All cells possess PAR-1 (thrombin) receptors and are affected by thrombin elevations, and thrombin effects on individual cell types are determined by their unique complement of PAR-1 receptors. Disruption of the vascular endothelium (VE) activates a tissue repair mechanism (TRM) consisting of the VE, tissue factor (TF), and circulating Factors VII, IX and X that governs localized thrombin elevations to activate clot formation and cellular effects that repair tissue damage. The culmination of the repair process occurs with the restoration of the VE followed by declines in thrombin production that causes Apoptosis ("programmed cell death") in wound-healing fibroblasts, which functions as a mechanism to draw wound edges together. The location and magnitude of TRM activity governs the location and magnitude of Factor VIII activity and clot formation, but the large size of Factor VIII prevents it from penetrating the clot formed by its activity, so that its effects are self-limiting. Factors VII, IX and X function primarily as tissue repair enzymes, while Factor VIII and Factor XIII are the only serine protease enzymes in the "Coagulation Cascade" that are exclusively associated with hemostasis.

  6. Perceived Attributes of Factors Influencing Consumers’ Engagement with Electronic Banking

    Directory of Open Access Journals (Sweden)

    Taiwo Adewale Muritala

    2012-08-01

    Full Text Available This study intends to critically analyze the relationship between perceived attributes as factors and consumers’ engagement with electronic banking technology. A survey method was used to gather data from 200 secondary school teachers from five selected local government in South-Western part of Nigeria namely; Ibadan North, Egbeda, Ido, Ibadan North-East and Ibadan North-West Local government. Data was collected with a structured questionnaire and analyzed with several descriptive statistics to identify consumers’ engagement in electronic banking technology in Nigeria. The results of the study therefore reveals that the most common influential factors hindering consumers’ adoption of electronic banking in Nigeria are relative advantage of economic gains and non-economic gains, social character, communication behavior, trialability as well as observability. Hence, it therefore recommends that the banks should create channels through which customers’ awareness will be enhanced and employ IT trained personnel to monitor and report any fraudulent transaction in order to secure customers’ trust on safety risk/security.

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

    Science.gov (United States)

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

    1998-04-15

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

  8. Assessment of doses caused by electrons in thin layers of tissue-equivalent materials, using MCNP.

    Science.gov (United States)

    Heide, Bernd

    2013-10-01

    Absorbed doses caused by electron irradiation were calculated with Monte Carlo N-Particle transport code (MCNP) for thin layers of tissue-equivalent materials. The layers were so thin that the calculation of energy deposition was on the border of the scope of MCNP. Therefore, in this article application of three different methods of calculation of energy deposition is discussed. This was done by means of two scenarios: in the first one, electrons were emitted from the centre of a sphere of water and also recorded in that sphere; and in the second, an irradiation with the PTB Secondary Standard BSS2 was modelled, where electrons were emitted from an (90)Sr/(90)Y area source and recorded inside a cuboid phantom made of tissue-equivalent material. The speed and accuracy of the different methods were of interest. While a significant difference in accuracy was visible for one method in the first scenario, the difference in accuracy of the three methods was insignificant for the second one. Considerable differences in speed were found for both scenarios. In order to demonstrate the need for calculating the dose in thin small zones, a third scenario was constructed and simulated as well. The third scenario was nearly equal to the second one, but a pike of lead was assumed to be inside the phantom in addition. A dose enhancement (caused by the pike of lead) of ∼113 % was recorded for a thin hollow cylinder at a depth of 0.007 cm, which the basal-skin layer is referred to in particular. Dose enhancements between 68 and 88 % were found for a slab with a radius of 0.09 cm for all depths. All dose enhancements were hardly noticeable for a slab with a cross-sectional area of 1 cm(2), which is usually applied to operational radiation protection.

  9. FACTORS INLFUENCING THE ADOPTION OF ELECTRONIC WORD OF MOUTH

    Directory of Open Access Journals (Sweden)

    Mihaela ABĂLĂESEI

    2015-12-01

    Full Text Available Web-based technologies have been in a continuous state of growth, especially in the last decade, which also brought better and higher Internet speed. This has led to an increased number of opportunities for people to get involved in electronic word of mouth (e-WOM communication. E-WOM is a new means of information sharing, allowing users to be inter-connected constantly, regardless of their time zone. Because of this unique quality, e-WOM has been identified as one of the key factors affecting online sales. However, there is little known about this phenomenon. Even if the literature has approached this topic from various angles, there is still a lot of uncertainty surrounding electronic word of mouth. One of the key research questions is targeted at factors which influence people in actively engaging in creating or receiving e-WOM. With this in mind, this article provides a general overview of the key factors analyzed in the literature, which determine adoption of e-WOM by online consumers.

  10. Grinding and polishing instead of sectioning for the tissue samples with a graft: Implications for light and electron microscopy.

    Science.gov (United States)

    Mukhamadiyarov, Rinat A; Sevostyanova, Victoria V; Shishkova, Daria K; Nokhrin, Andrey V; Sidorova, Olga D; Kutikhin, Anton G

    2016-06-01

    A broad use of the graft replacement requires a detailed investigation of the host-graft interaction, including both histological examination and electron microscopy. A high quality sectioning of the host tissue with a graft seems to be complicated; in addition, it is difficult to examine the same tissue area by both of the mentioned microscopy techniques. To solve these problems, we developed a new technique of epoxy resin embedding with the further grinding, polishing, and staining. Graft-containing tissues prepared by grinding and polishing preserved their structure; however, sectioning frequently required the explantation of the graft and led to tissue disintegration. Moreover, stained samples prepared by grinding and polishing may then be assessed by both light microscopy and backscattered scanning electron microscopy. Therefore, grinding and polishing outperform sectioning when applied to the tissues with a graft. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Mitochondrial biogenesis in brown adipose tissue is associated with differential expression of transcription regulatory factors

    Czech Academy of Sciences Publication Activity Database

    Villena, J. A.; Carmona, M. C.; Rodriguez de la Concepción, M.; Rossmeisl, Martin; Vinas, O.; Mampel, T.; Iglesias, R.; Giralt, M.; Villarroya, F.

    2002-01-01

    Roč. 59, č. 11 (2002), s. 1934-1944 ISSN 1420-682X Grant - others:Ministerio de Ciencia y Tecnología (ES) PM98.0188 Institutional research plan: CEZ:AV0Z5011922 Keywords : brown adipose tissue * mitochondria * transcription factors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.259, year: 2002

  12. Safer electronic health records safety assurance factors for EHR resilience

    CERN Document Server

    Sittig, Dean F

    2015-01-01

    This important volume provide a one-stop resource on the SAFER Guides along with the guides themselves and information on their use, development, and evaluation. The Safety Assurance Factors for EHR Resilience (SAFER) guides, developed by the editors of this book, identify recommended practices to optimize the safety and safe use of electronic health records (EHRs). These guides are designed to help organizations self-assess the safety and effectiveness of their EHR implementations, identify specific areas of vulnerability, and change their cultures and practices to mitigate risks.This book pr

  13. Factors promoting increased rate of tissue regeneration: the zebrafish fin as a tool for examining tissue engineering design concepts.

    Science.gov (United States)

    Boominathan, Vijay P; Ferreira, Tracie L

    2012-12-01

    Student interest in topics of tissue engineering is increasing exponentially as the number of universities offering programs in bioengineering are on the rise. Bioengineering encompasses all of the STEM categories: Science, Technology, Engineering, and Math. Inquiry-based learning is one of the most effective techniques for promoting student learning and has been demonstrated to have a high impact on learning outcomes. We have designed program outcomes for our bioengineering program that require tiered activities to develop problem solving skills, peer evaluation techniques, and promote team work. While it is ideal to allow students to ask unique questions and design their own experiments, this can be difficult for instructors to have reagents and supplies available for a variety of activities. Zebrafish can be easily housed, and multiple variables can be tested on a large enough group to provide statistical value, lending them well to inquiry-based learning modules. We have designed a laboratory activity that takes observation of fin regeneration to the next level: analyzing conditions that may impact regeneration. Tissue engineers seek to define the optimum conditions to grow tissue for replacement parts. The field of tissue engineering is likely to benefit from understanding natural mechanisms of regeneration and the factors that influence the rate of regeneration. We have outlined the results of varying temperature on fin regeneration and propose other inquiry modules such as the role of pH in fin regeneration. Furthermore, we have provided useful tools for developing critical thinking and peer review of research ideas, assessment guidelines, and grading rubrics for the activities associated with this exercise.

  14. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

    Directory of Open Access Journals (Sweden)

    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  15. Investigating important factors influencing electronic banking for export development

    Directory of Open Access Journals (Sweden)

    Vahid Abbas Zadeh

    2014-01-01

    Full Text Available Export is one of the most important indicators of a growing economy and it is the primary source of reaching sustainable growth on the market. This paper presents an empirical study to determine important factors influencing electronic banking in export development of Iranian organizations. The proposed study designs a questionnaire and distributes it among some regular customers who do internet banking with Parsian bank in city of Tehran, Iran. Cronbach alpha is calculated as 0.82, which is well above the minimum desirable limit of 0.70. In addition, Kaiser-Meyer-Olkin Measure of Sampling Adequacy and Approx. Chi-Square are 0.71 and 1955 with Sig. = 0.000, respectively. Using principal component analysis, the study has detected six factors including customer’s information, building trust, secure internet access, having good internet infrastructure and internet users.

  16. Diet-tissue stable isotope (Δ(13)C and Δ(15)N) discrimination factors for multiple tissues from terrestrial reptiles.

    Science.gov (United States)

    Steinitz, Ronnie; Lemm, Jeffrey M; Pasachnik, Stesha A; Kurle, Carolyn M

    2016-01-15

    Stable isotope analysis is a powerful tool for reconstructing trophic interactions to better understand drivers of community ecology. Taxon-specific stable isotope discrimination factors contribute to the best use of this tool. We determined the first Δ(13)C and Δ(15)N values for Rock Iguanas (Cyclura spp.) to better understand isotopic fractionation and estimate wild reptile foraging ecology. The Δ(13)C and Δ(15)N values between diet and skin, blood, and scat were determined from juvenile and adult iguanas held for 1 year on a known diet. We measured relationships between iguana discrimination factors and size/age and quantified effects of lipid extraction and acid treatment on stable isotope values from iguana tissues. Isotopic and elemental compositions were determined by Dumas combustion using an elemental analyzer coupled to an isotope ratio mass spectrometer using standards of known composition. The Δ(13)C and Δ(15)N values ranged from -2.5 to +6.5‰ and +2.2 to +7.5‰, respectively, with some differences among tissues and between juveniles and adults. The Δ(13)C values from blood and skin differed among species, but not the Δ(15)N values. The Δ(13)C values from blood and skin and Δ(15)N values from blood were positively correlated with size/age. The Δ(13)C values from scat were negatively correlated with size (not age). Treatment with HCl (scat) and lipid extraction (skin) did not affect the isotope values. These results should aid in the understanding of processes driving stable carbon and nitrogen isotope discrimination factors in reptiles. We provide estimates of Δ(13)C and Δ(15)N values and linear relationships between iguana size/age and discrimination factors for the best interpretation of wild reptile foraging ecology. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Determination of nitrosourea compounds in brain tissue by gas chromatography and electron capture detection.

    Science.gov (United States)

    Hassenbusch, S J; Colvin, O M; Anderson, J H

    1995-07-01

    A relatively simple, high-sensitivity gas chromatographic assay is described for nitrosourea compounds, such as BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] and MeCCNU [1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea], in small biopsy samples of brain and other tissues. After extraction with ethyl acetate, secondary amines in BCNU and MeCCNU are derivatized with trifluoroacetic anhydride. Compounds are separated and quantitated by gas chromatography using a capillary column with temperature programming and an electron capture detector. Standard curves of BCNU indicate a coefficient of variance of 0.066 +/- 0.018, a correlation coefficient of 0.929, and an extraction efficiency from whole brain of 68% with a minimum detectable amount of 20 ng in 5-10 mg samples. The assay has been facile and sensitive in over 1000 brain biopsy specimens after intravenous and intraarterial infusions of BCNU.

  18. Electronic portfolio motivational factors from students’ perspective: A qualitative study

    Directory of Open Access Journals (Sweden)

    Rokhsareh Mobarhan

    2015-06-01

    Full Text Available Electronic portfolio (e-Portfolio is known as an electronic learning record which collects the learning evidences, reflections and accomplishments. In fact, it tells the story of learning achievements. It is an important tool for students, lecturers, administrators and faculties to monitor the learning outcomes. Similarly to other technologies, e-Portfolio is also considered successful, if it is used by students continuously. Previous researches showed the importance of intrinsic and extrinsic motivations in using any technologies. However, lack of motivation has been a major concern for developing any successful online learning environments. The aim of this paper is to explain the e-Portfolio motivational factors from students’ perspective. Interviews are conducted with students from one university in Malaysia in order to get better understanding of the phenomena. The target interviewees are bachelor students chosen from different faculties. Based on the qualitative content analysis of the interviews, the motivational factors affecting the continuous use of e-portfolio are coded in eight themes and then they categorized in four main groups of individual, system, social and environmental characteristics. Finally they are classified into intrinsic or extrinsic motivations.

  19. [Expression of connective tissue growth factor in colorectal cancer and its association with prognosis].

    Science.gov (United States)

    Sun, Zheng; Yang, Ping; Liang, Li-yuan; Zhang, Tong; Zhang, Wei-jian; Cao, Jie

    2012-11-01

    To investigate the expression of connective tissue growth factor (CTGF) in colorectal cancer(CRC) and its association with clinicopathologic parameters and overall survival rate. Fresh tumor tissues and matched distal normal colon tissues were collected from 92 patients diagnosed as CRC by surgical operation. The expression level of CTGF mRNA was quantified by quantitative reverse transcription PCR. Thirty out of 92 pairs of tissue specimens were selected randomly to detect CTGF protein by immunohistochemistry. All the cases were followed up to identify prognostic factors for survival. CTGF mRNA expression was up-regulated in CRC. The positive rate of CTGF protein expression tissues (73.3%) was significantly higher than that in the corresponding normal tissues (23.3%, Ptissues was classified into high and low expression groups. The 5-year cumulative survival rate was lower in patients with low CTGF expression (29.3%) as compared to those with high CTGF expressions (68.3%) (P<0.01). Cox regression analysis revealed that the relative expression level of CTGF was independent factor of overall survival (RR=2.960, 95%CI:1.491-1.587, P<0.01). ROC curve analysis showed that sensitivity and specificity of CTGF mRNA expression for prediction of 5-year survival were 64.9% and 74.5%, respectively. The aberrant expression of CTGF is associated with the malignant biological behaviors of CRC. Low expression of CTGF is associated with worse prognosis of CRC.

  20. COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

    International Nuclear Information System (INIS)

    Asting, Annika Gustafsson; Carén, Helena; Andersson, Marianne; Lönnroth, Christina; Lagerstedt, Kristina; Lundholm, Kent

    2011-01-01

    Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue

  1. COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

    Directory of Open Access Journals (Sweden)

    Lagerstedt Kristina

    2011-06-01

    Full Text Available Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4 showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3 were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

  2. Risk factors for pedicled flap necrosis in hand soft tissue reconstruction: a multivariate logistic regression analysis.

    Science.gov (United States)

    Gong, Xu; Cui, Jianli; Jiang, Ziping; Lu, Laijin; Li, Xiucun

    2018-03-01

    Few clinical retrospective studies have reported the risk factors of pedicled flap necrosis in hand soft tissue reconstruction. The aim of this study was to identify non-technical risk factors associated with pedicled flap perioperative necrosis in hand soft tissue reconstruction via a multivariate logistic regression analysis. For patients with hand soft tissue reconstruction, we carefully reviewed hospital records and identified 163 patients who met the inclusion criteria. The characteristics of these patients, flap transfer procedures and postoperative complications were recorded. Eleven predictors were identified. The correlations between pedicled flap necrosis and risk factors were analysed using a logistic regression model. Of 163 skin flaps, 125 flaps survived completely without any complications. The pedicled flap necrosis rate in hands was 11.04%, which included partial flap necrosis (7.36%) and total flap necrosis (3.68%). Soft tissue defects in fingers were noted in 68.10% of all cases. The logistic regression analysis indicated that the soft tissue defect site (P = 0.046, odds ratio (OR) = 0.079, confidence interval (CI) (0.006, 0.959)), flap size (P = 0.020, OR = 1.024, CI (1.004, 1.045)) and postoperative wound infection (P < 0.001, OR = 17.407, CI (3.821, 79.303)) were statistically significant risk factors for pedicled flap necrosis of the hand. Soft tissue defect site, flap size and postoperative wound infection were risk factors associated with pedicled flap necrosis in hand soft tissue defect reconstruction. © 2017 Royal Australasian College of Surgeons.

  3. Method to characterize inorganic particulates in lung tissue biopsies using field emission scanning electron microscopy

    Science.gov (United States)

    Lowers, Heather; Breit, George N.; Strand, Matthew; Pillers, Renee M.; Meeker, Gregory P.; Todorov, Todor I.; Plumlee, Geoffrey S.; Wolf, Ruth E.; Robinson, Maura; Parr, Jane; Miller, Robert J.; Groshong, Steve; Green, Francis; Rose, Cecile

    2018-01-01

    Humans accumulate large numbers of inorganic particles in their lungs over a lifetime. Whether this causes or contributes to debilitating disease over a normal lifespan depends on the type and concentration of the particles. We developed and tested a protocol for in situ characterization of the types and distribution of inorganic particles in biopsied lung tissue from three human groups using field emission scanning electron microscopy (FE-SEM) combined with energy dispersive spectroscopy (EDS). Many distinct particle types were recognized among the 13 000 particles analyzed. Silica, feldspars, clays, titanium dioxides, iron oxides and phosphates were the most common constituents in all samples. Particles were classified into three general groups: endogenous, which form naturally in the body; exogenic particles, natural earth materials; and anthropogenic particles, attributed to industrial sources. These in situ results were compared with those using conventional sodium hypochlorite tissue digestion and particle filtration. With the exception of clays and phosphates, the relative abundances of most common particle types were similar in both approaches. Nonetheless, the digestion/filtration method was determined to alter the texture and relative abundances of some particle types. SEM/EDS analysis of digestion filters could be automated in contrast to the more time intensive in situ analyses.

  4. Dosimetric evaluation in heterogeneous tissue of anterior electron beam irradiation for treatment of retinoblastoma

    International Nuclear Information System (INIS)

    Kirsner, S.M.; Hogstrom, K.R.; Kurup, R.G.; Moyers, M.F.

    1987-01-01

    A dosimetric study of anterior electron beam irradiation for treatment of retinoblastoma was performed to evaluate the influence of tissue heterogeneities on the dose distribution within the eye and the accuracy of the dose calculated by a pencil beam algorithm. Film measurements were made in a variety of polystyrene phantoms and in a removable polystyrene eye incorporated into a tissue substitute phantom constructed from a human skull. Measurements in polystyrene phantoms were used to demonstrate the algorithm's ability to predict the effect of a lens block placed in the beam, as well as the eye's irregular surface shape. The eye phantom was used to measure dose distributions within the eye in both the sagittal and transverse planes in order to test the algorithm's ability to predict the dose distribution when bony heterogeneities are present. Results show (1) that previous treatment planning conclusions based on flat, uniform phantoms for central-axis depth dose are adequate; (2) that a three-dimensional heterogeneity correction is required for accurate dose calculations; and (3) that if only a two-dimensional heterogeneity correction is used in calculating the dose, it is more accurate for the sagittal than the transverse plane

  5. Transmission electron microscopy of heart and liver tissues from rats fed with gums arabic and tragacanth.

    Science.gov (United States)

    Anderson, D M; Ashby, P; Busuttil, A; Kempson, S A; Lawson, M E

    1984-04-01

    Transmission electron microscopy has been used to examine the ultrastructure of rat hearts and livers after diet supplementation with (a) 0, 0.5, 1.5, 2.5 and 3.5% (w/w) gum tragacanth (GT) for 91 days, (b) 0 and 1% GT for 5 days (c) 0, 1, 4 and 8% (w/w) gum arabic (GA) for 28 days. The preparation and scrutiny of the electron micrographs was undertaken by two independent teams of specialists. There were no detectable abnormalities in any of the organelles in the heart and liver specimens from any of the test animals and no inclusions nor other pathological changes were observed. All micrographs showed normal, healthy tissues; particular attention was given to the mitochondria in hepatocytes as they serve as sensitive indicators of the health and state of activity of cells. In addition, the data obtained from assays of the microsomal protein and cytochrome P-450 content of the livers showed that GA and GT did not cause inductive effects. These results do not support earlier suggestions, based on in vitro assays, that GA and GT cause changes in the function of rat heart and liver mitochondria and liver microsomes; however, they confirm a report by Zbinden that the ingestion of GT does not produce abnormalities in the cardiac function of rats.

  6. Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco.

    Science.gov (United States)

    Wojtukiewicz, Marek Z; Sierko, Ewa; Skalij, Piotr; Kamińska, Magda; Zimnoch, Lech; Brekken, Ralf A; Thorpe, Philip E

    2016-01-01

    Doxorubicin and docetaxel-based chemotherapy regimens used in breast cancer patients are associated with high risk of febrile neutropenia (FN). Granulocyte colony-stimulating factors (G-CSF) are recommended for both treating and preventing chemotherapy-induced neutropenia. Increased thrombosis incidence in G-CSF treated patients was reported; however, the underlying mechanisms remain unclear. The principal activator of blood coagulation in cancer is tissue factor (TF). It additionally contributes to cancer progression and stimulates angiogenesis. The main proangiogenic factor is vascular endothelial growth factor (VEGF). The aim of the study was to evaluate granulocyte-colony stimulating factor receptor (G-CSFR), tissue factor (TF) expression and vascular endothelial growth factor receptor (VEGF-R) bound VEGF in human breast cancer in loco. G-CSFR, TF and VEGFR bound VEGF (VEGF: VEGFR) were assessed in 28 breast cancer tissue samples. Immunohistochemical (IHC) methodologies according to ABC technique and double staining IHC procedure were employed utilizing antibodies against G-CSFR, TF and VEGF associated with VEGFR (VEGF: VEGFR). Expression of G-CSFR was demonstrated in 20 breast cancer tissue specimens (71%). In 6 cases (21%) the expression was strong (IRS 9-12). Strong expression of TF was observed in all investigated cases (100%). Moreover, expression of VEGF: VEGFR was visualized in cancer cells (IRS 5-8). No presence of G-CSFR, TF or VEGF: VEGFR was detected on healthy breast cells. Double staining IHC studies revealed co-localization of G-CSFR and TF, G-CSFR and VEGF: VEGFR, as well as TF and VEGF: VEGFR on breast cancer cells and ECs. The results of the study indicate that GCSFR, TF and VEGF: VEGFR expression as well as their co-expression might influence breast cancer biology, and may increase thromboembolic adverse events incidence.

  7. Market factors and electronic medical record adoption in medical practices.

    Science.gov (United States)

    Menachemi, Nir; Mazurenko, Olena; Kazley, Abby Swanson; Diana, Mark L; Ford, Eric W

    2012-01-01

    Previous studies identified individual or practice factors that influence practice-based physicians' electronic medical record (EMR) adoption. Less is known about the market factors that influence physicians' EMR adoption. The aim of this study was to explore the relationship between environmental market characteristics and physicians' EMR adoption. The Health Tracking Physician Survey 2008 and Area Resource File (2008) were combined and analyzed. Binary logistic regression was used to examine the relationship between three dimensions of the market environment (munificence, dynamism, and complexity) and EMR adoption controlling for several physician and practice characteristics. In a nationally representative sample of 4,720 physicians, measures of market dynamism including increases in unemployment, odds ratio (OR) = 0.95, 95% confidence interval (CI) [0.91, 0.99], or poverty rates, OR = 0.93, 95% CI [0.89, 0.96], were negatively associated with EMR adoption. Health maintenance organization penetration, OR = 3.01, 95% CI [1.49, 6.05], another measure of dynamism, was positively associated with EMR adoption. Physicians practicing in areas with a malpractice crisis, OR = 0.82, 95% CI [0.71, 0.94], representing environmental complexity, had lower EMR adoption rates. Understanding how market factors relate to practice-based physicians' EMR adoption can assist policymakers to better target limited resources as they work to realize the national goal of universal EMR adoption and meaningful use.

  8. Energy absorption buildup factors of human organs and tissues at energies and penetration depths relevant for radiotherapy and diagnostics

    DEFF Research Database (Denmark)

    Manohara, S. R.; Hanagodimath, S. M.; Gerward, Leif

    2011-01-01

    Energy absorption geometric progression (GP) fitting parameters and the corresponding buildup factors have been computed for human organs and tissues, such as adipose tissue, blood (whole), cortical bone, brain (grey/white matter), breast tissue, eye lens, lung tissue, skeletal muscle, ovary......, testis, soft tissue, and soft tissue (4-component), for the photon energy range 0.015-15 MeV and for penetration depths up to 40 mfp (mean free path). The chemical composition of human organs and tissues is seen to influence the energy absorption buildup factors. It is also found that the buildup factor...... of human organs and tissues changes significantly with the change of incident photon energy and effective atomic number, Zeff. These changes are due to the dominance of different photon interaction processes in different energy regions and different chemical compositions of human organs and tissues...

  9. Connective Tissue Disorders and Cardiovascular Complications: The indomitable role of Transforming Growth Factor-beta signaling

    Science.gov (United States)

    Wheeler, Jason B.; Ikonomidis, John S.; Jones, Jeffrey A.

    2015-01-01

    Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. Given the evidence of increased transforming growth factor-beta (TGF-β) signaling in MFS and LDS, this signaling pathway may represent the common link in this relationship. To further explore this hypothetical link, this chapter will review the TGF-β signaling pathway, heritable connective tissue syndromes related to TGF-β receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-β to these syndromes with a primary focus on the cardiovascular system. PMID:24443024

  10. Connective tissue growth factor immunohistochemical expression is associated with gallbladder cancer progression.

    Science.gov (United States)

    Garcia, Patricia; Leal, Pamela; Alvarez, Hector; Brebi, Priscilla; Ili, Carmen; Tapia, Oscar; Roa, Juan C

    2013-02-01

    Gallbladder cancer (GBC) is an aggressive neoplasia associated with late diagnosis, unsatisfactory treatment, and poor prognosis. Molecular mechanisms involved in GBC pathogenesis remain poorly understood. Connective tissue growth factor (CTGF) is thought to play a role in the pathologic processes and is overexpressed in several human cancers, including GBC. No information is available about CTGF expression in early stages of gallbladder carcinogenesis. Objective.- To evaluate the expression level of CTGF in benign and malignant lesions of gallbladder and its correlation with clinicopathologic features and GBC prognosis. Connective tissue growth factor protein was examined by immunohistochemistry on tissue microarrays containing tissue samples of chronic cholecystitis (n = 51), dysplasia (n = 15), and GBC (n = 169). The samples were scored according to intensity of staining as low/absent and high CTGF expressers. Statistical analysis was performed using the χ(2) test or Fisher exact probability test with a significance level of P Connective tissue growth factor expression showed a progressive increase from chronic cholecystitis to dysplasia and then to early and advanced carcinoma. Immunohistochemical expression (score ≥2) was significantly higher in advanced tumors, in comparison with chronic cholecystitis (P < .001) and dysplasia (P = .03). High levels of CTGF expression correlated with better survival (P = .04). Our results suggest a role for CTGF in GBC progression and a positive association with better prognosis. In addition, they underscore the importance of considering the involvement of inflammation on GBC development.

  11. First approach to studies of sulphur electron DOS in prostate cancer cell lines and tissues studied by XANES

    International Nuclear Information System (INIS)

    Kwiatek, Wojciech M.; Czapla, Joanna; Podgorczyk, Magdalena; Kisiel, Andrzej; Konior, Jerzy; Balerna, Antonella

    2011-01-01

    Urological cancers comprise approximately one-third of all cancers diagnosed in men worldwide and out of these, prostate cancer is the most common one (). Several risk factors such as age, hormone levels, environmental conditions and family history are suspected to play a role in the onset of this disease of otherwise obscure aetiology. It is therefore the medical need that drives multidisciplinary research in this field, carried out by means of various experimental and theoretical techniques. Out of many relevant factors, it is believed that sulphur can take an important part in cancer transformations. We have investigated the prostate cancer cell lines and tissues, along with selected organic and inorganic compounds used as references, by the X-ray absorption fine structure spectroscopy near the sulphur edge energy region. Particularly, the comparison of the experimental results collected during XANES measurements and theoretical calculations of electron density of states with use of the FEFF8 code and LAPW (linearised augmented plane-wave) method has been performed and in this work the first results of our studies are presented. - Highlights: → Different forms of sulphur has been found in prostate cancer cells. → FEFF8 code and LAPW method gave fairly good correspondence with the experiment. → LAPW is able to reproduce the fine structure of the absorption spectra. → Calculated DOS showed the influence of core atom on the shape of XANES spectra.

  12. Factors influencing equipment selection in electron beam processing

    Science.gov (United States)

    Barnard, J. W.

    2003-08-01

    During the eighties and nineties accelerator manufacturers dramatically increased the beam power available for high-energy equipment. This effort was directed primarily at meeting the demands of the sterilization industry. During this era, the perception that bigger (higher power, higher energy) was always better prevailed since the operating and capital costs of accelerators did not increase with power and energy as fast as the throughput. High power was needed to maintain per unit costs low for treatment. This philosophy runs counter to certain present-day realities of the sterilization business as well as conditions influencing accelerator selection in other electron beam applications. Recent experience in machine selection is described and factors affecting choice are presented.

  13. Limiting factors in single particle cryo electron tomography

    Directory of Open Access Journals (Sweden)

    Mikhail Kudryashev

    2012-07-01

    Full Text Available Modern methods of cryo electron microscopy and tomography allow visualization of protein nanomachines in their native state at the nanometer scale. Image processing methods including sub-volume averaging applied to repeating macromolecular elements within tomograms allow exploring their structures within the native context of the cell, avoiding the need for protein isolation and purification. Today, many different data acquisition protocols and software solutions are available to researchers to determine average structures of macromolecular complexes and potentially to classify structural intermediates. Here, we list the density maps reported in the literature, and analyze each structure for the chosen instrumental settings, sample conditions, main processing steps, and obtained resolution. We present conclusions that identify factors currently limiting the resolution gained by this approach.

  14. Human tissue factor: cDNA sequence and chromosome localization of the gene

    International Nuclear Information System (INIS)

    Scarpati, E.M.; Wen, D.; Broze, G.J. Jr.; Miletich, J.P.; Flandermeyer, R.R.; Siegel, N.R.; Sadler, J.E.

    1987-01-01

    A human placenta cDNA library in λgt11 was screened for the expression of tissue factor antigens with rabbit polyclonal anti-human tissue factor immunoglobulin G. Among 4 million recombinant clones screened, one positive, λHTF8, expressed a protein that shared epitopes with authentic human brain tissue factor. The 1.1-kilobase cDNA insert of λHTF8 encoded a peptide that contained the amino-terminal protein sequence of human brain tissue factor. Northern blotting identified a major mRNA species of 2.2 kilobases and a minor species of ∼ 3.2 kilobases in poly(A) + RNA of placenta. Only 2.2-kilobase mRNA was detected in human brain and in the human monocytic U937 cell line. In U937 cells, the quantity of tissue factor mRNA was increased several fold by exposure of the cells to phorbol 12-myristate 13-acetate. Additional cDNA clones were selected by hybridization with the cDNA insert of λHTF8. These overlapping isolates span 2177 base pairs of the tissue factor cDNA sequence that includes a 5'-noncoding region of 75 base pairs, an open reading frame of 885 base pairs, a stop codon, a 3'-noncoding region of 1141 base pairs, and a poly(a) tail. The open reading frame encodes a 33-kilodalton protein of 295 amino acids. The predicted sequence includes a signal peptide of 32 or 34 amino acids, a probable extracellular factor VII binding domain of 217 or 219 amino acids, a transmembrane segment of 23 acids, and a cytoplasmic tail of 21 amino acids. There are three potential glycosylation sites with the sequence Asn-X-Thr/Ser. The 3'-noncoding region contains an inverted Alu family repetitive sequence. The tissue factor gene was localized to chromosome 1 by hybridization of the cDNA insert of λHTF8 to flow-sorted human chromosomes

  15. Tissue factor-expressing tumor cells can bind to immobilized recombinant tissue factor pathway inhibitor under static and shear conditions in vitro.

    Directory of Open Access Journals (Sweden)

    Sara P Y Che

    Full Text Available Mammary tumors and malignant breast cancer cell lines over-express the coagulation factor, tissue factor (TF. High expression of TF is associated with a poor prognosis in breast cancer. Tissue factor pathway inhibitor (TFPI, the endogenous inhibitor of TF, is constitutively expressed on the endothelium. We hypothesized that TF-expressing tumor cells can bind to immobilized recombinant TFPI, leading to arrest of the tumor cells under shear in vitro. We evaluated the adhesion of breast cancer cells to immobilized TFPI under static and shear conditions (0.35 - 1.3 dyn/cm2. We found that high-TF-expressing breast cancer cells, MDA-MB-231 (with a TF density of 460,000/cell, but not low TF-expressing MCF-7 (with a TF density of 1,400/cell, adhered to recombinant TFPI, under static and shear conditions. Adhesion of MDA-MB-231 cells to TFPI required activated factor VII (FVIIa, but not FX, and was inhibited by a factor VIIa-blocking anti-TF antibody. Under shear, adhesion to TFPI was dependent on the TFPI-coating concentration, FVIIa concentration and shear stress, with no observed adhesion at shear stresses greater than 1.0 dyn/cm2. This is the first study showing that TF-expressing tumor cells can be captured by immobilized TFPI, a ligand constitutively expressed on the endothelium, under low shear in vitro. Based on our results, we hypothesize that TFPI could be a novel ligand mediating the arrest of TF-expressing tumor cells in high TFPI-expressing vessels under conditions of low shear during metastasis.

  16. Gamma-ray energy absorption and exposure buildup factor studies in some human tissues with endometriosis

    Energy Technology Data Exchange (ETDEWEB)

    Kurudirek, Murat, E-mail: mkurudirek@gmail.co [Faculty of Science, Department of Physics, Ataturk University, 25240 Erzurum (Turkey); Dogan, Bekir [Faculty of Science, Department of Physics, Ataturk University, 25240 Erzurum (Turkey); Ingec, Metin [Faculty of Medicine, Department of Obstetrics and Gynecology, Ataturk University, 25240 Erzurum (Turkey); Ekinci, Neslihan; Ozdemir, Yueksel [Faculty of Science, Department of Physics, Ataturk University, 25240 Erzurum (Turkey)

    2011-02-15

    Human tissues with endometriosis have been analyzed in terms of energy absorption (EABF) and exposure (EBF) buildup factors using the five-parameter geometric progression (G-P) fitting formula in the energy region 0.015-15 MeV up to a penetration depth of 40 mfp (mean free path). Chemical compositions of the tissue samples were determined using a wavelength dispersive X-ray fluorescence spectrometer (WDXRFS). Possible conclusions were drawn due to significant variations in EABF and EBF for the selected tissues when photon energy, penetration depth and chemical composition changed. Buildup factors so obtained may be of use when the method of choice for treatment of endometriosis is radiotherapy.

  17. Application of chitosan scaffolds on vascular endothelial growth factor and fibroblast growth factor 2 expressions in tissue engineering principles

    Directory of Open Access Journals (Sweden)

    Ariyati Retno Pratiwi

    2015-12-01

    Full Text Available Background: Tissue engineering has given satisfactory results as biological tissue substitutes to restore, replace, or regenerate tissues that have a defect. Chitosan is an organic biomaterial often used in the biomedical field. Chitosan has biocompatible, antifungal, and antibacterial properties. Chitosan is osteoconductive, suitable for bone regeneration applications. Bone defect healing begins with inflammatory phase as a response to the presence of vascular injury, so new vascularization is required. Vascular endothelial growth factor (VEGF and basic fibroblast growth factor-2 (FGF2 are indicators of the beginning of bone regeneration process, playing an important role in angiogenesis. Purpose: This research was aimed to determine the effects of chitosan scaffold application on the expressions of VEGF and FGF2 in tissue engineering principles. Method: Chitosan was dissolved in CH3COOH and NaOH to form a gel. Chitosan gel was then printed in mould to freeze dry for 24 hours. Those rats with defected bones were divided into two groups. Group 1 was the control group which defected bones were not administrated with chitosan scaffolds. Group 2 was the treatment group which defected bones were administrated with chitosan scaffolds. Those rats were sacrificed on day 14. Tissue preparations were made, and then immunohistochemical staining was conducted. Finally, a statistical analysis was conducted using Kruskal Wallis test. Result: There was no significant difference in the expressions of VEGF and FGF2 between the control group and the treatment group (p>0.05. Conclusion: Chitosan scaffolds do not affect the expressions of VEGF and FGF2 during bone regeneration process on day 14 in tissue engineering principles

  18. Connective tissue growth factor is necessary for retinal capillary basal lamina thickening in diabetic mice

    NARCIS (Netherlands)

    Kuiper, Esther J.; van Zijderveld, Rogier; Roestenberg, Peggy; Lyons, Karen M.; Goldschmeding, Roel; Klaassen, Ingeborg; van Noorden, Cornelis J. F.; Schlingemann, Reinier O.

    2008-01-01

    Experimental prevention of basal lamina (BL) thickening of retinal capillaries ameliorates early vascular changes caused by diabetes. Connective tissue growth factor (CTGF) is upregulated early in diabetes in the human retina and is a potent inducer of expression of BL components. We hypothesize

  19. Expression of Connective Tissue Growth Factor in Male Breast Cancer : Clinicopathologic Correlations and Prognostic Value

    NARCIS (Netherlands)

    Lacle, Miangela M.; van Diest, Paul J.; Goldschmeding, Roel; van der Wall, Elsken; Nguyen, Tri Q.

    2015-01-01

    Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of secreted proteins that are believed to play an important role in the development of neoplasia. In particular, CTGF has been reported to play an important role in mammary tumorigenesis and to have prognostic value in female

  20. Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair

    NARCIS (Netherlands)

    Lu, S.; Lam, J.; Trachtenberg, J.E.; Lee, E.J.; Seyednejad, H.; van den Beucken, J.J.; Tabata, Y.; Wong, M.E.; Jansen, J.A.; Mikos, A.G.; Kasper, F.K.

    2014-01-01

    The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the

  1. Involvement of Connective Tissue Growth Factor in Human and Experimental Hypertensive Nephrosclerosis

    NARCIS (Netherlands)

    Ito, Yasuhiko; Aten, Jan; Nguyen, Tri Q.; Joles, Jaap A.; Matsuo, Seiichi; Weening, Jan J.; Goldschmeding, Roel

    2011-01-01

    Background/Aims: Connective tissue growth factor (CTGF; CCN2) has been implicated as a marker and mediator of fibrosis in human and experimental renal disease. Methods: We performed a comparative analysis of CTGF expression in hypertensive patients with and without nephrosclerosis, and in

  2. Pro- and non-coagulant forms of non-cell-bound tissue factor in vivo

    NARCIS (Netherlands)

    Sturk-Maquelin, K. N.; Nieuwland, R.; Romijn, F. P. H. T. M.; Eijsman, L.; Hack, C. E.; Sturk, A.

    2003-01-01

    Background: Concentrations of non-cell-bound (NCB; soluble) tissue factor (TF) are elevated in blood collecting in the pericardial cavity of patients during cardiopulmonary bypass (CPB). Previously, we reported microparticles supporting thrombin generation in such blood samples. In this study we

  3. Tissue factor-dependent blood coagulation is enhanced following delivery irrespective of the mode of delivery

    NARCIS (Netherlands)

    Boer, K.; den Hollander, I. A.; Meijers, J. C. M.; Levi, M. [=Marcel M.

    2007-01-01

    BACKGROUND: The risk of thrombosis is clearly increased in the postpartum period. Mice with a targeted deletion of the transmembrane domain of tissue factor (TF) develop serious activation of blood coagulation and widespread thrombosis after delivery. OBJECTIVE AND METHODS: We hypothesized that TF,

  4. Expression of cyclooxygenase-1 and cyclooxygenase-2, syndecan-1 and connective tissue growth factor in benign and malignant breast tissue from premenopausal women.

    Science.gov (United States)

    Fahlén, M; Zhang, H; Löfgren, L; Masironi, B; von Schoultz, E; von Schoultz, B; Sahlin, L

    2017-05-01

    Stromal factors have been identified as important for tumorigenesis and metastases of breast cancer. From 49 premenopausal women, samples were collected from benign or malignant tumors and the seemingly normal tissue adjacent to the tumor. The factors studied, with real-time polymerase chain reaction (PCR) and immunohistochemistry, were cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), syndecan-1 (S-1) and connective tissue growth factor (CTGF). COX-1 and S-1 mRNA levels were higher in the malignant tumors than in normal and benign tissues. The COX-2 mRNA level was lower in the malignant tumor than in the normal tissue, while CTGF mRNA did not differ between the groups. COX-1 immunostaining was higher in stroma from malignant tumors than in benign tissues, whereas COX-2 immunostaining was higher in the malignant tissue. Glandular S-1 immunostaining was lower in malignant tumors compared to benign and normal tissues, and the opposite was found in stroma. Conclusively, mRNA levels of COX-1 and COX-2 were oppositely regulated, with COX-1 being increased in the malignant tumor while COX-2 was decreased. S-1 protein localization switched from glandular to stromal cells in malignant tissues. Thus, these markers are, in premenopausal women, localized and regulated differently in normal/benign breast tissue as compared to the malignant tumor.

  5. Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

    Science.gov (United States)

    Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

    2010-09-01

    A low-energy electronic brachytherapy source (EBS), the model S700 Axxent™ x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95

  6. Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

    Energy Technology Data Exchange (ETDEWEB)

    Shi Chengyu; Guo Bingqi; Eng, Tony; Papanikolaou, Nikos [Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, TX 78229 (United States); Cheng, Chih-Yao, E-mail: shic@uthscsa.ed [Radiation Oncology Department, Oklahoma University Health Science Center, Oklahoma, OK 73104 (United States)

    2010-09-21

    A low-energy electronic brachytherapy source (EBS), the model S700 Axxent(TM) x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V{sub 100} reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as

  7. Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

    International Nuclear Information System (INIS)

    Shi Chengyu; Guo Bingqi; Eng, Tony; Papanikolaou, Nikos; Cheng, Chih-Yao

    2010-01-01

    A low-energy electronic brachytherapy source (EBS), the model S700 Axxent(TM) x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V 100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95

  8. Recombinant nematode anticoagulant protein c2, an inhibitor of tissue factor/factor VIIa, attenuates coagulation and the interleukin-10 response in human endotoxemia

    NARCIS (Netherlands)

    de Pont, A. C. J. M.; Moons, A. H. M.; de Jonge, E.; Meijers, J. C. M.; Vlasuk, G. P.; Rote, W. E.; Büller, H. R.; van der Poll, T.; Levi, M. [=Marcel M.

    2004-01-01

    The tissue factor-factor (F)VIIa complex (TF/FVIIa) is responsible for the initiation of blood coagulation under both physiological and pathological conditions. Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of TF/FVIIa. mechanistically distinct from tissue factor

  9. CMG2 Expression Is an Independent Prognostic Factor for Soft Tissue Sarcoma Patients

    Directory of Open Access Journals (Sweden)

    Thomas Greither

    2017-12-01

    Full Text Available The capillary morphogenesis gene 2 (CMG2, also known as the anthrax toxin receptor 2 (ANTXR2, is a transmembrane protein putatively involved in extracellular matrix (ECM adhesion and tissue remodeling. CMG2 promotes endothelial cell proliferation and exhibits angiogenic properties. Its downregulation is associated with a worsened survival of breast carcinoma patients. Aim of this study was to analyze the CMG2 mRNA and protein expression in soft tissue sarcoma and their association with patient outcome. CMG2 mRNA was measured in 121 tumor samples of soft tissue sarcoma patients using quantitative real-time PCR. CMG2 protein was evaluated in 52 tumor samples by ELISA. CMG2 mRNA was significantly correlated with the corresponding CMG2 protein expression (rs = 0.31; p = 0.027. CMG2 mRNA expression was associated with the mRNA expressions of several ECM and tissue remodeling enzymes, among them CD26 and components of the uPA system. Low CMG2 mRNA expression was correlated with a worsened patients’ disease-specific survival in Kaplan-Meier analyses (mean patient survival was 25 vs. 96 months; p = 0.013, especially in high-stage tumors. A decreased CMG2 expression is a negative prognostic factor for soft tissue sarcoma patients. CMG2 may be an interesting candidate gene for the further exploration of soft tissue sarcoma genesis and progression.

  10. CMG2 Expression Is an Independent Prognostic Factor for Soft Tissue Sarcoma Patients.

    Science.gov (United States)

    Greither, Thomas; Wedler, Alice; Rot, Swetlana; Keßler, Jacqueline; Kehlen, Astrid; Holzhausen, Hans-Jürgen; Bache, Matthias; Würl, Peter; Taubert, Helge; Kappler, Matthias

    2017-12-07

    The capillary morphogenesis gene 2 (CMG2), also known as the anthrax toxin receptor 2 (ANTXR2), is a transmembrane protein putatively involved in extracellular matrix (ECM) adhesion and tissue remodeling. CMG2 promotes endothelial cell proliferation and exhibits angiogenic properties. Its downregulation is associated with a worsened survival of breast carcinoma patients. Aim of this study was to analyze the CMG2 mRNA and protein expression in soft tissue sarcoma and their association with patient outcome. CMG2 mRNA was measured in 121 tumor samples of soft tissue sarcoma patients using quantitative real-time PCR. CMG2 protein was evaluated in 52 tumor samples by ELISA. CMG2 mRNA was significantly correlated with the corresponding CMG2 protein expression (r s = 0.31; p = 0.027). CMG2 mRNA expression was associated with the mRNA expressions of several ECM and tissue remodeling enzymes, among them CD26 and components of the uPA system. Low CMG2 mRNA expression was correlated with a worsened patients' disease-specific survival in Kaplan-Meier analyses (mean patient survival was 25 vs. 96 months; p = 0.013), especially in high-stage tumors. A decreased CMG2 expression is a negative prognostic factor for soft tissue sarcoma patients. CMG2 may be an interesting candidate gene for the further exploration of soft tissue sarcoma genesis and progression.

  11. Muscle Tissue Engineering Using Gingival Mesenchymal Stem Cells Encapsulated in Alginate Hydrogels Containing Multiple Growth Factors.

    Science.gov (United States)

    Ansari, Sahar; Chen, Chider; Xu, Xingtian; Annabi, Nasim; Zadeh, Homayoun H; Wu, Benjamin M; Khademhosseini, Ali; Shi, Songtao; Moshaverinia, Alireza

    2016-06-01

    Repair and regeneration of muscle tissue following traumatic injuries or muscle diseases often presents a challenging clinical situation. If a significant amount of tissue is lost the native regenerative potential of skeletal muscle will not be able to grow to fill the defect site completely. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material, present an advantageous alternative therapeutic option for muscle tissue engineering in comparison to current treatment modalities available. To date, there has been no report on application of gingival mesenchymal stem cells (GMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of the current study were to develop an injectable 3D RGD-coupled alginate scaffold with multiple growth factor delivery capacity for encapsulating GMSCs, and to evaluate the capacity of encapsulated GMSCs to differentiate into myogenic tissue in vitro and in vivo where encapsulated GMSCs were transplanted subcutaneously into immunocompromised mice. The results demonstrate that after 4 weeks of differentiation in vitro, GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited muscle cell-like morphology with high levels of mRNA expression for gene markers related to muscle regeneration (MyoD, Myf5, and MyoG) via qPCR measurement. Our quantitative PCR analyzes revealed that the stiffness of the RGD-coupled alginate regulates the myogenic differentiation of encapsulated GMSCs. Histological and immunohistochemical/fluorescence staining for protein markers specific for myogenic tissue confirmed muscle regeneration in subcutaneous transplantation in our in vivo animal model. GMSCs showed significantly greater capacity for myogenic regeneration in comparison to hBMMSCs (p alginate hydrogel with multiple growth factor delivery capacity is a promising candidate for muscle tissue engineering.

  12. Expression of connective tissue growth factor in tumor tissues is an independent predictor of poor prognosis in patients with gastric cancer

    OpenAIRE

    Liu, Lu-Ying; Han, Yan-Chun; Wu, Shu-Hua; Lv, Zeng-Hua

    2008-01-01

    AIM: To examine the expression of connective tissue growth factor (CTGF), also known as CCN2, in gastric carcinoma (GC), and the correlation between the expression of CTGF, clinicopathologic features and clinical outcomes of patients with GC.

  13. Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation.

    Science.gov (United States)

    Akar, Banu; Jiang, Bin; Somo, Sami I; Appel, Alyssa A; Larson, Jeffery C; Tichauer, Kenneth M; Brey, Eric M

    2015-12-01

    Gradients of soluble factors play an important role in many biological processes, including blood vessel assembly. Gradients can be studied in detail in vitro, but methods that enable the study of spatially distributed soluble factors and multi-cellular processes in vivo are limited. Here, we report on a method for the generation of persistent in vivo gradients of growth factors in a three-dimensional (3D) biomaterial system. Fibrin loaded porous poly (ethylene glycol) (PEG) scaffolds were generated using a particulate leaching method. Platelet derived growth factor BB (PDGF-BB) was encapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres which were placed distal to the tissue-material interface. PLGA provides sustained release of PDGF-BB and its diffusion through the porous structure results in gradient formation. Gradients within the scaffold were confirmed in vivo using near-infrared fluorescence imaging and gradients were present for more than 3 weeks. The diffusion of PDGF-BB was modeled and verified with in vivo imaging findings. The depth of tissue invasion and density of blood vessels formed in response to the biomaterial increased with magnitude of the gradient. This biomaterial system allows for generation of sustained growth factor gradients for the study of tissue response to gradients in vivo. Published by Elsevier Ltd.

  14. Nuclear exclusion of transcription factors associated with apoptosis in developing nervous tissue

    Directory of Open Access Journals (Sweden)

    R. Linden

    1999-07-01

    Full Text Available Programmed cell death in the form of apoptosis involves a network of metabolic events and may be triggered by a variety of stimuli in distinct cells. The nervous system contains several neuron and glial cell types, and developmental events are strongly dependent on selective cell interactions. Retinal explants have been used as a model to investigate apoptosis in nervous tissue. This preparation maintains the structural complexity and cell interactions similar to the retina in situ, and contains cells in all stages of development. We review the finding of nuclear exclusion of several transcription factors during apoptosis in retinal cells. The data reviewed in this paper suggest a link between apoptosis and a failure in the nucleo-cytoplasmic partition of transcription factors. It is argued that the nuclear exclusion of transcription factors may be an integral component of apoptosis both in the nervous system and in other types of cells and tissues.

  15. PET Imaging of Tissue Factor in Pancreatic Cancer Using 64Cu-Labeled Active Site-Inhibited Factor VII

    DEFF Research Database (Denmark)

    Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Lotte K

    2016-01-01

    with advanced stage, increased microvessel density, metastasis, and poor overall survival. Imaging of TF expression is of clinical relevance as a prognostic biomarker and as a companion diagnostic for TF-directed therapies currently under clinical development. Factor VII (FVII) is the natural ligand to TF......UNLABELLED: Tissue factor (TF) is the main initiator of the extrinsic coagulation cascade. However, TF also plays an important role in cancer. TF expression has been reported in 53%-89% of all pancreatic adenocarcinomas, and the expression level of TF has in clinical studies correlated...

  16. Peritumoral adipose tissue as a source of inflammatory and angiogenic factors in colorectal cancer.

    Science.gov (United States)

    Amor, S; Iglesias-de la Cruz, M C; Ferrero, E; García-Villar, O; Barrios, V; Fernandez, N; Monge, L; García-Villalón, A L; Granado, M

    2016-02-01

    Obesity is a risk factor for the development of human colorectal cancer (CC). The aim of this work is to report the inflammatory and angiogenic scenario in lean (BMI  30 kg/m2) patients with and without CC and to assess the role of peritumoral adipose tissue in CC-induced inflammation. Patients were divided in four experimental groups: obese patients with CC (OB-CC), lean patients with CC (LEAN-CC), obese patients without CC (OB), and lean patients without CC (LEAN). Plasma levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-4, IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in OB-CC patients. Peritumoral adipose tissue (TF) explants and cultured mature adipocytes secreted higher amounts of nitrites and nitrates than did control and non-tumoral (NTF) adipose tissue both alone and in response to lipopolysaccharide (LPS). Nitrite and nitrate secretion was also increased in TF explants from OB-CC patients compared with that from LEAN-CC patients. Gene expression of adiponectin, tumor necrosis factor alpha (TNF-α), insulin-like growth factor type I (IGF-I), cyclooxygenase-2 (COX-2), and peroxisome proliferator-activated receptor γ (PPAR-γ) was increased in TF explants from CC patients. LPS increased the gene expression of IL-6, IL-10, TNF-α, vascular endothelial growth factor (VEGF), and COX-2 in OB and in TF explants from OB-CC patients. COX-2 and PPAR-γ inhibition further increased LPS-induced release of nitrites and nitrates in TF explants and adipocytes from OB-CC patients. In conclusion, OB-CC patients have increased plasma levels of pro-inflammatory and angiogenic factors. TF from OB-CC patients shows an increased secretion of inflammatory markers compared with both TF from LEAN-CC and non-tumoral adipose tissue (AT) through a COX-2- and PPAR-γ-independent mechanism.

  17. Synergistic and additive effects of hydrostatic pressure and growth factors on tissue formation.

    Directory of Open Access Journals (Sweden)

    Benjamin D Elder

    2008-06-01

    Full Text Available Hydrostatic pressure (HP is a significant factor in the function of many tissues, including cartilage, knee meniscus, temporomandibular joint disc, intervertebral disc, bone, bladder, and vasculature. Though studies have been performed in assessing the role of HP in tissue biochemistry, to the best of our knowledge, no studies have demonstrated enhanced mechanical properties from HP application in any tissue.The objective of this study was to determine the effects of hydrostatic pressure (HP, with and without growth factors, on the biomechanical and biochemical properties of engineered articular cartilage constructs, using a two-phased approach. In phase I, a 3x3 full-factorial design of HP magnitude (1, 5, 10 MPa and frequency (0, 0.1, 1 Hz was used, and the best two treatments were selected for use in phase II. Static HP at 5 MPa and 10 MPa resulted in significant 95% and 96% increases, respectively, in aggregate modulus (H(A, with corresponding increases in GAG content. These regimens also resulted in significant 101% and 92% increases in Young's modulus (E(Y, with corresponding increases in collagen content. Phase II employed a 3x3 full-factorial design of HP (no HP, 5 MPa static, 10 MPa static and growth factor application (no GF, BMP-2+IGF-I, TGF-beta1. The combination of 10 MPa static HP and TGF-beta1 treatment had an additive effect on both H(A and E(Y, as well as a synergistic effect on collagen content. This group demonstrated a 164% increase in H(A, a 231% increase in E(Y, an 85% increase in GAG/wet weight (WW, and a 173% increase in collagen/WW, relative to control.To our knowledge, this is the first study to demonstrate increases in the biomechanical properties of tissue from pure HP application, using a cartilage model. Furthermore, it is the only study to demonstrate additive or synergistic effects between HP and growth factors on tissue functional properties. These findings are exciting as coupling HP stimulation with growth

  18. Nuclear-polarization correction to the bound-electron g factor in heavy hydrogenlike ions

    OpenAIRE

    Nefiodov, A. V.; Plunien, G.; Soff, G.

    2002-01-01

    The influence of nuclear polarization on the bound-electron $g$ factor in heavy hydrogenlike ions is investigated. Numerical calculations are performed for the K- and L-shell electrons taking into account the dominant virtual nuclear excitations. This determines the ultimate limit for tests of QED utilizing measurements of the bound-electron $g$ factor in highly charged ions.

  19. Nuclear-polarization correction to the bound-electron g factor in heavy hydrogenlike ions.

    Science.gov (United States)

    Nefiodov, A V; Plunien, G; Soff, G

    2002-08-19

    The influence of nuclear polarization on the bound-electron g factor in heavy hydrogenlike ions is investigated. Numerical calculations are performed for the K- and L-shell electrons taking into account the dominant virtual nuclear excitations. This determines the ultimate limit for tests of QED utilizing measurements of the bound-electron g factor in highly charged ions.

  20. High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions.

    Science.gov (United States)

    Zhang, Dong-Mei; Jiao, Rui-Qing; Kong, Ling-Dong

    2017-03-29

    High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

  1. High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

    Directory of Open Access Journals (Sweden)

    Dong-Mei Zhang

    2017-03-01

    Full Text Available High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2 and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG, free fatty acid (FFA, uric acid (UA and methylglyoxal (MG. Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

  2. Positive semidefinite tensor factorizations of the two-electron integral matrix for low-scaling ab initio electronic structure.

    Science.gov (United States)

    Hoy, Erik P; Mazziotti, David A

    2015-08-14

    Tensor factorization of the 2-electron integral matrix is a well-known technique for reducing the computational scaling of ab initio electronic structure methods toward that of Hartree-Fock and density functional theories. The simplest factorization that maintains the positive semidefinite character of the 2-electron integral matrix is the Cholesky factorization. In this paper, we introduce a family of positive semidefinite factorizations that generalize the Cholesky factorization. Using an implementation of the factorization within the parametric 2-RDM method [D. A. Mazziotti, Phys. Rev. Lett. 101, 253002 (2008)], we study several inorganic molecules, alkane chains, and potential energy curves and find that this generalized factorization retains the accuracy and size extensivity of the Cholesky factorization, even in the presence of multi-reference correlation. The generalized family of positive semidefinite factorizations has potential applications to low-scaling ab initio electronic structure methods that treat electron correlation with a computational cost approaching that of the Hartree-Fock method or density functional theory.

  3. Positive semidefinite tensor factorizations of the two-electron integral matrix for low-scaling ab initio electronic structure

    Energy Technology Data Exchange (ETDEWEB)

    Hoy, Erik P.; Mazziotti, David A., E-mail: damazz@uchicago.edu [Department of Chemistry and The James Franck Institute, The University of Chicago, Chicago, Illinois 60637 (United States)

    2015-08-14

    Tensor factorization of the 2-electron integral matrix is a well-known technique for reducing the computational scaling of ab initio electronic structure methods toward that of Hartree-Fock and density functional theories. The simplest factorization that maintains the positive semidefinite character of the 2-electron integral matrix is the Cholesky factorization. In this paper, we introduce a family of positive semidefinite factorizations that generalize the Cholesky factorization. Using an implementation of the factorization within the parametric 2-RDM method [D. A. Mazziotti, Phys. Rev. Lett. 101, 253002 (2008)], we study several inorganic molecules, alkane chains, and potential energy curves and find that this generalized factorization retains the accuracy and size extensivity of the Cholesky factorization, even in the presence of multi-reference correlation. The generalized family of positive semidefinite factorizations has potential applications to low-scaling ab initio electronic structure methods that treat electron correlation with a computational cost approaching that of the Hartree-Fock method or density functional theory.

  4. Plasma Tissue Factor Pathway Inhibitor Levels in Angiographically Defined Coronary Artery Disease Among Saudis

    Directory of Open Access Journals (Sweden)

    Syed Shahid Habib

    2013-05-01

    Full Text Available Objectives: This study was aimed to determine plasma levels of total (TFPI-T and free (TFPI-F tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1, and tissue plasminogen activator (t-PA in a cohort of Saudi patients with chronic stable angiographically defined coronary artery disease (CAD and to determine its correlation with its severity.Methods: This cross sectional study was conducted in the department of physiology and department of cardiology, College of Medicine, and King Khalid University Hospital and King Saud University, Riyadh. Sixty known cases of CAD who had undergone angiography (35 males and 25 females were selected. A control group included 39 (20 males and 19 females healthy subjects. Fasting venous blood samples were analyzed for total (TFPI-T and free (TFPI-F tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1, and tissue plasminogen activator (t-PA. Gensini scores and vessel scores were determined for assessing CAD severity.Results: There were non-significant differences between age, body mass index (BMI and Blood pressure between the controls and CAD subjects. A comparison of hemostatic markers between control and CAD patients showed significantly higher levels of Fibrinogen, PAI-1, TFPI-T and TFPI-F in CAD patients compared to control subjects. But there was no difference in plasma t-PA levels. TFPI-T had a significant positive correlation with severity of disease determined by Gensini Scores (r=0.344; p=0.006 and vessel scores (r=0.338; p=0.015.Conclusion: Plasma levels of total tissue factor pathway inhibitor are significantly related with the presence and severity of CAD. Elevated levels of TFPI-T may be considered as useful diagnostic and prognostic markers in patients with CAD.

  5. O6-methylguanine DNA methyltransferase in human fetal tissues: fetal and maternal factors

    International Nuclear Information System (INIS)

    D'Ambrosio, S.M.; Samuel, M.J.; Dutta-Choudhury, T.A.; Wani, A.A.

    1986-01-01

    O 6 -Methylguanine methyltransferase (O 6 -MT) was measured and compared in extracts of 7 human fetal tissues obtained from 21 different fetal specimens as a function of fetal age and race, and maternal smoking and drug usage. Activity was determined from the proteinase-K solubilized radioactivity transferred from the DNA to the O 6 -MT. S9 homogenates were incubated with a heat depurinated [ 3 H]-methylnitrosourea alkylated DNA. Liver exhibited the highest activity followed by kidney, lung, small intestine, large intestine, skin and brain. Each of the tissues exhibited a 3- to 5-fold level of interindividual variation of O 6 -MT. There did not appear to be any significant difference of O 6 -MT in the tissues obtained from mothers who smoked cigarettes during pregnancy. Also, fetal race and age did not appear to account for the level of variation of O 6 -MT. The fetal tissues obtained from an individual using phenobarbital and smoking exhibited 4-fold increases in O 6 -MT activity. The tissues obtained from another individual on kidney dialysis were 2- to 3-fold higher than the normal population. These data suggest that the variation in human O 6 -MT can not be explained by racial or smoking factors, but may be modulated by certain drugs

  6. Expression and clinical significance of connective tissue growth factor in thyroid carcinomas.

    Science.gov (United States)

    Wang, Guimin; Zhang, Wei; Meng, Wei; Liu, Jia; Wang, Peisong; Lin, Shan; Xu, Liyan; Li, Enmin; Chen, Guang

    2013-08-01

    To examine expression of the connective tissue growth factor (CTGF) gene in human thyroid cancer and establish whether a correlation exists between the presence of CTGF protein and clinicopathological parameters of the disease. CTGF protein expression was investigated retrospectively by immunohistochemical analysis of CTGF protein levels in thyroid tumour tissue. Associations between immunohistochemical score and several clinicopathological parameters were examined. In total, 131 thyroid tissue specimens were included. High levels of CTGF protein were observed in papillary thyroid carcinoma tissue; benign thyroid tumour tissue scored negatively for CTGF protein. In papillary thyroid carcinoma, there was a significant relationship between high CTGF protein levels and Union for International Cancer Control disease stage III-IV, and presence of lymph node metastasis. In papillary thyroid carcinomas, CTGF protein levels were not significantly associated with sex or age. These findings suggest that the CTGF protein level is increased in papillary thyroid carcinoma cells compared with benign thyroid tumours. CTGF expression might play a role in the development of malignant tumours in the thyroid.

  7. Validity of the use of the neutron-reduction factor in assessing displacement damage to electronics in armoured vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Cousins, T.; Jamieson, T.J.

    1990-02-01

    The degree of protection from neutron irradiation afforded to electronics by armoured vehicles is most currently defined by the outside-to-inside ratio of the 1 MeV equivalent neutron fluence for Silicon. It has been proposed that this factor may be approximated by an experimentally measurable parameter - the neutron (tissue kerma) reduction factor. This report examines the validity of this assumption for a variety of realistic nuclear battlefield scenarios, calculated using the computer code VPF2. In addition the response of two neutron dosimeters in the calculated fields is examined.

  8. Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.

    Science.gov (United States)

    Gaut, Carrie; Sugaya, Kiminobu

    2015-01-01

    Articular cartilage defects often progress to osteoarthritis, which negatively impacts quality of life for millions of people worldwide and leads to high healthcare expenditures. Tissue engineering approaches to osteoarthritis have concentrated on proliferation and differentiation of stem cells by activation and suppression of signaling pathways, and by using a variety of scaffolding techniques. Recent studies indicate a key role of environmental factors in the differentiation of mesenchymal stem cells to mature cartilage-producing chondrocytes. Therapeutic approaches that consider environmental regulation could optimize chondrogenesis protocols for regeneration of articular cartilage. This review focuses on the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate and the current use of these environmental factors in tissue engineering research.

  9. Comparison between 3D conventional techniques, field-in-field and electronic tissue compensation for mantle fields planning

    International Nuclear Information System (INIS)

    Martins, Lais P.; Silva, Leonardo P.; Trindade, Cassia; Garcia, Paulo L.; Santos, Maira R.; Batista, Delano V.S.

    2012-01-01

    External radiotherapy treatment for Hodgkin's lymphoma over diaphragm region requires large radiation fields with protections applied to larynx, humerus head and lungs. The size and shape of the field, which covers different depths, make it difficult to distribute a homogeneous dose. Techniques such as field-in-field and electronic tissue compensation may be used to make dose homogeneous and compensate the obliquity from the tissue. Three types of planning were performed for diagnose of nodular sclerosis Hodgkin's lymphoma: one plan with two fields, AP-PA (AP plan), another with four fields field-in- field (FF plan), and a third one with two fields and electronic tissue compensation (ETC plan). Results showed better gradient, cover of PTV and dose distribution for the ETC plan, besides the advantage from this technique of does not require protection blocks. In the meanwhile, AP and FF plans require simpler dosimetry and fewer MU. Related to the uniformity of dose distribution, AP plan showed hot areas in the neck region, FF plan showed hot areas in the shoulder region and ETC plan showed most uniform distribution without hot areas. The electronic tissue compensation is a useful tool for large and shaped fields as the mantle field, however higher MU and complex dosimetry should be taken in account. (author)

  10. Modelling impulsive factors for electronics and restaurant coupons’ e-store display

    Science.gov (United States)

    Ariningsih, P. K.; Nainggolan, M.; Sandy, I. A.

    2018-04-01

    In many times, the increment of e-store visitors does not followed by sales increment. Most purchases through e-commerce are impulsive buying, however only small amount of study is available to understand impulsive factors of e-store display. This paper suggests a preliminary concept on understanding the impulsive factors in Electronics and Restaurant Coupons e-store display, which are two among few popular group products sold through e-commerce. By conducting literature study and survey, 31 attributes were identified as impulsive factors in electronics e-store display and 20 attributes were identified as impulsive factors for restaurant coupon e-store. The attributes were then grouped into comprehensive impulsive factors by factor analysis. Each group of impulsive attributes were generated into 3 factors. Accessibility Factors and Trust Factors appeared for each group products. The other factors are Internal Factors for electronics e-store and Marketing factors for restaurant coupons e-store. Structural Equation Model of the impulsive factors was developed for each type of e-store, which stated the covariance between Trust Factors and Accessibility Factors. Based on preliminary model, Internal Factor and Trust Factor are influencing impulsive buying in electronics store. Special factor for electronics e-store is Internal Factor, while for restaurant coupons e-store is Marketing Factor.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  12. Association of Geographical Factors With Administration of Tissue Plasminogen Activator for Acute Ischemic Stroke

    OpenAIRE

    Kunisawa, Susumu; Morishima, Toshitaka; Ukawa, Naoto; Ikai, Hiroshi; Otsubo, Tetsuya; Ishikawa, Koichi B.; Yokota, Chiaki; Minematsu, Kazuo; Fushimi, Kiyohide; Imanaka, Yuichi

    2013-01-01

    Background Intravenous tissue plasminogen activator (tPA) is an effective treatment for acute ischemic stroke if administered within a few hours of stroke onset. Because of this time restriction, tPA administration remains infrequent. Ambulance use is an effective strategy for increasing tPA administration but may be influenced by geographical factors. The objectives of this study are to investigate the relationship between tPA administration and ambulance use and to examine how patient trave...

  13. A hybrid electron and photon IMRT planning technique that lowers normal tissue integral patient dose using standard hardware.

    Science.gov (United States)

    Rosca, Florin

    2012-06-01

    To present a mixed electron and photon IMRT planning technique using electron beams with an energy range of 6-22 MeV and standard hardware that minimizes integral dose to patients for targets as deep as 7.5 cm. Ten brain cases, two lung, a thyroid, an abdominal, and a parotid case were planned using two planning techniques: a photon-only IMRT (IMRT) versus a mixed modality treatment (E+IMRT) that includes an enface electron beam and a photon IMRT portion that ensures a uniform target coverage. The electron beam is delivered using a regular cutout placed in an electron cone. The electron energy was chosen to provide a good trade-off between minimizing integral dose and generating a uniform, deliverable plan. The authors choose electron energies that cover the deepest part of PTV with the 65%-70% isodose line. The normal tissue integral dose, the dose for ring structures around the PTV, and the volumes of the 75%, 50%, and 25% isosurfaces were used to compare the dose distributions generated by the two planning techniques. The normal tissue integral dose was lowered by about 20% by the E+IMRT plans compared to the photon-only IMRT ones for most studied cases. With the exception of lungs, the dose reduction associated to the E+IMRT plans was more pronounced further away from the target. The average dose ratio delivered to the 0-2 cm and the 2-4 cm ring structures for brain patients for the two planning techniques were 89.6% and 70.8%, respectively. The enhanced dose sparing away from the target for the brain patients can also be observed in the ratio of the 75%, 50%, and 25% isodose line volumes for the two techniques, which decreases from 85.5% to 72.6% and further to 65.1%, respectively. For lungs, the lateral electron beams used in the E+IMRT plans were perpendicular to the mostly anterior/posterior photon beams, generating much more conformal plans. The authors proved that even using the existing electron delivery hardware, a mixed electron/photon planning

  14. Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

    Science.gov (United States)

    Shah, Nisarg J.; Hyder, Md. Nasim; Quadir, Mohiuddin A.; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J.; Nevins, Myron; Spector, Myron; Hammond, Paula T.

    2014-01-01

    Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. PMID:25136093

  15. Reduction of dose enhancement from backscattered radiation at tissue-metal interfaces irradiated with 6MeV electrons

    International Nuclear Information System (INIS)

    Steel, B.

    1996-01-01

    Due to Electron Back Scatter (EBS), electron irradiation of tissue having under lying lead shielding results in an increase in dose to the tissue on the entrance side of the lead. In these situations dose increases as high as 80% have been reported in the literature. Saunders (British Journal of Radiology, 47, 467-470) noted that dose enhancement is dependent on atomic number of the under lying material approximately as Z 0.5 , and it increases at lower incident electron energies. In our clinic we use 2mm of lead shielding to protect under lying normal tissue when 6MeV electrons are used to treat lips and ears. The object of this study was to find the thinnest combination of materials to reduce the total dose to an acceptable level, with the provisos that; the patient does not come into contact with the lead or other metals, the finished shield could comfortabley be placed between the patient's lip and teeth, and that the materials are sufficietly malleable to work into custom shields. Various combinations of dental wax and aluminium were trialed. That which proved to give the best compromise between reduction of EBS and total shielding thickness was, 1mm of aluminim on the beam side of the lead with 1mm of dental wax to completely enclose the shield. In practice the manufactured shields are approximately 6 mm thick, and are usually not uncomfortable for the patient. (author)

  16. A Method for Preparing Spaceflight RNAlater-Fixed Arabidopsis thaliana (Brassicaceae Tissue for Scanning Electron Microscopy

    Directory of Open Access Journals (Sweden)

    Eric R. Schultz

    2013-07-01

    Full Text Available Premise of the study: In spaceflight experiments, tissues for morphologic study are fixed in 3% glutaraldehyde, while tissues for molecular study are fixed in RNAlater; thus, an experiment containing both study components requires multiple fixation strategies. The possibility of using RNAlater-fixed materials for standard SEM-based morphometric investigation was explored to expand the library of tissues available for analysis and maximize usage of samples returned from spaceflight, but these technologies have wide application to any situation where recovery of biological resources is limited. Methods and Results: RNAlater-fixed samples were desalinated in distilled water, dehydrated through graded methanol, plunged into liquid ethane, and transferred to cryovials for freeze-substitution. Sample tissues were critical point dried, mounted, sputter-coated, and imaged. Conclusions: The protocol resulted in acceptable SEM images from RNAlater-fixed Arabidopsis thaliana tissue. The majority of the tissues remained intact, including general morphology and finer details such as root hairs and trichomes.

  17. Electronic prescription as contributing factor for hospitalized patients' safety.

    Directory of Open Access Journals (Sweden)

    Gimenes FRE

    2006-03-01

    Full Text Available The following study was performed to identify factors related to medication errors in the computerized physician order entry and their advantages and disadvantages according to doctors, nursing team and administrative officers. It is a survey descriptive study carried out at three units of a Brazilian academic hospital in the southeast area. The study was divided in two phases. In the first phase, we analyzed a total of 1,349 prescriptions from general medical unit, surgical and orthopaedic wards during 30 days consecutively. A semi-structured instrument, elaborated by a group of researchers for the study proposals, was used. In the second phase, a semi-structured questionnaire was applied to the health professionals containing closed and open items approaching their opinion about the composition of electronic prescription, the advantages and disadvantages of them, and their suggestions for its improvement. Out of 1,349 prescriptions observed, 17.5% presented deletions, 25.0% medicines written manually and 17.0% of them were incomplete. Some of the advantages pointed by health professionals were its legibility (37.5%, little time spent when elaborating and emitting them (20.5% and the way they are a practical and organized (8%. The disadvantages pointed were repetition of previous prescriptions (34%, typing mistakes (17%, dependence on computers (11% and alterations made manually (7%. We conclude, this way, that the computerized prescription order entry represents a great progress among the strategies used to minimize medication errors caused by prescriptions badly formulated. However, it doesn't eradicate the possibility of medication error occurrences, needing some system modifications.

  18. Prioritizing the client trust factors in electronic banking using analytic hierarchy process

    Directory of Open Access Journals (Sweden)

    Hossein vazifedust

    2014-04-01

    Full Text Available This paper prioritizes the trust factors among electronic banking clients of an Iranian bank named Parsian Bank. The study first analyzes and reviews the literature and interviews with experts of electronic banking and academicians and determines client trust as the most important factor for development of electronic banking. The study also determines different factors associated with trust, which includes individual factors, banking factors and infrastructural factors. The sample populations consist of 25 experts who are academicians, managers and bank officers, clients of electronic banking. The necessary data was collected through conducting interviews and questionnaires and they are analyzed using analytic hierarchy process (AHP. The research findings indicate that the attitudinal factors, telecommunication infrastructure and cultural factors were the most influential factors accordingly and the customer orientation and ease of access were the least influential factors.

  19. Virulence Factor Genes in Staphylococcus aureus Isolated From Diabetic Foot Soft Tissue and Bone Infections.

    Science.gov (United States)

    Víquez-Molina, Gerardo; Aragón-Sánchez, Javier; Pérez-Corrales, Cristian; Murillo-Vargas, Christian; López-Valverde, María Eugenia; Lipsky, Benjamin A

    2018-03-01

    The aim of this study is to describe the presence of genes encoding for 4 virulence factors (pvl, eta, etb, and tsst), as well as the mecA gene conferring resistance to beta-lactam antibiotics, in patients with diabetes and a staphylococcal foot infection. We have also analyzed whether isolates of Staphylococcus aureus from bone infections have a different profile for these genes compared with those from exclusively soft tissue infections. In this cross-sectional study of a prospectively recruited series of patients admitted to the Diabetic Foot Unit, San Juan de Dios Hospital, San José, Costa Rica with a moderate or severe diabetic foot infection (DFI), we collected samples from infected soft tissue and from bone during debridement. During the study period (June 1, 2014 to May 31, 2016), we treated 379 patients for a DFI. S aureus was isolated from 101 wound samples, of which 43 were polymicrobial infections; we only included the 58 infections that were monomicrobial S aureus for this study. Infections were exclusively soft tissue in 17 patients (29.3%) while 41 (70.7%) had bone involvement (osteomyelitis). The mecA gene was detected in 35 cases (60.3%), pvl gene in 4 cases (6.9%), and tsst gene in 3 (5.2%). We did not detect etA and etB in any of the cases. There were no differences in the profile of S aureus genes encoding for virulence factors (pvl, etA, etB, and tsst) recovered from DFIs between those with just soft tissue compared to those with osteomyelitis. However, we found a significantly higher prevalence of pvl+ strains of S aureus associated with soft tissue compared with bone infections. Furthermore, we observed a significantly longer time to healing among patients infected with mecA+ (methicillin-resistant) S aureus (MRSA).

  20. Distinctive diet-tissue isotopic discrimination factors derived from the exclusive bamboo-eating giant panda.

    Science.gov (United States)

    Han, Han; Wei, Wei; Nie, Yonggang; Zhou, Wenliang; Hu, Yibo; Wu, Qi; Wei, Fuwen

    2016-11-01

    Stable isotope analysis is very useful in animal ecology, especially in diet reconstruction and trophic studies. Differences in isotope ratios between consumers and their diet, termed discrimination factors, are essential for studies of stable isotope ecology and are species-specific and tissue-specific. Given the specialized bamboo diet and clear foraging behavior, here, we calculated discrimination factors for carbon and nitrogen isotopes from diet to tissues (tooth enamel, hair keratin and bone collagen) for the giant panda (Ailuropoda melanoleuca), a species derived from meat-eating ancestors. Our results showed that carbon discrimination factor obtained from giant panda tooth enamel (ε 13 C diet-enamel = 10.0‰) and nitrogen discrimination factors from hair keratin (Δ 15 N diet-hair = 2.2‰) and bone collagen (Δ 15 N diet-collagen = 2.3‰) were lower, and carbon discrimination factors from hair keratin (Δ 13 C diet-hair = 5.0‰) and bone collagen (Δ 13 C diet-collagen = 6.1‰) were higher than those of other mammalian carnivores, omnivores and herbivores. Such distinctive values are likely the result of a low-nutrient and specialized bamboo diet, carnivore-like digestive system and exceptionally low metabolism in giant pandas. © 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  1. Reprint of: Atmospheric scanning electron microscope observes cells and tissues in open medium through silicon nitride film.

    Science.gov (United States)

    Nishiyama, Hidetoshi; Suga, Mitsuo; Ogura, Toshihiko; Maruyama, Yuusuke; Koizumi, Mitsuru; Mio, Kazuhiro; Kitamura, Shinichi; Sato, Chikara

    2010-11-01

    Direct observation of subcellular structures and their characterization is essential for understanding their physiological functions. To observe them in open environment, we have developed an inverted scanning electron microscope with a detachable, open-culture dish, capable of 8 nm resolution, and combined with a fluorescence microscope quasi-simultaneously observing the same area from the top. For scanning electron microscopy from the bottom, a silicon nitride film window in the base of the dish maintains a vacuum between electron gun and open sample dish while allowing electrons to pass through. Electrons are backscattered from the sample and captured by a detector under the dish. Cells cultured on the open dish can be externally manipulated under optical microscopy, fixed, and observed using scanning electron microscopy. Once fine structures have been revealed by scanning electron microscopy, their component proteins may be identified by comparison with separately prepared fluorescence-labeled optical microscopic images of the candidate proteins, with their heavy-metal-labeled or stained ASEM images. Furthermore, cell nuclei in a tissue block stained with platinum-blue were successfully observed without thin-sectioning, which suggests the applicability of this inverted scanning electron microscope to cancer diagnosis. This microscope visualizes mesoscopic-scale structures, and is also applicable to non-bioscience fields including polymer chemistry. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. * Hierarchically Structured Electrospun Scaffolds with Chemically Conjugated Growth Factor for Ligament Tissue Engineering.

    Science.gov (United States)

    Pauly, Hannah M; Sathy, Binulal N; Olvera, Dinorath; McCarthy, Helen O; Kelly, Daniel J; Popat, Ketul C; Dunne, Nicholas J; Haut Donahue, Tammy Lynn

    2017-08-01

    The anterior cruciate ligament (ACL) of the knee is vital for proper joint function and is commonly ruptured during sports injuries or car accidents. Due to a lack of intrinsic healing capacity and drawbacks with allografts and autografts, there is a need for a tissue-engineered ACL replacement. Our group has previously used aligned sheets of electrospun polycaprolactone nanofibers to develop solid cylindrical bundles of longitudinally aligned nanofibers. We have shown that these nanofiber bundles support cell proliferation and elongation and the hierarchical structure and material properties are similar to the native human ACL. It is possible to combine multiple nanofiber bundles to create a scaffold that attempts to mimic the macroscale structure of the ACL. The goal of this work was to develop a hierarchical bioactive scaffold for ligament tissue engineering using connective tissue growth factor (CTGF)-conjugated nanofiber bundles and evaluate the behavior of mesenchymal stem cells (MSCs) on these scaffolds in vitro and in vivo. CTGF was immobilized onto the surface of individual nanofiber bundles or scaffolds consisting of multiple nanofiber bundles. The conjugation efficiency and the release of conjugated CTGF were assessed using X-ray photoelectron spectroscopy, assays, and immunofluorescence staining. Scaffolds were seeded with MSCs and maintained in vitro for 7 days (individual nanofiber bundles), in vitro for 21 days (scaled-up scaffolds of 20 nanofiber bundles), or in vivo for 6 weeks (small scaffolds of 4 nanofiber bundles), and ligament-specific tissue formation was assessed in comparison to non-CTGF-conjugated control scaffolds. Results showed that CTGF conjugation encouraged cell proliferation and ligament-specific tissue formation in vitro and in vivo. The results suggest that hierarchical electrospun nanofiber bundles conjugated with CTGF are a scalable and bioactive scaffold for ACL tissue engineering.

  3. Cartilage tissue engineering: Role of mesenchymal stem cells along with growth factors & scaffolds

    Directory of Open Access Journals (Sweden)

    M B Gugjoo

    2016-01-01

    Full Text Available Articular cartilage injury poses a major challenge for both the patient and orthopaedician. Articular cartilage defects once formed do not regenerate spontaneously, rather replaced by fibrocartilage which is weaker in mechanical competence than the normal hyaline cartilage. Mesenchymal stem cells (MSCs along with different growth factors and scaffolds are currently incorporated in tissue engineering to overcome the deficiencies associated with currently available surgical methods and to facilitate cartilage healing. MSCs, being readily available with a potential to differentiate into chondrocytes which are enhanced by the application of different growth factors, are considered for effective repair of articular cartilage after injury. However, therapeutic application of MSCs and growth factors for cartilage repair remains in its infancy, with no comparative clinical study to that of the other surgical techniques. The present review covers the role of MSCs, growth factors and scaffolds for the repair of articular cartilage injury.

  4. Some growth factors in neoplastic tissues of brain tumors of different histological structure

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2016-01-01

    Full Text Available Introduction. Pathologic angiogenesis is typical for angiogenic diseases including tumor growth. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, transforming growth factor alpha and beta (which are also known as “triggers” of angiogenesis, and other factors (Gacche, Meshram, 2013; Nijaguna et al., 2015 play a special role in its development. Evaluation of the important mechanisms of angiogenesis in physiological and pathological conditions remains to be a subject of heightened interest for the past 30 years. It is known that VEGF A is the main trigger of growing blood vessels into the tumor tissue. This is specific mitogen signal for endothelial cells that triggers the mechanisms of cell division and migration. VEGF-induced tumor vasculature has a number of structural and functional features that provide growth and progression of tumors, including increased permeability of blood vessels and their chaotic arrangement.Objective: to study in comparative aspect the level of certain growth factors in the following tissues: glioblastomas, brain metastasis of the breast cancer, meningiomas as well as corresponding peritumoral areas.Materials and methods. Tissue samples were obtained from 56 patients admitted to the surgical treatment in Rostov Research Institute of Oncology: 24 patients had glioblastomas, 19 patients had brain metastasis of the breast cancer, 13 patients with meningiomas without peritumoral edema. Histological control was carried out in all cases. Age of patients ranged from 35 to 72 years. The level of growth factor was detected in the samples of tumor tissue and regions immediately adjacent to the tumor foci (peritumoral area by the method of immunoassay and using standard test systems. The following growth factor were detected: VEGF-A and its receptors VEGF-R1 (BenderMedSystem, Austria, VEGF-C and its receptor VEGF-R3 (BenderMedSystem, Austria, EGF (Biosource, USA, IFR-1 and IFR-2 (Mediagnost, USA, TGF

  5. Hypoxia-Inducible Factors: Mediators of Cancer Progression; Prognostic and Therapeutic Targets in Soft Tissue Sarcomas

    International Nuclear Information System (INIS)

    Sadri, Navid; Zhang, Paul J.

    2013-01-01

    Soft-tissue sarcomas remain aggressive tumors that result in death in greater than a third of patients due to either loco-regional recurrence or distant metastasis. Surgical resection remains the main choice of treatment for soft tissue sarcomas with pre- and/or post-operational radiation and neoadjuvant chemotherapy employed in more advanced stage disease. However, in recent decades, there has been little progress in the average five-year survival for the majority of patients with high-grade soft tissue sarcomas, highlighting the need for improved targeted therapeutic agents. Clinical and preclinical studies demonstrate that tumor hypoxia and up-regulation of hypoxia-inducible factors (HIFs) is associated with decreased survival, increased metastasis, and resistance to therapy in soft tissue sarcomas. HIF-mediated gene expression regulates many critical aspects of tumor biology, including cell survival, metabolic programming, angiogenesis, metastasis, and therapy resistance. In this review, we discuss HIFs and HIF-mediated genes as potential prognostic markers and therapeutic targets in sarcomas. Many pharmacological agents targeting hypoxia-related pathways are in development that may hold therapeutic potential for treating both primary and metastatic sarcomas that demonstrate increased HIF expression

  6. Tissue Factor–Factor VII Complex as a Key Regulator of Ovarian Cancer Phenotypes

    Directory of Open Access Journals (Sweden)

    Shiro Koizume

    2015-01-01

    Full Text Available Tissue factor (TF is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF–fVII complex. Here, we discuss the roles of the TF–fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF–fVII function.

  7. Factors Associated with Decreased Lean Tissue Index in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Yi-Wen Wang

    2017-04-01

    Full Text Available Muscle wasting is common and is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD. However, factors associated with decreased muscle mass in CKD patients are seldom reported. We performed a cross-sectional study of 326 patients (age 65.8 ± 13.3 years with stage 3–5 CKD who were not yet on dialysis. Muscle mass was determined using the Body Composition Monitor (BCM, a multifrequency bioimpedance spectroscopy device, and was expressed as the lean tissue index (LTI, lean tissue mass/height2. An LTI of less than 10% of the normal value (low LTI indicates muscle wasting. Patients with low LTI (n = 40 tended to be diabetic, had significantly higher fat tissue index, urine protein creatinine ratio, and interleukin-6 and tumor necrosis factor-α levels, but had significantly lower serum albumin and hemoglobin levels compared with those with normal LTI. In multivariate linear regression analysis, age, sex, cardiovascular disease, and interleukin-6 were independently associated with LTI. Additionally, diabetes mellitus remained an independent predictor of muscle wasting according to low LTI by multivariate logistic regression analysis. We conclude that LTI has important clinical correlations. Determination of LTI may aid in clinical assessment by helping to identify muscle wasting among patients with stage 3–5 CKD.

  8. Tissue factor expression in rheumatoid synovium: a potential role in pannus invasion of rheumatoid arthritis.

    Science.gov (United States)

    Chen, Lujun; Lu, Yahua; Chu, Yang; Xie, Jun; Ding, Wen'ge; Wang, Fengming

    2013-09-01

    Angiogenesis, as well as pannus formation within the joint, plays an important role in the erosion of articular cartilage and bone in the pathological process of rheumatoid arthritis (RA). Tissue factor (TF), an essential initiator of the extrinsic pathway of blood coagulation, is also involved in the angiogenesis and the pannus formation of RA progression. In the present study, we used immunofluorescence and confocal scanning methods to characterize TF immunolocalization in RA synovium. We showed that positive staining of TF could be immunolocalized in synoviocytes, CD19(+) B cells and CD68(+) macrophages, whereas weak or negative staining of tissue factor could be found in CD34(+) endothelial cells of neo-vessels, CD3(+) T cells and CD14(+) monocytes in RA synovium tissues. Our study demonstrates a detailed local expression of TF in the rheumatoid synovium, and supports the notion that TF, expressed not only by the synoviocytes themselves, but also the infiltrating CD19(+) B cells and CD68(+) macrophages, is involved in the pannus invasion in the progression of rheumatoid arthritis. Copyright © 2013 Elsevier GmbH. All rights reserved.

  9. The roles of connective tissue growth factor in the development of anastomotic esophageal strictures.

    Science.gov (United States)

    Zhao, Haibin; Zhao, Lingna; Zhou, Zhihua; Wu, Yaoyi

    2015-08-12

    The aim of this study was to investigate the roles of connective tissue growth factor (CTGF) in the development of anastomotic strictures after surgical repair of the esophagus. Tissues collected from the patients were divided into three groups based on the results of endoscopy and clinical grading. Patients without dysphagia after esophagectomy were used as the control population. The protein levels of CTGF, TGF-β1, Smad2, and Smad4 were determined by immunohistochemistry (IHC) and western blot analyses, while the mRNA levels of the two growth factors were evaluated by real-time polymerase chain reaction. Compared with the control group, significantly increased (p tissues collected from the patients with stenosis were significantly up-regulated (p < 0.05) as compared with those from the control group. In addition, the levels of Smad2 and Smad4 protein were also significantly increased (p < 0.05) with the increasing severity of stenosis, and the protein levels were positively correlated with the levels of CTGF (r = 0.59, p < 0.05) and TGF-β1 (r = 0.63, p < 0.05). Inhibition of CTGF protein or mRNA expression may be a distinctive and effective therapy for the treatment of postoperative anastomotic strictures.

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

    Science.gov (United States)

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

    2004-02-15

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

  11. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

    Directory of Open Access Journals (Sweden)

    Rinaldo Florencio-Silva

    2015-01-01

    Full Text Available Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines and systemic (e.g., calcitonin and estrogens factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

  12. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells.

    Science.gov (United States)

    Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

    2015-01-01

    Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

  13. Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer.

    Science.gov (United States)

    Cui, X Y; Tinholt, M; Stavik, B; Dahm, A E A; Kanse, S; Jin, Y; Seidl, S; Sahlberg, K K; Iversen, N; Skretting, G; Sandset, P M

    2016-02-01

    ESSENTIALS: A hypoxic microenvironment is a common feature of tumors that may influence activation of coagulation. MCF-7 and SK-BR-3 breast cancer cells and breast cancer tissue samples were used. The results showed transcriptional repression of tissue factor pathway inhibitor expression in hypoxia. Hypoxia-inducible factor 1α may be a target for the therapy of cancer-related coagulation and thrombosis. Activation of coagulation is a common finding in patients with cancer, and is associated with an increased risk of venous thrombosis. As a hypoxic microenvironment is a common feature of solid tumors, we investigated the role of hypoxia in the regulation of tissue factor (TF) pathway inhibitor (TFPI) expression in breast cancer. To explore the transcriptional regulation of TFPI by hypoxia-inducible factor (HIF)-1α in breast cancer cells and their correlation in breast cancer tissues. MCF-7 and SK-BR-3 breast cancer cells were cultured in 1% oxygen or treated with cobalt chloride (CoCl2 ) to mimic hypoxia. Time-dependent and dose-dependent downregulation of TFPI mRNA (quantitative RT-PCR) and of free TFPI protein (ELISA) were observed in hypoxia. Western blotting showed parallel increases in the levels of HIF-1α protein and TF. HIF-1α inhibitor abolished or attenuated the hypoxia-induced downregulation of TFPI. Luciferase reporter assay showed that both hypoxia and HIF-1α overexpression caused strong repression of TFPI promoter activity. Subsequent chromatin immunoprecipitation and mutagenesis analysis demonstrated a functional hypoxia response element within the TFPI promoter, located at -1065 to -1060 relative to the transcriptional start point. In breast cancer tissue samples, gene expression analyses showed a positive correlation between the mRNA expression of TFPI and that of HIF-1α. This study demonstrates that HIF-1α is involved in the transcriptional regulation of the TFPI gene, and suggests that a hypoxic microenvironment inside a breast tumor may

  14. Detection of von Willebrand factor and tissue factor in platelets-fibrin rich coronary thrombi in acute myocardial infarction.

    Science.gov (United States)

    Yamashita, Atsushi; Sumi, Takahiro; Goto, Shinya; Hoshiba, Yasunari; Nishihira, Kensaku; Kawamoto, Riichirou; Hatakeyama, Kinta; Date, Haruhiko; Imamura, Takuroh; Ogawa, Hisao; Asada, Yujiro

    2006-01-01

    The rapid closure of coronary arteries due to occlusive thrombi is the major cause of acute myocardial infarction. However, the mechanisms of coronary thrombus formation have not been elucidated. We immunohistochemically assessed the localizations and their changes over time of glycoprotein IIb/IIIa, fibrin, von Willebrand factor (vWF), and tissue factor (TF), after the onset of chest pain (platelets, fibrin, vWF, and TF from the early phase of onset, and glycoprotein IIb/IIIa and fibrin were closely associated with vWF and TF, respectively. vWF and/or TF may contribute to occlusive thrombus formation and be novel therapeutic candidates for treating patients with coronary thrombosis.

  15. A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

    DEFF Research Database (Denmark)

    Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik

    2007-01-01

    Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD......) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation...... in the presence of TF or an active-site inhibitor. Based on MD simulations, a key switch of the TF-induced structural changes is identified as the interacting pair Leu305{163} and Phe374{225} in FVIIa, whose mutual conformations are guided by the presence of TF and observed to be closely linked to the structural...

  16. Critical success factors in the lithuanian electronic business market

    OpenAIRE

    Žvirblytė, Justina

    2007-01-01

    By seeking to be active participant in the global market without information technologies would be impossible to implement the innovative business decisions. Market conditions in growing economy and competition, business globalization as well as innovations in the field of information and communication technologies the companies stimulate to invest in development of the electronic business increasingly. Electronic business – is a use of modern means of information and communication technologi...

  17. Predictive model of thrombospondin-1 and vascular endothelial growth factor in breast tumor tissue.

    Science.gov (United States)

    Rohrs, Jennifer A; Sulistio, Christopher D; Finley, Stacey D

    2016-01-01

    Angiogenesis, the formation of new blood capillaries from pre-existing vessels, is a hallmark of cancer. Thus far, strategies for reducing tumor angiogenesis have focused on inhibiting pro-angiogenic factors, while less is known about the therapeutic effects of mimicking the actions of angiogenesis inhibitors. Thrombospondin-1 (TSP1) is an important endogenous inhibitor of angiogenesis that has been investigated as an anti-angiogenic agent. TSP1 impedes the growth of new blood vessels in many ways, including crosstalk with pro-angiogenic factors. Due to the complexity of TSP1 signaling, a predictive systems biology model would provide quantitative understanding of the angiogenic balance in tumor tissue. Therefore, we have developed a molecular-detailed, mechanistic model of TSP1 and vascular endothelial growth factor (VEGF), a promoter of angiogenesis, in breast tumor tissue. The model predicts the distribution of the angiogenic factors in tumor tissue, revealing that TSP1 is primarily in an inactive, cleaved form due to the action of proteases, rather than bound to its cellular receptors or to VEGF. The model also predicts the effects of enhancing TSP1's interactions with its receptors and with VEGF. To provide additional predictions that can guide the development of new anti-angiogenic drugs, we simulate administration of exogenous TSP1 mimetics that bind specific targets. The model predicts that the CD47-binding TSP1 mimetic dramatically decreases the ratio of receptor-bound VEGF to receptor-bound TSP1, in favor of anti-angiogenesis. Thus, we have established a model that provides a quantitative framework to study the response to TSP1 mimetics.

  18. Factors that influence soft tissue thickness over the greater trochanter: application to understanding hip fractures.

    Science.gov (United States)

    Levine, Iris C; Minty, Lauren E; Laing, Andrew C

    2015-03-01

    Fall-related hip injuries are a concern for the growing population of older adults. Evidence suggests that soft tissue overlying the greater trochanter attenuates the forces transmitted to the proximal femur during an impact, reducing mechanical risk of hip fracture. However, there is limited information about the factors that influence trochanteric soft tissue thickness. The current study used ultrasonography and electromyography to determine whether trochanteric soft tissue thickness could be quantified reproducibly and whether it was influenced by: (1) gender; (2) hip postures associated with potential falling configurations in the sagittal plane (from 30° of extension to 60° of flexion, at 15° intervals), combined adduction-flexion, and combined adduction-extension; and (3) activation levels of the tensor fascia lata (TFL) and gluteus medius (GM) muscles. Our results demonstrated that soft tissue thickness can be measured reliably in nine hip postures and three muscle activation conditions (for all conditions, ICC >0.98). Mean (SD) thickness in quiet stance was 2.52 cm. Thickness was 27.0% lower for males than females during quiet stance. It was 16.4% greater at maximum flexion than quiet standing, 27.2% greater at maximum extension, and 12.5% greater during combined adduction-flexion. However, there was no significant difference between combined adduction-extension and quiet standing. Thickness was not affected by changes in muscle activity. Forces applied to the femoral neck during a lateral fall decrease as trochanteric soft tissue thickness increases; gender and postural configuration at impact could influence the loads applied to the proximal femur (and thus hip fracture risk) during falls on the hip. © 2014 Wiley Periodicals, Inc.

  19. Factors associated with deep tissue injury in male wheelchair basketball players of a Japanese national team

    Directory of Open Access Journals (Sweden)

    Hirotaka Mutsuzaki

    2014-04-01

    Full Text Available Maintenance of the sporting activity of elite athletes in adapted sports can be difficult if a secondary disorder, such as a pressure ulcer, occurs. Pressure ulcers result from deep tissue injuries by external pressure. The purpose of this study was to use ultrasonography to investigate deep tissue injuries in male wheelchair basketball players of a Japanese national team, and to determine factors associated with the injuries (e.g., body mass index, class of wheelchair basketball, underlying disease, length of athletic career, and whether use of wheelchair is primarily for playing basketball. Twenty male Japanese wheelchair basketball players on the national team for the 2012 London Paralympic Games (12 representative players and eight candidate representative players participated in this study. The sacral region and bilateral ischial regions in each athlete were examined by ultrasonography to detect low-echoic lesions indicative of deep tissue injuries. Nine (45% players had low-echoic lesions, which were detected in 10 of 60 areas. Eight lesions were detected in the sacral region and two lesions were detected in the ischial region. More players with spinal cord injury had low-echoic lesions [9 (69.2% of 13 players], compared to players with skeletal system disease [0 (0% of 7 players, p = 0.002]. Players who used a wheelchair in daily life were more likely to have low-echoic lesions [8 (66.74% of 12 players], compared to players who primarily used a wheelchair for playing basketball [1 (12.5% of 8 players, p = 0.010]. Deep tissue injuries were detected in 45% of male Japanese wheelchair basketball players on the national team. Players with spinal cord injury and players who used a wheelchair in daily life were more likely to have deep tissue injuries, particularly in the sacral region. The lesions were small, but a periodic medical check should be performed to maintain athletes' sporting life.

  20. Mathematical Model of Growth Factor Driven Haptotaxis and Proliferation in a Tissue Engineering Scaffold

    KAUST Repository

    Pohlmeyer, J. V.

    2013-01-29

    Motivated by experimental work (Miller et al. in Biomaterials 27(10):2213-2221, 2006, 32(11):2775-2785, 2011) we investigate the effect of growth factor driven haptotaxis and proliferation in a perfusion tissue engineering bioreactor, in which nutrient-rich culture medium is perfused through a 2D porous scaffold impregnated with growth factor and seeded with cells. We model these processes on the timescale of cell proliferation, which typically is of the order of days. While a quantitative representation of these phenomena requires more experimental data than is yet available, qualitative agreement with preliminary experimental studies (Miller et al. in Biomaterials 27(10):2213-2221, 2006) is obtained, and appears promising. The ultimate goal of such modeling is to ascertain initial conditions (growth factor distribution, initial cell seeding, etc.) that will lead to a final desired outcome. © 2013 Society for Mathematical Biology.

  1. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

    Science.gov (United States)

    Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

    2016-06-23

    The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

  2. Dose-rate conversion factors for external exposure to photon and electron radiation from radionuclides occurring in routine releases from nuclear fuel cycle facilities

    International Nuclear Information System (INIS)

    Kocher, D.C.

    1980-01-01

    Dose-rate conversion factors for external exposure to photon and electron radiation are calculated for 240 radionuclides of potential importance in routine releases from nuclear fuel cycle facilities. Exposure modes considered are immersion in contaminated air, immersion in contaminated water, and irradiation from a contaminated ground surface. For each exposure mode, dose-rate conversion factors for photons and electrons are calculated for tissue-equivalent material at the body surface of an exposed individual. Dose-rate conversion factors for photons only are calculated for 22 body organs. (author)

  3. In vitro evidence of a tissue factor-independent mode of action of recombinant factor VIIa in hemophilia.

    Science.gov (United States)

    Augustsson, Cecilia; Persson, Egon

    2014-11-13

    Successful competition of activated factor VII (FVIIa) with zymogen factor VII (FVII) for tissue factor (TF) and loading of the platelet surface with FVIIa are plausible driving forces behind the pharmacological effect of recombinant FVIIa (rFVIIa) in hemophilia patients. Thrombin generation measurements in platelet-rich hemophilia A plasma revealed competition for TF, which potentially could reduce the effective (r)FVIIa:TF complex concentration and thereby attenuate factor Xa production. However, (auto)activation of FVII apparently counteracted the negative effect of zymogen binding; a small impact was observed at endogenous concentrations of FVII and FVIIa but was virtually absent at pharmacological amounts of rFVIIa. Moreover, corrections of the propagation phase in hemophilia A required rFVIIa concentrations above the range where a physiological level of FVII was capable to downregulate thrombin generation. These data strongly suggest that rFVIIa acts independently of TF in hemophilia therapy and that FVII displacement by rFVIIa is a negligible mechanistic component. © 2014 by The American Society of Hematology.

  4. Modulation of radiation effects in tissues by keratinocyte growth factor (KGF)

    International Nuclear Information System (INIS)

    Doerr, W.; Lacmann, A.; Noack, R.; Spekl, K.

    2000-01-01

    Keratinocyte Growth Factor (KGF) is a member of the fibroblast growth factor family. KGF is produced by mesenchymal cells, predominantly fibroblasts; target cells are epithelial cells in a variety of tissues. Hence, KGF is a mediator of the mesenchymal-epithelial communication and a regulator of tissue homeostasis in epithelia. Systemic administration of KGF in animal models induces stimulation of proliferation and modulation of migration and differentiation processes in squamous epithelia. This results in a transient increase in cell numbers and epithelial thickness. Radiation exposure of epithelia causes an imbalance between cell production and cell loss, which in consequence causes progressive cell depletion and eventually complete denudation. Systemic application of KGF reduces the radiation-induced cell loss. This effect is most pronounced when KGF is given after the radiation exposure. With regard to epithelial radiation tolerance, KGF-application in animal models results in a significant increase, by a factor of 1.7-2.3, in the doses required to induce epithelial ulceration as a clinically most relevant endpoint. After exposure with a given dose, this translates into a significant reduction of the clinical manifestation of the acute radiation sequelae. This effect is accompanied by a modification of the time course of the response. In conclusion, although the mechanisms underlying the protective efficacy remain unclear, KGF may represent an effective approach for amelioration of radiation effects in oral, gastrointestinal and cutaneous epithelia. Results from a clinical pilot study indicate that KGF is well tolerated and effective in humans. (orig.) [de

  5. Is NAA reduction in normal contralateral cerebral tissue in stroke patients dependent on underlying risk factors?

    Science.gov (United States)

    Walker, P M; Ben Salem, D; Giroud, M; Brunotte, F

    2006-05-01

    This retrospective study investigated the dependence of N-acetyl aspartate (NAA) ratios on risk factors for cerebral vasculopathy such as sex, age, hypertension, diabetes mellitus, carotid stenosis, and dyslipidaemia, which may have affected brain vessels and induced metabolic brain abnormalities prior to stroke. We hypothesise that in stroke patients metabolic alterations in the apparently normal contralateral brain are dependent on the presence or not of such risk factors. Fifty nine patients (31 male, 28 female: 58.8+/-16.1 years old) with cortical middle cerebral artery (MCA) territory infarction were included. Long echo time chemical shift imaging spectroscopy was carried out on a Siemens 1.5 T Magnetom Vision scanner using a multi-voxel PRESS technique. Metabolite ratios (NAA/choline, NAA/creatine, lactate/choline, etc) were studied using uni- and multivariate analyses with respect to common risk factors. The influence of age, stroke lesion size, and time since stroke was studied using a linear regression approach. Age, sex, and hypertension all appeared to individually influence metabolite ratios, although only hypertension was significant after multivariate analysis. In both basal ganglia and periventricular white matter regions in apparently normal contralateral brain, the NAA/choline ratio was significantly lower in hypertensive (1.37+/-0.16 and 1.50+/-0.19, respectively) than in normotensive patients (1.72+/-0.19 and 1.85+/-0.15, respectively). Regarding MCA infarction, contralateral tissue remote from the lesion behaves abnormally in the presence of hypertension, the NAA ratios in hypertensive patients being significantly lower. These data suggest that hypertension may compromise the use of contralateral tissue data as a reference for comparison with ischaemic tissue.

  6. Polybrominated diphenyl ethers in chicken tissues and eggs from an electronic waste recycling area in southeast China

    Institute of Scientific and Technical Information of China (English)

    Xiaofei Qin; Yongjian Yang; Zhanfen Qin; Yan Li; Yaxian Zhao; Xijuan Xia; Shishuai Yan; Mi Tian; Xingru Zhao; Xiaobai XU

    2011-01-01

    The levels and distributions of polybrominated diphenyl ethers (PBDEs) in chicken tissues from an electronic waste (e-waste)recycling area in southeast China were investigated. Human dietary intake by local residents via chicken muscle and eggs was estimated.The mean PBDEs concentrations in tissues ranged from 15.2 to 3138.1 ng/g lipid weight (lw) and in egg the concentration was 563.5 ng/g lw. The results showed that the level of total PBDEs (∑PBDEs) in the chicken tissue was 2-3 orders of magnitude higher than those reported in the literature. The large difference of ΣPBDEs concentrations between tissues confirmed that the distribution of PBDEs in tissues depend on tissue-specificity rather than the “lipid-compartment”. BDE-209 was the predominant congener (82.5%-94.7% of ∑PBDEs) in all chicken tissues except in brain (34.7% of ∑PBDEs), which indicated that deca-BDE (the major commercial PBDE formulation comprising 65%-70% of total production) was major pollution source in this area and could be bioaccumulated in terrestrial animals. The dietary PBDEs intake of the local residents from chicken muscle and egg, assuming only local bred chickens and eggs were consumed, ranged from 2.2 to 22.5 ng/(day·kg body weight (bw)) with a mean value of 13.5 ng/(day.kg bw), which was one order of magnitude higher than the value reported in previous studies for consumption of all foodstuffs.

  7. Polybrominated diphenyl ethers in chicken tissues and eggs from an electronic waste recycling area in southeast China.

    Science.gov (United States)

    Qin, Xiaofei; Qin, Zhanfen; Li, Yan; Zhao, Yaxian; Xia, Xijuan; Yan, Shishuai; Tian, Mi; Zhao, Xingru; Xu, Xiaobai; Yang, Yongjian

    2011-01-01

    The levels and distributions of polybrominated diphenyl ethers (PBDEs) in chicken tissues from an electronic waste (e-waste) recycling area in southeast China were investigated. Human dietary intake by local residents via chicken muscle and eggs was estimated. The mean PBDEs concentrations in tissues ranged from 15.2 to 3138.1 ng/g lipid weight (lw) and in egg the concentration was 563.5 ng/g lw. The results showed that the level of total PBDEs (sigmaPBDEs) in the chicken tissue was 2-3 orders of magnitude higher than those reported in the literature. The large difference of sigmaPBDEs concentrations between tissues confirmed that the distribution of PBDEs in tissues depend on tissue-specificity rather than the "lipid-compartment". BDE-209 was the predominant congener (82.5%-94.7% of sigmaPBDEs) in all chicken tissues except in brain (34.7% of sigmaPBDEs), which indicated that deca-BDE (the major commercial PBDE formulation comprising 65%-70% of total production) was major pollution source in this area and could be bioaccumulated in terrestrial animals. The dietary PBDEs intake of the local residents from chicken muscle and egg, assuming only local bred chickens and eggs were consumed, ranged from 2.2 to 22.5 ng/(day x kg body weight (bw)) with a mean value of 13.5 ng/(day x kg bw), which was one order of magnitude higher than the value reported in previous studies for consumption of all foodstuffs.

  8. Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors.

    Science.gov (United States)

    Butler, Jason M; Kobayashi, Hideki; Rafii, Shahin

    2010-02-01

    The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. We propose that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair not only by delivering nutrients and O2 but also through an 'angiocrine' mechanism by producing stem and progenitor cell-active trophogens. Identification of endothelial-derived instructive angiocrine factors will allow direct tumour targeting, while diminishing the unwanted side effects associated with the use of anti-angiogenic agents.

  9. Radiobiological influence of megavoltage electron pulses of ultra-high pulse dose rate on normal tissue cells.

    Science.gov (United States)

    Laschinsky, Lydia; Karsch, Leonhard; Leßmann, Elisabeth; Oppelt, Melanie; Pawelke, Jörg; Richter, Christian; Schürer, Michael; Beyreuther, Elke

    2016-08-01

    Regarding the long-term goal to develop and establish laser-based particle accelerators for a future radiotherapeutic treatment of cancer, the radiobiological consequences of the characteristic short intense particle pulses with ultra-high peak dose rate, but low repetition rate of laser-driven beams have to be investigated. This work presents in vitro experiments performed at the radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance). This accelerator delivered 20-MeV electron pulses with ultra-high pulse dose rate of 10(10) Gy/min either at the low pulse frequency analogue to previous cell experiments with laser-driven electrons or at high frequency for minimizing the prolonged dose delivery and to perform comparison irradiation with a quasi-continuous electron beam analogue to a clinically used linear accelerator. The influence of the different electron beam pulse structures on the radiobiological response of the normal tissue cell line 184A1 and two primary fibroblasts was investigated regarding clonogenic survival and the number of DNA double-strand breaks that remain 24 h after irradiation. Thereby, no considerable differences in radiation response were revealed both for biological endpoints and for all probed cell cultures. These results provide evidence that the radiobiological effectiveness of the pulsed electron beams is not affected by the ultra-high pulse dose rates alone.

  10. Radiobiological influence of megavoltage electron pulses of ultra-high pulse dose rate on normal tissue cells

    International Nuclear Information System (INIS)

    Laschinsky, Lydia; Karsch, Leonhard; Schuerer, Michael; Lessmann, Elisabeth; Beyreuther, Elke; Oppelt, Melanie; Pawelke, Joerg; Richter, Christian

    2016-01-01

    Regarding the long-term goal to develop and establish laser-based particle accelerators for a future radiotherapeutic treatment of cancer, the radiobiological consequences of the characteristic short intense particle pulses with ultra-high peak dose rate, but low repetition rate of laser-driven beams have to be investigated. This work presents in vitro experiments performed at the radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance). This accelerator delivered 20-MeV electron pulses with ultra-high pulse dose rate of 10"1"0 Gy/min either at the low pulse frequency analogue to previous cell experiments with laser-driven electrons or at high frequency for minimizing the prolonged dose delivery and to perform comparison irradiation with a quasi-continuous electron beam analogue to a clinically used linear accelerator. The influence of the different electron beam pulse structures on the radiobiological response of the normal tissue cell line 184A1 and two primary fibroblasts was investigated regarding clonogenic survival and the number of DNA double-strand breaks that remain 24 h after irradiation. Thereby, no considerable differences in radiation response were revealed both for biological endpoints and for all probed cell cultures. These results provide evidence that the radiobiological effectiveness of the pulsed electron beams is not affected by the ultra-high pulse dose rates alone. (orig.)

  11. How to make the fourth revolution: Human factors in the adoption of electronic instructional aids

    Science.gov (United States)

    Demerath, N. J.; Daniels, L. A.

    1973-01-01

    The prospects and problems of getting higher education in the United States (high school and above) to more fully utilize electronic technologies are examined. Sociological, psychological, and political factors are analyzed to determine the feasibility of adopting electronic instructional techniques. Differences in organizations, attitudes, and customs of different kinds of students, teachers, administrators, and publics are crucial factors in innovation.

  12. Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

    Energy Technology Data Exchange (ETDEWEB)

    Sawada, Keigo [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Takedachi, Masahide, E-mail: takedati@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Lee, Chun Man [Medical Center for Translational Research, Osaka University Hospital, Osaka (Japan); Okura, Hanayuki; Matsuyama, Akifumi [Research on Disease Bioresources, Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, Osaka (Japan); Kitamura, Masahiro; Murakami, Shinya [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan)

    2015-08-14

    Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation.

  13. Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

    International Nuclear Information System (INIS)

    Sawada, Keigo; Takedachi, Masahide; Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki; Lee, Chun Man; Okura, Hanayuki; Matsuyama, Akifumi; Kitamura, Masahiro; Murakami, Shinya

    2015-01-01

    Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation

  14. Nuclear factor 1 regulates adipose tissue-specific expression in the mouse GLUT4 gene

    International Nuclear Information System (INIS)

    Miura, Shinji; Tsunoda, Nobuyo; Ikeda, Shinobu; Kai, Yuko; Cooke, David W.; Lane, M. Daniel; Ezaki, Osamu

    2004-01-01

    Previous studies demonstrated that an adipose tissue-specific element(s) (ASE) of the murine GLUT4 gene is located between -551 and -506 in the 5'-flanking sequence and that a high-fat responsive element(s) for down-regulation of the GLUT4 gene is located between bases -701 and -552. A binding site for nuclear factor 1 (NF1), that mediates insulin and cAMP-induced repression of GLUT4 in 3T3-L1 adipocytes is located between bases -700 and -688. To examine the role of NF1 in the regulation of GLUT4 gene expression in white adipose tissues (WAT) in vivo, we created two types of transgenic mice harboring mutated either 5' or 3' half-site of NF1-binding sites in GLUT4 minigene constructs. In both cases, the GLUT4 minigene was not expressed in WAT, while expression was maintained in brown adipose tissue, skeletal muscle, and heart. This was an unexpected finding, since a -551 GLUT4 minigene that did not have the NF1-binding site was expressed in WAT. We propose a model that explains the requirement for both the ASE and the NF1-binding site for expression of GLUT4 in WAT

  15. Fibroblast Growth Factor 21 Deficiency Attenuates Experimental Colitis-Induced Adipose Tissue Lipolysis

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    Liming Liu

    2017-01-01

    Full Text Available Aims. Nutrient deficiencies are common in patients with inflammatory bowel disease (IBD. Adipose tissue plays a critical role in regulating energy balance. Fibroblast growth factor 21 (FGF21 is an important endocrine metabolic regulator with emerging beneficial roles in lipid homeostasis. We investigated the impact of FGF21 in experimental colitis-induced epididymal white adipose tissue (eWAT lipolysis. Methods. Mice were given 2.5% dextran sulfate sodium (DSS ad libitum for 7 days to induce colitis. The role of FGF21 was investigated using antibody neutralization or knockout (KO mice. Lipolysis index and adipose lipolytic enzymes were determined. In addition, 3T3-L1 cells were pretreated with IL-6, followed by recombinant human FGF21 (rhFGF21 treatment; lipolysis was assessed. Results. DSS markedly decreased eWAT/body weight ratio and increased serum concentrations of free fatty acid (FFA and glycerol, indicating increased adipose tissue lipolysis. eWAT intracellular lipolytic enzyme expression/activation was significantly increased. These alterations were significantly attenuated in FGF21 KO mice and by circulating FGF21 neutralization. Moreover, DSS treatment markedly increased serum IL-6 and FGF21 levels. IL-6 pretreatment was necessary for the stimulatory effect of FGF21 on adipose lipolysis in 3T3-L1 cells. Conclusions. Our results demonstrate that experimental colitis induces eWAT lipolysis via an IL-6/FGF21-mediated signaling pathway.

  16. Ontogeny of basic fibroblast growth factor binding sites in mouse ocular tissues

    International Nuclear Information System (INIS)

    Fayein, N.A.; Courtois, Y.; Jeanny, J.C.

    1990-01-01

    Basic fibroblast growth factor (bFGF) binding to ocular tissues has been studied by autoradiographical and biochemical approaches directly performed on sections during mouse embryonic and postnatal development. Frozen sections of embryos (9 to 18 days), newborns, and adults (1 day to 6 months) were incubated with iodinated bFGF. One specific FGF binding site (KD = 2.5 nM) is colocalized with heparan sulfate proteoglycans of the basement membranes and is heparitinase sensitive. It first appears at Day 9 around the neural tube, the optic vesicles, and below the head ectoderm and by Day 14 of embryonic development is found in all basement membranes of the eye. At Day 16, very intensely labeled patches appear, corresponding to mast cells which have been characterized by metachromatic staining of their heparin-rich granulations with toluidine blue. In addition to the latter binding, we have also observed a general diffuse distribution of silver grains on all tissues and preferentially in the ecto- and neuroectodermic tissues. From Days 17-18, there is heterogeneous labeling inside the retina, localized in the pigmented epithelium and in three different layers colocalized with the inner and outer plexiform layers and with the inner segments of the photoreceptors. This binding is heparitinase resistant but N-glycanase sensitive and may represent a second specific binding site corresponding to cellular FGF receptors (KD = 280 pM). Both types of binding patterns observed suggest a significant role for bFGF in eye development and physiology

  17. [Role of connective tissue growth factor (CTGF) in proliferation and migration of pancreatic cancer cells].

    Science.gov (United States)

    Bai, Yu-chun; Kang, Quan; Luo, Qing; Wu, Dao-qi; Ye, Wei-xia; Lin, Xue-mei; Zhao, Yong

    2011-10-01

    To explore the expression of connective tissue growth factor (CTGF) in pancreatic cancer and its influence on the proliferation and migration of cancer cells. The expression of CTGF in pancreatic cell line PANC-1 cells was analyzed by real-time PCR and in pancreatic carcinoma (50 cases) tissues by immunohistochemistry. The ability of proliferation and migration in vitro of PANC-1 cells was tested by MTT assay, scratch test and Boyden chamber test after the CTGF gene was overexpressed by Ad5-CTGF or silenced with Ad5-siCTGF transfection. CTGF was overexpressed in both pancreatic cancer cells and tissues. Overxpression of CTGF leads to increased proliferation and migration of PANC-1 cells. The CTGF-transfected PANC-1 cells showed apparent stronger proliferation ability and scratch-repair ability than that of empty vector controls. The results of Boyden chamber test showed that there were 34 cells/field (200× magnificantion) of the CTGF-transfected overexpressing cells, much more than the 11 cells/field of the empty vector control cells; and 6 cells/microscopic field of the Ad5-siCTGF-transfected silenced cells, much less than the 15 cells/field of the control cells. CTGF is overexpressed in both pancreatic cancer cells in vitro and in vivo, indicating that it may play an important role in the cell proliferation and migration in pancreatic cancer.

  18. Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

    Science.gov (United States)

    Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

    2017-02-01

    Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

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

    Science.gov (United States)

    Mast, Alan E

    2016-01-01

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

  20. Common Virulence Factors and Tissue Targets of Entomopathogenic Bacteria for Biological Control of Lepidopteran Pests

    Directory of Open Access Journals (Sweden)

    Anaïs Castagnola

    2014-01-01

    Full Text Available This review focuses on common insecticidal virulence factors from entomopathogenic bacteria with special emphasis on two insect pathogenic bacteria Photorhabdus (Proteobacteria: Enterobacteriaceae and Bacillus (Firmicutes: Bacillaceae. Insect pathogenic bacteria of diverse taxonomic groups and phylogenetic origin have been shown to have striking similarities in the virulence factors they produce. It has been suggested that the detection of phage elements surrounding toxin genes, horizontal and lateral gene transfer events, and plasmid shuffling occurrences may be some of the reasons that virulence factor genes have so many analogs throughout the bacterial kingdom. Comparison of virulence factors of Photorhabdus, and Bacillus, two bacteria with dissimilar life styles opens the possibility of re-examining newly discovered toxins for novel tissue targets. For example, nematodes residing in the hemolymph may release bacteria with virulence factors targeting neurons or neuromuscular junctions. The first section of this review focuses on toxins and their context in agriculture. The second describes the mode of action of toxins from common entomopathogens and the third draws comparisons between Gram positive and Gram negative bacteria. The fourth section reviews the implications of the nervous system in biocontrol.

  1. Sucrose-induced anthocyanin accumulation in vegetative tissue of Petunia plants requires anthocyanin regulatory transcription factors.

    Science.gov (United States)

    Ai, Trinh Ngoc; Naing, Aung Htay; Arun, Muthukrishnan; Lim, Sun-Hyung; Kim, Chang Kil

    2016-11-01

    The effects of three different sucrose concentrations on plant growth and anthocyanin accumulation were examined in non-transgenic (NT) and transgenic (T 2 ) specimens of the Petunia hybrida cultivar 'Mirage rose' that carried the anthocyanin regulatory transcription factors B-Peru+mPAP1 or RsMYB1. Anthocyanin accumulation was not observed in NT plants in any treatments, whereas a range of anthocyanin accumulation was observed in transgenic plants. The anthocyanin content detected in transgenic plants expressing the anthocyanin regulatory transcription factors (B-Peru+mPAP1 or RsMYB1) was higher than that in NT plants. In addition, increasing sucrose concentration strongly enhanced anthocyanin content as shown by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, wherein increased concentrations of sucrose enhanced transcript levels of the transcription factors that are responsible for the induction of biosynthetic genes involved in anthocyanin synthesis; this pattern was not observed in NT plants. In addition, sucrose affected plant growth, although the effects were different between NT and transgenic plants. Taken together, the application of sucrose could enhance anthocyanin production in vegetative tissue of transgenic Petunia carrying anthocyanin regulatory transcription factors, and this study provides insights about interactive effects of sucrose and transcription factors in anthocyanin biosynthesis in the transgenic plant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Calculated dose factors for the radiosensitive tissues in bone irradiated by surface-deposited radionuclides

    International Nuclear Information System (INIS)

    Spiers, F.W.; Whitwell, J.R.; Beddoe, A.H.

    1978-01-01

    The method of calculating dose factors for the haemopoietic marrow and endosteal tissues in human trabecular bone, used by Whitwell and Spiers for volume-seeking radionuclides, has been developed for the case of radionuclides which are deposited as very thin layers on bone surfaces. The Monte Carlo method is again used, but modifications to the computer program are made to allow for a surface rather than a volume source of particle emission. The principal change is the introduction of a surface-orientation factor which is shown to have a value of approximately 2, varying slightly with bone structure. Results are given for β-emitting radionuclides ranging from 171 Tm(anti Esub(β) = 0.025 MeV) to 90 Y(anti Esub(β) = 0.93 MeV), and also for the α-emitter 239 Pu. It is shown that where the particle ranges are short compared with the dimensions of the bone structures the dose factors for the surface seekers are much greater than those for the volume seekers. For long range particles the dose factors for surface- and volume-seeking radionuclides converge. Comparisons are given relating the dose factors calculated in this paper on the basis of measured bone structures to those of other workers based on single plane geometry. (author)

  3. Predictive and prognostic factors associated with soft tissue sarcoma response to chemotherapy

    DEFF Research Database (Denmark)

    Young, Robin J; Litière, Saskia; Lia, Michela

    2017-01-01

    BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) 62012 study was a Phase III trial of doxorubicin versus doxorubicin-ifosfamide chemotherapy in 455 patients with advanced soft tissue sarcoma (STS). Analysis of the main study showed that combination chemotherapy...... improved tumor response and progression-free survival, but differences in overall survival (OS) were not statistically significant. We analyzed factors prognostic for tumor response and OS, and assessed histological subgroup and tumor grade as predictive factors to identify patients more likely to benefit...... patients had improved tumor response compared to other histological subgroups, whilst patients with metastases other than lung, liver or bone had a poorer response [odds ratio (OR) 0.42, 95% confidence interval (CI) 0.23-0.78; p = 0.006]. Patients with bone metastases had reduced OS [hazard ratio (HR) 1...

  4. Growth factor and proteinase profile of Vivostat® platelet-rich fibrin linked to tissue repair

    DEFF Research Database (Denmark)

    Ågren, Sven Per Magnus; Rasmussen, Karina; Pakkenberg, Bente

    2014-01-01

    . Leucocyte, erythrocyte and platelet counts in whole blood and fibrin-I were determined by automated haematology analyser. Platelet concentration in PRF was quantified manually by stereologic analysis of Giemsa-stained tissue sections, and the total content of five growth factors and MMP-9 by enzyme......·001]. MMP-9 was reduced 139-fold (P tissue regenerative applications....

  5. Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation.

    Directory of Open Access Journals (Sweden)

    Karine M Yamashita

    2014-05-01

    Full Text Available BACKGROUND/AIMS: Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF, resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a whether TF and protein disulfide isomerase (PDI, an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b the involvement and significance of snake venom metalloproteinases (SVMP and serine proteinases (SVSP to hemostatic disturbances. METHODS/PRINCIPAL FINDINGS: Crude Bothrops jararaca venom (BjV was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. CONCLUSIONS: SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in

  6. General evaluation of hard dental tissue and risk factors of dental caries in young people

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    Антоніна Михайлівна Політун

    2016-04-01

    Full Text Available The prognostication of caries in youth is important for determination and prescription of individual prophylactic arrangements and its further influence on mineralization of the hard dental tissues.Aim of the work: the study of the prevalence and intensity of caries among the young people and determination of possible connection with the risk factor of caries development for further choice of the reasonable prophylactic arrangement.Materials and methods of research: epidemiological, clinical, statistic ones.Results of research: The article describes results of the comprehensive dental examination of 135 persons18-25 years old. There was determined the high prevalence of caries (96,3±0,74 % with considerable intensity (8,87±0,39. The main etiological factors among youth are: poor nutrition with prevalence of carbohydrate (74,81±0,56 %, lack of oral hygiene (59,27±0,73 %, quantitative and qualitative composition of oral fluid, presence of somatic diseases (40±0,30 %, bad habits (31,85±0,24 %, neglect of the sport (48,88±0,36 %, chronic emotional stress (38,51±0,29 %, due to the increased workload and related stress factors.Conclusions: the high prevalence (96,3±0,74 % and intensity of carious process (8,87±0,39 is caused by the unsatisfactory state of oral cavity, (1,91±0,06, under the influence of general factors (somatic diseases, stress, poor nutrition the reactivity of protective mechanisms is lowered and the risk of dental morbidity of youth increases. So, it proves the necessity of elaboration and introduction of the active arrangements of primary prophylaxis directed on the raise of caries resistance of the hard dental tissues in young people

  7. C-terminal peptides of tissue factor pathway inhibitor are novel host defense molecules.

    Science.gov (United States)

    Papareddy, Praveen; Kalle, Martina; Kasetty, Gopinath; Mörgelin, Matthias; Rydengård, Victoria; Albiger, Barbara; Lundqvist, Katarina; Malmsten, Martin; Schmidtchen, Artur

    2010-09-03

    Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation, but may, via its C terminus, also modulate cell surface, heparin, and lipopolysaccharide interactions as well as participate in growth inhibition. Here we show that C-terminal TFPI peptide sequences are antimicrobial against the gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungi Candida albicans and Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen for the "classic" human antimicrobial peptide LL-37. The killing of E. coli, but not P. aeruginosa, by the C-terminal peptide GGLIKTKRKRKKQRVKIAYEEIFVKNM (GGL27), was enhanced in human plasma and largely abolished in heat-inactivated plasma, a phenomenon linked to generation of antimicrobial C3a and activation of the classic pathway of complement activation. Furthermore, GGL27 displayed anti-endotoxic effects in vitro and in vivo in a mouse model of LPS shock. Importantly, TFPI was found to be expressed in the basal layers of normal epidermis, and was markedly up-regulated in acute skin wounds as well as wound edges of chronic leg ulcers. Furthermore, C-terminal fragments of TFPI were associated with bacteria present in human chronic leg ulcers. These findings suggest a new role for TFPI in cutaneous defense against infections.

  8. Common factors method to predict the carcass composition tissue in kid goats

    Directory of Open Access Journals (Sweden)

    Helen Fernanda Barros Gomes

    2013-03-01

    Full Text Available The objective of this work was to analyze the interrelations among weights and carcass measures of the longissimus lumborum muscle thickness and area, and of sternum tissue thickness, measured directly on carcass and by ultrasound scan. Measures were taken on live animals and after slaughter to develop models of multiple linear regression, to estimate the composition of shoulder blade, from selected variables in 89 kids of both genders and five breed groups, raised in feedlot system. The variables considered relevant and not redundant on the information they carry, for the common factor analysis, were used in the carcass composition estimate development models. The presuppositions of linear regression models relative to residues were evaluated, the estimated residues were subjected to analysis of variance and the means were compared by the Student t test. Based in these results, the group of 32 initial variables could be reduced to four variables: hot carcass weight, rump perimeter, leg length and tissue height at the fourth sternum bone. The analysis of common factors was shown as an effective technique to study the interrelations among the independent variables. The measures of carcass dimension, alone, did not add any information to hot carcass weight. The carcass muscle weight can be estimated with high precision from simple models, without the need for information related to gender and breed, and they could be built based on carcass weight, which makes it easy to be applied. The fat and bones estimate models were not as accurate.

  9. Microporous silk fibroin scaffolds embedding PLGA microparticles for controlled growth factor delivery in tissue engineering.

    Science.gov (United States)

    Wenk, Esther; Meinel, Anne J; Wildy, Sarah; Merkle, Hans P; Meinel, Lorenz

    2009-05-01

    The development of prototype scaffolds for either direct implantation or tissue engineering purposes and featuring spatiotemporal control of growth factor release is highly desirable. Silk fibroin (SF) scaffolds with interconnective pores, carrying embedded microparticles that were loaded with insulin-like growth factor I (IGF-I), were prepared by a porogen leaching protocol. Treatments with methanol or water vapor induced water insolubility of SF based on an increase in beta-sheet content as analyzed by FTIR. Pore interconnectivity was demonstrated by SEM. Porosities were in the range of 70-90%, depending on the treatment applied, and were better preserved when methanol or water vapor treatments were prior to porogen leaching. IGF-I was encapsulated into two different types of poly(lactide-co-glycolide) microparticles (PLGA MP) using uncapped PLGA (50:50) with molecular weights of either 14 or 35 kDa to control IGF-I release kinetics from the SF scaffold. Embedded PLGA MP were located in the walls or intersections of the SF scaffold. Embedment of the PLGA MP into the scaffolds led to more sustained release rates as compared to the free PLGA MP, whereas the hydrolytic degradation of the two PLGA MP types was not affected. The PLGA types used had distinct effects on IGF-I release kinetics. Particularly the supernatants of the lower molecular weight PLGA formulations turned out to release bioactive IGF-I. Our studies justify future investigations of the developed constructs for tissue engineering applications.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  11. PET Imaging of Tissue Factor in Pancreatic Cancer Using 64Cu-Labeled Active Site-Inhibited Factor VII.

    Science.gov (United States)

    Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Lotte K; Jensen, Mette M; El Ali, Henrik H; Madsen, Jacob; Wiinberg, Bo; Petersen, Lars C; Kjaer, Andreas

    2016-07-01

    Tissue factor (TF) is the main initiator of the extrinsic coagulation cascade. However, TF also plays an important role in cancer. TF expression has been reported in 53%-89% of all pancreatic adenocarcinomas, and the expression level of TF has in clinical studies correlated with advanced stage, increased microvessel density, metastasis, and poor overall survival. Imaging of TF expression is of clinical relevance as a prognostic biomarker and as a companion diagnostic for TF-directed therapies currently under clinical development. Factor VII (FVII) is the natural ligand to TF. The purpose of this study was to investigate the possibility of using active site-inhibited FVII (FVIIai) labeled with (64)Cu for PET imaging of TF expression. FVIIai was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with (64)Cu ((64)Cu-NOTA-FVIIai). Longitudinal in vivo PET imaging was performed at 1, 4, 15, and 36 h after injection of (64)Cu-NOTA-FVIIai in mice with pancreatic adenocarcinomas (BxPC-3). The specificity of TF imaging with (64)Cu-NOTA-FVIIai was investigated in subcutaneous pancreatic tumor models with different levels of TF expression and in a competition experiment. In addition, imaging of orthotopic pancreatic tumors was performed using (64)Cu-NOTA-FVIIai and PET/MRI. In vivo imaging data were supported by ex vivo biodistribution, flow cytometry, and immunohistochemistry. Longitudinal PET imaging with (64)Cu-NOTA-FVIIai showed a tumor uptake of 2.3 ± 0.2, 3.7 ± 0.3, 3.4 ± 0.3, and 2.4 ± 0.3 percentage injected dose per gram at 1, 4, 15, and 36 h after injection, respectively. An increase in tumor-to-normal-tissue contrast was observed over the imaging time course. Competition with unlabeled FVIIai significantly (P < 0.001) reduced the tumor uptake. The tumor uptake observed in models with different TF expression levels was significantly different from each other (P < 0.001) and was in agreement with

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

    Science.gov (United States)

    Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E; Jensen, Mette M; Kristensen, Lotte K; Madsen, Jacob; Petersen, Lars C; Kjaer, Andreas

    2016-01-01

    Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of factor VII. Active site-inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-(18)F-fluorobenzoate and purified. The corresponding product, (18)F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of (18)F-FVIIai in the tumors measured in vivo by PET imaging. The PET images showed high uptake of (18)F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3-9.3 MBq of (18)F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of (18)F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P < 0.001). The uptake of (18)F-FVIIai measured in vivo by PET imaging correlated (r = 0.72, P < 0.02) with TF protein level measured ex vivo. (18)F-FVIIai is a promising PET tracer for

  13. Connective tissue growth factor is involved in structural retinal vascular changes in long-term experimental diabetes

    NARCIS (Netherlands)

    Van Geest, Rob J; Leeuwis, Jan Willem; Dendooven, Amélie; Pfister, Frederick; Bosch, Klazien; Hoeben, Kees A; Vogels, Ilse M C; Van der Giezen, Dionne M; Dietrich, Nadine; Hammes, Hans-Peter; Goldschmeding, Roel; Klaassen, Ingeborg; Van Noorden, Cornelis J F; Schlingemann, Reinier O

    Early retinal vascular changes in the development of diabetic retinopathy (DR) include capillary basal lamina (BL) thickening, pericyte loss and the development of acellular capillaries. Expression of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family

  14. Connective tissue growth factor is involved in structural retinal vascular changes in long-term experimental diabetes

    NARCIS (Netherlands)

    van Geest, Rob J.; Leeuwis, Jan Willem; Dendooven, Amélie; Pfister, Frederick; Bosch, Klazien; Hoeben, Kees A.; Vogels, Ilse M. C.; van der Giezen, Dionne M.; Dietrich, Nadine; Hammes, Hans-Peter; Goldschmeding, Roel; Klaassen, Ingeborg; van Noorden, Cornelis J. F.; Schlingemann, Reinier O.

    2014-01-01

    Early retinal vascular changes in the development of diabetic retinopathy (DR) include capillary basal lamina (BL) thickening, pericyte loss and the development of acellular capillaries. Expression of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family

  15. Diet and lifestyle factors associated with miRNA expression in colorectal tissue

    Directory of Open Access Journals (Sweden)

    Slattery ML

    2016-12-01

    Full Text Available Martha L Slattery,1 Jennifer S Herrick,1 Lila E Mullany,1 John R Stevens,2 Roger K Wolff1 1Department of Internal Medicine, The University of Utah, Salt Lake City, 2Department of Mathematics and Statistics, Utah State University, Logan, UT, USA Abstract: MicroRNAs (miRNAs are small non-protein-coding RNA molecules that regulate gene expression. Diet and lifestyle factors have been hypothesized to be involved in the regulation of miRNA expression. In this study it was hypothesized that diet and lifestyle factors are associated with miRNA expression. Data from 1,447 cases of colorectal cancer to evaluate 34 diet and lifestyle variables using miRNA expression in normal colorectal mucosa as well as for differential expression between paired carcinoma and normal tissue were used. miRNA data were obtained using an Agilent platform. Multiple comparisons were adjusted for using the false discovery rate q-value. There were 250 miRNAs differentially expressed between carcinoma and normal colonic tissue by level of carbohydrate intake and 198 miRNAs differentially expressed by the level of sucrose intake. Of these miRNAs, 166 miRNAs were differentially expressed for both carbohydrate intake and sucrose intake. Ninety-nine miRNAs were differentially expressed by the level of whole grain intake in normal colonic mucosa. Level of oxidative balance score was associated with 137 differentially expressed miRNAs between carcinoma and paired normal rectal mucosa. Additionally, 135 miRNAs were differentially expressed in colon tissue based on recent NSAID use. Other dietary factors, body mass index, waist and hip circumference, and long-term physical activity levels did not alter miRNA expression after adjustment for multiple comparisons. These results suggest that diet and lifestyle factors regulate miRNA level. They provide additional support for the influence of carbohydrate, sucrose, whole grains, NSAIDs, and oxidative balance score on colorectal cancer risk

  16. Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.

    Directory of Open Access Journals (Sweden)

    Halima Rakhila

    Full Text Available Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2, cell adhesion (αv and β3 integrins, survival (B-cell lymphoma-2 and angiogenic (vascular endothelial cell growth factors relevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.

  17. Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.

    Science.gov (United States)

    Rakhila, Halima; Girard, Karine; Leboeuf, Mathieu; Lemyre, Madeleine; Akoum, Ali

    2014-01-01

    Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF) appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO) mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT) mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2), cell adhesion (αv and β3 integrins), survival (B-cell lymphoma-2) and angiogenic (vascular endothelial cell growth) factors relevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.

  18. The diagnostic value of plasma N-terminal connective tissue growth factor levels in children with heart failure.

    Science.gov (United States)

    Li, Gang; Song, Xueqing; Xia, Jiyi; Li, Jing; Jia, Peng; Chen, Pengyuan; Zhao, Jian; Liu, Bin

    2017-01-01

    The aim of this study was to assess the diagnostic value of plasma N-terminal connective tissue growth factor in children with heart failure. Methods and results Plasma N-terminal connective tissue growth factor was determined in 61 children, including 41 children with heart failure, 20 children without heart failure, and 30 healthy volunteers. The correlations between plasma N-terminal connective tissue growth factor levels and clinical parameters were investigated. Moreover, the diagnostic value of N-terminal connective tissue growth factor levels was evaluated. Compared with healthy volunteers and children without heart failure, plasma N-terminal connective tissue growth factor levels were significantly elevated in those with heart failure (p0.05), but it obviously improved the ability of diagnosing heart failure in children, as demonstrated by the integrated discrimination improvement (6.2%, p=0.013) and net re-classification improvement (13.2%, p=0.017) indices. Plasma N-terminal connective tissue growth factor is a promising diagnostic biomarker for heart failure in children.

  19. Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients.

    Science.gov (United States)

    Diaz, Alba; Alós, Llúcia; León, Agathe; Mozos, Anna; Caballero, Miguel; Martinez, Antonio; Plana, Montserrat; Gallart, Teresa; Gil, Cristina; Leal, Manuel; Gatell, Jose M; García, Felipe

    2010-08-24

    The factors associated with fibrosis in lymphoid tissue in long-term treated HIV-infected patients and their correlation with immune reconstitution were assessed. Tonsillar biopsies were performed in seven antiretroviral-naive patients and 29 successfully treated patients (median time on treatment, 61 months). Twenty patients received protease inhibitors-sparing regimens and nine protease inhibitor-containing regimens. Five tonsillar resections of HIV-negative individuals were used as controls. Lymphoid tissue architecture, collagen deposition (fibrosis) and the mean interfollicular CD4(+) cell count per mum were assessed. Naive and long-term treated HIV-infected patients had a higher proportion of fibrosis than did HIV-uninfected persons (P lymphoid tissue (P = 0.03) and smaller increase in peripheral CD4(+) T cells (r = -0.40, P = 0.05). The factors independently associated with fibrosis in lymphoid tissue were age (P lymphoid tissue viral load when compared with patients with undetectable lymphoid tissue viral load (median 5 vs. 12%, respectively, P = 0.017) and patients receiving a protease inhibitor-sparing vs. a protease inhibitor-containing regimen (median 8 vs. 2.5%, respectively, P = 0.04). Fibrosis in lymphoid tissue was associated with a poor reconstitution of CD4(+) T cells and long-term antiretroviral therapy did not reverse this abnormality. HIV infection, older age, a detectable level of lymphoid tissue viral load in treated patients and protease inhibitor-sparing regimens seem to favour fibrosis in lymphoid tissue.

  20. Electronic health records: critical success factors in implementation.

    Science.gov (United States)

    Safdari, Reza; Ghazisaeidi, Marjan; Jebraeily, Mohamad

    2015-04-01

    EHR implementation results in the improved quality of care, customer-orientation and timely access to complete information. Despite the potential benefits of EHR, its implementation is a difficult and complex task whose success depends on many factors. The purpose of this research is indeed to identify the key success factors of EHR. This is a cross-sectional survey conducted with participation of 340 work forces from different types of job from Hospitals of TUMS in 2014. Data were collected using a self-structured questionnaire which was estimated as both reliable and valid. The data were analyzed by SPSS software descriptive statistics and analytical statistics. 58.2% of respondents were female and their mean age and work experience were 37.7 and 11.2 years, respectively and most respondents (52.5%) was bachelor. In terms of job, the maximum rate was related to nursing (33 %) and physician (21 %). the main category of critical success factors in Implementation EHRs, the highest rate related to Project Management (4.62) and lowest related to Organizational factors (3.98). success in implementation EHRs requirement more centralization to project management and human factors. Therefore must be Creating to EHR roadmap implementation, establishment teamwork to participation of end-users and select prepare leadership, users obtains sufficient training to use of system and also prepare support from maintain and promotion system.

  1. Do methodological differences account for the current controversy on tissue factor expression in platelets?

    Science.gov (United States)

    Brambilla, Marta; Rossetti, Laura; Zara, Chiara; Canzano, Paola; Giesen, Peter L A; Tremoli, Elena; Camera, Marina

    2018-06-01

    Tissue factor (TF), the key activator of the blood coagulation cascade and of thrombus formation, is also expressed by circulating human platelets. Despite the documented in-depth characterization of platelet TF carried out in the past 15 years, some authors still fail to identify TF in platelets, especially when assessment in platelet-rich plasma (PRP) or washed platelets is carried out. This study aims to extend the characterization of the subset of TF-positive platelets in PRP from healthy subjects and to verify how different centrifugation forces, used to prepare the PRP, could affect the analysis of TF-positive platelets. Data indicate that large-size platelets express significantly higher amount of TF compared to small-size cells, in terms of both TF protein and TF mRNA. Upon stimulation, large platelets readily expose on the cell membrane TF, which is functionally active, i.e., able to generate factor Xa (FXa) as well as thrombin. By contrast, TF activity in small platelets is almost completely quenched by tissue factor pathway inhibitor (TFPI), becoming indeed detectable only after treatment with an anti-TFPI antibody. Our data highlight that particular attention must be paid to the preparation and collection of the PRP since such preanalytical variables may influence the platelet recovery and in turn affect subsequent analysis, whether it is flow cytometry, functional activity tests, proteome, or transcriptome analysis. Indeed, the TF-positive subset of large platelets can easily be lost if centrifugation protocols are not optimized, thus erroneously leading to a false-negative result.

  2. Relative merits and limiting factors for x-ray and electron microscopy of thick, hydrated organic materials.

    Science.gov (United States)

    Du, Ming; Jacobsen, Chris

    2018-01-01

    Electron and x-ray microscopes allow one to image the entire, unlabeled structure of hydrated materials at a resolution well beyond what visible light microscopes can achieve. However, both approaches involve ionizing radiation, so that radiation damage must be considered as one of the limits to imaging. Drawing upon earlier work, we describe here a unified approach to estimating the image contrast (and thus the required exposure and corresponding radiation dose) in both x-ray and electron microscopy. This approach accounts for factors such as plural and inelastic scattering, and (in electron microscopy) the use of energy filters to obtain so-called "zero loss" images. As expected, it shows that electron microscopy offers lower dose for specimens thinner than about 1 µm (such as for studies of macromolecules, viruses, bacteria and archaebacteria, and thin sectioned material), while x-ray microscopy offers superior characteristics for imaging thicker specimen such as whole eukaryotic cells, thick-sectioned tissues, and organs. The required radiation dose scales strongly as a function of the desired spatial resolution, allowing one to understand the limits of live and frozen hydrated specimen imaging. Finally, we consider the factors limiting x-ray microscopy of thicker materials, suggesting that specimens as thick as a whole mouse brain can be imaged with x-ray microscopes without significant image degradation should appropriate image reconstruction methods be identified. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Hypoxia-Inducible Factor-1α: A Potential Factor for the Enhancement of Osseointegration between Dental Implants and Tissue-Engineered Bone

    Directory of Open Access Journals (Sweden)

    Duohong Zou

    2011-07-01

    Full Text Available Introduction: Tissue-engineered bones are widely utilized to protect healthy tissue, reduce pain, and increase the success rate of dental implants. one of the most challenging obstacles lies in obtaining effective os-seointegration between dental implants and tissue-engineered structures. Deficiencies in vascularization, osteogenic factors, oxygen, and other nutrients inside the tissue-engineered bone during the early stages following implantation all inhibit effective osseointe-gration. Oxygen is required for aerobic metabolism in bone and blood vessel tissues, but oxygen levels inside tissue-engineered bone are not suf-ficient for cell proliferation. HIF-1α is a pivotal regulator of hypoxic and ischemic vascular responses, driving transcriptional activation of hundreds of genes involved in vascular reactivity, angiogenesis, arteriogenesis, and osteogenesis.The hypothesis: Hypoxia-Inducible Factor-1α seems a potential factor for the enhancement of osseointegration between dental implants and tissue-engineered bone.Evaluation of the hypothesis: Enhancement of HIF-1α protein expression is recognized as the most promising approach for angiogenesis, because it can induce multiple angiogenic targets in a coordinated manner. Therefore, it will be a novel potential therapeutic methods targeting HIF-1α expression to enhance osseointegration be-tween dental implants and tissue-engineered bone.

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

    Directory of Open Access Journals (Sweden)

    Cristina Puy

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

  5. Association of Polymorphisms in Connective Tissue Growth Factor and Epidermal Growth Factor Receptor Genes With Human Longevity.

    Science.gov (United States)

    Donlon, Timothy A; Morris, Brian J; He, Qimei; Chen, Randi; Masaki, Kamal H; Allsopp, Richard C; Willcox, D Craig; Tranah, Gregory J; Parimi, Neeta; Evans, Daniel S; Flachsbart, Friederike; Nebel, Almut; Kim, Duk-Hwan; Park, Joobae; Willcox, Bradley J

    2017-08-01

    Growth pathways play key roles in longevity. The present study tested single-nucleotide polymorphisms (SNPs) in the connective tissue growth factor gene (CTGF) and the epidermal growth factor receptor gene (EGFR) for association with longevity. Comparison of allele and genotype frequencies of 12 CTGF SNPs and 41 EGFR SNPs between 440 American men of Japanese ancestry aged ≥95 years and 374 men of average life span revealed association with longevity at the p cases, consistent with heterozygote advantage in living to extreme old age. No associations of the most significant SNPs were observed in whites or Koreans. In conclusion, the present findings indicate that genetic variation in CTGF and EGFR may contribute to the attainment of extreme old age in Japanese. More research is needed to confirm that genetic variation in CTGF and EGFR contributes to the attainment of extreme old age across human populations. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Investigating the effective factors on electronic trade by viral marketing

    Directory of Open Access Journals (Sweden)

    Nina Ghane

    2014-04-01

    Full Text Available This paper performs an investigation to explore a number of strategies underpinning virtual marketing. The study also provides several suggestions for marketers seeking to use viral marketing to position brands or to change a brand’s image, to encourage new product trials and to increase product uptake rates. In this article, we investigate the effect of external factors such as capturing the imagination, targeting credible sources, leveraging combinations of technology and easy to use product on virtual marketing. In addition, the study considers internal factors such as inclusion (the need to be part of a group, the need to be different and affection on viral marketing. The survey has been accomplished among 140 Iranian people, who were familiar with virtual marketing and they are selected, randomly. Using Pearson correlation as well as regression analysis, the study provides some evidences that there were some positive and meaningful relationship between some internal/external factors and virtual marketing.

  7. Risk Factors for Complications Differ Between Stages of Tissue-Expander Breast Reconstruction.

    Science.gov (United States)

    Lovecchio, Francis; Jordan, Sumanas W; Lim, Seokchun; Fine, Neil A; Kim, John Y S

    2015-09-01

    Tissue-expander (TE) placement followed by implant exchange is currently the most popular method of breast reconstruction. There is a relative paucity of data demonstrating patient factors that predict complications specifically by stage of surgery. The present study attempts to determine what complications are most likely to occur at each stage and how the risk factors for complications vary by stage of reconstruction. A retrospective chart review was performed on all 1275 patients who had TEs placed by the 2 senior authors between 2004 and 2013. Complication rates were determined at each stage of reconstruction, and these rates were further compared between patients who had pre-stage I radiation, post-stage I radiation, and no radiation exposure. Multivariate logistic regression was used to identify independent predictors of complications at each stage of reconstruction. A total of 1639 consecutive TEs were placed by the senior authors during the study period. The overall rate for experiencing a complication at any stage of surgery was 17%. Complications occurred at uniformly higher rates during stage I for all complications (92% stage I vs 7% stage II vs 1% stage III, P higher intraoperative percent fill (OR, 3.3; 95% CI, 1.7-6.3). Post-stage I radiation was the only independent risk factor for a stage II complication (OR, 4.5; 95% CI, 1.4-15.2). Complications occur at higher rates after stage I than after stage II, and as expected, stage III complications are exceedingly rare. Risk factors for stage I complications are different from risk factors for stage II complications. Body mass index and smoking are associated with complications at stage I, but do not predict complications at stage II surgery. The stratification of risk factors by stage of surgery will help surgeons and patients better manage both risk and expectations.

  8. Impact of pre-analytical factors on the proteomic analysis of formalin-fixed paraffin-embedded tissue.

    Science.gov (United States)

    Thompson, Seonaid M; Craven, Rachel A; Nirmalan, Niroshini J; Harnden, Patricia; Selby, Peter J; Banks, Rosamonde E

    2013-04-01

    Formalin-fixed paraffin-embedded (FFPE) tissue samples represent a tremendous potential resource for biomarker discovery, with large numbers of samples in hospital pathology departments and links to clinical information. However, the cross-linking of proteins and nucleic acids by formalin fixation has hampered analysis and proteomic studies have been restricted to using frozen tissue, which is more limited in availability as it needs to be collected specifically for research. This means that rare disease subtypes cannot be studied easily. Recently, improved extraction techniques have enabled analysis of FFPE tissue by a number of proteomic techniques. As with all clinical samples, pre-analytical factors are likely to impact on the results obtained, although overlooked in many studies. The aim of this review is to discuss the various pre-analytical factors, which include warm and cold ischaemic time, size of sample, fixation duration and temperature, tissue processing conditions, length of storage of archival tissue and storage conditions, and to review the studies that have considered these factors in more detail. In those areas where investigations are few or non-existent, illustrative examples of the possible importance of specific factors have been drawn from studies using frozen tissue or from immunohistochemical studies of FFPE tissue. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Insulin-like growth factor I enhances collagen synthesis in engineered human tendon tissue

    DEFF Research Database (Denmark)

    Herchenhan, Andreas; Bayer, Monika L.; Eliasson, Pernilla

    2015-01-01

    OBJECTIVE: Isolated human tendon cells form 3D tendon constructs that demonstrate collagen fibrillogenesis and feature structural similarities to tendon when cultured under tensile load. The exact role of circulating growth factors for collagen formation in tendon is sparsely examined. We...... investigated the influence of insulin-like growth factor I (IGF-I) on tendon construct formation in 3D cell culture. DESIGN: Tendon constructs were grown in 0.5 or 10% FBS with or without IGF-I (250 mg/ml) supplementation. Collagen content (fluorometric), mRNA levels (PCR) and fibril diameter (transmission...... electron microscopy) were determined at 7, 10, 14, 21 and 28 days. RESULTS: IGF-I revealed a stimulating effect on fibril diameter (up to day 21), mRNA for collagen (to day 28), tenomodulin (to day 28) and scleraxis (at days 10 and 14), and on overall collagen content. 10% FBS diminished the development...

  10. Controllable mineral coatings on scaffolds as carriers for growth factor release for bone tissue engineering

    Science.gov (United States)

    Saurez-Gonzalez, Darilis

    The work presented in this document, focused on the development and characterization of mineral coatings on scaffold materials to serve as templates for growth factor binding and release. Mineral coatings were formed using a biomimetic approach that consisted in the incubation of scaffolds in modified simulated body fluids (mSBF). To modulate the properties of the mineral coating, which we hypothesized would dictate growth factor release, we used carbonate (HCO3) concentration in mSBF of 4.2 mM, 25mM, and 100mM. Analysis of the mineral coatings formed using scanning electron microscopy indicated growth of a continuous layer of mineral with different morphologies. X-ray diffraction analysis showed peaks associated with hydroxyapatite. FTIR data confirmed the substitution of HCO3 in the mineral. As the extent of HCO3 substitution increased, the coating exhibited more rapid dissolution kinetics in an environment deficient in calcium and phosphate. The mineral coatings provided an effective mechanism for bioactive growth factor binding and release. Peptide versions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) were bound with efficiencies up to 90% to mineral-coated PCL scaffolds. Recombinant human vascular endothelial growth factor (rhVEGF) also bound to mineral coated scaffolds with lower efficiency (20%) and released with faster release kinetics compared to peptides growth factor. Released rhVEGF induced human umbilical vein endothelial cell (HUVEC) proliferation in vitro and enhanced blood vessel formation in vivo in an intramuscular sheep model. In addition to the use the mineral coatings for single growth factor release, we expanded the concept and bound both an angiogenic (rhVEGF) and osteogenic (mBMP2) growth factor by a simple double dipping process. Sustained release of both growth factors was demonstrated for over 60 days. Released rhVEGF enhanced blood vessel formation in vivo in sheep and its biological activity was

  11. A comparison of the relative biological effectiveness of low energy electronic brachytherapy sources in breast tissue: a Monte Carlo study.

    Science.gov (United States)

    White, Shane A; Reniers, Brigitte; de Jong, Evelyn E C; Rusch, Thomas; Verhaegen, Frank

    2016-01-07

    Electronic brachytherapy sources use low energy photons to treat the tumor bed during or after breast-conserving surgery. The relative biological effectiveness of two electronic brachytherapy sources was explored to determine if spectral differences due to source design influenced radiation quality and if radiation quality decreased with distance in the breast. The RBE was calculated through the number of DNA double strand breaks (RBEDSB) using the Monte Carlo damage simulator (MCDS) in combination with other Monte Carlo electron/photon spectrum calculations. 50kVp photons from the Intrabeam (Carl Zeiss Surgical) and Axxent (Xoft) through 40-mm spherical applicators were simulated to account for applicator and tissue attenuation in a variety of breast tissue compositions. 40kVp Axxent photons were also simulated. Secondary electrons (known to be responsible for most DNA damage) spectra at different distance were inputted into MCDS to calculate the RBEDSB. All RBEDSB used a cobalt-60 reference. RBEDSB data was combined with corresponding average photon spectrum energy for the Axxent and applied to model-based average photon energy distributions to produce an RBEDSB map of an accelerated partial breast irradiation (APBI) patient. Both Axxent and Intrabeam 50kVp spectra were shown to have a comparable RBEDSB of between 1.4 and 1.6 at all distances in spite of progressive beam hardening. The Axxent 40kVp also demonstrated a similar RBEDSB at distances. Most RBEDSB variability was dependent on the tissue type as was seen in rib (RBEDSB  ≈  1.4), gland (≈1.55), adipose (≈1.59), skin (≈1.52) and lung (≈1.50). RBEDSB variability between both sources was within 2%. A correlation was shown between RBEDSB and average photon energy and used to produce an RBEDSB map of a dose distribution in an APBI patient dataset. Radiation quality is very similar between electronic brachytherapy sources studied. No significant reductions in RBEDSB were observed with

  12. Overexpressed connective tissue growth factor in cardiomyocytes attenuates left ventricular remodeling induced by angiotensin II perfusion.

    Science.gov (United States)

    Zhang, Ying; Yan, Hua; Guang, Gong-Chang; Deng, Zheng-Rong

    2017-01-01

    To evaluate the improving effects of specifically overexpressed connective tissue growth factor (CTGF) in cardiomyocytes on mice with hypertension induced by angiotensin II (AngII) perfusion, 24 transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) were divided into two equal groups that were perfused with acetic acid and AngII, respectively, for 7 days. Another 24 cage-control wild-type C57BL/6 mice (NLC) were divided and treated identically. Blood pressure was detected by caudal artery cannulation. Cardiac structural and functional changes were observed by echocardiography. Cardiac fibrosis was detected by Masson staining. After AngII perfusion, blood pressures of NLC and Tg-CTGF mice, especially those of the formers, significantly increased. Compared with NLC + AngII group, Tg-CTGF + AngII group had significantly lower left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole as well as significantly higher left ventricular end-systolic diameter and left ventricular end-diastolic diameter (P tissues (P < 0.05). Tg-CTGF can protect AngII-induced cardiac remodeling of mice with hypertension by mitigating inflammatory response. CTGF may be a therapy target for hypertension-induced myocardial fibrosis, but the detailed mechanism still needs in-depth studies.

  13. Expression of Tissue Factor in Epithelial Ovarian Carcinoma Is Involved in the Development of Venous Thromboembolism.

    Science.gov (United States)

    Sakurai, Manabu; Matsumoto, Koji; Gosho, Masahiko; Sakata, Akiko; Hosokawa, Yoshihiko; Tenjimbayashi, Yuri; Katoh, Takashi; Shikama, Ayumi; Komiya, Haruna; Michikami, Hiroo; Tasaka, Nobutaka; Akiyama-Abe, Azusa; Nakao, Sari; Ochi, Hiroyuki; Onuki, Mamiko; Minaguchi, Takeo; Yoshikawa, Hiroyuki; Satoh, Toyomi

    2017-01-01

    Our 2007 study of 32 patients with ovarian cancer reported the possible involvement of tissue factor (TF) in the development of venous thromboembolism (VTE) before treatment, especially in clear cell carcinoma (CCC). This follow-up study further investigated this possibility in a larger cohort. We investigated the intensity of TF expression (ITFE) and other variables for associations with VTE using univariate and multivariate analyses in 128 patients with epithelial ovarian cancer initially treated between November 2004 and December 2010, none of whom had received neoadjuvant chemotherapy. Before starting treatment, all patients were ultrasonographically screened for VTE. The ITFE was graded based on immunostaining of surgical specimens. Histological types were serous carcinoma (n = 42), CCC (n = 12), endometrioid carcinoma (n = 15), mucinous carcinoma (n = 53), and undifferentiated carcinoma (n = 6). The prevalence of VTE was significantly higher in CCC (34%) than in non-CCC (17%, P = 0.03). As ITFE increased, the frequencies of CCC and VTE increased significantly (P epithelial ovarian cancer may involve TF expression in cancer tissues.

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

    Science.gov (United States)

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

    2013-01-01

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

  15. Generation of hyaline cartilaginous tissue from mouse adult dermal fibroblast culture by defined factors

    Science.gov (United States)

    Hiramatsu, Kunihiko; Sasagawa, Satoru; Outani, Hidetatsu; Nakagawa, Kanako; Yoshikawa, Hideki; Tsumaki, Noriyuki

    2011-01-01

    Repair of cartilage injury with hyaline cartilage continues to be a challenging clinical problem. Because of the limited number of chondrocytes in vivo, coupled with in vitro de-differentiation of chondrocytes into fibrochondrocytes, which secrete type I collagen and have an altered matrix architecture and mechanical function, there is a need for a novel cell source that produces hyaline cartilage. The generation of induced pluripotent stem (iPS) cells has provided a tool for reprogramming dermal fibroblasts to an undifferentiated state by ectopic expression of reprogramming factors. Here, we show that retroviral expression of two reprogramming factors (c-Myc and Klf4) and one chondrogenic factor (SOX9) induces polygonal chondrogenic cells directly from adult dermal fibroblast cultures. Induced cells expressed marker genes for chondrocytes but not fibroblasts, i.e., the promoters of type I collagen genes were extensively methylated. Although some induced cell lines formed tumors when subcutaneously injected into nude mice, other induced cell lines generated stable homogenous hyaline cartilage–like tissue. Further, the doxycycline-inducible induction system demonstrated that induced cells are able to respond to chondrogenic medium by expressing endogenous Sox9 and maintain chondrogenic potential after substantial reduction of transgene expression. Thus, this approach could lead to the preparation of hyaline cartilage directly from skin, without generating iPS cells. PMID:21293062

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

    Directory of Open Access Journals (Sweden)

    Federica Novelli

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

  17. Tissue factor activated thromboelastography correlates to clinical signs of bleeding in dogs

    DEFF Research Database (Denmark)

    Wiinberg, Bo; Jensen, Asger Lundorff; Rozanski, Elizabeth

    2009-01-01

    The ability of a laboratory assay to correlate to clinical phenotype is crucial for the accurate diagnosis and monitoring of haemostasis and is therefore challenging with currently used routine haemostasis assays. Thromboelastography (TEG) is increasingly used to evaluate haemostasis in humans...... and may well be of value in the workup of dogs suspected of having a haemostatic disorder. This study was undertaken to evaluate prospectively how tissue factor (TF) activated TEG correlated to clinical signs of bleeding in dogs, compared to a routine coagulation profile. A prospective case-control study...... was performed over a 2 year period from 2004-2006. Eligible dogs were those where the primary clinician requested a coagulation profile to evaluate haemostasis. The dogs were simultaneously evaluated with a TF-activated TEG assay. Twenty-seven dogs, characterised as hypo-coagulable based on the TEG parameter G...

  18. The g-factor of the bound electron in hydrogenic ions

    International Nuclear Information System (INIS)

    Quint, Wolfgang

    2001-01-01

    We report on the measurement of the g-factor of the electron bound in an atomic ion. A single hydrogenic ion ( 12 C 5+ ) is stored in a Penning trap. The electronic spin state of the ion is monitored via the continuous Stern-Gerlach effect in a quantum non-demolition measurement. Quantum jumps between the two spin states (spin up and spin down) are induced by a microwave field at the spin precession frequency of the bound electron. The g-factor of the bound electron is obtained by varying the microwave frequency and counting the number of spin flips for a fixed time interval. Applications of the continuous Stern-Gerlach effect include high-accuracy tests of bound-state quantum electrodynamics (QED), the measurement of the atomic mass of the electron, the determination of the fine structure constant α, and the measurement of nuclear g-factors

  19. Importance of Relativistic Effects and Electron Correlation in Structure Factors and Electron Density of Diphenyl Mercury and Triphenyl Bismuth.

    Science.gov (United States)

    Bučinský, Lukáš; Jayatilaka, Dylan; Grabowsky, Simon

    2016-08-25

    This study investigates the possibility of detecting relativistic effects and electron correlation in single-crystal X-ray diffraction experiments using the examples of diphenyl mercury (HgPh2) and triphenyl bismuth (BiPh3). In detail, the importance of electron correlation (ECORR), relativistic effects (REL) [distinguishing between total, scalar and spin-orbit (SO) coupling relativistic effects] and picture change error (PCE) on the theoretical electron density, its topology and its Laplacian using infinite order two component (IOTC) wave functions is discussed. This is to develop an understanding of the order of magnitude and shape of these different effects as they manifest in the electron density. Subsequently, the same effects are considered for the theoretical structure factors. It becomes clear that SO and PCE are negligible, but ECORR and scalar REL are important in low- and medium-order reflections on absolute and relative scales-not in the high-order region. As a further step, Hirshfeld atom refinement (HAR) and subsequent X-ray constrained wavefunction (XCW) fitting have been performed for the compound HgPh2 with various relativistic and nonrelativistic wave functions against the experimental structure factors. IOTC calculations of theoretical structure factors and relativistic HAR as well as relativistic XCW fitting are presented for the first time, accounting for both scalar and spin-orbit relativistic effects.

  20. Epicardial adipose tissue and cardiometabolic risk factors in overweight and obese children and adolescents.

    Science.gov (United States)

    Schusterova, I; Leenen, F H H; Jurko, A; Sabol, F; Takacova, J

    2014-02-01

    What is already known about this subject The prevalence of childhood obesity has increased markedly in the past 2 decades. Abdominal fat is a better predictor of risk than body mass index. Waist circumference (WC) as a measure of abdominal fat has limited sensitivity and specificity. What this study adds Epicardial adipose tissue (EAT) as measured by echocardiography represents a simple and reliable marker of visceral adiposity. In children, both body mass index and EAT show a similar or better correlation with markers of cardiometabolic risk than does waist circumference. Epicardial adipose tissue (EAT) is the visceral fat deposit around the heart and is commonly increased in obese subjects. EAT is related to cardiometabolic risk factors and non-alcoholic fatty liver disease (NAFLD) in adults, but this relationship is not well known in children. Echocardiographic assessment of EAT and its association with cardiometabolic risk factors in overweight and obese children. In 25 (mean age 13.0 ± 2.3) overweight and obese subjects and 24 lean controls, blood pressure (BP), WC, fasting plasma glucose and insulin, lipids, uric acid and hepatic enzymes were measured. EAT thickness was measured by transthoracic echocardiography. In overweight and obese subjects, EAT was significantly higher compared to normal weight children. Overweight and obese children had significantly higher body mass index (BMI), WC, BP, triglycerides (TAG), low-density lipoprotein and total cholesterol, hepatic enzymes alanine aminotransferase (ALT) and γ-glutamyl transferase, and lower high-density lipoprotein cholesterol (HDL-C). EAT correlated significantly with BP, TAG, uric acid, HDL-C, apoprotein B and ALT. Correlation coefficients were similar or better than for WC, but similar or lower than for BMI. EAT thickness in children is associated with an unfavourable cardiometabolic risk profile including biochemical signs of NAFLD and hyperuricaemia, but is not a stronger indicator than BMI.

  1. Factors That Impact Nurses’ Utilization of Electronic Mail (E-Mail).

    Science.gov (United States)

    1998-05-21

    of a system but did little to influence behavior. A study by Golden, Beauclair , & Sussman (1992) surveyed 200 electronic mail account holders at an...Aldine Publishing. Golden, P. A., Beauclair , R., & Sussman, L. (1992). Factors affecting electronic mail use. Computers in Human Behavior, 8, 297-311

  2. Inelastic magnetic electron scattering form factors of the 26 Mg nucleus

    Indian Academy of Sciences (India)

    Magnetic electron scattering (3) form factors with core polarization effects, ... to 3+ states of the 26Mg nucleus have been studied using shell model calculations. ... The wave functions of the radial single-particle matrix elements have been ...

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  4. Automation of 3D reconstruction of neural tissue from large volume of conventional serial section transmission electron micrographs.

    Science.gov (United States)

    Mishchenko, Yuriy

    2009-01-30

    We describe an approach for automation of the process of reconstruction of neural tissue from serial section transmission electron micrographs. Such reconstructions require 3D segmentation of individual neuronal processes (axons and dendrites) performed in densely packed neuropil. We first detect neuronal cell profiles in each image in a stack of serial micrographs with multi-scale ridge detector. Short breaks in detected boundaries are interpolated using anisotropic contour completion formulated in fuzzy-logic framework. Detected profiles from adjacent sections are linked together based on cues such as shape similarity and image texture. Thus obtained 3D segmentation is validated by human operators in computer-guided proofreading process. Our approach makes possible reconstructions of neural tissue at final rate of about 5 microm3/manh, as determined primarily by the speed of proofreading. To date we have applied this approach to reconstruct few blocks of neural tissue from different regions of rat brain totaling over 1000microm3, and used these to evaluate reconstruction speed, quality, error rates, and presence of ambiguous locations in neuropil ssTEM imaging data.

  5. Connective tissue growth factor/CCN2-null mouse embryonic fibroblasts retain intact transforming growth factor-β responsiveness

    International Nuclear Information System (INIS)

    Mori, Yasuji; Hinchcliff, Monique; Wu, Minghua; Warner-Blankenship, Matthew; Lyons, Karen M.; Varga, John

    2008-01-01

    Background: The matricellular protein connective tissue growth factor (CCN2) has been implicated in pathological fibrosis, but its physiologic role remains elusive. In vitro, transforming growth factor-β (TGF-β) induces CCN2 expression in mesenchymal cells. Because CCN2 can enhance profibrotic responses elicited by TGF-β, it has been proposed that CCN2 functions as an essential downstream signaling mediator for TGF-β. To explore this notion, we characterized TGF-β-induced activation of fibroblasts from CCN2-null (CCN2 -/- ) mouse embryos. Methods: The regulation of CCN2 expression was examined in vivo in a model of fibrosis induced by bleomycin. Cellular TGF-β signal transduction and regulation of collagen gene expression were examined in CCN2 -/- MEFs by immunohistochemistry, Northern, Western and RT-PCR analysis, immunocytochemistry and transient transfection assays. Results: Bleomycin-induced skin fibrosis in the mouse was associated with substantial CCN2 up-regulation in lesional fibroblasts. Whereas in vitro proliferation rate of CCN2 -/- MEFs was markedly reduced compared to wild type MEFs, TGF-β-induced activation of the Smad pathways, including Smad2 phosphorylation, Smad2/3 and Smad4 nuclear accumulation and Smad-dependent transcriptional responses, were unaffected by loss of CCN2. The stimulation of COL1A2 and fibronectin mRNA expression and promoter activity, and of corresponding protein levels, showed comparable time and dose-response in wild type and CCN2 -/- MEFs, whereas stimulation of alpha smooth muscle actin and myofibroblast transdifferentiation showed subtle impairment in MEFs lacking CCN2. Conclusion: Whereas endogenous CCN2 plays a role in regulation of proliferation and TGF-β-induced myofibroblast transdifferentiation, it appears to be dispensable for Smad-dependent stimulation of collagen and extracellular matrix synthesis in murine embryonic fibroblasts

  6. A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy

    NARCIS (Netherlands)

    van Geest, Rob J.; Lesnik-Oberstein, Sarit Y.; Tan, H. Stevie; Mura, Marco; Goldschmeding, Roel; van Noorden, Cornelis J. F.; Klaassen, Ingeborg; Schlingemann, Reinier O.

    2012-01-01

    Introduction In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) may cause blindness by neovascularisation followed by fibrosis of the retina. It has previously been shown that a shift in the balance between levels of CTGF

  7. Progestin and thrombin regulate tissue factor expression in human term decidual cells.

    Science.gov (United States)

    Lockwood, C J; Murk, W; Kayisli, U A; Buchwalder, L F; Huang, S-T; Funai, E F; Krikun, G; Schatz, F

    2009-06-01

    Perivascular cell membrane-bound tissue factor (TF) initiates hemostasis via thrombin generation. The identity and potential regulation of TF-expressing cells at the human maternal-fetal interface that confers hemostatic protection during normal and preterm delivery is unclear. The objective of the study were to identify TF-expressing cells at the maternal-fetal interface in term and preterm decidual sections by immunohistochemistry and evaluate progestin, thrombin, TNF-alpha, and IL-1beta effects on TF expression by cultured human term decidual cells (DCs). Serial placental sections were immunostained for TF. Leukocyte-free term DC monolayers were incubated with 10(-8) M estradiol (E2) or E2 plus 10(-7) M medroxyprogestrone acetate (MPA) +/- thrombin or TNF-alpha or IL-1beta. ELISA and Western blotting assessed TF in cell lysates. Quantitative real-time RT-PCR measured TF mRNA levels. Immunolocalized TF in DC membranes in preterm and term placental sections displayed higher Histologic Scores than villous mesenchymal cells (P term placental sections, DC-expressed TF exceeds that of other cell types at the maternal-fetal interface and is localized at the cell membranes in which it can bind to factor VII and meet the hemostatic demands of labor and delivery via thrombin formation. Unlike the general concept that TF is constitutive in cells that highly express it, MPA and thrombin significantly enhanced TF expression in term DC monolayers.

  8. Microcapsule Technology for Controlled Growth Factor Release in Musculoskeletal Tissue Engineering.

    Science.gov (United States)

    Della Porta, Giovanna; Ciardulli, Maria C; Maffulli, Nicola

    2018-06-01

    Tissue engineering strategies have relied on engineered 3-dimensional (3D) scaffolds to provide architectural templates that can mimic the native cell environment. Among the several technologies proposed for the fabrication of 3D scaffold, that can be attractive for stem cell cultivation and differentiation, moulding or bioplotting of hydrogels allow the stratification of layers loaded with cells and with specific additives to obtain a predefined microstructural organization. Particularly with bioplotting technology, living cells, named bio-ink, and additives, such as biopolymer microdevices/nanodevices for the controlled delivery of growth factors or biosignals, can be organized spatially into a predesigned 3D pattern by automated fabrication with computer-aided digital files. The technologies for biopolymer microcarrier/nanocarrier fabrication can be strategic to provide a controlled spatiotemporal delivery of specific biosignals within a microenvironment that can better or faster address the stem cells loaded within it. In this review, some examples of growth factor-controlled delivery by biopolymer microdevices/nanodevices embedded within 3D hydrogel scaffolds will be described, to achieve a bioengineered 3D interactive microenvironment for stem cell differentiation. Conventional and recently proposed technologies for biopolymer microcapsule fabrication for controlled delivery over several days will also be illustrated and critically discussed.

  9. Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells.

    Science.gov (United States)

    Ambrosio, Maria Rosaria; D'Esposito, Vittoria; Costa, Valerio; Liguoro, Domenico; Collina, Francesca; Cantile, Monica; Prevete, Nella; Passaro, Carmela; Mosca, Giusy; De Laurentiis, Michelino; Di Bonito, Maurizio; Botti, Gerardo; Franco, Renato; Beguinot, Francesco; Ciccodicola, Alfredo; Formisano, Pietro

    2017-12-12

    Type 2 diabetes and obesity are negative prognostic factors in patients with breast cancer (BC). We found that sensitivity to tamoxifen was reduced by 2-fold by 25 mM glucose (High Glucose; HG) compared to 5.5 mM glucose (Low Glucose; LG) in MCF7 BC cells. Shifting from HG to LG ameliorated MCF7 cell responsiveness to tamoxifen. RNA-Sequencing of MCF7 BC cells revealed that cell cycle-related genes were mainly affected by glucose. Connective Tissue Growth Factor (CTGF) was identified as a glucose-induced modulator of cell sensitivity to tamoxifen. Co-culturing MCF7 cells with human adipocytes exposed to HG, enhanced CTGF mRNA levels and reduced tamoxifen responsiveness of BC cells. Inhibition of adipocyte-released IL8 reverted these effects. Interestingly, CTGF immuno-detection in bioptic specimens from women with estrogen receptor positive (ER + ) BC correlated with hormone therapy resistance, distant metastases, reduced overall and disease-free survival. Thus, glucose affects tamoxifen responsiveness directly modulating CTGF in BC cells, and indirectly promoting IL8 release by adipocytes.

  10. Chronic intermittent hypoxia activates nuclear factor-κB in cardiovascular tissues in vivo

    International Nuclear Information System (INIS)

    Greenberg, Harly; Ye Xiaobing; Wilson, David; Htoo, Aung K.; Hendersen, Todd; Liu Shufang

    2006-01-01

    Obstructive sleep apnea (OSA) is an important risk factor for cardiovascular morbidity and mortality. The mechanisms through which OSA promotes the development of cardiovascular disease are poorly understood. In this study, we tested the hypotheses that chronic exposure to intermittent hypoxia and reoxygenation (CIH) is a major pathologic factor causing cardiovascular inflammation, and that CIH-induces cardiovascular inflammation and pathology by activating the NF-κB pathway. We demonstrated that exposure of mice to CIH activated NF-κB in cardiovascular tissues, and that OSA patients had markedly elevated monocyte NF-κB activity, which was significantly decreased when obstructive apneas and their resultant CIH were eliminated by nocturnal CPAP therapy. The elevated NF-κB activity induced by CIH is accompanied by and temporally correlated to the increased expression of iNOS protein, a putative and important NF-κB-dependent gene product. Thus, CIH-mediated NF-κB activation may be a molecular mechanism linking OSA and cardiovascular pathologies seen in OSA patients

  11. Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model.

    Science.gov (United States)

    Pawlinski, Rafal; Pedersen, Brian; Kehrle, Bettina; Aird, William C; Frank, Rolf D; Guha, Mausumee; Mackman, Nigel

    2003-05-15

    In septic shock, tissue factor (TF) activates blood coagulation, and cytokines and chemokines orchestrate an inflammatory response. In this study, the role of Egr-1 in lipopolysaccharide (LPS) induction of TF and inflammatory mediators in vivo was evaluated using Egr-1(+/+) and Egr-1(-/-) mice. Administration of LPS transiently increased the steady-state levels of Egr-1 mRNA in the kidneys and lungs of Egr-1(+/+) mice with maximal induction at one hour. Egr-1 was expressed in epithelial cells in the kidneys and lungs in untreated and LPS-treated mice. LPS induction of monocyte chemoattractant protein mRNA in the kidneys and lungs of Egr-1(-/-) mice was not affected at 3 hours, but its expression was significantly reduced at 8 hours compared with the expression observed in Egr-1(+/+) mice. Similarly, LPS induction of TF mRNA expression in the kidneys and lungs at 8 hours was reduced in Egr-1(-/-) mice. However, Egr-1 deficiency did not affect plasma levels of tumor necrosis factor alpha in endotoxemic mice. Moreover, Egr-1(+/+) and Egr-1(-/-) mice exhibited similar survival times in a model of acute endotoxemia. These data indicate that Egr-1 does not contribute to the early inflammatory response in the kidneys and lungs or the early systemic inflammatory response in endotoxemic mice. However, Egr-1 does contribute to the sustained expression of inflammatory mediators and to the maximal expression of TF at 8 hours in the kidneys and lungs.

  12. Extraction of carbon 14-labeled compounds from plant tissue during processing for electron microscopy

    International Nuclear Information System (INIS)

    Coetzee, J.; van der Merwe, C.F.

    1989-01-01

    Loss of 14 C-labeled compounds from bean leaf tissue was monitored during all the stages of routine specimen preparation. No significant differences in extraction were associated with the use of acetone, ethanol, or dioxane as dehydration fluids. Fixation at low temperature increased the loss of label. Prolonged fixation in glutaraldehyde increased the loss, but fixation in osmium solutions for periods as long as 4 hr had no influence on extraction. Buffer rinses and dehydration fluids caused appreciable amounts of label to be extracted. The use of propylene oxide as transition fluid resulted in low extraction. Some embedding media caused the loss of small amounts of labeled compounds, but one of the media tested (LR-white) extracted significant amounts of label

  13. Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.

    Science.gov (United States)

    Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Gullu Amuran, Gokce; Ozmen, Tolga; Gulluoglu, Bahadır M; Kaya, Handan; Ozer, Ayse

    2017-09-01

    Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. Telomeres were shorter in tumor tissues compared to controls (Pbreast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association. © 2016 Wiley Periodicals, Inc.

  14. Effect of connective tissue growth factor (CTGF) expression on radiation pulmonary fibrosis in rats

    International Nuclear Information System (INIS)

    Huang Shanying; Song Liangwen; Zhang Yong; Sun Li; Li Yang

    2005-01-01

    Objective: To explore the effect of connective tissue growth factor (CTGF) on initiation of radiation pulmonary fibrosis (RPF) and the relation to α-smooth muscle actin (α-SMA). Methods: The promotive effect of CTGF on proliferation of human lung fibroblasts (HLF) by 5 Gy of 60 Co γ-rays was determined by MTT colorimetry. The expressions of CTGF and α-SMA in HLF were observed by Western blot. Changes of collagen I and III in rat lungs were determined by Sirius red staining and polarization microscopy. Expressions of CTGF and α-SMA in RPF were observed with immunohisto-chemistry and analysis. Results: Expressions of CTGF and α-SMA were increased. CTGF reached its peak at 24 h after irradiation, whereas α-SMA still kept at a high level 72 h after irradiation. A small amount of collagen was produced in rat lung one month after irradiation, in which type III collagen was the primary component. However, a large amount of collagen was produced in rat lung 3-6 months after irradiation, in which type I was dominant. CTGF began to expression 1 week after irradiation in proliferative fibroblasts of rat lung, and it was most evident 3 months after irradiation. α-SMA began to express in proliferative myofibroblasts 1 week after irradiation, and the high peek was reached at 3 months after irradiation. Conclusion: Irradiation can induce expression of CTGF in pulmonary tissue and the later can promote the transformation of fibroblasts to myofibroblasts, strengthen the ability of synthesis and secretion of type I and III collagen. (authors)

  15. Investigating the association between polymorphisms in connective tissue growth factor and susceptibility to colon carcinoma.

    Science.gov (United States)

    Ahmad, Abrar; Askari, Shlear; Befekadu, Rahel; Hahn-Strömberg, Victoria

    2015-04-01

    There have been numerous studies on the gene expression of connective tissue growth factor (CTGF) in colorectal cancer, however very few have investigated polymorphisms in this gene. The present study aimed to determine whether single nucleotide polymorphisms (SNPs) in the CTGF gene are associated with a higher susceptibility to colon cancer and/or an invasive tumor growth pattern. The CTGF gene was genotyped for seven SNPs (rs6918698, rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) by pyrosequencing. Formalin‑fixed paraffin‑embedded tissue samples (n=112) from patients diagnosed with colon carcinoma, and an equal number of blood samples from healthy controls, were selected for genomic DNA extraction. The complexity index was measured using images of tumor samples (n=64) stained for cytokeratin‑8. The images were analyzed and correlated with the identified CTGF SNPs and clinicopathological parameters of the patients, including age, gender, tumor penetration, lymph node metastasis, systemic metastasis, differentiation and localization of tumor. It was demonstrated that the frequency of the SNP rs6918698 GG genotype was significantly associated (P=0.05) with an increased risk of colon cancer, as compared with the GC and CC genotypes. The other six SNPs (rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) exhibited no significant difference in the genotype and allele frequencies between patients diagnosed with colon carcinoma and the normal healthy population. A trend was observed between genotype variation at rs6918698 and the complexity index (P=0.052). The complexity index and genotypes for any of the studied SNPs were not significantly correlated with clinical or pathological parameters of the patients. These results indicate that the rs6918698 GG genotype is associated with an increased risk of developing colon carcinoma, and genetic variations at the rs6918698 are associated with the growth pattern of the tumor

  16. The Effects of Environmental Factors on Smooth Muscle Cells Differentiation from Adipose-Derived Stem Cells and Esophagus Tissues Engineering

    DEFF Research Database (Denmark)

    Wang, Fang

    Adipose-derived stem cells (ASCs) are increasingly being used for regenerative medicine and tissue engineering. Smooth muscle cells (SMCs) can be differentiated from ASCs. Oxygen is a key factor influencing the stem cell differentiation. Tissue engineered esophagus has been a preferred solution...... of esophagus was studied. Our results showed that both SMCs and ASCs could attach on the porcine esophageal acellular matrix (EAM) scaffold in vitro after 24 hours and survive until 7 days. Thus ASCs might be a substitute for SMCs in the construction of tissue engineered esophageal muscle layer....

  17. Deregulated expression of connective tissue growth factor (CTGF/CCN2) is linked to poor outcome in human cancer.

    Science.gov (United States)

    Wells, Julia E; Howlett, Meegan; Cole, Catherine H; Kees, Ursula R

    2015-08-01

    Connective tissue growth factor (CTGF/CCN2) has long been associated with human cancers. The role it plays in these neoplasms is diverse and tumour specific. Recurring patterns in clinical outcome, histological desmoplasia and mechanisms of action have been found. When CTGF is overexpressed compared to low-expressing normal tissue or is underexpressed compared to high-expressing normal tissue, the functional outcome favours tumour survival and disease progression. CTGF acts by altering proliferation, drug resistance, angiogenesis, adhesion and migration contributing to metastasis. The pattern of CTGF expression and tumour response helps to clarify the role of this matricellular protein across a multitude of human cancers. © 2014 UICC.

  18. Expression of connective tissue growth factor and interleukin-11 in intratumoral tissue is associated with poor survival after curative resection of hepatocellular carcinoma.

    Science.gov (United States)

    Xiang, Zuo-Lin; Zeng, Zhao-Chong; Fan, Jia; Tang, Zhao-You; Zeng, Hai-Ying

    2012-05-01

    In the present study, we evaluated the prognostic value of intratumoral and peritumoral expression of connective tissue growth factor (CTGF), transforming growth factor-beta 1 (TGF-β1), and interleukin-11 (IL-11) in patients with hepatocellular carcinoma (HCC) after curative resection. Expression of CTGF, TGF-β1, and IL-11 was assessed by immunohistochemical staining of tissue microarrays containing paired tumor and peritumoral liver tissue from 290 patients who had undergone hepatectomy for histologically proven HCC. The prognostic value of these and other clinicopathologic factors were evaluated. The median follow-up time was 54.3 months (range, 4.3-118.3 months). High intratumoral CTGF expression was associated with vascular invasion (P = 0.015), intratumoral IL-11 expression correlated with higher tumor node metastasis (TNM) stage (P = 0.009), and peritumoral CTGF overexpression correlated with lack of tumor encapsulation (P = 0.031). Correlation analysis of these proteins revealed that intratumoral CTGF and IL-11 correlated with high intratumoral TGF-β1 expression (r = 0.325, P < 0.001; and r = 0.273, P < 0.001, respectively). TNM stage (P < 0.001), high intratumoral CTGF levels (P = 0.010), and intratumoral IL-11 expression (P = 0.015) were independent prognostic factors for progression-free survival (PFS). Vascular invasion (P = 0.032), TNM stage (P < 0.001), high intratumoral CTGF levels (P = 0.036), and intratumoral IL-11 expression (P = 0.013) were independent prognostic factors for overall survival (OS). High intratumoral CTGF and intratumoral IL-11 expression were associated with PFS and OS after hepatectomy, and the combination of intratumoral CTGF with IL-11 may be predictive of survival.

  19. Effect of high energy electrons on the skin and on the underlying tissues of the rabbit. A clinical and histological study

    International Nuclear Information System (INIS)

    Legeay, G.; Vialettes, H.; Adnet, J.J.; Court, L.; Masse, R.

    1967-01-01

    The authors consider in this report the effects of high-energy electrons on rabbit teguments and on the underlying tissues after a single high dose irradiation. After briefly considering the mechanism of interaction between the electrons and matter as a function of their energy, the authors describe the dosimetry carried out, as a function of the irradiation device. The animal received surface doses of 5700 to 22100 rads in the thigh; the electron energy varied from 21 to 30 MeV. A clinical study was carried out over a period of nine months with a view to following the evolution of the damage and the functional degradation of the underlying tissues. A histological study of the induced damage was made after a second irradiation using 30 MeV electrons to produce doses of 16400 rads. Interesting observations were made concerning the damage caused to muscular and nerve tissues. (authors) [fr

  20. 3D imaging of cells and tissues by focused ion beam/scanning electron microscopy (FIB/SEM).

    Science.gov (United States)

    Drobne, Damjana

    2013-01-01

    Integration of a scanning electron microscope (SEM) and focused ion beam (FIB) technology into a single FIB/SEM system permits use of the FIB as a nano-scalpel to reveal site-specific subsurface microstructures which can be examined in great detail by SEM. The FIB/SEM technology is widely used in the semiconductor industry and material sciences, and recently its use in the life sciences has been initiated. Samples for FIB/SEM investigation can be either embedded in a plastic matrix, the traditional means of preparation of transmission electron microscopy (TEM) specimens, or simply dried as in samples prepared for SEM imaging. Currently, FIB/SEM is used in the life sciences for (a) preparation by the lift-out technique of lamella for TEM analysis, (b) tomography of samples embedded in a matrix, and (c) in situ site-specific FIB milling and SEM imaging using a wide range of magnifications. Site-specific milling and imaging has attracted wide interest as a technique in structural research of single eukaryotic and prokaryotic cells, small animals, and different animal tissue, but it still remains to be explored more thoroughly. In the past, preparation of samples for site-specific milling and imaging by FIB/SEM has typically adopted the embedding techniques used for TEM samples, and which have been very well described in the literature. Sample preparation protocols for the use of dried samples in FIB/SEM have been less well investigated. The aim of this chapter is to encourage application of FIB/SEM on dried biological samples. A detailed description of conventional dried sample preparation and FIB/SEM investigation of dried biological samples is presented. The important steps are described and illustrated, and direct comparison between embedded and dried samples of same tissues is provided. The ability to discover links between gross morphology of the tissue or organ, surface characteristics of any selected region, and intracellular structural details on the nanometer

  1. A novel, flat, electronically-steered phased array transducer for tissue ablation: preliminary results

    International Nuclear Information System (INIS)

    Ellens, Nicholas P K; Lucht, Benjamin B C; Gunaseelan, Samuel T; Hudson, John M; Hynynen, Kullervo H

    2015-01-01

    Flat, λ/2-spaced phased arrays for therapeutic ultrasound were examined in silico and in vitro. All arrays were made by combining modules made of 64 square elements with 1.5 mm inter-element spacing along both major axes. The arrays were designed to accommodate integrated, co-aligned diagnostic transducers for targeting and monitoring. Six arrays of 1024 elements (16 modules) and four arrays of 6144 elements (96 modules) were modelled and compared according to metrics such as peak pressure amplitude, focal size, ability to be electronically-steered far off-axis and grating lobe amplitude. Two 1024 element prototypes were built and measured in vitro, producing over 100 W of acoustic power. In both cases, the simulation model of the pressure amplitude field was in good agreement with values measured by hydrophone. Using one of the arrays, it was shown that the peak pressure amplitude dropped by only 24% and 25% of the on-axis peak pressure amplitude when steered to the edge of the array (40 mm) at depths of 30 mm and 50 mm. For the 6144 element arrays studied in in silico only, similarly high steerability was found: even when steered 100 mm off-axis, the pressure amplitude decrease at the focus was less than 20%, while the maximum pressure grating lobe was only 20%. Thermal simulations indicate that the modules produce more than enough acoustic power to perform rapid ablations at physiologically relevant depths and steering angles. Arrays such as proposed and tested in this study have enormous potential: their high electronic steerability suggests that they will be able to perform ablations of large volumes without the need for any mechanical translation. (paper)

  2. Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

    Science.gov (United States)

    Hafeman, Andrea E.; Li, Bing; Yoshii, Toshitaka; Zienkiewicz, Katarzyna; Davidson, Jeffrey M.; Guelcher, Scott A.

    2013-01-01

    Purpose The purpose of this work was to investigate the effects of triisocyanate composition on the biological and mechanical properties of biodegradable, injectable polyurethane scaffolds for bone and soft tissue engineering. Methods Scaffolds were synthesized using reactive liquid molding techniques, and were characterized in vivo in a rat subcutaneous model. Porosity, dynamic mechanical properties, degradation rate, and release of growth factors were also measured. Results Polyurethane scaffolds were elastomers with tunable damping properties and degradation rates, and they supported cellular infiltration and generation of new tissue. The scaffolds showed a two-stage release profile of platelet-derived growth factor, characterized by a 75% burst release within the first 24 h and slower release thereafter. Conclusions Biodegradable polyurethanes synthesized from triisocyanates exhibited tunable and superior mechanical properties compared to materials synthesized from lysine diisocyanates. Due to their injectability, biocompatibility, tunable degradation, and potential for release of growth factors, these materials are potentially promising therapies for tissue engineering. PMID:18516665

  3. Backscattered electron imaging: The role in calcified tissue and implant analysis

    International Nuclear Information System (INIS)

    Bloebaum, R.D.; Bachus, K.N.; Boyce, T.M.

    1990-01-01

    The working distance and tilt studies helped to clarify the influences of specimen variability when the BSE mode is used in calcified tissue research. This work has shown that the BSEPs of cortical bone may be accurately maintained within 2 percent error over a 10 degree range of tilt, or 300 microns working distance variation. If future bone and implant investigators wish to conduct accurate, quantitative mineral microanalysis in bone, then standard grinding and polishing techniques should be adequate if calibration procedures are developed. The BSEP characteristics of the pure metals make them suitable to be used for calibrating the BSE signal. BSE analysis, with correlated biomechanical studies, will lead us to a better understanding of the relationships between structure, function, and mineral content in bone. On-line BSEP analysis techniques will expand our understanding of the mineralization events in bone which are associated with aging, weightlessness, pharmaceutical therapies, and the presence of biomaterials. The future of the BSE imaging technology and the contributions to be made in understanding the histometry, biomechanics and mineral content of bone as well as bone's response to implant materials has just begun to unfold. 74 references

  4. Development and Characterization of Organic Electronic Scaffolds for Bone Tissue Engineering.

    Science.gov (United States)

    Iandolo, Donata; Ravichandran, Akhilandeshwari; Liu, Xianjie; Wen, Feng; Chan, Jerry K Y; Berggren, Magnus; Teoh, Swee-Hin; Simon, Daniel T

    2016-06-01

    Bones have been shown to exhibit piezoelectric properties, generating electrical potential upon mechanical deformation and responding to electrical stimulation with the generation of mechanical stress. Thus, the effects of electrical stimulation on bone tissue engineering have been extensively studied. However, in bone regeneration applications, only few studies have focused on the use of electroactive 3D biodegradable scaffolds at the interphase with stem cells. Here a method is described to combine the bone regeneration capabilities of 3D-printed macroporous medical grade polycaprolactone (PCL) scaffolds with the electrical and electrochemical capabilities of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT). PCL scaffolds have been highly effective in vivo as bone regeneration grafts, and PEDOT is a leading material in the field of organic bioelectronics, due to its stability, conformability, and biocompatibility. A protocol is reported for scaffolds functionalization with PEDOT, using vapor-phase polymerization, resulting in a conformal conducting layer. Scaffolds' porosity and mechanical stability, important for in vivo bone regeneration applications, are retained. Human fetal mesenchymal stem cells proliferation is assessed on the functionalized scaffolds, showing the cytocompatibility of the polymeric coating. Altogether, these results show the feasibility of the proposed approach to obtain electroactive scaffolds for electrical stimulation of stem cells for regenerative medicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Electronic mode of control to obtain increased torque and improved power factor from an asynchronous machine

    NARCIS (Netherlands)

    Wyk, van J.D.

    1970-01-01

    It is indicated that, by changing the electronic switching mode of the rotor current of an induction machine, it is possible to operate the machine at improved (capacitive) power factors and increased torque, or conversely at lower effective current and capacitive power factors at rated torque.

  6. Applications of factor analysis to electron and ion beam surface techniques

    International Nuclear Information System (INIS)

    Solomon, J.S.

    1987-01-01

    Factor analysis, a mathematical technique for extracting chemical information from matrices of data, is used to enhance Auger electron spectroscopy (AES), core level electron energy loss spectroscopy (EELS), ion scattering spectroscopy (ISS), and secondary ion mass spectroscopy (SIMS) in studies of interfaces, thin films, and surfaces. Several examples of factor analysis enhancement of chemical bonding variations in thin films and at interfaces studied with AES and SIMS are presented. Factor analysis is also shown to be of great benefit in quantifying electron and ion beam doses required to induce surface damage. Finally, examples are presented of the use of factor analysis to reconstruct elemental profiles when peaks of interest overlap each other during the course of depth profile analysis. (author)

  7. The serum levels of connective tissue growth factor in patients with systemic lupus erythematosus and lupus nephritis.

    Science.gov (United States)

    Wang, F-M; Yu, F; Tan, Y; Liu, G; Zhao, M-H

    2014-06-01

    The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis. Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed. The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 ± 12.17 ng/ml vs. 22.8 ± 3.0 ng/ml, plupus erythematosus and lupus nephritis group (34.14 ± 12.17 ng/ml vs. 44.1 ± 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 ± 51.4 ng/ml vs. 23.4 ± 9.7 ng/ml, plupus nephritis (63.3 ± 63.4 ng/ml vs. 38.3 ± 37.9 ng/ml, p = 0.035, respectively). Serum connective tissue growth factor levels were negatively associated with estimated glomerular filtration rate (r = -0.46, plupus nephritis (plupus and correlated with chronic renal interstitial injury and doubling of serum creatinine in patients with lupus nephritis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  8. Errors in estimating neutron quality factor using lineal energy distributions measured in tissue-equivalent proportional counters

    International Nuclear Information System (INIS)

    Borak, T.B.; Stinchcomb, T.G.

    1982-01-01

    Neutron dose equivalent is obtained from quality factors which are defined in terms of LET. It is possible to estimate the dose averaged quality factor, antiQ, directly from distributions in lineal energy, y, that are measured in tissue-equivalent proportional counters. This eliminates a mathematical transformation of the absorbed dose from D(y) to D(L). We evaluate the inherent error in computing Q from D(y) rather than D(L) for neutron spectra below 4 MeV. The effects of neutron energy and simulated tissue diameters within a gas cavity are examined in detail. (author)

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

    International Nuclear Information System (INIS)

    Fang, Jun; Gu, Lubing; Zhu, Ningxi; Tang, Hao; Alvarado, Carlos S; Zhou, Muxiang

    2008-01-01

    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

  10. Suppression of human monocyte tissue factor induction by red wine phenolics and synthetic derivatives of resveratrol.

    Science.gov (United States)

    Kaur, Gurjeet; Roberti, Marinella; Raul, Francis; Pendurthi, Usha R

    2007-01-01

    Prevention of cardiovascular disease through nutritional supplements is growing in popularity throughout the world. Multiple epidemiologic studies found that moderate consumption of alcohol, particularly red wine, lowers mortality rates from coronary heart diseases (CHD). Chronic inflammation and atherosclerosis associated with CHD culminate in aberrant intravascular expression of tissue factor (TF), which triggers blood coagulation leading to thrombosis, a major cause for heart attack. We showed earlier that two red wine phenolics, resveratrol and quercetin, suppressed TF induction in endothelial cells. In the present study, we investigated efficacy of seven resveratrol derivatives, which were shown to be effective in regulating cancer cell growth in vitro at much lower concentrations than the parent compound resveratrol, in inhibiting TF induction in peripheral blood mononuclear cells (PBMCs). We also tested possible synergistic effects of resveratrol and quercetin with the other major red wine phenolics in suppression of lipopolysaccharide-induced TF expression in human PBMCs. We found that several resveratrol derivatives were 2- to 10-fold more efficient than resveratrol in inhibiting TF induction. Our study found no evidence for synergism among red wine polyphenolics. These data suggest that structural alterations of resveratrol can be effective in producing potent antithrombotic agents that will have therapeutic potential in the improvement of cardiovascular health and prevention of CHD. Among major red wine phenolics, quercetin appears to be the predominant suppressor of TF induction.

  11. Suppression of human monocyte tissue factor induction by red wine phenolics and synthetic derivatives of resveratrol

    Science.gov (United States)

    Kaur, Gurjeet; Roberti, Marinella; Raul, Francis; Pendurthi, Usha R.

    2010-01-01

    Prevention of cardiovascular disease through nutritional supplements is growing in popularity throughout the world. Multiple epidemiologic studies found that moderate consumption of alcohol, particularly red wine, lowers mortality rates from coronary heart diseases (CHD). Chronic inflammation and atherosclerosis associated with CHD culminate in aberrant intravascular expression of tissue factor (TF), which triggers blood coagulation leading to thrombosis, a major cause for heart attack. We showed earlier that two red wine phenolics, resveratrol and quercetin, suppressed TF induction in endothelial cells. In the present study, we investigated efficacy of seven resveratrol derivatives, which were shown to be effective in regulating cancer cell growth in vitro at much lower concentrations than the parent compound resveratrol, in inhibiting TF induction in peripheral blood mononuclear cells (PBMCs). We also tested possible synergistic effects of resveratrol and quercetin with the other major red wine phenolics in suppression of lipopolysaccharide-induced TF expression in human PBMCs. We found that several resveratrol derivatives were 2- to 10-fold more efficient than resveratrol in inhibiting TF induction. Our study found no evidence for synergism among red wine polyphenolics. These data suggest that structural alterations of resveratrol can be effective in producing potent antithrombotic agents that will have therapeutic potential in the improvement of cardiovascular health and prevention of CHD. Among major red wine phenolics, quercetin appears to be the predominant suppressor of TF induction. PMID:16507316

  12. Tissue factor expression by myeloid cells contributes to protective immune response against Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Venkatasubramanian, Sambasivan; Tripathi, Deepak; Tucker, Torry; Paidipally, Padmaja; Cheekatla, Satyanarayana; Welch, Elwyn; Raghunath, Anjana; Jeffers, Ann; Tvinnereim, Amy R; Schechter, Melissa E; Andrade, Bruno B; Mackman, Nizel; Idell, Steven; Vankayalapati, Ramakrishna

    2016-02-01

    Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TF(Δ) ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL-10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2-like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)-2 and MMP-9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Hormonal receptors and vascular endothelial growth factor in juvenile nasopharyngeal angiofibroma: immunohistochemical and tissue microarray analysis.

    Science.gov (United States)

    Liu, Zhuofu; Wang, Jingjing; Wang, Huan; Wang, Dehui; Hu, Li; Liu, Quan; Sun, Xicai

    2015-01-01

    This work demonstrated that juvenile nasopharyngeal angiofibromas (JNAs) express high levels of hormone receptors and vascular endothelial growth factor (VEGF) compared with normal nasal mucosa. The interaction between hormone receptors and VEGF may be involved in the initiation and growth of JNA. JNA is a rare benign tumor that occurs almost exclusively in male adolescents. Although generally regarded as a hormone-dependent tumor, this has not been proven in previous studies. The aim of this study was to investigate the role of hormone receptors in JNA and the relationship with clinical characteristics. Standard immunohistochemical microarray analysis was performed on 70 JNA samples and 10 turbinate tissue samples. Specific antibodies for androgen receptor (AR), estrogen receptor-α (ER-α), estrogen receptor-β (ER-β), progesterone receptor (PR), and VEGF were examined, and the relationships of receptor expression with age, tumor stage, and bleeding were evaluated. RESULTS showed that JNA expressed ER-α (92.9%), ER-β (91.4%), AR (65.7%), PR (12.8%), and VEGF (95.7%) at different levels. High level of VEGF was linked to elevated ER-α and ER-β. There was no significant relationship between hormonal receptors and age at diagnosis, tumor stage or bleeding. However, overexpression of ER-α was found to be an indicator of poor prognosis (p = 0.031).

  14. Tissue tropisms in group A Streptococcus: what virulence factors distinguish pharyngitis from impetigo strains?

    Science.gov (United States)

    Bessen, Debra E

    2016-06-01

    Group A streptococci (GAS) are a common cause of pharyngitis and impetigo, and distinct throat strains and skin strains have been long recognized. This review aims to describe recent advances in molecular differences between throat and skin strains, and the pathogenic mechanisms used by virulence factors that may distinguish between these two groups. Recent findings include a new typing scheme for GAS strains based on sequence clusters of genes encoding the entire surface-exposed portion of M protein; correlations between emm-based typing schemes, clinical disease and surface adhesins; covalent bond formation mediated by GAS pili and other adhesins in binding to host ligands; a key role for superantigens in oropharyngeal infection via binding major histocompatibility complex class II antigen; and migration of GAS-specific Th17 cells from the upper respiratory tract to the brain, which may be relevant to autoimmune sequelae. The gap between molecular markers of disease (correlation) and virulence mechanisms (causation) in the establishment of tissue tropisms for GAS infection currently remains wide, but the gap also continues to narrow. Whole genome sequencing combined with mutant construction and improvements in animal models for oropharyngeal infection by GAS may help pave the way for new discoveries.

  15. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer.

    Science.gov (United States)

    Moran-Jones, Kim; Gloss, Brian S; Murali, Rajmohan; Chang, David K; Colvin, Emily K; Jones, Marc D; Yuen, Samuel; Howell, Viive M; Brown, Laura M; Wong, Carol W; Spong, Suzanne M; Scarlett, Christopher J; Hacker, Neville F; Ghosh, Sue; Mok, Samuel C; Birrer, Michael J; Samimi, Goli

    2015-12-29

    Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer.

  16. Downregulation of connective tissue growth factor reduces migration and invasiveness of osteosarcoma cells.

    Science.gov (United States)

    Huang, Yinjun; Zhao, Shichang; Zhang, Changqing; Li, Xiaolin

    2016-02-01

    As one of the most serious types of primary bone tumor, osteosarcoma (OSA) features metastatic lesions, and resistance to chemotherapy is common. The underlying mechanisms of these characteristics may account for the failure of treatments and the poor prognosis of patients with OSA. It has been reported that inhibition of Cyr61 suppresses OSA cell proliferation as it represents a target of statins. In addition to cystein‑rich protein 61 (Cyr61) and nephroblastoma overexpression, connective tissue growth factor (CTGF) is a member of the CCN family and may therefore exhibit effects on human OSA cells similar to those of Cyr61. In the current study, acridine orange/ethidium bromide staining were used to determine the rate of apoptosis. The present study demonstrated that small interfering RNA‑mediated silencing of CTGF promoted cell death and suppressed OSA cell migration and invasion, as indicated by wound healing and Transwell assays, while lentivirus‑mediated overexpression of CTGF reversed these effects. Furthermore, a colorimetric caspase assay demonstrated that CTGF knockdown enhanced the efficacy of chemotherapeutic drugs. The results of the present study provided a novel molecular target which may be utilized for the treatment of metastatic OSA.

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

    Science.gov (United States)

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

    2016-12-01

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

  18. Cardiovascular risk factors cause premature rarefaction of the collateral circulation and greater ischemic tissue injury.

    Science.gov (United States)

    Moore, Scott M; Zhang, Hua; Maeda, Nobuyo; Doerschuk, Claire M; Faber, James E

    2015-07-01

    Collaterals lessen tissue injury in occlusive disease. However, aging causes progressive decline in their number and smaller diameters in those that remain (collateral rarefaction), beginning at 16 months of age in mice (i.e., middle age), and worse ischemic injury-effects that are accelerated in even 3-month-old eNOS(-/-) mice. These findings have found indirect support in recent human studies. We sought to determine whether other cardiovascular risk factors (CVRFs) associated with endothelial dysfunction cause collateral rarefaction, investigate possible mechanisms, and test strategies for prevention. Mice with nine different models of CVRFs of 4-12 months of age were assessed for number and diameter of native collaterals in skeletal muscle and brain and for collateral-dependent perfusion and ischemic injury after arterial occlusion. Hypertension caused collateral rarefaction whose severity increased with duration and level of hypertension, accompanied by greater hindlimb ischemia and cerebral infarct volume. Chronic treatment of wild-type mice with L-N (G)-nitro-arginine methylester caused similar rarefaction and worse ischemic injury which were not prevented by lowering arterial pressure with hydralazine. Metabolic syndrome, hypercholesterolemia, diabetes mellitus, and obesity also caused collateral rarefaction. Neither chronic statin treatment nor exercise training lessened hypertension-induced rarefaction. Chronic CVRF presence caused collateral rarefaction and worse ischemic injury, even at relatively young ages. Rarefaction was associated with increased proliferation rate of collateral endothelial cells, effects that may promote accelerated endothelial cell senescence.

  19. Influence of Expression Plasmid of Connective Tissue Growth Factor and Tissue Inhibitor of Metalloproteinase-1 shRNA on Hepatic Precancerous Fibrosis in Rats.

    Science.gov (United States)

    Zhang, Qun; Shu, Fu-Li; Jiang, Yu-Feng; Huang, Xin-En

    2015-01-01

    In this study, influence caused by expression plasmids of connective tissue growth factor (CTGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) short hairpin RNA (shRNA) on mRNA expression of CTGF,TIMP-1,procol-α1 and PCIII in hepatic tissue with hepatic fibrosis, a precancerous condition, in rats is analyzed. To screen and construct shRNA expression plasimid which effectively interferes RNA targets of CTGF and TIMP-1 in rats. 50 cleaning Wistar male rats are allocated randomly at 5 different groups after precancerous fibrosis models and then injection of shRNA expression plasimids. Plasmid psiRNA-GFP-Com (CTGF and TIMP-1 included), psiRNA-GFP-CTGF, psiRNA-GFP-TIMP-1 and psiRNA- DUO-GFPzeo of blank plasmid are injected at group A, B, C and D, respectively, and as model control group that none plasimid is injected at group E. In 2 weeks after last injection, to hepatic tissue at different groups, protein expression of CTGF, TIMP-1, procol-α1and PC III is tested by immunohistochemical method and,mRNA expression of CTGF,TIMP-1,procol-α1 and PCIII is measured by real-time PCR. One-way ANOVA is used to comparison between-groups. Compared with model group, there is no obvious difference of mRNA expression among CTGF,TIMP-1,procol-α1,PC III and of protein expression among CTGF, TIMP-1, procol-α1, PC III in hepatic tissue at group injected with blank plasmid. Expression quantity of mRNA of CTGF, TIMP-1, procol-α1 and PCIII at group A, B and C decreases, protein expression of CTGF, TIMP-1, procol-α1, PC III in hepatic tissue is lower, where the inhibition of combination RNA interference group (group A) on procol-α1 mRNA transcription and procol-α1 protein expression is superior to that of single interference group (group B and C) (P<0.01 or P<0.05). RNA interference on CTGF and/or TIMP-1 is obviously a inhibiting factor for mRNA and protein expression of CTGF, TIMP-1, procol-α1 and PCIII. Combination RNA interference on genes of CTGF and TIMP-1 is superior

  20. Effects of gamma radiation on hard dental tissues of albino rats using scanning electron microscope - Part 1

    Science.gov (United States)

    El-Faramawy, Nabil; Ameen, Reham; El-Haddad, Khaled; Maghraby, Ahmed; El-Zainy, Medhat

    2011-12-01

    In the present study, 40 adult male albino rats were used to study the effect of gamma radiation on the hard dental tissues (enamel surface, dentinal tubules and the cementum surface). The rats were irradiated at 0.2, 0.5, 1.0, 2.0, 4.0 and 6.0 Gy gamma doses. The effects of irradiated hard dental tissues samples were investigated using a scanning electron microscope. For doses up to 0.5 Gy, there was no evidence of the existence of cracks on the enamel surface. With 1 Gy irradiation dose, cracks were clearly observed with localized erosive areas. At 2 Gy irradiation dose, the enamel showed morphological alterations as disturbed prismatic and interprismatic areas. An increase in dentinal tubules diameter and a contemporary inter-tubular dentine volume decrease were observed with higher irradiation dose. Concerning cementum, low doses,<0.5 Gy, showed surface irregularities and with increase in the irradiation dose to≥1 Gy, noticeable surface irregularities and erosive areas with decrease in Sharpey's fiber sites were observed. These observations could shed light on the hazardous effects of irradiation fields to the functioning of the human teeth.

  1. Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.

    Science.gov (United States)

    Johnson, Kevin C; Houseman, E Andres; King, Jessica E; Christensen, Brock C

    2017-07-10

    The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies. Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of established breast cancer risk factors, age, body mass index, parity, and family history of disease, with DNA methylation adjusting for potential variation in cell-type proportions. We identified 787 cytosine-guanine dinucleotide (CpG) sites that demonstrated significant associations (Q value breast cancer risk factors. Age-related DNA methylation changes are primarily increases in methylation enriched at breast epithelial cell enhancer regions (P = 7.1E-20), and binding sites of chromatin remodelers (MYC and CTCF). We validated the age-related associations in two independent populations, using normal breast tissue samples (n = 18) and samples of normal tissue adjacent to tumor tissue (n = 97). The genomic regions classified as age-related were more likely to be regions altered in both pre-invasive (n = 40, P = 3.0E-03) and invasive breast tumors (n = 731, P = 1.1E-13). DNA methylation changes with age occur at regulatory regions, and are further exacerbated in cancer, suggesting that age influences breast cancer risk in part through its contribution to epigenetic dysregulation in normal breast tissue.

  2. Electron microscopic studies of the matrix formation of hard tissue organized cell

    International Nuclear Information System (INIS)

    Chou, Ching-Eng

    1982-01-01

    In order to study the functions of odontoblast, especially on the matrix formation, odontoblasts of rats' incisor and molar teeth were used. The animals were sacrificed 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours and 24 hours after 3 H-proline administration to obtain the specimen. The specimens were processed for electron microscopic autoradiography. The following results were obtained. 1. 5 minutes after 3 H-proline administration: Silver grains indicated 3 H-proline uptake were already noted within the cells and localized in the rough surfaced endoplasmic reticulum and surrounding ribosomes, partially within the karyoplasm. 2. 15 minutes after 3 H-proline administration: The number of silver grains were generally increased as compared with the findings obtained in 5 minutes. The localization moved to the Golgi apparatus and their surroundings. 3. 30 minutes after 3 H-proline administration: Silver grains obtained in Tome's fibers area and some in predentin. In this area granules derived from Golgi body were found. 4. 1 hour after 3 H-proline administration: The number of silver grains were generally decreased and more pronounced movement toward predentin, the marked movement of silver grains were obtained onto the collagen fibers and surroundings. 5. 2 hours after 3 H-proline administration: Silver grains moved to the calcified area and there collagen fibers became more remarkable. 6. 24 hours after 3 H-proline administration: No silver grains were founded in the odontoblast side but deposited in the predentin calcified area with stable condition. Based on the results of these observations, odontoblasts were shown to perform the function of synthesis, storage, transportation and control of collagen formation in addition to the role of matrix formation. (author)

  3. Investigation of trefoil factor expression in saliva and oral mucosal tissues of patients with oral squamous cell carcinoma

    DEFF Research Database (Denmark)

    Chaiyarit, Ponlatham; Utrawichian, Akasith; Leelayuwat, Chanvit

    2012-01-01

    Objectives The aims of our study were to determine levels of trefoil factor (TFF) peptides in saliva and oral mucosal tissues from patients with oral squamous cell carcinoma (OSCC), and to evaluate whether individual members of TFFs (TFF1, TFF2, and TFF3) might act as biomarkers of disease....... Materials and methods Saliva samples were from 23 healthy subjects and 23 OSCC patients. Tissue samples were collected from 32 normal oral mucosa (NOM) and 32 OSCC biopsy specimens. ELISA and immunohistochemical methods were used to evaluate the expression of TFF1, TFF2, and TFF3 in saliva and oral mucosal...... tissues, respectively. Results Expression of TFF2 and TFF3 in oral mucosal tissues of OSCC patients was strongly downregulated when compared to healthy subjects (p 

  4. Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination.

    Science.gov (United States)

    Jiang, Cheng-Gang; Lv, Ling; Liu, Fu-Rong; Wang, Zhen-Ning; Liu, Fu-Nan; Li, Yan-Shu; Wang, Chun-Yu; Zhang, Hong-Yan; Sun, Zhe; Xu, Hui-Mian

    2011-09-28

    Connective tissue growth factor (CTGF) has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown. In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P cancer cells and decreased cyclin D1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines. These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.

  5. Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination

    Directory of Open Access Journals (Sweden)

    Zhang Hong-Yan

    2011-09-01

    Full Text Available Abstract Background Connective tissue growth factor (CTGF has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown. Results In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P 1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines. Conclusions These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.

  6. Prognostic factors in adult soft-tissue sarcomas of the head and neck

    International Nuclear Information System (INIS)

    Le, Quynh-Thu X.; Fu, Karen K.; Kroll, Stew; Fitts, Linda; Massullo, Vincent; Ferrell, Linda; Kaplan, Michael J.; Phillips, Theodore L.

    1997-01-01

    Purpose: The main objectives of this study were (a) to review the treatment results of primary head and neck soft-tissue sarcoma at our institution, (b) to identify important prognostic factors in local control and survival, and (c) to assess the efficacy of salvage therapy. Methods and Materials: Sixty-five patients were treated at the University of California, San Francisco, between 1961 and 1993. Seventeen patients (27%) had low-grade, 10 (15%) had intermediate-grade, and 38 (58%) had high-grade sarcomas. Tumors were > 5 cm in 35 patients. Local management consisted of surgery alone in 14 patients (22%), surgery and radiotherapy in 40 (61%), and radiotherapy alone in 11 (17%) patients. The median follow-up was 64 months. Results: The 5-year actuarial local control rate of the entire group was 66%. Tumor size and grade were important predictors for local control on multivariate analysis. The actuarial local control rate at 5 years was 92% for T1 vs. 40% for T2 primaries (p = 0.004), and 80% for Grade 1-2 vs. 48% for Grade 3 tumors (p 0.01). None of the patients treated with radiotherapy alone with a dose of 50-65 Gy were controlled locally. Combined radiotherapy and surgery appeared to yield superior local control compared to surgery alone (77% vs. 59%); however, the difference was not statistically significant. The 5-year actuarial overall and cause-specific survivals were 56% and 60%, respectively. Unfavorable prognostic factors for cause-specific survival on multivariate analysis were age > 55 (p = 0.009), high tumor grade (p 0.0002), inadequate surgery (p = 0.008), and positive surgical margins (p 0.0009). In patients who underwent salvage therapy for treatment failure, the 5-year actuarial survival after salvage treatment was 26%. Conclusion: Tumor size and grade were important predictors for local control. Age, grade, adequacy of surgery, and status of surgical margins were significant prognostic factors for survival. There was a trend of improved local

  7. Ab initio determination of effective electron-phonon coupling factor in copper

    Science.gov (United States)

    Ji, Pengfei; Zhang, Yuwen

    2016-04-01

    The electron temperature Te dependent electron density of states g (ε), Fermi-Dirac distribution f (ε), and electron-phonon spectral function α2 F (Ω) are computed as prerequisites before achieving effective electron-phonon coupling factor Ge-ph. The obtained Ge-ph is implemented into a molecular dynamics (MD) and two-temperature model (TTM) coupled simulation of femtosecond laser heating. By monitoring temperature evolutions of electron and lattice subsystems, the result utilizing Ge-ph from ab initio calculation shows a faster decrease of Te and increase of Tl than those using Ge-ph from phenomenological treatment. The approach of calculating Ge-ph and its implementation into MD-TTM simulation is applicable to other metals.

  8. A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration

    Directory of Open Access Journals (Sweden)

    Dyondi D

    2012-12-01

    Full Text Available Deepti Dyondi,1 Thomas J Webster,2 Rinti Banerjee11Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India; 2Nanomedicine Laboratories, Division of Engineering and Department of Orthopedics, Brown University, Providence, RI, USAAbstract: Gellan xanthan gels have been shown to be excellent carriers for growth factors and as matrices for several tissue engineering applications. Gellan xanthan gels along with chitosan nanoparticles of 297 ± 61 nm diameter, basic fibroblast growth factor (bFGF, and bone morphogenetic protein 7 (BMP7 were employed in a dual growth factor delivery system to promote the differentiation of human fetal osteoblasts. An injectable system with ionic and temperature gelation was optimized and characterized. The nanoparticle loaded gels showed significantly improved cell proliferation and differentiation due to the sustained release of growth factors. A differentiation marker study was conducted, analyzed, and compared to understand the effect of single vs dual growth factors and free vs encapsulated growth factors. Dual growth factor loaded gels showed a higher alkaline phosphatase and calcium deposition compared to single growth factor loaded gels. The results suggest that encapsulation and stabilization of growth factors within nanoparticles and gels are promising for bone regeneration. Gellan xanthan gels also showed antibacterial effects against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, the common pathogens in implant failure.Keywords: bone tissue engineering, bone morphogenetic protein 7 (BMP7, basic fibroblast growth factor (bFGF, hydrogel, nanoparticles, osteoblasts

  9. Cloning Changes the Response to Obesity of Innate Immune Factors in Blood, Liver, and Adipose Tissues in Domestic Pigs

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard; Skovgaard, Kerstin; Stagsted, Jan

    2013-01-01

    The objective of this study was to evaluate the usefulness of cloned pigs as porcine obesity models reflecting obesity-associated changes in innate immune factor gene expression profiles. Liver and adipose tissue expression of 43 innate immune genes as well as serum concentrations of six immune...... factors were analyzed in lean and diet-induced obese cloned domestic pigs and compared to normal domestic pigs (obese and lean). The number of genes affected by obesity was lower in cloned animals than in control animals. All genes affected by obesity in adipose tissues of clones were downregulated; both...... upregulation and downregulation were observed in the controls. Cloning resulted in a less differentiated adipose tissue expression pattern. Finally, the serum concentrations of two acute-phase proteins (APPs), haptoglobin (HP) and orosomucoid (ORM), were increased in obese clones as compared to obese controls...

  10. The rotator cuff: from bench to bedside. Developments in tissue engineering, surgical techniques and pathogenetic factors

    NARCIS (Netherlands)

    Longo, U.G.

    2012-01-01

    This thesis originates from the difficulties in the management of patients with rotator cuff tears. Since tendon healing rate is relatively slow compared with other connective tissues, we reviewed the available literature on tissue engineered biological augmentation for tendon healing, including

  11. Identification and Progression of Heart Disease Risk Factors in Diabetic Patients from Longitudinal Electronic Health Records

    Directory of Open Access Journals (Sweden)

    Jitendra Jonnagaddala

    2015-01-01

    Full Text Available Heart disease is the leading cause of death worldwide. Therefore, assessing the risk of its occurrence is a crucial step in predicting serious cardiac events. Identifying heart disease risk factors and tracking their progression is a preliminary step in heart disease risk assessment. A large number of studies have reported the use of risk factor data collected prospectively. Electronic health record systems are a great resource of the required risk factor data. Unfortunately, most of the valuable information on risk factor data is buried in the form of unstructured clinical notes in electronic health records. In this study, we present an information extraction system to extract related information on heart disease risk factors from unstructured clinical notes using a hybrid approach. The hybrid approach employs both machine learning and rule-based clinical text mining techniques. The developed system achieved an overall microaveraged F-score of 0.8302.

  12. Evaluation and analysis of the factors influencing the electron beam dynamics through the buncher of LINAC

    International Nuclear Information System (INIS)

    Ghasemi, F.; Abbasi, F.; Lamehi, M.; Shaker, H.

    2013-01-01

    In this paper, the importance of the buncher in linear electron accelerators is discussed and two types of bunchers, velocity-modulation and disk-loaded, are introduced. Higher bunching factor, larger initial phase range, and smaller final phase range are favorable in the disk-loaded buncher. Our investigations showed that the aforementioned situations can be met by appropriate changes in the field strength and the phase velocity. In this study, factors affecting the bunching of electrons have been surveyed using the equations of electron motion. The dynamics of the electron movement through the buncher has been simulated. The results of simulation and calculations revealed that: (1) in order to deliver the maximum energy to the electrons, phase velocity should vary so that a phase of - 90 degrees is achieved by the electrons after the bunching, (2) reducing the initial field strength also increases the initial phase range. If the field strength is large from the beginning, the phase velocity variations will be large and rapidly reach a value of 1. In this case, the initial phase range will become small, (3) the electron gun voltage changes the initial phase; the larger the value of the gun voltage, the wider the initial phase range, and vice versa. The result of this study is going to be applied for design and fabrication of the first Iranian linear accelerator that is under construction.

  13. Study on the output factors of asymmetrical rectangular electron beam field

    International Nuclear Information System (INIS)

    Chen Yinghai; Yang Yueqin; Ma Yuhong; Zheng Jin; Zou Lijuan

    2009-01-01

    Objective: To evaluate the variant regularity of the output factors of asymmetrical rectangular electron beam field. Methods: The output factors of three special fields with different applicators and energies were measured by ionization chamber method at different off-axis distances. Then deviations of the output factors between asymmetrical and symmetric rectangular fields were calculated. Results: The changes of output factor with different off-axis distances in asymmetrical rectangular fields were basically consistent with those in standard square fields with the same applicator. It revealed that the output factor of asymmetrical rectangular field was related with the off-axis ratio of standard square field. Applicator and field size did not show obvious influence on the output factor. Conclusions: The output factor changes of asymmetrical rectangular field are mainly correlated with the off-axis ratio of standard square field. The correction of the output factor is determined by the off-axis ratio changes in standard square field. (authors)

  14. Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

    Science.gov (United States)

    Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

    2016-12-01

    Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bosma, A.; Majoor, D.M.; Doorn, van J.; Cats, A.; Depla, A.; Timmer, R.; Witteman, B.J.M.; Wesseling, J.; Kampman, E.; van't Veer, L.J.

    2009-01-01

    Context: The insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are

  16. Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels.

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bosma, A.; Majoor, D.M.; Doorn, J. van; Cats, A.; Depla, A.C.; Timmer, R.; Witteman, B.J.; Wesseling, J.; Kampman, E.; Veer, L.J. van 't

    2009-01-01

    CONTEXT: The insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are

  17. Characterization of connective tissue growth factor expression in primary cultures of human tubular epithelial cells: modulation by hypoxia

    NARCIS (Netherlands)

    Kroening, Sven; Neubauer, Emily; Wullich, Bernd; Aten, Jan; Goppelt-Struebe, Margarete

    2010-01-01

    Kroening S, Neubauer E, Wullich B, Aten J, Goppelt-Struebe M. Characterization of connective tissue growth factor expression in primary cultures of human tubular epithelial cells: modulation by hypoxia. Am J Physiol Renal Physiol 298:F796-F806, 2010. First published December 23, 2009;

  18. Recombinant human tissue factor pathway inhibitor exerts anticoagulant, anti-inflammatory and antimicrobial effects in murine pneumococcal pneumonia

    NARCIS (Netherlands)

    van den Boogaard, F. E.; Brands, X.; Schultz, M. J.; Levi, M. [=Marcel M.; Roelofs, J. J. T. H.; van 't Veer, C.; van der Poll, T.

    2011-01-01

    Background: Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia and a major cause of sepsis. Recombinant human tissue factor pathway inhibitor (rh-TFPI) attenuates sepsis-induced coagulation and has been evaluated in clinical trials involving patients

  19. Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate

    NARCIS (Netherlands)

    Mizutani, Makoto; Ito, Yasuhiko; Mizuno, Masashi; Nishimura, Hayato; Suzuki, Yasuhiro; Hattori, Ryohei; Matsukawa, Yoshihisa; Imai, Masaki; Oliver, Noelynn; Goldschmeding, Roel; Aten, Jan; Krediet, Raymond T.; Yuzawa, Yukio; Matsuo, Seiichi

    2010-01-01

    Mizutani M, Ito Y, Mizuno M, Nishimura H, Suzuki Y, Hattori R, Matsukawa Y, Imai M, Oliver N, Goldschmeding R, Aten J, Krediet RT, Yuzawa Y, Matsuo S. Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate. Am J Physiol

  20. Factors affecting the mechanical behavior of collagen hydrogels for skin tissue engineering.

    Science.gov (United States)

    Pensalfini, Marco; Ehret, Alexander E; Stüdeli, Silvia; Marino, Daniela; Kaech, Andres; Reichmann, Ernst; Mazza, Edoardo

    2017-05-01

    The effect of the production factors yielding a functional dermal substitute was investigated by means of monotonic and cyclic uniaxial tensile tests, as well as electron microscopy visualizations. The role of (i) plastic compression, (ii) product incubation, and (iii) cell permanence in the collagenous matrix in order to achieve a skin-like behavior were characterized in terms of material and structural stiffness, in-plane kinematics, and cyclic response, as well as pore size and network density. The plastic compression resulted in a denser and stiffer material, while no corresponding change was observed in the behavior of the entire structure. This was related to the progressive reduction in product thickness and amount of excess water, rather than to formation of new crosslinks between fibers. Contrary, irrespective of the presence of human fibroblasts, the product incubation induced both material and structural stiffening, indicating the formation of a denser network. These results were confirmed by similar evolutions in the construct in-plane kinematics and cyclic stress reduction. Finally, comparison of constructs incubated in different culture media indicated a determinant contribution of the biochemical environment, rather than of the seeded cells, to the achieved mechanical properties. The observed features are relevant in terms of mechanical biocompatibility of the implant and might direct future optimizations of the production process in order to rapidly attain the desired mechanical properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Downregulation of Connective Tissue Growth Factor by Three-Dimensional Matrix Enhances Ovarian Carcinoma Cell Invasion

    Science.gov (United States)

    Barbolina, Maria V.; Adley, Brian P.; Kelly, David L.; Shepard, Jaclyn; Fought, Angela J.; Scholtens, Denise; Penzes, Peter; Shea, Lonnie D.; Sharon Stack, M

    2010-01-01

    Epithelial ovarian carcinoma (EOC) is a leading cause of death from gynecologic malignancy, due mainly to the prevalence of undetected metastatic disease. The process of cell invasion during intra-peritoneal anchoring of metastatic lesions requires concerted regulation of many processes, including modulation of adhesion to the extracellular matrix and localized invasion. Exploratory cDNA microarray analysis of early response genes (altered after 4 hours of 3-dimensional collagen culture) coupled with confirmatory real-time RT-PCR, multiple three-dimensional cell culture matrices, Western blot, immunostaining, adhesion, migration, and invasion assays were used to identify modulators of adhesion pertinent to EOC progression and metastasis. cDNA microarray analysis indicated a dramatic downregulation of connective tissue growth factor (CTGF) in EOC cells placed in invasion-mimicking conditions (3-dimensional type I collagen). Examination of human EOC specimens revealed that CTGF expression was absent in 46% of the tested samples (n=41), but was present in 100% of normal ovarian epithelium samples (n=7). Reduced CTGF expression occurs in many types of cells and may be a general phenomenon displayed by cells encountering a 3D environment. CTGF levels were inversely correlated with invasion such that downregulation of CTGF increased, while its upregulation reduced, collagen invasion. Cells adhered preferentially to a surface comprised of both collagen I and CTGF relative to either component alone using α6β1 and α3β1 integrins. Together these data suggest that downregulation of CTGF in EOC cells may be important for cell invasion through modulation of cell-matrix adhesion. PMID:19382180

  2. Connective Tissue Growth Factor Promotes Pulmonary Epithelial Cell Senescence and Is Associated with COPD Severity.

    Science.gov (United States)

    Jang, Jun-Ho; Chand, Hitendra S; Bruse, Shannon; Doyle-Eisele, Melanie; Royer, Christopher; McDonald, Jacob; Qualls, Clifford; Klingelhutz, Aloysius J; Lin, Yong; Mallampalli, Rama; Tesfaigzi, Yohannes; Nyunoya, Toru

    2017-04-01

    The purpose of this study was to determine whether expression of connective tissue growth factor (CTGF) protein in chronic obstructive pulmonary disease (COPD) is consistent in humans and animal models of COPD and to investigate the role of this protein in lung epithelial cells. CTGF in lung epithelial cells of ex-smokers with COPD was compared with ex-smokers without COPD by immunofluorescence. A total of twenty C57Bl/6 mice and sixteen non-human primates (NHPs) were exposed to cigarette smoke (CS) for 4 weeks. Ten mice of these CS-exposed mice and eight of the CS-exposed NHPs were infected with H3N2 influenza A virus (IAV), while the remaining ten mice and eight NHPs were mock-infected with vehicle as control. Both mRNA and protein expression of CTGF in lung epithelial cells of mice and NHPs were determined. The effects of CTGF overexpression on cell proliferation, p16 protein, and senescence-associated β-galactosidase (SA-β-gal) activity were examined in cultured human bronchial epithelial cells (HBECs). In humans, CTGF expression increased with increasing COPD severity. We found that protein expression of CTGF was upregulated in lung epithelial cells in both mice and NHPs exposed to CS and infected with IAV compared to those exposed to CS only. When overexpressed in HBECs, CTGF accelerated cellular senescence accompanied by p16 accumulation. Both CTGF and p16 protein expression in lung epithelia are positively associated with the severity of COPD in ex-smokers. These findings show that CTGF is consistently expressed in epithelial cells of COPD lungs. By accelerating lung epithelial senescence, CTGF may block regeneration relative to epithelial cell loss and lead to emphysema.

  3. HFE gene mutation is a risk factor for tissue iron accumulation in hemodialysis patients.

    Science.gov (United States)

    Turkmen, Ercan; Yildirim, Tolga; Yilmaz, Rahmi; Hazirolan, Tuncay; Eldem, Gonca; Yilmaz, Engin; Aybal Kutlugun, Aysun; Altindal, Mahmut; Altun, Bulent

    2017-07-01

    HFE gene mutations are responsible from iron overload in general population. Studies in hemodialysis patients investigated the effect of presence of HFE gene mutations on serum ferritin and transferrin saturation (TSAT) with conflicting results. However effect of HFE mutations on iron overload in hemodialysis patients was not previously extensively studied. 36 hemodialysis patients (age 51.3 ± 15.6, (18/18) male/female) and 44 healthy control subjects included in this cross sectional study. Hemoglobin, ferritin, TSAT in the preceding 2 years were recorded. Iron and erythropoietin (EPO) administered during this period were calculated. Iron accumulation in heart and liver was detected by MRI. Relationship between HFE gene mutation, hemoglobin, iron parameters and EPO doses, and tissue iron accumulation were determined. Iron overload was detected in nine (25%) patients. Hemoglobin, iron parameters, weekly EPO doses, and monthly iron doses of patients with and without iron overload were similar. There was no difference between control group and hemodialysis patients with respect to the prevalence of HFE gene mutations. Iron overload was detected in five of eight patients who had HFE gene mutations, but iron overload was present in 4 of 28 patients who had no mutations (P = 0.01). Hemoglobin, iron parameters, erythropoietin, and iron doses were similar in patients with and without gene mutations. HFE gene mutations remained the main determinant of iron overload after multivariate logistic regression analysis (P = 0.02; OR, 11.6). Serum iron parameters were not adequate to detect iron overload and HFE gene mutation was found to be an important risk factor for iron accumulation. © 2017 International Society for Hemodialysis.

  4. Expression of connective tissue growth factor in male breast cancer: clinicopathologic correlations and prognostic value.

    Science.gov (United States)

    Lacle, Miangela M; van Diest, Paul J; Goldschmeding, Roel; van der Wall, Elsken; Nguyen, Tri Q

    2015-01-01

    Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of secreted proteins that are believed to play an important role in the development of neoplasia. In particular, CTGF has been reported to play an important role in mammary tumorigenesis and to have prognostic value in female breast cancer (FBC). The aim of the present study was to investigate clinicopathologic correlations and prognostic value of CTGF in male breast cancer (MBC) and to compare these findings with FBC. For this, we studied CTGF protein expression by immunohistochemistry in 109 MBC cases and 75 FBC cases. In MBC, stromal CTGF expression was seen in the majority of the cases 78% (85/109) with high expression in 31/109 cases (28.4%), but expression in tumor cells was only seen in 9.2% (10/109) of cases. High stromal CTGF expression correlated with high grade and high proliferation index (>15%) assessed by MIB-1 immunohistochemical staining. CTGF expression in tumor epithelial cells did not correlate with any of the clinicopathologic features. In FBC, stromal CTGF expression positively correlated with mitotic count and tumor CTGF expression was associated with triple negative status of the tumor (p = 0.002). Neither stromal nor tumor epithelial cell CTGF expression had prognostic value in MBC and FBC. In conclusion, stromal CTGF expression was seen in a high percentage of MBC and was correlated with high grade and high proliferation index. In view of the important role of the microenvironment in cancer progression, this might suggest that stromal CTGF could be an interesting target for novel therapies and molecular imaging. However, the lack of association with prognosis warrants caution. The potential role of CTGF as a therapeutic target for triple negative FBC deserves to be further studied.

  5. Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment.

    Science.gov (United States)

    Yu, Yuanjie; Böing, Anita N; Hau, Chi M; Hajji, Najat; Ruf, Wolfram; Sturk, Auguste; Nieuwland, Rienk

    2018-06-01

    Tissue factor (TF) can be present in a non-coagulant and coagulant form. Whether the coagulant activity is affected by the plasma membrane microenvironment is unexplored.  This article studies the presence and coagulant activity of human TF in plasma membrane micro-domains.  Plasma membranes were isolated from human MIA PaCa2 cells, MDA-MB-231 cells and human vascular smooth muscle cells by Percoll gradient ultracentrifugation after cell disruption. Plasma membranes were fractionated by OptiPrep gradient ultracentrifugation, and the presence of TF, flotillin, caveolin, clathrin, protein disulphide isomerase (PDI), TF pathway inhibitor (TFPI) and phosphatidylserine (PS) were determined.  Plasma membranes contain two detergent-resistant membrane (DRM) compartments differing in density and biochemical composition. High-density DRMs (DRM-H) have a density ( ρ ) of 1.15 to 1.20 g/mL and contain clathrin, whereas low-density DRMs (DRM-L) have a density between 1.09 and 1.13 g/mL and do not contain clathrin. Both DRMs contain TF, flotillin and caveolin. PDI is detectable in DRM-H, TFPI is not detectable in either DMR-H or DRM-L and PS is detectable in DRM-L. The DRM-H-associated TF (> 95% of the TF antigen) lacks detectable coagulant activity, whereas the DRM-L-associated TF triggers coagulation. This coagulant activity is inhibited by lactadherin and thus PS-dependent, but seemed insensitive to 16F16, an inhibitor of PDI.  Non-coagulant and coagulant TF are present within different types of DRMs in the plasma membrane, and the composition of these DRMs may affect the TF coagulant activity. Schattauer GmbH Stuttgart.

  6. Molecular characterization of Quercus suber MYB1, a transcription factor up-regulated in cork tissues.

    Science.gov (United States)

    Almeida, Tânia; Menéndez, Esther; Capote, Tiago; Ribeiro, Teresa; Santos, Conceição; Gonçalves, Sónia

    2013-01-15

    The molecular processes associated with cork development in Quercus suber L. are poorly understood. A previous molecular approach identified a list of genes potentially important for cork formation and differentiation, providing a new basis for further molecular studies. This report is the first molecular characterization of one of these candidate genes, QsMYB1, coding for an R2R3-MYB transcription factor. The R2R3-MYB gene sub-family has been described as being involved in the phenylpropanoid and lignin pathways, both involved in cork biosynthesis. The results showed that the expression of QsMYB1 is putatively mediated by an alternative splicing (AS) mechanism that originates two different transcripts (QsMYB1.1 and QsMYB1.2), differing only in the 5'-untranslated region, due to retention of the first intron in one of the variants. Moreover, within the retained intron, a simple sequence repeat (SSR) was identified. The upstream regulatory region of QsMYB1 was extended by a genome walking approach, which allowed the identification of the putative gene promoter region. The relative expression pattern of QsMYB1 transcripts determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) revealed that both transcripts were up-regulated in cork tissues; the detected expression was several times higher in newly formed cork harvested from trees producing virgin, second or reproduction cork when compared with wood. Moreover, the expression analysis of QsMYB1 in several Q. suber organs showed very low expression in young branches and roots, whereas in leaves, immature acorns or male flowers, no expression was detected. These preliminary results suggest that QsMYB1 may be related to secondary growth and, in particular, with the cork biosynthesis process with a possible alternative splicing mechanism associated with its regulatory function. Copyright © 2012 Elsevier GmbH. All rights reserved.

  7. Pharmacokinetics and tissue distribution of recombinant human tumor necrosis factor-alpha in mice

    International Nuclear Information System (INIS)

    Ferraiolo, B.L.; Moore, J.A.; Crase, D.; Gribling, P.; Wilking, H.; Baughman, R.A.

    1988-01-01

    The serum pharmacokinetics and the major organs of accumulation of recombinant human tumor necrosis factor-alpha (rHuTNF) were determined in BDF1 mice after intravenous and intramuscular administration. Serum concentrations of immunoreactive protein were determined by enzyme-linked immunosorbent assay, and radioactivity was quantitated by beta and gamma scintigraphy. The serum pharmacokinetics of labeled and unlabeled rHuTNF were identical when administered by the intravenous route. After intravenous doses of 165 to 320 micrograms/kg, the clearance was 2.9-3.6 ml/hr, the initial volume of distribution was 1.4-1.6 ml (70-80 ml/kg), and the half-life was 18.5-19.2 min. Intramuscular administration of 320 micrograms/kg resulted in a peak serum concentration of 112 ng/ml. The time of the peak concentration was 1 hr, and the bioavailability of the intramuscular dose was 12%. The data suggest that the disposition of this protein may be biexponential. If this is the case, the terminal phase would appear to account for less than 1% of the total AUC. Since serum concentrations in the terminal phase are at the sensitivity limit of the assay, a single half-life is reported. 125I-Labeled and metabolically labeled 3H-rHuTNF were used to examine tissue distribution. After intravenous 125I-rHuTNF administration, the rank order of accumulation of the 125I-radiolabel in the major organs (per cent dose per organ over 1440 min) was: liver greater than kidney greater than lung greater than heart greater than spleen. This rank order of accumulation was confirmed by intravenous 3H-rHuTNF administration

  8. Factors Associated with Decision to Hospitalize Emergency Department Patients with Skin and Soft Tissue Infection

    Directory of Open Access Journals (Sweden)

    Talan, David A.

    2014-12-01

    Full Text Available Introduction: Emergency department (ED hospitalizations for skin and soft tissue infection (SSTI have increased, while concern for costs has grown and outpatient parenteral antibiotic options have expanded. To identify opportunities to reduce admissions, we explored factors that influence the decision to hospitalize an ED patient with a SSTI. Methods: We conducted a prospective study of adults presenting to 12 U.S. EDs with a SSTI in which physicians were surveyed as to reason(s for admission, and clinical characteristics were correlated with disposition. We employed chi-square binary recursive partitioning to assess independent predictors of admission. Serious adverse events were recorded. Results: Among 619 patients, median age was 38.7 years. The median duration of symptoms was 4.0 days, 96 (15.5% had a history of fever, and 46 (7.5% had failed treatment. Median maximal length of erythema was 4.0cm (IQR, 2.0-7.0. Upon presentation, 39 (6.3% had temperature >38oC, 81 (13.1% tachycardia, 35 (5.7%, tachypnea, and 5 (0.8% hypotension; at the time of the ED disposition decision, these findings were present in 9 (1.5%, 11 (1.8%, 7 (1.1%, and 3 (0.5% patients, respectively. Ninety-four patients (15.2% were admitted, 3 (0.5% to the intensive care unit (ICU. Common reasons for admission were need for intravenous antibiotics in 80 (85.1%; the only reason in 41.5%, surgery in 23 (24.5%, and underlying disease in 11 (11.7%. Hospitalization was significantly associated with the following factors in decreasing order of importance: history of fever (present in 43.6% of those admitted, and 10.5% discharged; maximal length of erythema >10cm (43.6%, 11.3%; history of failed treatment (16.1%, 6.0%; any co-morbidity (61.7%, 27.2%; and age >65 years (5.4%, 1.3%. Two patients required amputation and none had ICU transfer or died. Conclusion: ED SSTI patients with fever, larger lesions, and co-morbidities tend to be hospitalized, almost all to non-critical areas

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

    Directory of Open Access Journals (Sweden)

    Rucha Patil

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

  10. Effect of brain- and tumor-derived connective tissue growth factor on glioma invasion.

    Science.gov (United States)

    Edwards, Lincoln A; Woolard, Kevin; Son, Myung Jin; Li, Aiguo; Lee, Jeongwu; Ene, Chibawanye; Mantey, Samuel A; Maric, Dragan; Song, Hua; Belova, Galina; Jensen, Robert T; Zhang, Wei; Fine, Howard A

    2011-08-03

    Tumor cell invasion is the principal cause of treatment failure and death among patients with malignant gliomas. Connective tissue growth factor (CTGF) has been previously implicated in cancer metastasis and invasion in various tumors. We explored the mechanism of CTGF-mediated glioma cell infiltration and examined potential therapeutic targets. Highly infiltrative patient-derived glioma tumor-initiating or tumor stem cells (TIC/TSCs) were harvested and used to explore a CTGF-induced signal transduction pathway via luciferase reporter assays, chromatin immunoprecipitation (ChIP), real-time polymerase chain reaction, and immunoblotting. Treatment of TIC/TSCs with small-molecule inhibitors targeting integrin β1 (ITGB1) and the tyrosine kinase receptor type A (TrkA), and short hairpin RNAs targeting CTGF directly were used to reduce the levels of key protein components of CTGF-induced cancer infiltration. TIC/TSC infiltration was examined in real-time cell migration and invasion assays in vitro and by immunohistochemistry and in situ hybridization in TIC/TSC orthotopic xenograft mouse models (n = 30; six mice per group). All statistical tests were two-sided. Treatment of TIC/TSCs with CTGF resulted in CTGF binding to ITGB1-TrkA receptor complexes and nuclear factor kappa B (NF-κB) transcriptional activation as measured by luciferase reporter assays (mean relative luciferase activity, untreated vs CTGF(200 ng/mL): 0.53 vs 1.87, difference = 1.34, 95% confidence interval [CI] = 0.69 to 2, P < .001). NF-κB activation resulted in binding of ZEB-1 to the E-cadherin promoter as demonstrated by ChIP analysis with subsequent E-cadherin suppression (fold increase in ZEB-1 binding to the E-cadherin promoter region: untreated + ZEB-1 antibody vs CTGF(200 ng/mL) + ZEB-1 antibody: 1.5 vs 6.4, difference = 4.9, 95% CI = 4.8 to 5.0, P < .001). Immunohistochemistry and in situ hybridization revealed that TrkA is selectively expressed in the most infiltrative glioma cells in situ

  11. Connective Tissue Growth Factor Transgenic Mouse Develops Cardiac Hypertrophy, Lean Body Mass and Alopecia.

    Science.gov (United States)

    Nuglozeh, Edem

    2017-07-01

    Connective Tissue Growth Factor (CTGF/CCN2) is one of the six members of cysteine-rich, heparin-binding proteins, secreted as modular protein and recognised to play a major function in cell processes such as adhesion, migration, proliferation and differentiation as well as chondrogenesis, skeletogenesis, angiogenesis and wound healing. The capacity of CTGF to interact with different growth factors lends an important role during early and late development, especially in the anterior region of the embryo. CTGF Knockout (KO) mice have several craniofacial defects and bone miss shaped due to an impairment of the vascular system development during chondrogenesis. The aim of the study was to establish an association between multiple modular functions of CTGF and the phenotype and cardiovascular functions in transgenic mouse. Bicistronic cassette was constructed using pIRES expressing vector (Clontech, Palo Alto, CA). The construct harbours mouse cDNA in tandem with LacZ cDNA as a reporter gene under the control of Cytomegalovirus (CMV) promoter. The plasmid was linearised with NotI restriction enzyme, and 50 ng of linearised plasmid was injected into mouse pronucleus for the chimaera production. Immunohistochemical methods were used to assess the colocalisation renin and CTGF as well as morphology and rheology of the cardiovascular system. The chimeric mice were backcrossed against the wild-type C57BL/6 to generate hemizygous (F1) mouse. Most of the offsprings died as a result of respiratory distress and those that survived have low CTGF gene copy number, approximately 40 molecules per mouse genome. The copy number assessment on the dead pups showed 5×10 3 molecules per mouse genome explaining the threshold of the gene in terms of toxicity. Interestingly, the result of this cross showed 85% of the progenies to be positive deviating from Mendelian first law. All F2 progenies died excluding the possibility of establishing the CTGF transgenic mouse line, situation that

  12. Pulp tissue inflammation and angiogenesis after pulp capping with transforming growth factor β1

    Directory of Open Access Journals (Sweden)

    Sri Kunarti

    2008-06-01

    Full Text Available In Restorative dentistry the opportunity to develop biomemitic approaches has been signalled by the possible use of various biological macromolecules in direct pulp capping reparation. The presence of growth factors in dentin matrix and the putative role indicating odontoblast differentiation during embryogenesis has led to the examination on the effect of endogenous TGF-β1. TGF-β1 is one of the Growth Factors that plays an important role in pulp healing. The application of exogenous TGF-β1 in direct pulp capping treatment should be experimented in fibroblast tissue in-vivo to see the responses of inflammatory cells and development of new blood vessels. The increase in food supplies always occurs in the process of inflammation therefore the development of angiogenesis is required to fulfil the requirement. This in-vivo study done on orthodontic patients indicated for premolar extraction between 10–15 years of age. A class V cavity preparation was created in the buccal aspect 1 mm above gingival margin to pulp exposure. The cavity was slowly irrigated with saline solution and dried using a sterile small cotton pellet. The sterile absorbable collagen membrane was applied and soaked in 5 ml TGF-β1. It was covered by a Teflon pledge to separate from Glass Ionomer Cement restoration. Evaluation was performed on day 7; 14; and 21. All samples were histopathologycally examined and data was statistically analysed using one way ANOVA and Dunnet T3.There were no inflammatory symptoms in clinical examination on both Ca(OH2 and TGF-β1, but they increased the infiltration of inflammatory cells on histopathological examination. There were no significant differences (p > 0.05 between Ca(OH2 and TGF-β1 in inflammation cell and significant differences (p < 0.05 in angiogenesis on day 7 and 14. There were no significant differences (p > 0.05 in inflammation cell with in TGF-β1 groups and significant differences (p < 0.05 with in Ca(OH2 groups on day 7

  13. Transforming growth factor-β1/Smad/connective tissue growth factor axis: The main pathway in radiation-induced fibrosis of osteoradionecrosis?

    Directory of Open Access Journals (Sweden)

    Qian Wei Zhuang

    2013-01-01

    Full Text Available Introduction: Osteoradionecrosis (ORN of the mandible is a serious complication following radiation therapy for malignancies of the head and neck. Radiation-induced fibrosis (RIF is a new theory that accounts for the damage to normal tissues after radiotherapy, and the radiation-induced fibroatrophic mechanism includes the free-radical formation, endothelial dysfunction, inflammation, microvascular thrombosis, fibrosis and remodeling, and finally bone and tissue necrosis. The Hypothesis: Previous studies revealed that transforming growth factor-β1 (TGF-β1 is the master switch cytokine responsible for the regulation of fibroblast proliferation and differentiation that result in RIF. Among the targets of TGF-β1, connective tissue growth factor (CTGF is a downstream mediator through the Smad3/4 pathway and plays an important role in connective tissue homeostasis and fibroblast proliferation. Studies have proved that the TGF-β1/Smad/CTGF signaling pathway is involved in the RIF of soft tissues, so the authors put forward a hypothesis that the TGF-β1/Smad/CTGF axis is also the main pathway in RIF of ORN. Evaluation of the Hypothesis: The validation of our hypothesis may provide new insights for better understanding the pathogenesis of ORN and open new perspectives for anti-fibrotic therapies, and pioneer novel approaches to treat ORN.

  14. Expression of the stem cell factor in fibroblasts, endothelial cells, and macrophages in periapical tissues in human chronic periapical diseases.

    Science.gov (United States)

    Shen, S Q; Wang, R; Huang, S G

    2017-03-08

    Stem cell factor (SCF), an important stem cell cytokine, has multiple functions. Fibroblasts (FBs), mature mast cells, endothelial cells (ECs), and eosinophil granulocytes can produce SCF in the inflammatory process. Therefore, we aimed to observe SCF expression in FBs, ECs, and macrophages (MPs) in periapical tissues in human chronic periapical disease and investigate the effects of cells expressing SCF in pathogenesis of the disease. Healthy (N = 20), periapical cyst (N = 15), and periapical granuloma (N = 15) tissues were fixed in 10% formalin for 48 h, embedded in paraffin, and stained with hematoxylin and eosin to observe histological changes. SCF expression was observed in FBs, ECs, and MPs in periapical tissues by double immunofluorescence. CD334, CD31, and CD14 are specific markers of FBs, ECs, and MPs, respectively. Results showed that densities of CD334-SCF double-positive FBs, CD31-SCF double-positive ECs, and CD14-SCF double-positive MPs were significantly increased in periapical tissue groups (P periapical tissue groups (P > 0.05). CD14-SCF double-positive MP density was considerably higher in periapical granulomas than in cysts (P periapical tissues, suggesting that the cells might be related to occurrence, development, and pathogenesis of chronic periapical disease.

  15. Articular cartilage tissue engineering with plasma-rich in growth factors and stem cells with nano scaffolds

    Science.gov (United States)

    Montaser, Laila M.; Abbassy, Hadeer A.; Fawzy, Sherin M.

    2016-09-01

    The ability to heal soft tissue injuries and regenerate cartilage is the Holy Grail of musculoskeletal medicine. Articular cartilage repair and regeneration is considered to be largely intractable due to the poor regenerative properties of this tissue. Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or continue hypertrophic cartilage. The lack of efficient modalities of treatment has prompted research into tissue engineering combining stem cells, scaffold materials and environmental factors. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased cartilage functionality, has evoked intense interest and holds great potential for improving cartilage therapy. Plasma-rich in growth factors (PRGF) and/or stem cells may be effective for tissue repair as well as cartilage regenerative processes. There is a great promise to advance current cartilage therapies toward achieving a consistently successful approach for addressing cartilage afflictions. Tissue engineering may be the best way to reach this objective via the use of stem cells, novel biologically inspired scaffolds and, emerging nanotechnology. In this paper, current and emergent approach in the field of cartilage tissue engineering is presented for specific application. In the next years, the development of new strategies using stem cells, in scaffolds, with supplementation of culture medium could improve the quality of new formed cartilage.

  16. Central Role of Core Binding Factor β2 in Mucosa-Associated Lymphoid Tissue Organogenesis in Mouse.

    Science.gov (United States)

    Nagatake, Takahiro; Fukuyama, Satoshi; Sato, Shintaro; Okura, Hideaki; Tachibana, Masashi; Taniuchi, Ichiro; Ito, Kosei; Shimojou, Michiko; Matsumoto, Naomi; Suzuki, Hidehiko; Kunisawa, Jun; Kiyono, Hiroshi

    2015-01-01

    Mucosa-associated lymphoid tissue (MALT) is a group of secondary and organized lymphoid tissue that develops at different mucosal surfaces. Peyer's patches (PPs), nasopharynx-associated lymphoid tissue (NALT), and tear duct-associated lymphoid tissue (TALT) are representative MALT in the small intestine, nasal cavity, and lacrimal sac, respectively. A recent study has shown that transcriptional regulators of core binding factor (Cbf) β2 and promotor-1-transcribed Runt-related transcription factor 1 (P1-Runx1) are required for the differentiation of CD3-CD4+CD45+ lymphoid tissue inducer (LTi) cells, which initiate and trigger the developmental program of PPs, but the involvement of this pathway in NALT and TALT development remains to be elucidated. Here we report that Cbfβ2 plays an essential role in NALT and TALT development by regulating LTi cell trafficking to the NALT and TALT anlagens. Cbfβ2 was expressed in LTi cells in all three types of MALT examined. Indeed, similar to the previous finding for PPs, we found that Cbfβ2-/- mice lacked NALT and TALT lymphoid structures. However, in contrast to PPs, NALT and TALT developed normally in the absence of P1-Runx1 or other Runx family members such as Runx2 and Runx3. LTi cells for NALT and TALT differentiated normally but did not accumulate in the respective lymphoid tissue anlagens in Cbfβ2-/- mice. These findings demonstrate that Cbfβ2 is a central regulator of the MALT developmental program, but the dependency of Runx proteins on the lymphoid tissue development would differ among PPs, NALT, and TALT.

  17. Identify and rank key factors influencing the adoption of cloud computing for a healthy Electronics

    Directory of Open Access Journals (Sweden)

    Javad Shukuhy

    2015-02-01

    Full Text Available Cloud computing as a new technology with Internet infrastructure and new approaches can be significant benefits in providing medical services electronically. Aplying this technology in E-Health requires consideration of various factors. The main objective of this study is to identify and rank the factors influencing the adoption of e-health cloud. Based on the Technology-Organization-Environment (TOE framework and Human-Organization-Technology fit (HOT-fit model, 16 sub-factors were identified in four major factors. With survey of 60 experts, academics and experts in health information technology and with the help of fuzzy analytic hierarchy process had ranked these sub-factors and factors. In the literature, considering newness this study, no internal or external study, have not alluded these number of criteria. The results show that when deciding to adopt cloud computing in E-Health, respectively, must be considered technological, human, organizational and environmental factors.

  18. Energetic soft-tissue treatment technologies: an overview of procedural fundamentals and safety factors

    NARCIS (Netherlands)

    van de Berg, N. J.; van den Dobbelsteen, J. J.; Jansen, F. W.; Grimbergen, C. A.; Dankelman, J.

    2013-01-01

    Energy administered during soft-tissue treatments may cauterize, coagulate, seal, or otherwise affect underlying structures. A general overview of the functionality, procedural outcomes, and associated risks of these treatments, however, is not yet generally available. In addition, literature is

  19. Expression of vascular endothelial factor protein in the tumor tissues of patients with Stages I-II ovarian cancer

    Directory of Open Access Journals (Sweden)

    V. L. Karapetyan

    2010-01-01

    Full Text Available To define tumor markers is presently the most interesting and promising direction for the diagnosis of malignancies. The expression of the major angiogenesis factor vascular endothelial growth factor (VEGF in primary tumor tissue was studied in ovarian cancer (OC patients to define the prognostic value of the marker.The study enrolled 48 patients with OC. The immunohistochemical technique was used to examine VEGF expression in the primary tu- mor tissue. The frequency of VEGF expression, which was associated with lower relapse-free survival rates, was found to be high (85.4% in OC patients (p > 0.05.The tumor expression of the angiogenic factor VEGF was shown to provide prognostic information in early-stage ovarian epithelial cancer.

  20. Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

    Science.gov (United States)

    Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

    2015-07-01

    It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

  1. Electronic cigarette use: comparing smokers, vapers, and dual users on characteristics and motivational factors

    OpenAIRE

    Claire Schoren; Karin Hummel; Hein de Vries

    2017-01-01

    Introduction This study examined vaping behaviour, precursors of vaping, and motivational differences between smokers, dual users and vapers. The objectives were to assess a) vaping characteristics and reasons for use, b) differences in motivational factors and behavioural precursors associated with e-cigarette use, and c) socio-demographic and motivational factors associated with electronic cigarette use. Methods A cross-sectional survey among 259 vapers, 135 smokers, and 83 dual u...

  2. Extremity Regeneration of Soft Tissue Injury Using Growth Factor-Impregnated Gels

    Science.gov (United States)

    2017-10-01

    vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1). Repeated injections of growth factor-alginate material are... Vascularized endothelial growth factor (VEGF) Insulin-like growth factor-1 (IGF-1) Alginate gel Ischemia-reperfusion Large animal model...operative complications including skin necrosis and seroma development. The IACUC protocol was reevaluated and modified thought multiple discussions

  3. Direct measurement of electron beam quality conversion factors using water calorimetry

    Energy Technology Data Exchange (ETDEWEB)

    Renaud, James, E-mail: james.renaud@mail.mcgill.ca; Seuntjens, Jan [Medical Physics Unit, McGill University, Montréal, Québec H3G 1A4 (Canada); Sarfehnia, Arman [Medical Physics Unit, McGill University, Montréal, Québec H3G 1A4, Canada and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5S 3E2 (Canada); Marchant, Kristin [Allan Blair Cancer Centre, Saskatchewan Cancer Agency, Regina, Saskatchewan S4T 7T1, Canada and Department of Oncology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5A1 (Canada); McEwen, Malcolm; Ross, Carl [Ionizing Radiation Standards, National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada)

    2015-11-15

    Purpose: In this work, the authors describe an electron sealed water calorimeter (ESWcal) designed to directly measure absorbed dose to water in clinical electron beams and its use to derive electron beam quality conversion factors for two ionization chamber types. Methods: A functioning calorimeter prototype was constructed in-house and used to obtain reproducible measurements in clinical accelerator-based 6, 9, 12, 16, and 20 MeV electron beams. Corrections for the radiation field perturbation due to the presence of the glass calorimeter vessel were calculated using Monte Carlo (MC) simulations. The conductive heat transfer due to dose gradients and nonwater materials was also accounted for using a commercial finite element method software package. Results: The relative combined standard uncertainty on the ESWcal dose was estimated to be 0.50% for the 9–20 MeV beams and 1.00% for the 6 MeV beam, demonstrating that the development of a water calorimeter-based standard for electron beams over such a wide range of clinically relevant energies is feasible. The largest contributor to the uncertainty was the positioning (Type A, 0.10%–0.40%) and its influence on the perturbation correction (Type B, 0.10%–0.60%). As a preliminary validation, measurements performed with the ESWcal in a 6 MV photon beam were directly compared to results derived from the National Research Council of Canada (NRC) photon beam standard water calorimeter. These two independent devices were shown to agree well within the 0.43% combined relative uncertainty of the ESWcal for this beam type and quality. Absorbed dose electron beam quality conversion factors were measured using the ESWcal for the Exradin A12 and PTW Roos ionization chambers. The photon-electron conversion factor, k{sub ecal}, for the A12 was also experimentally determined. Nonstatistically significant differences of up to 0.7% were found when compared to the calculation-based factors listed in the AAPM’s TG-51 protocol

  4. Direct measurement of electron beam quality conversion factors using water calorimetry.

    Science.gov (United States)

    Renaud, James; Sarfehnia, Arman; Marchant, Kristin; McEwen, Malcolm; Ross, Carl; Seuntjens, Jan

    2015-11-01

    In this work, the authors describe an electron sealed water calorimeter (ESWcal) designed to directly measure absorbed dose to water in clinical electron beams and its use to derive electron beam quality conversion factors for two ionization chamber types. A functioning calorimeter prototype was constructed in-house and used to obtain reproducible measurements in clinical accelerator-based 6, 9, 12, 16, and 20 MeV electron beams. Corrections for the radiation field perturbation due to the presence of the glass calorimeter vessel were calculated using Monte Carlo (MC) simulations. The conductive heat transfer due to dose gradients and nonwater materials was also accounted for using a commercial finite element method software package. The relative combined standard uncertainty on the ESWcal dose was estimated to be 0.50% for the 9-20 MeV beams and 1.00% for the 6 MeV beam, demonstrating that the development of a water calorimeter-based standard for electron beams over such a wide range of clinically relevant energies is feasible. The largest contributor to the uncertainty was the positioning (Type A, 0.10%-0.40%) and its influence on the perturbation correction (Type B, 0.10%-0.60%). As a preliminary validation, measurements performed with the ESWcal in a 6 MV photon beam were directly compared to results derived from the National Research Council of Canada (NRC) photon beam standard water calorimeter. These two independent devices were shown to agree well within the 0.43% combined relative uncertainty of the ESWcal for this beam type and quality. Absorbed dose electron beam quality conversion factors were measured using the ESWcal for the Exradin A12 and PTW Roos ionization chambers. The photon-electron conversion factor, kecal, for the A12 was also experimentally determined. Nonstatistically significant differences of up to 0.7% were found when compared to the calculation-based factors listed in the AAPM's TG-51 protocol. General agreement between the relative

  5. MO-F-CAMPUS-J-04: Tissue Segmentation-Based MR Electron Density Mapping Method for MR-Only Radiation Treatment Planning of Brain

    Energy Technology Data Exchange (ETDEWEB)

    Yu, H [Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Lee, Y [Sunnybrook Odette Cancer Centre, Toronto, Ontario (Canada); Ruschin, M [Odette Cancer Centre, Toronto, ON (Canada); Karam, I [Sunnybrook Odette Cancer Center, Toronto, Ontario (Canada); Sahgal, A [University of Toronto, Toronto, ON (Canada)

    2015-06-15

    Purpose: Automatically derive electron density of tissues using MR images and generate a pseudo-CT for MR-only treatment planning of brain tumours. Methods: 20 stereotactic radiosurgery (SRS) patients’ T1-weighted MR images and CT images were retrospectively acquired. First, a semi-automated tissue segmentation algorithm was developed to differentiate tissues with similar MR intensities and large differences in electron densities. The method started with approximately 12 slices of manually contoured spatial regions containing sinuses and airways, then air, bone, brain, cerebrospinal fluid (CSF) and eyes were automatically segmented using edge detection and anatomical information including location, shape, tissue uniformity and relative intensity distribution. Next, soft tissues - muscle and fat were segmented based on their relative intensity histogram. Finally, intensities of voxels in each segmented tissue were mapped into their electron density range to generate pseudo-CT by linearly fitting their relative intensity histograms. Co-registered CT was used as a ground truth. The bone segmentations of pseudo-CT were compared with those of co-registered CT obtained by using a 300HU threshold. The average distances between voxels on external edges of the skull of pseudo-CT and CT in three axial, coronal and sagittal slices with the largest width of skull were calculated. The mean absolute electron density (in Hounsfield unit) difference of voxels in each segmented tissues was calculated. Results: The average of distances between voxels on external skull from pseudo-CT and CT were 0.6±1.1mm (mean±1SD). The mean absolute electron density differences for bone, brain, CSF, muscle and fat are 78±114 HU, and 21±8 HU, 14±29 HU, 57±37 HU, and 31±63 HU, respectively. Conclusion: The semi-automated MR electron density mapping technique was developed using T1-weighted MR images. The generated pseudo-CT is comparable to that of CT in terms of anatomical position of

  6. Factors Influencing Electronic Clinical Information Exchange in Small Medical Group Practices

    Science.gov (United States)

    Kralewski, John E.; Zink, Therese; Boyle, Raymond

    2012-01-01

    Purpose: The purpose of this study was to identify the organizational factors that influence electronic health information exchange (HIE) by medical group practices in rural areas. Methods: A purposive sample of 8 small medical group practices in 3 experimental HIE regions were interviewed to determine the extent of clinical information exchange…

  7. Prevalence and risk factors of electronic cigarette use among adolescents: Data from four Swedish municipalities

    Directory of Open Access Journals (Sweden)

    Geidne Susanna

    2016-07-01

    Full Text Available AIMS – To assess the prevalence rates and risk factors of electronic cigarette (e-cigarette use, with special focus on e-cigarettes containing nicotine, among grade 9 students (aged 15–16 years in four different municipalities in Sweden.

  8. Factors that Affect Emergent Literacy Development When Engaging with Electronic Books

    Science.gov (United States)

    Salmon, Lynda G.

    2014-01-01

    This article reviews extant literature with the purpose of identifying factors that affect the potential efficacy of electronic books to support literacy development during early childhood. Selection criteria include experimental, quasi-experimental, and observational studies from peer-reviewed journals from 2000 to 2013 with a target population…

  9. Calculations of electron fluence correction factors using the Monte Carlo code PENELOPE

    International Nuclear Information System (INIS)

    Siegbahn, E A; Nilsson, B; Fernandez-Varea, J M; Andreo, P

    2003-01-01

    In electron-beam dosimetry, plastic phantom materials may be used instead of water for the determination of absorbed dose to water. A correction factor φ water plastic is then needed for converting the electron fluence in the plastic phantom to the fluence at an equivalent depth in water. The recommended values for this factor given by AAPM TG-25 (1991 Med. Phys. 18 73-109) and the IAEA protocols TRS-381 (1997) and TRS-398 (2000) disagree, in particular at large depths. Calculations of the electron fluence have been done, using the Monte Carlo code PENELOPE, in semi-infinite phantoms of water and common plastic materials (PMMA, clear polystyrene, A-150, polyethylene, Plastic water TM and Solid water TM (WT1)). The simulations have been carried out for monoenergetic electron beams of 6, 10 and 20 MeV, as well as for a realistic clinical beam. The simulated fluence correction factors differ from the values in the AAPM and IAEA recommendations by up to 2%, and are in better agreement with factors obtained by Ding et al (1997 Med. Phys. 24 161-76) using EGS4. Our Monte Carlo calculations are also in good accordance with φ water plastic values measured by using an almost perturbation-free ion chamber. The important interdependence between depth- and fluence-scaling corrections for plastic phantoms is discussed. Discrepancies between the measured and the recommended values of φ water plastic may then be explained considering the different depth-scaling rules used

  10. Connective tissue growth factor (CTGF/CCN2 is negatively regulated during neuron-glioblastoma interaction.

    Directory of Open Access Journals (Sweden)

    Luciana F Romão

    Full Text Available Connective-tissue growth factor (CTGF/CCN2 is a matricellular-secreted protein involved in complex processes such as wound healing, angiogenesis, fibrosis and metastasis, in the regulation of cell proliferation, migration and extracellular matrix remodeling. Glioblastoma (GBM is the major malignant primary brain tumor and its adaptation to the central nervous system microenvironment requires the production and remodeling of the extracellular matrix. Previously, we published an in vitro approach to test if neurons can influence the expression of the GBM extracellular matrix. We demonstrated that neurons remodeled glioma cell laminin. The present study shows that neurons are also able to modulate CTGF expression in GBM. CTGF immnoreactivity and mRNA levels in GBM cells are dramatically decreased when these cells are co-cultured with neonatal neurons. As proof of particular neuron effects, neonatal neurons co-cultured onto GBM cells also inhibit the reporter luciferase activity under control of the CTGF promoter, suggesting inhibition at the transcription level. This inhibition seems to be contact-mediated, since conditioned media from embryonic or neonatal neurons do not affect CTGF expression in GBM cells. Furthermore, the inhibition of CTGF expression in GBM/neuronal co-cultures seems to affect the two main signaling pathways related to CTGF. We observed inhibition of TGFβ luciferase reporter assay; however phopho-SMAD2 levels did not change in these co-cultures. In addition levels of phospho-p44/42 MAPK were decreased in co-cultured GBM cells. Finally, in transwell migration assay, CTGF siRNA transfected GBM cells or GBM cells co-cultured with neurons showed a decrease in the migration rate compared to controls. Previous data regarding laminin and these results demonstrating that CTGF is down-regulated in GBM cells co-cultured with neonatal neurons points out an interesting view in the understanding of the tumor and cerebral microenvironment

  11. 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

    International Nuclear Information System (INIS)

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

    2011-01-01

    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- 51 chromium-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

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

    Science.gov (United States)

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

    2009-09-01

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

  13. Connective tissue growth factor and bone morphogenetic protein 2 are induced following myocardial ischemia in mice and humans.

    Science.gov (United States)

    Rutkovskiy, Arkady; Sagave, Julia; Czibik, Gabor; Baysa, Anton; Zihlavnikova Enayati, Katarina; Hillestad, Vigdis; Dahl, Christen Peder; Fiane, Arnt; Gullestad, Lars; Gravning, Jørgen; Ahmed, Shakil; Attramadal, Håvard; Valen, Guro; Vaage, Jarle

    2017-09-01

    We aimed to study the cardiac expression of bone morphogenetic protein 2, its receptor 1 b, and connective tissue growth factor, factors implicated in cardiac embryogenesis, following ischemia/hypoxia, heart failure, and in remodeling hearts from humans and mice. Biopsies from the left ventricle of patients with end-stage heart failure due to dilated cardiomyopathy or coronary artery disease were compared with donor hearts and biopsies from patients with normal heart function undergoing coronary artery bypass grafting. Mouse model of post-infarction remodeling was made by permanent ligation of the left coronary artery. Hearts were analyzed by real-time polymerase chain reaction and Western blotting after 24 hours and after 2 and 4 weeks. Patients with dilated cardiomyopathy and mice post-infarction had increased cardiac expression of connective tissue growth factor. Bone morphogenetic protein 2 was increased in human hearts failing due to coronary artery disease and in mice post-infarction. Gene expression of bone morphogenetic protein receptor 1 beta was reduced in hearts of patients with failure, but increased two weeks following permanent ligation of the left coronary artery in mice. In conclusion, connective tissue growth factor is upregulated in hearts of humans with dilated cardiomyopathy, bone morphogenetic protein 2 is upregulated in remodeling due to myocardial infarction while its receptor 1 b in human failing hearts is downregulated. A potential explanation might be an attempt to engage regenerative processes, which should be addressed by further, mechanistic studies.

  14. Characteristics of adipose tissue macrophages and macrophage-derived insulin-like growth factor-1 in virus-induced obesity.

    Science.gov (United States)

    Park, S; Park, H-L; Lee, S-Y; Nam, J-H

    2016-03-01

    Various pathogens are implicated in the induction of obesity. Previous studies have confirmed that human adenovirus 36 (Ad36) is associated with increased adiposity, improved glycemic control and induction of inflammation. The Ad36-induced inflammation is reflected in the infiltration of macrophages into adipose tissue. However, the characteristics and role of adipose tissue macrophages (ATMs) and macrophage-secreted factors in virus-induced obesity (VIO) are unclear. Although insulin-like growth factor-1 (IGF-1) is involved in obesity metabolism, the contribution of IGF secreted by macrophages in VIO has not been studied. Four-week-old male mice were studied 1 week and 12 weeks after Ad36 infection for determining the characteristics of ATMs in VIO and diet-induced obesity (DIO). In addition, macrophage-specific IGF-1-deficient (MIKO) mice were used to study the involvement of IGF-1 in VIO. In the early stage of VIO (1 week after Ad36 infection), the M1 ATM sub-population increased, which increased the M1/M2 ratio, whereas DIO did not cause this change. In the late stage of VIO (12 weeks after Ad36 infection), the M1/M2 ratio did not change because the M1 and M2 ATM sub-populations increased to a similar extent, despite an increase in adiposity. By contrast, DIO increased the M1/M2 ratio. In addition, VIO in wild-type mice upregulated angiogenesis in adipose tissue and improved glycemic control. However, MIKO mice showed no increase in adiposity, angiogenesis, infiltration of macrophages into adipose tissue, or improvement in glycemic control after Ad36 infection. These data suggest that IGF-1 secreted by macrophages may contribute to hyperplasia and hypertrophy in adipose tissue by increasing angiogenesis, which helps to maintain the 'adipose tissue robustness'.

  15. Obesity-associated insulin resistance is correlated to adipose tissue vascular endothelial growth factors and metalloproteinase levels

    Directory of Open Access Journals (Sweden)

    Tinahones Francisco

    2012-04-01

    Full Text Available Abstract Background The expansion of adipose tissue is linked to the development of its vasculature, which appears to have the potential to regulate the onset of obesity. However, at present, there are no studies highlighting the relationship between human adipose tissue angiogenesis and obesity-associated insulin resistance (IR. Results Our aim was to analyze and compare angiogenic factor expression levels in both subcutaneous (SC and omentum (OM adipose tissues from morbidly obese patients (n = 26 with low (OB/L-IR (healthy obese and high (OB/H-IR degrees of IR, and lean controls (n = 17. Another objective was to examine angiogenic factor correlations with obesity and IR. Here we found that VEGF-A was the isoform with higher expression in both OM and SC adipose tissues, and was up-regulated 3-fold, together with MMP9 in OB/L-IR as compared to leans. This up-regulation decreased by 23% in OB/-H-IR compared to OB/L-IR. On the contrary, VEGF-B, VEGF-C and VEGF-D, together with MMP15 was down-regulated in both OB/H-IR and OB/L-IR compared to lean patients. Moreover, MMP9 correlated positively and VEGF-C, VEGF-D and MMP15 correlated negatively with HOMA-IR, in both SC and OM. Conclusion We hereby propose that the alteration in MMP15, VEGF-B, VEGF-C and VEGF-D gene expression may be caused by one of the relevant adipose tissue processes related to the development of IR, and the up-regulation of VEGF-A in adipose tissue could have a relationship with the prevention of this pathology.

  16. Altered expression of hypoxia-inducible factor-1α (HIF-1α and its regulatory genes in gastric cancer tissues.

    Directory of Open Access Journals (Sweden)

    Jihan Wang

    Full Text Available Tissue hypoxia induces reprogramming of cell metabolism and may result in normal cell transformation and cancer progression. Hypoxia-inducible factor 1-alpha (HIF-1α, the key transcription factor, plays an important role in gastric cancer development and progression. This study aimed to investigate the underlying regulatory signaling pathway in gastric cancer using gastric cancer tissue specimens. The integration of gene expression profile and transcriptional regulatory element database (TRED was pursued to identify HIF-1α ↔ NFκB1 → BRCA1 → STAT3 ← STAT1 gene pathways and their regulated genes. The data showed that there were 82 differentially expressed genes that could be regulated by these five transcription factors in gastric cancer tissues and these genes formed 95 regulation modes, among which seven genes (MMP1, TIMP1, TLR2, FCGR3A, IRF1, FAS, and TFF3 were hub molecules that are regulated at least by two of these five transcription factors simultaneously and were associated with hypoxia, inflammation, and immune disorder. Real-Time PCR and western blot showed increasing of HIF-1α in mRNA and protein levels as well as TIMP1, TFF3 in mRNA levels in gastric cancer tissues. The data are the first study to demonstrate HIF-1α-regulated transcription factors and their corresponding network genes in gastric cancer. Further study with a larger sample size and more functional experiments is needed to confirm these data and then translate into clinical biomarker discovery and treatment strategy for gastric cancer.

  17. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    International Nuclear Information System (INIS)

    Tormoen, Garth W; Khader, Ayesha; Gruber, András; McCarty, Owen J T

    2013-01-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis. (paper)

  18. MUTIL, Asymmetry Factor of Mott Cross-Sections for Electron, Positron Scattering

    International Nuclear Information System (INIS)

    Idoeta, R.; Legarda, F.

    2002-01-01

    1 - Description of program or function: The asymmetry factor S of Mott's differential cross section for the scattering of electrons and positrons by point nuclei without screening is calculated for any energy, atomic number and angle of scattering. 2 - Method of solution: We have summed the conditionally convergent series, F and G, appearing in the asymmetry factor using two consecutive transformations: The one of Yennie, Ravenhall and Wilson and that of Euler till we have seven times six significant figures repeated in the factor S. 3 - Restrictions on the complexity of the problem: Those appearing in the use of Mott's cross section for unscreened point nuclei

  19. Increasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid

    Directory of Open Access Journals (Sweden)

    Ryan C. Bates

    2015-08-01

    Full Text Available Neural tissue exposure to valproic acid (VPA increases several pro-survival phospho-proteins that can be used as biomarkers for indicating a beneficial drug response (pAktSer473, pGSK3βSer9, pErk1/2Thr202/Tyr204. Unfortunately, targeting VPA to neural tissue is a problem due to severe asymmetrical distribution, wherein the drug tends to remain in peripheral blood rather than localizing within the brain. Intracerebral delivery of an amide-linked VPA–PEG conjugate could address these issues by enhancing retention and promoting cerebro-global increases in pro-survival phospho-proteins. It is necessary to assay for the retained bioactivity of a PEGylated valproic acid molecule, along with locating an intracranial cannula placement that optimizes the increase of a known downstream biomarker for chronic VPA exposure. Here we show an acute injection of VPA–PEG conjugate within brain tissue increased virtually all of the assayed phospho-proteins, including well-known pro-survival factors. In contrast, an acute injection of VPA expectedly decreased signaling throughout the hour. Needle penetration into whole brain tissue is the intentional cause of trauma in this procedure. The trauma to brain tissue was observed to overcome known phospho-protein increases for unmodified VPA in the injected solution, while VPA–PEG conjugate appeared to induce significant increases in pro-survival phospho-proteins, despite the procedural trauma.

  20. An analysis of main factors in electron beam flue gas purification

    International Nuclear Information System (INIS)

    Zhang Ming; Xu Guang

    2003-01-01

    Electron beam flue gas purification method is developing very quickly in recent years. Based on the experiment setting for electron beam flue gas purification in Institute of Nuclear Energy and Technology, Tsinghua University, how the technique factors affect the ratio of desulphurization and denitrogenation are described. Radiation dose (D), temperature (T), humidity (H), pour ammonia quantity (α) and initial concentration of SO 2 (C SO 2 ) and NO x (C NO x ) are main factors influencing flue gas purification. Using the methods of correlation analysis and regression analysis, the primary effect factors are found out and the regression equations are set to optimize the system process, predigest the system structure and to forecast the experimental results. (authors)

  1. Cloning changes the response to obesity of innate immune factors in blood, liver, and adipose tissues in domestic pigs.

    Science.gov (United States)

    Rødgaard, Tina; Skovgaard, Kerstin; Stagsted, Jan; Heegaard, Peter M H

    2013-06-01

    The objective of this study was to evaluate the usefulness of cloned pigs as porcine obesity models reflecting obesity-associated changes in innate immune factor gene expression profiles. Liver and adipose tissue expression of 43 innate immune genes as well as serum concentrations of six immune factors were analyzed in lean and diet-induced obese cloned domestic pigs and compared to normal domestic pigs (obese and lean). The number of genes affected by obesity was lower in cloned animals than in control animals. All genes affected by obesity in adipose tissues of clones were downregulated; both upregulation and downregulation were observed in the controls. Cloning resulted in a less differentiated adipose tissue expression pattern. Finally, the serum concentrations of two acute-phase proteins (APPs), haptoglobin (HP) and orosomucoid (ORM), were increased in obese clones as compared to obese controls as well as lean clones and controls. Generally, the variation in phenotype between individual pigs was not reduced in cloned siblings as compared to normal siblings. Therefore, we conclude that cloning limits both the number of genes responding to obesity as well as the degree of tissue-differentiated gene expression, concomitantly with an increase in APP serum concentrations only seen in cloned, obese pigs. This may suggest that the APP response seen in obese, cloned pigs is a consequence of the characteristic skewed gene response to obesity in cloned pigs, as described in this work. This should be taken into consideration when using cloned animals as models for innate responses to obesity.

  2. [Characteristics of sublingual vein and expressions of vascular endothelial growth factor and hypoxia-inducible factor 1alpha proteins in sublingual tissues of Beagle dogs with portal hypertension].

    Science.gov (United States)

    Li, Bai-yu; Wang, Li-na; Yue, Xiao-qiang; Li, Bai

    2009-05-01

    To observe sublingual vein characteristics and the expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1alpha (HIF-1alpha) proteins in sublingual tissues of Beagle dogs with cirrhotic portal hypertension. Twelve Beagle dogs were randomly divided into normal control group and cirrhotic portal hypertension group. There were 6 dogs in each group. A canine model of cirrhosis portal hypertension was established by injecting dimethylnitrosamine (DMN) into portal vein once a week for 7 weeks. The characteristics of sublingual vein were observed. Portal venous pressure was measured by using bioelectric recording techniques. The expressions of VEGF and HIF-1alpha proteins in sublingual vein were detected by immunohistochemical method. The shape and color of sublingual vein in beagle dogs in the cirrhotic portal hypertension group changed obviously as compared with the normal control group. Immunohistochemical results showed that there were almost no expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the normal control group; however, the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the cirrhotic portal hypertension group significantly increased. Changes of portal pressure may lead to the formation of the abnormal sublingual vein by increasing the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in Beagle dogs with portal hypertension.

  3. Genetic Testing and Tissue Banking for Personalized Oncology: Analytical and Institutional Factors.

    Science.gov (United States)

    Miles, George; Rae, James; Ramalingam, Suresh S; Pfeifer, John

    2015-10-01

    Personalized oncology, or more aptly precision oncogenomics, refers to the identification and implementation of clinically actionable targets tailored to an individual patient's cancer genomic information. Banking of human tissue and other biospecimens establishes a framework to extract and collect the data essential to our understanding of disease pathogenesis and treatment. Cancer cooperative groups in the United States have led the way in establishing robust biospecimen collection mechanisms to facilitate translational research, and combined with technological advances in molecular testing, tissue banking has expanded from its traditional base in academic research and is assuming an increasingly pivotal role in directing the clinical care of cancer patients. Comprehensive screening of tumors by DNA sequencing and the ability to mine and interpret these large data sets from well-organized tissue banks have defined molecular subtypes of cancer. Such stratification by genomic criteria has revolutionized our perspectives on cancer diagnosis and treatment, offering insight into prognosis, progression, and susceptibility or resistance to known therapeutic agents. In turn, this has enabled clinicians to offer treatments tailored to patients that can greatly improve their chances of survival. Unique challenges and opportunities accompany the rapidly evolving interplay between tissue banking and genomic sequencing, and are the driving forces underlying the revolution in precision medicine. Molecular testing and precision medicine clinical trials are now becoming the major thrust behind the cooperative groups' clinical research efforts. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Effects of growth factors and cytokins on soft tissue regeneration in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ekaterina Leonidovna Zaytseva

    2014-03-01

    Full Text Available Delayed wound healing is characteristic of a glycemic disorder and often results in trophic ulcer formation, ? a process still poorly understood but likely multifaceted. Current review addresses latest reports from cellular and molecular studies of soft tissue regeneration in patients with diabetes mellitus.

  5. State of oral hygiene and identification of the main risk factors for inflammatory diseases of periodontal tissues in young people.

    OpenAIRE

    Makarenko, M. V.

    2014-01-01

    A high percentage of prevalence of inflammatory periodontal diseases in young age causes urgency of treatment and prevention of inflammatory diseases of periodontal tissue in young age. Therefore, the research purpose was to investigate the hygienic condition and identification of the main risk factors for gingivitis in patients aged 18-30 years. 286 people aged from 18 to 30 years were observed in the study. To assess hygienic condition of the oral cavity and to determine the thickness of pl...

  6. The transcription factor GLI1 modulates the inflammatory response during pancreatic tissue remodeling.

    Science.gov (United States)

    Mathew, Esha; Collins, Meredith A; Fernandez-Barrena, Maite G; Holtz, Alexander M; Yan, Wei; Hogan, James O; Tata, Zachary; Allen, Benjamin L; Fernandez-Zapico, Martin E; di Magliano, Marina Pasca

    2014-10-03

    Pancreatic cancer, one of the deadliest human malignancies, is almost uniformly associated with a mutant, constitutively active form of the oncogene Kras. Studies in genetically engineered mouse models have defined a requirement for oncogenic KRAS in both the formation of pancreatic intraepithelial neoplasias, the most common precursor lesions to pancreatic cancer, and in the maintenance and progression of these lesions. Previous work using an inducible model allowing tissue-specific and reversible expression of oncogenic Kras in the pancreas indicates that inactivation of this GTPase at the pancreatic intraepithelial neoplasia stage promotes pancreatic tissue repair. Here, we extend these findings to identify GLI1, a transcriptional effector of the Hedgehog pathway, as a central player in pancreatic tissue repair upon Kras inactivation. Deletion of a single allele of Gli1 results in improper stromal remodeling and perdurance of the inflammatory infiltrate characteristic of pancreatic tumorigenesis. Strikingly, this partial loss of Gli1 affects activated fibroblasts in the pancreas and the recruitment of immune cells that are vital for tissue recovery. Analysis of the mechanism using expression and chromatin immunoprecipitation assays identified a subset of cytokines, including IL-6, mIL-8, Mcp-1, and M-csf (Csf1), as direct GLI1 target genes potentially mediating this phenomenon. Finally, we demonstrate that canonical Hedgehog signaling, a known regulator of Gli1 activity, is required for pancreas recovery. Collectively, these data delineate a new pathway controlling tissue repair and highlight the importance of GLI1 in regulation of the pancreatic microenvironment during this cellular process. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

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

    2012-10-01

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

  8. Revised age-dependent doses to members of the public from intake of radionuclides using the new tissue weighting factors

    International Nuclear Information System (INIS)

    Jain, S.C.; Gupta, M.M.; Nagaratnam, A.; Reddy, A.R.; Mehta, S.C.

    1992-01-01

    ICRP 56 gave age-dependent dose coefficients to members of the public from intake of most radiologically significant radionuclides that might be released to the environment due to various human activities. It has computed effective dose equivalent (now called effective dose) from these dose coefficients utilising the tissue weighting factors as given by ICRP 26. The recent ICRP 1990 recommendations have revised the tissue weighting factors based on new information on risk estimates of fatal cancer and hereditary disorders. This change in the tissue weighting factors will subsequently affect the computation of effective dose due to intake of various radio-nuclides considered by ICRP 56. The revised effective doses for ingested as well as inhaled radionuclides have been worked out and compared from corresponding earlier values. No change was found in the case of tritiated water, organically bound tritium and 14 C. For the majority of the radionuclides, the revised effective dose was within ± 20% of the earlier values. Larger variations in effective dose were noted for radionuclides which deposit preferentially in one or two organs. (author)

  9. The association between measurement sites of visceral adipose tissue and cardiovascular risk factors after caloric restriction in obese Korean women.

    Science.gov (United States)

    Lee, Hye-Ok; Yim, Jung-Eun; Lee, Jeong-Sook; Kim, Young-Seol; Choue, Ryowon

    2013-02-01

    Quantities as well as distributions of adipose tissue (AT) are significantly related to cardiovascular disease (CVD) risk factors and can be altered with caloric restriction. This study investigated which cross-sectional slice location of AT is most strongly correlated with changes in CVD risk factors after caloric restriction in obese Korean women. Thirty-three obese pre-menopausal Korean women (32.4 ± 8.5 yrs, BMI 27.1 ± 2.3 kg/m(2)) participated in a 12 weeks caloric restriction program. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured using computed tomography (CT) scans at the sites of L2-L3, L3-L4, and L4-L5. Fasting serum levels of glucose, insulin, triglyceride, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), leptin and homeostasis model assessment-insulin resistance (HOMA-IR) were observed. Pearson's partial correlation coefficients were used to assess the relationship between AT measurement sites and changes in CVD risk factors after calorie restriction. When calories were reduced by 350 kcal/day for 12 weeks, body weight (-2.7%), body fat mass (-8.2%), and waist circumference (-5.8%) all decreased (P restriction, serum levels of glucose (-4.6%), TC (-6.2%), LDL-C (-5.3%), leptin (-17.6%) and HOMA-IR (-18.2%) decreased significantly (P restriction.

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

    DEFF Research Database (Denmark)

    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, 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...

  11. Growth factor and proteinase profile of Vivostat® platelet-rich fibrin linked to tissue repair.

    Science.gov (United States)

    Agren, M S; Rasmussen, K; Pakkenberg, B; Jørgensen, B

    2014-07-01

    Autologous platelet-rich fibrin (PRF(®)) is prepared by the automatic Vivostat(®) system. Conflicting results with Vivostat PRF in acute wound healing prompted us to examine its cellular and biomolecular composition. Specifically, platelets, selected growth factors and matrix metalloproteinase (MMP)-9 were quantified using novel analytical methods. Ten healthy non-thrombocytopenic volunteers donated blood for generation of intermediate fibrin-I and final PRF. Anticoagulated whole blood and serum procured in parallel served as baseline controls. Leucocyte, erythrocyte and platelet counts in whole blood and fibrin-I were determined by automated haematology analyser. Platelet concentration in PRF was quantified manually by stereologic analysis of Giemsa-stained tissue sections, and the total content of five growth factors and MMP-9 by enzyme-linked immunosorbent assays. The number of leucocytes and erythrocytes was reduced (P platelets increased (P fibrin-I versus whole blood. PRF contained 982 ± 206 × 10(9) platelets/l representing 3·9-fold (P platelet-derived growth factor (PDGF)-AB [2·5-fold, P PDGF-BB [1·6-fold, P vascular endothelial growth factor > basic fibroblast growth factor [75-fold, P platelet enrichment and biomolecular constituents may guide clinicians in their optimal use of Vivostat PRF for tissue regenerative applications. © 2013 International Society of Blood Transfusion.

  12. Bus Participation Factor Analysis for Harmonic Instability in Power Electronics Based Power Systems

    DEFF Research Database (Denmark)

    Ebrahimzadeh, Esmaeil; Blaabjerg, Frede; Wang, Xiongfei

    2018-01-01

    Compared with the conventional power systems, large-scale power electronics based power systems present a more complex situation, where harmonic instability may be induced by the mutual interactions between the inner control loops of the converters. This paper presents an approach to locate which...... power converters and buses are more sensitive and have significant contribution to the harmonic instability. In the approach, a power electronics based system is introduced as a Multi-Input Multi-Output (MIMO) dynamic system by means of a dynamic admittance matrix. Bus Participation Factors (PFs......) are calculated by the oscillatory mode sensitivity analysis versus the elements of the MIMO transfer function matrix. The PF analysis detects which power electronic converters or buses have a higher participation in harmonic instability excitation than others or at which buses such instability problems have...

  13. Expression of connective tissue growth factor in tumor tissues is an independent predictor of poor prognosis in patients with gastric cancer.

    Science.gov (United States)

    Liu, Lu-Ying; Han, Yan-Chun; Wu, Shu-Hua; Lv, Zeng-Hua

    2008-04-07

    To examine the expression of connective tissue growth factor (CTGF), also known as CCN2, in gastric carcinoma (GC), and the correlation between the expression of CTGF, clinicopathologic features and clinical outcomes of patients with GC. One hundred and twenty-two GC patients were included in the present study. All patients were followed up for at least 5 years. Proteins of CTGF were detected using the Powervision two-step immunostaining method. Of the specimens from 122 GC patients analyzed for CTGF expression, 58 (58/122, 47.5%) had a high CTGF expression in cytoplasm of gastric carcinoma cells and 64 (64/122, 52.5%) had a low CTGF expression. Patients with a high CTGF expression showed a higher incidence of lymph node metastasis than those with a low CTGF expression (P = 0.032). Patients with a high CTGF expression had significantly lower 5-year survival rate than those with a low CTGF expression (27.6% vs 46.9%, P = 0.0178), especially those staging I + II + III (35.7% vs 65.2%, P = 0.0027). GC patients with an elevated CTGF expression have more lymph node metastases and a shorter survival time. CTGF seems to be an independent prognostic factor for the successful differentiation of high-risk GC patients staging I + II + III. Over-expression of CTGF in human GC cells results in an increased aggressive ability.

  14. Hydrogen isotope ratios of mouse tissues are influenced by a variety of factors other than diet

    International Nuclear Information System (INIS)

    DeNiro, M.J.; Epstein, S.

    1981-01-01

    Hydrogen isotopes are fractionated during biochemical reactions in a variety of organisms. A number of experiments have shown that the D/H ratios of animals and their tissues are not controlled solely by the D/H ratios of their food. The authors performed a simple experiment which indicated that the D/H ratios of a significant fraction of the organically bonded hydrogen in animal tissues must be determined by the isotopic composition of water that the samples encounter. Aliquots of dried mouse brain and liver and mouse food were exposed to water vapors of different D/H ratios prior to isotopic analysis. The results of the experiment showed that at least 16 percent of the hydrogen in mouse brain is exchangeable with the hydrogen of water; the corresponding values for mouse liver and mouse food were 25 to 29 percent

  15. Low light and low ammonium are key factors for guayule leaf tissue shoot organogenesis and transformation.

    Science.gov (United States)

    Dong, Niu; Montanez, Belen; Creelman, Robert A; Cornish, Katrina

    2006-02-01

    A new method has been developed for guayule tissue culture and transformation. Guayule leaf explants have a poor survival rate when placed on normal MS medium and under normal culture room light conditions. Low light and low ammonium treatment greatly improved shoot organogenesis and transformation from leaf tissues. Using this method, a 35S promoter driven BAR gene and an ubiquitin-3 promoter driven GUS gene (with intron) have been successfully introduced into guayule. These transgenic guayule plants were resistant to the herbicide ammonium-glufosinate and were positive to GUS staining. Molecular analysis showed the expected band and signal in all GUS positive transformants. The transformation efficiency with glufosinate selection ranged from 3 to 6%. Transformation with a pBIN19-based plasmid containing a NPTII gene and then selection with kanamycin also works well using this method. The ratio of kanamycin-resistant calli to total starting explants reached 50% in some experiments.

  16. Apoptotic factors in physiological and pathological processes of teeth and periodontal tissues – literature review

    Directory of Open Access Journals (Sweden)

    Orzedala-Koszel Urszula

    2014-12-01

    Full Text Available Apoptosis is a physiological process that occurs in the human body throughout the entire life span. This process can be seen in the tissues of the stomatognathic system. A disorder in such programmed cell death processes leads to the development of pathological lesions. Among these are inflammation, osteolytic lesions and neoplastic hyperplasia. We put forward that future studies should concentrate on how to use the knowledge of apoptotic processes and their inhibitors in therapeutic processes involving the stomatognathic system.

  17. Towards a Resolution of the Proton Form Factor Problem: New Electron and Positron Scattering Data

    Science.gov (United States)

    Adikaram, D.; Rimal, D.; Weinstein, L. B.; Raue, B.; Khetarpal, P.; Bennett, R. P.; Arrington, J.; Brooks, W. K.; Adhikari, K. P.; Afanasev, A. V.; Amaryan, M. J.; Anderson, M. D.; Anefalos Pereira, S.; Avakian, H.; Ball, J.; Battaglieri, M.; Bedlinskiy, I.; Biselli, A. S.; Bono, J.; Boiarinov, S.; Briscoe, W. J.; Burkert, V. D.; Carman, D. S.; Careccia, S.; Celentano, A.; Chandavar, S.; Charles, G.; Colaneri, L.; Cole, P. L.; Contalbrigo, M.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Deur, A.; Djalali, C.; Dodge, G. E.; Dupre, R.; Egiyan, H.; El Alaoui, A.; El Fassi, L.; Elouadrhiri, L.; Eugenio, P.; Fedotov, G.; Fegan, S.; Filippi, A.; Fleming, J. A.; Fradi, A.; Garillon, B.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Goetz, J. T.; Gohn, W.; Golovatch, E.; Gothe, R. W.; Griffioen, K. A.; Guegan, B.; Guidal, M.; Guo, L.; Hafidi, K.; Hakobyan, H.; Hanretty, C.; Harrison, N.; Hattawy, M.; Hicks, K.; Holtrop, M.; Hughes, S. M.; Hyde, C. E.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Jenkins, D.; Jiang, H.; Jo, H. S.; Joo, K.; Joosten, S.; Kalantarians, N.; Keller, D.; Khandaker, M.; Kim, A.; Kim, W.; Klein, A.; Klein, F. J.; Koirala, S.; Kubarovsky, V.; Kuhn, S. E.; Livingston, K.; Lu, H. Y.; MacGregor, I. J. D.; Markov, N.; Mattione, P.; Mayer, M.; McKinnon, B.; Mestayer, M. D.; Meyer, C. A.; Mirazita, M.; Mokeev, V.; Montgomery, R. A.; Moody, C. I.; Moutarde, H.; Movsisyan, A.; Camacho, C. Munoz; Nadel-Turonski, P.; Niccolai, S.; Niculescu, G.; Osipenko, M.; Ostrovidov, A. I.; Park, K.; Pasyuk, E.; Peña, C.; Pisano, S.; Pogorelko, O.; Price, J. W.; Procureur, S.; Prok, Y.; Protopopescu, D.; Puckett, A. J. R.; Ripani, M.; Rizzo, A.; Rosner, G.; Rossi, P.; Roy, P.; Sabatié, F.; Salgado, C.; Schott, D.; Schumacher, R. A.; Seder, E.; Sharabian, Y. G.; Simonyan, A.; Skorodumina, I.; Smith, E. S.; Smith, G. D.; Sober, D. I.; Sokhan, D.; Sparveris, N.; Stepanyan, S.; Stoler, P.; Strauch, S.; Sytnik, V.; Taiuti, M.; Tian, Ye; Trivedi, A.; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D. P.; Wei, X.; Wood, M. H.; Zachariou, N.; Zana, L.; Zhang, J.; Zhao, Z. W.; Zonta, I.; CLAS Collaboration

    2015-02-01

    There is a significant discrepancy between the values of the proton electric form factor, GEp, extracted using unpolarized and polarized electron scattering. Calculations predict that small two-photon exchange (TPE) contributions can significantly affect the extraction of GEp from the unpolarized electron-proton cross sections. We determined the TPE contribution by measuring the ratio of positron-proton to electron-proton elastic scattering cross sections using a simultaneous, tertiary electron-positron beam incident on a liquid hydrogen target and detecting the scattered particles in the Jefferson Lab CLAS detector. This novel technique allowed us to cover a wide range in virtual photon polarization (ɛ ) and momentum transfer (Q2) simultaneously, as well as to cancel luminosity-related systematic errors. The cross section ratio increases with decreasing ɛ at Q2=1.45 GeV2 . This measurement is consistent with the size of the form factor discrepancy at Q2≈1.75 GeV2 and with hadronic calculations including nucleon and Δ intermediate states, which have been shown to resolve the discrepancy up to 2 - 3 GeV2 .

  18. Communication: A Jastrow factor coupled cluster theory for weak and strong electron correlation

    International Nuclear Information System (INIS)

    Neuscamman, Eric

    2013-01-01

    We present a Jastrow-factor-inspired variant of coupled cluster theory that accurately describes both weak and strong electron correlation. Compatibility with quantum Monte Carlo allows for variational energy evaluations and an antisymmetric geminal power reference, two features not present in traditional coupled cluster that facilitate a nearly exact description of the strong electron correlations in minimal-basis N 2 bond breaking. In double-ζ treatments of the HF and H 2 O bond dissociations, where both weak and strong correlations are important, this polynomial cost method proves more accurate than either traditional coupled cluster or complete active space perturbation theory. These preliminary successes suggest a deep connection between the ways in which cluster operators and Jastrow factors encode correlation

  19. Somatomedin-C/insulin-like growth factor-I and Insulin-like growth factor-II mRNAs in rate fetal and adult tissues

    International Nuclear Information System (INIS)

    Lund, P.K.; Moats-Staats, B.M.; Hynes, M.A.; Simmons, J.G.; Jansen, M.; D'ercole, A.J.; Van Wyk, J.J.

    1986-01-01

    Somatomedin-C or insulin-like growth factor I (Sm-C/IGF-I) and insulin-like growth factor II (IGF-II) have been implicated in the regulation of fetal growth and development. In the present study 32 P-labeled complementary DNA probes encoding human and mouse Sm-C/IGF-I and human IGF-II were used in Northern blot hybridizations to analyze rat Sm-C/IGF-I and IGF-II mRNAs in poly(A + ) RNAs from intestine, liver, lung, and brain of adult rats and fetal rats between day 14 and 17 of gestation. In fetal rats, all four tissues contained a major mRNA of 1.7 kilobase (kb) that hybridized with the human Sm-C/IGF-I cDNA and mRNAs of 7.5, 4.7, 1.7, and 1.2 kb that hybridized with the mouse Sm-C/IGF-I cDNA. Adult rat intestine, liver, and lung also contained these mRNAs but Sm-C/IGF-I mRNAs were not detected in adult rat brain. These findings provide direct support for prior observations that multiple tissues in the fetus synthesize immunoreactive Sm-C/IGF-I and imply a role for Sm-C/IGF-I in fetal development as well as postnatally. Multiple IGF-II mRNAs of estimated sizes 4.7, 3.9, 2.2, 1.75, and 1.2 kb were observed in fetal rat intestine, liver, lung, and brain. The 4.7- and 3.9-kb mRNAs were the major hybridizing IGF-II mRNAs in all fetal tissues. Higher abundance of IGF-II mRNAs in rat fetal tissues compared with adult tissues supports prior hypotheses, based on serum IGF-II concentrations, that IGF-II is predominantly a fetal somatomedin. IGF-II mRNAs are present, however, in some poly(A + ) RNAs from adult rat tissues. The brain was the only tissue in the adult rat where the 4.7- and 3.9-kb IGF-II mRNAs were consistently detected. These findings suggest that a role for IGF-II in the adult rat, particularly in the central nervous system, cannot be excluded

  20. Evaluation of Frequency and Risk Factors of Soft Tissue Rheumatism of Upper Limbs in Diabetic Patients in Kerman in 2001

    Directory of Open Access Journals (Sweden)

    M.R. Shakibi

    2003-10-01

    Full Text Available Diabetes mellitus is a metabolic disorder that affect different systems in human. Wide range of musculoskeletal syndromes have been described in association with diabetes. To determine the prevalence of upper limb soft tissue rheumatism in diabetes patients. In a cross sectional study 300 diabetic patients was examined by COPCORD questionnaire. The examination was performed by internist and rheumatologist . Data was analyzed by logistic regression. 73.3% of patients were female. Average age of cases was 51.2±13.7 years and mean of duration of disease was 7±6.4 years. 152 cases (50.7% had soft tissue rheumatism in upper limbs. 66 cases had carpal tannel syndrome, 23 cases with Dupuytren’s disease, 23 cases with Flexortenosynovitis, 91 cases with shoulder periarthritis, 4 cases had limited joint mobility and 12 had Elbow Epicandititis. Logestic regression analysis showed that type 2 diabetes, weak control of blood sugur and duration of disease>5years were risk factors for incidence of soft tissue rheumatism in upper limbs. Results have showed the high prevalence of soft tissue rheumatism in diabetic patients.

  1. Determination of scattering coefficient considering wavelength and absorption dependence of anisotropy factor measured by polarized beam for biological tissues

    Science.gov (United States)

    Fukutomi, D.; Ishii, K.; Awazu, K.

    2015-12-01

    Anisotropy factor g, one of the optical properties of biological tissues, is the most important parameter to accurately determine scattering coefficient μs in the inverse Monte Carlo (iMC) simulation. It has been reported that g has wavelength and absorption dependence, however, there are few attempts in order to calculate μs of biological tissue considering the wavelength and absorption dependence of g. In this study, the scattering angular distributions of biological tissue phantoms were measured in order to determine g by using goniometric measurements with three polarization conditions at strongly and weakly absorbing wavelengths of hemoglobin. Then, optical properties, especially, μs were measured by integrating sphere measurements and iMC simulation in order to confirm the influence of measured g on optical properties in comparison of with general value of g (0.9) for soft biological tissue. Consequently, it was found that μs was overestimated at strongly absorbing wavelength, however, μs was underestimated at weakly absorbing wavelength if the g was not considered its wavelength and absorption dependence.

  2. Novel chitosan/collagen scaffold containing transforming growth factor-β1 DNA for periodontal tissue engineering

    International Nuclear Information System (INIS)

    Zhang Yufeng; Cheng Xiangrong; Wang Jiawei; Wang Yining; Shi Bin; Huang Cui; Yang Xuechao; Liu Tongjun

    2006-01-01

    The current rapid progression in tissue engineering and local gene delivery system has enhanced our applications to periodontal tissue engineering. In this study, porous chitosan/collagen scaffolds were prepared through a freeze-drying process, and loaded with plasmid and adenoviral vector encoding human transforming growth factor-β1 (TGF-β1). These scaffolds were evaluated in vitro by analysis of microscopic structure, porosity, and cytocompatibility. Human periodontal ligament cells (HPLCs) were seeded in this scaffold, and gene transfection could be traced by green fluorescent protein (GFP). The expression of type I and type III collagen was detected with RT-PCR, and then these scaffolds were implanted subcutaneously into athymic mice. Results indicated that the pore diameter of the gene-combined scaffolds was lower than that of pure chitosan/collagen scaffold. The scaffold containing Ad-TGF-β1 exhibited the highest proliferation rate, and the expression of type I and type III collagen up-regulated in Ad-TGF-β1 scaffold. After implanted in vivo, EGFP-transfected HPLCs not only proliferated but also recruited surrounding tissue to grow in the scaffold. This study demonstrated the potential of chitosan/collagen scaffold combined Ad-TGF-β1 as a good substrate candidate in periodontal tissue engineering

  3. Do Pocket Electronic Dictionaries Influence Word Retention and Reading Comprehension? Their Effects and Mediating Factors

    OpenAIRE

    小林, 千穂

    2011-01-01

    This study explores the effectiveness of pocket electronic dictionaries (EDs) compared with printed dictionaries (PDs) on searching behavior, word retention, and reading comprehension. It also investigates how factors such as test formats, learners' proficiency level, and text difficulty are related to the effects of EDs. Thirty-six Japanese university students participated in the study. They read an English text and answered comprehension questions, while circling the words they looked up. T...

  4. EFFECTS OF NEUTRINO ELECTROMAGNETIC FORM FACTORS ON NEUTRINO INTERACTION WITH FINITE TEMPERATURE ELECTRON MATTERS

    Directory of Open Access Journals (Sweden)

    Anto Sulaksono

    2011-11-01

    Full Text Available The differential cross-section of neutrino interaction with dense and warm electron gasses has been calculated by takinginto account the neutrino electromagnetic form factors. The significant effect of electromagnetic properties of neutrinocan be found if the neutrino dipole moment, μ ν , is ≥ 5.10-9 μB and neutrino charge radius, Rv, is ≥ 5.10-6 MeV-1. Theimportance of the retarded correction, detailed balance and Pauli blocking factors is shown and analyzed. Many-bodyeffects on the target matter which are included via random phase approximation (RPA correlation as well as photoneffective mass are also investigated.

  5. Parity Violation in Elastic Electron-Proton Scattering and the Proton's Strange Magnetic Form Factor

    International Nuclear Information System (INIS)

    Spayde, D. T.; Averett, T.; Barkhuff, D.; Beck, D. H.; Beise, E. J.; Benson, C.; Breuer, H.; Carr, R.; Covrig, S.; DelCorso, J.

    2000-01-01

    We report a new measurement of the parity-violating asymmetry in elastic electron scattering from the proton at backward scattering angles. This asymmetry is sensitive to the strange magnetic form factor of the proton as well as electroweak axial radiative corrections. The new measurement of A=-4.92±0.61±0.73 ppm provides a significant constraint on these quantities. The implications for the strange magnetic form factor are discussed in the context of theoretical estimates for the axial corrections. (c) 2000 The American Physical Society

  6. An empirical study on critical success factors for electronic commerce in the Chinese publishing industry

    Institute of Scientific and Technical Information of China (English)

    HUANG Jinghua; ZHAO Chunjun; LI Jingting

    2007-01-01

    Critical success factors for electronic commerce (e-commerce) have been a hot topic in both the academe and industry. This paper puts forward hypotheses on success factors for e-commerce of traditional companies first. Then, it conducts an empirical study on the Chinese publishing industry in order to verify the hypotheses. After testing the validity and reliability of the data, this paper verifies the hypotheses with regression analyses, and finally identifies factors impacting e-commerce success such as leadership, strategy, organization, management, IT, customers, comprehensive functions of website and customer- oriented functions. In addition, customers, strategy, IT and comprehensive functions of website are identified as the critical factors impacting e-commerce success. This research not only stimulates e-commerce research in China, but also has an instructional effect on the implementation of e-commerce so that Chinese publishing enterprises can increase the success rate of their e-commerce objectives.

  7. Study of the electromagnetic form factors of Helium-3 and Tritium nuclei by electron scattering

    International Nuclear Information System (INIS)

    Amroun, A.

    1989-01-01

    Accurate measurements of the tritium electromagnetic form factor demonstrated that, when the exchange currents are included, the theoretical and the experimental data are in agreement. Similar calculations carried out on helium-3 were not satisfactory. In this investigation, a new electromagnetic form factor of helium-3 is measured. The transfer zone of the diffraction spectra concerning the first minimum and the second maximum is considered. The aim of the study is to test on both nuclei the validity and the uncertainties of the models. The scattering of electrons on helium-3 is analyzed. The experiment was performed in the Saclay linear accelerator. The isoscalar and isovector form factors could be differentiated. By comparing the theoretical and the experimental data, it is demonstrated that the use of three body forces in the calculations has no effect on the form factor results [fr

  8. Factors that impact nurses' use of electronic mail (e-mail).

    Science.gov (United States)

    Hughes, J A; Pakieser, R A

    1999-01-01

    As electronic applications are used increasingly in healthcare, nurses are being challenged to adopt them. Electronic mail (e-mail) is an electronic tool with general as well as healthcare uses. E-mail use may be an opportunity to learn a tool that requires skills similar to those used in other applications. This study aimed to identify barriers and facilitators that impact nurses' use of e-mail in the workplace. Data for this study were gathered using focus group methodology. Content analysis identified and labeled factors into seven major categories. Specific factors identified were generally consistent with those previously described in the literature as affecting use of computers in general. However, there were several additional factors identified that were not reported in other previous studies: lack of face-to-face communication, individual writing skills, recency of any educational experience, volume of mail received, password integrity, and technical support. Findings from this study provide information for any individual involved in introducing or updating an e-mail system in a healthcare environment.

  9. Parity-Violating Electron Deuteron Scattering and the Proton's Neutral Axial Vector Form Factor

    International Nuclear Information System (INIS)

    Ito, T.

    2003-01-01

    The authors report on a new measurement of the parity-violating asymmetry in quasielastic electron scattering from the deuteron at the backward angles at electron beam energy of 125 MeV [Q 2 =0.038 (GeV/c) 2 ]. This quantity provides a determination of the neutral weak axial vector form factor of the nucleon. In addition to the tree level amplitude associated with Z-exchange, the neutral weak axial vector form factor as measured in electron scattering can potentially receive large electroweak corrections, including the anapole moment, that are absent in neutrino scattering. The measured asymmetry A -3.51 ± 0.57 (stat) ± 0.58 (sys) ppm is consistent with theoretical predictions. We also report on updated results of the previous experiment at 200 MeV [Q 2 = 0.091 (GeV/c) 2 ] on a deuterium target. The updated results are also consistent with theoretical predictions on the neutral weal axial vector form factor

  10. G-factors and diamagnetic coefficients of electrons, holes, and excitons in InAs/InP quantum dots

    NARCIS (Netherlands)

    Bree, van J.; Silov, A.Yu.; Koenraad, P.M.; Flatté, M.E.; Pryor, C.E.

    2012-01-01

    The electron, hole, and exciton g factors and diamagnetic coefficients have been calculated using envelope-function theory for cylindrical InAs/InP quantum dots in the presence of a magnetic field parallel to the dot symmetry axis. A clear connection is established between the electron g factor and

  11. A two-compartment mechanochemical model of the roles of transforming growth factor and tissue tension in dermal wound healing

    KAUST Repository

    Murphy, Kelly E.; Hall, Cameron L.; McCue, Scott W.; Sean McElwain, D.L.

    2011-01-01

    The repair of dermal tissue is a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and in a paracrine fashion. Recent experimental results have shown that transforming growth factor -β (TGF β) and tissue mechanics play roles in regulating cell proliferation, differentiation and the production of extracellular materials. We have developed a 1D mathematical model that considers the interaction between the cellular, chemical and mechanical phenomena, allowing the combination of TGF β and tissue stress to inform the activation of fibroblasts to myofibroblasts. Additionally, our model incorporates the observed feature of residual stress by considering the changing zero-stress state in the formulation for effective strain. Using this model, we predict that the continued presence of TGF β in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGF β significantly reduces the myofibroblast numbers resulting in an increase in wound size. Similar results were obtained by varying the rate at which fibroblasts differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate. Taken together, the implication is that elevated levels of myofibroblasts is the key factor behind wounds healing with excessive contraction, suggesting that clinical strategies which aim to reduce the myofibroblast density may reduce the appearance of contractures. © 2010 Elsevier Ltd.

  12. A two-compartment mechanochemical model of the roles of transforming growth factor and tissue tension in dermal wound healing

    KAUST Repository

    Murphy, Kelly E.

    2011-03-01

    The repair of dermal tissue is a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and in a paracrine fashion. Recent experimental results have shown that transforming growth factor -β (TGF β) and tissue mechanics play roles in regulating cell proliferation, differentiation and the production of extracellular materials. We have developed a 1D mathematical model that considers the interaction between the cellular, chemical and mechanical phenomena, allowing the combination of TGF β and tissue stress to inform the activation of fibroblasts to myofibroblasts. Additionally, our model incorporates the observed feature of residual stress by considering the changing zero-stress state in the formulation for effective strain. Using this model, we predict that the continued presence of TGF β in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGF β significantly reduces the myofibroblast numbers resulting in an increase in wound size. Similar results were obtained by varying the rate at which fibroblasts differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate. Taken together, the implication is that elevated levels of myofibroblasts is the key factor behind wounds healing with excessive contraction, suggesting that clinical strategies which aim to reduce the myofibroblast density may reduce the appearance of contractures. © 2010 Elsevier Ltd.

  13. Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1 in Human Macrophages

    Directory of Open Access Journals (Sweden)

    G. Chinetti-Gbaguidi

    2016-01-01

    Full Text Available Tissue factor (TF is the initiator of the blood coagulation cascade after interaction with the activated factor VII (FVIIa. Moreover, the TF/FVIIa complex also activates intracellular signalling pathways leading to the production of inflammatory cytokines. The TF/FVIIa complex is inhibited by the tissue factor pathway inhibitor-1 (TFPI-1. Peroxisome proliferator-activated receptor gamma (PPARγ is a transcription factor that, together with PPARα and PPARβ/δ, controls macrophage functions. However, whether PPARγ activation modulates the expression of TFP1-1 in human macrophages is not known. Here we report that PPARγ activation increases the expression of TFPI-1 in human macrophages in vitro as well as in vivo in circulating peripheral blood mononuclear cells. The induction of TFPI-1 expression by PPARγ ligands, an effect shared by the activation of PPARα and PPARβ/δ, occurs also in proinflammatory M1 and in anti-inflammatory M2 polarized macrophages. As a functional consequence, treatment with PPARγ ligands significantly reduces the inflammatory response induced by FVIIa, as measured by variations in the IL-8, MMP-2, and MCP-1 expression. These data identify a novel role for PPARγ in the control of TF the pathway.

  14. Expression of von Willebrand factor and caldesmon in the placental tissues of pregnancies complicated with intrauterine growth restriction.

    Science.gov (United States)

    Göksever Çelik, Hale; Uhri, Mehmet; Yildirim, Gökhan

    2017-11-02

    The decreased placental perfusion is the underlying reason for intrauterine growth restriction that in turn leads to reduced placental perfusion and ischemia. However, there are several issues to be understood in the pathophysiology of intrauterine growth restriction. We aimed to study whether any compensatory response in placental vascular bed occur in pregnancies complicated with intrauterine growth restriction by the immunohistochemical staining of von Willebrand factor and caldesmon in placental tissues. A total of 103 pregnant women was enrolled in the study including 50 patients who were complicated with IUGR and 50 uncomplicated control patients. The study was designed in a prospective manner. All placentas were also stained with von Willebrand factor and caldesmon monoclonal kits. The immunohistochemical staining of von Willebrand factor and caldesmon expressions in placental tissues were different between normal and intrauterine growth restriction group. The percentages of 2+ and 3+ von Willebrand factor expression were higher in the intrauterine growth restriction group comparing with the normal group, although the difference was not statistically significant. The intensity of caldesmon expression was significantly lower in the intrauterine growth restriction group in comparison with the normal group (p intrauterine growth restriction which is a hypoxic condition. But newly formed vessels are immature and not strong enough. Our study is important to clarify the pathophysiology and placental compensatory responses in intrauterine growth restriction.

  15. Growth differentiation factor-15 (GDF-15) suppresses in vitro angiogenesis through a novel interaction with connective tissue growth factor (CCN2).

    Science.gov (United States)

    Whitson, Ramon J; Lucia, Marshall Scott; Lambert, James R

    2013-06-01

    Growth differentiation factor-15 (GDF-15) and the CCN family member, connective tissue growth factor (CCN2), are associated with cardiac disease, inflammation, and cancer. The precise role and signaling mechanism for these factors in normal and diseased tissues remains elusive. Here we demonstrate an interaction between GDF-15 and CCN2 using yeast two-hybrid assays and have mapped the domain of interaction to the von Willebrand factor type C domain of CCN2. Biochemical pull down assays using secreted GDF-15 and His-tagged CCN2 produced in PC-3 prostate cancer cells confirmed a direct interaction between these proteins. To investigate the functional consequences of this interaction, in vitro angiogenesis assays were performed. We demonstrate that GDF-15 blocks CCN2-mediated tube formation in human umbilical vein endothelial (HUVEC) cells. To examine the molecular mechanism whereby GDF-15 inhibits CCN2-mediated angiogenesis, activation of αV β3 integrins and focal adhesion kinase (FAK) was examined. CCN2-mediated FAK activation was inhibited by GDF-15 and was accompanied by a decrease in αV β3 integrin clustering in HUVEC cells. These results demonstrate, for the first time, a novel signaling pathway for GDF-15 through interaction with the matricellular signaling molecule CCN2. Furthermore, antagonism of CCN2 mediated angiogenesis by GDF-15 may provide insight into the functional role of GDF-15 in disease states. Copyright © 2012 Wiley Periodicals, Inc.

  16. Bioaccumulation of short chain chlorinated paraffins in a typical freshwater food web contaminated by e-waste in south china: Bioaccumulation factors, tissue distribution, and trophic transfer.

    Science.gov (United States)

    Sun, Runxia; Luo, Xiaojun; Tang, Bin; Chen, Laiguo; Liu, Yu; Mai, Bixian

    2017-03-01

    Short chain chlorinated paraffins (SCCPs) are under review for inclusion into the Stockholm Convention on Persistent Organic Pollutants. However, limited information is available on their bioaccumulation and biomagnification in ecosystems, which is hindering evaluation of their ecological and health risks. In the present study, wild aquatic organisms (fish and invertebrates), water, and sediment collected from an enclosed freshwater pond contaminated by electronic waste (e-waste) were analyzed to investigate the bioaccumulation, distribution, and trophic transfer of SCCPs in the aquatic ecosystem. SCCPs were detected in all of the investigated aquatic species at concentrations of 1700-95,000 ng/g lipid weight. The calculated bioaccumulation factors (BAFs) varied from 2.46 to 3.49. The relationship between log BAF and the octanol/water partition coefficient (log K OW ) for benthopelagic omnivorous fish species followed the empirical model of bioconcentration, indicating that bioconcentration plays an important role in accumulation of SCCPs. In contrast, the relationship for the benthic carnivorous fish and invertebrates was not consistent with the empirical model of bioconcentration, implying that the bioaccumulation of SCCPs in these species could be more influenced by other complex factors (e.g., habitat and feeding habit). Preferential distribution in the liver rather than in other tissues (e.g., muscle, gills, skin, and kidneys) was noted for the SCCP congeners with higher log K OW , and bioaccumulation pathway (i.e. water or sediment) can affect the tissue distribution of SCCP congeners. SCCPs underwent trophic dilution in the aquatic food web, and the trophic magnification factor (TMF) values of SCCP congener groups significantly correlated with their corresponding log K OW values (p < 0.0001). The present study results improved our understanding on the environmental behavior and fate of SCCPs in aquatic ecosystem. Copyright © 2016 Elsevier Ltd. All rights

  17. The two-way relationship between iatrogenic factor and periodontal tissues

    Directory of Open Access Journals (Sweden)

    Sri Oktawati

    2016-06-01

    Full Text Available Iatrogenic factors refer to anyinadequate medical treatment or diagnostic proceduresconducted inadvertently by practitioners who precipitate adverse injuries or symptoms. The unavoidable consequences of these factors should be corrected promptly, as they may result in erroneous treatment or new injury either on the tooth or the periodontium or both. Periodontal disease has a multifactorial etiology, which results from the interaction of local and systemic factors, intrinsically or extrinsically. Therefore, in most cases of periodontal disease, aninterdisciplinary approach is needed, such as restorative treatment of interproximal cavities that may induced food impacted. In contrary, a periodontal therapy could also act as an iatrogenic factor in the case of dentinal hypersensitivity or gingival recessionthat frequently creates an adverse effect in esthetic. Our discussion here is presented so that dentists could treat carefully and give a lot of attention to potential danger of other consequences of iatrogenic factors.

  18. Dihydrotestosterone induces pro-angiogenic factors and assists homing of MSC into the cardiac tissue.

    Science.gov (United States)

    Popa, Mirel-Adrian; Mihai, Maria-Cristina; Constantin, Alina; Şuică, Viorel; Ţucureanu, Cătălin; Costache, Raluca; Antohe, Felicia; Dubey, Raghvendra K; Simionescu, Maya

    2018-01-01

    The use of mesenchymal stem cells (MSC) as a therapeutic tool in cardiovascular diseases is promising. Since androgens exert some beneficial actions on the cardiovascular system, we tested our hypothesis that this hormone could promote MSC-mediated repair processes, also. Cultured MSCs isolated from Wharton's jelly were exposed to 30 nM dihydrotestosterone (DHT) for 1 or 4 days and the effects of the hormone on their growth/migration/adhesion and the underlying mechanisms were assessed. Results were obtained by real-time cell impedance measurements, and DNA quantification showed that DHT increased MSC proliferation by ~30%. As determined by xCELLigence system, DHT augmented (~2 folds) the migration of MSC toward cardiac tissue slices (at 12 h), and this effect was blocked by flutamide, an androgen receptor (AR) antagonist. Exposure of cells to DHT, upregulated the gene and protein expression of AR , EMMPRIN and MMP-9 and downregulated the expression of MMP-2 DHT significantly induced the release of nitric oxide by MSC (≥2-fold) and flutamide blocked this effect. When MSCs were co-cultured with cardiac slices, immunohistochemical analysis and qRT-PCR showed that the integration of DHT-stimulated MSC was significantly higher than that of in controls. In conclusion, our findings provide the first evidence that DHT promotes MSC growth, migration and integration into the cardiac slices. The modulating effects of DHT were associated with upregulation of ARs and of key molecules known to promote tissue remodeling and angiogenesis. Our findings suggest that priming of MSC with DHT may potentially increase their capability to regenerate cardiac tissue; in vivo studies are needed to confirm our in vitro findings. © 2018 Society for Endocrinology.

  19. Fuz regulates craniofacial development through tissue specific responses to signaling factors.

    Directory of Open Access Journals (Sweden)

    Zichao Zhang

    Full Text Available The planar cell polarity effector gene Fuz regulates ciliogenesis and Fuz loss of function studies reveal an array of embryonic phenotypes. However, cilia defects can affect many signaling pathways and, in humans, cilia defects underlie several craniofacial anomalies. To address this, we analyzed the craniofacial phenotype and signaling responses of the Fuz(-/- mice. We demonstrate a unique role for Fuz in regulating both Hedgehog (Hh and Wnt/β-catenin signaling during craniofacial development. Fuz expression first appears in the dorsal tissues and later in ventral tissues and craniofacial regions during embryonic development coincident with cilia development. The Fuz(-/- mice exhibit severe craniofacial deformities including anophthalmia, agenesis of the tongue and incisors, a hypoplastic mandible, cleft palate, ossification/skeletal defects and hyperplastic malformed Meckel's cartilage. Hh signaling is down-regulated in the Fuz null mice, while canonical Wnt signaling is up-regulated revealing the antagonistic relationship of these two pathways. Meckel's cartilage is expanded in the Fuz(-/- mice due to increased cell proliferation associated with the up-regulation of Wnt canonical target genes and decreased non-canonical pathway genes. Interestingly, cilia development was decreased in the mandible mesenchyme of Fuz null mice, suggesting that cilia may antagonize Wnt signaling in this tissue. Furthermore, expression of Fuz decreased expression of Wnt pathway genes as well as a Wnt-dependent reporter. Finally, chromatin IP experiments demonstrate that β-catenin/TCF-binding directly regulates Fuz expression. These data demonstrate a new model for coordination of Hh and Wnt signaling and reveal a Fuz-dependent negative feedback loop controlling Wnt/β-catenin signaling.

  20. Extracellular vesicles, tissue factor, cancer and thrombosis – discussion themes of the ISEV 2014 Educational Day

    Directory of Open Access Journals (Sweden)

    Chris Gardiner

    2015-03-01

    Full Text Available Although the association between cancer and venous thromboembolism (VTE has long been known, the mechanisms are poorly understood. Circulating tissue factor–bearing extracellular vesicles have been proposed as a possible explanation for the increased risk of VTE observed in some types of cancer. The International Society for Extracellular Vesicles (ISEV and International Society on Thrombosis and Haemostasis (ISTH held a joint Educational Day in April 2014 to discuss the latest developments in this field. This review discusses the themes of that event and the ISEV 2014 meeting that followed.

  1. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy

    International Nuclear Information System (INIS)

    Gray, L.H.; Conger, A.D.; Ebert, M.; Hornsey, S.; Scott, O.C.A.

    1984-01-01

    The sensitivity of tumour cells to X rays has been shown to be about three times as great when irradiated in a well-oxygenated medium as under anoxic conditions. The manner in which sensitivity depends on oxygen tension closely resembles that found by other workers for plant and insect tissues. The sensitivity of the tumour cells to fast neutron radiation is only slightly affected by oxygen tension. Consideration is given to the supply of oxygen to tissues as a factor in radiotherapy, and it is concluded on the basis of existing knowledge that in certain circumstances the effectiveness of X-ray treatment might be increased if the patient were breathing oxygen at the time of irradiation

  2. Serial analysis of gene expression identifies connective tissue growth factor expression as a prognostic biomarker in gallbladder cancer.

    Science.gov (United States)

    Alvarez, Hector; Corvalan, Alejandro; Roa, Juan C; Argani, Pedram; Murillo, Francisco; Edwards, Jennifer; Beaty, Robert; Feldmann, Georg; Hong, Seung-Mo; Mullendore, Michael; Roa, Ivan; Ibañez, Luis; Pimentel, Fernando; Diaz, Alfonso; Riggins, Gregory J; Maitra, Anirban

    2008-05-01

    Gallbladder cancer (GBC) is an uncommon neoplasm in the United States, but one with high mortality rates. This malignancy remains largely understudied at the molecular level such that few targeted therapies or predictive biomarkers exist. We built the first series of serial analysis of gene expression (SAGE) libraries from GBC and nonneoplastic gallbladder mucosa, composed of 21-bp long-SAGE tags. SAGE libraries were generated from three stage-matched GBC patients (representing Hispanic/Latino, Native American, and Caucasian ethnicities, respectively) and one histologically alithiasic gallbladder. Real-time quantitative PCR was done on microdissected epithelium from five matched GBC and corresponding nonneoplastic gallbladder mucosa. Immunohistochemical analysis was done on a panel of 182 archival GBC in high-throughput tissue microarray format. SAGE tags corresponding to connective tissue growth factor (CTGF) transcripts were identified as differentially overexpressed in all pairwise comparisons of GBC (P Cancer Genome Anatomy Project web site and should facilitate much needed research into this lethal neoplasm.

  3. Hypoxia enhances the interaction between pancreatic stellate cells and cancer cells via increased secretion of connective tissue growth factor.

    Science.gov (United States)

    Eguchi, Daiki; Ikenaga, Naoki; Ohuchida, Kenoki; Kozono, Shingo; Cui, Lin; Fujiwara, Kenji; Fujino, Minoru; Ohtsuka, Takao; Mizumoto, Kazuhiro; Tanaka, Masao

    2013-05-01

    Pancreatic cancer (PC), a hypovascular tumor, thrives under hypoxic conditions. Pancreatic stellate cells (PSCs) promote PC progression by secreting soluble factors, but their functions in hypoxia are poorly understood. This study aimed to clarify the effects of hypoxic conditions on the interaction between PC cells and PSCs. We isolated human PSCs from fresh pancreatic ductal adenocarcinomas and analyzed functional differences in PSCs between normoxia (21% O2) and hypoxia (1% O2), including expression of various factors related to tumor-stromal interactions. We particularly analyzed effects on PC invasiveness of an overexpressed molecule-connective tissue growth factor (CTGF)-in PSCs under hypoxic conditions, using RNA interference techniques. Conditioned media from hypoxic PSCs enhanced PC cell invasiveness more intensely than that from normoxic PSCs (P cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Periodontitis increases rheumatic factor serum levels and citrullinated proteins in gingival tissues and alter cytokine balance in arthritic rats.

    Directory of Open Access Journals (Sweden)

    Mônica G Corrêa

    Full Text Available This study investigated some immunological features by experimental periodontitis (EP and rheumatoid arthritis (RA disease interact in destructive processes in arthritic rats. Rats were assigned to the following groups: EP +RA; RA; EP; and Negative Control. RA was induced by immunizations with type-II collagen and a local immunization with Complete Freund's adjuvant in the paw. Periodontitis was induced by ligating the right first molars. The serum level of rheumatoid factor (RF and anti-citrullinated protein antibody (ACCPA were measured before the induction of EP (T1 and at 28 days after (T2 by ELISA assay. ACCPA levels were also measured in the gingival tissue at T2. The specimens were processed for morphometric analysis of bone loss, and the gingival tissue surrounding the first molar was collected for the quantification of interleukin IL-1β, IL-4, IL-6, IL-17 and TNF-α using a Luminex/MAGpix assay. Paw edema was analyzed using a plethysmometer. Periodontitis increased the RF and ACCPA levels in the serum and in the gingival tissue, respectively. Besides, the level of paw swelling was increased by EP and remained in progress until the end of the experiment, when EP was associated with RA. Greater values of IL-17 were observed only when RA was present, in spite of PE. It can be concluded that periodontitis increases rheumatic factor serum levels and citrullinated proteins level in gingival tissues and alter cytokine balance in arthritic rats; at the same time, arthritis increases periodontal destruction, confirming the bidirectional interaction between diseases.

  5. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy

    Science.gov (United States)

    Askari, Arman T.; Unzek, Samuel; Popovic, Zoran B.; Goldman, Corey K.; Forudi, Farhad; Kiedrowski, Matthew; Rovner, Aleksandr; Ellis, Stephen G.; Thomas, James D.; DiCorleto, Paul E.; hide

    2003-01-01

    BACKGROUND: Myocardial regeneration via stem-cell mobilisation at the time of myocardial infarction is known to occur, although the mechanism for stem-cell homing to infarcted tissue subsequently and whether this approach can be used for treatment of ischaemic cardiomyopathy are unknown. We investigated these issues in a Lewis rat model (ligation of the left anterior descending artery) of ischaemic cardiomyopathy. METHODS: We studied the effects of stem-cell mobilisation by use of granulocyte colony-stimulating factor (filgrastim) with or without transplantation of syngeneic cells. Shortening fraction and myocardial strain by tissue doppler imaging were quantified by echocardiography. FINDINGS: Stem-cell mobilisation with filgrastim alone did not lead to engraftment of bone-marrow-derived cells. Stromal-cell-derived factor 1 (SDF-1), required for stem-cell homing to bone marrow, was upregulated immediately after myocardial infarction and downregulated within 7 days. 8 weeks after myocardial infarction, transplantation into the peri-infarct zone of syngeneic cardiac fibroblasts stably transfected to express SDF-1 induced homing of CD117-positive stem cells to injured myocardium after filgrastim administration (control vs SDF-1-expressing cardiac fibroblasts mean 7.2 [SD 3.4] vs 33.2 [6.0] cells/mm2, n=4 per group, pcell homing to injured myocardium and suggest a strategy for directed stem-cell engraftment into injured tissues. Our findings also indicate that therapeutic strategies focused on stem-cell mobilisation for regeneration of myocardial tissue must be initiated within days of myocardial infarction unless signalling for stem-cell homing is re-established.

  6. Factors of late radiosensitivity of normal tissues; Facteurs de radiosensibilite tardive des tissus sains

    Energy Technology Data Exchange (ETDEWEB)

    Azria, A. [CRLC Val d' Aurelle-Paul-Lamarque, departement de radiotherapie, 34 - Montpellier (France); Pointreau, Y. [CHRU Bretonneau, 37 - Tours (France); Toledano, A. [Clinique Hartman, 92 - Neuilly-sur-Seine (France); Ozsahin, M. [CHU Vaudois, Lausanne (Switzerland)

    2010-07-15

    The impact of curative radiotherapy depends mainly on the total dose delivered homogeneously in the targeted volume. Nevertheless, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. Two different side effects (acute and late) can occur during and after radiotherapy. Of particular interest are the radiation-induced sequelae due to their irreversibility and the potential impact on daily quality of life. In a same population treated in one centre with the same technique, it appears that individual radiosensitivity clearly exists. In the hypothesis that genetic is involved in this area of research, lymphocytes seem to be the tissue of choice due to easy accessibility. Recently, low percentage of CD4 and CD8 lymphocyte apoptosis were shown to be correlated with high grade of sequelae. In addition, recent data suggest that patients with severe radiation-induced late side effects possess four or more single nucleotide polymorphisms (SNP) in candidate genes (ATM, SOD2, TGFB1, XRCC1, and XRCC3) and low radiation-induced CD8 lymphocyte apoptosis in vitro. On-going studies are being analyzing the entire genome using a Genome-wide association study (GWAS) analysis. (authors)

  7. Monitoring of treatment with vitamin K antagonists: recombinant thromboplastins are more sensitive to factor VII than tissue-extract thromboplastins.

    Science.gov (United States)

    Biedermann, J S; van den Besselaar, A M H P; de Maat, M P M; Leebeek, F W G; Kruip, M J H A

    2017-03-01

    Essentials Differences in sensitivity to factor VII (FVII) have been suggested between thromboplastins. FVII-induced International Normalized Ratio (INR) changes differ between commercial reagents. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Thromboplastin choice may affect FVII-mediated INR stability. Background Differences regarding sensitivity to factor VII have been suggested for recombinant human and tissue-extract thromboplastins used for International Normalized Ratio (INR) measurement, but the evidence is scarce. Differences in FVII sensitivity are clinically relevant, as they can affect INR stability during treatment with vitamin K antagonists (VKAs). Objectives To determine whether commercial thromboplastins react differently to changes in FVII. Methods We studied the effect of addition of FVII on the INR in plasma by using three tissue-extract (Neoplastin C1+, Hepato Quick, and Thromborel S) and three recombinant human (Recombiplastin 2G, Innovin, and CoaguChek XS) thromboplastins. Three different concentrations of purified human FVII (0.006, 0.012 and 0.062 μg mL -1 plasma), or buffer, were added to five certified pooled plasmas of patients using VKAs (INR of 1.5-3.5). Changes in FVII activity were measured with two bioassays (Neoplastin and Recombiplastin), and relative INR changes were compared between reagents. Results After addition of 0.062 μg mL -1 FVII, FVII activity in the pooled plasmas increased by approximately 20% (Neoplastin) or 32% (Recombiplastin) relative to the activity in pooled normal plasma. All thromboplastins showed dose-dependent INR decreases. The relative INR change in the pooled plasmas significantly differed between the six thromboplastins. No differences were observed among recombinant or tissue-extract thromboplastins. Pooled results indicated that the FVII-induced INR change was greater for recombinant than for tissue-extract thromboplastins. Conclusions Differences

  8. Formation of proteoglycan and collagen-rich scaffold-free stiff cartilaginous tissue using two-step culture methods with combinations of growth factors.

    Science.gov (United States)

    Miyazaki, Tatsuya; Miyauchi, Satoshi; Matsuzaka, Satoshi; Yamagishi, Chie; Kobayashi, Kohei

    2010-05-01

    Tissue-engineered cartilage may be expected to serve as an alternative to autologous chondrocyte transplantation treatment. Several methods for producing cartilaginous tissue have been reported. In this study, we describe the production of scaffold-free stiff cartilaginous tissue of pig and human, using allogeneic serum and growth factors. The tissue was formed in a mold using chondrocytes recovered from alginate bead culture and maintained in a medium with transforming growth factor-beta and several other additives. In the case of porcine tissue, the tear strength of the tissue and the contents of proteoglycan (PG) and collagen per unit of DNA increased dose-dependently with transforming growth factor-beta. The length of culture was significantly and positively correlated with thickness, tear strength, and PG and collagen contents. Tear strength showed positive high correlations with both PG and collagen contents. A positive correlation was also seen between PG content and collagen content. Similar results were obtained with human cartilaginous tissue formed from chondrocytes expanded in monolayer culture. Further, an in vivo pilot study using pig articular cartilage defect model demonstrated that the cartilaginous tissue was well integrated with surrounding tissue at 13 weeks after the implantation. In conclusion, we successfully produced implantable scaffold-free stiff cartilaginous tissue, which characterized high PG and collagen contents.

  9. Comparison of effective doses using tissue-weighting factors in the 1977, 1990, and 2007 recommendations of the ICRP

    International Nuclear Information System (INIS)

    Matsunaga, Yuta; Kawaguchi, Ai; Suzuki, Shoichi

    2013-01-01

    The International Commission on Radiological Protection (ICRP) has established recommended tissue-weighting factors. Although there have been international reports on effective doses using the factors listed in the 1977, 1990, and 2007 recommendations of the ICRP, there have been no papers in Japan. The aim of this study was to evaluate effective doses using the tissue-weighting factors listed in each recommendation of the ICRP under 2011 exposure conditions in Japan. We used a human body phantom to estimate patient exposure doses during chest, abdomen, lumbar spine (anteroposterior and lateral), and head radiographs. With thermoluminescence dosimeters placed at various positions on and in the phantom, radiation doses were determined. There was little change in the effective doses to the chest and head from each recommendation. However, the effective doses recommended in 1977 were 0.2 mSv to the abdomen, 0.1 mSv to the lumbar spine anteroposteriorally, and 0.1 mSv to the lumbar spine laterally; these values are lower than those recommended in 1990 and 2007, which were 0.5 mSv to the abdomen, 0.4 mSv to the lumbar spine anteroposteriorally, and 0.6 mSv to the lumbar spine laterally. We could evaluate the effective doses using each recommendation and 2011 exposure conditions in Japan. (author)

  10. Operation with the low momentum compaction factor on an electron storage ring

    International Nuclear Information System (INIS)

    Hama, H.; Yamazaki, J.; Nakamura, E.; Isoyama, G.

    1994-01-01

    We have studied quasi-isochronous operation with the low momentum compaction factor to reduce the bunch length of the electron beam on the UVSOR storage ring. The momentum compaction factor α was reduced by changing the dispersion function in the bending magnets. Though effect of the second order α becomes dominant in the very low α region, we could compensate it by reducing strength of the focusing sextupole magnets. The momentum compaction factor was reduced to less than one hundredth with respect to the ordinary value. Using a streak camera, we measured the very short bunch, and confirmed the storage ring was operated nearly isochronously. The beam current dependence of the bunch length was also measured. The bunch lengthening was interpreted by potential-well distortion theory with a constant value of the effective longitudinal coupling impedance over the wide range of α. (author)

  11. Effect of the anisotropy of the electron g-factor in spin polarization

    Energy Technology Data Exchange (ETDEWEB)

    Miah, M. Idrish, E-mail: m.miah@griffith.edu.au [Queensland Micro- and Nanotechnology Centre, Griffith University, Nathan, Brisbane, QLD 4111 (Australia); School of Biomolecular and Physical Sciences, Griffith University, Nathan, Brisbane, QLD 4111 (Australia); Department of Physics, University of Chittagong, Chittagong, Chittagong 4331 (Bangladesh); Gray, E. MacA. [Queensland Micro- and Nanotechnology Centre, Griffith University, Nathan, Brisbane, QLD 4111 (Australia); School of Biomolecular and Physical Sciences, Griffith University, Nathan, Brisbane, QLD 4111 (Australia)

    2010-02-15

    Spin polarization in the presence of an external magnetic field and electric bias in quantum confined semiconductor structures has been studied by time- and polarization-resolved spectrometry. From measurements with angular variations of the magnetic field from the Voigt configuration (VC) it was found that both the frequency ({Omega}) and decay rate ({beta}) of the oscillatory component of the polarization increase with variation of the angle from the VC. Their dependences are discussed based on the electron spin dephasing related to the spread of the electron g-factor (g{sub e}) (i.e. unequal values of the longitudinal (g{sub e||}) and transverse (g{sub e}-perpendicular) components of g{sub e}) and the exchange interaction between the electron and hole spins. It is demonstrated that the increase in {Omega} upon deviation of the magnetic field from the VC relates to the anisotropy of g{sub e} (g{sub e||} and g{sub e}-perpendicular) resulting from the quantum confinement effect. However, the angular dependence on {beta} is related to the residual exchange interaction between the electron spin and rapidly relaxing hole spin.

  12. Correlation between increasing tissue ischemia and circulating levels of angiogenic growth factors in peripheral artery disease.

    Science.gov (United States)

    Jalkanen, Juho; Hautero, Olli; Maksimow, Mikael; Jalkanen, Sirpa; Hakovirta, Harri

    2018-04-21

    The aim of the present study was to assess the circulating levels of vascular endothelial growth factor (VEGF) and other suggested therapeutic growth factors with the degree of ischemia in patients with different clinical manifestations of peripheral arterial disease (PAD) according to the Rutherford grades. The study cohort consists of 226 consecutive patients admitted to a Department of Vascular Surgery for elective invasive procedures. PAD patients were grouped according to the Rutherford grades after a clinical assessment. Ankle-brachial pressure indices (ABI) and absolute toe pressure (TP) values were measured. Serum levels of circulating VEGF, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) were measured from serum and analysed against Rutherford grades and peripheral hemodynamic measurements. The levels of VEGF (P = 0.009) and HGF (P correlations between Rutherford grades was detected as follows; VEGF (Pearson's correlation = 0.183, P = 0.004), HGF (Pearson's correlation = 0.253, P Pearson's correlation = 0.169, P = 0.008) and PDGF (Pearson's correlation = 0.296, P correlation with ABI (Pearson's correlation -0.19, P = 0.009) and TP (Pearson's correlation -0.20, P = 0.005) measurements. Our present observations show that the circulating levels of VEGF and other suggested therapeutic growth factors are significantly increased along with increasing ischemia. These findings present a new perspective to anticipated positive effects of gene therapies utilizing VEGF, HGF, and bFGF, because the levels of these growth factors are endogenously high in end-stage PAD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors

    Directory of Open Access Journals (Sweden)

    Donald M. Bryant

    2017-01-01

    Full Text Available Mammals have extremely limited regenerative capabilities; however, axolotls are profoundly regenerative and can replace entire limbs. The mechanisms underlying limb regeneration remain poorly understood, partly because the enormous and incompletely sequenced genomes of axolotls have hindered the study of genes facilitating regeneration. We assembled and annotated a de novo transcriptome using RNA-sequencing profiles for a broad spectrum of tissues that is estimated to have near-complete sequence information for 88% of axolotl genes. We devised expression analyses that identified the axolotl orthologs of cirbp and kazald1 as highly expressed and enriched in blastemas. Using morpholino anti-sense oligonucleotides, we find evidence that cirbp plays a cytoprotective role during limb regeneration whereas manipulation of kazald1 expression disrupts regeneration. Our transcriptome and annotation resources greatly complement previous transcriptomic studies and will be a valuable resource for future research in regenerative biology.

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

    Science.gov (United States)

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

    2000-10-01

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

  15. Exchange enhancement of the electron g-factor in a two-dimensional semimetal in HgTe quantum wells

    Energy Technology Data Exchange (ETDEWEB)

    Bovkun, L. S., E-mail: bovkun@ipmras.ru; Krishtopenko, S. S.; Zholudev, M. S.; Ikonnikov, A. V.; Spirin, K. E. [Russian Academy of Sciences, Institute for Physics of Microstructures (Russian Federation); Dvoretsky, S. A.; Mikhailov, N. N. [Russian Academy of Sciences, Rzhanov Institute of Semiconductor Physics, Siberian Branch (Russian Federation); Teppe, F.; Knap, W. [Universite Montpellier II, Laboratoire Charles Coulomb (L2C), UMR CNRS 5221, GIS-TERALAB (France); Gavrilenko, V. I. [Russian Academy of Sciences, Institute for Physics of Microstructures (Russian Federation)

    2015-12-15

    The exchange enhancement of the electron g-factor in perpendicular magnetic fields to 12 T in HgTe/CdHgTe quantum wells 20 nm wide with a semimetal band structure is studied. The electron effective mass and g-factor at the Fermi level are determined by analyzing the temperature dependence of the amplitude of Shubnikov–de Haas oscillation in weak fields and near odd Landau-level filling factors ν ≤ 9. The experimental values are compared with theoretical calculations performed in the one-electron approximation using the eight-band kp Hamiltonian. The found dependence of g-factor enhancement on the electron concentration is explained by changes in the contributions of hole- and electron-like states to exchange corrections to the Landau-level energies in the conduction band.

  16. Validating Smoking Data From the Veteran’s Affairs Health Factors Dataset, an Electronic Data Source

    Science.gov (United States)

    Brandt, Cynthia A.; Skanderson, Melissa; Justice, Amy C.; Shahrir, Shahida; Butt, Adeel A.; Brown, Sheldon T.; Freiberg, Matthew S.; Gibert, Cynthia L.; Goetz, Matthew Bidwell; Kim, Joon Woo; Pisani, Margaret A.; Rimland, David; Rodriguez-Barradas, Maria C.; Sico, Jason J.; Tindle, Hilary A.; Crothers, Kristina

    2011-01-01

    Introduction: We assessed smoking data from the Veterans Health Administration (VHA) electronic medical record (EMR) Health Factors dataset. Methods: To assess the validity of the EMR Health Factors smoking data, we first created an algorithm to convert text entries into a 3-category smoking variable (never, former, and current). We compared this EMR smoking variable to 2 different sources of patient self-reported smoking survey data: (a) 6,816 HIV-infected and -uninfected participants in the 8-site Veterans Aging Cohort Study (VACS-8) and (b) a subset of 13,689 participants from the national VACS Virtual Cohort (VACS-VC), who also completed the 1999 Large Health Study (LHS) survey. Sensitivity, specificity, and kappa statistics were used to evaluate agreement of EMR Health Factors smoking data with self-report smoking data. Results: For the EMR Health Factors and VACS-8 comparison of current, former, and never smoking categories, the kappa statistic was .66. For EMR Health Factors and VACS-VC/LHS comparison of smoking, the kappa statistic was .61. Conclusions: Based on kappa statistics, agreement between the EMR Health Factors and survey sources is substantial. Identification of current smokers nationally within the VHA can be used in future studies to track smoking status over time, to evaluate smoking interventions, and to adjust for smoking status in research. Our methodology may provide insights for other organizations seeking to use EMR data for accurate determination of smoking status. PMID:21911825

  17. Effects of epidermal growth factor on neural crest cells in tissue culture

    International Nuclear Information System (INIS)

    Erickson, C.A.; Turley, E.A.

    1987-01-01

    Epidermal growth factor (EGF) stimulates the release of hyaluronic acid (HA) and chondroitin sulfate proteoglycan (CSPG) from quail trunk neural crest cultures in a dose-dependent fashion. It also promotes the expression of cell-associated heparan sulfate proteoglycan (HSPG) as detected by immunofluorescence and immunoprecipitation of the 3 H-labeled proteoglycan. Furthermore, EGF stimulates [ 3 H]thymidine incorporation into total cell DNA. These results raise the possibility that EGF or an analogous growth factor is involved in regulation of neural crest cell morphogenesis

  18. Tissue factor pathway inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study.

    Directory of Open Access Journals (Sweden)

    Aurélie Di Bartolomeo

    Full Text Available The study aimed to evaluate if the rate of tissue factor pathway inhibitor during pregnancy and following delivery could be a predictive factor for placenta-mediated adverse pregnancy outcomes in high-risk women.This was a prospective multicentre cohort study of 200 patients at a high risk of occurrence or recurrence of placenta-mediated adverse pregnancy outcomes conducted between June 2008 and October 2010. Measurements of tissue factor pathway inhibitor resistance (normalized ratio and tissue factor pathway inhibitor activity were performed for the last 72 patients at 20, 24, 28, 32, and 36 weeks of gestation and during the postpartum period.Overall, 15 patients presented a placenta-mediated adverse pregnancy outcome. There was no difference in normalized tissue factor pathway inhibitor ratios between patients with and without placenta-mediated adverse pregnancy outcomes during pregnancy and in the post-partum period. Patients with placenta-mediated adverse pregnancy outcomes had tissue factor pathway inhibitor activity rates that were significantly higher than those in patients without at as early as 24 weeks of gestation. The same results were observed following delivery.Among high-risk women, the tissue factor pathway inhibitor activity of patients with gestational vascular complications is higher than that in other patients. Hence, these markers could augment a screening strategy that includes an analysis of angiogenic factors as well as clinical and ultrasound imaging with Doppler measurement of the uterine arteries.

  19. Analysis of factors causing signal loss in the measurement of lung tissue water by nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Fukuzaki, Minoru; Shioya, Sumie; Haida, Munetaka

    1997-01-01

    The water content of lung, brain, and muscle tissue was measured by nuclear magnetic resonance (NMR) and compared with gravimetric determinations. The NMR signal intensity of water was measured by a single 90 degree pulse and by a spin-echo sequence. The absolute water content was determined by the difference in the sample's weight before and after desiccation. The NMR detectable water in each tissue was expressed as a percentage of the signal intensity for an equal weight of distilled water. Using the single pulse measurement, 67% of the gravimetrically-measured water was detected in collapsed lung samples (consisting of about 47% retained air), in contrast to 96% for brain and 98% for muscle. For degassed lung samples, the NMR detectability of water increased to 87% with the single pulse measurement and to 90% with the spin-echo measurement, but the values remained significantly less than those of brain or muscle. Factors that caused the NMR signal loss of 33% in collapsed lung samples were: air-tissue interfaces (20%), microscopic field inhomogeneity (3%), and a water component with an extremely short magnetization decay time constant (10%). (author)

  20. Elevation of transforming growth factor beta (TGFbeta) and its downstream mediators in subcutaneous foreign body capsule tissue.

    Science.gov (United States)

    Li, Allen G; Quinn, Matthew J; Siddiqui, Yasmin; Wood, Michael D; Federiuk, Isaac F; Duman, Heather M; Ward, W Kenneth

    2007-08-01

    Foreign body encapsulation represents a chronic fibrotic response and has been a major obstacle that reduces the useful life of implanted biomedical devices. The precise mechanism underlying such an encapsulation is still unknown. We hypothesized that, considering its central role in many other fibrotic conditions, transforming growth factor beta (TGFbeta) may play an important role during the formation of foreign body capsule (FBC). In the present study, we implanted mock sensors in rats subcutaneously and excised FBC samples at day 7, 21, and 48-55 postimplantation. The most abundant TGFbeta isoform in all tissues was TGFbeta1, which was expressed minimally in control tissue. The expression of both TGFbeta1 RNA and protein was significantly increased in FBC tissues at all time points, with the highest level in day 7 FBC. The number of cells stained for phosphorylated Smad2, an indication of activated TGFbeta signaling, paralleled the expression of TGFbeta. A similar dynamic change was also observed in the numbers of FBC myofibroblasts, which in response to TGFbeta, differentiate from quiescent fibroblasts and synthesize collagen. Type I collagen, the most prominent downstream target of TGFbeta in fibrosis, was found in abundance in the FBC, especially during the latter time periods. We suggest that TGFbeta plays an important role in the FBC formation. Inhibition of TGFbeta signaling could be a promising strategy in the prevention of FBC formation, thereby extending the useful life of subcutaneous implants.

  1. Effects of epidermal growth factor in artificial tear on vitamin C levels of corneal wounded eye tissues.

    Science.gov (United States)

    Gönül, B; Kaplan, B; Bilgihan, K; Budak, M T

    2001-04-01

    To investigate the effect of artificial tear (AT) solution and epidermal growth factor (EGF) treatment on the cornea and aqueous humour ascorbic acid (AA) levels of full-thickness corneal wounded eyes. The effect of EGF on the AA levels of aqueous humour and corneal wound tissue was determined in full-thickness corneal wounded rabbit eyes on the seventh post-operative day. There were three groups: untreated controls, AT-treated controls and an EGF+AT-treated experimental group (n = 6 in each group). Corneal wounded eyes were topically treated with 5 microl AT or 5 microl EGF in AT (1 mg/l EGF in AT prepaaration which contained 3.0% carbopol 940) twice daily for 6 days after operation. The wound strengths were also measured on the seventh post-operative day as a measure of wound healing. Statistical analysis was carried out using the Mann-Whitney U-test by Statview program. The wound strengths of corneas, and AA levels of wound tissues and aqueous humour, increased significantly following AT and EGF treatment (p < 0.05). In the corneal wounded eye, aqueous humour serves as a source of vitamin C and there may be a relation between EGF treatment in AT and AA levels of corneal wounded eye tissues.

  2. Connective tissue growth factor is activated by gastrin and involved in gastrin-induced migration and invasion.

    Science.gov (United States)

    Bhandari, Sabin; Bakke, Ingunn; Kumar, J; Beisvag, Vidar; Sandvik, Arne K; Thommesen, Liv; Varro, Andrea; Nørsett, Kristin G

    2016-06-17

    Connective tissue growth factor (CTGF) has been reported in gastric adenocarcinoma and in carcinoid tumors. The aim of this study was to explore a possible link between CTGF and gastrin in gastric epithelial cells and to study the role of CTGF in gastrin induced migration and invasion of AGS-GR cells. The effects of gastrin were studied using RT-qPCR, Western blot and assays for migration and invasion. We report an association between serum gastrin concentrations and CTGF abundancy in the gastric corpus mucosa of hypergastrinemic subjects and mice. We found a higher expression of CTGF in gastric mucosa tissue adjacent to tumor compared to normal control tissue. We showed that gastrin induced expression of CTGF in gastric epithelial AGS-GR cells via MEK, PKC and PKB/AKT pathways. CTGF inhibited gastrin induced migration and invasion of AGS-GR cells. We conclude that CTGF expression is stimulated by gastrin and involved in remodeling of the gastric epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Effects of hydrostatic pressure on the electron g|| factor and g-factor anisotropy in GaAs-(Ga, Al)As quantum wells under magnetic fields

    International Nuclear Information System (INIS)

    Porras-Montenegro, N; Duque, C A; Oliveira, L E; Reyes-Gomez, E

    2008-01-01

    The hydrostatic-pressure effects on the electron-effective Lande g || factor and g-factor anisotropy in semiconductor GaAs-Ga 1-x Al x As quantum wells under magnetic fields are studied. The g || factor is computed by considering the non-parabolicity and anisotropy of the conduction band through the Ogg-McCombe effective Hamiltonian, and numerical results are displayed as functions of the applied hydrostatic pressure, magnetic fields, and quantum-well widths. Good agreement between theoretical results and experimental measurements in GaAs-(Ga, Al)As quantum wells for the electron g factor and g-factor anisotropy at low values of the applied magnetic field and in the absence of hydrostatic pressure is obtained. Present results open up new possibilities for manipulating the electron-effective g factor in semiconductor heterostructures.

  4. Tissue engineering

    CERN Document Server

    Fisher, John P; Bronzino, Joseph D

    2007-01-01

    Increasingly viewed as the future of medicine, the field of tissue engineering is still in its infancy. As evidenced in both the scientific and popular press, there exists considerable excitement surrounding the strategy of regenerative medicine. To achieve its highest potential, a series of technological advances must be made. Putting the numerous breakthroughs made in this field into a broad context, Tissue Engineering disseminates current thinking on the development of engineered tissues. Divided into three sections, the book covers the fundamentals of tissue engineering, enabling technologies, and tissue engineering applications. It examines the properties of stem cells, primary cells, growth factors, and extracellular matrix as well as their impact on the development of tissue engineered devices. Contributions focus on those strategies typically incorporated into tissue engineered devices or utilized in their development, including scaffolds, nanocomposites, bioreactors, drug delivery systems, and gene t...

  5. Experimental determination of pcav factors for cylindrical ionisation chambers in electron beams

    International Nuclear Information System (INIS)

    Palm, Aa.; Mattsson, O.

    2000-01-01

    The electron beam method recommended for calibrating plane parallel ionisation chambers involves cavity correction factors for cylindrical chambers. The cavity correction factors in the IAEA TRS-381 Code of Practice are based on measurements at R 100 in a PMMA phantom using PMMA cylindrical chambers having different cavity radii. In the present work the recommended data were confirmed for electron beams delivered by modern medical accelerators by using the very same phantom and ionisation chambers that were used in the original work. From another series of measurements, using four specially designed wall-less chambers in a graphite phantom, the linear relation between p cav and the chamber radius that is the basis for the experimental method, was verified. The method was also used to determine the cavity correction factors for a set of Farmer-like graphite chambers placed in water. Compared to the TRS-381 Code of Practice a smaller correction was found for the cavity perturbation for the graphite chambers used in water. (author)

  6. Energy absorption buildup factors for thermoluminescent dosimetric materials and their tissue equivalence

    DEFF Research Database (Denmark)

    Manohara, S.R.; Hanagodimath, S.M.; Gerward, Leif

    2010-01-01

    Gamma ray energy-absorption buildup factors were computed using the five-parameter geometric progression (G-P) fitting formula for seven thermoluminescent dosimetric (TLD) materials in the energy range 0.015-15 MeV, and for penetration depths up to 40 mfp (mean free path). The generated energy-absorption...

  7. Radiation damage of hemopoietic tissue: circulating stem cells and growth factor responses

    International Nuclear Information System (INIS)

    Wagemaker, G.

    1997-01-01

    Briefly, evidence in rodents and nonhuman primates demonstrated two types of immature cells to be involved in regeneration following total body irradiation (X-rays). These cell populations can be separated and there is good responses differ. Related to these observations, experimental growth factor therapy has been ineffective at doses larger than 6-7 Gy X-rays and was shown to be optimally effective at the mid-lethal dose of 5 Gy. Consequently, at relatively high doses of radiation, treatment should initially be directed at reconstitution of growth factor responding stem cell subsets rather than at accelerated production of mature blood cells. Following cytotoxic insult to bone marrow, hemopoietic reconstitution is characterized by an increased fraction of stem cells that enters circulation. This might reflect a physiological mechanism to regulate the activities of the scattered bone marrow sites. In experimental studies with nonhuman primates, we showed that the number of circulating immature cells are proportional to those in the bone marrow and can be used for quantitative evaluation of residual stem cells numbers and to monitor the effectiveness of growth factor therapy at the immature cell level. The latter observations enables the design of growth factor treatment schedules for radiation induced myelosuppression in which thrombopenia is reduced and the recovery of immature bone marrow cells is promoted. (N.C.)

  8. Mathematical Model of Growth Factor Driven Haptotaxis and Proliferation in a Tissue Engineering Scaffold

    KAUST Repository

    Pohlmeyer, J. V.; Waters, S. L.; Cummings, L. J.

    2013-01-01

    nutrient-rich culture medium is perfused through a 2D porous scaffold impregnated with growth factor and seeded with cells. We model these processes on the timescale of cell proliferation, which typically is of the order of days. While a quantitative

  9. Factors causing risks of caries evolvement in dental solid tissues under acclimatization

    Directory of Open Access Journals (Sweden)

    R.S. Rakhmanov

    2017-12-01

    Full Text Available We analyzed parameters characterizing mineral balance in a body and dental state in two groups of healthy men (n = 15 in each, aged 34.7 ± 0.6 in hot and humid marine climate conditions; one group was made of people undergoing acclimatization, the second one consisted of local population. We assessed working conditions and their category, and metrological data with determining environmental thermal load (ETL-index. Both groups worked outdoors; their labor had IIb category; they had to work overtime and under increased psy-choemotional loads; their working conditions differed as per nutrition and accommodation. When people from both groups had to work beyond their permanent location, their nutrition was represented by individual rations. Labor hardness was assessed as 3.2; labor intensity, as 3.2. Daytime temperature reached 30,0 С, relative air humidity was 77.3 ± 2.6 %, wind speed was 4.3 ± 0.3 m/sec. Microclimate was assessed as having 3.1 hazard category. Overall, working conditions were assessed as hazardous (3.3 hazard category. Electrolyte balance in a body was violated and it was proved by ower contents of K, Na, and Cl in blood serum; it was more apparent in people who were undergoing acclimatization. 70.0 % of local people had Ca contents in blood serum lower than the physiological standard. Lower Ca and increased P contents in blood serum were also detected in those undergoing acclimatization which could be evidence that Ca was washed out of a body and greater risk of dental caries occurred. As per observation dynamics we detected the following processes in people undergoing acclimatization: pH saliva and its mineralizing function shifting to acidity, salivation rate, and lower enamel resistance; they proved there was a growth in dental solid tissues demineralization. These parameters corresponded to those detected in local population. It calls for primary prevention activities aimed at fighting caries of dental solid tissues.

  10. Endothelium trans differentiated from Wharton's jelly mesenchymal cells promote tissue regeneration: potential role of soluble pro-angiogenic factors.

    Science.gov (United States)

    Aguilera, Valeria; Briceño, Luis; Contreras, Hector; Lamperti, Liliana; Sepúlveda, Esperanza; Díaz-Perez, Francisca; León, Marcelo; Veas, Carlos; Maura, Rafael; Toledo, Jorge Roberto; Fernández, Paulina; Covarrubias, Ambart; Zuñiga, Felipe Andrés; Radojkovic, Claudia; Escudero, Carlos; Aguayo, Claudio

    2014-01-01

    Mesenchymal stem cells have a high capacity for trans-differentiation toward many adult cell types, including endothelial cells. Feto-placental tissue, such as Wharton's jelly is a potential source of mesenchymal stem cells with low immunogenic capacity; make them an excellent source of progenitor cells with a potential use for tissue repair. We evaluated whether administration of endothelial cells derived from mesenchymal stem cells isolated from Wharton's jelly (hWMSCs) can accelerate tissue repair in vivo. Mesenchymal stem cells were isolated from human Wharton's jelly by digestion with collagenase type I. Endothelial trans-differentiation was induced for 14 (hWMSC-End14d) and 30 (hWMSC-End30d) days. Cell phenotyping was performed using mesenchymal (CD90, CD73, CD105) and endothelial (Tie-2, KDR, eNOS, ICAM-1) markers. Endothelial trans-differentiation was demonstrated by the expression of endothelial markers and their ability to synthesize nitric oxide (NO). hWMSCs can be differentiated into adipocytes, osteocytes, chondrocytes and endothelial cells. Moreover, these cells show high expression of CD73, CD90 and CD105 but low expression of endothelial markers prior to differentiation. hWMSCs-End express high levels of endothelial markers at 14 and 30 days of culture, and also they can synthesize NO. Injection of hWMSC-End30d in a mouse model of skin injury significantly accelerated wound healing compared with animals injected with undifferentiated hWMSC or injected with vehicle alone. These effects were also observed in animals that received conditioned media from hWMSC-End30d cultures. These results demonstrate that mesenchymal stem cells isolated from Wharton's jelly can be cultured in vitro and trans-differentiated into endothelial cells. Differentiated hWMSC-End may promote neovascularization and tissue repair in vivo through the secretion of soluble pro-angiogenic factors.

  11. Predictive factors for complete removal in soft tissue sarcomas: a retrospective analysis in a series of 592 cases.

    Science.gov (United States)

    Sastre-Garau, X; Coindre, J M; Leroyer, A; Terrier, P; Ollivier, L; Stöckle, E; Bonichon, F; Collin, F; Le Doussal, V; Contesso, G; Vilain, M O; Jacquemier, J; Nguyen, B B

    1997-07-01

    In order to specify the indications for conservative surgery and preoperative therapeutic approaches of soft tissues sarcomas (STS), we looked for the clinico-pathological parameters associated with the failure to obtain a complete removal (CRm) of the tumor. We retrospectively analyzed a series of 592 cases of primary non-metastatic STS. Surgery was performed in 495 cases as a primary treatment and in 88 cases after chemo- or radiotherapy. Nine patients were treated by chemotherapy-radiotherapy. In a univariate analysis, 20 parameters were tested for their association with CRm. A multivariate analysis was then used to define the independent parameters linked to the achievement of a CRm. In the univariate analysis, 15 parameters were found to be linked to the achievement of a CRm. Three of them proved to be independent in the multivariate analysis: T in the TNM classification, tumor location, and tumor necrosis. By the combination of these risk factors, four groups of patients were defined, with respective rates of CRm of 97% (no factor), 95% (one factor), 70% (two factors), and 48% (three factors). The achievement of a CRm after surgery of STS depends not only on the accessibility of the lesion, but also on tumor aggressiveness, a reflection of which is necrosis. The detection of necrosis by imaging procedures may thus help predicting the resectability of tumors and defining the indications for neoadjuvant therapies, likely to broaden the use of conservative surgery.

  12. Serial section scanning electron microscopy (S3EM) on silicon wafers for ultra-structural volume imaging of cells and tissues.

    Science.gov (United States)

    Horstmann, Heinz; Körber, Christoph; Sätzler, Kurt; Aydin, Daniel; Kuner, Thomas

    2012-01-01

    High resolution, three-dimensional (3D) representations of cellular ultrastructure are essential for structure function studies in all areas of cell biology. While limited subcellular volumes have been routinely examined using serial section transmission electron microscopy (ssTEM), complete ultrastructural reconstructions of large volumes, entire cells or even tissue are difficult to achieve using ssTEM. Here, we introduce a novel approach combining serial sectioning of tissue with scanning electron microscopy (SEM) using a conductive silicon wafer as a support. Ribbons containing hundreds of 35 nm thick sections can be generated and imaged on the wafer at a lateral pixel resolution of 3.7 nm by recording the backscattered electrons with the in-lens detector of the SEM. The resulting electron micrographs are qualitatively comparable to those obtained by conventional TEM. S(3)EM images of the same region of interest in consecutive sections can be used for 3D reconstructions of large structures. We demonstrate the potential of this approach by reconstructing a 31.7 µm(3) volume of a calyx of Held presynaptic terminal. The approach introduced here, Serial Section SEM (S(3)EM), for the first time provides the possibility to obtain 3D ultrastructure of large volumes with high resolution and to selectively and repetitively home in on structures of interest. S(3)EM accelerates process duration, is amenable to full automation and can be implemented with standard instrumentation.

  13. Serial section scanning electron microscopy (S3EM on silicon wafers for ultra-structural volume imaging of cells and tissues.

    Directory of Open Access Journals (Sweden)

    Heinz Horstmann

    Full Text Available High resolution, three-dimensional (3D representations of cellular ultrastructure are essential for structure function studies in all areas of cell biology. While limited subcellular volumes have been routinely examined using serial section transmission electron microscopy (ssTEM, complete ultrastructural reconstructions of large volumes, entire cells or even tissue are difficult to achieve using ssTEM. Here, we introduce a novel approach combining serial sectioning of tissue with scanning electron microscopy (SEM using a conductive silicon wafer as a support. Ribbons containing hundreds of 35 nm thick sections can be generated and imaged on the wafer at a lateral pixel resolution of 3.7 nm by recording the backscattered electrons with the in-lens detector of the SEM. The resulting electron micrographs are qualitatively comparable to those obtained by conventional TEM. S(3EM images of the same region of interest in consecutive sections can be used for 3D reconstructions of large structures. We demonstrate the potential of this approach by reconstructing a 31.7 µm(3 volume of a calyx of Held presynaptic terminal. The approach introduced here, Serial Section SEM (S(3EM, for the first time provides the possibility to obtain 3D ultrastructure of large volumes with high resolution and to selectively and repetitively home in on structures of interest. S(3EM accelerates process duration, is amenable to full automation and can be implemented with standard instrumentation.

  14. Upregulation of innate antiviral restricting factor expression in the cord blood and decidual tissue of HIV-infected mothers.

    Science.gov (United States)

    Pereira, Nátalli Zanete; Cardoso, Elaine Cristina; Oliveira, Luanda Mara da Silva; de Lima, Josenilson Feitosa; Branco, Anna Cláudia Calvielli Castelo; Ruocco, Rosa Maria de Souza Aveiro; Zugaib, Marcelo; de Oliveira Filho, João Bosco; Duarte, Alberto José da Silva; Sato, Maria Notomi

    2013-01-01

    Programs for the prevention of mother-to-child transmission of HIV have reduced the transmission rate of perinatal HIV infection and have thereby increased the number of HIV-exposed uninfected (HEU) infants. Natural immunity to HIV-1 infection in both mothers and newborns needs to be further explored. In this study, we compared the expression of antiviral restricting factors in HIV-infected pregnant mothers treated with antiretroviral therapy (ART) in pregnancy (n=23) and in cord blood (CB) (n=16), placental tissues (n=10-13) and colostrum (n=5-6) samples and compared them to expression in samples from uninfected (UN) pregnant mothers (n=21). Mononuclear cells (MNCs) were prepared from maternal and CB samples following deliveries by cesarean section. Maternal (decidua) and fetal (chorionic villus) placental tissues were obtained, and colostrum was collected 24 h after delivery. The mRNA and protein expression levels of antiviral factors were then evaluated. We observed a significant increase in the mRNA expression levels of antiviral factors in MNCs from HIV-infected mothers and CB, including the apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5α (TRIM-5α), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-β, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and α-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5α protein levels in the villi and increased STING mRNA expression in both placental tissues were also observed in HIV-infected mothers compared with uninfected (UN) mothers. Additionally, colostrum cells from infected mothers showed increased tetherin and IFN-β mRNA levels and CXCL9 protein levels. The data presented here indicate that antiviral restricting factor expression can be induced in utero in HIV-infected mothers. Future studies are warranted to determine

  15. Factors affecting callus and protoplast production and regeneration of plants from garlic tissue cultures

    International Nuclear Information System (INIS)

    Al-Safadi, B.; Nabulsi, I.

    2001-08-01

    Five cultivars of garlic, two explants, six callusing media, six regeneration media, two kinds of light and several doses of gamma irradiation were used to determine the best conditions for callus induction and plant regeneration from garlic tissue cultures. Also, some experiments were conducted to study the possibility to isolate protoplast and regenerate plants. The experiment showed that medium MS9 was good for regenerating plant directly from basal plate without going through callus phase. ANOVA exhibited significant differences among used cultivars in their ability to form callus. No significant difference was observed between 16 hr light and complete darkness in callus growth. However, appearance of callus was generally better on darkness. Cultivar varied in their ability to regenerate and interaction between cultivars and media was observed. Cultivar kisswany was the best in regeneration (38%) and medium MS47 was the best among used media (35%). Light type played a significant role in regeneration of plants where red light was much better than white light in inducing regeneration (68% vs 36%). ANOVA revealed significant effect of low doses of gamma irradiation on stimulation regeneration of plant whereas high doses prevented regeneration. Many experiments were conducted to isolate protoplast and regenerate plants. The best method for culturing was the droplet and the best conditions for incubation were complete darkness at 25 Degreed centigrade. This lead to formation of cell wall but no cell division was observed (author)

  16. Overpotential-induced lability of the electronic overlap factor in long-range electrochemical electron transfer: charge and distance dependence

    DEFF Research Database (Denmark)

    Kornyshev, A. A.; Kuznetsov, A. M.; Nielsen, Jens Ulrik

    2000-01-01

    Long-distance electrochemical electron transfer exhibits approximately exponential dependence on the electron transfer distance. On the basis of a jellium model of the metal surface we show that the slope of the logarithm of the current vs. the transfer distance also depends strongly...

  17. Monte Carlo calculations of electron beam quality conversion factors for several ion chamber types

    Energy Technology Data Exchange (ETDEWEB)

    Muir, B. R., E-mail: Bryan.Muir@nrc-cnrc.gc.ca [Measurement Science and Standards, National Research Council Canada, 1200 Montreal Road, Ottawa, Ontario K1A 0R6 (Canada); Rogers, D. W. O., E-mail: drogers@physics.carleton.ca [Carleton Laboratory for Radiotherapy Physics, Physics Department, Carleton University, 1125 ColonelBy Drive, Ottawa, Ontario K1S 5B6 (Canada)

    2014-11-01

    Purpose: To provide a comprehensive investigation of electron beam reference dosimetry using Monte Carlo simulations of the response of 10 plane-parallel and 18 cylindrical ion chamber types. Specific emphasis is placed on the determination of the optimal shift of the chambers’ effective point of measurement (EPOM) and beam quality conversion factors. Methods: The EGSnrc system is used for calculations of the absorbed dose to gas in ion chamber models and the absorbed dose to water as a function of depth in a water phantom on which cobalt-60 and several electron beam source models are incident. The optimal EPOM shifts of the ion chambers are determined by comparing calculations of R{sub 50} converted from I{sub 50} (calculated using ion chamber simulations in phantom) to R{sub 50} calculated using simulations of the absorbed dose to water vs depth in water. Beam quality conversion factors are determined as the calculated ratio of the absorbed dose to water to the absorbed dose to air in the ion chamber at the reference depth in a cobalt-60 beam to that in electron beams. Results: For most plane-parallel chambers, the optimal EPOM shift is inside of the active cavity but different from the shift determined with water-equivalent scaling of the front window of the chamber. These optimal shifts for plane-parallel chambers also reduce the scatter of beam quality conversion factors, k{sub Q}, as a function of R{sub 50}. The optimal shift of cylindrical chambers is found to be less than the 0.5 r{sub cav} recommended by current dosimetry protocols. In most cases, the values of the optimal shift are close to 0.3 r{sub cav}. Values of k{sub ecal} are calculated and compared to those from the TG-51 protocol and differences are explained using accurate individual correction factors for a subset of ion chambers investigated. High-precision fits to beam quality conversion factors normalized to unity in a beam with R{sub 50} = 7.5 cm (k{sub Q}{sup ′}) are provided. These

  18. Promoter hypermethylation contributes to frequent inactivation of a putative conditional tumor suppressor gene connective tissue growth factor in ovarian cancer.

    Science.gov (United States)

    Kikuchi, Ryoko; Tsuda, Hitoshi; Kanai, Yae; Kasamatsu, Takahiro; Sengoku, Kazuo; Hirohashi, Setsuo; Inazawa, Johji; Imoto, Issei

    2007-08-01

    Connective tissue growth factor (CTGF) is a secreted protein belonging to the CCN family, members of which are implicated in various biological processes. We identified a homozygous loss of CTGF (6q23.2) in the course of screening a panel of ovarian cancer cell lines for genomic copy number aberrations using in-house array-based comparative genomic hybridization. CTGF mRNA expression was observed in normal ovarian tissue and immortalized ovarian epithelial cells but was reduced in many ovarian cancer cell lines without its homozygous deletion (12 of 23 lines) and restored after treatment with 5-aza 2'-deoxycytidine. The methylation status around the CTGF CpG island correlated inversely with the expression, and a putative target region for methylation showed promoter activity. CTGF methylation was frequently observed in primary ovarian cancer tissues (39 of 66, 59%) and inversely correlated with CTGF mRNA expression. In an immunohistochemical analysis of primary ovarian cancers, CTGF protein expression was frequently reduced (84 of 103 cases, 82%). Ovarian cancer tended to lack CTGF expression more frequently in the earlier stages (stages I and II) than the advanced stages (stages III and IV). CTGF protein was also differentially expressed among histologic subtypes. Exogenous restoration of CTGF expression or treatment with recombinant CTGF inhibited the growth of ovarian cancer cells lacking its expression, whereas knockdown of endogenous CTGF accelerated growth of ovarian cancer cells with expression of this gene. These results suggest that epigenetic silencing by hypermethylation of the CTGF promoter leads to a loss of CTGF function, which may be a factor in the carcinogenesis of ovarian cancer in a stage-dependent and/or histologic subtype-dependent manner.

  19. State of oral hygiene and identification of the main risk factors for inflammatory diseases of periodontal tissues in young people

    Directory of Open Access Journals (Sweden)

    Makarenko M.V.

    2014-09-01

    Full Text Available A high percentage of prevalence of inflammatory periodontal diseases in young age causes urgency of treatment and prevention of inflammatory diseases of periodontal tissue in young age. Therefore, the research purpose was to investigate the hygienic condition and identification of the main risk factors for gingivitis in patients aged 18-30 years. 286 people aged from 18 to 30 years were observed in the study. To assess hygienic condition of the oral cavity and to determine the thickness of plaque indices OHI-S (simplified oral hygiene index Green Vermilyona and Silness Loe were used. Studies of oral hygiene status suggests that in patients with different etiologies of periodontal tissue inflammation, oral hygienic condition ranged from "satisfactory" to "poor." Therefore the results of study of hygiene and periodontal indices and samples confirmed presence of moderately expressed inflammation in the gums in young adults with chronic catarrhal gingivitis. Most often inflammation in the gums, namely, chronic catarrhal gingivitis was determined in patients with fixed prosthesis designs in the mouth or in violation of the bite, related to the major risk factors for periodontal disease occurring in young adults aged from 18 to 30 years.

  20. Impact of geriatric factors on surgical and prognostic outcomes in elderly patients with soft-tissue sarcoma.

    Science.gov (United States)

    Tsuda, Yusuke; Ogura, Koichi; Kobayashi, Eisuke; Hiruma, Toru; Iwata, Shintaro; Asano, Naofumi; Kawai, Akira; Chuman, Hirokazu; Ishii, Takeshi; Morioka, Hideo; Kobayashi, Hiroshi; Kawano, Hirotaka

    2017-05-01

    Patients aged ≥65 years requiring surgery for soft-tissue sarcoma are a concern in an aging society. We aimed to reveal the association of clinical/geriatric factors with survival period or postoperative events in such patients who underwent surgery. We enrolled patients aged ≥65 years who underwent surgery for localized soft-tissue sarcoma at five institutions. We retrospectively collected clinical/geriatric factors and laboratory data, and analyzed their association with outcomes using univariate and multivariate analyses. Among the 202 patients included, mean age at presentation was 73 years. Surgical margin was R0 in 139 patients (69%). The Eastern Cooperative Oncology Group performance status was ≥2 in 15 (7%). Thirty patients (15%) showed thinness (body mass index sarcoma-specific survival (hazard ratio for R1 vs. R0, 3.17; P = 0.001) and event-free survival (hazard ratio for R1 vs. R0, 2.56; P sarcoma-specific survival (hazard ratio for ≥2 vs. 0 or 1, 2.15; P = 0.038), and higher sensitivity-modified Glasgow prognostic score was significantly associated with poor event-free survival (hazard ratio for ≥1 vs. 0, 1.74; P = 0.046). Severe thinness (body mass index sarcoma patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Tissue factor levels and the fibrinolytic system in thin and thick intraluminal thrombus and underlying walls of abdominal aortic aneurysms.

    Science.gov (United States)

    Siennicka, Aldona; Zuchowski, Marta; Kaczmarczyk, Mariusz; Cnotliwy, Miłosław; Clark, Jeremy Simon; Jastrzębska, Maria

    2018-03-20

    The hemostatic system cooperates with proteolytic degradation in processes allowing abdominal aortic aneurysm (AAA) formation. In previous studies, it has been suggested that aneurysm rupture depends on intraluminal thrombus (ILT) thickness, which varies across each individual aneurysm. We hypothesized that hemostatic components differentially accumulate in AAA tissue in relation to ILT thickness. Thick (A1) and thin (B1) segments of ILTs and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1) from one aneurysm sac were taken from 35 patients undergoing elective repair. Factor levels were measured using enzyme-linked immunosorbent assay of protein extract. Tissue factor (TF) activities were significantly higher in thinner segments of AAA (B1 vs A1, P = .003; B vs A, P thick thrombus-covered wall segments (A) than in B, A1, and B1 (P = .015, P thick ILT (P = .021) and thick ILT (A1; P thick ILT (A1). However, no correlations were found at B sites, except for a correlation between plasmin and TF activities (r = 0.55; P = .004). These results suggest that higher TF activities are present in thinner AAA regions. These parameters and local fibrinolysis may be part of the processes leading to destruction of the aneurysm wall. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  2. BMP9 inhibits the bone metastasis of breast cancer cells by downregulating CCN2 (connective tissue growth factor, CTGF) expression.

    Science.gov (United States)

    Ren, Wei; Sun, Xiaoxiao; Wang, Ke; Feng, Honglei; Liu, Yuehong; Fei, Chang; Wan, Shaoheng; Wang, Wei; Luo, Jinyong; Shi, Qiong; Tang, Min; Zuo, Guowei; Weng, Yaguang; He, Tongchuan; Zhang, Yan

    2014-03-01

    Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration, and apoptosis. BMP9, the latest BMP to be discovered, is reportedly expressed in a variety of human carcinoma cell lines, but the role of BMP9 in breast cancer has not been fully clarified. In a previous study, BMP9 was found to inhibit the growth, migration, and invasiveness of MDA-MB-231 breast cancer cells. In the current study, the effect of BMP9 on the bone metastasis of breast cancer cells was investigated. After absent or low expression of BMP9 was detected in the MDA-MB-231 breast cancer cells and breast non-tumor adjacent tissues using Western blot and immunohistochemistry, In our previous study, BMP9 could inhibit the proliferation and invasiveness of breast cancer cells MDA-MB-231 in vitro and in vivo. This paper shows that BMP9 inhibit the bone metastasis of breast cancer cells by activating the BMP/Smad signaling pathway and downregulating connective tissue growth factor (CTGF); however, when CTGF expression was maintained, the inhibitory effect of BMP9 on the MDA-MB-231 cells was abolished. Together, these observations indicate that BMP9 is an important mediator of breast cancer bone metastasis and a potential therapeutic target for treating this deadly disease.

  3. Human inter-α-inhibitor is a substrate for factor XIIIa and tissue transglutaminase

    DEFF Research Database (Denmark)

    Sonne-Schmidt, Carsten Scavenius; Sanggaard, Kristian W; Nikolajsen, Camilla L

    2011-01-01

    that inter-α-inhibitor is cross-linked to the fibrin clot in a 1:20 ratio relative to the known factor XIIIa substrate α2-antiplasmin. This interaction may protect fibrin or other Lys-donating proteins from adventitious proteolysis by increasing the local concentration of bikunin. In addition, the reaction...... may influence the TSG-6/heavy Chain 2-mediated transfer of heavy chains observed during inflammation....

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

    Science.gov (United States)

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

    2012-01-01

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

  5. Correlative two-photon and serial block face scanning electron microscopy in neuronal tissue using 3D near-infrared branding maps.

    Science.gov (United States)

    Lees, Robert M; Peddie, Christopher J; Collinson, Lucy M; Ashby, Michael C; Verkade, Paul

    2017-01-01

    Linking cellular structure and function has always been a key goal of microscopy, but obtaining high resolution spatial and temporal information from the same specimen is a fundamental challenge. Two-photon (2P) microscopy allows imaging d