WorldWideScience

Sample records for del receptor gm-csf

  1. Targeting the GM-CSF receptor for the treatment of CNS autoimmunity.

    Science.gov (United States)

    Ifergan, Igal; Davidson, Todd S; Kebir, Hania; Xu, Dan; Palacios-Macapagal, Daphne; Cann, Jennifer; Rodgers, Jane M; Hunter, Zoe N; Pittet, Camille L; Beddow, Sara; Jones, Clare A; Prat, Alexandre; Sleeman, Matthew A; Miller, Stephen D

    2017-11-01

    In multiple sclerosis (MS), there is a growing interest in inhibiting the pro-inflammatory effects of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to evaluate the therapeutic potential and underlying mechanisms of GM-CSF receptor alpha (Rα) blockade in animal models of MS. We show that GM-CSF signaling inhibition at peak of chronic experimental autoimmune encephalomyelitis (EAE) results in amelioration of disease progression. Similarly, GM-CSF Rα blockade in relapsing-remitting (RR)-EAE model prevented disease relapses and inhibited T cell responses specific for both the inducing and spread myelin peptides, while reducing activation of mDCs and inflammatory monocytes. In situ immunostaining of lesions from human secondary progressive MS (SPMS), but not primary progressive MS patients shows extensive recruitment of GM-CSF Rα + myeloid cells. Collectively, this study reveals a pivotal role of GM-CSF in disease relapses and the benefit of GM-CSF Rα blockade as a potential novel therapeutic approach for treatment of RRMS and SPMS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Molecular cloning of a second subunit of the receptor for human granulocyte - macrophage colony-stimulating factor (GM-CSF): Reconstitution of a high-affinity GM-CSF receptor

    International Nuclear Information System (INIS)

    Hayashida, Kazuhiro; Kitamura, Toshio; Gorman, D.M.; Miyajima, Atsushi; Arai, Kenichi; Yokota, Takashi

    1990-01-01

    Using the mouse interleukin 3 (IL-3) receptor cDNA as a probe, the authors obtained a monologous cDNA (KH97) from a cDNA library of a human hemopoietic cell line, TF-1. The protein encoded by the KH97 cDNA has 56% amino acid sequence identity with the mouse IL-3 receptor and retains features common to the family of cytokine receptors. Fibroblasts transfected with the KH97 cDNA expressed a protein of 120 kDa but did not bind any human cytokines, including IL-3 and granulocyte - macrophage colony-stimulating factor (GM-CSF). Interestingly, cotransfection of cDNAs for KH97 and the low-affinity human GM-CSF receptor in fibroblasts resulted in formation of a high-affinity receptor for GM-CSF. The dissociation rate of GM-CSF from the reconstituted high-affinity receptor was slower than that from the low-affinity site, whereas the association rate was unchanged. Cross-linking of 125 I-labeled GM-CSF to fibroblasts cotransfected with both cDNAs revealed the same cross-linking patterns as in TF-1 cells - i.e., two major proteins of 80 and 120 kDa which correspond to the low-affinity GM-CSF receptor and the KH97 protein, respectively. These results indicate that the high-affinity GM-CSF receptor is composed of at least two components in a manner analogous to the IL-2 receptor. They therefore propose to designate the low-affinity GM-CSF receptor and the KH97 protein as the α and β subunits of the GM-CSF receptor, respectively

  3. GM-CSF, IL-3 and G-CSF receptors on acute myeloid leukemia cells : function, regulation of expression, and ligand binding characteristics

    NARCIS (Netherlands)

    L.M. Budel (Leo)

    1993-01-01

    textabstractIL-3, GM-CSF and G-CSF stimulate proliferation of human acute myeloid leukemia in vitro, but patterns of response among clinical cases are diverse. As described in Chapters 2 and 3, numbers and affinity of IL-3, GM-CSF and G-CSF receptors on cells of patients with AML were assessed and

  4. GM-CSF/IL-3/IL-5 receptor common β chain (CD131 expression as a biomarker of antigen-stimulated CD8+ T cells

    Directory of Open Access Journals (Sweden)

    Maric Dragan

    2008-04-01

    Full Text Available Abstract Background Upon Ag-activation cytotoxic T cells (CTLs produce IFN-γ GM-CSF and TNF-α, which deliver simultaneously pro-apoptotic and pro-inflammatory signals to the surrounding microenvironment. Whether this secretion affects in an autocrine loop the CTLs themselves is unknown. Methods Here, we compared the transcriptional profile of Ag-activated, Flu-specific CTL stimulated with the FLU M1:58-66 peptide to that of convivial CTLs expanded in vitro in the same culture. PBMCs from 6 HLA-A*0201 expressing donors were expanded for 7 days in culture following Flu M1:58-66 stimulation in the presence of 300 IU/ml of interleukin-2 and than sorted by high speed sorting to high purity CD8+ expressing T cells gated according to FluM1:58-66 tetrameric human leukocyte antigen complexes expression. Results Ag-activated CTLs displayed higher levels of IFN-γ, GM-CSF (CSF2 and GM-CSF/IL-3/IL-5 receptor common β- chain (CD131 but lacked completely expression of IFN-γ receptor-II and IFN-stimulated genes (ISGs. This observation suggested that Ag-activated CTLs in preparation for the release of IFN-γ and GM-CSF shield themselves from the potentially apoptotic effects of the former entrusting their survival to GM-SCF. In vitro phenotyping confirmed the selective surface expression of CD131 by Ag-activated CTLs and their increased proliferation upon exogenous administration of GM-CSF. Conclusion The selective responsiveness of Ag-activated CTLs to GM-CSF may provide an alternative explanation to the usefulness of this chemokine as an adjuvant for T cell aimed vaccines. Moreover, the selective expression of CD131 by Ag-activated CTLs proposes CD131 as a novel biomarker of Ag-dependent CTL activation.

  5. Novel adapter proteins that link the human GM-CSF receptor to the phosphatidylino-sitol 3-kinase and Shc/Grb2/ras signaling pathways.

    Science.gov (United States)

    Jücker, M; Feldman, R A

    1996-01-01

    We have used a human GM-CSF-dependent hematopoietic cell line that responds to physiological concentrations of hGM-CSF to analyze a set of signaling events that occur in normal myelopoiesis and whose deregulation may lead to leukemogenesis. Stimulation of these cells with hGM-CSF induced the assembly of multimeric complexes that contained known and novel phosphotyrosyl proteins. One of the new proteins was a major phosphotyrosyl substrate of 76-85 kDa (p80) that was directly associated with the p85 subunit of phosphatidylinositol (PI) 3-kinase through the SH2 domains of p85. p80 also associated with the beta subunit of the activated hGM-CSF receptor, and assembly of this complex correlated with activation of PI 3-kinase. A second phosphotyrosyl protein we identified, p140, associated with the Shc and Grb2 adapter proteins by direct binding to a novel phosphotyrosine-interacting domain located at the N-terminus of Shc. and to the SH3 domains of Grb2, respectively. The Shc/p140/Grb2 complex was found to be constitutively activated in acute myeloid leukemia cells, indicating that activation of this pathway may be a necessary step in the development of some leukemias. The p80/p85/PI 3-kinase and the Shc/Grb2/p140 complexes were tightly associated with Src family kinases, which were prime candidates for phosphorylation of Shc, p80, p140 and other phosphotyrosyl substrates present in these complexes. Our studies suggest that p80 and p140 may link the hGM-CSF receptor to the PI 3-kinase and Shc/Grb2/ras signaling pathways, respectively, and that abnormal activation of hGM-CSF-dependent targets may play a role in leukemogenesis.

  6. The Activin A-Peroxisome Proliferator-Activated Receptor Gamma Axis Contributes to the Transcriptome of GM-CSF-Conditioned Human Macrophages.

    Science.gov (United States)

    Nieto, Concha; Bragado, Rafael; Municio, Cristina; Sierra-Filardi, Elena; Alonso, Bárbara; Escribese, María M; Domínguez-Andrés, Jorge; Ardavín, Carlos; Castrillo, Antonio; Vega, Miguel A; Puig-Kröger, Amaya; Corbí, Angel L

    2018-01-01

    GM-CSF promotes the functional maturation of lung alveolar macrophages (A-MØ), whose differentiation is dependent on the peroxisome proliferator-activated receptor gamma (PPARγ) transcription factor. In fact, blockade of GM-CSF-initiated signaling or deletion of the PPARγ-encoding gene PPARG leads to functionally defective A-MØ and the onset of pulmonary alveolar proteinosis. In vitro , macrophages generated in the presence of GM-CSF display potent proinflammatory, immunogenic and tumor growth-limiting activities. Since GM-CSF upregulates PPARγ expression, we hypothesized that PPARγ might contribute to the gene signature and functional profile of human GM-CSF-conditioned macrophages. To verify this hypothesis, PPARγ expression and activity was assessed in human monocyte-derived macrophages generated in the presence of GM-CSF [proinflammatory GM-CSF-conditioned human monocyte-derived macrophages (GM-MØ)] or M-CSF (anti-inflammatory M-MØ), as well as in ex vivo isolated human A-MØ. GM-MØ showed higher PPARγ expression than M-MØ, and the expression of PPARγ in GM-MØ was found to largely depend on activin A. Ligand-induced activation of PPARγ also resulted in distinct transcriptional and functional outcomes in GM-MØ and M-MØ. Moreover, and in the absence of exogenous activating ligands, PPARγ knockdown significantly altered the GM-MØ transcriptome, causing a global upregulation of proinflammatory genes and significantly modulating the expression of genes involved in cell proliferation and migration. Similar effects were observed in ex vivo isolated human A-MØ, where PPARγ silencing led to enhanced expression of genes coding for growth factors and chemokines and downregulation of cell surface pathogen receptors. Therefore, PPARγ shapes the transcriptome of GM-CSF-dependent human macrophages ( in vitro derived GM-MØ and ex vivo isolated A-MØ) in the absence of exogenous activating ligands, and its expression is primarily regulated by activin A

  7. CC chemokine receptor 4 is required for experimental autoimmune encephalomyelitis by regulating GM-CSF and IL-23 production in dendritic cells

    Science.gov (United States)

    Poppensieker, Karola; Otte, David-Marian; Schürmann, Britta; Limmer, Andreas; Dresing, Philipp; Drews, Eva; Schumak, Beatrix; Klotz, Luisa; Raasch, Jennifer; Mildner, Alexander; Waisman, Ari; Scheu, Stefanie; Knolle, Percy; Förster, Irmgard; Prinz, Marco; Maier, Wolfgang; Zimmer, Andreas; Alferink, Judith

    2012-01-01

    Dendritic cells (DCs) are pivotal for the development of experimental autoimmune encephalomyelitis (EAE). However, the mechanisms by which they control disease remain to be determined. This study demonstrates that expression of CC chemokine receptor 4 (CCR4) by DCs is required for EAE induction. CCR4−/− mice presented enhanced resistance to EAE associated with a reduction in IL-23 and GM-CSF expression in the CNS. Restoring CCR4 on myeloid cells in bone marrow chimeras or intracerebral microinjection of CCR4-competent DCs, but not macrophages, restored EAE in CCR4−/− mice, indicating that CCR4+ DCs are cellular mediators of EAE development. Mechanistically, CCR4−/− DCs were less efficient in GM-CSF and IL-23 production and also TH-17 maintenance. Intraspinal IL-23 reconstitution restored EAE in CCR4−/− mice, whereas intracerebral inoculation using IL-23−/− DCs or GM-CSF−/− DCs failed to induce disease. Thus, CCR4-dependent GM-CSF production in DCs required for IL-23 release in these cells is a major component in the development of EAE. Our study identified a unique role for CCR4 in regulating DC function in EAE, harboring therapeutic potential for the treatment of CNS autoimmunity by targeting CCR4 on this specific cell type. PMID:22355103

  8. Mapping of monoclonal antibody- and receptor-binding domains on human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) using a surface plasmon resonance-based biosensor.

    Science.gov (United States)

    Laricchia-Robbio, L; Liedberg, B; Platou-Vikinge, T; Rovero, P; Beffy, P; Revoltella, R P

    1996-10-01

    An automated surface plasmon resonance (SPR)-based biosensor system has been used for mapping antibody and receptor-binding regions on the recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) molecule. A rabbit antimouse IgG1-Fc antibody (RAM.Fc) was coupled to an extended carboxymethylated-hydrogel matrix attached to a gold surface in order to capture an anti-rhGM-CSF monoclonal antibody (MAb) injected over the sensing layer. rhGM-CSF was subsequently injected and allowed to bind to this antibody. Multisite binding assays were then performed, by flowing sequentially other antibodies and peptides over the surface, and the capacity of the latter to interact with the entrapped rhGM-CSF in a multimolecular complex was monitored in real time with SPR. Eleven MAb (all IgG1K), were analyzed: respectively, four antipeptide MAb raised against three distinct epitopes of the cytokine (two clones against residues 14-24, that includes part of the first alpha-helix toward the N-terminal region; one clone against peptide 30-41, an intrahelical loop; and one clone against residues 79-91, including part of the third alpha-helix) and seven antiprotein MAbs raised against the entire rhGM-CSF, whose target native epitopes are still undetermined. In addition, the binding capacity to rhGM-CSF of a synthetic peptide, corresponding to residues 238-254 of the extracellular human GM-CSF receptor alpha-chain, endowed with rhGM-CSF binding activity, was tested. The results from experiments performed with the biosensor were compared with those obtained by a sandwich enzyme-linked immunosorbent assay (ELISA), using the same reagents. The features of the biosensor technology (fully automated, measure in real time, sharpened yes/no response, less background disturbances, no need for washing step or labeling of the reagent) offered several advantages in these studies of MAb immunoreactivity and epitope mapping, giving a much better resolution and enabling more distinct

  9. Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis.

    Science.gov (United States)

    Al-Mossawi, M H; Chen, L; Fang, H; Ridley, A; de Wit, J; Yager, N; Hammitzsch, A; Pulyakhina, I; Fairfax, B P; Simone, D; Yi, Yao; Bandyopadhyay, S; Doig, K; Gundle, R; Kendrick, B; Powrie, F; Knight, J C; Bowness, P

    2017-11-15

    Spondyloarthritis encompasses a group of common inflammatory diseases thought to be driven by IL-17A-secreting type-17 lymphocytes. Here we show increased numbers of GM-CSF-producing CD4 and CD8 lymphocytes in the blood and joints of patients with spondyloarthritis, and increased numbers of IL-17A + GM-CSF + double-producing CD4, CD8, γδ and NK cells. GM-CSF production in CD4 T cells occurs both independently and in combination with classical Th1 and Th17 cytokines. Type 3 innate lymphoid cells producing predominantly GM-CSF are expanded in synovial tissues from patients with spondyloarthritis. GM-CSF + CD4 + cells, isolated using a triple cytokine capture approach, have a specific transcriptional signature. Both GM-CSF + and IL-17A + GM-CSF + double-producing CD4 T cells express increased levels of GPR65, a proton-sensing receptor associated with spondyloarthritis in genome-wide association studies and pathogenicity in murine inflammatory disease models. Silencing GPR65 in primary CD4 T cells reduces GM-CSF production. GM-CSF and GPR65 may thus serve as targets for therapeutic intervention of spondyloarthritis.

  10. Granulocyte macrophage colony stimulating factor (GM-CSF biological actions on human dermal fibroblasts

    Directory of Open Access Journals (Sweden)

    S Montagnani

    2009-12-01

    Full Text Available Fibroblasts are involved in all pathologies characterized by increased ExtraCellularMatrix synthesis, from wound healing to fibrosis. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF is a cytokine isolated as an hemopoietic growth factor but recently indicated as a differentiative agent on endothelial cells. In this work we demonstrated the expression of the receptor for GM-CSF (GMCSFR on human normal skin fibroblasts from healthy subjects (NFPC and on a human normal fibroblast cell line (NHDF and we try to investigate the biological effects of this cytokine. Human normal fibroblasts were cultured with different doses of GM-CSF to study the effects of this factor on GMCSFR expression, on cell proliferation and adhesion structures. In addition we studied the production of some Extra-Cellular Matrix (ECM components such as Fibronectin, Tenascin and Collagen I. The growth rate of fibroblasts from healthy donors (NFPC is not augmented by GM-CSF stimulation in spite of increased expression of the GM-CSFR. On the contrary, the proliferation of normal human dermal fibroblasts (NHDF cell line seems more influenced by high concentration of GM-CSF in the culture medium. The adhesion structures and the ECM components appear variously influenced by GM-CSF treatment as compared to fibroblasts cultured in basal condition, but newly only NHDF cells are really induced to increase their synthesis activity. We suggest that the in vitro treatment with GM-CSF can shift human normal fibroblasts towards a more differentiated state, due or accompanied by an increased expression of GM-CSFR and that such “differentiation” is an important event induced by such cytokine.

  11. Molecular cloning, sequencing and structural studies of granulocyte-macrophage colony-stimulating factor (GM-CSF) from Indian water buffalo (Bubalus bubalis)

    KAUST Repository

    Sugumar, Thennarasu; Ganesan, Pugalenthi; Harishankar, Murugesan; Dhinakar Raj, Gopal

    2013-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that is essential for growth and development of progenitors of granulocytes and monocytes/macrophages. In this study, we report molecular cloning, sequencing and characterization of GM-CSF from Indian water buffalo, Bubalus bubalis. In addition, we performed sequence and structural analysis for buffalo GM-CSF. Buffalo GM-CSF has been compared with 17 mammalian GM-CSFs using multiple sequence alignment and phylogenetic tree. Three-dimensional model for buffalo GM-CSF and human receptor complex was built using homology modelling to study cross-reactivity between two species. Detailed analysis was performed to study GM-CSF interface and various interactions at the interface. © 2013 John Wiley & Sons Ltd.

  12. Molecular cloning, sequencing and structural studies of granulocyte-macrophage colony-stimulating factor (GM-CSF) from Indian water buffalo (Bubalus bubalis)

    KAUST Repository

    Sugumar, Thennarasu

    2013-06-25

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that is essential for growth and development of progenitors of granulocytes and monocytes/macrophages. In this study, we report molecular cloning, sequencing and characterization of GM-CSF from Indian water buffalo, Bubalus bubalis. In addition, we performed sequence and structural analysis for buffalo GM-CSF. Buffalo GM-CSF has been compared with 17 mammalian GM-CSFs using multiple sequence alignment and phylogenetic tree. Three-dimensional model for buffalo GM-CSF and human receptor complex was built using homology modelling to study cross-reactivity between two species. Detailed analysis was performed to study GM-CSF interface and various interactions at the interface. © 2013 John Wiley & Sons Ltd.

  13. Pivotal Roles of GM-CSF in Autoimmunity and Inflammation

    Science.gov (United States)

    Shiomi, Aoi; Usui, Takashi

    2015-01-01

    Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor, which stimulates the proliferation of granulocytes and macrophages from bone marrow precursor cells. In autoimmune and inflammatory diseases, Th17 cells have been considered as strong inducers of tissue inflammation. However, recent evidence indicates that GM-CSF has prominent proinflammatory functions and that this growth factor (not IL-17) is critical for the pathogenicity of CD4+ T cells. Therefore, the mechanism of GM-CSF-producing CD4+ T cell differentiation and the role of GM-CSF in the development of autoimmune and inflammatory diseases are gaining increasing attention. This review summarizes the latest knowledge of GM-CSF and its relationship with autoimmune and inflammatory diseases. The potential therapies targeting GM-CSF as well as their possible side effects have also been addressed in this review. PMID:25838639

  14. Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy

    Science.gov (United States)

    Bhattacharya, Palash; Budnick, Isadore; Singh, Medha; Thiruppathi, Muthusamy; Alharshawi, Khaled; Elshabrawy, Hatem; Holterman, Mark J.

    2015-01-01

    Granulocyte macrophage colony stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine. Its inflammatory activity is primarily due its role as a growth and differentiation factor for granulocyte and macrophage populations. In this capacity, among other clinical applications, it has been used to bolster anti-tumor immune responses. GM-CSF-mediated inflammation has also been implicated in certain types of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Thus, agents that can block GM-CSF or its receptor have been used as anti-inflammatory therapies. However, a review of literature reveals that in many situations GM-CSF can act as an anti-inflammatory/regulatory cytokine. We and others have shown that GM-CSF can modulate dendritic cell differentiation to render them “tolerogenic,” which, in turn, can increase regulatory T-cell numbers and function. Therefore, the pro-inflammatory and regulatory effects of GM-CSF appear to depend on the dose and the presence of other relevant cytokines in the context of an immune response. A thorough understanding of the various immunomodulatory effects of GM-CSF will facilitate more appropriate use and thus further enhance its clinical utility. PMID:25803788

  15. Epithelial GM-CSF induction by Candida glabrata.

    Science.gov (United States)

    Li, L; Dongari-Bagtzoglou, A

    2009-08-01

    The main cytokine induced by the interaction of oral epithelial cells with C. glabrata is granulocyte monocyte colony-stimulating factor (GM-CSF); however, the mechanisms regulating this response are unknown. Based on previously published information on the interactions of C. albicans with oral epithelial cells, we hypothesized that interaction with viable C. glabrata triggers GM-CSF synthesis via NF-kappaB activation. We found that C. glabrata-induced GM-CSF synthesis was adhesion-dependent, enhanced by endocytosis, and required fungal viability. NF-kappaB activation was noted during interaction of epithelial cells with C. glabrata, and pre-treatment with an NF-kappaB inhibitor partly inhibited GM-CSF synthesis. Blocking TLR4 with anti-TLR4 antibody did not inhibit GM-CSF production. In contrast, an anti-CDw17 antibody triggered significant inhibition of NF-kappaB activation and GM-CSF synthesis. beta-glucans did not stimulate GM-CSF synthesis, suggesting that the CDw17/NF-kappaB/GM-CSF pathway may be beta-glucan-independent. This study provides new insights into the mechanism of GM-CSF induction by C. glabrata.

  16. Activation of adenosine A3 receptors potentiates stimulatory effects of IL-3, SCF, and GM-CSF on mouse granulocyte-macrophage hematopoietic progenitor cells

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Vacek, Antonín; Pospíšil, Milan; Holá, Jiřina; Štreitová, Denisa; Znojil, V.

    2009-01-01

    Roč. 58, č. 2 (2009), s. 247-252 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/06/0015; GA ČR(CZ) GA305/08/0158 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : hematopoiesis * adenosine A3 receptor agonist * hematopoietic growth factors Subject RIV: BO - Biophysics Impact factor: 1.430, year: 2009

  17. Delivery of GM-CSF to Protect against Influenza Pneumonia

    Science.gov (United States)

    Subramaniam, Renuka; Hillberry, Zachary; Chen, Han; Feng, Yan; Fletcher, Kalyn; Neuenschwander, Pierre; Shams, Homayoun

    2015-01-01

    Background Since adaptive immunity is thought to be central to immunity against influenza A virus (IAV) pneumonias, preventive strategies have focused primarily on vaccines. However, vaccine efficacy has been variable, in part because of antigenic shift and drift in circulating influenza viruses. Recent studies have highlighted the importance of innate immunity in protecting against influenza. Methods Granulocyte-macrophage colony stimulating factor (GM-CSF) contributes to maturation of mononuclear phagocytes, enhancing their capacity for phagocytosis and cytokine production. Results Overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) in the lung of transgenic mice provides remarkable protection against IAV, which depends on alveolar macrophages (AM). In this study, we report that pulmonary delivery of GM-CSF to wild type young and aged mice abrogated mortality from IAV. Conclusion We also demonstrate that protection is species specific and human GM-CSF do not protect the mice nor stimulates mouse immunity. We also show that IAV-induced lung injury is the culprit for side-effects of GM-CSF in treating mice after IAV infection, and introduce a novel strategy to deliver the GM-CSF to and retain it in the alveolar space even after IAV infection. PMID:25923215

  18. Delivery of GM-CSF to Protect against Influenza Pneumonia.

    Directory of Open Access Journals (Sweden)

    Renuka Subramaniam

    Full Text Available Since adaptive immunity is thought to be central to immunity against influenza A virus (IAV pneumonias, preventive strategies have focused primarily on vaccines. However, vaccine efficacy has been variable, in part because of antigenic shift and drift in circulating influenza viruses. Recent studies have highlighted the importance of innate immunity in protecting against influenza.Granulocyte-macrophage colony stimulating factor (GM-CSF contributes to maturation of mononuclear phagocytes, enhancing their capacity for phagocytosis and cytokine production.Overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF in the lung of transgenic mice provides remarkable protection against IAV, which depends on alveolar macrophages (AM. In this study, we report that pulmonary delivery of GM-CSF to wild type young and aged mice abrogated mortality from IAV.We also demonstrate that protection is species specific and human GM-CSF do not protect the mice nor stimulates mouse immunity. We also show that IAV-induced lung injury is the culprit for side-effects of GM-CSF in treating mice after IAV infection, and introduce a novel strategy to deliver the GM-CSF to and retain it in the alveolar space even after IAV infection.

  19. Distinct changes in pulmonary surfactant homeostasis in common beta-chain-and GM-CSF-deficient mice

    NARCIS (Netherlands)

    Reed, JA; Ikegami, M; Robb, L; Begley, CG; Ross, G; Whitsett, JA

    Pulmonary alveolar proteinosis (PAP) is caused by inactivation of either granulocyte-macrophage colony-stimulating factor (GMCSF) or GM receptor common beta-chain (beta(c)) genes in mice [GM(-/-), beta(c)(-/-)], demonstrating a critical role of GM-CSF signaling in surfactant homeostasis. To

  20. Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

    Energy Technology Data Exchange (ETDEWEB)

    Malur, Anagha; Huizar, Isham [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Wells, Greg [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Barna, Barbara P. [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Malur, Achut G. [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Thomassen, Mary Jane, E-mail: thomassenm@ecu.edu [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. Black-Right-Pointing-Pointer Up-regulation of ABCG1 improves lung function. Black-Right-Pointing-Pointer Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) and the PPAR{gamma}-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an upregulator of PPAR{gamma}. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO) mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPAR{gamma} plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPAR{gamma} or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by

  1. Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

    International Nuclear Information System (INIS)

    Malur, Anagha; Huizar, Isham; Wells, Greg; Barna, Barbara P.; Malur, Achut G.; Thomassen, Mary Jane

    2011-01-01

    Highlights: ► Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. ► Up-regulation of ABCG1 improves lung function. ► Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ) and the PPARγ-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte–macrophage colony stimulating factor (GM-CSF), an upregulator of PPARγ. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO) mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPARγ plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPARγ or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by analysis of bronchoalveolar lavage fluid. Lung compliance was diminished in untreated GMCSF KO mice

  2. GM-CSF enhances tumor invasion by elevated MMP-2, -9, and -26 expression

    International Nuclear Information System (INIS)

    Gutschalk, Claudia M; Yanamandra, Archana K; Linde, Nina; Meides, Alice; Depner, Sofia; Mueller, Margareta M

    2013-01-01

    Granulocyte–macrophage colony-stimulating factor (GM-CSF) promotes tumor progression in different tumor models in an autocrine and paracrine manner. However, at the same time GM-CSF is used in cancer therapies to ameliorate neutropenia. We have previously shown in GM-CSF and G-CSF expressing or negative skin or head and neck squamous cell carcinoma that GM-CSF expression is associated with a highly angiogenic and invasive tumor phenotype. To determine the functional contribution of GM-CSF to tumor invasion, we stably transfected a GM-CSF negative colon adenocarcinoma cell line HT-29 with GM-CSF or treated the same cell line with exogenous GM-CSF. While GM-CSF overexpression and treatment reduced tumor cell proliferation and tumor growth in vitro and in vivo, respectively, it contributed to tumor progression. Together with an enhanced migratory capacity in vitro, we observed a striking increase in tumor cell invasion into the surrounding tissue concomitant with the induction of an activated tumor stroma in GM-CSF overexpressing or GM-CSF treated tumors. In a complex 3D in vitro model, enhanced GM-CSF expression was associated with a discontinued basement membrane deposition that might be mediated by the increased expression and activation of MMP-2, -9, and -26. Treatment with GM-CSF blocking antibodies reversed this effect. The increased presence and activity of these tumor cell derived proteases was confirmed in vivo. Here, expression of MMP-26 protein was predominantly located in pre- and early-invasive areas suggesting MMP-26 expression as an early event in promoting GM-CSF dependent tumor invasion

  3. Recombinant Granulocyte-Macrophage Colony-Stimulating Factor (rGM-CSF) : A Review of its Pharmacological Properties and Prospective Role in the Management of Myelosuppression.

    Science.gov (United States)

    Grant, Susan M; Heel, Rennie C

    1992-04-01

    their use remain to be clarified. Nonetheless, as one of a small group of novel agents rGM-CSF has major potential in the management of myelosuppression secondary to cytoreductive therapy with or without bone marrow transplantation, and in amelioration of disturbed myelopoiesis. It represents an important application of biotechnology to a difficult area of therapeutics. Endogenous GM-CSF is produced by T-lymphocytes, macrophages, fibroblasts and endothelial cells, and participates both in the complex regulation of blood cell formation and in activation of mature leucocytes. It is a polypeptide which is variably glycosylated in its native state although the carbohydrate content is not essential for its biological effects, and the 3 available recombinant forms (which differ in extent of glycosylation) are similarly active in vivo. Proliferative activity and priming of mature cells are manifest at similar picomolar concentrations of GM-CSF, and it is the programming of the cell which appears to determine the response to binding of GM-CSF to its cell surface receptor. In concert with other colony-stimulating factors, GM-CSF facilitates lineage commitment and subsequently supports or amplifies the clonogenic activity of lineage-restricted factors, with the strongest effect seen on the granulocyte-macrophage lineage. A biphasic response was seen when rGM-CSF was administered in doses up to 1000 µg/m 2 /day or 60 µg/kg/day by subcutaneous or intravenous routes in phase I/II trials. Peripheral blood leucocyte counts decreased rapidly and profoundly secondary to sequestration within the lungs. Re-entry of these cells into the circulation restores counts to baseline in 2 to 4 hours and thereafter an increase in the proliferative fraction of haematopoietic cells in bone marrow probably accounts for the progressive rise in the number of neutrophils, eosinophils and monocytes. This effect is dose-proportional. GM-CSF stimulates proliferation of leukaemic progenitors from patients

  4. Novel insights in preventing Gram-negative bacterial infection in cirrhotic patients: review on the effects of GM-CSF in maintaining homeostasis of the immune system.

    Science.gov (United States)

    Xu, Dong; Zhao, Manzhi; Song, Yuhu; Song, Jianxin; Huang, Yuancheng; Wang, Junshuai

    2015-01-01

    Cirrhotic patients with dysfunctional and/or low numbers of leukocytes are often infected with bacteria, especially Gram-negative bacteria, which is characterized by producing lipopolysaccharide (LPS). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that influences the production, maturation, function, and survival of various immune cells. In this paper, we reviewed not only Toll-like receptors 4 (TLR4) signaling pathway and its immunological effect, but also the specific stimulating function and autocrine performance of GM-CSF on hematopoietic cells, as well as the recent discovery of innate response activator-B cells in protection against microbial sepsis and the direct LPS-TLR4 signaling on hematopoiesis. Thus we concluded that GM-CSF might play important roles in preventing Gram-negative bacterial infections in cirrhotic patients through maintaining immune system functions and homeostasis.

  5. MDSCs are involved in the protumorigenic potentials of GM-CSF in colitis-associated cancer.

    Science.gov (United States)

    Ma, Ning; Liu, Qilin; Hou, Lin; Wang, Yalin; Liu, Ziling

    2017-06-01

    Chronic inflammation is thought to be a major driving force for the development of colitis-associated colorectal cancer (CAC). As one member of proinflammatory cytokine family, granulocyte macrophage colony-stimulating factor (GM-CSF) has been identified to play a key role in CAC pathogenesis recently. The underlying mechanisms, however, remain largely unknown. In this study, we found that myeloid-derived suppressor cells (MDSCs) accumulated increasingly in the lesions during the progression from colitis to cancer, which was critical for CAC formation. Importantly, this MDSC accumulation was controlled by GM-CSF. MDSC number decreased significantly in GM-CSF-deficient mice suffering from CAC induction, and transfusion of MDSCs from wild-type CAC-bearing mice into GM-CSF-deficient counterparts led to recurrence of CAC. Furthermore, the supernatants of CAC lesions or GM-CSF alone was sufficient to differentiate hematopoietic precursors into MDSCs. Addition of neutralizing anti-GM-CSF antibody impaired the MDSC-differentiating effects of the supernatants of CAC lesions. Overall, these findings shed new insights into the mechanisms of GM-CSF underlying CAC development, by inducing/recruiting CAC-promoting MDSCs. Blocking GM-CSF activity or MDSC function may represent new therapeutic strategies for CAC in clinic.

  6. GM-CSF augments the immunosuppressive capacity of neonatal spleen cells in vitro

    International Nuclear Information System (INIS)

    Morrissey, P.J.; Ireland, R.

    1991-01-01

    Addition of exogenous granulocyte-macrophage colony stimulating factor (GM-CSF) to cultures of adult murine spleen cells with sheep red blood cells (SRBC) results in an augmented plaque forming cell (PFC) response. The influence of GM-CSF on the ability of neonatal spleen cells to suppress the anti-SRBC plaque forming response of adult spleen cells was tested by adding GM-CSF to cultures of neonatal and adult spleen cells. The suppressive capacity of the neonatal spleen cells was augmented by exogenous GM-CSF. The augmented suppression of the neonatal spleen cells was dependent on a G-10 adherent population since the addition of GM-CSF to cultures containing G-10 passed neonatal spleen cells resulted in an augmented PFC response and not suppression. Neonatal splenic glass adherent cells were also capable of suppressing the response. Neonatal spleen cells or purified neonatal glass adherent spleen cells cultured in the presence of GM-CSF had markedly increased levels of PGE2 in the culture supernatant. Neonatal spleen cells cultured with GM-CSF had increased numbers of morphologically identifiable macrophages after 48 hr of culture. Both irradiation and G-10 passage of the neonatal spleen diminished the numbers of macrophages formed in response to GM-CSF, and both of these manipulations resulted in reversal of suppression in response to GM-CSF. Thus, the augmented suppressive capacity of neonatal spleen cells in response to GM-CSF is probably mediated by its ability to drive monocyte to macrophage differentiation as well as increase the suppressive capacity of the existing neonatal splenic macrophages by increasing their production of PGE2

  7. MafB antagonizes phenotypic alteration induced by GM-CSF in microglia

    Energy Technology Data Exchange (ETDEWEB)

    Koshida, Ryusuke, E-mail: rkoshida-myz@umin.ac.jp; Oishi, Hisashi, E-mail: hoishi@md.tsukuba.ac.jp; Hamada, Michito; Takahashi, Satoru

    2015-07-17

    Microglia are tissue-resident macrophages which are distributed throughout the central nervous system (CNS). Recent studies suggest that microglia are a unique myeloid population distinct from peripheral macrophages in terms of origin and gene expression signature. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic cytokine regulating myeloid development, has been shown to stimulate proliferation and alter phenotype of microglia in vitro. However, how its signaling is modulated in microglia is poorly characterized. MafB, a bZip transcriptional factor, is highly expressed in monocyte-macrophage lineage cells including microglia, although its role in microglia is largely unknown. We investigated the crosstalk between GM-CSF signaling and MafB by analyzing primary microglia. We found that Mafb-deficient microglia grew more rapidly than wild-type microglia in response to GM-CSF. Moreover, the expression of genes associated with microglial differentiation was more downregulated in Mafb-deficient microglia cultured with GM-CSF. Notably, such differences between the genotypes were not observed in the presence of M-CSF. In addition, we found that Mafb-deficient microglia cultured with GM-CSF barely extended their membrane protrusions, probably due to abnormal activation of RhoA, a key regulator of cytoskeletal remodeling. Altogether, our study reveals that MafB is a negative regulator of GM-CSF signaling in microglia. These findings could provide new insight into the modulation of cytokine signaling by transcription factors in microglia. - Highlights: • GM-CSF alters the phenotype of microglia in vitro more potently than M-CSF. • Transcription factor MafB antagonizes the effect of GM-CSF on microglia in vitro. • MafB deficiency leads to RhoA activation in microglia in response to GM-CSF. • We show for the first time the function of MafB in microglia.

  8. GM-CSF ameliorates microvascular barrier integrity via pericyte-derived Ang-1 in wound healing.

    Science.gov (United States)

    Yan, Min; Hu, Yange; Yao, Min; Bao, Shisan; Fang, Yong

    2017-11-01

    Skin wound healing involves complex coordinated interactions of cells, tissues, and mediators. Maintaining microvascular barrier integrity is one of the key events for endothelial homeostasis during wound healing. Vasodilation is observed after vasoconstriction, which causes blood vessels to become porous, facilitates leukocyte infiltration and aids angiogenesis at the wound-area, postinjury. Eventually, vessel integrity has to be reestablished for vascular maturation. Numerous studies have found that granulocyte macrophage colony-stimulating factor (GM-CSF) accelerates wound healing by inducing recruitment of repair cells into the injury area and releases of cytokines. However, whether GM-CSF is involving in the maintaining of microvascular barrier integrity and the underlying mechanism remain still unclear. Aim of this study was to investigate the effects of GM-CSF on modulation of microvascular permeability in wound healing and underlying mechanisms. Wound closure and microvascular leakage was investigated using a full-thickness skin wound mouse model after GM-CSF intervention. The endothelial permeability was measured by Evans blue assay in vivo and in vitro endothelium/pericyte co-culture system using a FITC-Dextran permeability assay. To identify the source of angiopoietin-1 (Ang-1), double staining is used in vivo and ELISA and qPCR are used in vitro. To determine the specific effect of Ang-1 on GM-CSF maintaining microvascular stabilization, Ang-1 siRNA was applied to inhibit Ang-1 production in vivo and in vitro. Wound closure was significantly accelerated and microvascular leakage was ameliorated after GM-CSF treatment in mouse wound sites. GM-CSF decreased endothelial permeability through tightening endothelial junctions and increased Ang-1 protein level that was derived by perictye. Furthermore, applications of siRNAAng-1 inhibited GM-CSF mediated protection of microvascular barrier integrity both in vivo and in vitro. Our data indicate that GM-CSF

  9. GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Stojić-Vukanić, Zorica; Pilipović, Ivan; Vujnović, Ivana; Nacka-Aleksić, Mirjana; Petrović, Raisa; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Leposavić, Gordana

    2016-01-01

    Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+IFN-γ+, IL-17+IFN-γ-, and IL-17-IFN-γ+ cells accompanied by higher frequency of IL-17-IFN-γ- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+IFN-γ+ Th17 cells in SC) on GM-CSF+IFN-γ+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+IFN-γ+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1β, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45hi cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms

  10. Chimeric HIV-1 Envelope Glycoproteins with Potent Intrinsic Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Activity*

    Science.gov (United States)

    Boot, Maikel; Cobos Jiménez, Viviana; Kootstra, Neeltje A.; Sanders, Rogier W.

    2013-01-01

    HIV-1 acquisition can be prevented by broadly neutralizing antibodies (BrNAbs) that target the envelope glycoprotein complex (Env). An ideal vaccine should therefore be able to induce BrNAbs that can provide immunity over a prolonged period of time, but the low intrinsic immunogenicity of HIV-1 Env makes the elicitation of such BrNAbs challenging. Co-stimulatory molecules can increase the immunogenicity of Env and we have engineered a soluble chimeric Env trimer with an embedded granulocyte-macrophage colony-stimulating factor (GM-CSF) domain. This chimeric molecule induced enhanced B and helper T cell responses in mice compared to Env without GM-CSF. We studied whether we could optimize the activity of the embedded GM-CSF as well as the antigenic structure of the Env component of the chimeric molecule. We assessed the effect of truncating GM-CSF, removing glycosylation-sites in GM-CSF, and adjusting the linker length between GM-CSF and Env. One of our designed EnvGM-CSF chimeras improved GM-CSF-dependent cell proliferation by 6-fold, reaching the same activity as soluble recombinant GM-CSF. In addition, we incorporated GM-CSF into a cleavable Env trimer and found that insertion of GM-CSF did not compromise Env cleavage, while Env cleavage did not compromise GM-CSF activity. Importantly, these optimized EnvGM-CSF proteins were able to differentiate human monocytes into cells with a macrophage-like phenotype. Chimeric EnvGM-CSF should be useful for improving humoral immunity against HIV-1 and these studies should inform the design of other chimeric proteins. PMID:23565193

  11. Chimeric HIV-1 envelope glycoproteins with potent intrinsic granulocyte-macrophage colony-stimulating factor (GM-CSF activity.

    Directory of Open Access Journals (Sweden)

    Gözde Isik

    Full Text Available HIV-1 acquisition can be prevented by broadly neutralizing antibodies (BrNAbs that target the envelope glycoprotein complex (Env. An ideal vaccine should therefore be able to induce BrNAbs that can provide immunity over a prolonged period of time, but the low intrinsic immunogenicity of HIV-1 Env makes the elicitation of such BrNAbs challenging. Co-stimulatory molecules can increase the immunogenicity of Env and we have engineered a soluble chimeric Env trimer with an embedded granulocyte-macrophage colony-stimulating factor (GM-CSF domain. This chimeric molecule induced enhanced B and helper T cell responses in mice compared to Env without GM-CSF. We studied whether we could optimize the activity of the embedded GM-CSF as well as the antigenic structure of the Env component of the chimeric molecule. We assessed the effect of truncating GM-CSF, removing glycosylation-sites in GM-CSF, and adjusting the linker length between GM-CSF and Env. One of our designed Env(GM-CSF chimeras improved GM-CSF-dependent cell proliferation by 6-fold, reaching the same activity as soluble recombinant GM-CSF. In addition, we incorporated GM-CSF into a cleavable Env trimer and found that insertion of GM-CSF did not compromise Env cleavage, while Env cleavage did not compromise GM-CSF activity. Importantly, these optimized Env(GM-CSF proteins were able to differentiate human monocytes into cells with a macrophage-like phenotype. Chimeric Env(GM-CSF should be useful for improving humoral immunity against HIV-1 and these studies should inform the design of other chimeric proteins.

  12. Recombinant rabies virus expressing dog GM-CSF is an efficacious oral rabies vaccine for dogs.

    Science.gov (United States)

    Zhou, Ming; Wang, Lei; Zhou, Songqin; Wang, Zhao; Ruan, Juncheng; Tang, Lijun; Jia, Ziming; Cui, Min; Zhao, Ling; Fu, Zhen F

    2015-11-17

    Developing efficacious oral rabies vaccines is an important step to increase immunization coverage for stray dogs, which are not accessible for parenteral vaccination. Our previous studies have demonstrated that recombinant rabies virus (RABV) expressing cytokines/chemokines induces robust protective immune responses after oral immunization in mice by recruiting and activating dendritic cells (DCs) and B cells. To develop an effective oral rabies vaccine for dogs, a recombinant attenuated RABV expressing dog GM-CSF, designated as LBNSE-dGM-CSF was constructed and used for oral vaccination in a dog model. Significantly more DCs or B cells were activated in the peripheral blood of dogs vaccinated orally with LBNSE-dGM-CSF than those vaccinated with the parent virus LBNSE, particularly at 3 days post immunization (dpi). As a result, significantly higher levels of virus neutralizing antibodies (VNAs) were detected in dogs immunized with LBNSE-dGM-CSF than with the parent virus. All the immunized dogs were protected against a lethal challenge with 4500 MICLD50 of wild-type RABV SXTYD01. LBNSE-dGM-CSF was found to replicate mainly in the tonsils after oral vaccination as detected by nested RT-PCR and immunohistochemistry. Taken together, our results indicate that LBNSE-dGM-CSF could be a promising oral rabies vaccine candidate for dogs.

  13. Electronegative L5-LDL induces the production of G-CSF and GM-CSF in human macrophages through LOX-1 involving NF-κB and ERK2 activation.

    Science.gov (United States)

    Yang, Tzu-Ching; Chang, Po-Yuan; Kuo, Tzu-Ling; Lu, Shao-Chun

    2017-12-01

    Circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) are associated with the severity of acute myocardial infarction (AMI). However, what causes increases in G-CSF and GM-CSF is unclear. In this study, we investigated whether L5-low-density lipoprotein (LDL), a mildly oxidized LDL from AMI, can induce G-CSF and GM-CSF production in human macrophages. L1-LDL and L5-LDL were isolated through anion-exchange chromatography from AMI plasma. Human macrophages derived from THP-1 and peripheral blood mononuclear cells were treated with L1-LDL, L5-LDL, or copper-oxidized LDL (Cu-oxLDL) and G-CSF and GM-CSF protein levels in the medium were determined. In addition, the effects of L5-LDL on G-CSF and GM-CSF production were tested in lectin-type oxidized LDL receptor-1 (LOX-1), CD36, extracellular signal-regulated kinase (ERK) 1, and ERK2 knockdown THP-1 macrophages. L5-LDL but not L1-LDL or Cu-oxLDL significantly induced production of G-CSF and GM-CSF in macrophages. In vitro oxidation of L1-LDL and L5-LDL altered their ability to induce G-CSF and GM-CSF, suggesting that the degree of oxidation is critical for the effects. Knockdown and antibody neutralization experiments suggested that the effects were caused by LOX-1. In addition, nuclear factor (NF)-κB and ERK1/2 inhibition resulted in marked reductions of L5-LDL-induced G-CSF and GM-CSF production. Moreover, knockdown of ERK2, but not ERK1, hindered L5-LDL-induced G-CSF and GM-CSF production. The results indicate that L5-LDL, a naturally occurring mild oxidized LDL, induced G-CSF and GM-CSF production in human macrophages through LOX-1, ERK2, and NF-κB dependent pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Use of rhu-GM-CSF in pulmonary tuberculosis patients: results of a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Diana Brasil Pedral-Sampaio

    Full Text Available It has been postulated that deficient or incomplete clinical and/or microbiological response to tuberculosis treatment is associated with cell-mediated immunological dysfunction involving monocytes and macrophages. A phase 2 safety trial was conducted by treating patients with either recombinant human granulocyte-macrophage colony-stimulating factor (rhu-GM-CSF or a placebo, both in combination with anti-tuberculosis chemotherapy. Thirty-one patients with documented pulmonary tuberculosis were treated with rifampin/isoniazid for six months, plus pyrazinamide for the first two months. At the beginning of treatment, rhu-GM-CSF (125µg/M² was randomly assigned to 16 patients and injected subcutaneously twice weekly for four weeks; the other 15 patients received a placebo. The patients were accompanied in the hospital for two weeks, then monthly on an out patient basis, for 12 months. Clinical outcomes were similar in both groups, with no difference in acid-fast bacilli (AFB clearance in sputum at the end of the fourth week of treatment. Nevertheless, a trend to faster conversion to negative was observed in the rhu-GM-CSF group until the eighth week of treatment (p=0.07, after which all patients converted to AFB negative. Adverse events in the rhu-GM-CSF group were local skin inflammation and an increase in the leukocyte count after each injection, returning to normal 72 hours after rhu-GM-CSF injection. Three patients developed SGOP and SGPT > 2.5 times the normal values. All patients included in the GM-CSF group were culture negative at six months, except one who had primary TB resistance. None of the patients had to discontinue the treatment in either group. We conclude that rhu-GM-CSF adjuvant immunotherapy could be safely explored in a phase 3 trial with patients who have active tuberculosis.

  15. Use of rhu-GM-CSF in pulmonary tuberculosis patients: results of a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Pedral-Sampaio Diana Brasil

    2003-01-01

    Full Text Available It has been postulated that deficient or incomplete clinical and/or microbiological response to tuberculosis treatment is associated with cell-mediated immunological dysfunction involving monocytes and macrophages. A phase 2 safety trial was conducted by treating patients with either recombinant human granulocyte-macrophage colony-stimulating factor (rhu-GM-CSF or a placebo, both in combination with anti-tuberculosis chemotherapy. Thirty-one patients with documented pulmonary tuberculosis were treated with rifampin/isoniazid for six months, plus pyrazinamide for the first two months. At the beginning of treatment, rhu-GM-CSF (125µg/M² was randomly assigned to 16 patients and injected subcutaneously twice weekly for four weeks; the other 15 patients received a placebo. The patients were accompanied in the hospital for two weeks, then monthly on an out patient basis, for 12 months. Clinical outcomes were similar in both groups, with no difference in acid-fast bacilli (AFB clearance in sputum at the end of the fourth week of treatment. Nevertheless, a trend to faster conversion to negative was observed in the rhu-GM-CSF group until the eighth week of treatment (p=0.07, after which all patients converted to AFB negative. Adverse events in the rhu-GM-CSF group were local skin inflammation and an increase in the leukocyte count after each injection, returning to normal 72 hours after rhu-GM-CSF injection. Three patients developed SGOP and SGPT > 2.5 times the normal values. All patients included in the GM-CSF group were culture negative at six months, except one who had primary TB resistance. None of the patients had to discontinue the treatment in either group. We conclude that rhu-GM-CSF adjuvant immunotherapy could be safely explored in a phase 3 trial with patients who have active tuberculosis.

  16. GM-CSF Controls Nonlymphoid Tissue Dendritic Cell Homeostasis but Is Dispensable for the Differentiation of Inflammatory Dendritic Cells

    Science.gov (United States)

    Greter, Melanie; Helft, Julie; Chow, Andrew; Hashimoto, Daigo; Mortha, Arthur; Agudo-Cantero, Judith; Bogunovic, Milena; Gautier, Emmanuel L.; Miller, Jennifer; Leboeuf, Marylene; Lu, Geming; Aloman, Costica; Brown, Brian D.; Pollard, Jeffrey W.; Xiong, Huabao; Randolph, Gwendalyn J.; Chipuk, Jerry E.; Frenette, Paul S.; Merad, Miriam

    2012-01-01

    SUMMARY GM-CSF (Csf-2) is a critical cytokine for the in vitro generation of dendritic cells (DCs) and is thought to control the development of inflammatory DCs and resident CD103+ DCs in some tissues. Here we showed that in contrast to the current understanding, Csf-2 receptor acts in the steady state to promote the survival and homeostasis of nonlymphoid tissue-resident CD103+ and CD11b+ DCs. Absence of Csf-2 receptor on lung DCs abrogated the induction of CD8+ T cell immunity after immunization with particulate antigens. In contrast, Csf-2 receptor was dispensable for the differentiation and innate function of inflammatory DCs during acute injuries. Instead, inflammatory DCs required Csf-1 receptor for their development. Thus, Csf-2 is important in vaccine-induced CD8+ T cell immunity through the regulation of nonlymphoid tissue DC homeostasis rather than control of inflammatory DCs in vivo. PMID:22749353

  17. GM-CSF: An Immune Modulatory Cytokine that can Suppress Autoimmunity

    Science.gov (United States)

    Bhattacharya, Palash; Thiruppathi, Muthusamy; Elshabrawy, Hatem A.; Alharshawi, Khaled; Kumar, Prabhakaran; Prabhakar, Bellur S.

    2015-01-01

    GM-CSF was originally identified as a colony stimulating factor (CSF) because of its ability to induce granulocyte and macrophage populations from precursor cells. Multiple studies have demonstrated that GM-CSF is also an immune-modulatory cytokine, capable of affecting not only the phenotype of myeloid lineage cells, but also T-cell activation through various myeloid intermediaries. This property has been implicated in the sustenance of several autoimmune diseases like arthritis and multiple sclerosis. In contrast, several studies using animal models have shown that GM-CSF is also capable of suppressing many autoimmune diseases like Crohn's disease, Type-1 diabetes, Myasthenia gravis and experimental autoimmune thyroiditis. Knockout mouse studies have suggested that the role of GM-CSF in maintaining granulocyte and macrophage populations in the physiological steady state is largely redundant. Instead, its immune-modulatory role plays a significant role in the development or resolution of autoimmune diseases. This is mediated either through the differentiation of precursor cells into specialized non-steady state granulocytes, macrophages and dendritic cells, or through the modulation of the phenotype of mature myeloid cells. Thus, outside of myelopoiesis, GM-CSF has a profound role in regulating the immune response and maintaining immunological tolerance. PMID:26113402

  18. Tumour-derived GM-CSF promotes granulocyte immunosuppression in mesothelioma patients.

    Science.gov (United States)

    Khanna, Swati; Graef, Suzanne; Mussai, Francis; Thomas, Anish; Wali, Neha; Yenidunya, Bahar Guliz; Yuan, Constance M; Morrow, Betsy; Zhang, Jingli; Korangy, Firouzeh; Greten, Tim F; Steinberg, Seth M; Stetler-Stevenson, Maryalice; Middleton, Gary; De Santo, Carmela; Hassan, Raffit

    2018-03-30

    The cross talk between tumour cells, myeloid cells, and T cells play a critical role in tumour pathogenesis and response to immunotherapies. Although the aetiology of mesothelioma is well understood the impact of mesothelioma on the surrounding immune microenvironment is less well studied. In this study the effect of the mesothelioma microenvironment on circulating and infiltrating granulocytes and T cells is investigated. Tumour and peripheral blood from mesothelioma patients were evaluated for presence of granulocytes, which were then tested for their T cell suppression. Co-cultures of granulocytes, mesothelioma cells, T cells were used to identify the mechanism of T cell inhibition. Analysis of tumours showed that the mesothelioma microenvironment is enriched in infiltrating granulocytes, which inhibit T cell proliferation and activation. Characterisation of the blood at diagnosis identified similar, circulating, immunosuppressive CD11b+CD15+HLADR- granulocytes at increased frequency compared to healthy controls. Culture of healthy-donor granulocytes with human mesothelioma cells showed that GM-CSF upregulates NOX2 expression and the release of Reactive Oxygen Species (ROS) from granulocytes, resulting in T cell suppression. Immunohistochemistry and transcriptomic analysis revealed that a majority of mesothelioma tumours express GM-CSF and that higher GM-CSF expression correlated with clinical progression. Blockade of GM-CSF with neutralising antibody, or ROS inhibition, restored T cell proliferation suggesting that targeting of GM-CSF could be of therapeutic benefit in these patients. Our study presents the mechanism behind the cross-talk between mesothelioma and the immune micro-environment and indicates that targeting GM-CSF could be a novel treatment strategy to augment immunotherapy. Copyright ©2018, American Association for Cancer Research.

  19. Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage

    Science.gov (United States)

    Ushach, Irina; Zlotnik, Albert

    2016-01-01

    M-CSF and GM-CSF are 2 important cytokines that regulate macrophage numbers and function. Here, we review their known effects on cells of the macrophage-monocyte lineage. Important clues to their function come from their expression patterns. M-CSF exhibits a mostly homeostatic expression pattern, whereas GM-CSF is a product of cells activated during inflammatory or pathologic conditions. Accordingly, M-CSF regulates the numbers of various tissue macrophage and monocyte populations without altering their "activation" status. Conversely, GM-CSF induces activation of monocytes/macrophages and also mediates differentiation to other states that participate in immune responses [i.e., dendritic cells (DCs)]. Further insights into their function have come from analyses of mice deficient in either cytokine. M-CSF signals through its receptor (CSF-1R). Interestingly, mice deficient in CSF-1R expression exhibit a more significant phenotype than mice deficient in M-CSF. This observation was explained by the discovery of a novel cytokine (IL-34) that represents a second ligand of CSF-1R. Information about the function of these ligands/receptor system is still developing, but its complexity is intriguing and strongly suggests that more interesting biology remains to be elucidated. Based on our current knowledge, several therapeutic molecules targeting either the M-CSF or the GM-CSF pathways have been developed and are currently being tested in clinical trials targeting either autoimmune diseases or cancer. It is intriguing to consider how evolution has directed these pathways to develop; their complexity likely mirrors the multiple functions in which cells of the monocyte/macrophage system are involved. PMID:27354413

  20. In vivo characterization of fusion protein comprising of A1 subunit of Shiga toxin and human GM-CSF: Assessment of its immunogenicity and toxicity.

    Science.gov (United States)

    Oloomi, Mana; Bouzari, Saeid; Shariati, Elaheh

    2010-10-01

    Most cancer cells become resistant to anti-cancer agents. In the last few years, a new approach for targeted therapy of human cancer has been developed using immunotoxins which comprise both the cell targeting and the cell killing moieties. In the present study, the recombinant Shiga toxin A1 subunit fused to human granulocyte-macrophage colony stimulating factor (A1-GM-CSF), previously produced in E. coli, was further characterized. The recombinant protein could cause 50% cytotoxicity and induced apoptosis in cells bearing GM-CSF receptors. The non-specific toxicity of the fusion protein was assessed in C57BL/6 and BALB/c mice. No mortality was observed in either group of mice, with different concentration of fusion protein. The lymphocyte proliferation assay, induction of specific IgG response and a mixed (Th1/Th2) response were observed only in BALB/c mice. The mixed response in BALB/c mice (Th1/Th2) could be explained on the basis of the two components of the fusion protein i.e. A1 and GM-CSF.

  1. Improved survival and marrow engraftment of mice transplanted with bone marrov of GM-CSF-treated donors

    International Nuclear Information System (INIS)

    Ballin, A.; Sagi, O.; Schiby, G.; Meytes, D.

    1993-01-01

    Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) administered to bone marrow (BM) transplant recipients is associated with earlier recovery. We have investigated the possibility of stimulating normal donor mice in vivo with GM-CSF. Donor balb/c mice were injected i.p. with GM-CSF (5000 u) or saline. Seventy-two hours later 5 x 105 BM cells from either GM-CSF-treated or control donors were infused into lethally irradiated (850 R) recipients. In the recipients of BM from GM-CSF-treated donors, significantly higher CFU-S and significantly higher survival rate (57% [n = 65]; vs. 30% [n = 63]; p < 0.05) were noted. Donor mice of the GM-CSF group did not differ in bone-marrow cellularity and composition from their controls. However, recipients of BM from GM-CSF-treated mice had higher blood counts of haemoglobin, Leukocytes and platelets compared to controls. These data demonstrate that pretreatment of BM donors with GM-CSF may be of benefit in improving survival and marrow engraftment in mice. (au) (13 refs.)

  2. Clinical role of GM-CSF in neutrophil recovery in relation to health care parameters

    NARCIS (Netherlands)

    Hofstra, LS; DeVries, EGE; UylDeGroot, CA; Vellenga, E

    Recombinant human growth factors, particularly granulocyte-macrophage colony-stimulating factor (GM-CSF), have been only available for a few years. Since their introduction they have affected the management of drug-induced neutropenia, the use of dose intensive chemotherapy regimens and in the

  3. [The therapeutic effect of HSV1-hGM-CSF combined with doxorubicin on the mouse breast cancer model].

    Science.gov (United States)

    Zhuang, X F; Zhang, S R; Liu, B L; Wu, J L; Li, X Q; Gu, H G; Shu, Y

    2018-03-23

    Objective: To evaluate the oncolytic effect of herpes simplex virus type 1 which carried recombined human granulocyte-macrophage colony-stimulating factor (HSV1-hGM-CSF) on the mouse breast cancer cell line 4T1 and compare the anticancer effects of HSV1-hGM-CSF, doxorubicin alone or combination on the breast cancer in mice. Methods: We investigated the cytotoxic effect on 4T1 cells in vitro, the cell growth, cell apoptosis and cell cycle of 4T1 cells treated with oncolytic HSV1-hGM-CSF at different MOIs (0, 0.5, 1 and 2) and doxorubicin at different concentrations (0, 2, 4 and 8 μg/ml). The effects of oncolytic HSV1-hGM-CSF and doxorubicin on the tumor growth, survival time and their side effects on the mouse breast cancer model were observed. Results: Both oncolytic HSV1-hGM-CSF and doxorubicin significantly inhibited the proliferation of 4T1 cells in vitro . Doxorubicin induced the G(2)/M phase arrest of 4T1 cells, while the cytotoxicity of oncolytic HSV1-hGM-CSF was no cell cycle-dependent.At day 16 after treatment with doxorubicin and HSV1-hGM-CSF, the tumor volume of 4T1 tumor bearing mice were (144.40±27.68)mm(3,) (216.80±57.18)mm(3,) (246.10±21.90)mm(3,) (327.50±44.24)mm(3,) (213.30±32.31)mm(3) and (495.80±75.87)mm(3) in the groups of doxorubicin combined with high dose HSV1-hGM-CSF, doxorubicin combined with low dose HSV1-hGM-CSF, doxorubicin alone, high dose HSV1-hGM-CSF alone, low dose HSV1-hGM-CSF alone and control, respectively.Compared with the control group, both doxorubicin and HSV1-hGM-CSF treatment exhibited significant reduction of primary tumor volume in vivo ( P CSF alone and low dose HSV1-hGM-CSF alone were significantly longer than that of control ( P CSF is observed in 4T1 mouse breast cancer.

  4. ZO-1 expression is suppressed by GM-CSF via miR-96/ERG in brain microvascular endothelial cells.

    Science.gov (United States)

    Zhang, Hu; Zhang, Shuhong; Zhang, Jilin; Liu, Dongxin; Wei, Jiayi; Fang, Wengang; Zhao, Weidong; Chen, Yuhua; Shang, Deshu

    2018-05-01

    The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases in some disorders such as vascular dementia, Alzheimer's disease, and multiple sclerosis. We previously reported that in Alzheimer's disease patients, a high level of GM-CSF in the brain parenchyma downregulated expression of ZO-1, a blood-brain barrier tight junction protein, and facilitated the infiltration of peripheral monocytes across the blood-brain barrier. However, the molecular mechanism underlying regulation of ZO-1 expression by GM-CSF is unclear. Herein, we found that the erythroblast transformation-specific (ETS) transcription factor ERG cooperated with the proto-oncogene protein c-MYC in regulation of ZO-1 transcription in brain microvascular endothelial cells (BMECs). The ERG expression was suppressed by miR-96 which was increased by GM-CSF through the phosphoinositide-3 kinase (PI3K)/Akt pathway. Inhibition of miR-96 prevented ZO-1 down-regulation induced by GM-CSF both in vitro and in vivo. Our results revealed the mechanism of ZO-1 expression reduced by GM-CSF, and provided a potential target, miR-96, which could block ZO-1 down-regulation caused by GM-CSF in BMECs.

  5. ILC3 GM-CSF production and mobilisation orchestrate acute intestinal inflammation.

    Science.gov (United States)

    Pearson, Claire; Thornton, Emily E; McKenzie, Brent; Schaupp, Anna-Lena; Huskens, Nicky; Griseri, Thibault; West, Nathaniel; Tung, Sim; Seddon, Benedict P; Uhlig, Holm H; Powrie, Fiona

    2016-01-18

    Innate lymphoid cells (ILCs) contribute to host defence and tissue repair but can induce immunopathology. Recent work has revealed tissue-specific roles for ILCs; however, the question of how a small population has large effects on immune homeostasis remains unclear. We identify two mechanisms that ILC3s utilise to exert their effects within intestinal tissue. ILC-driven colitis depends on production of granulocyte macrophage-colony stimulating factor (GM-CSF), which recruits and maintains intestinal inflammatory monocytes. ILCs present in the intestine also enter and exit cryptopatches in a highly dynamic process. During colitis, ILC3s mobilize from cryptopatches, a process that can be inhibited by blocking GM-CSF, and mobilization precedes inflammatory foci elsewhere in the tissue. Together these data identify the IL-23R/GM-CSF axis within ILC3 as a key control point in the accumulation of innate effector cells in the intestine and in the spatio-temporal dynamics of ILCs in the intestinal inflammatory response.

  6. Research Upregulation of CD23 (FcεRII Expression in Human Airway Smooth Muscle Cells (huASMC in Response to IL-4, GM-CSF, and IL-4/GM-CSF

    Directory of Open Access Journals (Sweden)

    Lew D Betty

    2005-05-01

    Full Text Available Abstract Background Airway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE. Methods Serum starved huASMC were stimulated with either IL-4, GM-CSF, IL-13, IL-5, PGD2, LTD4, tryptase or a combination of IL-4, IL-5, IL-13 each with GM-CSF for a period of 24 h. CD23 expression was analyzed by flow cytometry, western blot, and indirect immunofluorescence. Results The CD23 protein expression was upregulated in huASMC in response to IL-4, GM-CSF, and IL-4/GM-CSF. The percentage of cells with increased fluorescence intensity above the control was 25.1 ± 4.2% (IL-4, 15.6 ± 2.7% (GM-CSF and 32.9 ± 13.9% (IL-4/GMCSF combination(n = 3. The protein content of IL-4/GMCSF stimulated cells was significantly elevated. Expression of CD23 in response to IL-4, GM-CSF, IL-4/GM-CSF was accompanied by changes in cell morphology including depolymerization of isoactin fibers, cell spreading, and membrane ruffling. Western blot revealed abundant expression of the IL-4Rα and a low level expression of IL-2Rγc in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rγc. Conclusion CD23 on huASMC is upregulated by IL-4, GM-CSF, and IL-4/GM-CSF. The expression of CD23 is accompanied by an increase in cell volume and an increase in protein content per cell, suggesting hypertrophy. Upregulation of CD23 by IL-4/GM-CSF results in phenotypic changes in huASMC that could play a role in cell migration or a change in the synthetic function of the cells. Upregulation of CD23 in huASMC by IL-4 and GM-CSF can contribute to changes in huASMC and may provide an avenue

  7. Influence of rhTPO/GM-CSF fusion protein on hemopoiesis in mice irradiated with 60Co γ-rays

    International Nuclear Information System (INIS)

    Cao Hua; Ge Zhongliang; Zhang Qunwei; Liu Xiuzhen

    1999-01-01

    Objective: To find a new biological therapy for secondary hematopoietic failure including anemia, infection and hemorrhage after administration of chemotherapeutic drugs etc. Methods: hGM-CSF gene was ligated with hTPO gene isolated from human fetal liver mRNA and a new fusion protein rh TPO/GM-CSF obtained. Results: The new fusion protein could promote recovery of peripheral WBC and PLT of 5.0 Gy irradiated mice. BFU-E, CFU-Meg and CFU-GM in bone marrow of mice after irradiation recovered significantly by treatment with rhTPO/GM-CSF fusion protein for 10 days. Conclusion: These results suggest that the new fusion protein has the biological activity of both hTPO and hGM-CSF simultaneously and can stimulate the proliferation of megakaryocytes and granulocyte progenitors

  8. Enhancement of an Allogeneic GM-CSF-Secreting Breast Cancer Vaccine by Immunomodulatory Doses of Cyclophosphamide and Doxorubicin

    National Research Council Canada - National Science Library

    Emens, Leisha

    2003-01-01

    .... We have applied the use of tumor cells genetically modified to secrete GM-CSF to the preclinical neu transgenic mouse model, characterized by spontaneous tumor development and pre-existing immune tolerance to HER-2/neu...

  9. Regulation of dendritic cell development by GM-CSF: molecular control and implications for immune homeostasis and therapy.

    Science.gov (United States)

    van de Laar, Lianne; Coffer, Paul J; Woltman, Andrea M

    2012-04-12

    Dendritic cells (DCs) represent a small and heterogeneous fraction of the hematopoietic system, specialized in antigen capture, processing, and presentation. The different DC subsets act as sentinels throughout the body and perform a key role in the induction of immunogenic as well as tolerogenic immune responses. Because of their limited lifespan, continuous replenishment of DC is required. Whereas the importance of GM-CSF in regulating DC homeostasis has long been underestimated, this cytokine is currently considered a critical factor for DC development under both steady-state and inflammatory conditions. Regulation of cellular actions by GM-CSF depends on the activation of intracellular signaling modules, including JAK/STAT, MAPK, PI3K, and canonical NF-κB. By directing the activity of transcription factors and other cellular effector proteins, these pathways influence differentiation, survival and/or proliferation of uncommitted hematopoietic progenitors, and DC subset-specific precursors, thereby contributing to specific aspects of DC subset development. The specific intracellular events resulting from GM-CSF-induced signaling provide a molecular explanation for GM-CSF-dependent subset distribution as well as clues to the specific characteristics and functions of GM-CSF-differentiated DCs compared with DCs generated by fms-related tyrosine kinase 3 ligand. This knowledge can be used to identify therapeutic targets to improve GM-CSF-dependent DC-based strategies to regulate immunity.

  10. The role of granulocyte macrophage colony stimulating factor (GM-CSF) in radiation-induced tumor cell migration.

    Science.gov (United States)

    Vilalta, Marta; Brune, Jourdan; Rafat, Marjan; Soto, Luis; Graves, Edward E

    2018-03-13

    Recently it has been observed in preclinical models that that radiation enhances the recruitment of circulating tumor cells to primary tumors, and results in tumor regrowth after treatment. This process may have implications for clinical radiotherapy, which improves control of a number of tumor types but which, despite continued dose escalation and aggressive fractionation, is unable to fully prevent local recurrences. By irradiating a single tumor within an animal bearing multiple lesions, we observed an increase in tumor cell migration to irradiated and unirradiated sites, suggesting a systemic component to this process. Previous work has identified the cytokine GM-CSF, produced by tumor cells following irradiation, as a key effector of this process. We evaluated the ability of systemic injections of a PEGylated form of GM-CSF to stimulate tumor cell migration. While increases in invasion and migration were observed for tumor cells in a transwell assay, we found that daily injections of PEG-GM-CSF to tumor-bearing animals did not increase migration of cells to tumors, despite the anticipated changes in circulating levels of granulocytes and monocytes produced by this treatment. Combination of PEG-GM-CSF treatment with radiation also did not increase tumor cell migration. These findings suggest that clinical use of GM-CSF to treat neutropenia in cancer patients will not have negative effects on the aggressiveness of residual cancer cells. However, further work is needed to characterize the mechanism by which GM-CSF facilitates systemic recruitment of trafficking tumor cells to tumors.

  11. In whole blood, LPS, TNF-alpha and GM-CSF increase monocyte uptake of {sup 99m}technetium stannous colloid but do not affect neutrophil uptake

    Energy Technology Data Exchange (ETDEWEB)

    Ramsay, Stuart C. [Townsville Nuclear Medicine, Mater Hospital, Pimlico, Queensland 4812 (Australia) and School of Medicine, James Cook University, Townsville, Queensland 4811 (Australia)]. E-mail: stuart.ramsay1@jcu.edu.au; Maggs, Jacqueline [Department of Nuclear Medicine, Townsville Hospital, Townsville, Queensland 4814 (Australia); Powell, Kellie [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); School of Medicine, James Cook University, Townsville, Queensland 4811 (Australia); Barnes, Jodie [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Ketheesan, Natkunam [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); School of Medicine, James Cook University, Townsville, Queensland 4811 (Australia)

    2006-07-15

    Introduction: {sup 99m}Technetium stannous colloid (TcSnC) is used in white cell scanning. It labels neutrophils and monocytes via phagocytosis, with uptake mediated by the phagocytic receptor CD11b/CD18 in neutrophils. Uptake of TcSnC is altered by gram-negative infection, possibly due to the endotoxin component lipopolysaccharide (LPS) or to cytokines released during infection (e.g., TNF-alpha and IFN-gamma). Endotoxemia and increased TNF-alpha levels also occur in inflammatory bowel disease. Another potential confounder in cell labeling is that sepsis patients may be treated with GM-CSF and G-CSF, which alter phagocytic cell function. This study aimed to determine how these factors affect TcSnC cellular uptake. Methods: Whole blood from six healthy volunteers was incubated with LPS, TNF-alpha, IFN-gamma, GM-CSF or G-CSF. Samples were then mixed with TcSnC. Blood was separated across density gradients and imaged using a gamma camera. Three radioactive count peaks were observed in each tube: free plasma activity, mononuclear cell uptake and neutrophil uptake. Results: Compared with controls, significant increases in mononuclear cell uptake were induced by LPS, TNF-alpha and GM-CSF stimulation. It was incidentally noted that exogenous estrogens appear to affect TcSnC labeling and may influence the neutrophil response to stimulation. Neutrophil uptake and plasma activity were not significantly affected. IFN-gamma and G-CSF had no significant effect. Conclusions: In whole blood, the effect of LPS on TcSnC monocyte uptake is different to its effect on neutrophils, consistent with previously reported differences in CD11b/CD18 expression. TNF-alpha response parallels LPS response. GM-CSF also increases TcSnC uptake by monocytes. These effects should be considered when using TcSnC for imaging purposes, as they will tend to increase monocyte labeling. Estrogens may also affect TcSnC labeling. Responses to IFN-gamma and G-CSF are consistent with previously reported effects

  12. GM-CSF production from human airway smooth muscle cells is potentiated by human serum

    Directory of Open Access Journals (Sweden)

    Maria B. Sukkar

    2000-01-01

    Full Text Available Recent evidence suggests that airway smooth muscle cells (ASMC actively participate in the airway inflammatory process in asthma. Interleukin–1β (IL–1β and tumour necrosis factor–α (TNF–α induce ASMC to release inflammatory mediators in vitro. ASMC mediator release in vivo, however, may be influenced by features of the allergic asthmatic phenotype. We determined whether; (1 allergic asthmatic serum (AAS modulates ASMC mediator release in response to IL–1β and TNF–α, and (2 IL–1β/TNF–α prime ASMC to release mediators in response to AAS. IL–5 and GMCSF were quantified by ELISA in culture supernatants of; (1 ASMC pre-incubated with either AAS, non-allergic non-asthmatic serum (NAS or MonomedTM (a serum substitute and subsequently stimulated with IL–1β and TNF–α and (2 ASMC stimulated with IL–1β/TNF–α and subsequently exposed to either AAS, NAS or MonomedTM. IL-1g and TNF–α induced GM-CSF release in ASMC pre-incubated with AAS was not greater than that in ASMC pre-incubated with NAS or MonomedTM. IL–1β and TNF–α, however, primed ASMC to release GM-CSF in response to human serum. GM-CSF production following IL–1β/TNF–α and serum exposure (AAS or NAS was significantly greater than that following IL–1β /TNF–α and MonomedTM exposure or IL–1β/TNF–α exposure only. Whilst the potentiating effects of human serum were not specific to allergic asthma, these findings suggest that the secretory capacity of ASMC may be up-regulated during exacerbations of asthma, where there is evidence of vascular leakage.

  13. Human autologous in vitro models of glioma immunogene therapy using B7-2, GM-CSF, and IL12

    International Nuclear Information System (INIS)

    Parney, I.F.; Farr-Jones, M.A.; Kane, K.; Chang, L.-J.; Petruk, K.C.

    2002-01-01

    Cancer immunogene therapy is based on vaccination with radiated, autologous tumor cells transduced with immunostimulatory genes. To help determine an optimal glioma immunogene therapy strategy, we stimulated lymphocytes with autologous human glioma cells transduced with B7-2 (CD86), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin-12 (IL12). A human glioma-derived cell culture (Ed147.BT) was transduced with B7-2, GM-CSF, and/or IL12 using retroviral vectors. Autologous peripheral blood mononuclear cells (PBMC) were co-cultured with irradiated gene-transduced tumor alone or a combination of radiated wild type and gene-transduced cells. Peripheral blood mononuclear cells proliferation was determined by serial cell counts. Peripheral blood mononuclear cells phenotype was assessed by flow cytometry for CD4, CD8, and CD16. Anti-tumor cytotoxicity was determined by chromium-51 ( 51 Cr) release assay. Peripheral blood mononuclear cells cell numbers all decreased during primary stimulation but tumor cells expressing B7-2 or GM-CSF consistently caused secondary proliferation. Tumors expressing B7-2 and GM-CSF or B7-2,GM-CSF,and IL12 consistently increased PBMC CD8+ (cytotoxic T) and CD16+ (natural killer) percentages. Interestingly, anti-tumor cytotoxicity only exceeded that of PBMC stimulated with wild type tumor alone when peripheral blood mononuclear cells were stimulated with both wild type tumor and B7-2/GM-CSF- (but not IL12) transduced cells. PBMC proliferation and phenotype is altered as expected by exposure to immunostimulatory gene-transduced tumor. However, transduced tumor cells alone do not stimulate greater anti-tumor cytotoxicity than wild type tumor. Only B7-2/GM-CSF-transduced cells combined with wild type produced increased cytotoxicity. This may reflect selection of turnor subclones with limited antigenic spectra during retrovirus-mediated gene transfer. (author)

  14. The influence of protein malnutrition on the production of GM-CSF and M-CSF by macrophages

    Directory of Open Access Journals (Sweden)

    Dalila Cunha de Oliveira

    Full Text Available ABSTRACT It is well established that protein malnutrition (PM impairs immune defenses and increases susceptibility to infection. Macrophages are cells that play a central role in innate immunity, constituting one of the first barriers against infections. Macrophages produce several soluble factors, including cytokines and growth factors, important to the immune response. Among those growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF and macrophage colony-stimulating factor (M-CSF. GM-CSF and M-CSF are important to monocyte and macrophage development and stimulation of the immune response process. Knowing the importance of GM-CSF and M-CSF, we sought to investigate the influence of PM on macrophage production of these growth factors. Two-month-old male BALB/c mice were subjected to PM with a low-protein diet (2% and compared to a control diet (12% mouse group. Nutritional status, hemogram and the number of peritoneal cells were evaluated. Additionally, peritoneal macrophages were cultured and the production of GM-CSF and M-CSF and mRNA expression were evaluated. To determine if PM altered macrophage production of GM-CSF and M-CSF, they were stimulated with TNF-α. The PM animals had anemia, leukopenia and a reduced number of peritoneal cells. The production of M-CSF was not different between groups; however, cells from PM animals, stimulated with or without TNF-α, presented reduced capability to produce GM-CSF. These data imply that PM interferes with the production of GM-CSF, and consequently would affect the production and maturation of hematopoietic cells and the immune response.

  15. Reduced expression of granule proteins during extended survival of eosinophils in splenocyte culture with GM-CSF.

    Science.gov (United States)

    Ryu, Seul Hye; Na, Hye Young; Sohn, Moah; Han, Sun Murray; Choi, Wanho; In, Hyunju; Hong, Sookyung; Jeon, Hyejin; Seo, Jun-Young; Ahn, Jongcheol; Park, Chae Gyu

    2016-05-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifaceted hematopoietic cytokine and the culture of mouse bone marrow with GM-CSF produces a variety of myeloid cells including granulocytes, macrophages, and dendritic cells. In the present study, we cultured mouse splenocytes with GM-CSF and examined the changes in hematopoietic cell populations over a week. Most of the splenic hematopoietic cells disappeared significantly from culture within 6days with or without the presence of GM-CSF. Among the splenic granulocyte populations, only eosinophils fully survived throughout the culture with GM-CSF for more than a week. During 10days of culture with GM-CSF, splenic eosinophils maintained their morphology as well as most of their surface molecules at high levels, including CCR3 and Siglec F. Meanwhile, the expression of mRNAs encoding major basic protein-1 (MBP-1) and eosinophil peroxidase (EPO), two major eosinophil-derived granule proteins, was diminished significantly from the cultured eosinophils. EPO assays also revealed that eosinophils in culture for more than 5days retained 30% or less EPO activity compared to those in uncultured splenocytes. In contrast, culture of splenocytes with GM-CSF did not change the capacity of eosinophils to migrate in response to eotaxin-1. Our results indicate that mouse splenic eosinophils are effectively cultured for lengthy periods while their expression of eosinophil-derived granule proteins is specifically suppressed. The relevance of these findings to eosinophilic inflammatory response is discussed. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  16. Coadministration of cruzipain and GM-CSF DNAs, a new immunotherapeutic vaccine against Trypanosoma cruzi infection.

    Science.gov (United States)

    Cerny, Natacha; Sánchez Alberti, Andrés; Bivona, Augusto E; De Marzi, Mauricio C; Frank, Fernanda M; Cazorla, Silvia I; Malchiodi, Emilio L

    2016-01-01

    Therapeutic vaccine research and development are especially important in Chagas disease considering the characteristics of the chronic infection and the number of people in the Americas living with a parasite infection for decades. We have previously reported the efficacy of attenuated Salmonella enterica (S) carrying plasmid encoding cruzipain (SCz) to protect against Trypanosoma cruzi infection. In the present work we investigated whether Cz DNA vaccine immunotherapy could be effective in controlling an ongoing T. cruzi infection in mice. We here report the intramuscular administration of naked Cz DNA or the oral administration of Salmonella as Cz DNA delivery system as therapeutic vaccines in mice during acute or chronic infection. The coadministration of a plasmid encoding GM-CSF improved vaccine performance, indicating that the stimulation of innate immune cells is needed in the event of an ongoing infection. These therapeutic vaccines were able to address the response to a protective and sustained Th1 biased profile not only against Cz but also against a variety of parasite antigens. The combined therapeutic vaccine during the chronic phase of infection prevents tissue pathology as shown by a reduced level of enzyme activity characteristic of tissue damage and a tissue status compatible with normal tissue. The obtained results suggest that immunotherapy with Cz and GM-CSF DNAs, either alone or in combination with other drug treatments, may represent a promising alternative for Chagas disease therapy.

  17. Human papillomavirus infection is associated with decreased levels of GM-CSF in cervico-vaginal fluid of infected women.

    Science.gov (United States)

    Comar, Manola; Monasta, Lorenzo; Zanotta, Nunzia; Vecchi Brumatti, Liza; Ricci, Giuseppe; Zauli, Giorgio

    2013-10-01

    Although human papillomavirus (HPV) is the most common sexually transmitted infection, there are very scant data about the influence of this virus on the in vitro fertilization outcome. To assess the presence of HPV in the cervico-vaginal fluid in relationship to the in vitro fertilization (IVF) outcome and to the concentration of selected cytokines, known to affect embryo implantation and gestation: granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF). Cervico-vaginal samples were collected on the day of oocyte pick-up from 82 women. Vaginas were flushed with 50 mL of sterile water and 3 mL of fluid was collected. Twelve women (15%) were positive for HPV. Interestingly, among HPV(+) women live birth rate was about half of the rate in HPV(-) women, although the differences were not statistically significant due to the low number of cases. Cervico-vaginal samples of a sub-group of 29 (8 HPV(+) and 21 HPV(-)) women were analyzed for GM-CSF and G-CSF by ELISA. GM-CSF but not G-CSF was significantly lower in the cervico-vaginal fluid of HPV(+) than in HPV(-) women. Since GM-CSF plays an important role during pregnancy, the reduced levels of GM-CSF in the cervico-vaginal fluid of HPV(+) women might contribute to explain the reduced live birth rate observed in HPV(+) women. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF Factor on Corneal Epithelial Cells in Corneal Wound Healing Model.

    Directory of Open Access Journals (Sweden)

    Chang Rae Rho

    Full Text Available Granulocyte-macrophage colony-stimulating factor (GM-CSF is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs. We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF. An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml. MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration.

  19. Clinical significance of determination of changes of serum GM-CSF, IL-8, IL-6 levels after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Xue Hongfeng

    2006-01-01

    Objective: To investigate the changes of serum GM-CSF, IL-8 and IL-6 levels both before and after treatment in pediatric patients with bronchial asthma. Methods: Serum GM-CSF, IL-8 and IL-6 levels were measured with RIA in 32 pediatric patients with bronchial asthma both before and after treatment as well as in 30 controls. Results: Before treatment, the serum GM-CSF, IL-8, IL-6 levels were significantly higher in the patients than those in the controls (P 0.05). Conclusion: Abnormal high serum GM-CSF, IL-8, IL-6 levels played important role in the pathogenesis of bronchial asthma in children. (authors)

  20. [Effects of cell-mediated immunity induced by intramuscular chitosan-pJME/ GM-CSF nano-DNA vaccine in BAlb/c mice].

    Science.gov (United States)

    Zhai, Yong-Zhen; Zhou, Yan; Ma, Li; Feng, Guo-He

    2014-07-01

    This study aimed to investigate the immune adjuvant effect and mechanism induced by chitosan nanoparticles carrying pJME/GM-CSF. In this study, plasmid DNA (pJME/GM-CSF) was encapsulated in chitosan to prepare chitosan-pJME/GM-CSF nanoparticles using a complex coacervation process. Immunohistochemistry was used to detect the type of infiltrating cells at the site of intramuscular injection. The phenotype and functional changes of splenic DCs were measured by flow cytometry after different immunogens were injected intramuscularly. The killing activity of CTLs was assessed using the lactate dehydrogenase (LDH) release assay. The preparation of chitosan-pJME/GM-CSF nanoparticles matched the expected theoretical results. Our results also found that, after pJME/GM-CSF injection, the incoming cells were a mixture of macrophages, neutrophils, and immature DCs. Meanwhile, pJME/GM-CSF increased the expression of MHC class II molecules on splenic DCs, and enhanced their Ag capture and presentation functions. Cell-mediated immunity was induced by the vaccine. Furthermore, chitosan-pJME/GM-CSF nanoparticles outperformed the administration of standard pJME/GM-CSF in terms of DC recruitment, antigen processing and presentation, and vaccine enhancement. These findings reveal that chitosan could be used as delivery vector for DNA vaccine intramuscular immunizations, and enhance pJME/GM-CSF-induced cellular immune responses.

  1. Clinical significance of determination of changes of serum GM-CSF and platelet granular membrance protein (PGMP) contents after treatment in patients with cerebral infarction

    International Nuclear Information System (INIS)

    Zang Zhizhong; Pan Shengying; Tang Yong; Wang Jun

    2006-01-01

    Objective: To investigate the changes of serum GM-CSF and PGMP levels after treatment in patients with cerebral infarction. Methods: Serum GM-CSF and PGMP contents were measured with RIA in 36 patients with cerebral infarction both before and after treatment as well as in 30 controls. Results: Before treatment, the serum GM-CSF and PGMP levels in the patients were significantly higher than those in the controls (P<0.01). After 6 months' treatment, the levels (though dropped markedly), remained significantly higher (P<0.05). Conclusion: Serum GM-CSF and PGMP levels might be of prognostic value in patients with cerebral infarction. (authors)

  2. Clinical significance of determination of changes of serum GM-CSF, CGRP levels after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Xu Lihua

    2007-01-01

    Objective: To explore the changes of serum GM-CSF and CGRP levels both before and after treatment in pediatric patients with bronchial asthma. Methods: Serum GM-CSF and CGRP levels were measured with RIA in 33 pediatric patients with bronchial asthma both before and after treatment as well as in 35 controls. Results: Before treatment, the serum GM-CSF levels was significantly higher in the patients than those in the controls (P 0.05). Conclusion: Abnormal high serum GM -CSF and low CGRP levels played important role in the pathogenesis of bronchial asthma in children. (authors)

  3. Clinical significance of determination of changes of serum NO, NOS and GM-CSF levels after treatment in children with bronchopneumonia

    International Nuclear Information System (INIS)

    Li Hongmei

    2007-01-01

    Objective: To investigate the clinical significance of changes of serum NO, NOS and GM-CSF levels after treatment in children with bronchopneumonia. Methods: Serum GM-CSF levels were determined with RIA, and serum NO, NOS levels were determined with biochemical methods both before and after treatment in 48 children with bronehopneumonia as well as in 35 controls. Results: Before treatment the serum concentrations of NO, NOS and GM-CSF in the patients were significantly higher than those in controls (P 0.05). Conclusion: Detection of serum NO, NOS and GM-CSF levels were useful for assessment of therapeutic efficacy. (authors)

  4. Clinical significance of determination of serum TNF, IL-8 and GM-CSF levels in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Xu Donglin

    2005-01-01

    Objective: To investigate the clinical significance of changes of serum TNF, IL-8 and GM-CSF in pediatric patients with bronchial asthma. Methods: Serum TNF, IL-8 and GM-CSF levels were measured with RIA in 32 pediatric patients with bronchial asthma and 30 controls. Results: Serum levels of TNF, IL-8 and GM-CSF were very significantly higher in pediatric patients with bronchial asthma than those in controls (P<0.01). After one week treatment, the levels dropped considerably but still remained significantly higher than those in controls (P<0.05). Conclusion: These cytokines participated in the pathogenesis of bronchial asthma. Monitoring the changes of their serum levels was helpful for the management of the diseases. (authors)

  5. [Therapeutic use of hematopoietic growth factors. II. GM-CSF and G-CSF].

    Science.gov (United States)

    Royer, B; Arock, M

    1998-01-01

    The second part of this review on haematopoietic growth factors is focused on the therapeutic use of GM-CSF and G-CSF. Such therapeutic applications have raised very great hopes for clinical haematology. However, it should not be forgotten that these haematopoietic growth factors, which are very costly, are powerful two-edged weapons capable of triggering a cascade of reactions, and have a field of activity that often goes beyond the single highly specific property which it is hoped they possess. The risks and costs of their use are currently being evaluated. Waited developments concerning these molecules focus on three axes: a best use of factors already commercialized, especially concerning adaptation of posologies and new indications, the development of hybrid molecules from already known haematopoietic growth factors, possessing the advantages of respective factors, but not their disadvantages, the discovery of new haematopoietic growth factors with potential therapeutic application.

  6. Effects of prostaglandin E2 and cAMP elevating drugs on GM-CSF release by cultured human airway smooth muscle cells. Relevance to asthma therapy.

    Science.gov (United States)

    Lazzeri, N; Belvisi, M G; Patel, H J; Yacoub, M H; Chung, K F; Mitchell, J A

    2001-01-01

    Human airway smooth muscle (HASM) cells release granulocyte macrophage-colony stimulating factor (GM-CSF) and express cyclooxygenase (COX)-2 (resulting in the release of prostaglandin [PG] E2) after stimulation with cytokines. Because COX-2 activity can regulate a number of inflammatory processes, we have assessed its effects, as well as those of agents that modulate cyclic adenosine monophosphate (cAMP), on GM-CSF release by HASM cells. Cells stimulated with a combination of proinflammatory cytokines (interleukin-1beta and tumor necrosis factor-alpha each at 10 ng/ml) for 24 h released significant amounts of PGE2 (measured by radioimmunoassay) and GM-CSF (measured by enzyme-linked immunosorbent assay). Indomethacin and other COX-1/COX-2 inhibitors caused concentration-dependent inhibitions of PGE2 concomitantly with increases in GM-CSF formation. Addition of exogenous PGE2 or the beta2-agonist fenoterol, which increase cAMP, to cytokine-treated HASM cells had no effect on GM-CSF release unless COX activity was first blocked with indomethacin. The type 4 phosphodiesterase inhibitors rolipram and SB 207499 both caused concentration-dependent reductions in GM-CSF production. Thus, when HASM cells are activated with cytokines they release PGE2, which acts as a "braking mechanism" to limit the coproduction of GM-CSF. Moreover, agents that elevate cAMP also reduce GM-CSF formation by these cells.

  7. A randomized clinical trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium for in vitro fertilization

    DEFF Research Database (Denmark)

    Ziebe, Søren; Loft, Anne; Povlsen, Betina B

    2013-01-01

    To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium on ongoing implantation rate (OIR).......To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium on ongoing implantation rate (OIR)....

  8. Specific Contributions of CSF-1 and GM-CSF to the Dynamics of the Mononuclear Phagocyte System.

    Science.gov (United States)

    Louis, Cynthia; Cook, Andrew D; Lacey, Derek; Fleetwood, Andrew J; Vlahos, Ross; Anderson, Gary P; Hamilton, John A

    2015-07-01

    M-CSF (or CSF-1) and GM-CSF can regulate the development and function of the mononuclear phagocyte system (MPS). To address some of the outstanding and sometimes conflicting issues surrounding this biology, we undertook a comparative analysis of the effects of neutralizing mAbs to these CSFs on murine MPS populations in the steady-state and during acute inflammatory reactions. CSF-1 neutralization, but not of GM-CSF, in normal mice rapidly reduced the numbers of more mature Ly6C(-) monocytes in blood and bone marrow, without any effect on proliferating precursors, and also the numbers of the resident peritoneal macrophages, observations consistent with CSF-1 signaling being essential only at a relatively late state in steady-state MPS development; in contrast, GM-CSF neutralization had no effect on the numbers of these particular populations. In Ag-induced peritonitis (AIP), thioglycolate-induced peritonitis, and LPS-induced lung inflammation, CSF-1 neutralization lowered inflammatory macrophage number; in the AIP model, this reduced number was not due to suppressed proliferation. More detailed studies with the convenient AIP model indicated that CSF-1 neutralization led to a relatively uniform reduction in all inflammatory cell populations; GM-CSF neutralization, in contrast, was more selective, resulting in the preferential loss among the MPS populations of a cycling, monocyte-derived inflammatory dendritic cell population. Some mechanistic options for the specific CSF-dependent biologies enumerated are discussed. Copyright © 2015 by The American Association of Immunologists, Inc.

  9. Clinical significance of determination of changes of serum IGF-II, GM-CSF and TNF-α levels after treatment in children with acute nephritis

    International Nuclear Information System (INIS)

    Xu Xiaoyan; Zhou Hong; Xu Weiqin; Li Xinghua

    2008-01-01

    Objective: To explore the clinical significance of determination of changes of serum IGF-II, GM-CSF and TNF- α levels after treatment in children with acute nephritis. Methods: Serum IGF-II, GM-CSF and TNF-α levels (with RIA) were measured in 31 pediatric patients with acute nephritis and 35 controls. Results: Before treatment, the serum IGF-II, GM-CSF and TNF-α levels in the patients were significantly higher than those in controls (P< O.01). After treatment for 3 months, the serum IGF-II, GM-CSF and TNF-α levels, though markedly corrected, remained significantly higher than those in controls (P<0.05). Conclusion: Determination of changes of serum IGF-II, GM-CSF and TNF-α contents after treatment might be of prognostic importance in pediatric patients with acute nephritis. (authors)

  10. CD1d(hi)CD5+ B cells expanded by GM-CSF in vivo suppress experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Sheng, Jian Rong; Quan, Songhua; Soliven, Betty

    2014-09-15

    IL-10-competent subset within CD1d(hi)CD5(+) B cells, also known as B10 cells, has been shown to regulate autoimmune diseases. Whether B10 cells can prevent or suppress the development of experimental autoimmune myasthenia gravis (EAMG) has not been studied. In this study, we investigated whether low-dose GM-CSF, which suppresses EAMG, can expand B10 cells in vivo, and whether adoptive transfer of CD1d(hi)CD5(+) B cells would prevent or suppress EAMG. We found that treatment of EAMG mice with low-dose GM-CSF increased the proportion of CD1d(hi)CD5(+) B cells and B10 cells. In vitro coculture studies revealed that CD1d(hi)CD5(+) B cells altered T cell cytokine profile but did not directly inhibit T cell proliferation. In contrast, CD1d(hi)CD5(+) B cells inhibited B cell proliferation and its autoantibody production in an IL-10-dependent manner. Adoptive transfer of CD1d(hi)CD5(+) B cells to mice could prevent disease, as well as suppress EAMG after disease onset. This was associated with downregulation of mature dendritic cell markers and expansion of regulatory T cells resulting in the suppression of acetylcholine receptor-specific T cell and B cell responses. Thus, our data have provided significant insight into the mechanisms underlying the tolerogenic effects of B10 cells in EAMG. These observations suggest that in vivo or in vitro expansion of CD1d(hi)CD5(+) B cells or B10 cells may represent an effective strategy in the treatment of human myasthenia gravis. Copyright © 2014 by The American Association of Immunologists, Inc.

  11. Differential transfection efficiency rates of the GM-CSF gene into human renal cell carcinoma lines by lipofection.

    Science.gov (United States)

    Hernández, A; Zöller, K; Enczmann, J; Ebert, T; Schmitz-Draeger, B; Ackermann, R; Wernet, P

    1997-01-01

    One of the major questions in any gene therapy approach is the selection of the appropriate vector system. Here, the optimization of a gene transfer protocol for renal cell carcinoma using lipofection as a nonviral gene transduction system was evaluated. To select the promoter which gives the highest expression, different plasmids which are able to express Escherichia coli beta-galactosidase gene as a reporter gene under the control of different promoters were tested: human cytomegalovirus promoter (pCMVbeta), simian virus 40 promoter (pSVbeta), adenovirus promoter (ADbeta), and herpes simplex virus thymidine kinase promoter (TKbeta). The pCMVbeta revealed the highest expression of the beta-gal gene in the renal cell carcinoma (RCC) lines. Thus this CMV promoter was selected for the expression of the granulocyte-macrophage colony stimulator factor (GM-CSF) gene. Three different lipids (LipofectAmine, LipofectAce, and Lipofectin) were compared for their transduction efficiency, and the optimal conditions for quantitatively high lipofection rates were established. The consistently best results regarding gene expression as well as viability of the RCC lines were obtained when Lipofectin was used. Gene expression was monitored by a specific enzyme-linked immunosorbent assay and functionally validated by a cell proliferation test. The GM-CSF expression profile showed a peak at 48 hours after transfection and was still detectable after 5 days. Here the feasibility of efficient lipofection of the GM-CSF gene into RCC lines is demonstrated. Most importantly, considerable differences in the relative quantity of GM-CSF gene transfer into the different RCC lines was observed here. This may be of critical relevance for the design of any clinical gene transduction protocol in tumor cell vaccination attempts.

  12. A sequential erythropoietin and GM-CSF schedule offers clinical benefits in the treatment of anaemia in myelodysplastic syndromes.

    Science.gov (United States)

    Bernell, P; Stenke, L; Wallvik, J; Hippe, E; Hast, R

    1996-08-01

    In order to reduce anaemia in patients with myelodysplastic syndromes (MDS) a stepwise treatment protocol including erythropoietin (EP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) was designed. Thirty-seven MDS patients (stages I-III) with symptomatic anaemia were first given EPO 10,000 U s.c. 3 times weekly for 6 weeks. Those not responding, i.e. increased their haemoglobin levels > 15 g/l, proceeded into the second phase of the study where GM-CSF (200 micrograms/d. s.c. on weeks 1-6) was combined with EPO (10,000 U s.c. 3 times weekly on weeks 5-14). Following the initial EPO treatment phase, 14 of the 37 patients (38%) responded with increased haemoglobin levels. Responders were significantly different from non-responders in that their pre-treatment values of s-EPO, s-LDH and bone marrow blast cell counts were lower, their baseline haemoglobin levels higher and their transfusion dependency less pronounced. Eighteen of the 23 non-responders proceeded into the second phase, 13 of those were evaluable having completed the entire schedule. Three of the 13 initially EPO resistant patients (23%) responded to the GM-CSF/EPO combination with increased haemoglobin levels, suggesting a positive synergy between the two cytokines. Thus, the overall response rate to the present protocol was 46% (17 of 37 cases), but only a limited subset of the patients did clearly benefit from the combined GM-CSF/EPO administration. Therefore, we believe this step-wise approach to multiple growth factor treatment in MDS, starting with EPO alone and reserving the combination for refractory cases, has considerable advantages, taking into account both medical and socio-economical aspects.

  13. Functional paralysis of GM-CSF-derived bone marrow cells productively infected with ectromelia virus.

    Directory of Open Access Journals (Sweden)

    Lidia Szulc-Dąbrowska

    Full Text Available Ectromelia virus (ECTV is an orthopoxvirus responsible for mousepox, a lethal disease of certain strains of mice that is similar to smallpox in humans, caused by variola virus (VARV. ECTV, similar to VARV, exhibits a narrow host range and has co-evolved with its natural host. Consequently, ECTV employs sophisticated and host-specific strategies to control the immune cells that are important for induction of antiviral immune response. In the present study we investigated the influence of ECTV infection on immune functions of murine GM-CSF-derived bone marrow cells (GM-BM, comprised of conventional dendritic cells (cDCs and macrophages. Our results showed for the first time that ECTV is able to replicate productively in GM-BM and severely impaired their innate and adaptive immune functions. Infected GM-BM exhibited dramatic changes in morphology and increased apoptosis during the late stages of infection. Moreover, GM-BM cells were unable to uptake and process antigen, reach full maturity and mount a proinflammatory response. Inhibition of cytokine/chemokine response may result from the alteration of nuclear translocation of NF-κB, IRF3 and IRF7 transcription factors and down-regulation of many genes involved in TLR, RLR, NLR and type I IFN signaling pathways. Consequently, GM-BM show inability to stimulate proliferation of purified allogeneic CD4+ T cells in a primary mixed leukocyte reaction (MLR. Taken together, our data clearly indicate that ECTV induces immunosuppressive mechanisms in GM-BM leading to their functional paralysis, thus compromising their ability to initiate downstream T-cell activation events.

  14. The Combined Impact of Surgery and Immunomodulation With Low Dose Cytoxan and GM-CSF in the Early Treatment of Breast Cancer

    National Research Council Canada - National Science Library

    Kendra, Kari L

    2004-01-01

    The purpose of this study was to evaluate the combined impact of surgery and immunomodulation with low dose cytoxan and GM-CSF on the development of dendritic cells and the activation of T cells in vivo...

  15. X-ray-induced production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by mouse spleen cells in culture

    International Nuclear Information System (INIS)

    Onoda, M.; Shinoda, M.; Tsuneoka, K.; Shikita, M.

    1980-01-01

    Spleen cells were collected from normal mice and cultured in a medium containing 20% calf serum. Addition of lipopolysaccharide (LPS) in the culture significantly increased the production of granulocyte-macrophage colony-stimulating factor (GM-CSF), and a maximum induction was attained in 5 days. Irradiation of the spleen cells with 300 to 3000 R x rays also enhanced the production of GM-CSF, but there was a latent period of about 5 days before the factor appeared in the culture medium. The observed difference between LPS and x rays in the timing of inducing GM-CSF production in the spleen cell culture was consistent with the difference observed in animals. These results suggest that different mechanisms of GM-CSF production operate in the spleen in response to either LPS or x rays

  16. Clinical significance of determination of changes of serum NO, NOS and GM-CSF levels after massage therapy in patients with periarthritis of shoulder diseases

    International Nuclear Information System (INIS)

    Liu Feng; Chen Lixia; Pan Xiaohong

    2011-01-01

    Objective: To explore the clinical significance of changes of serum NO, NOS and GM-CSF levels after massage therapy in patients with periarthritis of shoulder diseases. Methods: Serum GM-CSF level was determined with RIA and serum NO, NOS levels were determined with chemical methods both before and after massage therapy in 33 patients with periarthritis of shoulder diseases as well as in 35 normal healthy controls. Results: Before massage therapy the serum concertration of NO, NOS and GM-CSF in the patients were significantly higher than those in controls (P 0.05). Conclusion: Detection of serum NO, NOS and GM-CSF levels were closely related to the occurrence and development of the disease also provides important value clinically. (authors)

  17. Clinical significance of measurement of changes in serum TNF-α and GM-CSF levels after treatment in children with bronchial asthma

    International Nuclear Information System (INIS)

    Liu Heng

    2006-01-01

    Objective: To study the clinical significance of the changes of levels of tumor necrosis factor-α (TNF-α) and granulocyte-macrophage colony stimulating factor (GM-CSF) after treatment in children with bronchial asthma. Methods: Serum TNF-α and GM-CSF levels were measured with RIA in 32 patients with bronchial asthma both before and after treatment as well as in 30 controls. Results: Before treatment the serum TNF-α and GM-CSF levels in patients were significantly higher than those in the controls (P 0.05 ). Conclusion: Changes of serum TNF-α and GM-CSF levels contents after treatment might be of prognostic importance in children with bronchial asthma. (authors)

  18. Clinical significance of determination of changes of serum IL-6, IL-10 and GM-CSF levels after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Qin Wenjing

    2008-01-01

    Objective: To explore the changes of Serum IL-6, IL-10 and GM-CSF levels after treatment in pediatric patients with bronchial asthma. Methods: Serum IL-6, IL-10 and GM-CSF levels were measured with RIA in 33 pediatric patients with bronchial asthma both before and after treatment as well as in 30 controls. Results: Before treatment, the serum IL-6, IL-10 and GM-CSF levels were significantly higher than those in controls (P 0.05). Conclusion: Detection of serum IL-6, IL-10 and GM-CSF levels were useful for assessment of therapeutic efficacy and were of important clinical values in pediatric patients with bronchial asthma. (authors)

  19. Clinical significance of determination of serum IL-2, IL-6 and GM-CSF levels after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Wang Zhuo; Sun Jin; Yao Li

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IL-2, IL-6 and GM-CSF levels after treatment in pediatric patients with bronchial asthma. Methods: Serum levels of IL-2, IL-6 and GM-CSF were measured with RIA in 36 pediatric patients with bronchiol asthma and 30 controls. Results: Before treatment, the serum levels of IL-6, GM-CSF were significantly higher in the patients than those in controls (P 0.05), Serum IL-2 levels were negatively correlated with the IL-6 and GM-CSF levels (r=-0.5846, -0.6018, P<0.01). Conclusion: These cytokines participated in the pathogenesis of bronchial asthma in pediatric patients. Mornitoring the changes of their serum levels was helpful for the management of the diseases. (authors)

  20. GM-CSF produced by non-hematopoietic cells is required for early epithelial cell proliferation and repair of injured colonic mucosa1,2

    Science.gov (United States)

    Egea, Laia; McAllister, Christopher S.; Lakhdari, Omar; Minev, Ivelina; Shenouda, Steve; Kagnoff, Martin F.

    2012-01-01

    GM-CSF is a growth factor that promotes the survival and activation of macrophages and granulocytes, and dendritic cell (DC) differentiation and survival in vitro. The mechanism by which exogenous GM-CSF ameliorates the severity of Crohn’s disease in humans and colitis in murine models has been considered mainly to reflect its activity on myeloid cells. We used GM-CSF deficient (GM-CSF−/−) mice to probe the functional role of endogenous host-produced GM-CSF in a colitis model induced after injury to the colon epithelium. Dextran sodium sulfate (DSS) at doses that resulted in little epithelial damage and mucosal ulceration in wild type (WT) mice resulted in marked colon ulceration and delayed ulcer healing in GM-CSF−/− mice. Colon crypt epithelial cell proliferation in vivo was significantly decreased in GM-CSF−/− mice at early times after DSS injury. This was paralleled by decreased expression of crypt epithelial cell genes involved in cell cycle, proliferation, and wound healing. Decreased crypt cell proliferation and delayed ulcer healing in GM-CSF−/− mice were rescued by exogenous GM-CSF, indicating the lack of a developmental abnormality in the epithelial cell proliferative response in those mice. Non-hematopoietic cells and not myeloid cells produced the GM-CSF important for colon epithelial proliferation after DSS-induced injury as revealed by bone marrow chimera and DC depletion experiments, with colon epithelial cells being the cellular source of GM-CSF. Endogenous epithelial cell produced GM-CSF has a novel non-redundant role in facilitating epithelial cell proliferation and ulcer healing in response to injury of the colon crypt epithelium. PMID:23325885

  1. Adenoviral vector-mediated GM-CSF gene transfer improves anti-mycobacterial immunity in mice - role of regulatory T cells.

    Science.gov (United States)

    Singpiel, Alena; Kramer, Julia; Maus, Regina; Stolper, Jennifer; Bittersohl, Lara Friederike; Gauldie, Jack; Kolb, Martin; Welte, Tobias; Sparwasser, Tim; Maus, Ulrich A

    2018-03-01

    Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in differentiation, survival and activation of myeloid and non-myeloid cells with important implications for lung antibacterial immunity. Here we examined the effect of pulmonary adenoviral vector-mediated delivery of GM-CSF (AdGM-CSF) on anti-mycobacterial immunity in M. bovis BCG infected mice. Exposure of M. bovis BCG infected mice to AdGM-CSF either applied on 6h, or 6h and 7days post-infection substantially increased alveolar recruitment of iNOS and IL-12 expressing macrophages, and significantly increased accumulation of IFNγ pos T cells and particularly regulatory T cells (Tregs). This was accompanied by significantly reduced mycobacterial loads in the lungs of mice. Importantly, diphtheria toxin-induced depletion of Tregs did not influence mycobacterial loads, but accentuated immunopathology in AdGM-CSF-exposed mice infected with M. bovis BCG. Together, the data demonstrate that AdGM-CSF therapy improves lung protective immunity against M. bovis BCG infection in mice independent of co-recruited Tregs, which however critically contribute to limit lung immunopathology in BCG-infected mice. These data may be relevant to the development of immunomodulatory strategies to limit immunopathology-based lung injury in tuberculosis in humans. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. CD14-dependent monocyte isolation enhances phagocytosis of listeria monocytogenes by proinflammatory, GM-CSF-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Caroline Neu

    Full Text Available Macrophages are an important line of defence against invading pathogens. Human macrophages derived by different methods were tested for their suitability as models to investigate Listeria monocytogenes (Lm infection and compared to macrophage-like THP-1 cells. Human primary monocytes were isolated by either positive or negative immunomagnetic selection and differentiated in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF or macrophage colony-stimulating factor (M-CSF into pro- or anti-inflammatory macrophages, respectively. Regardless of the isolation method, GM-CSF-derived macrophages (GM-Mφ stained positive for CD206 and M-CSF-derived macrophages (M-Mφ for CD163. THP-1 cells did not express CD206 or CD163 following incubation with PMA, M- or GM-CSF alone or in combination. Upon infection with Lm, all primary macrophages showed good survival at high multiplicities of infection whereas viability of THP-1 was severely reduced even at lower bacterial numbers. M-Mφ generally showed high phagocytosis of Lm. Strikingly, phagocytosis of Lm by GM-Mφ was markedly influenced by the method used for isolation of monocytes. GM-Mφ derived from negatively isolated monocytes showed low phagocytosis of Lm whereas GM-Mφ generated from positively selected monocytes displayed high phagocytosis of Lm. Moreover, incubation with CD14 antibody was sufficient to enhance phagocytosis of Lm by GM-Mφ generated from negatively isolated monocytes. By contrast, non-specific phagocytosis of latex beads by GM-Mφ was not influenced by treatment with CD14 antibody. Furthermore, phagocytosis of Lactococcus lactis, Escherichia coli, human cytomegalovirus and the protozoan parasite Leishmania major by GM-Mφ was not enhanced upon treatment with CD14 antibody indicating that this effect is specific for Lm. Based on these observations, we propose macrophages derived by ex vivo differentiation of negatively selected human primary monocytes as the most

  3. A novel combination treatment of armed oncolytic adenovirus expressing IL-12 and GM-CSF with radiotherapy in murine hepatocarcinoma

    International Nuclear Information System (INIS)

    Kim, Wonwoo; Seong, Jinsil; Oh, Hae-Jin; Koom, Woong-Sub; Choi, Kyung-Joo; Yun, Chae-Ok

    2011-01-01

    In this study, a novel combination treatment of armed oncolytic adenovirus expressing interleukin 12 (IL-12) and granulocyte-macrophage colony-stimulating factor (GM-CSF) with radiation was investigated for antitumor and antimetastatic effect in a murine hepatic cancer (HCa-I) model. Tumor bearing syngeneic mice were treated with radiation, armed oncolytic virus Ad-ΔE1Bmt7 (dB7) expressing both IL-12 and GM-CSF (armed dB7), or a combination of both. The adenovirus was administered by intratumoral injection 1 x 10 8 plaque forming units (PFU) per tumor in 50 μl of phosphate buffered saline (PBS) four times every other day. Tumor response to treatment was determined by a tumor growth delay assay. Metastatic potential was evaluated by a lung metastasis model. To understand the underlying mechanism, the level of apoptosis was examined as well as the change in microvessel density and expression of immunological markers: CD4+, CD8+ and Cd11c. The combination of armed dB7 and radiation resulted in significant growth delay of murine hepatic cancer, HCa-1, with an enhancement factor of 4.3. The combination treatment also resulted in significant suppression of lung metastasis. Increase of apoptosis level as well as decrease of microvessel density was shown in the combination treatment, suggesting an underlying mechanism for the enhancement of antitumor effect. Expression of immunological markers: CD4+, CD8+ and Cd11c also increased in the combination treatment. This study showed that a novel combination treatment of radiotherapy with armed oncolytic adenovirus expressing IL-12 and GM-CSF was effective in suppressing primary tumor growth. (author)

  4. Granulocyte macrophage-colony stimulating factor (GM-CSF) and sucralfate in prevention of radiation-induced mucositis: a prospective randomized study

    International Nuclear Information System (INIS)

    Makkonen, Tuula A.; Minn, Heikki; Jekunen, Antti; Vilja, Pekka; Tuominen, Juhani; Joensuu, Heikki

    2000-01-01

    Purpose: To compare subcutaneously given molgramostim (GM-CSF) and sucralfate mouth washings to sucralfate mouth washings in prevention of radiation-induced mucositis. Methods and Materials: Forty head and neck cancer patients were randomly assigned to use either GM-CSF and sucralfate (n = 20) or sucralfate alone (n = 20) during radiotherapy. Sucralfate was used as 1.0 g mouth washing 6 times daily after the first 10 Gy of radiotherapy, and 150-300 μg GM-CSF was given subcutaneously. The grade of radiation mucositis and blood cell counts were monitored weekly. Salivary lactoferrin was measured as a surrogate marker for oral mucositis. Results: We found no significant difference between the molgramostim and the control groups in the oral mucositis grade, oral pain, use of analgesic drugs, weight loss, or survival. The median maximum neutrophil counts (median, 9.2 x 10 9 /L vs. 5.9 x 10 9 /L, p = 0.0005), eosinophil counts (median, 1.3 x 10 9 /L vs. 0.2 x 10 9 /L, p = 0.0004), and salivary lactoferrin concentrations were higher in patients who received GM-CSF. The most common toxicities in the GM-CSF plus sucralfate group were skin reactions at the GM-CSF injection site (65%), fever (30%), bone pain (25%), and nausea (15%), whereas the toxicity of sucralfate given alone was minimal. Conclusion: We found no evidence indicating that subcutaneously given GM-CSF reduces the severity of radiation-induced mucositis

  5. GM-CSF and IL-3 Modulate Human Monocyte TNF-α Production and Renewal in In Vitro Models of Trained Immunity.

    Science.gov (United States)

    Borriello, Francesco; Iannone, Raffaella; Di Somma, Sarah; Loffredo, Stefania; Scamardella, Eloise; Galdiero, Maria Rosaria; Varricchi, Gilda; Granata, Francescopaolo; Portella, Giuseppe; Marone, Gianni

    2016-01-01

    GM-CSF and IL-3 are hematopoietic cytokines that also modulate the effector functions of several immune cell subsets. In particular, GM-CSF and IL-3 exert a significant control on monocyte and macrophage effector functions, as assessed in experimental models of inflammatory and autoimmune diseases and also in human studies. Here, we sought to investigate the mechanisms and the extent to which GM-CSF and IL-3 modulate the pro-inflammatory, LPS-mediated, activation of human CD14 + monocytes taking into account the new concept of trained immunity (i.e., the priming stimulus modulates the response to subsequent stimuli mainly by inducing chromatin remodeling and increased transcription at relevant genetic loci). We demonstrate that GM-CSF and IL-3 priming enhances TNF-α production upon subsequent LPS stimulation (short-term model of trained immunity) in a p38- and SIRT2-dependent manner without increasing TNF primary transcript levels (a more direct measure of transcription), thus supporting a posttranscriptional regulation of TNF-α in primed monocytes. GM-CSF and IL-3 priming followed by 6 days of resting also results in increased TNF-α production upon LPS stimulation (long-term model of trained immunity). In this case, however, GM-CSF and IL-3 priming induces a c-Myc-dependent monocyte renewal and increase in cell number that is in turn responsible for heightened TNF-α production. Overall, our results provide insights to understand the biology of monocytes in health and disease conditions in which the hematopoietic cytokines GM-CSF and IL-3 play a role and also extend our knowledge of the cellular and molecular mechanisms of trained immunity.

  6. GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization.

    Science.gov (United States)

    Halstead, E Scott; Umstead, Todd M; Davies, Michael L; Kawasawa, Yuka Imamura; Silveyra, Patricia; Howyrlak, Judie; Yang, Linlin; Guo, Weichao; Hu, Sanmei; Hewage, Eranda Kurundu; Chroneos, Zissis C

    2018-01-05

    Influenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract. Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established. Mice were infected intranasally with influenza A virus (PR8 strain). Supra-physiologic levels of GM-CSF were induced in the airways using the double transgenic GM-CSF (DTGM) or littermate control mice starting on 3 days post-infection (dpi). Assessment of respiratory mechanical parameters was performed using the flexiVent rodent ventilator. RNA sequence analysis was performed on FACS-sorted airway macrophage subsets at 8 dpi. Supra-physiologic levels of GM-CSF conferred a survival benefit, arrested the deterioration of lung mechanics, and reduced the abundance of protein exudates in bronchoalveolar (BAL) fluid to near baseline levels. Transcriptome analysis, and subsequent validation ELISA assays, revealed that excess GM-CSF re-directs macrophages from an "M1-like" to a more "M2-like" activation state as revealed by alterations in the ratios of CXCL9 and CCL17 in BAL fluid, respectively. Ingenuity pathway analysis predicted that GM-CSF surplus during IAV infection elicits expression of anti-inflammatory mediators and moderates M1 macrophage pro-inflammatory signaling by Type II interferon (IFN-γ). Our data indicate that application of high levels of GM-CSF in the lung after influenza A virus infection alters pathogenic "M1-like" macrophage inflammation. These results indicate a possible therapeutic strategy for respiratory virus-associated pneumonia and acute lung injury.

  7. Synovial CD4+ T-cell-derived GM-CSF supports the differentiation of an inflammatory dendritic cell population in rheumatoid arthritis

    Science.gov (United States)

    Reynolds, G; Gibbon, J R; Pratt, A G; Wood, M J; Coady, D; Raftery, G; Lorenzi, A R; Gray, A; Filer, A; Buckley, C D; Haniffa, M A; Isaacs, J D; Hilkens, C M U

    2016-01-01

    Objective A population of synovial inflammatory dendritic cells (infDCs) has recently been identified in rheumatoid arthritis (RA) and is thought to be monocyte-derived. Here, we investigated the role and source of granulocyte macrophage-colony-stimulating factor (GM-CSF) in the differentiation of synovial infDC in RA. Methods Production of GM-CSF by peripheral blood (PB) and synovial fluid (SF) CD4+ T cells was assessed by ELISA and flow cytometry. In vitro CD4+ T-cell polarisation experiments were performed with T-cell activating CD2/CD3/CD28-coated beads in the absence or presence of pro-Th1 or pro-Th17 cytokines. CD1c+ DC and CD16+ macrophage subsets were flow-sorted and analysed morphologically and functionally (T-cell stimulatory/polarising capacity). Results RA-SF CD4+ T cells produced abundant GM-CSF upon stimulation and significantly more than RA-SF mononuclear cells depleted of CD4+ T cells. GM-CSF-producing T cells were significantly increased in RA-SF compared with non-RA inflammatory arthritis SF, active RA PB and healthy donor PB. GM-CSF-producing CD4+ T cells were expanded by Th1-promoting but not Th17-promoting conditions. Following coculture with RA-SF CD4+ T cells, but not healthy donor PB CD4+ T cells, a subpopulation of monocytes differentiated into CD1c+ infDC; a process dependent on GM-CSF. These infDC displayed potent alloproliferative capacity and enhanced GM-CSF, interleukin-17 and interferon-γ production by CD4+ T cells. InfDC with an identical phenotype to in vitro generated cells were significantly enriched in RA-SF compared with non-RA-SF/tissue/PB. Conclusions We demonstrate a therapeutically tractable feedback loop of GM-CSF secreted by RA synovial CD4+ T cells promoting the differentiation of infDC with potent capacity to induce GM-CSF-producing CD4+ T cells. PMID:25923217

  8. Efficacy and safety of granulocyte macrophage-colony stimulating factor (GM-CSF) on the frequency and severity of radiation mucositis in patients with head and neck carcinoma

    International Nuclear Information System (INIS)

    Kannan, V.; Bapsy, Poonamallee P.; Anantha, Naranappa; Doval, Dinesh Chandra; Vaithianathan, Hema; Banumathy, G.; Reddy, Krishnamurthy B.; Kumaraswamy, Saklaspur Veerappaiah; Shenoy, Ashok Mohan

    1997-01-01

    Purpose: Based on the clinical evidence of mucosal protection by GM-CSF during cytotoxic chemotherapy, a pilot study was undertaken to determine the safety and mucosal reaction of patients receiving GM-CSF while undergoing definitive conventional fractionated radiotherapy in head and neck carcinoma. Methods and Materials: Patients were considered eligible if buccal mucosa and oropharynx were included in the teleradiation field. Ten adult patients with squamous cell carcinoma of head and neck (buccal mucosa--8 and posterior (1(3)) tongue--2) were entered into the trial. Radiation therapy was delivered with telecobalt machine at conventional 2 Gy fraction and 5 fractions/week. The radiation portals consisted of two parallel opposing lateral fields. GM-CSF was given subcutaneously at a dose of 1 μg/kg body weight, daily, after 20 Gy until the completion of radiation therapy. Patients were evaluated daily for mucosal reaction, pain, and functional impairment. Results: The median radiation dose was 66 Gy. Eight patients received ≥60 Gy. The tolerance to GM-CSF was good. All 10 patients completed the planned daily dose of GM-CSF without interruption. Mucosal toxicity was Grade I in four patients till the completion of radiotherapy (dose range 50-66 Gy). Six patients developed Grade II reaction, fibrinous mucosal lesions of maximum size 1.0-1.5 cm, during radiotherapy. None developed Grade III mucositis. The maximum mucosal pain was Grade I during GM-CSF therapy. In two patients after starting GM-CSF the pain reduced in intensity. Functional impairment was mild to moderate. All patients were able to maintain adequate oral intake during the treatment period. Total regression of mucosal reaction occurred within 8 days following completion of radiotherapy. Conclusions: GM-CSF administration concurrently with conventional fractionated radiotherapy was feasible without significant toxicity. The acute side effects of radiotherapy namely mucositis, pain, and functional

  9. GM-CSF and IL-4 produced by NKT cells inversely regulate IL-1β production by macrophages.

    Science.gov (United States)

    Ahn, Sehee; Jeong, Dongjin; Oh, Sae Jin; Ahn, Jiye; Lee, Seung Hyo; Chung, Doo Hyun

    2017-02-01

    Natural Killer T (NKT) cells are distinct T cell subset that link innate and adaptive immune responses. IL-1β, produced by various immune cells, plays a key role in the regulation of innate immunity in vivo. However, it is unclear whether NKT cells regulate IL-1β production by macrophages. To address this, we co-cultured NKT cells and peritoneal macrophages in the presence of TCR stimulation and inflammasome activators. Among cytokines secreted from NKT cells, GM-CSF enhanced IL-1β production by macrophages via regulating LPS-mediated pro-IL-1β expression and NLRP3-dependent inflammasome activation, whereas IL-4 enhanced M2-differentiation of macrophages and decreased IL-1β production. Together, our findings suggest the NKT cells have double-sided effects on IL-1β-mediated innate immune responses by producing IL-4 and GM-CSF. These findings may be helpful for a comprehensive understanding of NKT cell-mediated regulatory mechanisms of the pro-inflammatory effects of IL-1β in inflammatory diseases in vivo. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  10. Summary of bi-shRNA/GM-CSF augmented autologous tumor cell immunotherapy (FANG™) in advanced cancer of the liver.

    Science.gov (United States)

    Nemunaitis, John; Barve, Minal; Orr, Douglas; Kuhn, Joseph; Magee, Mitchell; Lamont, Jeffrey; Bedell, Cynthia; Wallraven, Gladice; Pappen, Beena O; Roth, Alyssa; Horvath, Staci; Nemunaitis, Derek; Kumar, Padmasini; Maples, Phillip B; Senzer, Neil

    2014-01-01

    Therapies for advanced hepatocellular carcinoma (HCC) are limited. We carried out a phase I trial of a novel autologous whole-cell tumor cell immunotherapy (FANG™), which incorporates a dual granulocyte macrophage colony-stimulating factor (GM-CSF) expressive/bifunctional small hairpin RNA interference (bi-shRNAi) vector. The bi-shRNAi DNA targets furin, which is a proconvertase of transforming growth factors beta (TGFβ) 1 and 2. Safety, mechanism, immunoeffectiveness, and suggested benefit were previously shown [Senzer et al.: Mol Ther 2012;20:679-689; Senzer et al.: J Vaccines Vaccin 2013;4:209]. We now provide further follow-up of a subset of 8 HCC patients. FANG manufacturing was successful in 7 of 8 attempts (one failure due to insufficient cell yield). Median GM-CSF expression was 144 pg/10(6) cells, TGFβ1 knockdown was 100%, and TGFβ2 knockdown was 93% of the vector-transported cells. Five patients were vaccinated (1 or 2.5×10(7) cells/intradermal injection, 6-11 vaccinations). No FANG toxicity was observed. Three of these patients demonstrated evidence of an immune response to the autologous tumor cell sample. Long-term follow-up demonstrated survival of 319, 729, 784, 931+, and 1,043+ days of the FANG-treated patients. In conclusion, evidence supports further assessment of the FANG immunotherapy in HCC. © 2014 S. Karger AG, Basel.

  11. Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas.

    Science.gov (United States)

    Malhotra, Sandeep; Kim, Teresa; Zager, Jonathan; Bennett, Joseph; Ebright, Michael; D'Angelica, Michael; Fong, Yuman

    2007-04-01

    Oncolytic cancer therapy using herpes simplex viruses (HSV) that have direct tumoricidal effects and cancer immunotherapy using the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) have each been effective in preclinical testing. NV1034 is a multimutated oncolytic HSV carrying the gene for murine GM-CSF that attempts to combine these 2 anticancer strategies. The purpose of this study was to compare NV1034 to NV1023, the parent HSV mutants lacking GM-CSF, to determine if such combined oncolytic and immunotherapy using a single vector has advantages over oncolytic therapy alone. Expression GM-CSF in vitro did not alter the infectivity, cytotoxicity, or replication of NV1034 compared to the noncytokine-secreting control. Tumors infected with NV1034 produced GM-CSF in picogram quantities. In vivo efficacy of the viruses against murine colorectal carcinoma CT26 and murine hepatoma Hepa l-6 was then tested in subcutaneous tumors in syngeneic Balb/c and C57 L/J mice, respectively. In these immune-competent models, NV1034 and NV1023 each demonstrated potent antitumor activity. Treatment with NV1034 had significantly better antitumor effect compared to treatment with NV1023. Furthermore, there was no difference in the antitumor efficacy of these viruses in mice depleted of CD4+ and CD8+ T lymphocytes. Viral vectors combining oncolytic and immunotherapy are promising agents in treatment of colorectal carcinoma and hepatoma.

  12. Local application of GM-CSF for treatment of chemoirradiation-induced mucositis in patients with advanced carcinoma of the head and neck: results of controlled clinical trial

    International Nuclear Information System (INIS)

    Reichtomann, K.A.

    2002-01-01

    Purpose: the study was designed to assess prospectively the efficacy of GM-CSF (granulocyte-macrophage colony-stimulating factor) mouthwash solution in the management of chemoirradiation induced oral mucositis for head and neck cancer patients. Methods and materials: thirty-five patients with advanced carcinoma of the head and neck were evaluated for mucositis during the first cycle of chemoirradiation therapy. GM-CSF 400 μg in 250 cc of water for 1 h of mouth washing was prescribed. Active comparator was a conventional mucositis therapy combination. The procedure started once mucositis grade 1 (using the WHO grading) was detected. Patients, examined twice a week, were evaluated for oral mucositis and oral infections. Assessment of subjective pain was provided using a visual analogue scale. Blood tests were taken weekly. Results: the results of statistical evaluation of mucositis using the WHO-grading showed no significant differences between the two treatment groups. Local application of GM-CSF significantly reduced subjective pain during the second week of chemoirradiation therapy. Statistical analysis of the leucocytes-, platelet count, haemoglobin level and development of oral infections revealed no significant differences between the two treatment groups. Conclusion: in combined chemoirradiation therapy schemes the RTOG/EORTC toxicity scale should be used. In selected cases of mucositis attended with severe pain, GM-CSF should be observed within the therapeutic considerations. Controlled clinical trials with larger patient population are required to evaluate the role of GM-CSF in this indication. (author)

  13. Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis.

    Science.gov (United States)

    Hirota, Keiji; Hashimoto, Motomu; Ito, Yoshinaga; Matsuura, Mayumi; Ito, Hiromu; Tanaka, Masao; Watanabe, Hitomi; Kondoh, Gen; Tanaka, Atsushi; Yasuda, Keiko; Kopf, Manfred; Potocnik, Alexandre J; Stockinger, Brigitta; Sakaguchi, Noriko; Sakaguchi, Shimon

    2018-06-19

    Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete the cytokine GM-CSF and also expanded synovial-resident innate lymphoid cells (ILCs) in inflamed joints. Activated synovial ILCs, which expressed CD25, IL-33Ra, and TLR9, produced abundant GM-CSF upon stimulation by IL-2, IL-33, or CpG DNA. Loss of GM-CSF production by either ILCs or radio-resistant stromal cells prevented Th17 cell-mediated arthritis. GM-CSF production by Th17 cells augmented chronic inflammation but was dispensable for the initiation of arthritis. We showed that GM-CSF-producing ILCs were present in inflamed joints of rheumatoid arthritis patients. Thus, a cellular cascade of autoimmune Th17 cells, ILCs, and stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Determination of the levels of serum TNF-α, GM-CSF and HA in asthmatic patients

    International Nuclear Information System (INIS)

    Li Qing; Ma Yunbao

    2002-01-01

    Objective: To study the relationship between the diversity of the state of asthma and the three serum markers (TNF-α, GM-CSF and HA). Methods: RIA was adopted to measure the three markers in 66 asthmatic patients and 30 controls. Results: The levels of the three markers in patients during attack (n = 36) were significantly higher than those in controls (p < 0.01, p < 0.01, p < 0.05). The three markers declined significantly in remission group (n = 30), but were still significantly higher than those in controls (p < 0.05). Conclusion: There is a close relationship between the levels of the three markers and the attack of asthma. Immunomodulator is therefore suggested to be used in addition to anti inflammatory treatment

  15. Recombinant Newcastle disease virus (NDV) with inserted gene coding for GM-CSF as a new vector for cancer immunogene therapy

    NARCIS (Netherlands)

    Janke, M.; Peeters, B.P.H.; Leeuw, de O.S.; Moormann, R.J.M.; Arnold, A.; Fournier, P.; Schirrmacher, V.

    2007-01-01

    This is the first report describing recombinant (rec) Newcastle disease virus (NDV) as vector for gene therapy of cancer. The gene encoding granulocyte/macrophage colony-stimulating factor (GM-CSF) was inserted as an additional transcription unit at two different positions into the NDV genome. The

  16. Experimental study of changes of skin blister fluid NPY, IL-12, sICAM-1 and GM-CSF levels in patients with vitiligo in progressive stage

    International Nuclear Information System (INIS)

    Bi Mingye; Huang Haifen

    2011-01-01

    Objective: To explore the significance of changes of skin blister fluid NPY, IL-12, sICAM-1 and GM-CSF levels in patients with vitiligo in progressive stage. Methods: 80 patients with vitiligo in progressive stage were divided into two groups (vulgaris vitiligo groups : n=54, segmental vitiligo groups : n=26) Their blister fluid levels of NPY and GM-CSF were determined by radioimmunoassay(RIA), and IL-12 and sICAM-1 were determined by enzyme immunoassay. Results: The levels of skin blister fluid NPY were definitely higher in vitiliginous skin than those in non-vitiliginous patches in segmental vitiligo groups (P 0.05). The levels of skin blister fluid IL-12, sICAM-1 and GM-CSF were all obviously higher in vitiliginous skin than that in non-vitiliginous patches in vulgaris vitiligo groups (P 0.05). Conclusion: The changes of skin blister fluid NPY, IL-12, sICAM-1 and GM-CSF levels in vitiliginous skin may be closely related to development of difference type vitiligo patients with vitiligo, determination of 4 indexes might be helpful for studying the pathogenesis and clinical diagnosis of vitiligo. (authors)

  17. Cost-effectiveness and quality-of-life assessment of GM-CSF as an adjunct to intensive remission induction chemotherapy in elderly patients with acute myeloid leukaemia

    NARCIS (Netherlands)

    Uyl-de Groot, CA; Lowenberg, B; Vellenga, E; Suciu, S; Willemze, R; Rutten, FFH

    We conducted a prospective, randomized, multicentre clinical trial comparing the effects and costs of GM-CSF as an adjunct to intensive chemotherapy in elderly patients with acute myeloid leukaemia (AML). The patients were randomized to either daunomycin-cytosine arabinoside (control arm: rr = 161)

  18. Cellular immunotherapy using irradiated lung cancer cell vaccine co-expressing GM-CSF and IL-18 can induce significant antitumor effects

    International Nuclear Information System (INIS)

    Tian, Hongwei; Zhang, Xiaomei; Dai, Lei; Chen, Xiaolei; Zhang, Shuang; Yang, Yang; Yu, Dechao; Wei, Yuquan; Deng, Hongxin; Shi, Gang; Yang, Guoyou; Zhang, Junfeng; Li, Yiming; Du, Tao; Wang, Jianzhou; Xu, Fen; Cheng, Lin

    2014-01-01

    Although the whole tumor cell vaccine can provide the best source of immunizing antigens, there is still a limitation that most tumors are not naturally immunogenic. Tumor cells genetically modified to secrete immune activating cytokines have been proved to be more immunogenic. IL-18 could augment proliferation of T cells and cytotoxicity of NK cells. GM-CSF could stimulate dendritic cells, macrophages and enhance presentation of tumor antigens. In our study, we used mouse GM-CSF combined with IL-18 to modify Lewis lung cancer LL/2, then investigated whether vaccination could suppress tumor growth and promote survival. The Lewis lung cancer LL/2 was transfected with co-expressing mouse GM-CSF and IL-18 plasmid by cationic liposome, then irradiated with a sublethal dose X ray (100 Gy) to prepare vaccines. Mice were subcutaneously immunized with this inactivated vaccine and then inoculated with autologous LL/2 to estimate the antitumor efficacy. The studies reported here showed that LL/2 tumor cell vaccine modified by a co-expressing mouse GM-CSF and IL-18 plasmid could significantly inhibit tumor growth and increased survival of the mice bearing LL/2 tumor whether prophylactic or adoptive immunotherapy in vivo. A significant reduction of proliferation and increase of apoptosis were also observed in the tumor treated with vaccine of co-expressing GM-CSF and IL-18. The potent antitumor effect correlated with higher secretion levels of pro-inflammatory cytokines such as IL-18, GM-CSF, interferon-γ in serum, the proliferation of CD4 + IFN-γ + , CD8 + IFN-γ + T lymphocytes in spleen and the infiltration of CD4 + , CD8 + T in tumor. Furthermore, the mechanism of tumor-specific immune response was further proved by 51 Cr cytotoxicity assay in vitro and depletion of CD4, CD8, NK immune cell subsets in vivo. The results suggested that the antitumor mechanism was mainly depended on CD4 + , CD8 + T lymphocytes. These results provide a new insight into therapeutic mechanisms

  19. Multi-response model for rheumatoid arthritis based on delay differential equations in collagen-induced arthritic mice treated with an anti-GM-CSF antibody.

    Science.gov (United States)

    Koch, Gilbert; Wagner, Thomas; Plater-Zyberk, Christine; Lahu, Gezim; Schropp, Johannes

    2012-02-01

    Collagen-induced arthritis (CIA) in mice is an experimental model for rheumatoid arthritis, a human chronic inflammatory destructive disease. The therapeutic effect of neutralizing the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) by an antibody was examined in the mouse disease in a view of deriving a pharmacokinetic/pharmacodynamic (PKPD) model. In CIA mice the development of disease is measured by a total arthritic score (TAS) and an ankylosis score (AKS). We present a multi-response PKPD model which describes the time course of the unperturbed and perturbed TAS and AKS. The antibody acts directly on GM-CSF by binding to it. Therefore, a compartment for the cytokine GM-CSF is an essential component of the mathematical model. This compartment drives the disease development in the PKPD model. Different known properties of arthritis development in the CIA model are included in the PKPD model. Firstly, the inflammation, driven by GM-CSF, dominates at the beginning of the disease and decreases after some time. Secondly, a destructive (ankylosis) part evolves in the TAS that is delayed in time. In order to model these two properties a delay differential equation was used. The PKPD model was applied to different experiments with doses ranging from 0.1 to 100 mg/kg. The influence of the drug was modeled by a non-linear approach. The final mathematical model consists of three differential equations representing the compartments for GM-CSF, inflammation and destruction. Our mathematical model described well all available dosing schedules by a simultaneous fit. We also present an equivalent and easy reformulation as ordinary differential equation which grants the use of standard PKPD software.

  20. GM-CSF Monocyte-Derived Cells and Langerhans Cells As Part of the Dendritic Cell Family

    Directory of Open Access Journals (Sweden)

    Manfred B. Lutz

    2017-10-01

    Full Text Available Dendritic cells (DCs and macrophages (Mph share many characteristics as components of the innate immune system. The criteria to classify the multitude of subsets within the mononuclear phagocyte system are currently phenotype, ontogeny, transcription patterns, epigenetic adaptations, and function. More recently, ontogenetic, transcriptional, and proteomic research approaches uncovered major developmental differences between Flt3L-dependent conventional DCs as compared with Mphs and monocyte-derived DCs (MoDCs, the latter mainly generated in vitro from murine bone marrow-derived DCs (BM-DCs or human CD14+ peripheral blood monocytes. Conversely, in vitro GM-CSF-dependent monocyte-derived Mphs largely resemble MoDCs whereas tissue-resident Mphs show a common embryonic origin from yolk sac and fetal liver with Langerhans cells (LCs. The novel ontogenetic findings opened discussions on the terminology of DCs versus Mphs. Here, we bring forward arguments to facilitate definitions of BM-DCs, MoDCs, and LCs. We propose a group model of terminology for all DC subsets that attempts to encompass both ontogeny and function.

  1. IL-2 and GM-CSF are regulated by DNA demethylation during activation of T cells, B cells and macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yan [College of Animal Science and Technology, Northwest A and F University, Yangling, Shaanxi 712100 (China); Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, ACT 2601 (Australia); Ohms, Stephen J. [ACRF Biomolecular Resource Facility, John Curtin School of Medical Research, The Australian National University, ACT 2601 (Australia); Shannon, Frances M. [Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, ACT 2601 (Australia); The University of Canberra, ACT 2602 (Australia); Sun, Chao, E-mail: sunchao2775@163.com [College of Animal Science and Technology, Northwest A and F University, Yangling, Shaanxi 712100 (China); Fan, Jun Y., E-mail: jun.fan@anu.edu.au [Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, ACT 2601 (Australia)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer DNA methylation is dynamic and flexible and changes rapidly upon cell activation. Black-Right-Pointing-Pointer DNA methylation controls the inducible gene expression in a given cell type. Black-Right-Pointing-Pointer Some enzymes are involved in maintaining the methylation profile of immune cells. -- Abstract: DNA demethylation has been found to occur at the promoters of a number of actively expressed cytokines and is believed to play a critical role in transcriptional regulation. While many DNA demethylation studies have focused on T cell activation, proliferation and differentiation, changes in DNA methylation in other types of immune cells are less well studied. We found that the expression of two cytokines (IL-2 and GM-CSF) responded differently to activation in three types of immune cells: EL4, A20 and RAW264.7 cells. Using the McrBC and MeDIP approaches, we observed decreases in DNA methylation at a genome-wide level and at the promoters of the genes of these cytokines. The expression of several potential enzymes/co-enzymes involved in the DNA demethylation pathways seemed to be associated with immune cell activation.

  2. IL-2 and GM-CSF are regulated by DNA demethylation during activation of T cells, B cells and macrophages

    International Nuclear Information System (INIS)

    Li, Yan; Ohms, Stephen J.; Shannon, Frances M.; Sun, Chao; Fan, Jun Y.

    2012-01-01

    Highlights: ► DNA methylation is dynamic and flexible and changes rapidly upon cell activation. ► DNA methylation controls the inducible gene expression in a given cell type. ► Some enzymes are involved in maintaining the methylation profile of immune cells. -- Abstract: DNA demethylation has been found to occur at the promoters of a number of actively expressed cytokines and is believed to play a critical role in transcriptional regulation. While many DNA demethylation studies have focused on T cell activation, proliferation and differentiation, changes in DNA methylation in other types of immune cells are less well studied. We found that the expression of two cytokines (IL-2 and GM-CSF) responded differently to activation in three types of immune cells: EL4, A20 and RAW264.7 cells. Using the McrBC and MeDIP approaches, we observed decreases in DNA methylation at a genome-wide level and at the promoters of the genes of these cytokines. The expression of several potential enzymes/co-enzymes involved in the DNA demethylation pathways seemed to be associated with immune cell activation.

  3. Enrichment of Ly6Chi monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model.

    Science.gov (United States)

    Zhao, Weidong; Zhou, Xian; Zhao, Gan; Lin, Qing; Wang, Xianzheng; Yu, Xueping; Wang, Bin

    2017-12-02

    Adjuvants are considered a necessary component for HBV therapeutic vaccines but few are licensed in clinical practice due to concerns about safety or efficiency. In our recent study, we established that a combination protocol of 3-day pretreatments with GM-CSF before a vaccination (3 × GM-CSF+VACCINE) into the same injection site could break immune tolerance and cause over 90% reduction of HBsAg level in the HBsAg transgenic mouse model. Herein, we further investigated the therapeutic potential of the combination in AAV8-1.3HBV-infected mice. After 4 vaccinations, both serum HBeAg and HBsAg were cleared and there was a 95% reduction of HBV-positive hepatocytes, in addition to the presence of large number of infiltrating CD8 + T cells in the livers. Mechanistically, the HBV-specific T-cell responses were elicited via a 3 × GM-CSF+VACCINE-induced conversion of CCR2-dependent CD11b + Ly6C hi monocytes into CD11b + CD11c + DCs. Experimental depletion of Ly6C hi monocytes resulted in a defective HBV-specific immune response thereby abrogating HBV eradication. This vaccination strategy could lead to development of an effective therapeutic protocol against chronic HBV in infected patients.

  4. Clinical significance of measurement of plasma relevant cytokines (GM-CSF, IL-2, TPO, EPO) levels in patients with aplastic anemia

    International Nuclear Information System (INIS)

    Yu Tintin

    2006-01-01

    Objective: To investigate the role of relevant cytokines in the development and pathogenesis of aplastic anemia. Methods: Plasma GM-CSF, IL-2, TPO (with RIA) and EPO (with CLIA) contents were measured in 100 patients (acute 43, chronic 57) with aplastic anemia and 50 controls. Complete blood count was also performed in all these subjects. Results: The peripheral RBC, WBC, platelet counts and GM-CSF contents were significantly lower in the patients with aplastic anemia than those in the controls (P<0.05), while the IL-2, EPO and TPO contents were significantly higher in the patients (P<0.05). GM-CSF contents were positively correlated with the WBC numbers. EPO contents were negatively correlated with the RBC counts and TPO contents were correlated (negatively) with the platelet counts. Conclusion: There was correlationship between each blood elements (WBC, RBC, platelet) and its corresponding cytokine (GS-CSF, EPO, TPO respectively). IL-2 contents were not correlated with WBC counts. (authors)

  5. GM-CSF production allows the identification of immunoprevalent antigens recognized by human CD4+ T cells following smallpox vaccination.

    Directory of Open Access Journals (Sweden)

    Valeria Judkowski

    Full Text Available The threat of bioterrorism with smallpox and the broad use of vaccinia vectors for other vaccines have led to the resurgence in the study of vaccinia immunological memory. The importance of the role of CD4+ T cells in the control of vaccinia infection is well known. However, more CD8+ than CD4+ T cell epitopes recognized by human subjects immunized with vaccinia virus have been reported. This could be, in part, due to the fact that most of the studies that have identified human CD4+ specific protein-derived fragments or peptides have used IFN-γ production to evaluate vaccinia specific T cell responses. Based on these findings, we reasoned that analyzing a large panel of cytokines would permit us to generate a more complete analysis of the CD4 T cell responses. The results presented provide clear evidence that TNF-α is an excellent readout of vaccinia specificity and that other cytokines such as GM-CSF can be used to evaluate the reactivity of CD4+ T cells in response to vaccinia antigens. Furthermore, using these cytokines as readout of vaccinia specificity, we present the identification of novel peptides from immunoprevalent vaccinia proteins recognized by CD4+ T cells derived from smallpox vaccinated human subjects. In conclusion, we describe a "T cell-driven" methodology that can be implemented to determine the specificity of the T cell response upon vaccination or infection. Together, the single pathogen in vitro stimulation, the selection of CD4+ T cells specific to the pathogen by limiting dilution, the evaluation of pathogen specificity by detecting multiple cytokines, and the screening of the clones with synthetic combinatorial libraries, constitutes a novel and valuable approach for the elucidation of human CD4+ T cell specificity in response to large pathogens.

  6. Cytokine-primed bone marrow stem cells vs. peripheral blood stem cells for autologous transplantation: a randomized comparison of GM-CSF vs. G-CSF.

    Science.gov (United States)

    Weisdorf, D; Miller, J; Verfaillie, C; Burns, L; Wagner, J; Blazar, B; Davies, S; Miller, W; Hannan, P; Steinbuch, M; Ramsay, N; McGlave, P

    1997-10-01

    Autologous transplantation for non-Hodgkins lymphoma and Hodgkin's disease is widely used as standard therapy for those with high-risk or relapsed tumor. Peripheral blood stem cell (PBSC) collections have nearly completely replaced bone marrow stem cell (BMSC) harvests because of the perceived advantages of more rapid engraftment, less tumor contamination in the inoculum, and better survival after therapy. The advantage of PBSC, however, may derive from the hematopoietic stimulating cytokines used for PBSC mobilization. Therefore, we tested a randomized comparison of GM-CSF vs. G-CSF used to prime either BMSC or PBSC before collection for use in autologous transplantation. Sixty-two patients receiving transplants (31 PBSC; 31 BMSC) for non-Hodgkin's lymphoma (n = 51) or Hodgkin's disease (n = 11) were treated. All patients received 6 days of randomly assigned cytokine. Those with cellular marrow in morphologic remission underwent BMSC harvest, while those with hypocellular marrow or microscopic marrow tumor involvement had PBSC collected. Neutrophil recovery was similarly rapid in all groups (median 14 days; range 10-23 days), though two patients had delayed neutrophil recovery using GM-CSF primed PBSC (p = 0.01). Red cell and platelet recovery were significantly quicker after BMSC mobilized with GM-CSF or PBSC mobilized with G-CSF. This speedier hematologic recovery resulted in earlier hospital discharge as well. However, in multivariate analysis, neither the stem cell source nor randomly assigned G-CSF vs. GM-CSF was independently associated with earlier multilineage hematologic recovery or shorter hospital stay. Relapse-free survival was not independently affected by either the assigned stem cell source or the randomly assigned priming cytokine, though malignant relapse was more frequent in those assigned to PBSC (RR of relapse 3.15, p = 0.03). These data document that BMSC, when collected following cytokine priming, can yield a similarly rapid hematologic

  7. Coadministration of Recombinant Adenovirus Expressing GM-CSF with Inactivated H5N1 Avian Influenza Vaccine Increased the Immune Responses and Protective Efficacy Against a Wild Bird Source of H5N1 Challenge.

    Science.gov (United States)

    Wang, Xiangwei; Wang, Xinglong; Jia, Yanqing; Wang, Chongyang; Tang, Qiuxia; Han, Qingsong; Xiao, Sa; Yang, Zengqi

    2017-10-01

    Wild birds play a key role in the spread of avian influenza virus (AIV). There is a continual urgent requirement for AIV vaccines to address the ongoing genetic changes of AIV. In the current study, we trialed a novel AIV vaccine against the wild bird source of H5N1 type AIV with recombinant adenovirus expressing granulocyte monocyte colony-stimulating factor (GM-CSF) as an adjuvant. A total of 150-day-old commercial chicks, with AIV-maternal-derived antibody, were divided into 6 groups. The primary vaccination was performed at day 14 followed by a subsequent boosting and intramuscular challenge on day 28 and 42, respectively. Recombinant GM-CSF (rGM-CSF) expressed by adenovirus, named as rAd-GM-CSF, raised the hemagglutination inhibition (HI) titers (log 2 ) against AIV from 7.0 (vaccinate with inactivated vaccine alone) to 8.4 after booster immunization. Moreover, the rGM-CSF addition markedly increased the expression of interferon-γ, interleukin-4, and major histocompatibility complex-II in the lungs, compared with those immunized with inactivated vaccine alone on day 29, that is, 18 h post booster immunization. Following challenge, chicks inoculated with the inactivated AIV vaccine and rAd-GM-CSF together exhibited mild clinical signs and 62% survivals compared to 33% in the group immunized with inactivated AIV vaccine alone. Higher level of HI titers, immune related molecule expressions, and protection ratio demonstrates a good potential of rGM-CSF in improving humoral and cell mediated immune responses of inactivated AIV vaccines.

  8. Affinity purification of human granulocyte macrophage colony-stimulating factor receptor alpha-chain. Demonstration of binding by photoaffinity labeling

    International Nuclear Information System (INIS)

    Chiba, S.; Shibuya, K.; Miyazono, K.; Tojo, A.; Oka, Y.; Miyagawa, K.; Takaku, F.

    1990-01-01

    The human granulocyte macrophage colony-stimulating factor (GM-CSF) receptor alpha-chain, a low affinity component of the receptor, was solubilized and affinity-purified from human placenta using biotinylated GM-CSF. Scatchard analysis of 125 I-GM-CSF binding to the placental membrane extract disclosed that the GM-CSF receptor had a dissociation constant (Kd) of 0.5-0.8 nM, corresponding to the Kd value of the GM-CSF receptor alpha-chain on the intact placental membrane. Affinity labeling of the solubilized protein using a photoreactive cross-linking agent, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB), demonstrated a single specific band of 70-95 kDa representing a ligand-receptor complex. Approximately 2 g of the placental membrane extract was subjected to a biotinylated GM-CSF-fixed streptavidin-agarose column, resulting in a single major band at 70 kDa on a silver-stained sodium dodecyl sulfate gel. The radioiodination for the purified material disclosed that the purified protein had an approximate molecular mass of 70 kDa and a pI of 6.6. Binding activity of the purified material was demonstrated by photoaffinity labeling using HSAB- 125 I-GM-CSF, producing a similar specific band at 70-95 kDa as was demonstrated for the crude protein

  9. Overcoming HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice.

    Science.gov (United States)

    Wang, Xianzheng; Dong, Aihua; Xiao, Jingjing; Zhou, Xingjun; Mi, Haili; Xu, Hanqian; Zhang, Jiming; Wang, Bin

    2016-11-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to be a potential vaccine adjuvant despite contradictory results from animal and human studies. The discrepancies may be due to the different doses and regimens of GM-CSF that were used, given that either mature or immature dendritic cells (DCs) could be induced under different conditions. To test the hypothesis that GM-CSF can be used as a novel adjuvant for a hepatitis B virus (HBV) therapeutic vaccine, we administered GM-CSF once per day for three days prior to vaccination with recombinant HBV vaccine (rHBVvac) in mice. We observed greater DC maturation in these pre-treated animals at day 3 as compared to day 1 or day 2 of daily GM-CSF administration. This strategy was further investigated for its ability to break the immune tolerance established in hepatitis B surface antigen-transgenic (HBsAg-Tg) animals. We found that the levels of induced anti-HBsAg antibodies were significantly higher in animals following three days of GM-CSF pre-treatment before rHBV vaccination after the third immunization. In addition to the increase in anti-HBsAg antibody levels, cell-mediated anti-HBsAg responses, including delayed-type hypersensitivity, T-cell proliferation, interferon-γ production, and cytotoxic T lymphocytes, were dramatically enhanced in the three-day GM-CSF pre-treated group. After adoptive transfers of CD8 + T cells from immunized animals, antigen-specific CD8 + T cells were observed in the livers of recipient HBsAg-Tg animals. Moreover, the three-day pre-treatments with GM-CSF prior to rHBVvac vaccination could significantly eliminate HBsAg-positive hepatocytes, suggesting beneficial therapeutic effects. Therefore, this protocol utilizing GM-CSF as an adjuvant in combination with the rHBVvac vaccine has the potential to become a novel immunotherapy for chronic hepatitis B patients.

  10. Interleukin-4 enhances trafficking and functional activities of GM-CSF-stimulated mouse myeloid-derived dendritic cells at late differentiation stage

    International Nuclear Information System (INIS)

    Yin, Shu-Yi; Wang, Chien-Yu; Yang, Ning-Sun

    2011-01-01

    Mouse bone marrow-derived dendritic cells (BMDCs) are being employed as an important model for translational research into the development of DC-based therapeutics. For such use, the localization and specialized mobility of injected BMDCs within specific immune tissues are known to define their immunity and usefulness in vivo. In this study, we demonstrate that IL-4, a key driving factor for in vitro propagation and differentiation of BMDCs, when added during a late culture stage can enhance the in vivo trafficking activity of granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced BMDCs. It suggests that the temporal control of IL-4 stimulation during the in vitro generation of DCs drastically affects the DC trafficking efficiency in vivo. With this modification of IL-4 stimulation, we also show that much less cytokine was needed to generate BMDCs with high purity and yield that secrete a high level of cytokines and possess a good capacity to induce proliferation of allogeneic CD4 + T cells, as compared to the conventional method that uses a continuous supplement of GM-CSF and IL-4 throughout cultivation. These results provide us with an important know-how for differentiation of BMDCs from myeloid stem cells, and for use of other immune cells in related medical or stem cell applications.

  11. Interleukin-4 enhances trafficking and functional activities of GM-CSF-stimulated mouse myeloid-derived dendritic cells at late differentiation stage

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Shu-Yi, E-mail: in_shuyi@hotmail.com [Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, ROC (China); Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC (China); Taiwan International Graduate Program (TIGP), Molecular and Biological Agricultural Sciences Program, Academia Sinica, Taipei, Taiwan, ROC (China); Wang, Chien-Yu, E-mail: sallywang1973@hotmail.com [Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, ROC (China); Yang, Ning-Sun, E-mail: nsyang@gate.sinica.edu.tw [Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, ROC (China); Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC (China); Taiwan International Graduate Program (TIGP), Molecular and Biological Agricultural Sciences Program, Academia Sinica, Taipei, Taiwan, ROC (China)

    2011-09-10

    Mouse bone marrow-derived dendritic cells (BMDCs) are being employed as an important model for translational research into the development of DC-based therapeutics. For such use, the localization and specialized mobility of injected BMDCs within specific immune tissues are known to define their immunity and usefulness in vivo. In this study, we demonstrate that IL-4, a key driving factor for in vitro propagation and differentiation of BMDCs, when added during a late culture stage can enhance the in vivo trafficking activity of granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced BMDCs. It suggests that the temporal control of IL-4 stimulation during the in vitro generation of DCs drastically affects the DC trafficking efficiency in vivo. With this modification of IL-4 stimulation, we also show that much less cytokine was needed to generate BMDCs with high purity and yield that secrete a high level of cytokines and possess a good capacity to induce proliferation of allogeneic CD4{sup +}T cells, as compared to the conventional method that uses a continuous supplement of GM-CSF and IL-4 throughout cultivation. These results provide us with an important know-how for differentiation of BMDCs from myeloid stem cells, and for use of other immune cells in related medical or stem cell applications.

  12. CCR6+ Th cells in the cerebrospinal fluid of persons with multiple sclerosis are dominated by pathogenic non-classic Th1 cells and GM-CSF-only-secreting Th cells.

    Science.gov (United States)

    Restorick, S M; Durant, L; Kalra, S; Hassan-Smith, G; Rathbone, E; Douglas, M R; Curnow, S J

    2017-08-01

    Considerable attention has been given to CCR6 + IL-17-secreting CD4 + T cells (Th17) in the pathology of a number of autoimmune diseases including multiple sclerosis (MS). However, other Th subsets also play important pathogenic roles, including those that secrete IFNγ and GM-CSF. CCR6 expression by Th17 cells allows their migration across the choroid plexus into the cerebrospinal fluid (CSF), where they are involved in the early phase of experimental autoimmune encephalomyelitis (EAE), and in MS these cells are elevated in the CSF during relapses and contain high frequencies of autoreactive cells. However, the relatively low frequency of Th17 cells suggests they cannot by themselves account for the high percentage of CCR6 + cells in MS CSF. Here we identify the dominant CCR6 + T cell subsets in both the blood and CSF as non-classic Th1 cells, including many that secrete GM-CSF, a key encephalitogenic cytokine. In addition, we show that Th cells secreting GM-CSF but not IFNγ or IL-17, a subset termed GM-CSF-only-secreting Th cells, also accumulate in the CSF. Importantly, in MS the proportion of IFNγ- and GM-CSF-secreting T cells expressing CCR6 was significantly enriched in the CSF, and was elevated in MS, suggesting these cells play a pathogenic role in this disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Serum concentrations of GM-CSF and G-CSF correlate with the Th1/Th2 cytokine response in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

    DEFF Research Database (Denmark)

    Moser, Claus; Jensen, Peter Østrup; Pressler, Tacjana

    2005-01-01

    mobilizing monocytes and PMNs from the bone marrow, GM-CSF, G-CSF and IL-3 select subsets of dendritic cells, which subsequently induce distinct Th responses. Therefore, the present study examines the correlation between the mobilizing cytokines in serum and the Th responses. The IFN-gamma and IL-4...... production by peripheral blood mononuclear cells, and the concentrations of GM-CSF and G-CSF in serum as well as lung function, were determined in 37 CF patients with and 6 CF patients without chronic P. aeruginosa lung infection. The GM-CSF/G-CSF ratio correlated both with the IFN-gamma production and good...... lung function. In addition, an inverse correlation between IL-3 and IFN-gamma was observed. The results indicate involvement of endogenous GM-CSF, G-CSF and IL-3 in the skewed Th response in CF, and change to a Th1-dominated response might be achieved with GM-CSF treatment....

  14. Effect of intramammary infusion of recombinant bovine GM-CSF and IL-8 on CMT score, somatic cell count, and milk mononuclear cell populations in Holstein cows with Staphylococcus aureus subclinical mastitis.

    Science.gov (United States)

    Kiku, Yoshio; Ozawa, Tomomi; Takahashi, Hideyuki; Kushibiki, Shiro; Inumaru, Shigeki; Shingu, Hiroyuki; Nagasawa, Yuya; Watanabe, Atsushi; Hata, Eiji; Hayashi, Tomohito

    2017-09-01

    The effect of intramammary infusion of recombinant bovine granulocyte-macrophage colony-stimulating factor (rbGM-CSF) and interleukin-8 (rbIL-8) on mononuclear cell populations in quarters, somatic cell count (SCC) and the California Mastitis Test (CMT) score were investigated. From the selected cows with naturally occurring Staphylococcus aureus subclinical mastitis, one quarter of each cow were selected for the infusions of rbGM-CSF (400 μg/5 mL/quarter, n = 9), rbIL-8 (1 mg/5 mL/quarter, n = 9), and phosphate-buffered saline (5 mL/quarter, n = 7). The CMT score of both cytokines post infusion temporarily increased between days 0 and 1 and significantly decreased between days 7 and 14 compared to the preinfusion level. The SCC on day 14 after infusions of rbGM-CSF tended to be lower than that of the control group. The percentage of CD14+ cells increased on days 1 and 2 post infusion of rbGM-CSF. The percentage of CD4+ and CD8+ cells also increased on days 2 and 3, suggesting that the infusion of rbGM-CSF enhanced cellular immunity in the mammary gland. In contrast, the percentage of CD14+ cells decreased on days 0.25 and 1 post infusion of rbIL-8. No significant changes in the percentages of CD4+ and CD8+ cells in milk after infusion of rbIL-8 were evident during the experimental period, which suggested that rbIL-8 had little effect on the function of T cells in the mammary gland. These results indicated that rbGM-CSF and rbIL-8 decreased the CMT score by a different mechanism and may have a potential as therapeutic agents for subclinical mastitis.

  15. Granulocyte-macrophage stimulating factor (GM-CSF increases circulating dendritic cells but does not abrogate suppression of adaptive cellular immunity in patients with metastatic colorectal cancer receiving chemotherapy

    Directory of Open Access Journals (Sweden)

    Martinez Micaela

    2012-01-01

    Full Text Available Abstract Background Advanced cancer and chemotherapy are both associated with immune system suppression. We initiated a clinical trial in patients receiving chemotherapy for metastatic colorectal cancer to determine if administration of GM-CSF in this setting was immunostimulatory. Methods Between June, 2003 and January, 2007, 20 patients were enrolled in a clinical trial (NCT00257322 in which they received 500 ug GM-CSF daily for 4 days starting 24 hours after each chemotherapy cycle. There were no toxicities or adverse events reported. Blood was obtained before chemotherapy/GM-CSF administration and 24 hours following the final dose of GM-CSF and evaluated for circulating dendritic cells and adaptive immune cellular subsets by flow cytometry. Peripheral blood mononuclear cell (PBMC expression of γ-interferon and T-bet transcription factor (Tbx21 by quantitative real-time PCR was performed as a measure of Th1 adaptive cellular immunity. Pre- and post-treatment (i.e., chemotherapy and GM-CSF samples were evaluable for 16 patients, ranging from 1 to 5 cycles (median 3 cycles, 6 biologic sample time points. Dendritic cells were defined as lineage (- and MHC class II high (+. Results 73% of patients had significant increases in circulating dendritic cells of ~3x for the overall group (5.8% to 13.6%, p = 0.02 and ~5x excluding non-responders (3.2% to 14.5%, p Tbx21 levels declined by 75% following each chemotherapy cycle despite administration of GM-CSF (p = 0.02. PBMC γ-interferon expression, however was unchanged. Conclusions This clinical trial confirms the suppressive effects of chemotherapy on Th1 cellular immunity in patients with metastatic colorectal cancer but demonstrates that mid-cycle administration of GM-CSF can significantly increase the proportion of circulating dendritic cells. As the role of dendritic cells in anti-tumor immunity becomes better defined, GM-CSF administration may provide a non-toxic intervention to augment this arm

  16. Successful use of a defined antigen/GM-CSF adjuvant vaccine to treat mucosal leishmaniasis refractory to antimony: a case report

    Directory of Open Access Journals (Sweden)

    Badaro Roberto

    2001-01-01

    Full Text Available Immunotherapy has been proposed as a method to treat mucosal leishmaniasis for many years, but the approach has been hampered by poor definition and variability of antigens used, and results have been inconclusive. We report here a case of antimonial-refractory mucosal leishmaniasis in a 45 year old male who was treated with three single injections (one per month with a cocktail of four Leishmania recombinant antigens selected after documented hypo-responsiveness of the patient to these antigens, plus 50mg of GM-CSF as vaccine adjuvant. Three months after treatment, all lesions had resolved completely and the patient remains without relapse after two years. Side effects of the treatment included only moderate erythema and induration at the injection site after the second and third injections. We conclude that carefully selected microbial antigens and cytokine adjuvant can be successful as immunotherapy for patients with antimonial-refractory mucosal leishmaniasis.

  17. GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates.

    Directory of Open Access Journals (Sweden)

    Peter T Loudon

    2010-06-01

    Full Text Available The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99 HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun was analyzed in rhesus macaques.Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine.These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract.

  18. Combination of intratumoral injections of vaccinia virus MVA expressing GM-CSF and immunization with DNA vaccine prolongs the survival of mice bearing HPV16 induced tumors with downregulated expression of MHC class I molecules

    Czech Academy of Sciences Publication Activity Database

    Němečková, Š.; Šmahel, M.; Hainz, P.; Macková, J.; Zurková, K.; Gabriel, P.; Indrová, Marie; Kutinová, L.

    2007-01-01

    Roč. 54, č. 4 (2007), s. 326-333 ISSN 0028-2685 R&D Projects: GA MZd NR8004 Institutional research plan: CEZ:AV0Z50520514 Keywords : vaccinia virus MVA expressing GM- CSF * DNA vaccine * HPV16 induced tumors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.208, year: 2007

  19. Growth factors G-CSF and GM-CSF differentially preserve chemotaxis of neutrophils aging in vitro

    NARCIS (Netherlands)

    Wolach, Baruch; van der Laan, Luc J. W.; Maianski, Nikolai A.; Tool, Anton T. J.; van Bruggen, Robin; Roos, Dirk; Kuijpers, Taco W.

    2007-01-01

    OBJECTIVE: The ability of human neutrophils to migrate was studied during culture in vitro. METHODS: Neutrophils were isolated from human blood and cultured at 37 degrees C. Apoptosis was determined by Annexin-V fluorescein isothiocyanate binding. Receptor expression was measured by fluorescence in

  20. Heat shock protein 27-derived atheroprotection involves reverse cholesterol transport that is dependent on GM-CSF to maintain ABCA1 and ABCG1 expression in ApoE-/- mice.

    Science.gov (United States)

    Pulakazhi Venu, Vivek Krishna; Adijiang, Ayinuer; Seibert, Tara; Chen, Yong-Xiang; Shi, Chunhua; Batulan, Zarah; O'Brien, Edward R

    2017-06-01

    Recently, we demonstrated that heat shock protein (HSP)-27 is protective against the development of experimental atherosclerosis, reducing plaque cholesterol content by more than 30%. Moreover, elevated HSP-27 levels are predictive of relative freedom from clinical cardiovascular events. HSP-27 signaling occurs via the activation of NF-κB, which induces a marked up-regulation in expression of granulocyte-monocyte colony-stimulating factor (GM-CSF), a cytokine that is known to alter ABC transporters involved in reverse cholesterol transport (RCT). Therefore, we hypothesized that HSP-27-derived GM-CSF has a potent role in impeding plaque formation by promoting macrophage RCT and sought to better characterize this pathway. Treatment of THP-1 cells, RAW-Blue cells, and primary macrophages with recombinant HSP-27 resulted in NF-κB activation via TLR-4 and was inhibited by various pharmacologic blockers of this pathway. Moreover, HSP-27-induced upregulation of GM-CSF expression was dependent on TLR-4 signaling. Recombinant (r)HSP-27 treatment of ApoE -/- female (but not male) mice for 4 wk yielded reductions in plaque area and cholesterol clefts of 33 and 47%, respectively, with no effect on GM-CSF -/- ApoE -/- mice. With 12 wk of rHSP-27 treatment, both female and male mice showed reductions in plaque burden (55 and 42%, respectively) and a 60% reduction in necrotic core area but no treatment effect in GM-CSF -/- ApoE -/- mice. In vitro functional studies revealed that HSP-27 enhanced the expression of ABCA1 and ABCG1, as well as facilitated cholesterol efflux in vitro by ∼10%. These novel findings establish a paradigm for HSP-27-mediated RCT and set the stage for the development of HSP-27 atheroprotective therapeutics.-Pulakazhi Venu, V. K., Adijiang, A., Seibert, T., Chen, Y.-X., Shi, C., Batulan, Z., O'Brien, E. R. Heat shock protein 27-derived atheroprotection involves reverse cholesterol transport that is dependent on GM-CSF to maintain ABCA1 and ABCG1

  1. [Cytokines in cancer chemotherapy: present state and problems in use of G- and GM-CSF for solid tumors in Japan].

    Science.gov (United States)

    Ogawara, M

    1998-01-01

    The present state and the problems of G and GM-CSF in cancer chemotherapy, especially for solid tumors in Japan, were reviewed. One of the problems is that adaptation is restricted to several tumors, and the other that recommended doses are about half or one-fourth as much as in North America or Europe. With G-CSF after dose-intensive chemotherapy in small-cell lung cancer, three studies showed G-CSF shortened the duration of neutropenia, and reduced the incidence of neutropenic fever, use of antibiotics and hospitalization, while they showed no advantages in terms of response rate and the incidence of infection-related death. Moreover, the effect on survival has not been proved. In afebrile neutropenic patients, G-CSF could accelerate recovery from neutropenia, but did not reduce the incidence of neutropenic fever. In febrile neutropenic patients with antibiotics, it could also accelerate recovery from neutropenia, but did not reduce neutropenic fever compared with no CSF except in some subsets. Our retrospective study showed the effects of G-CSF in grade 4 neutropenia were comparable with grade 3 neutropenia. The functions of neutrophils with G-CSF after chemotherapy were reported to be increased or maintained. Clinical benefits were only obtained in certain dose-intensive chemotherapy or in limited subsets. Additional clinical trials and a guideline like ASCO's should be planned.

  2. Disabled infectious single cycle herpes simplex virus (DISC-HSV) is a candidate vector system for gene delivery/expression of GM-CSF in human prostate cancer therapy.

    Science.gov (United States)

    Parkinson, Richard J; Mian, Shahid; Bishop, Michael C; Gray, Trevor; Li, Geng; McArdle, Stephanie E B; Ali, Selman; Rees, Robert C

    2003-06-15

    DISC-HSV is a replication incompetent herpes simplex virus that is a highly efficient vector for the transduction of genes in vivo and in vitro. We examine the ability of DISC-HSV to infect human prostate cancer cell-lines and xenograft tumor models, and induce expression of reporter and therapeutic cytokine genes. Infection was confirmed by cellular staining for the beta-galactosidase reporter gene product, and by EM. Human GM-CSF production following DISC-hGMCSF infection was measured using ELISA. The metabolic activity of infected cells was determined by NADP/NADPH assay. Cell death was estimated by cell-cycle analysis using flow cytometry with propidium iodide staining. Infection of DU145, PC3 and LNCaP cells with DISC-HSV was dose dependent. Cells infected with DISC-hGM-CSF released significant levels of hGM-CSF for 3 days. NADP/NADPH assay suggested that infected cells continued to be metabolically active for 3 days post-infection, which was consistent with flow cytometry findings that cell death did not occur within 7 days of infection. Tumor xenografts injected with DISC-HSV expressed beta-galactosidase, and intracellular viral particles were demonstrated using EM. We have previously reported the rejection of established tumors following intra-tumoral injection of DISC-GMCSF. This study demonstrates the ability of DISC-HSV to infect prostate cancer and express GMCSF at significant levels. We suggest that prostate cancer is a potential target for therapy using DISC-HSV containing GM-CSF. Copyright 2003 Wiley-Liss, Inc.

  3. Effect of the association of IGF-I, IGF-II, bFGF, TGF-beta1, GM-CSF, and LIF on the development of bovine embryos produced in vitro.

    Science.gov (United States)

    Neira, J A; Tainturier, D; Peña, M A; Martal, J

    2010-03-15

    This study examined the influence of the following growth factors and cytokines on early embryonic development: insulin-like growth factors I and II (IGF-I, IGF-II), basic fibroblast growth factor (bFGF), transforming growth factor (TGF-beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), and leukemia inhibitory factor (LIF). Synthetic oviduct fluid (SOF) was used as the culture medium. We studied the development of bovine embryos produced in vitro and cultured until Day 9 after fertilization. TGF-beta1, bFGF, GM-CSF, and LIF used on their own significantly improved the yield of hatched blastocysts. IGF-I, bFGF, TGF-beta1, GM-CSF, and LIF significantly accelerated embryonic development, especially the change from the expanded blastocyst to hatched blastocyst stages. Use of a combination of these growth factors and cytokines (GF-CYK) in SOF medium produced higher percentages of blastocysts and hatched blastocysts than did use of SOF alone (45% and 22% vs. 24% and 12%; PGM-CSF, produces similar results to 10% fetal calf serum for the development of in vitro-produced bovine embryos. This entirely synthetic method of embryo culture has undeniable advantages for the biosecurity of embryo transfer. Copyright 2010 Elsevier Inc. All rights reserved.

  4. Distinct Properties of Human M-CSF and GM-CSF Monocyte-Derived Macrophages to Simulate Pathological Lung Conditions In Vitro: Application to Systemic and Inflammatory Disorders with Pulmonary Involvement.

    Science.gov (United States)

    Lescoat, Alain; Ballerie, Alice; Augagneur, Yu; Morzadec, Claudie; Vernhet, Laurent; Fardel, Olivier; Jégo, Patrick; Jouneau, Stéphane; Lecureur, Valérie

    2018-03-17

    Macrophages play a central role in the pathogenesis of inflammatory and fibrotic lung diseases. However, alveolar macrophages (AM) are poorly available in humans to perform in vitro studies due to a limited access to broncho-alveolar lavage (BAL). In this study, to identify the best alternative in vitro model for human AM, we compared the phenotype of AM obtained from BAL of patients suffering from three lung diseases (lung cancers, sarcoidosis and Systemic Sclerosis (SSc)-associated interstitial lung disease) to human blood monocyte-derived macrophages (MDMs) differentiated with M-CSF or GM-CSF. The expression of eight membrane markers was evaluated by flow cytometry. Globally, AM phenotype was closer to GM-CSF MDMs. However, the expression levels of CD163, CD169, CD204, CD64 and CD36 were significantly higher in SSc-ILD than in lung cancers. Considering the expression of CD204 and CD36, the phenotype of SSc-AM was closer to MDMs, from healthy donors or SSc patients, differentiated by M-CSF rather than GM-CSF. The comparative secretion of IL-6 by SSc-MDMs and SSc-AM is concordant with these phenotypic considerations. Altogether, these results support the M-CSF MDM model as a relevant in vitro alternative to simulate AM in fibrotic disorders such as SSc.

  5. Needle-free Biojector injection of a dengue virus type 1 DNA vaccine with human immunostimulatory sequences and the GM-CSF gene increases immunogenicity and protection from virus challenge in Aotus monkeys

    International Nuclear Information System (INIS)

    Raviprakash, Kanakatte; Ewing, Dan; Simmons, Monika; Porter, Kevin R.; Jones, Trevor R.; Hayes, Curtis G.; Stout, Richard; Murphy, Gerald S.

    2003-01-01

    A dengue-1 DNA vaccine containing sequences encoding premembrane and envelope proteins (DIME) was previously shown to elicit virus neutralizing antibodies in rhesus and Aotus monkeys, and the primates were partially protected from viremia upon challenge. To increase the neutralizing antibody levels and subsequent protection from virus challenge, four strategies were evaluated: (a) coimmunization with a plasmid expressing Aotus GM-CSF gene; (b) coimmunization with a plasmid containing human immunostimulatory sequences (ISS); (c) coimmunization with both the GM-CSF gene and ISS; and (d) delivery of vaccine using the needle-free Biojector system. Vaccination with the mixed formulation containing DIME, GM-CSF gene, and ISS, by either needle injection or Biojector, led to neutralizing antibody titers that were stable for up to 6 months after vaccination. Furthermore, 6 of 7 monkeys (85%), and 7 of 8 monkeys (87%) receiving this formulation were completely protected from viremia when challenged 1 and 6 months after vaccination, respectively. This is a significant improvement compared to our previous study in which one of three monkeys (33%) receiving just the DIME vaccine was completely protected from viremia at 6 months after immunization

  6. SV-BR-1-GM, a Clinically Effective GM-CSF-Secreting Breast Cancer Cell Line, Expresses an Immune Signature and Directly Activates CD4+ T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Markus D. Lacher

    2018-05-01

    Full Text Available Targeted cancer immunotherapy with irradiated, granulocyte–macrophage colony-stimulating factor (GM-CSF-secreting, allogeneic cancer cell lines has been an effective approach to reduce tumor burden in several patients. It is generally assumed that to be effective, these cell lines need to express immunogenic antigens coexpressed in patient tumor cells, and antigen-presenting cells need to take up such antigens then present them to patient T cells. We have previously reported that, in a phase I pilot study (ClinicalTrials.gov NCT00095862, a subject with stage IV breast cancer experienced substantial regression of breast, lung, and brain lesions following inoculation with clinical formulations of SV-BR-1-GM, a GM-CSF-secreting breast tumor cell line. To identify diagnostic features permitting the prospective identification of patients likely to benefit from SV-BR-1-GM, we conducted a molecular analysis of the SV-BR-1-GM cell line and of patient-derived blood, as well as a tumor specimen. Compared to normal human breast cells, SV-BR-1-GM cells overexpress genes encoding tumor-associated antigens (TAAs such as PRAME, a cancer/testis antigen. Curiously, despite its presumptive breast epithelial origin, the cell line expresses major histocompatibility complex (MHC class II genes (HLA-DRA, HLA-DRB3, HLA-DMA, HLA-DMB, in addition to several other factors known to play immunostimulatory roles. These factors include MHC class I components (B2M, HLA-A, HLA-B, ADA (encoding adenosine deaminase, ADGRE5 (CD97, CD58 (LFA3, CD74 (encoding invariant chain and CLIP, CD83, CXCL8 (IL8, CXCL16, HLA-F, IL6, IL18, and KITLG. Moreover, both SV-BR-1-GM cells and the responding study subject carried an HLA-DRB3*02:02 allele, raising the question of whether SV-BR-1-GM cells can directly present endogenous antigens to T cells, thereby inducing a tumor-directed immune response. In support of this, SV-BR-1-GM cells (which also carry the HLA-DRB3*01:01 allele treated with

  7. Silencing of Foxp3 enhances the antitumor efficacy of GM-CSF genetically modified tumor cell vaccine against B16 melanoma

    Directory of Open Access Journals (Sweden)

    Miguel A

    2017-01-01

    Full Text Available Antonio Miguel,1 Luis Sendra,1 Verónica Noé,2 Carles J Ciudad,2 Francisco Dasí,3,4 David Hervas,5 María José Herrero,1,6 Salvador F Aliño17 1Department of Pharmacology, Faculty of Medicine, University of Valencia, 2Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Barcelona, 3Research University Hospital of Valencia, INCLIVA Health Research Institute, 4Department of Physiology, Faculty of Medicine, University of Valencia Foundation, 5Biostatistics Unit, 6Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe (IIS La Fe, 7Clinical Pharmacology Unit, ACM Hospital Universitario y Politécnico La Fe, Valencia, Spain Abstract: The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg, which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment. This study aims to evaluate whether combining therapeutic vaccination with CTLA4 or Foxp3 gene silencing enhances the antitumor response. First, the “in vitro” cell entrance and gene silencing efficacy of two tools, 2'-O-methyl phosphorotioate-modified oligonucleotides (2'-OMe-PS-ASOs and polypurine reverse Hoogsteen hairpins (PPRHs, were evaluated in EL4 cells and cultured primary lymphocytes. Following B16 tumor transplant, C57BL6 mice were vaccinated with irradiated B16 tumor cells engineered to produce granulocyte-macrophage colony-stimulating factor (GM-CSF and were intraperitoneally treated with CTLA4 and Foxp3 2'-OMe-PS-ASO before and after vaccination. Tumor growth, mice survival, and CTLA4 and Foxp3 expression in blood cells were measured. The following

  8. Characterization and molecular features of the cell surface receptor for human granulocyte-macrophage colony-stimulating factor

    International Nuclear Information System (INIS)

    Chiba, S.; Tojo, A.; Kitamura, T.; Urabe, A.; Miyazono, K.; Takaku, F.

    1990-01-01

    The receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF) on the surfaces of normal and leukemic myeloid cells were characterized using 125I-labeled bacterially synthesized GM-CSF. The binding was rapid, specific, time dependent, and saturable. Scatchard analysis of the 125I-GM-CSF binding to peripheral blood neutrophils indicated the presence of a single class of binding site (Kd = 99 +/- 21 pM; 2,304 +/- 953 sites/cell). However, for peripheral blood monocytes and two GM-CSF-responsive myeloid cell lines (U-937 and TF-1), the Scatchard plots were biphasic curvilinear, which were best fit by curves derived from two binding site model: one with high affinity (Kd1 = 10-40 pM) and the other with low affinity (Kd2 = 0.9-2.0 nM). For U-937 cells, the number of high-affinity receptors was 1,058 +/- 402 sites/cell and that of low-affinity receptors was estimated to be 10,834 +/- 2,396 sites/cell. Cross-linking studies yielded three major bands with molecular masses of 150 kDa, 115 kDa, and 95 kDa, which were displaced by an excess amount of unlabeled GM-CSF, suggesting 135-kDa, 100-kDa, and 80-kDa species for the individual components of the human GM-CSF receptor. These bands comigrated for different cell types including peripheral blood neutrophils, U-937 cells and TF-1 cells. In experiments using U-937 cells, only the latter two bands appeared to be labeled in a dose-dependent manner in a low-affinity state. These results suggest that the human GM-CSF receptor possibly forms a multichain complex

  9. A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer.

    Science.gov (United States)

    Morse, Michael A; Niedzwiecki, Donna; Marshall, John L; Garrett, Christopher; Chang, David Z; Aklilu, Mebea; Crocenzi, Todd S; Cole, David J; Dessureault, Sophie; Hobeika, Amy C; Osada, Takuya; Onaitis, Mark; Clary, Bryan M; Hsu, David; Devi, Gayathri R; Bulusu, Anuradha; Annechiarico, Robert P; Chadaram, Vijaya; Clay, Timothy M; Lyerly, H Kim

    2013-12-01

    To determine whether 1 of 2 vaccines based on dendritic cells (DCs) and poxvectors encoding CEA (carcinoembryonic antigen) and MUC1 (PANVAC) would lengthen survival in patients with resected metastases of colorectal cancer (CRC). Recurrences after complete resections of metastatic CRC remain frequent. Immune responses to CRC are associated with fewer recurrences, suggesting a role for cancer vaccines as adjuvant therapy. Both DCs and poxvectors are potent stimulators of immune responses against cancer antigens. Patients, disease-free after CRC metastasectomy and perioperative chemotherapy (n = 74), were randomized to injections of autologous DCs modified with PANVAC (DC/PANVAC) or PANVAC with per injection GM-CSF (granulocyte-macrophage colony-stimulating factor). Endpoints were recurrence-free survival overall survival, and rate of CEA-specific immune responses. Clinical outcome was compared with that of an unvaccinated, contemporary group of patients who had undergone CRC metastasectomy, received similar perioperative therapy, and would have otherwise been eligible for the study. Recurrence-free survival at 2 years was similar (47% and 55% for DC/PANVAC and PANVAC/GM-CSF, respectively) (χ P = 0.48). At a median follow-up of 35.7 months, there were 2 of 37 deaths in the DC/PANVAC arm and 5 of 37 deaths in the PANVAC/GM-CSF arm. The rate and magnitude of T-cell responses against CEA was statistically similar between study arms. As a group, vaccinated patients had superior survival compared with the contemporary unvaccinated group. Both DC and poxvector vaccines have similar activity. Survival was longer for vaccinated patients than for a contemporary unvaccinated group, suggesting that a randomized trial of poxvector vaccinations compared with standard follow-up after metastasectomy is warranted. (NCT00103142).

  10. PU.1 is essential for CD11c expression in CD8(+/CD8(- lymphoid and monocyte-derived dendritic cells during GM-CSF or FLT3L-induced differentiation.

    Directory of Open Access Journals (Sweden)

    Xue-Jun Zhu

    Full Text Available Dendritic cells (DCs regulate innate and acquired immunity through their roles as antigen-presenting cells. Specific subsets of mature DCs, including monocyte-derived and lymphoid-derived DCs, can be distinguished based on distinct immunophenotypes and functional properties. The leukocyte integrin, CD11c, is considered a specific marker for DCs and it is expressed by all DC subsets. We created a strain of mice in which DCs and their progenitors could be lineage traced based on activity of the CD11c proximal promoter. Surprisingly, we observed levels of CD11c promoter activity that were similar in DCs and in other mature leukocytes, including monocytes, granulocytes, and lymphocytes. We sought to identify DNA elements and transcription factors that regulate DC-associated expression of CD11c. The ets transcription factor, PU.1, is a key regulator of DC development, and expression of PU.1 varies in different DC subsets. GM-CSF increased monocyte-derived DCs in mice and from mouse bone marrow cultured in vitro, but it did not increase CD8(+ lymphoid-derived DCs or B220(+ plasmacytoid DCs. FLT3L increased both monocyte-derived DCs and lymphoid-derived DCs from mouse bone marrow cultured in vitro. GM-CSF increased the 5.3 Kb CD11c proximal promoter activity in monocyte-derived DCs and CD8(+ lymphoid-derived DCs, but not in B220(+ plasmacytoid DCs. In contrast, FLT3L increased the CD11c proximal promoter activity in both monocyte-derived DCs and B220(+ plasmacytoid DCs. We used shRNA gene knockdown and chromatin immunoprecipitation to demonstrate that PU.1 is required for the effects of GM-CSF or FLT3L on monocyte-derived DCs. We conclude that both GM-CSF and FLT3L act through PU.1 to activate the 5.3 Kb CD11c proximal promoter in DCs and to induce differentiation of monocyte-derived DCs. We also confirm that the CD11c proximal promoter is not sufficient to direct lineage specificity of CD11c expression, and that additional DNA elements are required

  11. IL-12 and GM-CSF in DNA/MVA immunizations against HIV-1 CRF12_BF Nef induced T-cell responses with an enhanced magnitude, breadth and quality.

    Directory of Open Access Journals (Sweden)

    Ana María Rodríguez

    Full Text Available In Argentina, the HIV epidemic is characterized by the co-circulation of subtype B and BF recombinant viral variants. Nef is an HIV protein highly variable among subtypes, making it a good tool to study the impact of HIV variability in the vaccine design setting. We have previously reported a specific cellular response against NefBF with low cross-reactivity to NefB in mice. The aim of this work was to analyze whether the co-administration of IL-12 and GM-CSF, using DNA and MVA vaccine vectors, could improve the final cellular response induced. Mice received three DNA priming doses of a plasmid that express NefBF plus DNAs expressing IL-12 and/or GM-CSF. Afterwards, all the groups were boosted with a MVAnefBF dose. The highest increase in the magnitude of the NefBF response, compared to that induced in the control was found in the IL-12 group. Importantly, a response with higher breadth was detected in groups which received IL-12 or GM-CSF, evidenced as an increased frequency of recognition of homologous (BF and heterologous (B Nef peptides, as well as a higher number of other Nef peptide pools representing different viral subtypes. However, these improvements were lost when both DNA cytokines were simultaneously administered, as the response was focused against the immunodominant peptide with a detrimental response towards subdominant epitopes. The pattern of cytokines secreted and the specific-T-cell proliferative capacity were improved in IL-12 and IL-12+GM-CSF groups. Importantly IL-12 generated a significant higher T-cell avidity against a B heterologous peptide.This study indicates that the incorporation of DNA expressing IL-12 in DNA/MVA schemes produced the best results in terms of improvements of T-cell-response key properties such as breadth, cross-reactivity and quality (avidity and pattern of cytokines secreted. These relevant results contribute to the design of strategies aimed to induce T-cell responses against HIV antigens with

  12. Prolongation of the survival of breast cancer-bearing mice immunized with GM-CSF-secreting syngeneic/allogeneic fibroblasts transfected with a cDNA expression library from breast cancer cells.

    Science.gov (United States)

    Kim, Tae S; Jung, Mi Y; Cho, Daeho; Cohen, Edward P

    2006-10-30

    Breast cancer cells, like other types of neoplastic cells, form weakly immunogenic tumor-associated antigens. The antigenic properties of the tumor-associated antigens can be enhanced if they are expressed by highly immunogenic cells. In this study, a cancer vaccine was prepared by transfer of a cDNA expression library from SB5b breast carcinoma into mouse fibroblast cells of C3H/He mouse origin (H-2(k)), that had been previously modified to secrete GM-CSF and to express allogeneic class I-determinants (H-2(b)). The transfected syngeneic/allogeneic fibroblasts secreting GM-CSF were used as a vaccine in C3H/He mice. Robust cell-mediated immunity toward the breast cancer cells was generated in mice immunized with the cDNA-based vaccine. The immunity, mediated predominantly by CD8(+) T lymphocytes, was directed toward the breast cancer cells, but not against either of two other non-cross-reactive neoplasms of C3H/He mice. The immunity was sufficient to prolong the survival of mice with established breast cancer. Among other advantages, preparation of the vaccine by cDNA-transfer into a fibroblast cell line enabled the recipient cells to be modified in advance of DNA-transfer to augment their immunogenic properties. As the transferred DNA is replicated as the transfected cells divide, the vaccine could be prepared from microgram quantities of tumor tissue.

  13. The frequency of clinical pregnancy and implantation rate after cultivation of embryos in a medium with granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with preceding failed attempts of ART.

    Science.gov (United States)

    Tevkin, S; Lokshin, V; Shishimorova, M; Polumiskov, V

    2014-10-01

    The application in IVF practice of modern techniques can improve positive outcome of each cycle in the assisted reproductive technology (ART) programs and the effectiveness of treatment as a whole. There are embryos in the female reproductive tract in physiological medium which contain various cytokines and growth factors. It plays an important role in the regulation of normal embryonic development, improve implantation and subsequently optimizing the development of the fetus and the placenta. Granulocyte macrophage colony-stimulating factor (GM-CSF is one of the cytokines playing an important role in reproductive function. Addition of recombinant GM-CSF to the culture medium can makes closer human embryos culture to in vivo conditions and improve the efficacy ART cycles. The analysis of culture embryos in EmbryoGen medium has shown that fertilization rate embryo culture and transfer to patients with previous unsuccessful attempts increases clinical pregnancy rate compared to the control group 39.1 versus 27.8%, respectively. It is noted that the implantation rate (on 7 weeks' gestation) and progressive clinical pregnancy rate (on 12 weeks' gestation) were significantly higher in group embryos culture in EmbryoGen medium compared to standard combination of medium (ISM1+VA), and were 20.4 and 17.4% versus 11.6 and 9.1%, respectively.

  14. TL1A increases expression of CD25, LFA-1, CD134 and CD154, and induces IL-22 and GM-CSF production from effector CD4 T-cells

    DEFF Research Database (Denmark)

    Reichwald, Kirsten; Jørgensen, Tina Z.; Skov, Søren

    2014-01-01

    Elevated levels of the cytokine TL1A is associated with several autoimmune diseases e.g. rheumatoid arthritis and inflammatory bowel disease. However, the exact role of TL1A remains elusive. In this study, we investigated the function of TL1A in a pro-inflammatory setting. We show that TL1A toget...... of CD25 (IL-2Rα) and CD11a (α-chain of LFA-1) on CD4 T-cells, likely governing increased IL-2/IL-15 sensitivity and cell-cell contact. Along with this, TL1A co-stimulation caused a specific induction of IL-22 and GM-CSF from the activated T-cells. These results substantially contribute...

  15. Identification of a new adapter protein that may link the common beta subunit of the receptor for granulocyte/macrophage colony-stimulating factor, interleukin (IL)-3, and IL-5 to phosphatidylinositol 3-kinase.

    Science.gov (United States)

    Jücker, M; Feldman, R A

    1995-11-17

    Binding of human granulocyte/macrophage colony-stimulating factor (hGM-CSF) to its receptor induces the rapid activation of phosphatidylinositol-3 kinase (PI 3-kinase). As hGM-CSF receptor (hGMR) does not contain a consensus sequence for binding of PI 3-kinase, hGMR must use a distinct mechanism for its association with and activation of PI 3-kinase. Here, we describe the identification of a tyrosine-phosphorylated protein of 76-85 kDa (p80) that associates with the common beta subunit of hGMR and with the SH2 domains of the p85 subunit of PI 3-kinase in hGM-CSF-stimulated cells. Src/Yes and Lyn were tightly associated with the p80.PI 3-kinase complex, suggesting that p80 and other phosphotyrosyl proteins present in the complex were phosphorylated by Src family kinases. Tyrosine phosphorylation of p80 was only detected in hGM-CSF or human interleukin-3-stimulated cells, suggesting that activation of p80 might be specific for signaling via the common beta subunit. We postulate that p80 functions as an adapter protein that may participate in linking the hGM-CSF receptor to the PI 3-kinase signaling pathway.

  16. Mechanism of interleukin-13 production by granulocyte-macrophage colony-stimulating factor-dependent macrophages via protease-activated receptor-2.

    Science.gov (United States)

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

    2015-06-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes classically activated M1 macrophages. GM-CSF upregulates protease-activated receptor-2 (PAR-2) protein expression and activation of PAR-2 by human neutrophil elastase (HNE) regulates cytokine production. This study investigated the mechanism of PAR-2-mediated interleukin (IL)-13 production by GM-CSF-dependent macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. After stimulation with HNE to activate the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, IL-13 mRNA and protein levels were assessed by the reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. PAR-2 protein was detected in GM-CSF-dependent macrophages by Western blotting. Unexpectedly, PD98059 (an ERK1 inhibitor) increased IL-13 production, even at higher concentrations. Interestingly, U0126 (an ERK1/2 inhibitor) reduced IL-13 production in a concentration-dependent manner. Neither SB203580 (a p38alpha/p38beta inhibitor) nor BIRB796 (a p38gamma/p38delta inhibitor) affected IL-13 production, while TMB-8 (a calcium chelator) diminished IL-13 production. Stimulation with HNE promoted the production of IL-13 (a Th2 cytokine) by GM-CSF-dependent M1 macrophages. PAR-2-mediated IL-13 production may be dependent on the Ca(2+)/ERK2 signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Proteomic Analysis Reveals Distinct Metabolic Differences Between Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Macrophage Colony Stimulating Factor (M-CSF) Grown Macrophages Derived from Murine Bone Marrow Cells.

    Science.gov (United States)

    Na, Yi Rang; Hong, Ji Hye; Lee, Min Yong; Jung, Jae Hun; Jung, Daun; Kim, Young Won; Son, Dain; Choi, Murim; Kim, Kwang Pyo; Seok, Seung Hyeok

    2015-10-01

    Macrophages are crucial in controlling infectious agents and tissue homeostasis. Macrophages require a wide range of functional capabilities in order to fulfill distinct roles in our body, one being rapid and robust immune responses. To gain insight into macrophage plasticity and the key regulatory protein networks governing their specific functions, we performed quantitative analyses of the proteome and phosphoproteome of murine primary GM-CSF and M-CSF grown bone marrow derived macrophages (GM-BMMs and M-BMMs, respectively) using the latest isobaric tag based tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Strikingly, metabolic processes emerged as a major difference between these macrophages. Specifically, GM-BMMs show significant enrichment of proteins involving glycolysis, the mevalonate pathway, and nitrogen compound biosynthesis. This evidence of enhanced glycolytic capability in GM-BMMs is particularly significant regarding their pro-inflammatory responses, because increased production of cytokines upon LPS stimulation in GM-BMMs depends on their acute glycolytic capacity. In contrast, M-BMMs up-regulate proteins involved in endocytosis, which correlates with a tendency toward homeostatic functions such as scavenging cellular debris. Together, our data describes a proteomic network that underlies the pro-inflammatory actions of GM-BMMs as well as the homeostatic functions of M-BMMs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Regulation of CTL responses to MHC-restricted class I peptide of the gp70 tumour antigen by splenic parenchymal CD4+ T cells in mice failing immunotherapy with DISC-mGM-CSF.

    Science.gov (United States)

    Ahmad, Murrium; Rees, Robert C; McArdle, Stephanie E; Li, Geng; Mian, Shahid; Entwisle, Claire; Loudon, Peter; Ali, Selman A

    2005-07-20

    Direct intratumour injection of the disabled infectious single-cycle-herpes simplex virus-encoding murine granulocyte/macrophage colony-stimulating factor (DISC-HSV-mGM-CSF) into established colon carcinoma CT26 tumours induced complete tumour rejection in up to 70% of treated animals (regressors), while the remaining mice developed progressive tumours (progressors). This murine Balb/c model was used to dissect the cellular mechanisms involved in tumour regression or progression following immunotherapy. CTLs were generated by coculturing lymphocytes and parenchymal cells from the same spleens of individual regressor or progressor animals in the presence of the relevant AH-1 peptide derived from the gp70 tumour-associated antigens expressed by CT26 tumours. Tumour regression was correlated with potent CTL responses, spleen weight and cytokine (IFN-gamma) production. Conversely, progressor splenocytes exhibited weak to no CTL activity and poor IFN-gamma production, concomitant with the presence of a suppressor cell population in the progressor splenic parenchymal cell fraction. Further fractionation of this parenchymal subpopulation demonstrated that cells inhibitory to the activation of AH-1-specific CTLs, restimulated in vitro with peptide, were present in the nonadherent parenchymal fraction. In vitro depletion of progressor parenchymal CD3+/CD4+ T cells restored the CTL response of the cocultured splenocytes (regressor lymphocytes and progressor parenchymal cells) and decreased the production of IL-10, suggesting that CD3+CD4+ T lymphocytes present in the parenchymal fraction regulated the CTL response to AH-1. We examined the cellular responses associated with tumour rejection and progression, identifying regulatory pathways associated with failure to respond to immunotherapy. Copyright 2005 Wiley-Liss, Inc.

  19. Increased expression of chemokine receptors CCR1 and CCR3 in nasal polyps: molecular basis for recruitment of the granulocyte infiltrate

    Czech Academy of Sciences Publication Activity Database

    Fundová, Petra; Funda, David P.; Kovář, D.; Holý, R.; Navara, M.; Tlaskalová-Hogenová, Helena

    2013-01-01

    Roč. 58, č. 3 (2013), s. 219-224 ISSN 0015-5632 R&D Projects: GA MZd NS10054 Institutional support: RVO:61388971 Keywords : INTESTINAL EPITHELIAL-CELLS * GM- CSF * TOLL-LIKE RECEPTORS Subject RIV: EE - Microbiology, Virology Impact factor: 1.145, year: 2013

  20. CXC chemokine receptor 3 expression on CD34(+) hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor

    DEFF Research Database (Denmark)

    Jinquan, T; Quan, S; Jacobi, H H

    2000-01-01

    -induced CD34(+) progenitor chemotaxis. These chemotactic attracted CD34(+) progenitors are colony-forming units-granulocyte-macrophage. gamma IP-10 and Mig also induced GM-CSF-stimulated CD34(+) progenitor adhesion and aggregation by means of CXCR3, a finding confirmed by the observation that anti-CXCR3 m......Ab blocked these functions of gammaIP-10 and Mig but not of chemokine stromal cell-derived factor 1 alpha. gamma IP-10-induced and Mig-induced up-regulation of integrins (CD49a and CD49b) was found to play a crucial role in adhesion of GM-CSF-stimulated CD34(+) progenitors. Moreover, gamma IP-10 and Mig...... stimulated CXCR3 redistribution and cellular polarization in GM-CSF-stimulated CD34(+) progenitors. These results indicate that CXCR3-gamma IP-10 and CXCR3-Mig receptor-ligand pairs, as well as the effects of GM-CSF on them, may be especially important in the cytokine/chemokine environment...

  1. Granulocyte-macrophage colony-stimulating factor primes interleukin-13 production by macrophages via protease-activated receptor-2.

    Science.gov (United States)

    Aoki, Manabu; Yamaguchi, Rui; Yamamoto, Takatoshi; Ishimaru, Yasuji; Ono, Tomomichi; Sakamoto, Arisa; Narahara, Shinji; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo

    2015-04-01

    Chronic inflammation is often linked to the presence of type 2-polarized macrophages, which are induced by the T helper type 2 cytokines interleukin-4 and interleukin-13 (IL-13). IL-13 is a key mediator of tissue fibrosis caused by T helper type 2-based inflammation. Human neutrophil elastase (HNE) plays a pivotal role in the pathogenesis of pulmonary fibrosis. This study investigated the priming effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on IL-13 expression by macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. Expression of IL-13 mRNA and protein by GM-CSF-dependent macrophages was investigated after stimulation with HNE, using the polymerase chain reaction and enzyme-linked immunosorbent assay. GM-CSF had a priming effect on IL-13 mRNA and protein expression by macrophages stimulated with HNE, while this effect was not observed for various other cytokines. GM-CSF-dependent macrophages showed a significant increase in the expression of protease activated receptor-2 (PAR-2) mRNA and protein. The response of IL-13 mRNA to HNE was significantly decreased by pretreatment with alpha1-antitrypsin, a PAR-2 antibody (SAM11), or a PAR-2 antagonist (ENMD-1068). These findings suggest that stimulation with HNE can induce IL-13 production by macrophages, especially GM-CSF-dependent macrophages. Accordingly, neutrophil elastase may have a key role in fibrosis associated with chronic inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Perfil antiinflamatorio del paricalcitol en el receptor de trasplante renal

    Directory of Open Access Journals (Sweden)

    Javier Donate-Correa

    2017-11-01

    Conclusiones: La administración del paricalcitol a receptores de trasplante renal se asocia con efectos beneficiosos sobre su estado inflamatorio, lo que podría asociarse a un potencial beneficio clínico.

  3. Insulin use, hormone receptor status and hematopoietic cytokines׳ circulation in women with diabetes mellitus and breast cancer

    Directory of Open Access Journals (Sweden)

    Zachary A.P. Wintrob

    2017-04-01

    The data presented here is among the first to show a relationship between pre-existing use of injectable insulin in women diagnosed with breast cancer and type 2 diabetes mellitus, hematopoietic cytokine profiles at time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between G-CSF, GM-CSF, and IL-7 stratified by insulin use, controls, as well as by estrogen and progesterone receptor status is also provided.

  4. Combination Immunotherapy of B16 Melanoma Using Anti–Cytotoxic T Lymphocyte–Associated Antigen 4 (Ctla-4) and Granulocyte/Macrophage Colony-Stimulating Factor (Gm-Csf)-Producing Vaccines Induces Rejection of Subcutaneous and Metastatic Tumors Accompanied by Autoimmune Depigmentation

    Science.gov (United States)

    van Elsas, Andrea; Hurwitz, Arthur A.; Allison, James P.

    1999-01-01

    We examined the effectiveness of cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) blockade, alone or in combination with a granulocyte/macrophage colony-stimulating factor (GM-CSF)–expressing tumor cell vaccine, on rejection of the highly tumorigenic, poorly immunogenic murine melanoma B16-BL6. Recently established tumors could be eradicated in 80% (68/85) of the cases using combination treatment, whereas each treatment by itself showed little or no effect. Tumor rejection was dependent on CD8+ and NK1.1+ cells but occurred irrespective of the presence of CD4+ T cells. Mice surviving a primary challenge rejected a secondary challenge with B16-BL6 or the parental B16-F0 line. The same treatment regimen was found to be therapeutically effective against outgrowth of preestablished B16-F10 lung metastases, inducing long-term survival. Of all mice surviving B16-BL6 or B16-F10 tumors after combination treatment, 56% (38/68) developed depigmentation, starting at the site of vaccination or challenge and in most cases progressing to distant locations. Depigmentation was found to occur in CD4-depleted mice, strongly suggesting that the effect was mediated by CTLs. This study shows that CTLA-4 blockade provides a powerful tool to enhance T cell activation and memory against a poorly immunogenic spontaneous murine tumor and that this may involve recruitment of autoreactive T cells. PMID:10430624

  5. Granulocyte-macrophage colony-stimulating factor does not increase the potency or efficacy of a foot-and-mouth disease virus subunit vaccine Fator estimulante de colônias de granu-lócitos e macrófagos (GM-CSF não aumenta a eficácia ou potência da vacina de subunidades da febre aftosa em suínos

    Directory of Open Access Journals (Sweden)

    Luizinho Caron

    2005-09-01

    Full Text Available Foot-and-mouth disease (FMD is one of the most feared diseases of livestock worldwide. Vaccination has been a very effective weapon in controlling the disease, however a number of concerns with the current vaccine including the inability of approved diagnostic tests to reliably distinguish vaccinated from infected animals and the need for high containment facilities for vaccine production, have limited its use during outbreaks in countries previously free of the disease. A number of FMD vaccine candidates have been tested and a replication-defective human adenovirus type 5 (Ad5 vector containing the FMDV capsid (P1-2A and 3C protease coding regions has been shown to completely protect pigs against challenge with the homologous virus (FMDV A12 and A24. An Ad5-P1-2A+3C vaccine for FMDV O1 Campos (Ad5-O1C, however, only induced a low FMDV-specific neutralizing antibody response in swine potency tests. Granulocyte-macrophage colony-stimulating factor (GM-CSF has been successfully used to stimulate the immune response in vaccine formulations against a number of diseases, including HIV, hepatitis C and B. To attempt to improve the FMDV-specific immune response induced by Ad5-O1C, we inoculated swine with Ad5-O1C and an Ad5 vector containing the gene for porcine GM-CSF (pGM-CSF. However, in the conditions used in this trial, pGM-CSF did not improve the immune response to Ad5-O1C and adversely affected the level of protection of swine challenged with homologous FMDV.A febre aftosa é uma das doenças mais temidas nos rebanhos em todo o mundo. A vacinação tem sido uma arma eficiente no controle da doença, no entanto há preocupações com as vacinas atualmente utilizadas incluindo a necessidade de instalações de alta segurança para a produção dessas vacinas e a falta de um teste de diagnóstico aprovado que faça distinção precisa entre animais vacinados dos infectados. Várias vacinas têm sido testadas contra a febre aftosa e uma dessas

  6. RECEPTORES NUCLEARES: DEL NÚCLEO AL CITOPLASMA

    Directory of Open Access Journals (Sweden)

    Bibiana Ortega-Domínguez

    2015-01-01

    Full Text Available Los receptores nucleares (RNs constituyen una familia de factores transcripcionales activados por ligando que regulan la expresión de un gran número de genes de forma dependiente del tipo y contexto celular. La localización subcelular de los RNs es altamente dinámica y repercute sobre sus funciones como factores transcripcionales. En presencia de su ligando específico, los RNs se acumulan en el núcleo para modular la expresión de sus genes blanco. Por ende, la salida desde el núcleo a citoplasma de los RNs disminuye su acumulación nuclear y abate su actividad transcripcional. Por lo tanto, la exportación nuclear constituye un importante mecanismo de regulación de la actividad de los RNs. A pesar de su importancia, el proceso de exportación nuclear de los RNs no ha sido completamente explorado, sin embargo, los estudios que se tienen hasta ahora sugieren la participación de las proteínas CRM–1 y la Calreticulina (CRT como mediadoras de este proceso. En esta revisión se destaca la exportación nuclear como un mecanismo regulador de las funciones de los RNs y se discuten las características estructurales y funcionales de las exportinas CRM–1 y CRT.

  7. Influencia del perfil clínico del donante, receptor y tiempo de isquemia en la supervivencia del trasplante cardíaco. Subanálisis del Registro Español de Trasplante Cardíaco

    Directory of Open Access Journals (Sweden)

    María J. Paniagua

    2015-11-01

    Conclusiones: Muchas características del donante y el receptor, así como el tiempo de isquemia, influyen en la supervivencia del TC. El acúmulo de variables consideradas no óptimas repercutirá negativamente y de forma significativa en la supervivencia del TC.

  8. Dexamethasone-Induced Myeloid-Derived Suppressor Cells Prolong Allo Cardiac Graft Survival through iNOS- and Glucocorticoid Receptor-Dependent Mechanism

    Directory of Open Access Journals (Sweden)

    Yang Zhao

    2018-02-01

    Full Text Available How to induce immune tolerance without long-term need for immunosuppressive drugs has always been a central problem in solid organ transplantation. Modulating immunoregulatory cells represents a potential target to resolve this problem. Myeloid-derived suppressor cells (MDSCs are novel key immunoregulatory cells in the context of tumor development or transplantation, and can be generated in vitro. However, none of current systems for in vitro differentiation of MDSCs have successfully achieved long-term immune tolerance. Herein, we combined dexamethasone (Dex, which is a classic immune regulatory drug in the clinic, with common MDSCs inducing cytokine granulocyte macrophage colony stimulating factor (GM-CSF to generate MDSCs in vitro. Addition of Dex into GM-CSF system specifically increased the number of CD11b+ Gr-1int/low MDSCs with an enhanced immunosuppressive function in vitro. Adoptive transfer of these MDSCs significantly prolonged heart allograft survival and also favored the expansion of regulatory T cells in vivo. Mechanistic studies showed that inducible nitric oxide sythase (iNOS signaling was required for MDSCs in the control of T-cell response and glucocorticoid receptor (GR signaling played a critical role in the recruitment of transferred MDSCs into allograft through upregulating CXCR2 expression on MDSCs. Blockade of GR signaling with its specific inhibitor or genetic deletion of iNOS reversed the protective effect of Dex-induced MDSCs on allograft rejection. Together, our results indicated that co-application of Dex and GM-CSF may be a new and important strategy for the induction of potent MDSCs to achieve immune tolerance in organ transplantation.

  9. Importancia del Factor de Crecimiento del Endotelio Vascular (VEGF) y de sus receptores en el ciclo ovárico. Revisión

    OpenAIRE

    Ana María Rosales Torres; Adrián Guzmán Sánchez

    2012-01-01

    El objetivo de esta revisión fue recopilar y analizar la información más reciente acerca del papel del Factor de Crecimiento del Endotelio Vascular (VEGF, por sus siglas en inglés), sus receptores de membrana (VEGFR1 y VEGFR2) y receptores solubles (sVEGFR1 y sVEGFR2), durante los procesos involucrados en el ciclo ovárico. La principal función del sistema VEGF (VEGF y sus receptores), es controlar la formación de nuevos vasos sanguíneos y la protección de células endoteliales y de la granulos...

  10. Molecular mechanisms of glucocorticoid receptor signaling Mecanismos moleculares de señalización del receptor de glucocorticoides

    Directory of Open Access Journals (Sweden)

    Marta Labeur

    2010-10-01

    Full Text Available This review highlights the most recent findings on the molecular mechanisms of the glucocorticoid receptor (GR. Most effects of glucocorticoids are mediated by the intracellular GR which is present in almost every tissue and controls transcriptional activation via direct and indirect mechanisms. Nevertheless the glucocorticoid responses are tissue -and gene- specific. GR associates selectively with corticosteroid ligands produced in the adrenal gland in response to changes of humoral homeostasis. Ligand interaction with GR promotes either GR binding to genomic glucocorticoid response elements, in turn modulating gene transcription, or interaction of GR monomers with other transcription factors activated by other signalling pathways leading to transrepression. The GR regulates a broad spectrum of physiological functions, including cell differentiation, metabolism and inflammatory responses. Thus, disruption or dysregulation of GR function will result in severe impairments in the maintenance of homeostasis and the control of adaptation to stress.Esta revisión destaca los más recientes hallazgos sobre los mecanismos moleculares del receptor de glucocorticoides (GR. La mayoría de los efectos de los glucocorticoides son mediados por los GR intracelulares presentes en casi todos los tejidos y controlan la activación transcripcional por mecanismos directos e indirectos. Las respuestas a los glucocorticoides son específicas para cada gen y tejido. Los GR se asocian en forma selectiva con ligandos producidos en la glándula adrenal, corticosteroides, en respuesta a cambios neuroendocrinos. La interacción del ligando con el GR promueve: a la unión del GR a elementos genómicos de respuesta a glucocorticoides, modulando la transcripción; b la interacción de monómeros del GR con otros factores de transcripción activados por otras vías, llevando a la transrepresión. El GR regula un amplio espectro de funciones fisiológicas, incluyendo la

  11. Production of two hemopoietic growth factors is differentially regulated in single T lymphocytes activated with an anti-T cell receptor antibody

    DEFF Research Database (Denmark)

    Kelso, A; Owens, T

    1988-01-01

    A method has been developed to measure the production by single activated T lymphocytes of two hemopoietic growth factors, granulocyte-macrophage CSF (GM-CSF) and multipotential CSF (multi-CSF or IL-3). When individual cells of the L3T4 (CD4)+ F23.1+ T cell clone E9.D4 were transferred by microma......A method has been developed to measure the production by single activated T lymphocytes of two hemopoietic growth factors, granulocyte-macrophage CSF (GM-CSF) and multipotential CSF (multi-CSF or IL-3). When individual cells of the L3T4 (CD4)+ F23.1+ T cell clone E9.D4 were transferred...... by micromanipulation into wells coated with the monoclonal anti-T cell receptor antibody F23.1, up to 90% of cells produced CSF as detected by CSF-dependent hemopoietic cell lines. Production occurred in the absence of proliferation and did not require the addition of accessory cells or IL-2. Both the frequency of CSF......-producing cells and the average production per positive cell depended on the density of the immobilized stimulating ligand, indicating that the response of each cell is not an all-or-none phenomenon but varies with the strength of stimulation. Individual cells of the clone varied over a 100-fold range...

  12. Cytokine and surface receptor diversity of NK cells in resistant C3H/HeN and susceptible BALB/c mice with chronic Pseudomonas aeruginosa lung infection

    DEFF Research Database (Denmark)

    Calum, Henrik; Moser, Claus; Jensen, Peter Østrup

    2003-01-01

    The purpose of the present study was to investigate whether NK cells from resistant C3H/HeN mice and susceptible BALB/c mice showed different release of cytokines and expression of surface molecules during chronic P. aeruginosa lung infection using alginate-embedded P. aeruginosa mimicking...... the infection in cystic fibrosis. Lung cell suspensions were depleted of lymphocytes by magnetic cell sorting. The concentrations of IFN-gamma, IL-1beta and GM-CSF were estimated by ELISA at day 1 and 2 after infection. Non-infected mice were used as controls. Flow cytometry was used to estimate the surface...... expression of the LFA-1 and Fc receptors on NK cells. At day 2, IFN-gamma levels increased in C3H/HeN mice but decreased in BALB/c mice. The GM-CSF levels increased only in the C3H/HeN mice at day 1 and 2. Surface expression of LFA-1 on the NK cells was higher in C3H/HeN mice at day 1 and 2. In contrast...

  13. Monitoreo del Clima Espacial desde Colombia mediante Radio-receptores Butterworth de Orden Superior

    Directory of Open Access Journals (Sweden)

    Andrés Felipe Jaramillo Alvarado

    2017-01-01

    Full Text Available Contexto: las fulguraciones solares y las eyecciones de masa coronal liberan al espacio grandes cantidades de radiación que, al alcanzar las capas exteriores de la atmósfera terrestre, alteran sus características eléctricas. El conjunto de fenómenos derivados de esta interacción se conoce como clima espacial y sus consecuencias incluyen fallas en los sistemas de geolocalización, las telecomunicaciones, las operaciones vía satélite, el seguimiento espacial, la radionavegación y la sobrecarga de redes eléctricas. Método: en este trabajo se presenta el desarrollo de un radio receptor que permite adelantar el monitoreo del clima espacial desde Colombia. Además, se describe una metodología novedosa para el diseño de filtros analógicos de orden superior de característica Butterworth, a partir de la interconexión en paralelo de bancos de filtros de primero y segundo orden, obteniéndose la función de transferencia deseada. Resultados: el radio receptor desarrollado se instaló en la estación de monitoreo del clima espacial del Observatorio Astronómico de la Universidad Tecnológica de Pereira (OAUTP, Colombia, entrando en operación en diciembre de 2015. Desde esa fecha, el sistema ha registrado la actividad solar de forma ininterrumpida, detectando cuatro potentes explosiones solares clase C presentadas los días 15, 16 y 17 del mes de abril de 2016. Las señales recibidas por el radio receptor son enviadas a la base de datos global del Stanford Solar Center, de Stanford University, con el código UTP 0383. Conclusiones: el radio telescopio desarrollado permite al Observatorio Astronómico OAUTP adelantar el monitoreo del clima espacial y de la actividad solar, enviando la información recibida a repositorios de acceso público a nivel mundial. No existen otros receptores de radio de este tipo operando en la actualidad en países ecuatoriales, una región de la Tierra donde los efectos de la actividad solar pueden conducir a

  14. Metilación del receptor de la hormona estimulante del tiroides: marcador diagnóstico de malignidad en cáncer de tiroides Methylation of the thyroid stimulating hormone receptor: diagnostic marker of malignity in thyroid cancer

    Directory of Open Access Journals (Sweden)

    María Teresa Marrero Rodríguez

    2007-12-01

    Full Text Available Se analizó el estado de metilación del promotor del gen para el receptor de la hormona estimulante del tiroides (TSH en el diagnóstico de tumores tiroideos de origen epitelial. El estudio se realizó en tejido tiroideo obtenido de bloques de parafina de diferentes patologías tiroideas (carcinoma papilar, folicular e indiferenciado, y adenomas foliculares. El trabajo se realizó empleando la técnica de modificación del ADN con bisulfito de sodio y el análisis del estado de la metilación del gen RTSH se realizó por el método de reacción en cadena de la polimerasa específica para metilación. Encontramos metilación del promotor para el gen del receptor de TSH en los carcinomas papilares (33 de 40; 82,5 %, en los 10 carcinomas indiferenciados (100 % y en 10 de los 15 carcinomas foliculares analizados (66,6 %. En cambio, no se observó metilación en los 8 adenomas foliculares analizados. Se propone la metilación del gen para el receptor de TSH como un nuevo marcador diagnóstico de malignidad, y una base para emplear agentes desmetilantes conjuntamente con la terapia con radioyodo, en los pacientes con cáncer de tiroides de origen epitelial que no respondan a la terapia.The methylation state of the gene promoter for the receptor of the thyroid stimulating hormone (TSH in the diagnosis of thyroid tumors of epithelial origin was analyzed. The study was conducted in thyroid tissue obtained from paraffin blocks of different thyroid pathologies (papillary, follicular and undifferentiated carcinoma and follicular adenomas. The work was done by using the DNA modification technique with sodium bisulfite, and polymerase chain reaction was applied to analyze the gene methylation state. Methylation of the promoter for the gene of the TSH receptor was found in the papillary carcinomas (33 of 40; 82.5 %, in 10 undifferentiated carcinomas (100 %, and in 10 of the 15 follicular carcinomas analyzed (66.6 %. No methylation was observed in the 8

  15. Importancia del Factor de Crecimiento del Endotelio Vascular (VEGF y de sus receptores en el ciclo ovárico. Revisión

    Directory of Open Access Journals (Sweden)

    Ana María Rosales Torres

    2012-01-01

    Full Text Available El objetivo de esta revisión fue recopilar y analizar la información más reciente acerca del papel del Factor de Crecimiento del Endotelio Vascular (VEGF, por sus siglas en inglés, sus receptores de membrana (VEGFR1 y VEGFR2 y receptores solubles (sVEGFR1 y sVEGFR2, durante los procesos involucrados en el ciclo ovárico. La principal función del sistema VEGF (VEGF y sus receptores, es controlar la formación de nuevos vasos sanguíneos y la protección de células endoteliales y de la granulosa. Es conocido que durante el ciclo ovárico, los cambios vasculares son importantes para controlar el desarrollo folicular, la ovulación y la formación y regresión del cuerpo lúteo (CL. En la selección folicular, VEGF y el receptor VEGFR2 incrementan su expresión para favorecer el aporte de nutrientes al folículo. En la ovulación VEGF, VEGFR1 y VEGFR2m reducen su expresión para evitar una hemorragia, y se incrementa inmediatamente después para promover la formación de vasos sanguíneos y el desarrollo del CL. Finalmente durante la regresión del CL el VEGF y VEGFR2 reducen su expresión coincidiendo con la muerte de las células que lo forman. Las evidencias revisadas permiten sugerir que VEGF y VEGFR2 son los principales promotores de la angiogénesis y protección celular en el desarrollo del folículo y CL, sin embargo los otros miembros del sistema VEGF; VEGFR1 y sVEGFR1 y sVEGFR2, parecen desempeñar funciones anti-angiogénicas en los procesos ováricos mencionados.

  16. Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, Patricia C., E-mail: ryanp@medimmune.com [MedImmune, LLC, Gaithersburg, MD (United States); Sleeman, Matthew A. [MedImmune, LLC, Cambridge (United Kingdom); Rebelatto, Marlon [MedImmune, LLC, Gaithersburg, MD (United States); Wang, Bing; Lu, Hong [MedImmune, LLC, Moutain View, CA (United States); Chen, Xiaomin [Novartis, East Hanover, NJ (United States); Wu, Chi-Yuan [MedImmune, LLC, Moutain View, CA (United States); Hinrichs, Mary Jane; Roskos, Lorin [MedImmune, LLC, Gaithersburg, MD (United States); Towers, Heidi [MedImmune, LLC, Cambridge (United Kingdom); McKeever, Kathleen; Dixit, Rakesh [MedImmune, LLC, Gaithersburg, MD (United States)

    2014-09-01

    Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters other than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus monkeys.

  17. Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

    International Nuclear Information System (INIS)

    Ryan, Patricia C.; Sleeman, Matthew A.; Rebelatto, Marlon; Wang, Bing; Lu, Hong; Chen, Xiaomin; Wu, Chi-Yuan; Hinrichs, Mary Jane; Roskos, Lorin; Towers, Heidi; McKeever, Kathleen; Dixit, Rakesh

    2014-01-01

    Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters other than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus monkeys.

  18. Polimorfismos del receptor adrenérgico b1 y sus implicaciones farmacodinámicas

    Directory of Open Access Journals (Sweden)

    Ignacio Rodríguez

    2000-02-01

    Full Text Available

    Introducción: Los betabloqueadores son uno de los grupos farmacológicos que cuentan con mayor efectividad clínica comprobada; se ha demostrado que disminuyen la mortalidad y morbilidad por enfermedad cerebrovascular, eventos coronarios y falla cardíaca. Todos estos medicamentos tienen como común denominador el antagonismo de los receptores adrenérgicos b1, los cuales, se encuentran ubicados principalmente en cardiomiocitos, células yuxtaglomerulares y adipocitos; donde producen, en respuesta al estimulo por catecolaminas, aumento de la contractilidad y frecuencia cardíacas, liberación de renina y lipólisis respectivamente. Recientemente se descubrieron dos polimorfismos en este receptor. El primero de ellos, una sustitución de A por G en el nucleótido 145, genera un cambio del aminoácido Serina por Glicina en la posición 49 (Gly49Ser. El segundo polimorfismo, una sustitución de G por C en el nucleótido 1165, produce un cambio del aminoácido Arginina por Glicina en la posición 389 (Arg389Gly ubicado en la cola citoplasmática del receptor, que es una de las regiones de interacción con la proteína G(1. Estudios in vitro con las dos variantes polimórficas Arg389Gly del receptor, han demostrado que los receptores con Arg389 IN VITRO INTERACTION OF INFLUENZA VIRUS A(H1N1pdm09 WITH MONOCYTIC MACROPHAGES: INDIVIDUAL RESPONSES OF TLR7 AND RIG1 RECEPTOR GENES

    Directory of Open Access Journals (Sweden)

    T. M. Sokolova

    2017-01-01

    Full Text Available In vitro differentiation of donor blood monocytes to macrophages (Mph following GM-CSF treatment was accompanied by a significant increase in the levels of gene transcription signaling receptors TLR7 or RIG1. The levels of intracellular viral RNA (M1 gene in Mph remained high upon infection by influenza virus A H1N1pdm (Moscow 2009 for 24-96 hours. The innate immunity reactions caused by influenza virus show individual features: they are decreased in Mph from donor 1 which had initially high level of endosomal TLR7 gene activity, and it increased by influenza virus in MPh from donor 2 who had a very low level of TLR7 gene expression. The influenza H1N1pdm virus weakly stimulated expression of gene RIG1 and production of inflammatory cytokines in Mf in donor 1. The differences may be connected with individual sensitivity of the donors to influenza infection.

  19. Cytokine and surface receptor diversity of NK cells in resistant C3H/HeN and susceptible BALB/c mice with chronic Pseudomonas aeruginosa lung infection

    DEFF Research Database (Denmark)

    Calum, Henrik; Moser, Claus; Jensen, Peter Østrup

    2003-01-01

    The purpose of the present study was to investigate whether NK cells from resistant C3H/HeN mice and susceptible BALB/c mice showed different release of cytokines and expression of surface molecules during chronic P. aeruginosa lung infection using alginate-embedded P. aeruginosa mimicking...... expression of the LFA-1 and Fc receptors on NK cells. At day 2, IFN-gamma levels increased in C3H/HeN mice but decreased in BALB/c mice. The GM-CSF levels increased only in the C3H/HeN mice at day 1 and 2. Surface expression of LFA-1 on the NK cells was higher in C3H/HeN mice at day 1 and 2. In contrast...

  1. Endothelial-derived GM-CSF influences expression of oncostatin M

    Science.gov (United States)

    During and following transendothelial migration, neutrophils undergo a number of phenotypic changes resulting from encounters with endothelial-derived factors. This report uses an in vitro model with HUVEC and isolated human neutrophils to examine the effects of two locally-derived cytokines, granul...

  2. Hemopoietic stem cells in rhesus monkeys : surface antigens, radiosensitivity, and responses to GM-CSF

    NARCIS (Netherlands)

    J.J. Wielenga (Jenne)

    1990-01-01

    textabstractRhesus monkeys (Macaca mulatta) were bred at the Primate Center TNO, Rijswijk, The Netherlands!. Both male and female animals were used for the experiments. The monkeys weighed 2.5-4 kg and were 2-4 years old at the time of the experiment. They were all typed for RhLA-A, -B and -DR

  3. Supervivencia del injerto y del receptor en el trasplante renal en el hospital Guillermo Gran Benavente (Concepción, Chile

    Directory of Open Access Journals (Sweden)

    Magali Rodríguez Vidal

    2014-12-01

    Full Text Available Al ser el trasplante renal la mejor opción terapéutica para el tratamiento de la Insuficiencia Renal Terminal, en la ciudad de Concepción (Chile, se inició el programa de Trasplante Renal (TX en el año 1994. El objetivo de este trabajo es caracterizar la supervivencia del injerto renal de los TX realizados un hospital, de dicha ciudad mediante un estudio descriptivo, transversal, correlacional y comparativo de los resultados obtenidos en dos periodos, A: de 1994 a 2003 y, B: de 2004 a 2012. El análisis estadístico se realizó con el software SPSSv20.0. La funcion de supervivencia con la prueba no-paramétrica de Kaplan-Meier; y para comparaciones de variables se utilizó el test log-rank. De los resultados obtenidos cabe destacar que la supervivencia del paciente trasplantado en el período A fue mejor el primer al año (96%, pero fue menor a los 3 (90%, 5 (86% y 10 años (72% respecto al período B en que los valores fueron al año 95%, a los 3 el 90% a los 5 y 10 años el 87% y a los 10 años. La supervivencia del injerto también fue mayor en el periodo A que en el B, y mejor cuando hubo un tiempo de isquemia inferior a 24 horas y sin diferencias en relación al sexo del donante y del receptor y al tipo de tratamiento inmunosupreso. Las infeciones fueron la primera causa de muerte del paciente y las complicaciones quirúrgicas la principal causa de la pérdida del injerto.

  4. PURIFICACIÓN DE IgY CONTRA LA SUBUNIDAD NR3 DEL RECEPTOR NMDA DE CEREBRO DE RATA

    Directory of Open Access Journals (Sweden)

    Gina Méndez C

    2008-04-01

    Full Text Available Objetivo. Obtener anticuerpos tipo IgY contra péptidos sintéticos de las subunidades NR3A y NR3B del receptor NMDA de ratas, para reconocer y seguir la expresión de estas subunidades en extractos de cerebro de rata de diferentes edades. Materiales y métodos. Se diseñaron dos péptidos empleando los sistemas de la base de datos Entrez y el programa ClustalW-PBIL de alineamientos múltiples contra las subunidades NR3A y NR3B del receptor NMDA; una vez sintetizados por el método SSPS-fmoc fueron utilizados para inocular gallinas (Gallus gallus, variedad Hy Line Brown de 16 semanas de edad; al cabo de 57 días postinoculación se purificó IgY específica y se enfrentaron a extractos de cerebro de rata postnatal y adulta. Resultados. Se detectaron las subunidades NR3A y NR3B y se relacionó su expresión con la edad del animal; siendo mayor la expresión de la subunidad NR3A en extracto de cerebro de rata postnatal. No se encontró diferencia marcada en la expresión de la subunidad NR3B en las edades mencionadas. Conclusiones. Esta es la primera investigación que emplea proteína nativa para el reconocimiento de la subunidad NR3 del receptor NMDA, lo cual muestra la especificidad de los anticuerpos generados y contribuye con el entendimiento de las funciones de este receptor y su relación con la regulación de la memoria espacial.

  5. Efecto del polimorfismo del receptor ? 2 adrenérgico sobre la respuesta antihipertensiva en pacientes con hipertensión esencial

    Directory of Open Access Journals (Sweden)

    Juan McEwen

    2004-02-01

    Full Text Available La hipertensión arterial esencial (HTE es uno de los principales factores de riesgo cardiovascular y generador indirecto de la enfermedad coronaria, la mayor causa de muertes en Colombia y el mundo [1].
    El Sistema Nervioso Simpático (SNS modifica la resistencia
    arterial periférica a través del receptor ? 2 adrenérgico,  generando señales intracelulares que regulan la relajación del
    músculo liso vascular. Este receptor experimenta un proceso
    denominado desensibilización, es decir, cuando es activado por
    un agonista por tiempo prolongado, la respuesta no será de la
    misma intensidad a la inicial. La desensibilización del receptor
    ? 2 parece estar determinada por la estructura de aminoácidos
    polimórficos: Arginina 16 Glicina y Ácido glutámico 27 Glutamina
    amino terminales. Estas variantes son codificadas por polimorfismos de un solo nucleótido (SNP 46 y 79. La función
    de estos polimorfismos y su efecto en la función vascular es
    controversial. Evidencias clínica e in vitro sugieren que la Glicina
    16 se desensibiliza mas rápido que la Arginina; igualmente, el
    Ácido glutámico 27 facilita la desensibilización versus
    glutamina[2].

  6. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  7. Hipercalcemia hipocalciúrica debida a una mutación de novo del gen del receptor sensor de calcio Hypocalciuric hypercalcemia due to de novo mutation of the calcium sensing receptor

    Directory of Open Access Journals (Sweden)

    Marcelo Sarli

    2004-08-01

    Full Text Available El objetivo de este trabajo es presentar el inusual caso clínico de una paciente de 34 años que consultó para establecer diagnóstico de certeza y conducta terapéutica ante una hipercalcemia asintomática, detectada en un examen bioquímico de rutina. La elevación de la calcemia en ausencia de inhibición de la secreción de parathormona orientó hacia una patología paratiroidea. La persistencia de la hipercalcemia concomitante con hipocalciuria y coincidente con una relación clearance de calcio/clearance de creatinina inferior a 0.01, hicieron sospechar el diagnóstico de hipercalcemia hipocalciúrica familiar. La falta de antecedentes familiares llevó a realizar un estudio molecular de la paciente y su grupo familiar. Los resultados de los estudios nos permitieron concluir que la paciente es portadora de una mutación de novo (inactivante del gen del receptor sensor del calcio. Se incluyen los datos del estudio molecular y una breve revisión bibliográfica del tema.The aim of this paper is to refer the unusual case of a 34 years old woman who consulted because of asymptomatic hypercalcemia, detected in a biochemical routine examination. The elevated values of serum calcium without blunted parathyroid hormone secretion suggested a parathyroid pathology. The concomitance of hypocalciuria with hypercalcemia and a calcium clearance/creatinine clearance ratio less than 0.01 reverted the diagnosis of familial hypocalciuric hypercalcemia, the first option. The absence of familial background led to the molecular study of the patient and her family. The latter confirmed the diagnosis of a de novo inactivating mutation of the calcium sensing receptor. Details on the molecular study and a brief review of this subject are included.

  8. Regulación de la acción de la Aldosterona al nivel del receptor mineralocorticoide

    Directory of Open Access Journals (Sweden)

    Roberto Franco Saenz

    2001-08-01

    Full Text Available

    Se revisan nuevos conceptos acerca de la secreción de aldosterona y de la interacción de la aldosterona con el receptor mineralocorticoide así como el papel de la enzima 11b-hidroxisteroid dehidrogenasa tipo 2 (11b-HSD-2 en la protección del receptor mineralocorticoides contra la acción de los glucocorticoides endógenos. Alteraciónes en la actividad de esta enzima causan hipertensión arterial en humanos y animales de experimentación. En vista del papel crítico que esta enzima juega en la reabsorción de sodio y el volumen sanguíneo en este estudio se investiga la regulación del gen de la 11b-HSD-2 en el riñón de la rata Dahl, un modelo experimental de hipertensión genética sensible al sodio dietético y se muestra que el sodio dietético aumenta la expresión del gen en el riñón de estas ratas.

    Introducción
    La aldosterona es una hormona mineralocorticoide producida por las células glomerulosas de la corteza adrenal. La aldosterona actúa en el riñón, en el túbulo convoluto distal causando retención de sodio y eliminación de potasio y iones de hidrógeno. La aldosterona juega un papel principal en el mantenimiento del volumen sanguíneo y de la presión arterial. En este manuscrito se revisan nuevos conceptos en la regulación de la secreción de aldosterona y el papel de la enzima 11b-hidroxisteroid dehydrogenasa (11b-HSD en la acción de la aldosterona y en la protección del receptor mineralocorticoide contra los glucocorticoides.

    También se reportan estudios de la regulación del gen de la 11b-HSD-2 en el riñón de la rata Dahl, un modelo experimental de hipertensión genética con sensibilidad al sodio dietético.

  9. Dual Mechanism of Interleukin-3 Receptor Blockade by an Anti-Cancer Antibody

    Directory of Open Access Journals (Sweden)

    Sophie E. Broughton

    2014-07-01

    Full Text Available Interleukin-3 (IL-3 is an activated T cell product that bridges innate and adaptive immunity and contributes to several immunopathologies. Here, we report the crystal structure of the IL-3 receptor α chain (IL3Rα in complex with the anti-leukemia antibody CSL362 that reveals the N-terminal domain (NTD, a domain also present in the granulocyte-macrophage colony-stimulating factor (GM-CSF, IL-5, and IL-13 receptors, adopting unique “open” and classical “closed” conformations. Although extensive mutational analyses of the NTD epitope of CSL362 show minor overlap with the IL-3 binding site, CSL362 only inhibits IL-3 binding to the closed conformation, indicating alternative mechanisms for blocking IL-3 signaling. Significantly, whereas “open-like” IL3Rα mutants can simultaneously bind IL-3 and CSL362, CSL362 still prevents the assembly of a higher-order IL-3 receptor-signaling complex. The discovery of open forms of cytokine receptors provides the framework for development of potent antibodies that can achieve a “double hit” cytokine receptor blockade.

  10. Papel del receptor del ácido lisofosfatídico LPA1 en la neurogénesis hipocampal adulta y la memoria espacial en situaciones de estrés crónico

    OpenAIRE

    Castilla Ortega, María Estela

    2012-01-01

    Este estudio muestra que los ratones carentes del receptor del ácido lisofosfatídico LPA1 (LPA1-nulos) presentan déficit de memoria espacial. Además, el efecto del estrés crónico sobre la neurogénesis hipocampal adulta y la memoria espacial es más severo en los LPA1-nulos que en animales normales, demostrándose que la ausencia del receptor agrava las consecuencias del estrés. La modulación de la señalización mediada por el LPA1 podría intervenir en la patología asociada al estrés y al hipocam...

  11. Toll-like receptor 2 -196 to -174 del polymorphism influences the susceptibility of Han Chinese people to Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Mao Cai-Xia

    2011-10-01

    Full Text Available Abstract Background Toll-like receptor 2 (TLR2 represents a reasonable functional and positional candidate gene for Alzheimer's disease (AD as it is located under the linkage region of AD on chromosome 4q, and functionally is involved in the microglia-mediated inflammatory response and amyloid-β clearance. The -196 to -174 del polymorphism affects the TLR2 gene and alters its promoter activity. Methods We recruited 800 unrelated Northern Han Chinese individuals comprising 400 late-onset AD (LOAD patients and 400 healthy controls matched for gender and age. The -196 to -174 del polymorphism in the TLR2 gene was genotyped using the polymerase chain reaction (PCR method. Results There were significant differences in genotype (P = 0.026 and allele (P = 0.009 frequencies of the -196 to -174 del polymorphism between LOAD patients and controls. The del allele was associated with an increased risk of LOAD (OR = 1.31, 95% CI = 1.07-1.60, Power = 84.9%. When these data were stratified by apolipoprotein E (ApoE ε4 status, the observed association was confined to ApoE ε4 non-carriers. Logistic regression analysis suggested an association of LOAD with the polymorphism in a recessive model (OR = 1.64, 95% CI = 1.13-2.39, Bonferroni corrected P = 0.03. Conclusions Our data suggest that the -196 to -174 del/del genotype of TLR2 may increase risk of LOAD in a Northern Han Chinese population.

  12. Diagnóstico y clasificación molecular del virus BK en receptores de trasplante renal

    OpenAIRE

    Riva, Omar; Cobos, Marisa; Raimondi, J. Clemente

    2010-01-01

    La infección primaria por virus BK ocurre durante la infancia permaneciendo latente en el tracto urogenital. En individuos que presentan alteraciones en la inmunidad celular, el virus se reactiva haciendo posible su detección en orina y sangre. En receptores de trasplante renal, la nefropatía producida por el virus BK puede llevar a la pérdida de la función del injerto. El virus BK es miembro de la familia Polyomaviridae, presenta un genoma de ADN circular doble cadena unido en forma covalent...

  13. Elaboración de un modelo 3D del receptor Humano de NK1 a partir del receptor delta Opiode

    OpenAIRE

    Vílchez Cruz, Ángela

    2015-01-01

    La publicación de la primera estructura cristalográfica de resolución atómica de un miembro de la familia de los receptores acoplados a proteínas G (GPCR) como es la Rodopsina Bovina (Rho) (1)marcó el comienzo de los estudios sobre la relación entre la actividad biológica y la estructura de estas proteínas (1,2). Si bien se han llevado a cabo numerosos estudios de difracción de rayos X de las estructuras de GPCRs desde ese momento, dada la dificultad de cristalización de es...

  14. Encefalitis por anticuerpos contra el receptor de NMDA: experiencia con seis pacientes pediátricos. Potencial eficacia del metotrexato

    Science.gov (United States)

    Bravo-Oro, Antonio; Abud-Mendoza, Carlos; Quezada-Corona, Arturo; Dalmau, Josep; Campos-Guevara, Verónica

    2016-01-01

    Introducción La encefalitis por anticuerpos contra el receptor de N-metil-D-aspartato (NMDA) es una entidad cada vez más diagnosticada en edad pediátrica. A diferencia de los adultos, en muchos casos no se asocia a tumores y las manifestaciones iniciales en niños más frecuentes son crisis convulsivas y trastornos del movimiento, mientras que en los adultos predominan las alteraciones psiquiátricas. Casos clínicos Presentamos seis casos pediátricos confirmados con anticuerpos contra la subunidad NR1 del receptor de NMDA en suero y líquido cefalorraquídeo. Cinco de los casos comenzaron con crisis convulsivas como manifestación clínica inicial antes de desarrollar el cuadro clásico de esta entidad. En todos los casos se utilizaron esteroides como primera línea de tratamiento, con los que sólo se observó control de las manifestaciones en uno, por lo que el resto de los pacientes requirió inmunomoduladores de segunda línea. Todos los pacientes recibieron metotrexato como tratamiento inmunomodulador para evitar recaídas y la evolución fue a la mejoría en todos ellos. Conclusiones En nuestra serie de pacientes con encefalitis por anticuerpos contra el receptor de NMDA, ninguno se asoció a tumores. Todos los casos recibieron metotrexato por lo menos durante un año, no observamos eventos adversos clínicos ni por laboratorio, ni hubo secuelas neurológicas ni recaídas durante el tratamiento. Aunque es una serie pequeña y es deseable incrementar el número y tiempo de evolución, consideramos el metotrexato una excelente alternativa como tratamiento inmunomodulador para esta patología. PMID:24150952

  15. MODELO PARA SIMULAR LA HOMEÓSTASIS NEURONAL DURANTE UN INFLUJO INCREMENTADO DEL CALCIO A TRAVÉS DEL CANAL ASOCIADO AL RECEPTOR IONOTRÓPICO DE GLUTAMATO ACTIVADO POR N-METIL-D-ASPARTATO

    Directory of Open Access Journals (Sweden)

    L. Lareo

    2005-12-01

    Full Text Available Dada la importancia del receptor ionotrópico de glutamato activado por N-Metil-D-Aspartato en los procesos de aprendizaje y la formación de la memoria mediados por el transporte de calcio a través del canal asociado a dicho receptor resulta importante desarrollar modelos que permitan comprender la homeóstasis que le permite a la neurona manejar incrementos en el flujo de dicho catión sin llegar a desarrollar procesos necróticos ni apoptóticos. Este trabajo presenta una sencilla simulación de parte de los procesos metabólicos asociados al receptor como un paso inicial para comprender los mecanismos subyacentes al aprendizaje y memoria.

  16. Expression and prognostic value of hemopoietic cytokine receptors in acute myeloid leukemia (AML): implications for future therapeutical strategies.

    Science.gov (United States)

    Graf, Michaela; Hecht, Karin; Reif, Susanne; Pelka-Fleischer, Renate; Pfister, Karin; Schmetzer, Helga

    2004-02-01

    Hemopoietic cytokines regulate hemopoietic cell functions via specific cell surface receptors. There is evidence to suggest, that those receptors (R) could play a role in leukemia with respect to cell differentiations and its regulation, prognosis, and pathobiology. Knowledge of individual cytokine receptor (CKR) profiles could provide new discoveries about CKR-supported therapeutic considerations. We have studied the expression of CKR on mononuclear bone marrow (BM) cells of 89 patients with acute myeloid leukemia (AML) at first diagnosis, three patients at relapse or with persisting AML and eight healthy probands by fluorescence-activated cell sorting (FACS) analysis using directly fluorescein-conjugated antibodies: CD114 (hG-CSF-R), CD116 (hGM-CSF-R), CD117 (hSCF-R), CD123 (hIL-3-R), CD130 (gp130subunit), CD135 (hFL-R). A case was defined as positive, if more than 20% of the cells expressed the regarding CKR. All investigated CKR were more frequently expressed in AML-samples than in healthy BM-samples, except CD130, which was only expressed on 5-6% of AML-blasts in all and with only one healthy BM-sample being CD130(+). Within the French-American-British (FAB) types we observed a maturation- and lineage (granulocytic/monocytic)-committed expression profile. Monocytic subtypes (FAB-type M4/M5) showed significantly more GM-CSF-R(+) (P = 0.001) and FL-R(+) (P = 0.001) and significantly less stem cell factor-R (SCF-R(+)) (P = 0.02) cases. Highest proportions of G-CSF-R(+) blasts were observed in FAB-type M3. In undifferentiated leukemias (FAB-type M1, M2) high amounts of SCF-R(+), IL-3-R(+), and FL-R(+) blasts could be detected. FL-R was the only CKR, which was positive in FAB-type M0 (n = 2). No differences in CKR-expression were detected between primary (p) and secondary (s). Separating our patient cohorts in cytogenetic risk groups we could detect a significant higher proportion of G-CSF-R(+) blasts in the cytogenetic good risk group than in the bad risk group (P

  17. Uso de una conantokina y anticuerpos policlonales para identificar la subunidad NR2B del receptor

    Directory of Open Access Journals (Sweden)

    Leonardo Lareo,†

    2010-12-01

    Full Text Available Objetivo. Proponer una metodología de identificación de la subunidad NR2B, mediante el uso de conantokina G, así como una adecuada extracción de la subunidad NR2B. Materiales y métodos. Se ensayaron dos metodologías para la extracción de la subunidad NR2B de cerebro de rata adulta, la primera buscó la extracción de la subunidad a partir de la membrana mediante la utilización del detergente deoxicolato de sodio y la segunda, garantizó primero la solubilización y eliminación de proteínas citoplasmáticas para luego realizar la extracción de la subunidad mediante el uso del mismo detergente, a partir del pellet generado en la centrifugación del extracto obtenido. Adicionalmente se biotiniló la conantokina G para evaluar su eficiencia en la identificación de la subunidad y comparar los resultados con los obtenidos por metodologías tradicionales como DOT-BLOT, WESTERN-BLOT, ELISA e Inmunohistoquímica. Resultados. La segunda metodología mostró mayor extracción de NR2B por lo que se seleccionó para la realización de los extractos posteriores. Los ensayos de identificación con la conantokina biotinilada evidenciaron interferencia en el reconocimiento, haciéndose necesaria la identificación de la presencia de la subunidad NR2B mediante el uso de anticuerpos policlonales en los ensayos mencionados. Conclusiones. Se propone que hay un impedimento de tipo estérico en el marcaje de la conantokina con la biotina lo que no favorece la interacción de este péptido con la subunidad.

  18. Seguimiento longitudinal de la masa ósea en mujeres postmenopáusicas en función de los polimorfismo BSMI y APAI del gen del receptor de la vitamina D (VDR)

    OpenAIRE

    Pedrera Canal, María

    2015-01-01

    La Osteoporosis es una condición poligénica que está determinada por la influencia de diversos genes, cada uno de los cuales tiene un efecto modesto sobre la masa ósea. El objetivo del presente trabajo de tesis doctoral fue determinar como los polimorfismos del gen receptor de la vitamina D (BsmI y ApaI) están asociados con la densidad mineral ósea (DMO), los valores de DMO en mujeres osteoporóticas y la respuesta al tratamiento en mujeres osteoporóticas postmenopáusicas españolas. Un total d...

  19. Influencia del polimorfismo del receptor de andrógenos en la masa ósea, masa muscular y condición física en niños y niñas

    OpenAIRE

    Rodríguez García, Lorena

    2015-01-01

    Programa de doctorado: Actividad Física, Salud y Rendimiento Deportivo Premio Extraordinario de Doctorado. Rama Ciencias Sociales y Jurídicas [ES]Para determinar el efecto de ciertos polimorfismos del gen del receptor de andrógenos sobre la masa muscular y la masa ósea, se estudió una muestra poblacional de 152 niños y 116 niñas sanos y físicamente activos (estudios I y II). La composición corporal se determinó mediante absorciometría fotónica dual de rayos X (DXA) y antropometría. La c...

  20. Efectos moduladores del etanol sobre el sistema inmunitario: papel de los receptores TLR4

    OpenAIRE

    Fernández Lizarbe, Sara

    2010-01-01

    Trabajos clínicos y experimentales han demostrado que el etanol altera al sistema inmunitario. Aunque los mecanismos moleculares se desconocen, se ha demostrado que sus acciones sobre el sistema inmunitario son complejas y dependen de la dosis, el tiempo de exposición (agudo o crónico), tipo celular y presencia o ausencia de estímulos adicionales, como patógenos. Evidencias recientes indican el papel de los receptores tipo Toll (TLR) en la respuesta inmunitaria innata y, posiblemente, en...

  1. Relación del polimorfismo TaqI del gen del receptor de la vitamina D con la lepra lepromatosa en población mexicana Association between the TaqI polymorphism of Vitamin D Receptor gene and lepromatous leprosy in a Mexican population sample

    Directory of Open Access Journals (Sweden)

    Jesús Salvador Velarde Félix

    2009-02-01

    Full Text Available OBJETIVO: Determinar la relación del polimorfismo TaqI del gen del receptor de la vitamina D (RVD con la lepra lepromatosa (LL en individuos originarios de Sinaloa, México. MATERIAL Y MÉTODOS: Se amplificó un fragmento de 740 pb del gen RVD en muestras de ADN de 71 pacientes con LL y 144 controles en el Hospital General de Culiacán durante el periodo 2004-2007. El polimorfismo se identificó mediante la endonucleasa TaqI. RESULTADOS: Se observó un aumento de relevancia estadística del genotipo TT en pacientes con LL en comparación con los controles (p= 0.040; RM= 1.82. CONCLUSIÓN: Se demuestra un nexo entre el genotipo TT y la susceptibilidad a la LL.OBJETIVE: To establish the association of the vitamin D receptor gene TaqI polymorphism with lepromatous leprosy (LL in individuals from Sinaloa, Mexico. MATERIAL AND METHODS: A 740 bp fragment was amplified from the VDR gene in DNA samples of 71 patients with LL and 144 controls in the Hospital General de Culiacán during 2004-2007. Polymorphism was identified through TaqI endonuclease. RESULTS: A significant increase in the genotype TT of the VDR gene was observed in patients when compared to controls (p = 0.040; OR = 1.82. CONCLUSIONS: Our data support the association between the TT genotype and susceptibility to LL in this Mexican population.

  2. Role of Granulocyte-Macrophage Colony-Stimulating Factor Production by T Cells during Mycobacterium tuberculosis Infection.

    Science.gov (United States)

    Rothchild, Alissa C; Stowell, Britni; Goyal, Girija; Nunes-Alves, Cláudio; Yang, Qianting; Papavinasasundaram, Kadamba; Sassetti, Christopher M; Dranoff, Glenn; Chen, Xinchun; Lee, Jinhee; Behar, Samuel M

    2017-10-24

    Mice deficient for granulocyte-macrophage colony-stimulating factor (GM-CSF -/- ) are highly susceptible to infection with Mycobacterium tuberculosis , and clinical data have shown that anti-GM-CSF neutralizing antibodies can lead to increased susceptibility to tuberculosis in otherwise healthy people. GM-CSF activates human and murine macrophages to inhibit intracellular M. tuberculosis growth. We have previously shown that GM-CSF produced by iNKT cells inhibits growth of M. tuberculosis However, the more general role of T cell-derived GM-CSF during infection has not been defined and how GM-CSF activates macrophages to inhibit bacterial growth is unknown. Here we demonstrate that, in addition to nonconventional T cells, conventional T cells also produce GM-CSF during M. tuberculosis infection. Early during infection, nonconventional iNKT cells and γδ T cells are the main source of GM-CSF, a role subsequently assumed by conventional CD4 + T cells as the infection progresses. M. tuberculosis -specific T cells producing GM-CSF are also detected in the peripheral blood of infected people. Under conditions where nonhematopoietic production of GM-CSF is deficient, T cell production of GM-CSF is protective and required for control of M. tuberculosis infection. However, GM-CSF is not required for T cell-mediated protection in settings where GM-CSF is produced by other cell types. Finally, using an in vitro macrophage infection model, we demonstrate that GM-CSF inhibition of M. tuberculosis growth requires the expression of peroxisome proliferator-activated receptor gamma (PPARγ). Thus, we identified GM-CSF production as a novel T cell effector function. These findings suggest that a strategy augmenting T cell production of GM-CSF could enhance host resistance against M. tuberculosis IMPORTANCE Mycobacterium tuberculosis is the bacterium that causes tuberculosis, the leading cause of death by any infection worldwide. T cells are critical components of the immune

  3. Peroxisome-proliferator-activated receptor-γ agonists inhibit the release of proinflammatory cytokines from RSV-infected epithelial cells

    International Nuclear Information System (INIS)

    Arnold, Ralf; Koenig, Wolfgang

    2006-01-01

    The epithelial cells of the airways are the target cells for respiratory syncytial virus (RSV) infection and the site of the majority of the inflammation associated with the disease. Recently, peroxisome-proliferator-activated receptor γ (PPARγ), a member of the nuclear hormone receptor superfamily, has been shown to possess anti-inflammatory properties. Therefore, we investigated the role of PPARγ agonists (15d-PGJ 2 , ciglitazone and troglitazone) on the synthesis of RSV-induced cytokine release from RSV-infected human lung epithelial cells (A549). We observed that all PPARγ ligands inhibited dose-dependently the release of TNF-α, GM-CSF, IL-1α, IL-6 and the chemokines CXCL8 (IL-8) and CCL5 (RANTES) from RSV-infected A549 cells. Concomitantly, the PPARγ ligands diminished the cellular amount of mRNA encoding for IL-6, CXCL8 and CCL5 and the RSV-induced binding activity of the transcription factors NF-κB (p65/p50) and AP-1 (c-fos), respectively. Our data presented herein suggest a potential application of PPARγ ligands in the anti-inflammatory treatment of RSV infection

  4. Action of granulopoiesis-stimulating cytokines rhG-CSF, rhGM-CSF, and rmGM-CSF on murine hematopoietic progenitor cells for granulocytes and macrophages (GM-CFC)

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Vacek, Antonín; Weiterová, Lenka

    2005-01-01

    Roč. 54, - (2005), s. 207-213 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) IBS5004009; GA AV ČR(CZ) KSK5011112; GA ČR(CZ) GP305/03/D050 Institutional research plan: CEZ:AV0Z50040507 Keywords : murine hematopoiesis * GM-CFC * rhG- CSF Subject RIV: BO - Biophysics Impact factor: 1.806, year: 2005

  5. Sphingosine 1 Phosphate at the Blood Brain Barrier: Can the Modulation of S1P Receptor 1 Influence the Response of Endothelial Cells and Astrocytes to Inflammatory Stimuli?

    Directory of Open Access Journals (Sweden)

    Simona F Spampinato

    Full Text Available The ability of the Blood Brain Barrier (BBB to maintain proper barrier functions, keeping an optimal environment for central nervous system (CNS activity and regulating leukocytes' access, can be affected in CNS diseases. Endothelial cells and astrocytes are the principal BBB cellular constituents and their interaction is essential to maintain its function. Both endothelial cells and astrocytes express the receptors for the bioactive sphingolipid S1P. Fingolimod, an immune modulatory drug whose structure is similar to S1P, has been approved for treatment in multiple sclerosis (MS: fingolimod reduces the rate of MS relapses by preventing leukocyte egress from the lymph nodes. Here, we examined the ability of S1P and fingolimod to act on the BBB, using an in vitro co-culture model that allowed us to investigate the effects of S1P on endothelial cells, astrocytes, and interactions between the two. Acting selectively on endothelial cells, S1P receptor signaling reduced cell death induced by inflammatory cytokines. When acting on astrocytes, fingolimod treatment induced the release of a factor, granulocyte macrophage colony-stimulating factor (GM-CSF that reduced the effects of cytokines on endothelium. In an in vitro BBB model incorporating shear stress, S1P receptor modulation reduced leukocyte migration across the endothelial barrier, indicating a novel mechanism that might contribute to fingolimod efficacy in MS treatment.

  6. Toll like receptor 3 & 4 responses of human turbinate derived mesenchymal stem cells: stimulation by double stranded RNA and lipopolysaccharide.

    Directory of Open Access Journals (Sweden)

    Se Hwan Hwang

    Full Text Available BACKGROUND AND OBJECTIVES: Multipotent mesenchymal stromal cells (MSCs represent a promising cell-based therapy for a number of inflammatory or autoimmune diseases. Herein, Toll like receptor (TLR expression by MSCs and their immune regulatory roles are investigated. In this study, we investigated the influence of TLR on the immune response, proliferation, and differentiation potential of human turbinated MSC (hTMSC cultures in vitro. SUBJECTS AND METHODS: After isolating hTMSCs from discarded inferior turbinate tissue, FACS analysis was used to assess the expression of TLRs such as TLR2, TLR3, TLR4, and TLR5 in hTMSCs and cell proliferation was assessed using a cell counting kit (CCK-8. Cytokine and chemokine secretions were analyzed with multiplex immunoassays for IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, IP-10 (CXCL10, RANTES (CCL5, TNF-a, GM-CSF, and IFN-γ. The differentiation potential of hTMSCs was evaluated in the osteogenic, chondogenic, and adipogeinc media and analyzed by histology and gene expression related to differentiation. RESULTS: FACS analysis revealed that TLR3 and TLR4 expression consisted of a relatively high percentage of the surface proteins expressed by hTMSCs. The proliferation of hTMSCs was influenced and significantly increased by the presence of TLR4 agonists. In particular, hTMSCs produced a set of cytokines and chemokines and the expression of IL-6, IL-8, IL-12, IP-10 (CXCL10, RANTES (CCL5, TNF-α, and GM-CSF were up-regulated in response to the TLR4 agonist LPS. The osteogenic and adipogeinc differentiation potential of hTMSCs was not affected by TLR agonists. CONCLUSIONS: We conclude that TLR4 stimulation affects TLR expression, proliferation, and the immunomodulation potential of hTMSCs. Understanding the mechanism behind TLR's influence on hTMSCs and their immunomodulating properties would be useful for providing a novel target to exploit in the improvement of stem cell-based therapeutic strategies.

  7. Regulation of dendritic cell development by GM-CSF: Molecular control and implications for immune homeostasis and therapy

    NARCIS (Netherlands)

    L. van de Laar (Lianne); P.J. Coffer (Paul); A.M. Woltman (Andrea)

    2012-01-01

    textabstractDendritic cells (DCs) represent a small and heterogeneous fraction of the hematopoietic system, specialized in antigen capture, processing, and presentation. The different DC subsets act as sentinels throughout the body and perform a key role in the induction of immunogenic as well as

  8. Cuscuta chinensis Ameliorates Immunosuppression and Urotoxic Effect of Cyclophosphamide by Regulating Cytokines - GM-CSF and TNF-Alpha.

    Science.gov (United States)

    Raju, Nidhi; Sakthivel, Kunnathur Murugesan; Kannan, Narayanan; Vinod Prabhu, Venugopal; Guruvayoorappan, Chandrasekaran

    2015-06-01

    Cancer is the leading cause of death worldwide. Cyclophosphamide (CTX) is commonly used as anticancer drug which causes toxicity by its reactive metabolites such as acroline and phosphoramide mustard. In this study, Cuscuta chinensis (C. chinensis) (family: Convolvulaceae) was assessed for ability to restore mice against CTX-induced toxicity. Coadministration of C. chinensis extract (10 mg/kg BW, IP, daily) for ten consecutive days reduced CTX-induced (25 mg/kg BW, IP, daily) toxicity. Treatment with C. chinensis extract significantly (p < 0.01) increased the relative organ weight and body weight. Moreover, administration of C. chinensis extract significantly increased bone marrow cellulatity and α-esterase activity in CTX-treated mice which suggested its protective role on the hematopoietic system. The GSH content was drastically reduced by CTX administration in urinary bladder which was enhanced by treatment with C. chinensis extract, indicating that preventing acroline-mediated tissue damage or cell toxicity and also the extract decreased the urinary bladder nitric oxide (NO) level which proves recovery over urinary tract injury associated with CTX treatment. The administration of C. chinensis extract decreased serum urea, creatinine, and bilirubin levels when compared to CTX-alone-treated group. Histopathological analysis of the urinary bladder of CTX-alone-treated group showed necrotic damage whereas the C. chinensis-treated group showed normal bladder architecture. The above data clearly demonstrates chemoprotective role of C. chinensis against CTX-induced toxicities by regulating antioxidant and inflammatory mediators.

  9. Chimeric HIV-1 envelope glycoproteins with potent intrinsic granulocyte-macrophage colony-stimulating factor (GM-CSF) activity

    NARCIS (Netherlands)

    Isik, Gözde; van Montfort, Thijs; Boot, Maikel; Cobos Jiménez, Viviana; Kootstra, Neeltje A.; Sanders, Rogier W.

    2013-01-01

    HIV-1 acquisition can be prevented by broadly neutralizing antibodies (BrNAbs) that target the envelope glycoprotein complex (Env). An ideal vaccine should therefore be able to induce BrNAbs that can provide immunity over a prolonged period of time, but the low intrinsic immunogenicity of HIV-1 Env

  10. Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma

    Science.gov (United States)

    2015-12-01

    Hepatocellular Carcinoma; Hepatoma; Liver Cancer, Adult; Liver Cell Carcinoma; Liver Cell Carcinoma, Adult; Cancer of Liver; Cancer of the Liver; Cancer, Hepatocellular; Hepatic Cancer; Hepatic Neoplasms; Hepatocellular Cancer; Liver Cancer; Neoplasms, Hepatic; Neoplasms, Liver

  11. Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34+ cells of juvenile myelomonocytic leukemia

    Directory of Open Access Journals (Sweden)

    Yozo Nakazawa

    2016-03-01

    Full Text Available Abstract Background Juvenile myelomonocytic leukemia (JMML is a fatal, myelodysplastic/myeloproliferative neoplasm of early childhood. Patients with JMML have mutually exclusive genetic abnormalities in granulocyte-macrophage colony-stimulating factor (GM-CSF receptor (GMR, CD116 signaling pathway. Allogeneic hematopoietic stem cell transplantation is currently the only curative treatment option for JMML; however, disease recurrence is a major cause of treatment failure. We investigated adoptive immunotherapy using GMR-targeted chimeric antigen receptor (CAR for JMML. Methods We constructed a novel CAR capable of binding to GMR via its ligand, GM-CSF, and generated piggyBac transposon-based GMR CAR-modified T cells from three healthy donors and two patients with JMML. We further evaluated the anti-proliferative potential of GMR CAR T cells on leukemic CD34+ cells from six patients with JMML (two NRAS mutations, three PTPN11 mutations, and one monosomy 7, and normal CD34+ cells. Results GMR CAR T cells from healthy donors suppressed the cytokine-dependent growth of MO7e cells, but not the growth of K562 and Daudi cells. Co-culture of healthy GMR CAR T cells with CD34+ cells of five patients with JMML at effector to target ratios of 1:1 and 1:4 for 2 days significantly decreased total colony growth, regardless of genetic abnormality. Furthermore, GMR CAR T cells from a non-transplanted patient and a transplanted patient inhibited the proliferation of respective JMML CD34+ cells at onset to a degree comparable to healthy GMR CAR T cells. Seven-day co-culture of GMR CAR T cells resulted in a marked suppression of JMML CD34+ cell proliferation, particularly CD34+CD38− cell proliferation stimulated with stem cell factor and thrombopoietin on AGM-S3 cells. Meanwhile, GMR CAR T cells exerted no effects on normal CD34+ cell colony growth. Conclusions Ligand-based GMR CAR T cells may have anti-proliferative effects on stem and progenitor cells in JMML.

  12. Bloqueo del receptor del factor de crecimiento semejante a la Insulina Tipo I utilizando oligodeoxinucleótidos antisentido en cáncer de mama experimental Type I insulin-like growth factor receptor antisense strategies in experimental breast cancer

    Directory of Open Access Journals (Sweden)

    Mariana Salatino

    2004-04-01

    Full Text Available Evaluamos el efecto del bloqueo de la expresión del receptor del factor de crecimiento semejante a la insulina tipo I (IGF-IR sobre el crecimiento in vivo de cáncer de mama empleando una estrategia "antisentido". Utilizamos el adenocarcinoma mamario murino progestágeno-dependiente C4HD. La administración intratumoral o sistémica de oligodeoxinucleótidos antisentido fosfotiolados al ARNm del IGF-IR (AS[S]ODN inhibió el crecimiento tumoral. El efecto antitumoral fue específico debido a su dosis-dependencia y a la falta de efecto en ratones tratados con el S[S]ODN "sentido". Los tumores obtenidos de ratones tratados con AS[S]ODN mostraron: disminución en la expresión de IGF-IR y en la fosforilación del sustrato del receptor de insulina-1, inhibición de la activación de PI-3K/Akt, p42/p44MAPK y ErbB-2, mientras que la expresión y activación del receptor de progesterona no se afectó. Es la primera demostración que el crecimiento de cáncer de mama puede ser inhibido por la administración in vivo de AS[S]ODN al IGF-IR.We addressed the effect of targeting type I insulin-like growth factor receptor (IGF-IR, with antisense strategies in in vivo growth of breast cancer cells. We used C4HD tumors from an experimental model of hormonal carcinogenesis in which medroxyprogesterone acetate induced mammary adenocarcinomas in Balb/c mice. Intratumor or systemic administration of phosphorothiolated antisense oligodeoxynucleotides (AS[S]ODN to IGF-IR mRNA resulted in a significant inhibition of C4HD tumor growth. The antitumor effect was specific since inhibition of tumor growth was dose-dependent and no effect was observed in mice treated with sense S[S]ODN. Tumors from AS[S]ODN-treated mice showed a decrease in IGF-IR expression and in insulin receptor substrate-1 tyrosine phosphorylation. Activation of PI-3K/Akt, p42/p44 MAPK and ErbB-2 was abolished in tumors treated with AS[S]ODN. Progesterone receptor expression or activity remained

  13. La desnutrición proteica estimula la expresión de receptores de la hormona del crecimiento en linfocitos B esplénicos de rata

    Directory of Open Access Journals (Sweden)

    Wilson Mejía-Naranjo

    2004-12-01

    Full Text Available La interacción recíproca entre los sistemas endocrino e immune ha sido objeto en la última década de numerosas investigaciones que han aportado evidencia sustancial sobre el papel del eje GH/IGF-I en el sistema inmune. Recientemente, se ha postulado que el eje GH/IGF-I ejerce una función importante en la modulación de condiciones de estrés, tales como estados catabólicos, trastornos asociados con el envejecimiento, síndrome de inmunodeficiencia adquirida y desnutrición. No se conoce aún si estos efectos son ejercidos a través de mecanismos endocrinos, autocrinos o paracrinos en los diferentes tipos de tejidos del sistema inmune. El objetivo de este estudio fue establecer los principales subtipos celulares linfoides que son blanco de la acción de la hormona de crecimiento. Además, se estudió el efecto regulador del estrés inducido por la desnutrición proteica sobre la distribución relativa de células linfoides positivas al receptor de GH (GHR. Ratas normales se sometieron a dietas isocalóricas de contenido variable de proteína (0, 4, 8, 12 y 20% durante 14 días y se aislaron los linfocitos de bazo, ganglios linfáticos y sangre periférica. Mediante citometría de flujo se analizó la unión a Fluos-rrGH y los linfocitos CD4+, CD8+ y B se definieron empleando anticuerpos monoclonales específicos marcados con PE. Se encontró que el patrón de expresión de GHR varía con el tejido y tipo celular linfoide. El bazo es el órgano más sensible al déficit de proteína, y la mayor expresión de receptores para GH se presenta en las células B seguidas por las células CD4+. Al reducir el contenido de proteína en la dieta de 20% a 0% se observó un incremento del 12% al 52% en el número de células B positivas para el receptor de GH y del 8% al 17% en las células CD4+ positivas para GHR en el bazo. En contraste, sólo el 10%-13% de linfocitos de los ganglios linfáticos y 2%-4% de la sangre periférica presentaron receptores

  14. The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus.

    Directory of Open Access Journals (Sweden)

    Chad Steele

    2005-12-01

    Full Text Available Alveolar macrophages represent a first-line innate host defense mechanism for clearing inhaled Aspergillus fumigatus from the lungs, yet contradictory data exist as to which alveolar macrophage recognition receptor is critical for innate immunity to A. fumigatus. Acknowledging that the A. fumigatus cell wall contains a high beta-1,3-glucan content, we questioned whether the beta-glucan receptor dectin-1 played a role in this recognition process. Monoclonal antibody, soluble receptor, and competitive carbohydrate blockage indicated that the alveolar macrophage inflammatory response, specifically the production of tumor necrosis factor-alpha (TNF-alpha, interleukin-1alpha (IL-1alpha, IL-1beta, IL-6, CXCL2/macrophage inflammatory protein-2 (MIP-2, CCL3/macrophage inflammatory protein-1alpha (MIP-1alpha, granulocyte-colony stimulating factor (G-CSF, and granulocyte monocyte-CSF (GM-CSF, to live A. fumigatus was dependent on recognition via the beta-glucan receptor dectin-1. The inflammatory response was triggered at the highest level by A. fumigatus swollen conidia and early germlings and correlated to the levels of surface-exposed beta glucans, indicating that dectin-1 preferentially recognizes specific morphological forms of A. fumigatus. Intratracheal administration of A. fumigatus conidia to mice in the presence of a soluble dectin-Fc fusion protein reduced both lung proinflammatory cytokine/chemokine levels and cellular recruitment while modestly increasing the A. fumigatus fungal burden, illustrating the importance of beta-glucan-initiated dectin-1 signaling in defense against this pathogen. Collectively, these data show that dectin-1 is centrally required for the generation of alveolar macrophage proinflammatory responses to A. fumigatus and to our knowledge provides the first in vivo evidence for the role of dectin-1 in fungal innate defense.

  15. Macrophage colony-stimulating factor, CSF-1, and its proto-oncogene-encoded receptor

    International Nuclear Information System (INIS)

    Sherr, C.J.; Rettenmier, C.W.; Roussel, M.F.

    1988-01-01

    The macrophage colony-stimulating factor, CSF-1, or M-CSF, is one of a family of hematopoietic growth factors that stimulates the proliferation of monocytes, macrophages, and their committed bone marrow progenitors. Unlike pluripotent hemopoietins such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3 or multi-CSF), which affect the growth of myeloid cells of several different hematopoietic lineages, CSF-1 acts only on cells of the mononuclear phagocyte series to stimulate their growth and enhance their survival. Retroviral transduction of the feline c-fms gene in the Susan McDonough and Hardy Zuckerman-5 (HZ-5) strains of feline sarcoma virus (FeSV) led to genetic alterations that endowed the recombined viral oncogene (v-fms) with the ability to transform cells in culture morphologically and to induce firbrosarcomas and hematopoietic neoplasms in susceptible animals. The v-fms oncogene product differs from the normal CSF-1 receptor in certain of its cardinal biochemical properties, most notably in exhibiting constitutively high basal levels of tyrosine kinase activity in the absence of its ligand. Comparative studies of the c-fms and v-fms genes coupled with analyses of engineered mutants and receptor chimeras have begun to pinpoint pertinent genetic alterations in the normal receptor gene that unmask its latent oncogenic potential. In addition, the availability of biologically active c-fms, v-fms, and CSF-1 cDNAs has allowed these genes to be mobilized and expressed in naive cells, thereby facilitating assays for receptor coupling with downstream components of the mitogenic pathway in diverse cell types

  16. BÚSQUEDA DE LA MUTACIÓN Phe-809 EN EL GEN DEL SUSTRATO DEL RECEPTOR DE INSULINA -1 (IRS-1 EN RATAS DIABÉTICAS eSS

    Directory of Open Access Journals (Sweden)

    Stella Maris Daniele

    2010-01-01

    Full Text Available El gen del sustrato del receptor de insulina IRS-1 juega un rol clave en la transducción de señales de insulina en músculo esquelético. Diversos polimorfismos del gen IRS-1 han sido reportados en estados de insulinorresistencia como obesidad y diabetes tipo 2.Las ratas eSS desarrollan espontáneamente diabetes tipo 2 magra, con insulinoresistencia caracterizada por hiperglucemia e hiperinsulinemia. Durante el segundo año existe disminución progresiva de la insulinemia y agravamiento del síndrome. Nuestro propósito fue buscar la mutación Phe-809 en el gen IRS-1, que implica sustitución del aminoácido Ser por Phe en el codon 809; dicho sitio se halla conservado en la rata. Esta variante fue identificada en pacientes diabéticos tipo 2. El gen del IRS-1 consta de un solo exón.Se analizó un fragmento de 281pb del gen IRS-1, que posee 90% de homología con el mismo fragmento en humanos. Se purificó ADN de leucocitos de un pool de sangre de ratas machos eSS y controles Wistar. Se cuantificó y amplificó por PCR utilizando un par de primers para amplificar ese mismo fragmento en el gen IRS-1 en humanos. Se usó sangre humana como control de amplificación. Se empleó el método de Sanger en la secuenciación del fragmento obtenido por PCR, previa extracción del mismo de un gel de agarosa al 2%. Se observó que la rata eSS y las controles mantuvieron la lectura esperada para ese fragmento, no encontrándose la mutación investigada. Se descarta la mutación Phe-809 como origen de la insulinoresistencia de la rata eSS.

  17. Inhibición dual de la neprilisina y del receptor de la angiotensina (ARNI: una alternativa en los pacientes con falla cardiaca

    Directory of Open Access Journals (Sweden)

    Beatriz Wills

    2016-03-01

    Full Text Available La falla cardiaca (FC es la causa más común de admisión hospitalaria en adultos en el mundo. Además, de su importante prevalencia la FC tiene un alta tasa de mortalidad, se estima que aproximadamente el 50% de los pacientes con FC mueren a los 5 años posterior al egreso hospitalario. Esto ha motivado el desarrollo de nuevas terapias seguras y efectivas para el manejo de esta entidad. El LCZ696 es un inhibidor dual de la neprilisina y del receptor de angiotensina II que demostró en estudios de fase III disminuir el desenlace primario de muerte cardiovascular y hospitalización por empeoramiento de la FC y muerte global. Probablemente el LCZ696 se convertirá en la piedra angular del manejo en pacientes con FC con fracción de eyección deprimida.

  18. El receptor de estrógenos alfa como mediador del efecto proliferativo de progestágenos en cáncer de mama

    Directory of Open Access Journals (Sweden)

    Sebastián Giulianelli

    2012-08-01

    Full Text Available En carcinomas mamarios murinos (C4-HD y en células de cáncer de mama humano (T47D observamos que el progestágeno sintético, acetato de medroxiprogesterona (MPA, induce la activación del receptor de estrógenos alfa (REa y su asociación nuclear con el receptor de progesterona (RP. En este trabajo postulamos que dicha interacción a nivel genómico sería fundamental para desarrollar respuestas proliferativas mediadas por progestágenos. Demostramos que el antiestrógeno fulvestrant (FUL, ICI182.780 indujo la regresión completa de tumores C4-HD creciendo con MPA. El progestágeno indujo la expresión temprana de CCND1 y MYC en células T47D y este efecto fue revertido al bloquear el REa. En células tratadas con MPA utilizamos ensayos de inmunoprecipitación de la cromatina (ChIP y corroboramos la colocalización nuclear de RP/REa en los mismos sitios de los promotores de CCND1 y MYC. El ICI no afectó la unión de RP a ambas secuencias regulatorias, pero sí inhibió la unión del REa. Confirmamos la interacción nuclear entre REa y RP en muestras de cáncer de mama humano. Los resultados demuestran que la presencia del REa, interactuando con el RP, en promotores de CCND1 y MYC es fundamental para la transcripción génica y la proliferación celular inducida por el progestágeno.

  19. Innate immune receptors in human airway smooth muscle cells: activation by TLR1/2, TLR3, TLR4, TLR7 and NOD1 agonists.

    Directory of Open Access Journals (Sweden)

    Anne Månsson Kvarnhammar

    Full Text Available BACKGROUND: Pattern-recognition receptors (PRRs, including Toll-like receptors (TLRs, NOD-like receptors (NLRs and RIG-I-like receptors (RLRs, recognize microbial components and trigger a host defense response. Respiratory tract infections are common causes of asthma exacerbations, suggesting a role for PRRs in this process. The present study aimed to examine the expression and function of PRRs on human airway smooth muscle cells (HASMCs. METHODS: Expression of TLR, NLR and RLR mRNA and proteins was determined using real-time RT-PCR, flow cytometry and immunocytochemistry. The functional responses to ligand stimulation were investigated in terms of cytokine and chemokine release, cell surface marker expression, proliferation and proteins regulating the contractile state. RESULTS: HASMCs expressed functional TLR2, TLR3, TLR4, TLR7 and NOD1. Stimulation with the corresponding agonists Pam3CSK4, poly(I:C, LPS, R-837 and iE-DAP, respectively, induced IL-6, IL-8 and GM-CSF release and up-regulation of ICAM-1 and HLA-DR, while poly(I:C also affected the release of eotaxin and RANTES. The proliferative response was slightly increased by LPS. Stimulation, most prominently with poly(I:C, down-regulated myosin light chain kinase and cysteinyl leukotriene 1 receptor expression and up-regulated β2-adrenoceptor expression. No effects were seen for agonist to TLR2/6, TLR5, TLR8, TLR9, NOD2 or RIG-I/MDA-5. CONCLUSION: Activation of TLR2, TLR3, TLR4, TLR7 and NOD1 favors a synthetic phenotype, characterized by an increased ability to release inflammatory mediators, acquire immunomodulatory properties by recruiting and interacting with other cells, and reduce the contractile state. The PRRs might therefore be of therapeutic use in the management of asthma and infection-induced disease exacerbations.

  20. Detección del receptor de factor de crecimiento epidérmico en lesiones orales premalignas por relaxometría

    OpenAIRE

    Alonso Geli, Yamirka; De la Cruz, Enrique Reynaldo; Dutok Sánchez, Carlos M.; Álvarez Guerra, Eloy D

    2014-01-01

    Objetivo: detectar la sobreexpresión del receptor de factor de crecimiento epidérmico en células epiteliales de lesiones premalignas de la mucosa bucal, marcadas magnéticamente por relaxometría. Métodos: las células exfoliadas de mucosa oral de individuos sanos y enfermos se marcaron con el sistema: IgG anti-EGF-R biotinilada/IgG anti-biotina conjugada con partículas superparamagnéticas y se midieron los tiempos de relajación T1 y T2. Resultados: disminuyeron los tiempos de relajación (T1 y T...

  1. Los niños del Cauca II. Receptor de la vitamina D con secuencia normal en un foco de pacientes con raquitismo dependiente de la vitamina D, tipo II

    Directory of Open Access Journals (Sweden)

    Luis Fernando García-Ramirez

    1993-12-01

    Full Text Available El Raquitismo Dependiente de Vitamina D, tipo II (RDVD II, es una enfermedad de herencia autosómica recesiva que se caracteriza por resistencia generalizada a la 1,25-dihidroxivitamina D, originada en alteraciones que comprometen la función del receptor para la vitamina D (RVD. El clonaje y caracterización del cDNA del RVD ha permitido el estudio de su secuencia en pacientes con RDVD II y el hallazgo de diversas mutaciones puntuales que explican el cuadro clínico. En este estudio, hemos utilizado las técnicas de PCR y clonación, para secuenciar el RVD de dos pacientes pertenecientes a un foco descrito previamente en el departamento del Cauca (Colombia, cuyas manifestaciones clínicas y de laboratorio son compatibles con RDVD II. La secuencia del RVD de nuestros pacientes fue normal, sugiriendo una alteración a nivel postranscripcional o postraduccional relacionada con la función del receptor, en lo que podría corresponder a una nueva variante de resistencia a la vitamina D.

  2. El significado del capital social "individual" en diabéticos receptores de cuidado en un contexto urbano colombiano

    Directory of Open Access Journals (Sweden)

    Eliana Martínez-Herrera

    2015-04-01

    Full Text Available Comprender el significado del capital social de la diabetes tipo 2 según género, dentro un contexto urbano colombiano. Investigación cualitativa del interaccionismo simbólico. 25 mujeres y 16 hombres, diabéticos, familiares, vecinos y personal asistencial participaron en seis grupos focales. Emergieron 850 códigos que se integraron en un set de 142 códigos de códigos para el ego, el alter y alter ego. Tres categorías y veinte subcategorías fueron identificadas para el diseño del "paradigma de la codificación". El significado no es igual para hombres y mujeres. Los vínculos sociales de las redes sociales, creados cotidianamente por la confianza y la solidaridad para el cuidado, son valorados de manera diferente, debido a experiencias y hechos sociales resultantes de la autoconfianza, la autoeficacia para el apoyo social principalmente y, la autoestima frente al manejo y control de la enfermedad. Los recursos sociales de un individuo son reificados para el manejo y cuidado de la enfermedad como estrategia para disminuir las inequidades en salud

  3. Functional effects of Toll-like receptor (TLR3, 7, 9, RIG-I and MDA-5 stimulation in nasal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Lotta Tengroth

    Full Text Available The human nasal epithelium is an important physical barrier, and a part of the innate immune defense that protect against pathogens. The epithelial cells recognize microbial components by pattern-recognition receptors (PRRs, and thereby trigger an immune response. Even though TLR3, TLR7, TLR9, RIG-I and MDA-5 are all known to respond to viral stimulation, their potential role in chronic airway inflammation triggered by local cytokine release remains to be established.mRNA and corresponding protein expression of TLR3, TLR7, TLR9, RIG-I and MDA-5 were analyzed in nasal biopsies and various upper airway epithelial cell lines using real-time reverse transcription PCR, immunohistochemistry and flow cytometry. Ligand induced, cytokine release, was evaluated with ELISA.Nasal biopsies were found to express TLR3, TLR7, TLR9, RIG-I and MDA-5, with the most abundant expression in the surface epithelium. These receptors were verified in primary human nasal epithelial cell (HNEC as well as in the airway epithelial cell lines Detroit-562 and FaDu. Poly(I:C (TLR3 and R-837 (TLR7 stimulation increased secretion of IL-6 and GM-CSF from the nasal mucosa and the epithelial cell lines. CpG (TLR9 stimulation caused release of IL-8 in the nasal mucosa and in FaDu. Poly(I:C/LyoVec (RIG-I/MDA-5 stimulation activated the secretion of IFN-β in the nasal mucosa. A corresponding release was also detected from HNEC and Detroit-562.The nasal epithelium has the ability to recognize viral intrusion through TLR and RLR receptors, and the subsequent response might have a role in exacerbation of inflammatory diseases like allergic rhinitis and chronic rhinosinusitis.

  4. Arteriosclerosis and the promise of GPIIb/IIIa inhibitors in stroke Arteriosclerosis y nuevas perspectivas de los inhibidores del receptor GPIIb/IIIa en stroke

    Directory of Open Access Journals (Sweden)

    GUSTAVO SAPOSNIK

    2000-03-01

    Full Text Available Ischemic mechanisms in patients with brain and heart attacks have been studied for more than 150 years. Antiplatelets agents did show benefit in secondary prevention. Aspirin is the most common antiaggregant in clinical use today. However, the benefit produced by the "best" antiplatelet regimen in stroke prevention is lower than 40%. The adherence of circulating platelets to the subendothelium is mediated by glycoprotein (GP residing on the cell's surface. GPIIb/IIIa is the most important platelet membrane receptor that mediates the process of platelet aggregation, and thrombus formation. Thus, new drugs that block the GPIIb/IIIa receptor have recently emerged. Clinical trials using these agents have shown effectiveness in acute coronary syndromes. However, the absence of studies in cerebrovascular disease and the potential hemorrhagic complications questioned their use in stroke prevention. We review the clinical trials using the new GPIIb/IIIa agents in myocardial ischemia, and consider the potential implications for cerebrovascular disease.Los mecanismos de isquemia en infarto de miocardio y enfermedad cerebrovascular (ECV han sido estudiados por mas de 150 años. Drogas antiplaquetarias mostraron un beneficio en la prevención secundaria. La aspirina es el mas común de los antiagregantes usados en la practica clínica. No obstante, el beneficio producido, aun con el "mejor" tratamiento antiagregante, en la prevención de ECV es inferior al 40%. La adhesión plaquetaria es un proceso mediado por glicoproteinas (GP de la membrana celular. GPIIb/IIIa es un receptor de membrana plaquetaria que interviene en el proceso de agregación plaquetaria y formación del trombo. Estudios clínicos con nuevos agentes que bloquean a este receptor mostraron ser efectivos en los síndromes coronarios agudos. No obstante, la falta de estudios en ECV y las potenciales complicaciones hemorrágicas, limitan su uso en la prevención de stroke. Revisamos los

  5. Genes del receptor variable beta de células T en células circulantes de pacientes con lupus eritematoso generalizado y sus familiares sanos.

    Science.gov (United States)

    Jakez-Ocampo, Juan; Paulín-Vera, Carmen María; Rivadeneyra-Espinoza, Liliana; Gómez-Martín, Diana; Carrillo-Maravilla, Eduardo; Lima, Guadalupe; Vargas-Rojas, María Inés; Pérez-Romano, Beatriz; Calva-Cevenini, Gabriella; García-Carrasco, Mario; Ruiz-Argüelles, Alejandro; Llorente, Luis

    Se investigó la proporción de la expresión génica del receptor variable beta de células T (Vβ TCR) en linfocitos periféricos CD3+ en pacientes con lupus eritematoso generalizado (LEG) familiar y no familiar. El repertorio de Vβ TCR se estudió en 14 familias que presentaban más de un miembro con LEG. El uso de Vβ TCR en pacientes con LEG (n = 27) se comparó con el de los miembros sanos de estas familias (n = 47), con 37 pacientes con LEG esporádico y con 15 controles sanos. La expresión del repertorio de Vβ TCR se estudió por citometría de flujo multiparamétrica utilizando un arreglo de 24 diferentes anticuerpos monoclonales específicos de genes familiares para Vβ TCR. Se encontró el mismo perfil de expresión en las comparaciones entre los casos de LEG esporádico y familiar, así como en los consanguíneos sanos de las familias multicasos, que incluía una expresión incrementada de Vβ 5.2, Vβ 11 y Vβ 16, y una menor expresión de Vβ 3, Vβ4, Vβ 7.1 y Vβ 7. De manera interesante, solo Vβ 17 se expresó de modo diferente entre casos familiares y esporádicos de LEG. Igualmente, la expresión incrementada de Vβ 9 fue el distintivo entre los casos de LEG familiar (casos y consanguíneos sanos) y los controles sanos. Estos resultados refuerzan la noción de que el perfil final del repertorio Vβ TCR observado en LEG familiar y no familiar parece surgir de la interacción de factores genéticos, ambientales e inmunorreguladores, además de que pueden explicar las alteraciones inmunitarias que se observan en los consanguíneos sanos de pacientes con LEG. Copyright: © 2018 SecretarÍa de Salud

  6. RELACION DE LA EXPRESION DEL RECEPTOR DE INSULINA CON LA EXPRESION DE LAS ENZIMAS GLICOGENICAS (GS1 Y GS2) Y GLUCONEOGENICAS EN LAS CELULAS DE TUBULO PROXIMAL DE RATAS NORMALES Y DIABETICAS

    OpenAIRE

    GATICA GUTIERREZ, RODRIGO ORLANDO; GATICA GUTIERREZ, RODRIGO ORLANDO

    2012-01-01

    En el presente estudio se determinó los efectos sobre la expresión y localización del receptor de insulina (InsR), de glicógeno sin tasa (GS) y de las enzimas glicolíticas y gluconeogénicas en diabetes de largo plazo. Insulina es esencial para el manejo energético del cuerpo, sin embargo, su rol a nivel renal es poco conocido. Su unión al receptor de insulina provoca una cascada de señalización intracelular, que regula múltiples procesos biológicos, tales corno el metabolismo lipídico y pr...

  7. In vivo effect of human granulocyte-macrophage colony-stimulating factor on megakaryocytopoiesis

    International Nuclear Information System (INIS)

    Aglietta, M.; Monzeglio, C.; Sanavio, F.; Apra, F.; Morelli, S.; Stacchini, A.; Piacibello, W.; Bussolino, F.; Bagnara, G.; Zauli, G.

    1991-01-01

    The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on megakaryocytopoiesis and platelet production was investigated in patients with normal hematopoiesis. Three findings indicated that GM-CSF plays a role in megakaryocytopoiesis. During treatment with GM-CSF (recombinant mammalian, glycosylated; Sandoz/Schering-Plough, 5.5 micrograms protein/kg/d, subcutaneously for 3 days) the percentage of megakaryocyte progenitors (megakaryocyte colony forming unit [CFU-Mk]) in S phase (evaluated by the suicide technique with high 3H-Tdr doses) increased from 31% +/- 16% to 88% +/- 11%; and the maturation profile of megakaryocytes was modified, with a relative increase in more immature stage I-III forms. Moreover, by autoradiography (after incubation of marrow cells with 125I-labeled GM-CSF) specific GM-CSF receptors were detectable on megakaryocytes. Nevertheless, the proliferative stimulus induced on the progenitors was not accompanied by enhanced platelet production (by contrast with the marked granulomonocytosis). It may be suggested that other cytokines are involved in the regulation of the intermediate and terminal stages of megakaryocytopoiesis in vivo and that their intervention is an essential prerequisite to turn the GM-CSF-induced proliferative stimulus into enhanced platelet production

  8. Effects of granulocyte-macrophage colony-stimulating factor and interleukin 6 on the growth of leukemic blasts in suspension culture.

    Science.gov (United States)

    Tsao, C J; Cheng, T Y; Chang, S L; Su, W J; Tseng, J Y

    1992-05-01

    We examined the stimulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL)-6 on the in vitro proliferation of leukemic blast cells from patients with acute leukemia. Bone marrow or peripheral blood leukemic blast cells were obtained from 21 patients, including 14 cases of acute myeloblastic leukemia (AML), four cases of acute lymphoblastic leukemia (ALL), two cases of acute undifferentiated leukemia, and one case of acute mixed-lineage leukemia. The proliferation of leukemic blast cells was evaluated by measuring the incorporation of 3H-thymidine into cells incubated with various concentrations of cytokines for 3 days. GM-CSF stimulated the DNA synthesis (with greater than 2.0 stimulation index) of blast cells in 9 of 14 (64%) AML cases, two cases of acute undifferentiated leukemia and one case of acute mixed-lineage leukemia. Only two cases of AML blasts responded to IL-6 to grow in the short-term suspension cultures. GM-CSF and IL-6 did not display a synergistic effect on the growth of leukemic cells. Moreover, GM-CSF and IL-6 did not stimulate the proliferation of ALL blast cells. Binding study also revealed the specific binding of GM-CSF on the blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia. Our results indicated that leukemic blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia possessed functional GM-CSF receptors.

  9. Sarcoma de Kaposi por virus del herpes humano de tipo 8 en un receptor de trasplante hepático pediátrico: Caso clínico

    OpenAIRE

    Malla, Ivone; Pérez, Celeste; Cheang, Yu; Silva, Marcelo

    2013-01-01

    Los pacientes que reciben tratamiento inmunosupresor están en riesgo de desarrollar tumores malignos. La infección primaria o reactivación del virus del herpes humano de tipo 8 (HHV-8) puede predisponer al sarcoma de Kaposi después del trasplante de un órgano sólido. En los receptores de trasplantes pediátricos, este sarcoma tiene baja incidencia y mal pronóstico. Se informa la presentación clínica de un sarcoma de Kaposi en un ganglio linfático luego de una infección por HHV-8 en un niño a l...

  10. Efeito analgésico de antagonistas do receptor da histamina H1 em modelo de dor provocada por formalina em ratos Efecto analgésico de antagonistas del receptor de la histamina H1 en un modelo de dolor provocado por formalina en ratones Analgesic effects of H1 receptor antagonists in the rat model of formalin-induced pain

    Directory of Open Access Journals (Sweden)

    Hazem Adel Ashmawi

    2009-08-01

    sistema nervioso periférico. No queda claro si el efecto analgésico local es de clase específico o un fármaco específico. MÉTODO: Para responder a esa pregunta, utilizamos tres diferentes antagonistas del receptor H1 (pirilamina, prometazina y cetirizina, administrados directamente en la pata del ratón, por vía intraperitoneal o por bloqueo de nervio periférico en modelo de dolor inducido por formalina. Observamos el efecto de los fármacos en el comportamiento del número de elevaciones de la pata. RESULTADOS: En la fase I, la pirilamina local redujo el número de elevaciones de la pata de forma dosis dependiente. En la dosis más alta, la reducción fue de un 97,8%. Para la prometazina, la disminución fue de un 92% y para la cetizirina de 23.9%. En la fase II, la pirilamina redujo el número de elevaciones de la pata en un 93,5%, la prometazina, un 78,2% y la cetirizina un 80,1%. La administración de los fármacos por vía intraperitoneal no alteró el comportamiento doloroso. Cuando se usaron para bloqueo del nervio periférico en la fase I, la pirilamina redujo el número de elevaciones de la pata en un 96,7%, la prometazina en un 73,3% y la cetirizina en un 23,9%. En la fase II, la pirilamina redujo un 86,6%, la prometazina un 64,4% y la cetirizina un 19,9%. CONCLUSIONES: Los resultados mostraron que los antagonistas del receptor de la histamina H1 presentaron efectos analgésicos locales, diferentes del efecto sistémico, siendo uno de ellos antiinflamatorio y clase específico, y el otro específico para la prometazina y la pirilamina, parecido con el efecto clínico anestésico local.BACKGROUND AND OBJECTIVES: Histamine receptors mediate nociceptive pathways, especially in the central nervous system. Some studies have demonstrated the analgesic effects of histamine receptor antagonists in the peripheral nervous system. It is not clear whether the local analgesic effect is class-specific or drug-specific. METHODS: To answer this question, we used three

  11. Effect on Antibody and T-Cell Responses of Mixing Five GMP-Produced DNA Plasmids and Administration With Plasmid Expressing GM-CSF

    National Research Council Canada - National Science Library

    Sedegah, M; Charoenvit, Y; Aguiar, J; Sacci, J; Hedstrom, R; Kumar, S; Belmonte, A; Lanar, DE; Jones, TR; Abot, E

    2004-01-01

    .... In preparation for a clinical trial, we assessed the immunogenicity of GMP-produced plasmids encoding five Plasmodium falciparum proteins, PfCSP, PfSSP2, PfEXP1, PfLSA1, and PfLSA3, given as a mixture, or alone...

  12. Treatment of minimal residual disease after surgery or chemotherapy in mice carrying HPV16-associated tumours: cytokine and gene therapy with IL-2 and GM-CSF

    Czech Academy of Sciences Publication Activity Database

    Mikyšková, Romana; Indrová, Marie; Šímová, Jana; Jandlová, Táňa; Bieblová, Jana; Jinoch, P.; Bubeník, Jan; Vonka, V.

    2004-01-01

    Roč. 24, č. 1 (2004), s. 161-167 ISSN 1019-6439 R&D Projects: GA MZd NC7148; GA MZd NC7552; GA ČR GA301/01/0985 Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV16 * gene therapy * minimal residual tumour disease Subject RIV: FD - Oncology ; Hematology Impact factor: 3.056, year: 2004

  13. CER-001, a HDL-mimetic, stimulates the reverse lipid transport and atherosclerosis regression in high cholesterol diet-fed LDL-receptor deficient mice.

    Science.gov (United States)

    Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Ackermann, Rose; Sy, Gavin; Bluteau, Alice; Cholez, Guy; Keyserling, Constance; Lalwani, Narendra; Paolini, John F; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

    2014-01-01

    CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and phospholipids that was designed to mimic the beneficial properties of nascent pre-β HDL. In this study, we have evaluated the capacity of CER-001 to perform reverse lipid transport in single dose studies as well as to regress atherosclerosis in LDLr(-/-) mice after short-term multiple-dose infusions. CER-001 induced cholesterol efflux from macrophages and exhibited anti-inflammatory response similar to natural HDL. Studies with HUVEC demonstrated CER-001 at a concentration of 500 μg/mL completely suppressed the secretion of cytokines IL-6, IL-8, GM-CSF and MCP-1. Following infusion of CER-001 (10mg/kg) in C57Bl/6J mice, we observed a transient increase in the mobilization of unesterified cholesterol in HDL particles containing recombinant human apoA-I. Finally we show that cholesterol elimination was stimulated in CER-001 treated animals as demonstrated by the increased cholesterol concentration in liver and feces. In a familial hypercholesterolemia mouse model (LDL-receptor deficient mice), the infusion of CER-001 caused 17% and 32% reductions in plaque size, 17% and 23% reductions in lipid content after 5 and 10 doses given every 2 days, respectively. Also, there was an 80% reduction in macrophage content in the plaque following 5 doses, and decreased VCAM-1 expression by 16% and 22% in the plaque following 5 and 10 intravenous doses of CER-001, respectively. These data demonstrate that CER-001 rapidly enhances reverse lipid transport in the mouse, reducing vascular inflammation and promoting regression of diet-induced atherosclerosis in LDLr(-/-) mice upon a short-term multiple dose treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Leukotriene D4 induces chemotaxis in human eosinophilc cell line, EoL-1 cells via CysLT1 receptor activation.

    Science.gov (United States)

    Shirasaki, Hideaki; Kanaizumi, Etsuko; Himi, Tetsuo

    2017-11-01

    Numerous reports have shown that cysteinyl leukotrienes (CysLTs) contribute to tissue accumulation of eosinophils in allergic airway inflammation. To date, only a few studies have reported that CysLTs promote chemotactic activity of human eosinophils in vitro. The purpose of this study was to investigate whether CysLTs promote chemotaxis in the human eosinophilic cell line, EoL-1. EoL-1 cells were induced to differentiate into mature eosinophil-like cells via incubation with butyric acid and cytokines (IL-3, IL-5 and GM-CSF). The chemotactic activity of the differentiated EoL-1 cells was assessed using the commercial cell migration assay kit. LTD 4 elicited dose-related chemotactic activity in the differntiated EoL-1 cells in the range of 1-100 nM. A typical bell-shaped dose-response curve was observed with optimal activity at 10 nM. The chemotactic activity elicited by LTD 4 (10 nM) was significantly inhibited by montelukast (control, 345 ± 19.2 × 10 3 RFU; LTD 4 10 nM alone, 511 ± 39.2 × 10 3 RFU; LTD 4 10 nM plus montelukast 100 nM, 387 ± 28.2 × 10 3 RFU). LTD 4 induces migration in eosinophilic cells via activation of CysLT1 receptor. The present in vitro model may be useful for elucidation of the mechanism underlying CysLT-induced tissue eosinophilia.

  15. Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients.

    Science.gov (United States)

    Morse, Michael A; Chapman, Robert; Powderly, John; Blackwell, Kimberly; Keler, Tibor; Green, Jennifer; Riggs, Renee; He, Li-Zhen; Ramakrishna, Venky; Vitale, Laura; Zhao, Biwei; Butler, Stephen A; Hobeika, Amy; Osada, Takuya; Davis, Thomas; Clay, Timothy; Lyerly, H Kim

    2011-07-15

    The use of tumor-derived proteins as cancer vaccines is complicated by tolerance to these self-antigens. Tolerance may be broken by immunization with activated, autologous, ex vivo generated and antigen-loaded, antigen-presenting cells (APC); however, targeting tumor antigen directly to APC in vivo would be a less complicated strategy. We wished to test whether targeted delivery of an otherwise poorly immunogenic, soluble antigen to APC through their mannose receptors (MR) would induce clinically relevant immunity. Two phase I studies were conducted with CDX-1307, a vaccine composed of human chorionic gonadotropin beta-chain (hCG-β) fused to an MR-specific monoclonal antibody, administered either locally (intradermally) or systemically (intravenously) in patients with advanced epithelial malignancies. An initial dose escalation of single-agent CDX-1307 was followed by additional cohorts of CDX-1307 combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) and the Toll-like receptor (TLR) 3 agonist polyinosinic-polycytidylic acid (poly-ICLC) and TLR7/8 agonist resiquimod to activate the APC. CDX-1307 induced consistent humoral and T-cell responses to hCG-β when coadministered with TLR agonists. Greater immune responses and clinical benefit, including the longest duration of stable disease, were observed with immunization combined with local TLR agonists. Immune responses were induced equally efficiently in patients with elevated and nonelevated levels of serum hCG-β. Antibodies within the serum of vaccinated participants had tumor suppressive function in vitro. Toxicity consisted chiefly of mild injection site reactions. APC targeting and activation induce adaptive immunity against poorly immunogenic self-antigens which has implications for enhancing the efficacy of cancer immunotherapy.

  16. Efecto del lipopolisacárido en cultivos de células dendríticas humanas y su inhibición por la polimixina B.

    Directory of Open Access Journals (Sweden)

    Adriana Cuéllar

    2004-12-01

    Full Text Available Algunos estímulos de maduración utilizados en cultivos de células dendríticas, como las proteínas recombinantes obtenidas en sistemas bacterianos o los extractos proteicos de ectoparásitos, contienen lipopolisacáridos (LPS y su presencia afecta el comportamiento de las células dendríticas en cultivo. En este trabajo se evaluó el efecto del LPS en un sistema de cultivo de células dendríticas humanas y la actividad de la polimixina B como inhibidor del efecto del LPS. Para esto, los monocitos obtenidos a partir de sangre periférica humana se diferenciaron a células dendríticas con IL-4 y GM-CSF y como estímulo de maduración se utilizó LPS o PGE2/FNT?. La expresión de marcadores y la secreción de citocinas se evaluaron por citometría de flujo. Los resultados mostraron que la preexposición a endotoxina disminuyó la expresión de CD83, inhibió la secreción de IL-12p70, FNT? e IL-10 y disminuyó la secreción de IL-6 en células dendríticas. Además, la utilización de 10 mg/ml de polimixina B fue efectiva en la inhibición de la actividad de 1 mg/ml de LPS y la máxima concentración de polimixina B que no afectó la morfología de las células fue de 50 mg/ml. En conclusión, la polimixina B es efectiva para inhibir la actividad del LPS en los cultivos de células dendríticas.

  17. Adição de Bloqueador do receptor de angiotensina II na insuficiência cardíaca descompensada Adición de bloqueante del receptor de angiotensina II en la insuficiencia cardiaca descompensada Angiotensin II receptor blocker add-on therapy for low cardiac output in decompensated heart failure

    Directory of Open Access Journals (Sweden)

    Marcelo E. Ochiai

    2010-02-01

    Full Text Available FUNDAMENTO: Durante a descompensação da insuficiência cardíaca, ocorre uma intensa ativação do sistema renina-angiotensina-aldosterona, entretanto, o uso de inibidor da enzima de conversão de angiotensina (IECA não pode bloqueá-lo completamente. De outro modo, a adição de bloqueador do receptor de angiotensina II (BRA pode ser útil quando ocorre a dependência de inotrópico. Avaliamos a eficiência da associação BRA-IECA para retirada da dobutamina na insuficiência cardíaca avançada e descompensada. OBJETIVO: Avaliar a eficácia da associação de bloqueador do receptor AT1 de angiotensina II ao inibidor de enzima de conversão, para a retirada da dobutamina em pacientes com dependência de suporte inotrópico decorrente da descompensação aguda da insuficiência cardíaca crônica. MÉTODOS: Em um estudo caso-controle (N = 24, selecionamos pacientes internados por descompensação da insuficiência cardíaca e com uso por mais de 15 dias de dobutamina, ou uma ou mais tentativas sem sucesso de retirada; dose otimizada de IECA; e FEVE FUNDAMENTO: Durante la descompensación de la insuficiencia cardiaca, ocurre una intensa activación del sistema renina-angiotensina-aldosterona, sin embargo, el empleo de inhibidor de la enzima de conversión de angiotensina (IECA no puede bloquearlo completamente. De otro modo, la adición de bloqueante del receptor de angiotensina II (BRA puede ser útil cuando ocurre la dependencia de inotrópico. Evaluamos la eficiencia de la asociación BRA-IECA para retirada de la dobutamina en la insuficiencia cardiaca avanzada y descompensada. OBJETIVO: Evaluar la eficacia de la asociación de bloqueante del receptor AT1 de angiotensina II al inhibidor de enzima de conversión, para la retirada de la dobutamina en pacientes con dependencia de soporte inotrópico que trascurre de la descompensación aguda de la insuficiencia cardiaca crónica. MÉTODOS: En un estudio caso-control (N = 24, seleccionamos a

  18. Efecto de los suplementos de calcio, vitamina D e isoflavonas sobre marcadores del remodelado óseo en mujeres postmenopaúsicas recientes: papel de polimorfismos del receptor de vitamina D

    OpenAIRE

    Pérez Alonso, María

    2016-01-01

    La osteoporosis es una enfermedad de elevada prevalencia, morbimortalidad y alto coste económica que se hace clínicamente evidente cuando aparecen las fracturas características. La vitamina D juega un importante papel en el mantenimiento de la integridad del esqueleto y de la resistencia ósea, principal determinante de la aparición de fracturas. Pot otra parte la incidencia de la hipovitaminosis D es muy frecuente con hiperparatiroidismo secundario asociado y aumento del remodelado óseo Ob...

  19. Enhancement of the grafting efficiency of transplanted marrow cells by preincubation with interleukin-3 and granulocyte-macrophage colony-stimulating factor

    Energy Technology Data Exchange (ETDEWEB)

    Tavassoli, M.; Konno, M.; Shiota, Y.; Omoto, E.; Minguell, J.J.; Zanjani, E.D.

    1991-04-01

    To improve the grafting efficiency of transplanted murine hematopoietic progenitors, we briefly preincubated mouse bone marrow cells with interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) ex vivo before their transplantation into irradiated recipients. This treatment was translated into an increase in the seeding efficiency of colony-forming unit-spleen (CFU-S) and CFU-GM after transplantation. Not only was the concentration of CFU-S in the tibia increased 2 and 24 hours after transplantation, but the total cell number and CFU-S and CFU-GM concentrations were persistently higher in IL-3- and GM-CSF-treated groups 1 to 3 weeks after transplantation. In addition, the survival of animals as a function of transplanted cell number was persistently higher in IL-3- and GM-CSF-treated groups compared with controls. The data indicate that the pretreatment of marrow cells with IL-3 and GM-CSF before transplantation increases the seeding efficiency of hematopoietic stem cells and probably other progenitor cells after transplantation. This increased efficiency may be mediated by upward modulation of homing receptors. Therefore, ex vivo preincubation of donor marrow cells with IL-3 and GM-CSF may be a useful tactic in bone marrow transplantation.

  20. Characterization of Toll-like receptors in primary lung epithelial cells: strong impact of the TLR3 ligand poly(I:C on the regulation of Toll-like receptors, adaptor proteins and inflammatory response

    Directory of Open Access Journals (Sweden)

    Weith Andreas

    2005-11-01

    Full Text Available Abstract Background Bacterial and viral exacerbations play a crucial role in a variety of lung diseases including COPD or asthma. Since the lung epithelium is a major source of various inflammatory mediators that affect the immune response, we analyzed the inflammatory reaction of primary lung epithelial cells to different microbial molecules that are recognized by Toll-like receptors (TLR. Methods The effects of TLR ligands on primary small airway epithelial cells were analyzed in detail with respect to cytokine, chemokine and matrix metalloproteinase secretion. In addition, the regulation of the expression of TLRs and their adaptor proteins in small airway epithelial cells was investigated. Results Our data demonstrate that poly(I:C, a synthetic analog of viral dsRNA, mediated the strongest proinflammatory effects among the tested ligands, including an increased secretion of IL-6, IL-8, TNF-α, GM-CSF, GRO-α, TARC, MCP-1, MIP-3α, RANTES, IFN-β, IP-10 and ITAC as well as an increased release of MMP-1, MMP-8, MMP-9, MMP-10 and MMP-13. Furthermore, our data show that poly(I:C as well as type-1 and type-2 cytokines have a pronounced effect on the expression of TLRs and molecules involved in TLR signaling in small airway epithelial cells. Poly(I:C induced an elevated expression of TLR1, TLR2 and TLR3 and increased the gene expression of the general TLR adaptor MyD88 and IRAK-2. Simultaneously, poly(I:C decreased the expression of TLR5, TLR6 and TOLLIP. Conclusion Poly(I:C, an analog of viral dsRNA and a TLR3 ligand, triggers a strong inflammatory response in small airway epithelial cells that is likely to contribute to viral exacerbations of pulmonary diseases like asthma or COPD. The pronounced effects of poly(I:C on the expression of Toll-like receptors and molecules involved in TLR signaling is assumed to influence the immune response of the lung epithelium to viral and bacterial infections. Likewise, the regulation of TLR expression by type

  1. Regulación del flujo sanguíneo uterino. I. Funciones de estrógeno y receptores estrogénicos α/β en el endotelio vascular uterino durante el embarazo

    Science.gov (United States)

    Mayra, Pastore R.; Rosalina, Villalón L.; López, Gladys; Iruretagoyena, Jesús; Magness, Ronald

    2015-01-01

    Resumen El estrógeno y los receptores estrogénicos clásicos (REs), RE-α y RE-β, han demostrado ser parcialmente responsable por las adaptaciones endoteliales uterinas durante el embarazo al corto y largo plazo. Las diferencias moleculares y estructurales, junto con los diferentes efectos causados por estos receptores en las células y los tejidos, sugieren que su función varía dependiendo de la manera en la cual el estrógeno se comunica con sus receptores. En ésta revisión bibliográfica se discuten la función del estrógeno y sus receptores clásicos en las adaptaciones cardiovasculares durante el embarazo y la expresión de los Res in vivo e in vitro en el endotelio de la arteria uterina durante el ciclo ovárico y el embarazo, a la vez comparado con la expresión en endotelio arterial de tejidos reproductivos y no reproductivos. Estos temas integran el conocimiento actual de este amplio campo científico con interpretaciones e hipótesis diversas relacionadas con los efectos estrogénicos mediados bien sea por uno o los dos REs. Esta revisión también incluye la relación con las adaptaciones vasodilatadoras y angiogénicas requeridas para modular el dramático incremento fisiológico en la perfusión útero-placentaria observada durante un embarazo normal. PMID:26113750

  2. Modulación del tono vascular por la sobre-expresión de receptores a canabinoides CB1 y CB2 en arterioesclerosis inducida en ratas

    OpenAIRE

    Espinoza P., María Rosa

    2013-01-01

    La arteriosclerosis, es un proceso degenerativo responsable de la mayor parte de las enfermedades cardiovasculares, es una enfermedad compleja que se produce a partir de múltiples factores de riesgo. Se ha observado que los compuestos derivados de la planta cannabis sativa provocan efectos vasorelajantes por medio de receptores específicos CB1 y CB2. ACPA y JWH 133 son potentes agonistas a estos receptores, se desconoce el papel que desempeñan en la arteriosclerosis provocando una relajación ...

  3. Receptores de insulina en hematíes: caracterización del sistema. Estudios en pacientes obesos y con infarto de miocardio

    OpenAIRE

    Griera Borras, José Luis

    1982-01-01

    Tras la publicación a finales de 1978 por GAMBHIR y Cols. de la existencia de receptores de insulina en hematíes, iniciamos este trabajo con la idea de utilizar este tipo de célula para el estudio de la interacción insulina-receptor, ya que ofrecía “a priori” una serie de ventajas sobre los tejidos diana “clásicos” (músculo, hígado, tejido graso) y otros de más reciente adquisición (v.g. monocitos ...

  4. Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils.

    Science.gov (United States)

    Liu, L Y; Wang, H; Xenakis, J J; Spencer, L A

    2015-07-01

    Priming with cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the excessive accumulation of eosinophils within the bronchial mucosa of asthmatics. However, mechanisms that drive GM-CSF priming are incompletely understood. Notch signaling is an evolutionarily conserved pathway that regulates cellular processes, including migration, by integrating exogenous and cell-intrinsic cues. This study investigates the hypothesis that the priming-induced enhanced migration of human eosinophils requires the Notch signaling pathway. Using pan Notch inhibitors and newly developed human antibodies that specifically neutralize Notch receptor 1 activation, we investigated a role for Notch signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and in the airway accumulation of mouse eosinophils in vivo. Notch receptor 1 was constitutively active in freshly isolated human blood eosinophils, and inhibition of Notch signaling or specific blockade of Notch receptor 1 activation during GM-CSF priming impaired priming-enhanced eosinophil transendothelial migration in vitro. Inclusion of Notch signaling inhibitors during priming was associated with diminished ERK phosphorylation, and ERK-MAPK activation was required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil accumulation within allergic airways was impaired following systemic treatment with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with Notch inhibitor. These data identify Notch signaling as an intrinsic pathway central to GM-CSF priming-induced eosinophil tissue migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. EG-VEGF, BV8, and their receptor expression in human bronchi and their modification in cystic fibrosis: Impact of CFTR mutation (delF508).

    Science.gov (United States)

    Chauvet, Sylvain; Traboulsi, Wael; Thevenon, Laura; Kouadri, Amal; Feige, Jean-Jacques; Camara, Boubou; Alfaidy, Nadia; Benharouga, Mohamed

    2015-08-01

    Enhanced lung angiogenesis has been reported in cystic fibrosis (CF). Recently, two highly homologous ligands, endocrine gland vascular endothelial growth factor (EG-VEGF) and mammalian Bv8, have been described as new angiogenic factors. Both ligands bind and activate two closely related G protein-coupled receptors, the prokineticin receptor (PROKR) 1 and 2. Yet, the expression, regulation, and potential role of EG-VEGF, BV8, and their receptors in normal and CF lung are still unknown. The expression of the receptors and their ligands was examined using molecular, biochemical, and immunocytochemistry analyses in lungs obtained from CF patients vs. control and in normal and CF bronchial epithelial cells. Cystic fibrosis transmembrane conductance regulator (CFTR) activity was evaluated in relation to both ligands, and concentrations of EG-VEGF were measured by ELISA. At the mRNA level, EG-VEGF, BV8, and PROKR2 gene expression was, respectively, approximately five, four, and two times higher in CF lungs compared with the controls. At the cellular level, both the ligands and their receptors showed elevated expressions in the CF condition. Similar results were observed at the protein level. The EG-VEGF secretion was apical and was approximately two times higher in CF compared with the normal epithelial cells. This secretion was increased following the inhibition of CFTR chloride channel activity. More importantly, EG-VEGF and BV8 increased the intracellular concentration of Ca(2+) and cAMP and stimulated CFTR-chloride channel activity. Altogether, these data suggest local roles for epithelial BV8 and EG-VEGF in the CF airway peribronchial vascular remodeling and highlighted the role of CFTR activity in both ligand biosynthesis and secretion. Copyright © 2015 the American Physiological Society.

  6. IL-3 maintains activation of the P90S6K/RPS6 pathway and increases translation in human eosinophils1

    Science.gov (United States)

    Esnault, Stephane; Kelly, Elizabeth A.B.; Shen, Zhong-Jian; Johansson, Mats W.; Malter, James S.; Jarjour, Nizar N.

    2015-01-01

    IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines IL-5, IL-3, and GM-CSF are typically present in atopic diseases including allergic asthma. Due to the functional redundancy of these 3 cytokines on eosinophils and the loss of IL-5 receptor on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these 3 cytokines signal through a common β-chain receptor, and yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce production of proteins such as semaphorin-7A without affecting mRNA level suggests a unique influence by IL-3 on translation. The purpose of this study is to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared to IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein (RP) S6 and the upstream kinase, p90S6K. Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared to circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations place IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions. PMID:26276876

  7. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  8. ASOCIACIÓN ENTRE NIVELES SÉRICOS DE VITAMINA D, RESPUESTA IgE Y VARIANTES GENÉTICAS DEL GEN DEL RECEPTOR DE LA VITAMINA D EN NIÑOS OBESOS DEL CARIBE COLOMBIANO: UN ESTUDIO DE CASOS Y CONTROLES

    Directory of Open Access Journals (Sweden)

    Eduardo A. Egea Bermejo

    2016-07-01

    Full Text Available

    Introducción: Estudios previos han evaluado la relación entre vitamina D y atopía. En pacientes obesos es incierta esta asociación, sin embargo se acepta hoy que polimorfismos en el receptor de vitamina D pueden asociarse con obesidad. Actualmente son escasos los estudios que han buscado esta asociación en grupos en el litoral Caribe.

    Objetivo: Analizar la asociación entre los polimorfismos de los SNPs del receptor de vitamina D con la susceptibilidad para obesidad, su influencia en los niveles séricos de vitamina D e IgE en una población infantil.

    Metodología: Se realizó un estudio analítico de casos (n=120 y controles (n=182 con niños obesos entre los 5 y 17 años de edad, procedentes de la costa caribe colombiana. Los niveles séricos de 25(OH vitamina D e IgE Total se midieron mediante ELISA. Valores de p<0.05 fueron estadísticamente significativos.

    Resultados y conclusiones: Se encontró asociación entre niveles altos de vitamina-D y obesidad infantil. El 48,3% (n=58 de los casos presentaron niveles >100 ng/mL en comparación a un 0,5% (n = 1 de los controles. Ambos grupos presentaron altos niveles de IgE, (317,07±331,5 vs. 280,6±272.7; p = 0,786. Nuestros resultados no mostraron asociación alguna entre las variantes genéticas con los niveles séricos de vitamina-D con IgE total, como tampoco con obesidad. Todos los SNPs estuvieron en equilibrio Hardy-Weingber. Nuestros resultados no muestran asociación de deficiencia de Vitamina D con obesidad en este grupo poblacional, pero sí IgE elevada en la mayoría de la población, sin tener ninguna relación entre ellos. (Rho spearman: 0,023; p = 0,641.

    ASSOCIATION BETWEEN SERUM LEVELS OF VITAMIN D, IgE RESPONSE AND GENETIC VARIANTS OF THE GENE FOR VITAMIN D RECEPTOR IN OBESE CHILDREN IN THE COLOMBIAN CARIBBEAN

  9. Estudio de la modulación del receptor µ opioide por el receptor dopaminérgico D4. Implicación en la adicción a morfina

    OpenAIRE

    Valderrama Carvajal, Alejandra

    2015-01-01

    La morfina se utiliza en el ámbito clínico por ser un potente analgésico, sin embargo produce efectos adversos como la adicción. La administración de morfina induce una liberación masiva de dopamina en el estriado, produciendo los efectos de refuerzo y consolidación de hábitos adictivos. La actividad de las neuronas dopaminérgicas de la sustancia negra compacta está regulada por proyecciones GABAérgicas de la sustancia negra reticular (SNr) y del caudado putamen (CPu). En ambas regiones se lo...

  10. Peces del Noroeste del Ecuador

    OpenAIRE

    Barriga, Ramiro

    1994-01-01

    La ictiofauna del occidente del Ecuador es poco conocida. Los peces del noroccidente son diferentes a los del suroccidente del Ecuador. 34 familias y 82 especies fueron colectadas que equivale al 11 % de las especies de peces continentales registradas en el Ecuador. Icteogeográficamente se sabe que la costa ecuatoriana posee dos provincias: la del Pacifico Norte y la del Guayas, se determinó que el límite de las dos provincias es el río Santiago ya que las especies del mencionado río so...

  11. Inactivación selectiva del receptor de glucocorticoides en la epidermis de ratón. Defectos en el desarrollo y cáncer de piel

    OpenAIRE

    Latorre Roselló, Víctor

    2014-01-01

    Los glucocorticoides y su receptor Los glucocorticoides (GCs) son hormonas esteroideas que se sintetizan y secretan en las glándulas adrenales como respuesta a señales de estrés externas y cuya síntesis está regulada por el eje hipotálamo-pituitaria-adrenal (HPA) (Taves et al., 2011). Los GCs, cortisol en humanos y corticosterona en ratones, regulan numerosos procesos fisiológicos como el metabolismo de glucosa y lípidos, la respuesta inflamatoria e inmune, el desarrollo fetal y la prolife...

  12. Actualización, adaptación y evolución del sistema de automedidas de receptores analógicos de TV

    OpenAIRE

    Domínguez González, Raúl

    2016-01-01

    Actualización, adaptación y evolución de un sistema automático de medidas para receptores analógicos de TV. Aumentando la calidad de las medidas, así como reduciendo el tiempo de medida y el coste de diseño. El proyecto consiste en la elaboración de un programa en entorno LabView para realizar medidas automáticas de sintonizadores de TV para la empresa Sony. Partimos de un programa básico de medidas semi-automáticas con la idea de desarrollar los siguientes objetivos: Control remoto de la ...

  13. Determinación inmunohistoquímica y utilidad pronóstica del receptor del factor de crecimiento epidérmico en los tumores estromales gastrointestinales Immnunohistochemical expression of epidermal growth factor and its prognostic value for gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    D. Padilla

    2008-12-01

    Full Text Available Introducción: el receptor del factor de crecimiento epidérmico, EGFR(HER-1, es un receptor de tirosina quinasas cuya activación permite un aumento de la proliferación celular, angiogénesis, proceso metastásico y disminución de la apoptosis celular. Nuestro objetivo es conocer el valor pronóstico de la inmunotinción de EGFR en tumores estromales gastrointestinales (GIST. Pacientes y método: estudio retrospectivo que incluye todos los GIST intervenidos quirúrgicamente entre 1995-2007 en el Servicio de Cirugía General y del Aparato Digestivo del Hospital General de Ciudad Real. Variables clínicas: edad, sexo, clínica, mortalidad, recidiva. Variables patológicas: a macroscópicas: localización, diámetro; b microscópicas: necrosis tumoral, índice mitótico, tipo celular; y c inmunohistoquímicas: vimentina (V9, Dako A/s; actina del músculo liso (HHF-35, Biogenex; CD34 (QBEND/10; S100 (Policlonal Dako A/S; CD117 (c-kit Rabbit, antihuman polyclonal antibody, 1:600; PDGFR-alfa (Rabbit polyclonal antibody, 1:50, Sta. Cruz Biotechnology. Variables moleculares pronósticas: P-53, PAb240 (DakoCytomation, 1:75, Ki-67, clona MIB1 (Dako, 1:120 y EGFR pharmDx™ Dako Autostainer (Dako, Dinamarca. Criterios de malignidad: criterios de Fletcher. Resultados: entre 1995 y 2007, 35 GIST, fueron intervenidos quirúrgicamente en nuestro Servicio. Edad media: 61,11 ± 11,02, siendo mujeres en el 62,9% de los casos. Debutaron con hemorragia digestiva en un 40%. La mediana de seguimiento fue de 28 meses (3-133. La mortalidad fue de 54,3%, con recidiva del 40%. Variables morfológicas: la localización más frecuente fue gástrica, 51,4% (18. Existió necrosis tumoral en un 57,1%, 20. El patrón celular fue fusocelular en un 57,1%, y epitelioide en un 14,3%. El diámetro máximo fue de 9,58 ± 6,29. El índice mitótico por 50 campos de gran aumento fue de 13,44 ± 16,08. En un 51,45%, 18, fueron neoplasias de alto riesgo. Valores inmunohistoqu

  14. IL-3 Maintains Activation of the p90S6K/RPS6 Pathway and Increases Translation in Human Eosinophils.

    Science.gov (United States)

    Esnault, Stephane; Kelly, Elizabeth A B; Shen, Zhong-Jian; Johansson, Mats W; Malter, James S; Jarjour, Nizar N

    2015-09-15

    IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines, such as IL-5, IL-3, and GM-CSF, are typically present in atopic diseases, including allergic asthma. As a result of the functional redundancy of these three cytokines on eosinophils and the loss of IL-5R on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these three cytokines signal through a common β-chain receptor but yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce the production of proteins, such as semaphorin-7A, without affecting mRNA levels suggests a unique influence of IL-3 on translation. The purpose of this study was to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared with IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF, or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein S6 (RPS6) and the upstream kinase 90-kDa ribosomal S6 kinase (p90S6K). Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared with circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations identify IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. Estudio de la expresión y función del receptor de IFN y ?en pacientes con manifestaciones atípicas en infecciones por gérmenes intracelulares

    Directory of Open Access Journals (Sweden)

    Pablo Javier Patiño Grajales

    2000-02-01

    Full Text Available


     

    La inmunidad protectora a microorganismos intracelulares, como por ejemplo micobacaterium, se conoce que es dependiente de la inmunidad mediada por células (IMC. El principal mecanismo efector de la IMC depende de la activación del macrófago infectado mediante las citoquinas tipo I, particularmente el interferón gamma (IFNγ. Esta citoquina es una glicoproteína homodimérica, producida por células T y células NK. La transcripción de su gen se inicia por activación antigénica y se incrementa por efecto de otras citoquinas como la IL-2 y la IL-12. Entre sus principales efectos está el de activar las células NK y los fagotitos mononucleares, aumentar la expresión de moléculas del Complejo Mayor de Histocompatibilidad clase I y II, promover la diferenciación funcional de las células CD4+ hacia el patrón funcional TH1 e inducir la maduración de los linfocitos CD8+ hacia células citotóxicas. En las células B promueve el cambio isotípico de inmunoglobulinas hacia IgG1 e IgG3.

    Recientemente se identificaron los primeros casos de deficiencia del receptor de IFN gamma (IFNγR en humanos. Esta deficiencia es un desorden autosómico recesivo, que ha sido caracterizado en niños que presentan una infección diseminada por micobacterias. Aparece como consecuencia de mutaciones del gen IFNEstudio del CH interestelar

    Science.gov (United States)

    Olano, C.; Lemarchand, G.; Sanz, A. J.; Bava, J. A.

    El objetivo principal de este proyecto consiste en el estudio de la distribución y abundancia del CH en nubes interestelares a través de la observación de las líneas hiperfinas del CH en 3,3 GHz. El CH es una molécula de amplia distribución en el espacio interestelar y una de las pocas especies que han sido observadas tanto con técnicas de radio como ópticas. Desde el punto de vista tecnológico se ha desarrollado un cabezal de receptor que permitirá la realización de observaciones polarimétricas en la frecuencia de 3,3 GHz, con una temperatura del sistema de 60 K y un ancho de banda de 140 MHz, y que será instalado en el foco primario de la antena parabólica del IAR. El cabezal del receptor es capaz de detectar señales polarizadas, separando las componentes de polarización circular derecha e izquierda. Para tal fin el cabezal consta de dos ramas receptoras que amplificarán la señal y la trasladarán a una frecuencia más baja (frecuencia intermedia), permitiendo de esa forma un mejor transporte de la señal a la sala de control para su posterior procesamiento. El receptor además de tener características polarimétricas, podrá ser usado en el continuo y en la línea, utilizando las ventajas observacionales y de procesamiento de señal que actualmente posee el IAR.

  16. Transducción de señales generadas a partir del receptor antigénico de los linfocitos T Transduction of signal generated from the antigenic receptor of T lymphocytes

    Directory of Open Access Journals (Sweden)

    Carlos Julio Montoya Guarín

    1999-04-01

    Full Text Available A diferencia de lo observado para los linfocitos B, que reconocen antígenos libres en forma nativa, los linfocitos T han evolucionado para reconocer pequeños péptidos antigénicos presentados por moléculas de histocompatibilidad en la superficie de células presentadoras especializadas o de células diana. Para ello los linfocitos T maduros cuentan con un grupo de proteínas de membrana que en conjunto se denominan complejo TCR. Este grupo de cadenas polipeptídicas se expresan en la membrana de los linfocitos T y cumplen una función doble: reconocer los fragmentos antigénicos presentados por las moléculas de histocompatibilidad y transmitir las señales de ese reconocimiento al interior del linfocito. Las consecuencias de esta señalización pueden variar desde la activación funcional hasta la anergia o la apoptosis. Gracias a una intensa investigación en esta área, en los últimos años se han revelado muchas de las proteínas involucradas en la transducción de señales en los linfocitos T y sus mecanismos de acción. En esta revisión se examinan los modelos que explican la dinámica de la ligación del TCR, las principales vías de transducción de señales, los agentes farmacológicos que han permitido su estudio y dos modelos de enfermedades humanas que presentan entre sus mecanismos fisiopatológicos alteraciones en las vías de señalización a través del TCR. T lymphocytes, in contrast to B lymphocytes which bind free antigens in a native form, recognize little antigenic peptides displayed on histocompatibility molecules in the surface of specialized or target cells. For this, mature T lymphocytes have a group of membrane proteins that together are named TCR complex. This group of polypeptide chains expresses in the membrane and has a double function: to recognize the antigenic fragments bound to histocompatibility molecules and to transmit signals arisen from the recognition to the inner of the lymphocyte. The consequences

  17. Acute radiation syndrome (ARS – treatment of the reduced host defense

    Directory of Open Access Journals (Sweden)

    Heslet L

    2012-01-01

    Full Text Available Lars Heslet1, Christiane Bay2, Steen Nepper-Christensen31Serendex ApS, Gentofte; 2University of Copenhagen, Medical Faculty, Copenhagen; 3Department of Head and Neck Surgery, Otorhinolaryngology, Køge University Hospital, Køge, DenmarkBackground: The current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS. The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF] in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes.Methods: Review of the current literature.Results: The lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage’s important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS.Recommendation: Preemptive treatment should be initiated after suspected exposure of a radiation dose of at least ~2 Gy by prompt dosing of 250–400 µg GM-CSF/m2 or 5 µg/kg G-CSF administered systemically and concomitant inhalation of

  18. EXPRESIÓN DEL RECEPTOR DE FACTOR DE CRECIMIENTO EPIDÉRMICO (EGFR EN EL CARCINOMA COLORRECTAL PRIMARIO Y METASTÁSICO.

    Directory of Open Access Journals (Sweden)

    Manuel Claver Criado

    2008-01-01

    Full Text Available We studied Epidermal Growth Factor Receptor (EGFR expression in primary and metastatic tumor of 50 consecutive patients treated at the Oncology Service in General Yag�e Hospital in Burgos, with metastatic disease of colorectal tumours.In addition to evaluate EGFR expression in primary and metastatic tumor, we analyzed the relationship between the histological type or degree of tumor differentiation, and the degree of cytologic atypia with EGFR expression, and the differences in time to progression of the disease and the tumor differentiation when EGFR is expressed both in the primary tumor and metastasis, or when that expression occurs only in the primary tumor or metastasis only.Our data show that EGFR expression can appear on the primary tumour, metastasis, or both, but we can not predict whether or not metastasis expressed that factor from its expression in the primary tumor. On the other hand, Epidermal Growth Factor expression is not related to cytologic atypia alone regarding the tumor differentiation, but yes if tumor differentiation is considered. It is more frequent in more undifferentiated tumors, and this relationship have statistical significance.

  19. Multi-functional system of radiotherapy and thermal phototherapy for tumors that over-express receptors of the gastrin releasing peptide; Sistema multifuncional de radioterapia y fototerapia termica para tumores que sobre-expresan receptores del peptido liberador de gastrina

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez M, N. P.

    2014-07-01

    The aim of this research was to prepare and characterize a multifunctional system of {sup 177}Lu and {sup 99m}Tc-labelled gold nanoparticles conjugated to Tat(49 57)-Lys{sup 3} bombesin ({sup 177}Lu/{sup 99m}Tc- AuNP-Tat-Bn) and to evaluate the radiation absorbed dose in GRP receptor positive PC3 tumours induced in mice (human prostate cancer cells), as well as to evaluate the thermal effect produced by the multifunctional system in PC3 cancer cells. The preparation of the system involved the conjugation of Bn-Tat, DOTA-GGC and HYNICTOC peptides to AuNP of 20 nm or 5 nm in diameter. The radiolabeling of the system with {sup 99m}Tc was carried out through the ligand HYNIC-TOC and with the {sup 177}Lu through DOTA-GGC. The functionalization of peptides to AuNP, was accomplished through a spontaneous reaction of thiol groups. The system was characterized by spectroscopic techniques while radiochemical purity was determined by size-exclusion molecular chromatography and ultrafiltration. Various internalization trials and non-specific binding were tested to demonstrate the affinity of the system to PC3 cells. The thermal effect was evaluated incubating the system into PC3 cells and irradiating it with a Nd:YAG pulsed laser beam and monitoring the temperature; after irradiation, cell viability was measured. In the evaluation of absorbed dose in mice with induced tumours, the system was administered intratumorally and later, mice were sacrificed, relevant organs and tumor were extracted, activity was quantified and radiopharmaceutical models were obtained for each organ and tumor to be used in the accumulated activity and absorbed dose calculation by the MIRD methodology. Finally, to establish the system location at cellular level, fluorescent images of the system incubated in PC3 cells were acquired with an epi fluorescent microscope. Tem, UV-Vis, XP S and Far-IR spectroscopy techniques demonstrated that AuNPs were functionalized with peptides through interactions with

  1. Cinéfilos del siglo XXI. De receptores, aficionados y fans... y otros roles en la era de la web 2.0

    Directory of Open Access Journals (Sweden)

    María Purificación Subires Mancera

    2011-12-01

    Full Text Available Internet, y en especial, la denominada web 2.0, con las posibilidades que ofrece a los usuarios para producir y compartir contenidos, convirtiéndose de esta forma en “prosumidores”, ha permitido que aficionados y amantes del cine puedan informarse y debatir acerca de sus obras, actores y directores favoritos, además de establecer incluso en algunos casos contacto directo con ellos, gracias a las herramientas de participación existentes. A su vez ha hecho posible que puedan hacer su propia crítica de cine, como alternativa a la especializada, realizada por expertos, dando a todos la oportunidad de compartir con los demás su propia opinión sobre el autor o la obra, más allá de la crítica experta. Además, al amparo de las herramientas de la web 2.0 que permiten la aplicación y desarrollo de nuevos métodos de trabajo en equipo, han surgido experiencias virtuales de cine colaborativo, como las wikipelis. En el presente artículo vamos a llevar a cabo el análisis de diversas experiencias con el fin de dilucidar qué ha significado la irrupción de la web 2.0 para el aficionado al cine, centrándonos en el caso español. Para ello vamos a servirnos de una metodología de corte cualitativo, basada en el estudio de casos.

  2. DHEAS increases levels of GluR2/3 and GluR2, AMPA receptor subunits, in C57BL/6 mice hippocampus El DHEAS incrementa la expresión de GluR2/3 y GLUR2 del receptor AMPA en el hipocampo de ratones C57/BL6

    Directory of Open Access Journals (Sweden)

    Diego Sepúlveda Falla

    2010-05-01

    -US;" lang="EN-US"> 

    Due to the role of AMPA receptor, specifically  GluR2  subunit  in  the  regulation of intracellular  calcium  levels, cellular  apoptosis, and  synaptic  plasticity, the  study  of

    neurosteroids as a therapeutic strategy in neurodegenerative diseases and cerebrovascular events is very relevant.

    El DHEAS es un neuroesteroide con efecto neuromodulador de la transmisión sináptica y en la neuroprotección, sin embargo las vías moleculares a través de las cuales se inducen estos cambios no están completamente claras. Como varios de los neuroesteroides actúan a través de los recetores ionotrópicos de glutamato, se evaluó el efecto del DHEAS en las subunidades GluR2 y GluR3 del receptor AMPA para esclarecer sus efectos. Con este fin se administró DHEAS o una sustancia control durante 7 días a ratones C57/BL6. La expresión de las subunidades se evaluó por Western blotting.

    Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  3. The closely related CD103+ dendritic cells (DCs and lymphoid-resident CD8+ DCs differ in their inflammatory functions.

    Directory of Open Access Journals (Sweden)

    Zhijun Jiao

    Full Text Available Migratory CD103+ and lymphoid-resident CD8+ dendritic cells (DCs share many attributes, such as dependence on the same transcription factors, cross-presenting ability and expression of certain surface molecules, such that it has been proposed they belong to a common sub-lineage. The functional diversity of the two DC types is nevertheless incompletely understood. Here we reveal that upon skin infection with herpes simplex virus, migratory CD103+ DCs from draining lymph nodes were more potent at inducing Th17 cytokine production by CD4+ T cells than CD8+ DCs. This superior capacity to drive Th17 responses was also evident in CD103+ DCs from uninfected mice. Their differential potency to induce Th17 differentiation was reflected by higher production of IL-1β and IL-6 by CD103+ DCs compared with CD8+ DCs upon stimulation. The two types of DCs from isolated lymph nodes also differ in expression of certain pattern recognition receptors. Furthermore, elevated levels of GM-CSF, typical of those found in inflammation, substantially increased the pool size of CD103+ DCs in lymph nodes and skin. We argue that varied levels of GM-CSF may explain the contrasting reports regarding the positive role of GM-CSF in regulating development of CD103+ DCs. Together, we find that these two developmentally closely-related DC subsets display functional differences and that GM-CSF has differential effect on the two types of DCs.

  4. Minocycline Blocks Asthma-associated Inflammation in Part by Interfering with the T Cell Receptor-Nuclear Factor κB-GATA-3-IL-4 Axis without a Prominent Effect on Poly(ADP-ribose) Polymerase*

    Science.gov (United States)

    Naura, Amarjit S.; Kim, Hogyoung; Ju, Jihang; Rodriguez, Paulo C.; Jordan, Joaquin; Catling, Andrew D.; Rezk, Bashir M.; Elmageed, Zakaria Y. Abd; Pyakurel, Kusma; Tarhuni, Abdelmetalab F.; Abughazleh, Mohammad Q.; Errami, Youssef; Zerfaoui, Mourad; Ochoa, Augusto C.; Boulares, A. Hamid

    2013-01-01

    Minocycline protects against asthma independently of its antibiotic function and was recently reported as a potent poly(ADP-ribose) polymerase (PARP) inhibitor. In an animal model of asthma, a single administration of minocycline conferred excellent protection against ovalbumin-induced airway eosinophilia, mucus hypersecretion, and Th2 cytokine production (IL-4/IL-5/IL-12(p70)/IL-13/GM-CSF) and a partial protection against airway hyperresponsiveness. These effects correlated with pronounced reduction in lung and sera allergen-specific IgE. A reduction in poly(ADP-ribose) immunoreactivity in the lungs of minocycline-treated/ovalbumin-challenged mice correlated with decreased oxidative DNA damage. The effect of minocycline on PARP may be indirect, as the drug failed to efficiently block direct PARP activation in lungs of N-methyl-N′-nitro-N-nitroso-guanidine-treated mice or H2O2-treated cells. Minocycline blocked allergen-specific IgE production in B cells potentially by modulating T cell receptor (TCR)-linked IL-4 production at the mRNA level but not through a modulation of the IL-4-JAK-STAT-6 axis, IL-2 production, or NFAT1 activation. Restoration of IL-4, ex vivo, rescued IgE production by minocycline-treated/ovalbumin-stimulated B cells. IL-4 blockade correlated with a preferential inhibition of the NF-κB activation arm of TCR but not GSK3, Src, p38 MAPK, or ERK1/2. Interestingly, the drug promoted a slightly higher Src and ERK1/2 phosphorylation. Inhibition of NF-κB was linked to a complete blockade of TCR-stimulated GATA-3 expression, a pivotal transcription factor for IL-4 expression. Minocycline also reduced TNF-α-mediated NF-κB activation and expression of dependent genes. These results show a potentially broad effect of minocycline but that it may block IgE production in part by modulating TCR function, particularly by inhibiting the signaling pathway, leading to NF-κB activation, GATA-3 expression, and subsequent IL-4 production. PMID:23184953

  5. Minocycline blocks asthma-associated inflammation in part by interfering with the T cell receptor-nuclear factor κB-GATA-3-IL-4 axis without a prominent effect on poly(ADP-ribose) polymerase.

    Science.gov (United States)

    Naura, Amarjit S; Kim, Hogyoung; Ju, Jihang; Rodriguez, Paulo C; Jordan, Joaquin; Catling, Andrew D; Rezk, Bashir M; Abd Elmageed, Zakaria Y; Pyakurel, Kusma; Tarhuni, Abdelmetalab F; Abughazleh, Mohammad Q; Errami, Youssef; Zerfaoui, Mourad; Ochoa, Augusto C; Boulares, A Hamid

    2013-01-18

    Minocycline protects against asthma independently of its antibiotic function and was recently reported as a potent poly(ADP-ribose) polymerase (PARP) inhibitor. In an animal model of asthma, a single administration of minocycline conferred excellent protection against ovalbumin-induced airway eosinophilia, mucus hypersecretion, and Th2 cytokine production (IL-4/IL-5/IL-12(p70)/IL-13/GM-CSF) and a partial protection against airway hyperresponsiveness. These effects correlated with pronounced reduction in lung and sera allergen-specific IgE. A reduction in poly(ADP-ribose) immunoreactivity in the lungs of minocycline-treated/ovalbumin-challenged mice correlated with decreased oxidative DNA damage. The effect of minocycline on PARP may be indirect, as the drug failed to efficiently block direct PARP activation in lungs of N-methyl-N'-nitro-N-nitroso-guanidine-treated mice or H(2)O(2)-treated cells. Minocycline blocked allergen-specific IgE production in B cells potentially by modulating T cell receptor (TCR)-linked IL-4 production at the mRNA level but not through a modulation of the IL-4-JAK-STAT-6 axis, IL-2 production, or NFAT1 activation. Restoration of IL-4, ex vivo, rescued IgE production by minocycline-treated/ovalbumin-stimulated B cells. IL-4 blockade correlated with a preferential inhibition of the NF-κB activation arm of TCR but not GSK3, Src, p38 MAPK, or ERK1/2. Interestingly, the drug promoted a slightly higher Src and ERK1/2 phosphorylation. Inhibition of NF-κB was linked to a complete blockade of TCR-stimulated GATA-3 expression, a pivotal transcription factor for IL-4 expression. Minocycline also reduced TNF-α-mediated NF-κB activation and expression of dependent genes. These results show a potentially broad effect of minocycline but that it may block IgE production in part by modulating TCR function, particularly by inhibiting the signaling pathway, leading to NF-κB activation, GATA-3 expression, and subsequent IL-4 production.

  6. IL-5 and IL-5 receptor in asthma

    Directory of Open Access Journals (Sweden)

    ATC Kotsimbos

    1997-12-01

    Full Text Available Eosinophils, along with mast cells are key cells involved in the innate immune response against parasitic infection whereas the adaptive immune response is largely dependent on lymphocytes. In chronic parasitic disease and in chronic allergic disease, IL-5 is predominantly a T cell derived cytokine which is particularly important for the terminal differentiation, activation and survival of committed eosinophil precursors. The human IL-5 gene is located on chromosome 5 in a gene cluster that contains the evolutionary related IL-4 family of cytokine genes. The human IL-5 receptor complex is a heterodimer consisting of a unique a subunit (predominantly expressed on eosinophils and a beta subunit which is shared between the receptors for IL-3 & GM-CSF (more widely expressed. The a subunit is required for ligand-specific binding whereas association with the beta subunit results in increased binding affinity. The alternative splicing of the alphaIL-5R gene which contains 14 exons can yield several alphaIL-5R isoforms including a membrane-anchored isoform (alphaIL-5Rm and a soluble isoform (alphaIL-5Rs. Cytokines such as IL-5 produce specific and non-specific cellular responses through specific cell membrane receptor mediated activation of intracellular signal transduction pathways which, to a large part, regulate gene expression. The major intracellular signal transduction mechanism is activation of non-receptor associated tyrosine kinases including JAK and MAP kinases which can then transduce signals via a novel family of transcriptional factors named signal transducers and activators of transcription (STATS. JAK2, STAT1 and STAT 5 appear to be particularly important in IL-5 mediated eosinophil responses. Asthma is characterized by episodic airways obstruction, increased bronchial responsiveness, and airway inflammation. Several studies have shown an association between the number of activated T cells and eosinophils in the airways and abnormalities

  7. Potencial del Agua del suelo

    Directory of Open Access Journals (Sweden)

    Bustamante Heliodoro

    1986-12-01

    Full Text Available La energía potencial del agua presenta diferencias de un punto del suelo a otro; esas diferencias son las que originan el movimiento del agua de acuerdo a la tendencia universal de la materia en el sentido de moverse de donde la energía potencial es mayor a donde dicha energía es menor. En el suelo el agua en consecuencia se mueve hacia donde su energía decrece hasta lograr su estado de equilibrio. Se desprende entonces que la cantidad de energía potencial absoluta contenida en el agua, no es importante por sí misma, sino por su relación con la energía en diferentes lugares dentro del suelo. El concepto Potencial de agua del suelo es un criterio para esta energía.

  8. Adenosine potentiates stimulatory effects on granulocyte-macrophage hematopoietic progenitor cells in vitro of IL-3 and SCF, but not those of G-CSF, GM-CSF and IL-11

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Vacek, Antonín; Pospíšil, Milan; Weiterová, Lenka; Holá, Jiřina; Štreitová, Denisa; Znojil, V.

    2006-01-01

    Roč. 55, č. 5 (2006), s. 591-596 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/06/0015 Institutional research plan: CEZ:AV0Z50040507 Keywords : hematopoiesis * adenosine * cytokines Subject RIV: BO - Biophysics Impact factor: 2.093, year: 2006

  9. Phase I trial of anti-GD2 monoclonal antibody hu3F8 plus GM-CSF: Impact of body weight, immunogenicity and anti-GD2 response on pharmacokinetics and survival.

    Science.gov (United States)

    Cheung, Irene Y; Kushner, Brian H; Modak, Shakeel; Basu, Ellen M; Roberts, Stephen S; Cheung, Nai-Kong V

    2017-01-01

    Fifty-seven stage 4 patients with refractory/relapsed neuroblastoma were enrolled in a phase I trial (Clinicaltrials.gov NCT01757626) using humanized anti-GD2 monoclonal antibody hu3F8 in combination with granulocyte-macrophage colony-stimulating factor. The influence of body weight and human anti-human antibody (HAHA) on the pharmacokinetics (PK) of hu3F8, and the effect of de novo anti-GD2 response on patient outcome were explored. Serum samples before hu3F8 infusion, and serially up to day 12 during treatment cycle #1, and at 5 min after each hu3F8 infusion for all subsequent cycles were collected. PK was analyzed using non-compartmental modeling. Immunogenicity was assayed by HAHA response, and vaccination effect by induced host anti-GD2 response measured periodically until disease progression or last followup. Progression-free and overall survival was estimated by the Kaplan-Meier method. Despite dosing being based on body weight, smaller patients had consistently lower area-under-the-curve and faster clearance over the 15 dose levels (0.9 to 9.6 mg/kg per treatment cycle) in this trial. Positive HAHA, defined by the upper limit of normal, when measured within 10 days from the last hu3F8 dose received, was associated with significantly lower serum hu3F8. Despite prior sensitization to other anti-GD2 antibody, e.g. mouse 3F8 or ch14.18, 75% of the patients never developed HAHA response even after getting more treatment cycles. Hu3F8 induced a de novo anti-GD2 response in patients, which was prognostic of progression-free survival. We conclude that hu3F8 had low immunogenicity. During treatment, positive HAHA and low body weight affected PK adversely, whereas induced anti-GD2 response was an outcome predictor.

  10. Chemoimmunotherapy in mice carrying HPV16-associated, MHC class I+ and class I- tumours: effects of CBM-4A potentiated with IL-2, IL-12, GM-CSF and genetically modified tumour vaccines

    Czech Academy of Sciences Publication Activity Database

    Indrová, Marie; Bubeník, Jan; Mikyšková, Romana; Mendoza, Luis; Šímová, Jana; Bieblová, Jana; Jandlová, Táňa; Jinoch, P.; Šmahel, M.; Vonka, V.; Pajtasz-Piasecka, E.

    2003-01-01

    Roč. 22, č. 3 (2003), s. 691-695 ISSN 1019-6439 R&D Projects: GA MZd NC7148; GA ČR GA301/00/0114; GA ČR GA301/01/0985; GA AV ČR IAA5052203; GA AV ČR IAA7052002 Grant - others:KBN(PL) P04A12314; Liga proti rakovině(CZ) - Institutional research plan: CEZ:AV0Z5052915 Keywords : chemotherapy -induced residual tumour disease * immunotherapy * HPV16-associated tumours Subject RIV: FD - Oncology ; Hematology Impact factor: 2.536, year: 2003

  11. Receptor assay

    Energy Technology Data Exchange (ETDEWEB)

    Kato, K; Ibayashi, H [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1975-05-01

    This paper summarized present status and problems of analysis of hormone receptor and a few considerations on clinical significance of receptor abnormalities. It was pointed that in future clinical field quantitative and qualitative analysis of receptor did not remain only in the etiological discussion, but that it was an epoch-making field of investigation which contained the possiblity of artificial change of sensitivity of living body on drugs and the development connected directly with treatment of various diseases.

  12. Consentimiento estatal al arbitraje del CIADI

    Directory of Open Access Journals (Sweden)

    Pérez Pacheco , Yaritza

    2013-12-01

    Full Text Available El arbitraje en materia de inversión extranjera con especial atención a la jurisdicción del Centro Internacional de Arreglo de Diferencias Relativas a Inversiones, conocido como CIADI, es parte del Derecho Internacional de las Inversiones. El CIADI creado en el Convenio de Washington de 1965 se ha constituido en el foro natural para conocer de las controversias entre un Estado receptor y un inversor nacional de otro Estado. En este contexto se cuestionan varios aspectos vinculados a la formación del consentimiento para someterse al arbitraje internacional, en particular las modalidades (contrato, legislación y tratados y efectos de la manifestación del consentimiento por parte del Estado receptor de la inversión. En este trabajo se ha empleado el método de análisis de casos para extraer parámetros generales en la materia. En la actualidad el arbitraje internacional es una garantía ofrecida por el Estado, lo cual ha generado un clima de mayor seguridad para los inversores extranjeros en el trato con los Estados receptores de inversión y ha incentivado el crecimiento del comercio internacional.

  13. del alcoholismo

    Directory of Open Access Journals (Sweden)

    Rodrigo Arias Duque

    2005-01-01

    Full Text Available Desde el punto de vista farmacológico, es importante comprender qué es el alcohol y cómo actúa en el organismo. No existe una causa simple, sino una interacción complicada de factores neuroquímicos, fisiológicos, psicológicos y sociales que originan y desarrollan esta grave enfermedad fármaco-dependiente. La acción psicofisiológica y farmacodinámica del alcohol es fundamentalmente depresiva, por la reducción de la transmisión sináptica en el sistema nervioso humano. Es un hecho conocido que el consumo excesivo de alcohol causa una disfunción aguda y crónica del cerebro, produciendo trastornos en el sistema nervioso central, presentando alteraciones en la memoria y en las funciones intelectuales como cálculo, comprensión y aprendizaje. A nivel hepático tiene lugar, en su mayoría, el metabolismo del alcohol, produciéndose un hígado graso alcohólico, aumentando el tamaño, terminando en necrosis e inflamación grave del hígado; esto se llama hepatitis alcohólica, y si se sigue consumiendo alcohol se desarrollará la cirrosis. El alcohol también ha estado relacionado con alteraciones del miocardio; se ha constatado en animales de experimentación sanos que tanto la velocidad de contracción del músculo cardiaco y su máxima tensión disminuyen en presencia del alcohol, como consecuencia, la fuerza de cada contracción y el aumento de presión en el ventrículo izquierdo son menores, perdiendo eficacia el corazón como bomba.

  14. Culturas del Mundo

    DEFF Research Database (Denmark)

    Benwell, Ann Fenger; Costa, Alberto; Waehle, Espen

    2006-01-01

    ’Culturas del mundo. Colecciones del Museo Nacional de Dinamarca’ with Ann Fenger Benwell in Culturas del Mundo. Colecciones del Museo Nacional de Dinamarca, ed. Silvia Sauquet, Fundación "la Caixa", Barcelona 2006, pp. 31-39......’Culturas del mundo. Colecciones del Museo Nacional de Dinamarca’ with Ann Fenger Benwell in Culturas del Mundo. Colecciones del Museo Nacional de Dinamarca, ed. Silvia Sauquet, Fundación "la Caixa", Barcelona 2006, pp. 31-39...

  15. LA EXTENSION DE RAMAS COLATERALES LUEGO DE UNA LESION A LA MEDULA ESPINAL ES GATILLADA POR LA DEGENERACION AXONAL Y DEPENDE DE LA EXPRESION DEL RECEPTOR DE NEUROTROFINAS P75

    OpenAIRE

    COLLYER SAAVEDRA, EILEEN TEHANI; COLLYER SAAVEDRA, EILEEN TEHANI

    2013-01-01

    Las lesiones a la médula espinal (LME) presentan un pronóstico de recuperación prácticamente nulo debido a la baja capacidad regenerativa que tiene el sistema nervioso central (SNC) de los mamíferos. Este hecho estaría determinado por factores restrictivos microambientales que impiden la regeneración y no por una incapacidad intrínseca regenerativa de las neuronas del SNC. A pesar de que los axones del SNC que han sido dañados no son capaces de regenerar, luego de una LME parcial se observ...

  16. Actividad del Sistema Renina-Angiotensina en relación con sus polimorfismos genéticos

    OpenAIRE

    Morcillo Hidalgo, Luis

    2015-01-01

    La realización del presente estudio sobre sujetos jóvenes y sanos no hipertensos tiene dos objetivos primordiales: El primero es analizar la relación de los polimorfismos de los genes del Sistema Renina-Angiotensina, el M235T del gen del angiotensinógeno, el Inserción/Delección del gen de la ECA y el A1166C del gen del receptor AT1 para la angiotensina II, con los niveles en plasma de angiotensina I, angiotensina II y angiotensina-(1-7), todas sustancias peptídicas activas del sistema E...

  17. Cristalización y predicción de la estructura tridimensional de la proteína homóloga del receptor activado para la quinasa c (lack de leishmania

    Directory of Open Access Journals (Sweden)

    Edwin Patiño González

    2014-10-01

    Full Text Available Los parásitos del género Leishmania son los causantes de la enfermedad conocida como Leishmaniasis. Esta enfermedad es endémica en 98 países. Veinte especies de Leishmania sp han sido descritas como patógenos en humanos y varias de ellas presentan manifestaciones clínicas diferentes. No se dispone de vacuna, a pesar del considerable esfuerzo de muchos grupos de investigación. Las alternativas para descubrir nuevos medicamentos están basadas en el diseño de compuestos que interaccionen con blancos específicos, principalmente, proteínas encargadas de procesos metabólicos o celulares del patógeno, e.g. la parasitación de las células del huésped vertebrado. La eficiente parasitación del huésped vertebrado por Leishmania depende de la expresión de diferentes proteínas, incluyendo la proteína Lack. Parásitos deficientes de Lack no sobreviven internalizados en las células de los vertebrados. Este artículo presenta las condiciones de renaturalización, purificación y cristalización de la proteína Lack del patógeno humano Leishmania (Viannia panamensis. Además, los resultados de modelación estructural de esta proteína muestran una conformación proteica similar a un ventilador organizado en 7 aspas, cada una compuesta de 4 hojas β. La estructura de la proteína Lack resultó similar a la proteína asociada a ribosoma RACK1 de Trypanosoma brucei y Saccharomyces cerevisiae, y a la de otros eucariotas. Las características estructurales de la proteína Lack podrían ser usadas para la exploración de nuevos fármacos.

  18. Assessing the Mechanisms of MDS and Its Transformation to Leukemia in a Novel Humanized Mouse

    Science.gov (United States)

    2016-05-01

    Intrahepatic injection has several advantages : 1) At time of birth hematopoiesis occurs in the bone marrow and newborn liver with progressive...revealed, exogenous expression of mutant splicing factors does not provide the expected clonal advantage over wildtype cells. This has significantly...crossreactive cytokines, namely M- CSF , IL-3, GM- CSF , and Thrombopoietin as well as human macrophage receptor signal regulatory protein-alpha (SIRPα) from

  19. Il dono del racconto

    DEFF Research Database (Denmark)

    Polito, Paola

    1998-01-01

    L'articolo indaga a vari livelli strutturali del romanzo "Il coraggio del pettirosso" (rete metaforica, dialogismo diegetico, dialogismo come fenomeno di voce, strategie discorsive messe in atto dalla voce narrante, stile colloquiale) la complessa realizzazione testuale del genere narrativo...

  1. Estudio del sistema regulador formado por la serotonina y sus receptores en las células troncales MSC aisladas de médula ósea humana. Adipogénesis.

    OpenAIRE

    González Méndez, Laura

    2014-01-01

    Tesis doctoral inédita, leída en Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 21/03/2014 En los últimos años se ha identificado a la serotonina como un regulador crítico de la masa ósea, regulando tanto directa como indirectamente la actividad de las células responsables del proceso de remodelación ósea, osteoclastos y osteoblastos. El presente trabajo muestra que las MSCs aisladas de la médula ósea humana, células precursoras ...

  2. del cambio

    Directory of Open Access Journals (Sweden)

    Alejandro Canales

    2006-01-01

    Full Text Available El artículo analiza las propuestas y los compromisos en materia de cobertura y de financiamiento en el periodo 2000-2006. En particular, revisa las modificaciones y los ajustes de los tres principales documentos en los que se expresaron las iniciativas: el de la Asociación Nacional de Universidades e Instituciones de Educación Superior, el del equipo de la transición y el programa sectorial. Los resultados muestran que las cifras de atención a la demanda educativa e inversión quedaron lejos de las metas autoimpuestas por el gobierno federal y que será necesario realizar mayores esfuerzos para atender tales desafíos.

  3. Inhibición de la síntesis de neurotransmisor en neuronas dopaminérgicas de los ganglios basales. Localización celular del receptor H3 de histamina

    OpenAIRE

    González Sepúlveda, Marta

    2011-01-01

    En esta tesis se pretende aportar datos experimentales que ayuden a comprender las interacciones entre el sistema neuronal histaminérgico y otros sistemas de neurotransmisores presentes en los ganglios basales, particularmente el dopaminérgico. Dicho conocimiento podría ayudar a paliar patologías tales como la adicción a drogas de abuso, la esquizofrenia o la enfermedad de Parkinson. Al intentar estudiar efectos de ligandos de receptores sobre la síntesis de dopamina nos encont...

  4. Valor pronóstico del análisis de marcadores moleculares mediante proteómica dirigida en cáncer de mama precoz con receptores hormonales positivos

    OpenAIRE

    Martinez del Prado, María Purificación

    2018-01-01

    Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 22-03-2018 Introducción: El cáncer de mama (CM) es una enfermedad heterogénea a nivel molecular. La proteómica dirigida permite la investigación de potenciales biomarcadores, factores pronósticos, predictivos, diagnósticos y nuevas dianas terapéuticas en el cáncer de mama. En una serie inicial de pacientes (cohorte de descubrimiento) con CM, receptores hormon...

  5. Receptores para el virus de la rabia

    Directory of Open Access Journals (Sweden)

    Jaime E. Castellanos

    2001-12-01

    Full Text Available El virus de la rabia causa una infección en el sistema nervioso que puede provocar la muerte. La patogenia y el neurotropismo de este virus han sido estudiados extensamente con el objeto de explicar el porque la letalidad de la enfermedad y proponer nuevas alternativas terapéuticas. El proceso de adsorción del virus a la célula bianco se considera un evento que define el neurotropismo del virus. Se piensa que debe existir una molécula en la superficie de las neuronas que une con alta afinidad al virus y da comienzo al proceso infeccioso. Durante los últimos años se han propuesto varias proteínas, carbohidratos y lipidos complejos, como receptores para el virus de rabia y se han hecho nuevas proposiciones de terapia antirreceptor. Además de los gangliósidos y fosfolípidos para los que se ha hallado evidencia sobre su participación en la adsorción del virus de la rabia, hay datos experimentales sobre la participación del receptor nicotinico de acetilcolina. la molécula de adhesión celular neural y el receptor de baja afinidad para neurotrofinas en la infección neurona1 En este articulo se hace una revisión de los datos que sustentan a cada una de las moléculas propuestas, se discuten sus implicaciones para la explicación del neurotropismo del virus de rabia y la exploración de nuevas terapias antivirales.

  6. Sensibilidad y especificidad del cuestionario de preocupación y ansiedad para la detección del trastorno de ansiedad generalizada en la edad avanzada

    OpenAIRE

    Nuevo Benítez, Roberto

    2005-01-01

    Este trabajo se dirige a comprobar, mediante el análisis de las curvas COR (características operativas del receptor), la capacidad para identificar la presencia de trastorno de ansiedad generalizada (TAG) en personas mayores del Cuestionario de Preocupa

  7. La superaci??n del modelo del ??ngel del hogar:

    OpenAIRE

    Hurtado Mu??oz, M??nica

    2012-01-01

    La Tesis Doctoral titulada "La superaci??n del modelo del "??ngel del hogar". Recuperaci??n de la escritora Leonor Canalejas y Fustegueras (1869-1945)" aborda, en primer lugar, un an??lisis sociol??gico de las circunstancias que rodearon a la mujer espa??ola en el cambio de siglo en el ??mbito social y educativo, en un intento de esclarecer las caracter??sticas propias del contexto en el que la mujer accede a la intelectualidad en general y a la literatura en particular. Esta parte concluye q...

  8. Treating residual water according to the demands of its ulterior use: case of Neuquen river, Patagonia, Argentina; Optimizacion de requisitos de tratamiento de aguas residuales basado en la calidad del agua de acuerdo con el uso del cuerpo receptor: caso rio Neuquen, Patagonia, Argentina

    Energy Technology Data Exchange (ETDEWEB)

    Polla, Gabriela Maria; Dufilho, Ana Cecilia; Horne, Federico [Universidad Nacional del Comahue (Argentina)

    2006-07-15

    A developed methodology allows making a regional pacification based on the river's water quality and their guide levels for different uses. To get this methodology it was used an optimization model that allows obtaining the best combination of town and industrial liquid treatments of the region, which can make cheaper their construction and maintenance costs. The established regional stages of economical development, were simulated with the QUAL2E model, from this model was obtained the restriction coefficients of the optimization model. More over, this model allowed to prognosticate the behavior of the principal water quality components (dissolved and biochemical demand of oxygen, nitrogen, phosphorus and others) for different proposed stages. This methodology was applied over a section of Neuquen River (Argentina) which receives urban, industrial and farming effluents of three cities Centenario (Plant 1), Cinco Saltos (Plant 2) and Parque Industrial (Plant 3). From results, it can be affirmed that under present situation, there is not contamination hazard. However, under future scenarios, advanced and secondary treatment is required to assure meeting the quality standards, particularly when river discharge approach it annual minimum. [Spanish] Se desarrollo una metodologia que permite hacer una planificacion regional basada en la calidad de agua del rio y sus niveles guias para distintos usos. Para ello se utilizo un modelo de optimizacion que permite obtener la mejor combinacion de tratamientos de liquidos municipales e industriales de la region que minimicen sus costos de construccion y mantenimiento. Los escenarios de desarrollo economico regional planteados se simularon con el modelo QUAL2E, de donde se obtuvieron los coeficientes de las restricciones del modelo de optimizacion. El modelo de simulacion permitio, ademas, pronosticar el comportamiento de los principales componentes de calidad del agua (oxigeno disuelto, demanda bioquimica de oxigeno

  9. Receptores de progesterona en meningioma.

    Directory of Open Access Journals (Sweden)

    Herminio Ojeda Di Ninno

    1995-04-01

    Full Text Available Objetivo: Determinar la presencia de los receptores de progesterona en meningiomas y su frecuencia mediante la inmunohistoquímica. Material y Métodos: Se analizaron 24 muestras provenientes de pacientes intervenidos quirúrgicamente en el Instituto Nacional de Enfermedades Neoplásicas entre los años 1990 y 1992 con diagnóstico anatomopatológico de meningioma. La determinación de los receptores se hizo mediante una técnica de inmunohistoquímica rápida que permite el estudio de tejidos fijados previamente en parafina. Resultados: De los 24 casos estudiados, nueve resultaron ser positivos en la determinación de receptores de progesterona (37%. Se pudo observar un marcado predominio dentro del grupo femenino quienes constituyeron 8/9 casos positivos. Conclusiones: El empleo de esta reciente técnica de inmunohistoquímica aplicada a tejido de fijado en parafina, nos ha permitido confirmar la presencia de receptores de progesterona en meningiomas con una frecuencia elevada que creemos amerita un estudio más amplio de manera sistemática que incluya la intervención terapéutica mediante el uso de antiprogestágenos, como el Mifepristone o RU 486. De este estudio podrían beneficiarse no sólo pacientes operados recientemente sino aquellos que, intervenidos en el pasado sean detectados como portadores de receptores de progesterona mediante la aplicación de esta novedosa técnica (Rev Med Hered 1995; 6: 121-130.

  10. The LDL receptor.

    Science.gov (United States)

    Goldstein, Joseph L; Brown, Michael S

    2009-04-01

    In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life.

  11. Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    OBJECTIVE: To investigate the effect of different cytokines that are present in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell transmigration. DESIGN: Laboratory study. SETTING: University hospital, Ireland. MATERIAL: Isolated human PMN and cultured human breast tumour cell line, MDA-MB-231. Interventions: Human PMN treated with either tumour-conditioned medium or different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231 cells were plated on macrovascular and microvascular endothelial monolayers in collagen-coated transwells to assess migration of tumour cells. MAIN OUTCOME MEASURES: Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration. RESULTS: tumour-conditioned medium contained high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced transmigration of tumour cells treated with tumour-conditioned medium (p < 0.05), whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In addition, anti-GM-CSF MoAb, but not anti-VEGF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05). CONCLUSION: These results indicate that the GM-CSF that is present in tumour-conditioned medium may be involved, at least in part, in alterations in PMN function mediated by the medium and subsequently PMN-induced transmigration of tumour cells.

  12. Coxsackievirus B4 Can Infect Human Peripheral Blood-Derived Macrophages

    Directory of Open Access Journals (Sweden)

    Enagnon Kazali Alidjinou

    2015-11-01

    Full Text Available Beyond acute infections, group B coxsackieviruses (CVB are also reported to play a role in the development of chronic diseases, like type 1 diabetes. The viral pathogenesis mainly relies on the interplay between the viruses and innate immune response in genetically-susceptible individuals. We investigated the interaction between CVB4 and macrophages considered as major players in immune response. Monocyte-derived macrophages (MDM generated with either M-CSF or GM-CSF were inoculated with CVB4, and infection, inflammation, viral replication and persistence were assessed. M-CSF-induced MDM, but not GM-CSF-induced MDM, can be infected by CVB4. In addition, enhancing serum was not needed to infect MDM in contrast with parental monocytes. The expression of viral receptor (CAR mRNA was similar in both M-CSF and GM-CSF MDM. CVB4 induced high levels of pro-inflammatory cytokines (IL-6 and TNFα in both MDM populations. CVB4 effectively replicated and persisted in M-CSF MDM, but IFNα was produced in the early phase of infection only. Our results demonstrate that CVB4 can replicate and persist in MDM. Further investigations are required to determine whether the interaction between the virus and MDM plays a role in the pathogenesis of CVB-induced chronic diseases.

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

    Science.gov (United States)

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

    2016-03-01

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

  14. Acerca del moho

    Science.gov (United States)

    El moho forma parte del medio ambiente natural. Afuera del hogar, el moho juega un papel en la naturaleza al desintegrar materias organicas tales como las hojas que se han caido o los arboles muertos. El moho puede crecer adentro del hogar cuando las espor

  15. Del bit al qubit

    OpenAIRE

    Torras Font, Josep

    2011-01-01

    Aquest document pretén donar una visió del desenvolupament dels computadors electrònics i dels components que els han fet possibles. Dintre de les opcions de futur en computació, també intenta donar una visió de les bases en que es fonamenta la computació quàntica.

  16. Algunas aclaraciones acerca del conocimiento del singular.

    Directory of Open Access Journals (Sweden)

    Carlos Llano Cifuentes

    2013-11-01

    Full Text Available Llano tries to explain the main purpose of El Conocimiento del Singular, showing how the individuals about which the book is concerned are basically human individuals: people as decision makers.

  17. Moléculas que participan en el transporte de hierro materno-fetal: importancia del receptor 1 de transferrina y de la ferroportina en la placenta humana = Molecules implicated in maternal-fetal iron transport across the placental barrier: Role of Transferrin Receptor 1 and Ferroportin

    Directory of Open Access Journals (Sweden)

    Corrales Agudelo, Lady Vanessa

    2011-03-01

    Full Text Available La adecuada transferencia placentaria de hierro es crucial para satisfacer los altos requerimientos del feto y promover su adecuado crecimiento y desarrollo intrauterino; de otra parte, contribuye a prevenir la ferropenia y la anemia, entidades altamente prevalentes en los lactantes durante los primeros dos años de edad, que se asocian con mayor morbilidad y mortalidad en la infancia. La placenta es un órgano capaz de realizar diferentes adaptaciones en la producción de moléculas que participan en el transporte de hierro materno-fetal en respuesta al estado de hierro celular, para proveer la mayor disponibilidad de este mineral al feto. Esta revisión, pretende acercar al lector a los mecanismos metabólicos y moleculares relacionados con la captación, el transporte y la salida de hierro por la placenta hacia el feto, así como su regulación, para proporcionar elementos que le permitan comprender en forma integrada, la importancia de un adecuado estado de hierro materno antes y durante la gestación.

  18. Regulación del flujo sanguíneo uterino. II. Funciones de estrógeno y receptores estrogénicos α/β en acciones genómicas y no-genómicas del endotelio uterino *

    Science.gov (United States)

    Mayra, Pastore R.; Rosalina, Villalón L.; López, Gladys; Iruretagoyena, Jesús; Magness, Ronald

    2015-01-01

    Resumen El embarazo está marcado por cambios y adaptaciones cardiovasculares que son importantes para el crecimiento y mantenimiento de la placenta y el feto. Durante este periodo, las adaptaciones vasculares uterinas manifiestan cambios clasificados como de corto o largo plazo los cuales están relacionados con adaptaciones vasodilatadoras, angiogénicas o de remodelación. El estrógeno y los receptores estrogénicos clásicos (REs), RE-α y RE-β, han demostrado ser parcialmente responsables por facilitar el incremento dramático en el fluido sanguíneo uterino necesario durante el embarazo. En ésta revisión bibliográfica se discuten la base estructural para la diversidad y selectividad funcional de los REs por el estrógeno, el papel de los REs sobre los efectos genómicos y no-genómicos en células endoteliales de arterias uterinas (CEAU). Estos temas integran el conocimiento científico sobre la regulación molecular de CEAU para mantener el incremento fisiológico en la perfusión útero-placentaria observada durante un embarazo normal. PMID:26113751

  19. Muscarinic, adenosine and tropomyosin-related kinase B receptors modulate the neuromuscular developmental synapse elimination process

    OpenAIRE

    Nadal Magriñà, Laura

    2017-01-01

    El desarrollo del sistema nervioso periférico implica una inicial exuberante producción de neuronas y, una posterior reducción dependiente de actividad del número de sinapsis en las uniones neuromusculares (NMJ). Este proceso se denomina eliminación sináptica. Al final de la segunda semana postnatal, cada fibra muscular esta inervadas por una solo motoneurona. Los receptores muscarínicos de acetilcolina (mAChR), los receptores de adenosina (AR) y el receptor quinasa de tropomiosina B (TrkB) p...

  20. Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

    Science.gov (United States)

    Fuxe, K; Marcellino, D; Rivera, A; Diaz-Cabiale, Z; Filip, M; Gago, B; Roberts, D C S; Langel, U; Genedani, S; Ferraro, L; de la Calle, A; Narvaez, J; Tanganelli, S; Woods, A; Agnati, L F

    2008-08-01

    Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D(2) receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D(2) RM, located in the dorsal striato-pallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D(2) interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D(2)/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D(2) signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D(2)-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably

  1. Assignment of CSF-1 to 5q33.1: evidence for clustering of genes regulating hematopoiesis and for their involvement in the deletion of the long arm of chromosome 5 in myeloid disorders

    International Nuclear Information System (INIS)

    Pettenati, M.J.; Le Beau, M.M.; Lemons, R.S.; Shima, E.A.; Kawasaki, E.S.; Larson, R.A.; Sherr, C.J.; Diaz, M.O.; Rowley, J.D.

    1987-01-01

    The CSF-1 gene encodes a hematopoietic colony-stimulating factor (CSF) that promotes growth, differentiation, and survival of mononuclear phagocytes. By using somatic cell hybrids and in situ hybridization, the authors localized this gene to human chromosome 5 at bands q31 to q35, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the CSF-1 gene was found to be deleted in the 5q- chromosome of a patient with refractory anemia who had a del(5) (q15q33.3) and in that of a second patient with acute nonlymphocytic leukemia de novo who had a similar distal breakpoint [del(5)(q13q33.3)]. The gene was present in the deleted chromosome of a third patient, with therapy-related acute nonlymphocytic leukemia, who had a more proximal breakpoint in band q33 [del(5)(q22q33.1)]. Hybridization of the CSF-1 probe to metaphase cells of a fourth patient, with acute nonlymphocytic leukemia de novo, who had a rearrangement of chromosomes 5 and 21 resulted in labeling of the breakpoint junctions of both rearranged chromosomes; this suggested that CSF-1 is located at 5q33.1. Thus, a small segment of chromosome 5 contains GM-CSF (the gene encoding the granulocyte-macrophage CSF), CSF-1, and FMS, which encodes the CSF-1 receptor, in that order from the centromere; this cluster of genes may be involved in the altered hematopoiesis associated with a deletion of 5q

  2. Eficiencia en la productividad desde la perspectiva del cliente interno y externo en las empresas recicladoras del plástico en el departamento de la Guajira-Colombia

    OpenAIRE

    Victor Jos Iguaran Manjarr; Ledis Esther Campo Rivadeneira

    2017-01-01

    La finalidad del presente artículo es analizar la eficiencia en la productividad, desde la perspectiva del cliente interno y externo, en las empresas recicladoras del plástico en el departamento de la Guajira-Colombia. Se determina primero la repercusión del cliente interno, que es el personal que labora en las empresas recicladoras, el cual se considera el receptor primario de la visión, misión y estrategias formuladas para lograr la satisfacción del cliente externo. En este orden de ideas, ...

  3. Psicodrama del duelo.

    OpenAIRE

    José Antonio Espina Barrio; Marisol Filgueira Bouza

    1997-01-01

    La pérdida de rituales agrava y alarga la reacción del duelo. Se define el Psicodrama Antropológico y su intervención en el proceso del duelo. El Psicodrama Focal del Duelo es una psicoterapia breve centrada en el proceso de Duelo. Se comentan varios casos y resultados. Se concluye con un programa sencillo para el duelo en Atención Primaria.

  4. Psicoanálisis y comunicación: la existencia del otro

    Directory of Open Access Journals (Sweden)

    Allan Castelnuovo

    2015-01-01

    Full Text Available En América Latina se acostumbra a marginar la sicología del resto de las ciencias sociales, y los comunicadores tienden a usarla superficialmente. En cambio, los mentalizadores del marketing social toman en serio sus enseñanzas. Este desperdicio conceptual puede explicar parte de los fracasos de las campañas de comunicación. No conocer la sicología del cliente receptor de una campaña es negar su existencia. Lograr conocerlo en nuestras sociedades heterogéneas puede ser la tarea más importante del comunicador.

  5. Fractura triple del complejo suspensorio del hombro

    Directory of Open Access Journals (Sweden)

    Eraclio Delgado Rifá

    2015-06-01

    Full Text Available El complejo suspensorio del hombro es una estructura sumamente importante, compuesta por un anillo de huesos y tejidos blandos. Las lesiones aisladas de este complejo anatómico son frecuentes y no afectan su estabilidad. La interrupción doble conduce a la inestabilidad de esta estructura y usualmente requiere tratamiento quirúrgico. La triple interrupción, por su parte, es sumamente rara y es encontrada en casos de trauma de alta energía a menudo en asociación con otras lesiones. Se presenta una triple lesión del complejo suspensorio del hombro en un paciente de 46 años de edad, con una fractura de la glenoides, del acromion tipo III de Kuhn y de la coracoides tipo II de Ogawa. En este caso, la fractura del acromion fue tratada con fijación percutánea con alambres de Kirschner, por tener asociado lesiones de partes blandas que contraindicaron la reducción abierta. La fractura de la glenoides y de la apófisis coracoides fueron tratadas conservadoramente. Después de 6 meses de evolución, el paciente tuvo un resultado funcional aceptable, con una abducción de 90 grados, los 30 grados de rotación externa y 70 de rotación interna, además asintomático y consolidación de todas las fracturas. A pesar de ser catalogada de una lesión grave del cinturón escapular y estar asociada a otras lesiones se obtuvo un resultado satisfactorio al final del tratamiento.

  6. Vigencia del Darwinismo

    OpenAIRE

    Lessa, Enrique P

    2009-01-01

    En este ensayo se presenta una revisión histórica del signifcado y legado del darwinismo, con énfasis en el último siglo. La principal conclusión es que la visión darwiniana de la evolución, con las modifcaciones requeridas para dar cuenta de los grandes desarrollos de la disciplina, se ha impuesto y mantiene vigencia en nuestros días. En particular, el papel del azar, la evolución como proceso de “descendencia con modifcación” a lo largo de diversas ramas del árbol de la vida, el pensamiento...

  7. Acetylcholine receptor antibody

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood of ...

  8. Cooperative ethylene receptor signaling

    OpenAIRE

    Liu, Qian; Wen, Chi-Kuang

    2012-01-01

    The gaseous plant hormone ethylene is perceived by a family of five ethylene receptor members in the dicotyledonous model plant Arabidopsis. Genetic and biochemical studies suggest that the ethylene response is suppressed by ethylene receptor complexes, but the biochemical nature of the receptor signal is unknown. Without appropriate biochemical measures to trace the ethylene receptor signal and quantify the signal strength, the biological significance of the modulation of ethylene responses ...

  9. La luz del origen del universo

    Directory of Open Access Journals (Sweden)

    Casas, Alberto

    2015-10-01

    Full Text Available Penzias and Wilson discovered the cosmic microwave background, a luminous echo of the Big Bang, in 1965. The amount of information encoded in this relic of the early universe is truly extraordinary. At present, the most precise data about the origin and structure of the universe comes from the study of this primordial light, the full potential of which has yet to be explored.En 1965 se descubrió el fondo de radiación de microondas, un eco luminoso de la Gran Explosión (Big Bang. La cantidad de información contenida en esta reliquia del universo primitivo es verdaderamente extraordinaria. En la actualidad los datos más precisos sobre el origen y estructura del universo provienen del estudio de esta luz primigenia, que aún no ha sido explorada en todo su potencial.

  10. Archivo del Duelo

    OpenAIRE

    Ferrera, Tamara

    2010-01-01

    Photos taken from the Archive of Mourning following the March 11 terrorist attacks El Archivo del Duelo. Creación de un archivo etnográfico de los Atentados del 11 de marzo en Madrid. Ministerio de Educación y Ciencia HUM2005-03490.

  11. Displasias del seno

    Directory of Open Access Journals (Sweden)

    Ernesto Andrade Valderrama

    1971-04-01

    Full Text Available En general, las Displasias no se presentan antes de la iniciación del estímulo Gonadal y tienden a desaparecer con el climaterio. Se definen entonces como las afecciones benignas del Seno, de origen endocrino.

  12. Seroprevalencia de citomegalovirus en donantes de órganos y receptores de trasplante renal, Colombia, 2010-2014

    Directory of Open Access Journals (Sweden)

    Yazmín Rocío Arias-Murillo

    2016-08-01

    Conclusiones. Los resultados del presente estudio evidenciaron que las tasas de infección por citomegalovirus fueron altas y que la categorización del riesgo de los receptores de trasplante señala la necesidad de que los equipos médicos tratantes tomen medidas para minimizar los riesgos.

  13. La crisi del diritto del lavoro

    Directory of Open Access Journals (Sweden)

    Alessandro Garilli

    2012-01-01

    Full Text Available Riassunto - L’Autore ripercorre in chiave critica l’evoluzione delle politiche legislative in materia di lavoro, alla luce dell’attuale fase di crisi economico finanziaria. Nell’esaminare i principali interventi normativi attuati da inizio secolo, l’Autore mette in evidenza le scelte di metodo e gli elementi di continuità che accomunano i vari provvedimenti, individuandoli nell’affannosa ricerca del punto di equilibrio tra flessibilità e garantismo. La riflessione si chiude con alcuni interrogativi sulle ultime linee di riforma del mercato del lavoro e con l’auspicio che, anche al cospetto delle imprescindibili ragioni dell’economia, il diritto del lavoro possa continuare a svolgere il proprio tradizionale ruolo di disciplina di tutela della persona.   Abstract - The author analyzes, with a critically oriented approach, the development of the employment law, in the light of the current economic and financial crisis. In examining the main regulatory measures implemented since the beginning of the century, the author highlights the methodological choices and the elements of continuity that unite the various measures, focusing them in a hard research of a point of balance between flexibility and security. The discussion concludes with some questions about the last lines of the reform of the labor market and with the hope that, even in the face of compelling reasons of economy, labor law can continue to play its traditional role of governing the protection of person.

  14. OBJETIVO DEL DESARROLLO DEL MILENIO 7

    Directory of Open Access Journals (Sweden)

    Margarita M. Pérez O.

    2013-10-01

    Full Text Available Los Objetivos de Desarrollo del Milenio, también conocidos como los Objetivos del Milenio, constituyeron las metas finales que aprobaron los dirigentes mundiales, 189 jefes de estado y de gobierno en la Cumbre del Milenio de las Naciones Unidas celebrada en Nueva York en el año 2000, en la cual los Estados miembros de la organización reafirmaron su compromiso de luchar por un mundo en el que el desarrollo sostenible y la eliminación de la pobreza tuvieran máxima prioridad1 . En la cumbre se definió la Declaración del Milenio, la cual detalla los objetivos, principios, valores, metas y acciones para erradicar la pobreza Mundial hacia el año 2015, todos ellos ratificados con alto interés y acción estratégica de carácter global, como marco para la medición de los progresos en materia de desarrollo.

  15. Elementos del sistema electoral del Congreso Mexicano

    Directory of Open Access Journals (Sweden)

    Aldo Medina García

    2013-08-01

    Full Text Available El presente artículo es un estudio de los componentes del sistema electoral, diseñado por el legislador mexicano para integrar al parlamento federal. Estudio desarrollado a sabiendas de la importancia que reviste el sistema electoral como un medio que permite a los ciudadanos convertir su voto expresado en las urnas en escaños a favor de determinado candidato o partido. En dicho análisis tomamos en cuenta la evolución constitucional del sistema electoral mexicano, la participación de las fuerzas minoritarias en la integración del Senado y de la Cámara de Diputados, la división que se hace del territorio en circunscripciones electorales, la barrera electoral que se fija a los partidos políticos para acceder a la representación en el Parlamento, la fórmula de asignación que se aplica a la votación obtenida, para finalmente concluir que el sistema electoral mexicano es esencialmente mayoritario aun cuando se vista de proporcional.

  16. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  17. GABA receptor imaging

    International Nuclear Information System (INIS)

    Lee, Jong Doo

    2007-01-01

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  18. Castillo del Real. Olocau

    OpenAIRE

    AUÑÓN VALLEJO, JONATAN

    2012-01-01

    El objetivo que se quiere alcanzar con este proyecto es el de realizar un estudio lo más cercano posible del Catillo del Real, de manera que se pueda conocer su origen, su evolución a lo largo de la historia, así como las diferentes técnicas y sistemas constructivos utilizados en su construcción. Auñón Vallejo, J. (2011). Castillo del Real. Olocau. http://hdl.handle.net/10251/14244. Archivo delegado

  19. La Representabilidad del Genocidio

    OpenAIRE

    Cardona González, Lorena

    2012-01-01

    El presente artículo intenta hacer una aproximación histórica y analítica al fenómeno del Genocidio, sus implicaciones sociales y culturales que dieron como resultado la reformulación analítica y conceptual de hechos que hasta entonces superaban el conocimiento y la moral humana. De este modo, se hace un trayecto histórico de la paulatina aparición del asesinato masivo como practica de Estado, enmarcado en las experiencias del genocidio armenio y el alemán. A su vez, se hace una mirada sobre ...

  20. Significado presente del CSIC

    OpenAIRE

    Garrido Gallardo, Miguel Angel

    2000-01-01

    Not available

    Este artículo, elaborado en 1999, ofrece una panorámica de la realidad del Consejo Superior de Investigaciones Científicas en la actualidad. Repasa su organización, su volumen de publicaciones, sus indicadores de productividad, su capacidad de obtener recursos y, en suma, su lugar en el conjunto del sistema español de Ciencia y Tecnología, considerado en sí mismo y en relación con la Universidad. Como conclusión del repaso de datos, se afirma que, aunque la fó...

  1. Tratamiento del pie equino

    OpenAIRE

    Robles, Fernanda

    2012-01-01

    El pie equino varo es una patología frecuente en los pacientes con Encefalopatía crónica no evolutiva (ECNE).Se observó que existe una mayor frecuencia en el sexo masculino. Se realizó un estudio descriptivo, comparativo y secundario, durante el periodo de septiembre del 2006 a septiembre del 2011, con un total de 125 pacientes con Ecne, de los cuales se encontraron 101 con pie equino varo congénito. Objetivo: observar los resultados obtenidos en la rehabilitación del pie equino, en niños de ...

  2. Del Pasadismo al Futurismo

    OpenAIRE

    Agudo-Martínez, M. J.

    2003-01-01

    Uno de los habituales prejuicios a la hora de abordar el análisis del movimiento futurista, al igual que sucede con el constructivismo, es la consideración del contexto político en el que se desarrollaron ambas vanguardias. Sin embargo, y dejando a un lado un enfoque del arte con finalidad política de signo diverso, habría que insistir en el hecho de que posiblemente sean tanto el futurismo italiano como el constructivismo ruso, los movimientos que con mayor entusiasmo se manifestaron, en un ...

  3. Glucocorticoid receptor modulators.

    Science.gov (United States)

    Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan

    2018-06-01

    The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  4. Del-1 Expression as a Potential Biomarker in Triple-Negative Early Breast Cancer.

    Science.gov (United States)

    Lee, Soo Jung; Lee, Jeeyeon; Kim, Wan Wook; Jung, Jin Hyang; Park, Ho Yong; Park, Ji-Young; Chae, Yee Soo

    2018-01-01

    A differential diagnostic role for plasma Del-1 was proposed for early breast cancer (EBC) in our previous study. We examined tumoral Del-1 expression and analyzed its prognostic impact among patients with EBC. Del-1 mRNA expression was assessed in breast epithelial and cancer cells. Meanwhile, the tumoral expression of Del-1 was determined based on tissue microarrays and immunohistochemistry results from 440 patients. While a high Del-1 mRNA expression was found in all the breast cancer cell lines, the expression was significantly higher in MDA-MB-231. Tumoral expression of Del-1 was also significantly associated with a negative expression of estrogen receptor or progesterone receptor, and low expression of Ki-67, particularly in the case of triple-negative breast cancer (TNBC) (p breast cancer cell lines exhibited Del-1 expression, the expression rate and intensity were specifically prominent in TNBC. In addition, based on its relationship to an unfavorable histology and worse survival trend, Del-1 could act as a molecular target in TNBC patients. © 2018 S. Karger AG, Basel.

  5. Dengue virus receptor

    OpenAIRE

    Hidari, Kazuya I.P.J.; Suzuki, Takashi

    2011-01-01

    Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

  6. Uso del Propanolol en Hipertiroidismo

    Directory of Open Access Journals (Sweden)

    Alfredo Jácome Roca

    1993-08-01

    las manifestaciones de hipertiroidismo son de naturaleza hiperadrenérgica. Entre ellas están el nerviosismo, la hiperdiaforesis, en parte la intolerancia al calor, las palpitaciones, manifestaciones gastrointestinales, la taquicardia y/o fibrilación auricular, la piel caliente y húmeda, el soplo tiroideo o el temblor. El betabloqueo se traducirá en un rápido alivio de buena parte de la sintomatología (2.

    Durante el manejo médico agudo del hipertiroidismo encontramos que el paciente tiene un aumento en la termogénesis y una respuesta exagerada a los estímulos beta-adrenérgicos, produciendo esto último nerviosismo y ansiedad, taquicardia y temblor. La terapia de apoyo para contrarrestar estos efectos incluye puntos tales como educación, mejoría del estado nutricional, reducción de las demandas cardiovasculares y el empleo de los betabloqueadores de los cuales el más usado es el propanolol.

    Esta droga fue desarrollada por Sir James Black, recientemente galardonado con el Premio Nobel de Medicina. Se ha convertido en el prototipo de los beta-bloqueadores por la extensa experiencia clínica que de él se tiene. No es selectivo porque interactúa con igual afinidad con los receptores beta uno y beta dos; no bloquea los receptores alfa-adrenérgicos ni tiene actividad simpático-mimética intrínseca.

    Al hacer el bloqueo, disminuyen proporcionalmente las respuestas cronotrópicas, inotrópicas y vasodilatadoras a la estimulación beta-adrenérgica; es altamente lipofílico y aunque se absorbe casi completamente cuando se da por vía oral, tiene un alto metabolismo de primer paso hepático y sólo un 25%llega a la circulación sistémica.

    No existe una correlación simple entre el nivel plasmático o la dosis administrada y el efecto terapéutico y la gama de sensibilidad a las dosis utilizadas en clínica es amplia puesto que el tono simpático varía ampliamente entre individuos. Está contraindicado principalmente en asmáticos e

  7. Preferencias del Turista

    Directory of Open Access Journals (Sweden)

    Jose Luis Leiva Olivencia

    2015-01-01

    Full Text Available Actualmente existen aplicaciones orientadas al turismo basadas en realidad aumentada, pero no integran técnicas de recomendación. Este articulo describe RAMCAT (Realidad Aumentada Móvil Contextual Aplicada al Turismo un modelo de guía turística, que recomienda puntos de interés, teniendo en cuenta factores como preferencias personales y atributos contextuales. Se presentan los componentes teóricos de la arquitectura propuesta, así como sus características, destacando la integración de diferentes sistemas de recomendación, que permiten añadir nuevos motores en el futuro. El articulo se centra en describir sus funcionalidades y el modulo correspondiente al sistema de recomendación basado en el perfil del turista. Otra característica importante del sistema propuesto es la retroalimentación del mismo mediante calificaciones del turista y su trazabilidad.

  8. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Luis Eladio Proaño

    2015-01-01

    Full Text Available La millonaria contratación del futbolista David Beckham, un fenómeno del mercado, ha provocado cuestionamientos a los que se busca respuesta. Es tema de análisis el por qué el betseller "Harry Potter" ha causado tanta conmoción en la opinión pública. Respecto al periodista cibernético, se señalan los contornos del presente y atisban las posibilidades del futuro de esta nueva profesión. El tratamiento de los mitos de la prensa, los temores de la Ley mordaza venezolana y la brutalidad de los video juegos e Internet son temas de enorme interés. Se comenta las pocas veces que la prensa reflexiona sobre la comunicación corporal y la anorexia.

  9. Los muertos del Floreanismo

    Directory of Open Access Journals (Sweden)

    Enrique Ayala Mora

    2008-06-01

    Full Text Available El artículo analiza el crimen político durante las primeras décadas de vida de la República del Ecuador. Específicamente centra su estudio en el período dominado por la figura de Juan José Flores, primer presidente del Ecuador. La inestabilidad política, la precariedad de las alianzas entre las élites regionales, la crisis económica generada por las guerras de Independencia, las conspiraciones y la violencia que caracterizaron al período de surgimiento de las repúblicas andinas hicieron del crimen político un “vicio de nacimiento”. El asesinato del general Antonio José de Sucre, la muerte de los miembros de la sociedad El Quiteño Libre, el homicidio de Juan Otamendi, entre otros, hicieron patente esta característica.

  10. Niveles del aprendizaje organizacional

    OpenAIRE

    Garzón Castrillón, Manuel Alfonso

    2005-01-01

    En la propuesta de modelo de aprendizaje organizacional (AO), la segunda variable se denomina niveles del aprendizaje organizacional ; los niveles de aprendizaje que contemplamos para nuestra investigación son: individual, de equipo, organizacional e interorganizacional.

  11. La escritura del Yo

    Directory of Open Access Journals (Sweden)

    Patricio Landaeta Mardones

    2013-11-01

    Full Text Available Si la creación de una imagen fidedigna del mundo fue la condición de la conquista cognitiva y económica de la tierra, las imágenes mediáticas circulan hoy en día a la manera de un montaje que organiza los sujetos como elementos de un territorio. En esta presentación abordaremos el cruce entre estos dos hechos, entre la escritura del mundo y la de los sujetos, a partir de la idea de Fabulación para mostrar otra escritura del mundo y del yo, leyendo textos e imágenes de la Primera buena Corónica y Buen Gobierno de Felipe Guaman Poma de Ayala.

  12. Consideraciones alrededor del Libro del Almismo, el Libro del Pensar.

    Directory of Open Access Journals (Sweden)

    MartaLucía Tamayo Fernandez

    1999-12-01

    Full Text Available

    La doctora MarthaLucía Tamayo comparte muchas inquietudes alrededor del Libro del Almismo, el Libro del Pensar; de dónde salió ese nombre; de juntar en medicina y en genética a tres escritores como lo son Jorge Luis Borges, Macedonio Fernández y Julio Cortázar. Su conferencia dice así:

    El término almismo fue ideado por Macedonio Fernández porque defendía mucho el ensimismamiento y el pensamiento hacia el interior, mirar hacia adentro; cada uno somos un “sí mismo” que nos hace diferentes aunque al mismo tiempo podemos ser iguales. Todos tenemos esa parte interior que la medicina debe trabajar y que no puede olvidar.

    “El Libro del Almismo, el libro del pensar” nos lleva a replantear y a repensar un poco la medicina que queremos, una medicina vuelta a pensar.

    Quiero contarles la historia de cómo se llegó a este libro y por qué y para qué se sigue trabajando en estos temas: Después de mi internado y de un trabajo un poco triste de rural, volví al Instituto de Genética y a la Universidad Javeriana en donde encontré al doctor Bernal y un espacio que estaba buscando para esa medicina diferente que quería, con un grupo de personas que me permitía no sólo ver la medicina sino ver muchas otras cosas más; había espacio para la literatura, para Mafalda, para hablar de niños, de locos, había incluso tiempo para hablar de medicina dentro del golf, de carros antiguos y de todo eso fui aprendiendo.

    Eso era lo que estaba buscando. Una medicina que diera espacios diferentes, que fuera más humanizada. Rápidamente me ubiqué y me quedé! No me arrepiento en lo absoluto de haberme quedado porque fue, ha sido y sigue siendo, una experiencia enriquecedora, de muchas vivencias importantes. Sabía exactamente dónde estaba y sabía que había que seguir rápido y había que trabajar muchos aspectos de esa medicina que estábamos buscando y de esa genética especial.

    Rápidamente empezamos a trabajar

  13. Actualidad del relativismo cultural

    OpenAIRE

    Sánchez Durá, Nicolás

    2013-01-01

    Este ensayo tiene tres propósitos. En primer lugar, propone examinar las relaciones entre etnocentrismo y relativismo. El etnocentrismo puede tomar tres formas distintas: a saber, la de una universalidad impostada, la del exotismo y la de un particularismo narcisista exacerbado. El relativismo cultural es una postura que asume la inconmensurabilidad de los conceptos y valores que deben ser considerados como válidos dentro de las imágenes del mundo definidas. En segundo lugar, se argumenta que...

  14. el Valle del Cauca

    Directory of Open Access Journals (Sweden)

    Carlos Humberto Ortiz

    2007-01-01

    Full Text Available Este artículo se enfoca en la identi- ficación de aquellos factores estructurales que explican la pérdida de dinamismo económico de largo plazo en Colombia y, en particular, en el Valle del Cauca. Se examina la competitividad del Valle en relación con Colombia y con el resto del mundo. Se cuestiona la insistencia en una estrategia exportadora como dinamizadora del desarrollo económico. Se identifica que una gran parte de la población está excluida de los beneficios del desarrollo económico. Para construir un modelo de desarrollo que incluya a esta población se recomienda recuperar la senda de la industrialización, invertir en el capital humano (educación de alta calidad, salud, salubridad y nutrición, e invertir en infraestructura. La participación del Estado en estas inversiones sociales es necesaria para disminuir la desigualdad y aumentar el crecimiento económico.

  15. Espectroscopia del Cometa Halley

    Science.gov (United States)

    Naranjo, O.; Fuenmayor, F.; Ferrin, L.; Bulka, P.; Mendoza, C.

    1987-05-01

    Se reportan observaciones espectroscópicas del cometa Halley. Los espectros fueron tomados usando el espectrógrafo del telescopio reflector de 1 metro del Observatorio Nacional de Venezuela. Se utilizó óptica azul, con una red de difracción de 600 lineas/min, obteniéndose una dispersión de 74.2 A/mm y una resolución de 2.5 A, en el rango espectral de 3500 a 6500 A. Seis placas fueron tomadas con emulsión IIa-O y dos con IIa-D. Los tiempos de exposición fueron entre 10 y 150 minutos. El cometa se encontraba entre 0.70 y 1.04 UA del Sol, y entre 1.28 y 0.73 UA de la Tierra. Las emisiones más prominentes en el espectro, son las del CN, C2, y C3. Otras emisiones detectadas corresponden a CH, NH2 y Na. Los espectros muestran un fuerte continuo, indicando un contenido significativo de polvo. Se detectó mayor intensidad del contínuo, en la dirección anti solar, lo cual es evidencia de la cola de polvo.

  16. Inventario nacional del uso actual del agua

    OpenAIRE

    Oficina Nacional de Evaluación de Recursos Naturales

    1984-01-01

    Establece como se emplea el agua en el Perú, teniendo en cuenta el tipo de uso, consuntivo y no consuntivo, discriminando según sea el destino: agrícola, pecuario, poblacional,industrial, minero, energético y pesquero, así como su localización geográfica; ello con la finalidad de que sirva de información básica para la planificación del desarrollo.

  17. Situación actual del turismo en la Argentina

    Directory of Open Access Journals (Sweden)

    Marta Sammarchi

    2001-01-01

    Full Text Available El turismo, fenómeno esencialmente geográfico corresponde tal vez a una de las expresiones más acabadas de la sociedad de consumo. Es por eso que la Geografía del Turismo recobra hoy mayor vigor ya que ella se encarga del estudio del espacio donde se distingue un espacio emisor, un espacio receptor y el espacio de tránsito. Por sus componentes territoriales y ambientales, el aporte desde la Geografía contribuye, sin duda en forma fructífera para comprender las actividades del tiempo libre, del ocio y el turismo. En este artículo se analiza el incremento del Turismo receptivo e interno en la Argentina, como así también la oferta hotelera, el número de plazas y los recursos humanos empleados en esta actividad como así también el nivel de educación alcanzados por ellos pues el turismo en la Argentina ha representado un aumento en el período 1990-98 de un 116,8%.

  18. Gerencia del cuidado-gerencia del servicio

    Directory of Open Access Journals (Sweden)

    Marta Palmet Jiménez

    2016-01-01

    Full Text Available La gerencia de este siglo debe estar plenamente identificada con la administración para planear, organizar, decidir y obtener resultados definidos, evaluados y alcanzados a través de las personas. Para poder gerenciar el cuidado se debe saber administrar. El objetivo de enfermería es cuidar; el objetivo de la gerencia es la conducción de la producción de bienes o servicios en las organizaciones. La gerencia del cuidado implica: motivación, creatividad, responsabilidad y ética por parte del cuidador y de quien cuida, claridad de actitud frente al ser y al qué hacer por parte del cuidador. Se puede concluir que la gerencia (administración, el cuidado (producto de calidad, el servicio (valor intangible, querer servir son un trinomio que deben ir de la mano de manera integrada para el logro de los objetivos propuestos por la organización de salud y de enfermería.

  19. Lack of effect of the alpha2C-adrenoceptor Del322-325 polymorphism on inhibition of cyclic AMP production in HEK293 cells.

    Science.gov (United States)

    Montgomery, M D; Bylund, D B

    2010-02-01

    The alpha(2C)-adrenoceptor has multiple functions, including inhibiting release of noradrenaline from presynaptic nerve terminals. A human alpha(2C) polymorphism, Del322-325, a potential risk factor for heart failure, has been reported to exhibit reduced signalling in CHO cells. To further understand the role of the Del322-325 polymorphism on receptor signalling, we attempted to replicate and further study the reduced signalling in HEK293 cells. Human alpha(2C) wild-type (WT) and Del322-325 adrenoceptors were stably transfected into HEK293 cells. Radioligand binding was performed to determine affinities for both receptors. In intact cells, inhibition of forskolin-stimulated cyclic AMP production by WT and Del322-325 clones with a range of receptor densities (200-2320 fmol.mg(-1) protein) was measured following agonist treatment. Noradrenaline, brimonidine and clonidine exhibited similar binding affinities for WT and Del322-325. Brimonidine and clonidine also had similar efficacies and potencies for both receptors for the inhibition of cyclic AMP production at all receptor densities tested. A linear regression analysis comparing efficacy and potency with receptor expression levels showed no differences in slopes between WT and Del322-325. The alpha(2C) WT and Del322-325 adrenoceptors exhibited similar binding properties. Additionally, inhibition of cyclic AMP production by Del322-325 was similar to that of WT over a range of receptor densities. Therefore, in intact HEK293 cells, the alpha(2C)-Del322-325 polymorphism does not exhibit reduced signalling to adenylyl cyclase and may not represent a clinically important phenotype.

  20. Determinantes del ingreso y del gasto corriente de los hogares

    OpenAIRE

    Muñoz C., Manuel

    2004-01-01

    Este ensayo de investigación empírica analiza los determinantes del ingreso y del gasto en los hogares colombianos. Utilizando un modelo del ciclo de vida con datos de la encuesta de hogares de 1994 y 1995, muestra que el comportamiento del ingreso está afectado principalmente por las características demográficas del hogar y los rasgos socio ocupacionales de sus miembros. El comportamiento del gasto está determinado ante todo por el ingreso y, en menor medida, por las características sociales...

  1. Las fluctuaciones del nivel del mar durante el Cuaternario

    OpenAIRE

    Pousa, Jorge Lorenzo; Isla, Federico Ignacio; Schnack, Enrique Jorge

    2002-01-01

    Los cambios del nivel del mar han ejercido una fuerte influencia en la evolución del planeta y en la historia de la humanidad. En una escala de tiempo geológico, las variaciones de los niveles oceánicos han dejado un registro ampliamente distribuido en la forma de depósitos sedimentarios. El descenso del nivel del mar durante la Ultima Glaciación, que alcanzó unos 120 metros hace 18.000 años, permitió la emergencia del estrecho de Bering y la migración humana desde Eurasia hacia América. Se e...

  2. Angiotensin type 2 receptors

    DEFF Research Database (Denmark)

    Sumners, Colin; de Kloet, Annette D; Krause, Eric G

    2015-01-01

    In most situations, the angiotensin AT2-receptor (AT2R) mediates physiological actions opposing those mediated by the AT1-receptor (AT1R), including a vasorelaxant effect. Nevertheless, experimental evidence vastly supports that systemic application of AT2R-agonists is blood pressure neutral...

  3. La imagen del pase.

    Directory of Open Access Journals (Sweden)

    Hernando Bernal.

    1999-11-01

    Full Text Available A partir de un texto del poeta Octavio Paz llamado «La imagen», se busca proseguir la equivalencia entre las imágenes de la poesía y la función que ellas tienen para el poeta, y el fantasma fundamental y su función para el analizante que está en el momento del pase. Se parte de la idea de que la poesía busca entrar en el ser así como el psicoanálisis tiene como finalidad apuntar al corazón del ser del sujeto. Se hace entonces una distinción del concepto de «ser» para el psicoanálisis, haciendo alusión también al discurso de la filosofía. Esclarecido el sentido de lo que es el «ser» para el psicoanálisis, se aborda de lleno – entre otras cosas, relacionadas con la experiencia del pase específicamente- la equivalencia entre la definición que hace Octavio Paz de «La Imagen» y el momento del pase en el análisis de un sujeto, imagen que, al igual que el mito para la filosofía, las leyes para la ciencia y el matema para el psicoanálisis, se constituyen en los instrumentos con los que cada una de estas disciplinas horadan en lo real.

  4. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  5. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

  6. Association between a promoter dopamine D2 receptor gene variant and the personality trait detachment.

    Science.gov (United States)

    Jönsson, Erik G; Cichon, Sven; Gustavsson, J Petter; Grünhage, Frank; Forslund, Kaj; Mattila-Evenden, Marja; Rylander, Gunnar; Asberg, Marie; Farde, Lars; Propping, Peter; Nöthen, Markus M

    2003-04-01

    Personality traits have shown considerable heritable components. Striatal dopamine D(2) receptor density, as determined by positron-emission tomography, has been associated with detached personality, as assessed by the Karolinska Scales of Personality. A putative functional promoter polymorphism in the dopamine D(2) receptor gene (DRD2), -141C ins/del, has been associated with dopamine D(2) receptor density. In this study healthy subjects (n = 235) who filled in at least one of several personality questionnaires (Karolinska Scales of Personality, Swedish Universities Scales of Personality, Health-relevant Five-factor Personality Inventory, and Temperament and Character Inventory) were analyzed with regard to the DRD2 -141C ins/del variant. There was an association (p =.001) between the DRD2 -141C ins/del variant and Karolinska Scales of Personality Detachment scale, indicating higher scores in subjects with the -141C del variant. There were also associations between the DRD2 -141C ins/del variant and a number of Karolinska Scales of Personality and Swedish Universities Scales of Personality Neuroticism-related scales, but of these only Swedish Universities Scales of Personality Lack of Assertiveness scale (p =.001) survived correction for multiple testing. These results add further support for the involvement of dopamine D(2) receptor in certain personality traits. The results should be treated with caution until replicated.

  7. HIPERTENSIÓN Y EMBARAZO: UN ESTUDIO VASCULAR DE LOS RECEPTORES α1-ADRENÉRGICOS

    OpenAIRE

    Pérez Ordaz, Leticia

    2012-01-01

    Los receptores α1-adrenérgicos medan la contracción del musculo liso vascular. Son activados por catecolaminas, adrenalina y noradrenalina para inducir un incremento en la concentración de calcio intracelular. Tres subtipos de receptores α1-adrenérgicos forman esta familia (α1A, α1B y α1D). Cambios en la respuesta contráctil del musculo liso vascular han sido establecidos en hipertensión y embarazo, y cuando estos factores fueron individualmente evaluados, respuestas increme...

  8. Lipophorin Receptor: The Insect Lipoprotein Receptor

    Indian Academy of Sciences (India)

    IAS Admin

    Director of ... function of the Lp is to deliver lipids throughout the insect body for metabolism ... Lipid is used as a major energy source for development as well as other metabolic .... LpR4 receptor variant was expressed exclusively in the brain and.

  9. Estudio del dominio carboxi-terminal del receptor de GLP-1(7-36) amida

    OpenAIRE

    Vázquez Pérez, Patricia

    2002-01-01

    El péptido relacionado con el glucagón de tipo 1 (GLP-1), está implicado en muchas funciones biológicas, como son el aumento de al secreción de insulina dependiente de glucosa, así como la estimación de la presión arterial y producción de surfactante pulmonar. A nivel central el GLP-1(7-36)amida estimula la liberación selectiva de neurotransmisores y participa en la regulación de procesos tales como la ingesta de alimentos y agua, la temperatura corporal y el control de ciertas funciones card...

  10. del Estado Aragua

    Directory of Open Access Journals (Sweden)

    Joselys Cintia Zerpa

    2008-01-01

    Full Text Available Diagnostica la situación actual de los bienes que conforman al patrimonio histórico-cultural del Municipio Zamora, Estado Aragua, Venezuela. La Investigación es descriptiva y de campo, comprendió la elaboración de un inventario de los bienes inmuebles, festividades religiosas y manifestaciones artesanales del municipio. Se estudiaron la condición física y uso actual de estos bienes y los planes y proyectos existentes. Analizó el marco normativo que los rige. Se obtuvo la opinión de los representantes de organismos públicos relacionados con la actividad turística del Municipio, de los visitantes, cronistas e historiadores. Aportes: La mayoría de los bienes se encuentran en buen estado de conservación, Las manifestaciones culturales, festividades y la artesanía se desarrollan periódicamente pero no son aprovechadas turísticamente, Se determinó que existe un marco normativo para tales bienes y No existen propuestas actuales referentes a estos bienes. Se reflejó el interés de los sectores institucional y privado para la incorporación de estos bienes a la oferta turística del Municipio y del Estado

  11. APOSTILLAS ACERCA DEL POSTRABAJO

    Directory of Open Access Journals (Sweden)

    Arturo Torrecilla

    2000-01-01

    Full Text Available El más reciente debate en torno al postrabajo transforma la herencia de los dos ciclos que le precedieron desde los años setenta. El primero se correspondía con la crítica de la división social y técnica de labores informada por una filosofía de la alienación o bien por una rectificación de la arquitectónica marxista pero salvaguardando la promesa laborista del buen trabajo. El segundo ciclo hacía eco del rechazo a las cadenas de montaje fordistas y se abría al horizonte de la abolición del trabajo salarial, manteniendo sin embargo el abolengo del sujeto unitario de la historia. La presente escena asume una densidad mayor, producto del encuentro entre las nuevas tecnologías informacionales, las discusiones en el ámbito de la sociología y la antropología, de la tecnología y la ciencia, junto al dueto que inaugura el posmodernismo.

  12. Apostillas acerca del postrabajo

    Directory of Open Access Journals (Sweden)

    Arturo Torrecilla

    2000-04-01

    Full Text Available El más reciente debate en torno al postrabajo transforma la herencia de los dos ciclos que le precedieron desde los años setenta. El primero se correspondía con la crítica de la división social y técnica de labores informada por una filosofía de la alienación o bien por una rectificación de la arquitectónica marxista pero salvaguardando la promesa laborista del buen trabajo. El segundo ciclo hacía eco del rechazo a las cadenas de montaje fordistas y se abría al horizonte de la abolición del trabajo salarial, manteniendo sin embargo el abolengo del sujeto unitario de la historia. La presente escena asume una densidad mayor, producto del encuentro entre las nuevas tecnologías informacionales, las discusiones en el ámbito de la sociología y la antropología, de la tecnología y la ciencia, junto al dueto que inaugura el posmodernismo.

  13. La universidad del futuro

    Directory of Open Access Journals (Sweden)

    FERNANDO SANCÉN CONTRERAS

    2013-01-01

    Full Text Available El trabajo señala la necesidad de reconstruir la Universidad, dado el dinamismo que muestra la ciencia y la sociedad, pues trae consigo cambios sustanciales en la visión del mundo y en el aumento del poder del hombre sobre la naturaleza. Se analizan los supuestos epistemológicos de la universidad tradicional y se propone una nueva explicación del conocimiento humano, enfatizando el conocimiento científico. Postula una docencia fundada en las propiedades de la ciencia, cuyo método inductivo basado en los paradigmas vigentes: analítico, crítico, pragmático, ofrece una herramienta para la docencia, la investigación y la difusión de la cultura. Se propone una educación centrada en el sujeto que se hace a sí mismo (etopoiética y que insiste en el proceso de auto-creación del individuo y de la sociedad.

  14. Significado presente del CSIC

    Directory of Open Access Journals (Sweden)

    Garrido Gallardo, Miguel Angel

    2000-05-01

    Full Text Available Not available

    Este artículo, elaborado en 1999, ofrece una panorámica de la realidad del Consejo Superior de Investigaciones Científicas en la actualidad. Repasa su organización, su volumen de publicaciones, sus indicadores de productividad, su capacidad de obtener recursos y, en suma, su lugar en el conjunto del sistema español de Ciencia y Tecnología, considerado en sí mismo y en relación con la Universidad. Como conclusión del repaso de datos, se afirma que, aunque la fórmula del CSIC, como organismo nacional e interdisciplinario, no es la única posible, la organización del Estado de las Autonomías, así como la evaluación de los datos con que se cuenta, la hacen vivamente recomendable. No hay, pues, sino que seguir con su desarrollo.

  15. Dalt del tren

    Directory of Open Access Journals (Sweden)

    Jaume Subirana

    2001-11-01

    Full Text Available Ens consta que la saviesa popular hi toca més del que a aquest temps d’enquestes, telèfons mòbils i targetes de crèdit li ve de gust admetre, per això em fa gràcia, en veure la pausada però continuada intrusió de la cultura catalana a Internet, recordar les cançons de quan era petit: “Dalt del tren, tots anem-hi dalt del tren, hi ha lloc per tota la gent”, dèiem, i “El tren pinxo de Banyoles és el més bonic que hi ha, ple de llaunes i cassoles i barrets de capellà”. I resulta que per una vegada a la vida hem pujat, efectivament, dalt del tren que passava per l’estació de Catalunya i en cinc anys hem passat de gairebé res a prou pàgines amb un contingut, a més, apreciable i, sobretot, a un petit teixit de persones i institucions que han entès la importància de la revolució comunicativa que Internet representa i que hi teixeixen i projecten webs amb el convenciment dels conversos.

  16. Las carreras del futuro

    Directory of Open Access Journals (Sweden)

    Luis Piscoya Hermoza

    2011-07-01

    Full Text Available La primera década del siglo XXI ha estado signada por un énfasis en los estudiosde prospectiva, los mismos que, a partir de procesos de complejizacióny articulación de la sociedad planetaria como son la digitalización, el progresivodeterioro del medio ambiente, la necesidad del cambio de la matriz energéticay la globalización del mercado, han ensayado hipótesis para identificar lastendencias que se fortalecerán y profundizarán durante las próximas décadas.Desde el punto de vista metodológico, existen muchas maneras de clasificarlaspara conceptualizarlas y entenderlas mejor. Sin embargo, considerando lanaturaleza de esta edición nos proponemos enfocar directamente aquellas queestán estrechamente ligadas a la formación universitaria.Naturalmente, no pensamos que estamos ante tendencias inevitables en lamedida que epistemológicamente la creencia en leyes históricas deterministases insostenible y la práctica social nos muestra que la construcción del futuroes nuestra responsabilidad y siempre rebasa las mejores previsiones.

  17. Observaciones del CH interestelar y el continuo en 3,3 GHz

    Science.gov (United States)

    Olano, C. A.; Combi, J. A.; Pöppel, W.; Benaglia, P.; Sanz, A. J.; Bava, J. A.

    Se informa sobre el proyecto que se lleva a cabo en el IAR con el propósito de observar las líneas hiperfinas del estado fundamental del CH y el continuo en la banda de 3,3 GHz. El nuevo receptor construído en nuestro laboratorio para tal fin se instaló sobre uno de los radiotelescopios, funcionando conjuntamente con los sistemas de procesamiento actuales del IAR. Los resultados de las primeras observaciones, realizadas tanto en las líneas espectrales como en el continuo sobre fuentes conocidas, fueron satisfactorios.

  18. Componente Cultura del Agua del PMGRH: plan de trabajo

    OpenAIRE

    Autoridad Nacional del Agua; Proyecto de Modernización de la Gestión de Recursos Hídricos

    2012-01-01

    Describe el plan de trabajo del Componente Cultura del Agua del Proyecto de Modernización de la Gestión de Recursos Hídricos (PMGRH) en relacion a dos aspectos estructurales del proyecto: 1. Mejora de la capacidad de la Gestión Integrada de Recursos Hídricos (GIRH) a nivel nacional y 2. Fortalecimiento de las capacidades de GIRH en las cuencas.

  19. En busca del concepto de gerencia del cuidado

    Directory of Open Access Journals (Sweden)

    Ligia Teresa Mora-Delgado

    2005-12-01

    Full Text Available Este articulo, presenta los conceptos de gerencia del cuidado de enfermería, desarrollado por las enfermeras profesionales que laboran en le Empresa social del estado Hospital Universitario Erasmo Meoz de las Ciudad de Cúcuta, desde su desempeño en la asistencia, administración y docencia. Se pretende además precisar los elementos gerenciales, sociales, humanísticos y éticos que deben hacer parte del concepto de gerencia del cuidado.

  20. LA PERSISTENCIA DEL SUBALTERNO

    Directory of Open Access Journals (Sweden)

    John Beverley

    2002-01-01

    Full Text Available Este trabajo es el texto literal de una ponencia presentada en un panel sobre los estudios culturales latinoamericanos en el congreso de LASA en 2001 en Washington DC. Representa la posición desarrollada en el trabajo colectivo del llamado Grupo de Estudios Subalternos Latinoamericano, desde nuestra fundación en 1992 hasta la disolución del grupo en 2001, que sirve como pretexto introductorio para la ponencia. Los otros participantes en el panel eran Walter Mignolo, representando los estudios poscoloniales, Néstor García Canclini y John Kraniauskas, representando los estudios culturales, y Nelly Richard representando la llamada crítica cultural. El trabajo dialoga y debate con cada una de estas posiciones respectivamente desde el punto de vista específico de los estudios subalternos. Concluye con un llamado a una crítica del saber académico en sí.

  1. Acalasia. Controversias del tratamiento

    OpenAIRE

    Restrepo P, Antonio J; Rey T, Mario H; Garzón O, Martín A; Farfán Q, Yesid A; Molano V, Juan C; Marulanda, Juan C; Lizarazo, Jorge I

    2007-01-01

    La acalasia es un desorden motor del esófago caracterizado por pérdida de la peristalsis esofágica con falta en la relajación o relajación incompleta del esfínter esofágico inferior (EEI) (1). La causa exacta de este trastorno es desconocida. Los síntomas más comunes son disfagia, regurgitación, pérdida de peso y dolor torácico (2). La manometría esofágica es el principal método diagnóstico, mostrando aperistalsis del cuerpo esofágico con aumento de la presión, falta de relajación o relajació...

  2. Procedimiento Del Triple Fin

    Directory of Open Access Journals (Sweden)

    Oscar L. Bellido Aguilera

    2008-01-01

    Full Text Available Presenta un procedimiento novedoso basado en un método dialéctico - sistémico - integrador, que facilita la precisión de los fines u objetivos más generales de un proceso de desarrollo comunitario o de otros procesos de cambio deseados (un proyecto sociocultural, una investigación social, un proceso de mejoramiento organizacional, etc.. Su importancia radica en que los fines, según Marx, son una guía que rige como una ley la actuación del hombre y determinarlos es parte esencial del planeamiento del cambio. Se trata de un asunto aparentemente simple, sin embargo, en la práctica es mucho más problemático de lo que comúnmente se cree.

  3. Mente, cultura y teoría: aproximaciones a la psicología del arte

    OpenAIRE

    Pazos-López, Ángel

    2014-01-01

    El presente artículo es una revisión crítica de las relaciones entre la Historia del Arte y el campo de la Psicología, acotándose el territorio que se ha denominado "Psicología del Arte", dedicado al estudio del arte como producto de la mente humana desde la visión del creador, el receptor y el objeto artístico. El estudio de las ideas que están detrás de las producciones artísticas, o de la sociedad que las descifra y conserva, ha pasado por distintas etapas de desarrollo desde finales del s...

  4. Mente, cultura y teoría: aproximaciones a la Psicología del Arte

    OpenAIRE

    Pazos-López, Ángel

    2014-01-01

    El presente artículo es una revisión crítica de las relaciones entre la Historia del Arte y el campo de la Psicología, acotándose el territorio que se ha denominado "Psicología del Arte", dedicado al estudio del arte como producto de la mente humana desde la visión del creador, el receptor y el objeto artístico. El estudio de las ideas que están detrás de las producciones artísticas, o de la sociedad que las descifra y conserva, ha pasado por distintas etapas de desarrollo desde finales del s...

  5. Efecto del silicio y plaguicidas en la fertilidad del suelo y rendimiento del arroz

    OpenAIRE

    Furcal-Beriguete, Parménides; Herrera-Barrantes, Alejandra

    2013-01-01

    Efecto del silicio y plaguicidas en la fertilidad del suelo y rendimiento del arroz. El objetivo de este trabajo fue evaluar el efecto del silicio en la fertilidad del suelo, la incidencia de enfermedades y plagas insectiles, el rendimiento y la calidad de granos del cultivo de arroz. El estudio se realizó en La Vega, Florencia, San Carlos, Costa Rica entre mayo y octubre en los años 2010 y 2011, en el mismo lote con la variedad CR 4477. Se establecieron cinco tratamientos: silicio al suelo, ...

  6. Storia del pensiero matematico

    CERN Document Server

    Kline, Morris

    1999-01-01

    Costruita con l'intento di presentare le idee oltre ai protagonisti della matematica, questa storia ha il duplice pregio dell'esaustività e della chiarezza. Essa prevede infatti vari livelli di lettura: lo specialista vi trova una messe di dati, fonti e spunti di ricerca, mentre lo studente ha a disposizione un formidabile strumento di consultazione e sintesi. L'arco temporale coperto è vasto: dalla Mesopotamia a Euclide, da Fibonacci all'invenzione del calcolo infinitesimale, da Gauss a Poincare, con un'appendice dedicata agli sviluppi piu recenti scritta appositamente per la prima edizione italiana del 1991, nei «Manuali» Einaudi.

  7. La escritura del quechua

    OpenAIRE

    Authier, Martine du

    2015-01-01

    La mayor fantasía ha acompañado siempre la transcripción del quechua. El primer intento de sistematización fue el sistema de la Paz, en 1953. Sin embargo, no existe en el comercio un diccionario satisfactorio en lo que se refiere al quechua del Cusco y, prácticamente, nada se edita en quechua, fuera de algunos trabajos antropológicos bilingües. Bajo la égida de la UNESCO, la Academia Peruana de la Lengua Quechua, que tiene su sede en el Cusco, ha colaborado en un diccionario de doce de los tr...

  8. El lenguaje del cerebro

    Directory of Open Access Journals (Sweden)

    Antonio Ibáñez Molina

    2011-04-01

    Full Text Available La introducción de nuevas técnicas de análisis de ritmos EEG en estudio de la comprensión del lenguaje permite explorar esta habilidad humana desde una perspectiva de integración de grupos de redes neuronales. Los ritmos de disparo neuronal que generan estos grupos pueden conectarse por sincronía formando unidades funcionales transitorias distribuidas en diversas áreas del cerebro. En esta revisión comentamos algunos de estos ritmos y su relación con el lenguaje.

  9. Plasticidad del sistema nervioso

    Directory of Open Access Journals (Sweden)

    L. M. Garcia-Segura

    1976-06-01

    Full Text Available En este trabajo se revisan los conocimientos más recientes sobre el fenómeno de la plasticidad del sistéma nervioso, tanto a nivel morfológico como a nivel fisiológico y molecular. Se estudian los cambios morfólogicos y fisiológicos de las neuronas frente a la experiencia. Tambien se considera la adaptación molecular del sistéma nervioso a la información que recibe como la base de todo tipo de plasticidad.

  10. Las causas del desempleo

    OpenAIRE

    García Balbás, Salomé

    2014-01-01

    En este documento vamos a tratar de dar respuesta a la siguiente pregunta: ¿cuáles son las causas del desempleo? Para ello realizaremos un repaso de las principales teorías económicas del desempleo llegando a la conclusión de que existe una causa fundamental que lo genera: la rigidez de los salarios a la baja. Consideramos el desempleo como la existencia de un exceso de oferta en el mercado de trabajo y haremos alusión, únicamente, a la existencia de desempleo involuntario. La exposición de l...

  11. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  12. Inventario del Archivo del conde de Bornos

    Directory of Open Access Journals (Sweden)

    Pedro Antonio Porras Arboledas

    1995-01-01

    Full Text Available Mi primer contacto con esta Casa se remonta a algunos años atrás, cuando me Mamó la atención un documento muy interesante, publicado a comienzos del presente siglo por el ilustre erudito ubetense don Alfredo Cazaban, por el que los Reyes Católicos hacían merced a su secretario y jefe de la artillería real durante la Guerra contra Granada, Francisco Ramírez de Madrid, personaje madrileño de origen cántabro, de una heredad en término de Jaén —el cortijo de Bornos— por sus grandes esfuerzos en la conquista de las plazas, hasta el momento inexpugnables, de Cambil y Alhabar. Posteriormente, al realizar un estudio sobre el régimen señorial en el Reino de Jaén, intenté localizar los archivos de las diferentes casas nobiliarias asentadas en esta provincia, gracias a lo cual pude saber que la documentación del Condado de Bornos se hallaba en Madrid, bien en la Biblioteca Nacional o en el Archivo Histórico, ya que el actual Conde, el Excmo. Sr. Don Ignacio Ramírez de Haro, así me lo comunicó en marzo de 1983.

  13. Combination of roflumilast with a beta-2 adrenergic receptor agonist inhibits proinflammatory and profibrotic mediator release from human lung fibroblasts

    Directory of Open Access Journals (Sweden)

    Tannheimer Stacey L

    2012-03-01

    Full Text Available Abstract Background Small airway narrowing is an important pathology which impacts lung function in chronic obstructive pulmonary disease (COPD. The accumulation of fibroblasts and myofibroblasts contribute to inflammation, remodeling and fibrosis by production and release of mediators such as cytokines, profibrotic factors and extracellular matrix proteins. This study investigated the effects of the phosphodiesterase 4 inhibitor roflumilast, combined with the long acting β2 adrenergic agonist indacaterol, both approved therapeutics for COPD, on fibroblast functions that contribute to inflammation and airway fibrosis. Methods The effects of roflumilast and indacaterol treatment were characterized on transforming growth factor β1 (TGFβ1-treated normal human lung fibroblasts (NHLF. NHLF were evaluated for expression of the profibrotic mediators endothelin-1 (ET-1 and connective tissue growth factor (CTGF, expression of the myofibroblast marker alpha smooth muscle actin, and fibronectin (FN secretion. Tumor necrosis factor-α (TNF-α was used to induce secretion of chemokine C-X-C motif ligand 10 (CXCL10, chemokine C-C motif ligand 5 (CCL5 and granulocyte macrophage colony-stimulating factor (GM-CSF from NHLF and drug inhibition was assessed. Results Evaluation of roflumilast (1-10 μM showed no significant inhibition alone on TGFβ1-induced ET-1 and CTGF mRNA transcripts, ET-1 and FN protein production, alpha smooth muscle expression, or TNF-α-induced secretion of CXCL10, CCL5 and GM-CSF. A concentration-dependent inhibition of ET-1 and CTGF was shown with indacaterol treatment, and a submaximal concentration was chosen for combination studies. When indacaterol (0.1 nM was added to roflumilast, significant inhibition was seen on all inflammatory and fibrotic mediators evaluated, which was superior to the inhibition seen with either drug alone. Roflumilast plus indacaterol combination treatment resulted in significantly elevated phosphorylation

  14. Competencia Desarrollo del Pensamiento Creativo

    OpenAIRE

    Rodríguez, Eric; Miceli, Francisco; Tiburcio, Georgina; Gómez, Orlando

    2012-01-01

    1. ¿Qué significa la competencia Desarrollo del Pensamiento Creativo? 2. ¿Por qué es relevante que adquiera la competencia Desarrollo del Pensamiento Creativo en mi formación? 3. ¿Cómo aprendo la competencia Desarrollo del Pensamiento Creativo? 4. ¿Cómo aplico la competencia Desarrollo del Pensamiento Creativo? 5. ¿Cómo puedo autoevaluar mi competencia (con miras a un constante crecimiento)?

  15. A new and efficient culture method for porcine bone marrow-derived M1- and M2-polarized macrophages.

    Science.gov (United States)

    Gao, Jiye; Scheenstra, Maaike R; van Dijk, Albert; Veldhuizen, Edwin J A; Haagsman, Henk P

    2018-06-01

    Macrophages play an important role in the innate immune system as part of the mononuclear phagocyte system (MPS). They have a pro-inflammatory signature (M1-polarized macrophages) or anti-inflammatory signature (M2-polarized macrophages) based on expression of surface receptors and secretion of cytokines. However, very little is known about the culture of macrophages from pigs and more specific about the M1 and M2 polarization in vitro. Porcine monocytes or mononuclear bone marrow cells were used to culture M1- and M2-polarized macrophages in the presence of GM-CSF and M-CSF, respectively. Surface receptor expression was measured with flow cytometry and ELISA was used to quantify cytokine secretion in response to LPS and PAM 3 CSK 4 stimulation. Human monocyte-derived macrophages were used as control. Porcine M1- and M2-polarized macrophages were cultured best using porcine GM-CSF and murine M-CSF, respectively. Cultures from bone marrow cells resulted in a higher yield M1- and M2-polarized macrophages which were better comparable to human monocyte-derived macrophages than cultures from porcine monocytes. Porcine M1-polarized macrophages displayed the characteristic fried egg shape morphology, lower CD163 expression and low IL-10 production. Porcine M2-polarized macrophages contained the spindle-like morphology, higher CD163 expression and high IL-10 production. Porcine M1- and M2-polarized macrophages can be most efficiently cultured from mononuclear bone marrow cells using porcine GM-CSF and murine M-CSF. The new culture method facilitates more refined studies of porcine macrophages in vitro, important for both porcine and human health since pigs are increasingly used as model for translational research. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Different angiogenic phenotypes in primary and secondary glioblastomas.

    Science.gov (United States)

    Karcher, Sibylle; Steiner, Hans-Herbert; Ahmadi, Rezvan; Zoubaa, Saida; Vasvari, Gergely; Bauer, Harry; Unterberg, Andreas; Herold-Mende, Christel

    2006-05-01

    Primary and secondary glioblastomas (pGBM, sGBM) are supposed to evolve through different genetic pathways, including EGF receptor and PDGF and its receptor and thus genes that are involved in tumor-induced angiogenesis. However, whether other angiogenic cytokines are also differentially expressed in these glioblastoma subtypes is not known so far, but this knowledge might be important to optimize an antiangiogenic therapy. Therefore, we studied the expression of several angiogenic cytokines, including VEGF-A, HGF, bFGF, PDGF-AB, PDGF-BB, G-CSF and GM-CSF in pGBMs and sGBMs as well as in gliomas WHO III, the precursor lesions of sGBMs. In tumor tissues, expression of all cytokines was observed albeit with marked differences concerning intensity and distribution pattern. Quantification of the cytokines in the supernatant of 30 tissue-corresponding glioma cultures revealed a predominant expression of VEGF-A in pGBMs and significantly higher expression levels of PDGF-AB in sGBMs. HGF and bFGF were determined in nearly all tumor cultures but with no GBM subtype or malignancy-related differences. Interestingly, GM-CSF and especially G-CSF were produced less frequently by tumor cells. However, GM-CSF secretion occurred together with an increased number of simultaneously secreted cytokines and correlated with a worse patient prognosis and may thus represent a more aggressive angiogenic phenotype. Finally, we confirmed an independent contribution of each tumor-derived cytokine analyzed to tumor-induced vascularization. Our data indicate that an optimal antiangiogenic therapy may require targeting of multiple angiogenic pathways that seem to differ markedly in pGBMs and sGBMs. 2005 Wiley-Liss, Inc.

  17. Ruptura del projecte parental i disposició dels preembrions

    OpenAIRE

    Farnós Amorós, Esther

    2010-01-01

    La tesi doctoral "Ruptura del projecte parental i disposició dels preembrions" analitza els efectes del consentiment a les tècniques de reproducció assistida prestat en el marc d'un projecte parental. La tesi ofereix una resposta als conflictes que enfronten exesposos o exconvivents en relació al destí dels preembrions sobrants d'un cicle de fecundació "in vitro" iniciat durant la relació. Aquests conflictes constitueixen un grup de casos al voltant del qual no hi ha solucions legislatives qu...

  18. La equinoterapia en las distintas alteraciones del desarrollo del menor.

    OpenAIRE

    Chamorro González, Mireya

    2015-01-01

    La equinoterapia consiste en la utilización del caballo como un método terapéutico para rehabilitar a personas con discapacidad. Esta terapia es considerada una gran alternativa para aumentar el autoestima de los que sufren algún tipo de discapacidad, también a través de esta terapia se mejora y fortalece el estado emocional, así del mismo modo ayuda a mejorar la manera de desenvolverse en su entorno social. Esta terapia se realiza a través de la trasmisión del calor corporal del caballo, del...

  19. Gestión del riesgo del cambio (segunda parte)

    OpenAIRE

    Zorrilla Salgador, Juan Pablo

    2004-01-01

    Segunda parte del artículo acerca del uso de futuros sobre el tipo de cambio. Esta continuación abarca estrategias, definiciones, metodología y explicaciones sobre todo lo relacionado con el Ratio de cobertura de los futuros y la aparición del riesgo base.Segunda parte del artículo acerca del uso de futuros sobre el tipo de cambio. Esta continuación abarca estrategias, definiciones, metodología y explicaciones sobre todo lo relacionado con el Ratio de cobertura de los futuros y la aparición d...

  20. del's Proof

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 12; Issue 5. Gödel's Proof - Incompleteness Theorems. S M Srivastava. General Article Volume 12 Issue 5 May 2007 pp 71-84. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/012/05/0071-0084. Keywords.

  1. Marketing Mix del Software.

    Directory of Open Access Journals (Sweden)

    Yudith del Carmen Rodríguez Pérez

    2006-03-01

    Por ello, en este trabajo se define el concepto de producto software, se caracteriza al mismo y se exponen sus atributos de calidad. Además, se aborda la mezcla de marketing del software necesaria y diferente a la de otros productos para que este triunfe en el mercado.

  2. Gerencia del servicio

    OpenAIRE

    Nancy Peña Acosta

    1992-01-01

    Estamos en la era de la pirámide invertida donde el cliente es primero por lo que es fundamental incentivar la calidad desde abajo; hacer que el trabajador defina su misión, sienta que es parte de la compañía para que la satisfacción del negocio realizado sea de todos.

  3. El Juego del Juego

    OpenAIRE

    Carvalho, Nazaré Cristina

    2012-01-01

    DUVIGNAUD, Jean. El Juego del Juego. Santafé de Bogotá, Colômbia: Fondo de Cultura Econômica, 1997.The game gameDUVIGNAUD, Jean. The Game Game. Santafé de Bogotá, Colombia: Fondo de Cultura Econômica, 1997

  4. El helor del cuerpo

    OpenAIRE

    Sánchez-Biosca, Vicente

    1992-01-01

    Ensayo sobre las formas clásicas y modernas de la metamorfosis. En esta figura mitológica se advierte de manera privilegiada la entrada del imaginario científico, biológico y genético en el dominio de las construcciones literarias y cinematográficas.

  5. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Luis Eladio Proaño

    2014-12-01

    Full Text Available La publicación se centra en temas como: Procesos electorales en México e Italia, se analizan los procesos comunicacionales y sus efectos; las infiltraciones de las agencias de seguridad en la actividad periodística en Europa; la radio y la televisión pública en los EE.UU. Para conocer cómo la prensa enfrenta los problemas críticos entre países, esta el caso de Uruguay y Argentina (discrepancia por la planta de procesamiento de papel y la contaminación del Río de La Plata. Otro artículo refiere la difícil relación entre los medios de comunicación y el gobierno de Chávez en Venezuela. Se aborda el caso brasileño para entender el crecimiento de los Observatorios de Medios; otro sobre el crecimiento del "periodismo confidencial" en la web y la prensa gratuita. Se estudia el impacto de la telenovela "pasión de gavilanes". Para quienes interese la penetración del Internet está: "Usos y competencias del weblog en las corporaciones" más otro sobre la lucha sorda que mantienen los gigantes de la autopista de la información Google y Yahoo.

  6. Punctualizaciones del CERN

    CERN Multimedia

    2002-01-01

    "Viene de la pagina anterior. Puntualizaciones del CERN. La valoracion que me merece la aprobacion en el Consejo de Ministros el 24 de mayo de un acuerdo de colaboracion entre el MCYT y el CERN para el proyecto de neutrinos al Gran Sasso es positiva" (1 page).

  7. Software del sistema osteomioarticular

    Directory of Open Access Journals (Sweden)

    Dianelys León Medina

    2015-06-01

    Full Text Available Introducción: la aplicación en la enseñanza de las Tecnologías de la Informática y las Comunicaciones, es una de las líneas que ha trazado el sistema de salud cubano en estudiantes de las ciencias médicas. La anatomía es una de las ciencias que integra la disciplina de Morfofisiología y para facilitar su comprensión resulta necesario el empleo de recursos y estrategias, entre los que puede figurar un software educativo. Objetivo: diseñar un software sobre la anatomía del sistema osteomioarticular de cabeza y cuello para los estudiantes de primer año de la carrera de Estomatología de Pinar del Río. Material y método: se realizó un estudio cualitativo. Para obtener los resultados se utilizó el método materialista dialéctico. Para la dialéctica del desarrollo del proceso estudiado se utilizaron los métodos teóricos, empíricos, el estudio profundo del tema, tipo de plataforma a utilizar y criterios de los especialistas. Para su procesamiento se utilizaron técnicas estadísticas descriptivas e inferenciales no paramétricas. Resultados: debido a la necesidad de fortalecer en los estudiantes las habilidades en la utilización de las tecnologías de la informática y las comunicaciones, se elaboró el software de la anatomía del sistema osteomioarticular de cabeza y cuello "Aprendiendo anatomía" mediante imágenes, videos y textos. Conclusiones: el software constituye un aporte al proceso enseñanza aprendizaje, el cual facilita el trabajo independiente y autopreparación mediante la interactividad con el contenido, retroalimentación y evaluación utilizando medios de enseñanza modernos, lo cual tributa al modo de actuación del futuro egresado.

  8. Historia deldel = History of Padel

    Directory of Open Access Journals (Sweden)

    Bernardino Javier Sánchez-Alcaraz Martínez

    2013-10-01

    Full Text Available El presente trabajo resume la historia del deporte deldel. Existen dos versiones sobre el origen deldel. La primera versión relaciona los antecedentes deldel con los de otros deportes de raqueta como el tenis o el bádminton, siendo su origen común el jeu de la paume francés. Posteriormente, surgen variantes en Estados Unidos como el Paddle Tennis y el Platform Tennis, siendo versiones reducidas del tenis, pero con elementos muy comunes al pádel actual. La segunda versión, aprobada por la Federación Internacional de Pádel, afirma que este deporte nació en México, en 1969, a través del empresario Enrique Corcuera.--------------------------------------------------------------------This research summarizes the history of paddle sport. There are two versions about the origin of paddle. The first version relates the history of paddle with other racket sports like tennis or badminton, and its common origin of the Jeu de Paume French. Later, in in the United States, appear two sports called Paddle Tennis and Platform Tennis, which are reduced versions of tennis sport, but these have lot of common characteristics with paddle. The second version, approved by the International Padel Federation, said the sport was born in Mexico in 1969, through the businessman Enrique Corcuera.

  9. Determinantes del ingreso y del gasto corriente de los hogares

    Directory of Open Access Journals (Sweden)

    Muñoz C., Manuel

    2004-06-01

    Full Text Available Este ensayo de investigación empírica analiza los determinantes del ingreso y del gasto en los hogares colombianos. Utilizando un modelo del ciclo de vida con datos de la encuesta de hogares de 1994 y 1995, muestra que el comportamiento del ingreso está afectado principalmente por las características demográficas del hogar y los rasgos socio ocupacionales de sus miembros. El comportamiento del gasto está determinado ante todo por el ingreso y, en menor medida, por las características sociales del hogar y el gasto de otros hogares con características similares. También examina la influencia de la incertidumbre acerca de los ingresos en el gasto de los hogares para comprobar si estos actúan con motivos de precaución.

  10. La pluridimensionalidad del rol del docente hospitalario

    Directory of Open Access Journals (Sweden)

    Marian Serradas Fonseca

    2015-07-01

    Full Text Available Este trabajo es el fruto de la observación y la investigación en la trayectoria personal y profesional de la autora dedicada a la educación de niños y niñas en situación de enfermedad u hospitalización. El objetivo de este ensayo es intentar definir de manera específica, el papel, tareas y competencias que el profesional del ámbito educativo tiene en la atención educativa hospitalaria; haciendo especial énfasis en la importancia de la formación de este profesional abogándose por una preparación que permita brindar una atención educativa de calidad a los niños y niñas en situación de enfermedad u hospitalizados.

  11. Functional responses of pre- and postsynaptic dopamine D2 receptors in rat brain striatum

    OpenAIRE

    Ma, Guofen

    2014-01-01

    El sistema dopaminèrgic has estat molt estudiat en els darrers anys, principalment degut a la seva implicació en diverses patologies com la malaltia de Parkinson, la esquizofrènia o la síndrome de Tourette, així com també en l'abús de drogues. S'han descrit cinc subtipus de receptors per la dopamina (DA), tots els quals pertanyen a la família de receptors acoblats a proteïnes G (GPCRs). D'aquests cinc subtipus, els receptors D2 son la diana principal dels antipsicòtics (antagonistes) i també ...

  12. ABC del Ajedrez. I

    Directory of Open Access Journals (Sweden)

    Marisel Piñeiro Gomez

    2009-03-01

    Full Text Available La promoción del Ajedrez, su conocimiento y práctica por la población constituye uno de los programas de la Revolución, por tal motivo el presente trabajo está encaminado a proponer un material bibliográfico con variadas posiciones sobre el movimiento-captura de las piezas y los sistemas de notación para los masificadores de Ajedrez del municipio Pinar del Río. En esta investigación se utilizaron variados métodos: teóricos, empíricos y estadísticos, además, como método rector el dialéctico materialista. Constituye una novedad científica porque aporta un material bibliográfico que contiene: la composición,  disposición  e  identificación  del  tablero de  ajedrez;  identificación, colocación, movimiento y captura de las piezas de ajedrez; la promoción del Peón; el valor absoluto de las piezas; los sistemas de notación: descriptivo y algebraico. Se le incluyen más de trescientos gráficos, conceptos que son trabajados de lo simple a lo complejo de manera tal que el masificador de Ajedrez lo utilice en sus clases donde se viabilice el conocimiento gracias a las facilidades que le aporta el material; ofrece algoritmos que le guiarán a elaborar nuevas posiciones, los cuales son inexistentes para este propósito en otras bibliografías; su significación práctica radica en que proporciona, tanto al estudiantado como profesorado, ejercicios de ajedrez sencillos que les permitirá a los primeros para que les sirva en su comportamiento, y a los segundos utilizarlos en su auto preparación; el interés social se halla en que pueden ser utilizados por profesores, personal de apoyo a la docencia,  técnicos  del  INDER,  familiares  de  los  estudiantes  para  ayudarlos;  el interés educativo reside en que a través de esos ejercicios contribuimos al fortalecimiento de valores.

  13. Arco del milenio

    Directory of Open Access Journals (Sweden)

    Adell, Josep Mª

    2005-02-01

    the most significant stages in the erection of the Millennium Arch outside the Palacio de Congresos, venue for the 12th IBMAC.
    These pictures are divided into six chapters: Background, Components, Springline, Piers, Arch, Centring Erection and Removal, and Trimming.

    A lo largo de la historia, el Arco de fábrica ha sido el componente constructivo más característico de la Arquitectura y la Ingeniería desde que después de sus inicios etruscos en la época romana fuera desarrollado adelantándose con ello a la cultura helénica.
    El Arco, desde entonces, viene empleándose como una solución constructiva eficiente para cubrir espacios con materiales que no soportan tracciones. La originalidad técnica del Arco lo ha llevado a imponerse como símbolo de las hazañas bélicas como era el Arco de Triunfo.
    En el cambio de siglo y milenio en el que nos encontramos, un salto técnico fundamental se desvela en este Congreso, el Sistema de Albañilería Integral, que abre la posibilidad de ampliar el campo de aplicación de la albañilería con la incorporación del acero, a través de las perforaciones de las piezas, lográndose por fin armar en las tres direcciones del espacio cualquier muro de fábrica que se desee.
    El Arco del Milenio conmemoró el 12th IBMAC de Madrid, mostrando en él los avances técnicos que el Sistema de Albañilería Integral permite, al tratarse de un arco inclinado en el espacio y, por tanto, el primer arco de fábrica construido fuera de la vertical, mediante fábrica de Ladriflor aparejada a tizón, reforzada con barras y cercos.
    El Arco del Milenio, diseñado por J.M. Adell (Presidente del 12th IBMAC, parte de un cilindro de 14 m de diámetro, inclinado 30º sobre el terreno, y construido con fábrica de ladrillo de un pie de grueso, alternando una hilada de color amarillo de cada seis en rojo. El hueco deja un paso libre de 10 m de lado y 5,5 m de altura. La fábrica está armada regularmente por tendeles con cerchas cada

  14. Ionotropic crustacean olfactory receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Corey

    Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  15. Determinantes del trabajo infantil y la escolaridad: el caso del Valle del Cauca en Colombia

    Directory of Open Access Journals (Sweden)

    Sebastián Urueña Abadía

    2009-10-01

    Full Text Available Colombia, al igual que la mayoría de países latinoamericanos, consciente de las repercusiones sociales y económicas negativas del trabajo infantil, se ha comprometido en la lucha por la erradicación de este fenómeno. Prueba de ello es la ratificación por parte del gobierno colombiano en el año 2007, del Convenio 182 de la OIT sobre la Prohibición de las Peores Formas de Trabajo Infantil y la Acción Inmediata para su Eliminación. En el plano regional, como parte del Plan de Desarrollo del Departamento del Valle del Cauca 2008-2011, se está implementando actualmente una estrategia territorial de erradicación del trabajo infantil en sus 42 municipios. Considerando este panorama, este trabajo indaga cuáles son los determinantes del trabajo infantil y la escolaridad en el departamento del Valle a partir de los datos de la Encuesta Nacional de Calidad de Vida del año 2003. Para el análisis se emplea un modelo econométrico Probit Bivariado, que permite el estudio conjunto e interrelacionado de decisiones diferentes, en este caso la asistencia escolar y el trabajo.

  16. En defensa del indigenismo

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Huamán

    2011-05-01

    Full Text Available El indigenismo como movimiento literario, cultural, ideológico y políticoconstituye un hito, una referencia obligada de nuestra tradición culturaly literaria nacional. Su debate no se reduce ni limita a las primerasdécadas del siglo XX, etapa privilegiada en forma recurrente en los estudiosiniciales sobre esta corriente. Podemos afirmar, sin temor a equivocarnos,que no hay momento ni periodo, más o menos visible, en elque no se haya evaluado en forma crítica este acontecimiento, el mismoque ha resurgido con otras denominaciones o referencias (regionalismo,andinismo, mariateguismo, humalismo, etc., a lo largo de nuestro procesohistórico, pero imbuidas de la perspectiva inicial. El propósito deeste artículo es hacer una defensa del indigenismo contestando algunasposiciones contrarias como la de Mirko Lauer.

  17. RESPONSABILIDAD DEL ODONTOPEDIATRA

    OpenAIRE

    Guillen B., Celso

    2014-01-01

    La Responsabilidad de la atención del niño, requiere de una formación y preparación universitaria de la Segunda Especialidad en Odontopediatría para manejar organismos en proceso de crecimiento somático y psicológico. Es por eso que con el proceso de la ciencia se ha comprendido la importancia de la atención del niño desde que nace. Es así que se ha creado sistemas integrales de atención odontopediátrica durante los primeros años de vida, debido a la alta vulnerabilidad de contraer las enferm...

  18. Responsabilidad Constitucional del Gobierno

    Directory of Open Access Journals (Sweden)

    Francisco Zúñiga Urbina

    2006-01-01

    Full Text Available El artículo analiza la responsabilidad constitucional del Gobierno y sostiene que es jurídico-política, de lejano cuño penal y administrativo, y el procedimiento empleado para hacerla efectiva es la acusación en juicio político, que es un típico caso de "justicia política". A la responsabilidad constitucional se suman las responsabilidades civil y penal de Derecho Público del Presidente de la República y sus ministrosThis paper analyses constitutional responsibility of the government and sustains that it is political and juridical, of distant penal and administrative inspiration, and that the procedure used for persecution is impeachment in political trials, demonstrating a typical case of "political justice." Added to the constitutional responsibility of the government are the civil and penal responsibilities of the President and minister's public law

  19. Infecciones del tracto urinario

    Directory of Open Access Journals (Sweden)

    K. Andrés Wurgaft, Dr.

    2010-07-01

    Full Text Available La infección del tracto urinario (ITU, con sus múltiples presentaciones clínicas, está entre las enfermedades infecciosas más frecuentes, tanto en pacientes ambulatorios como hospitalizados. El uso del examen de orina completa y de urocultivo debe ser racional. La bacteriuria asintomática no debe ser buscada ni tratada, en parte porque esto favorece el desarrollo de bacterias resistentes a antibióticos. Distintos cuadros clínicos requieren de distintas duraciones de terapia antibiótica, y tanto el exceso de días de tratamiento como su falta deben evitarse. Se requiere investigación en la búsqueda de estrategias más efectivas para prevenir las ITU recurrentes y en el desarrollo de nuevos antibióticos orales para las ITU resistentes.

  20. Las cruces del olvido

    Directory of Open Access Journals (Sweden)

    Carla Fernandes

    2012-08-01

    Full Text Available Les tragiques événements du « mars paraguayen » ont signifié la disparition de l’espoir en la transition démocratique dans laquelle le pays s’était engagé depuis presque une dizaine d’années. Renée Ferrer, poète, dramaturge, auteur de plusieurs recueils de contes et de deux romans, consigne alors le témoignage poétique de ce drame national dans le recueil Las cruces del olvido (2001. Elle a auparavant publié d’autres textes qui peuvent rentrer dans la catégorie de la poésie sociale : c’est le cas en particulier de Viaje a destiempo (1989 dédié aux victimes de la dictature. Las cruces del olvido, dès son paratexte, insiste sur la fonction de témoignage que l’auteur souhaite assigner à ses vers et sur le rôle que ceux-ci peuvent jouer dans la transmission d’une mémoire collective. La voix d’un jeune disparu de ce « mars paraguayen », le dédoublement qu’il subit et travers lequel il évoque son entrée dans la mort et son absence du monde des vivants, rendent possible l’écriture de cette expérience de l’indicible qu’est la disparition.Los trágicos acontecimientos del «marzo paraguayo» significaron la desaparición de la esperanza en la transición democrática que el país está viviendo desde unos diez años. Renée Ferrer, poeta, dramaturga, autora de varios libros de cuentos y de dos novelas, escribe entonces el testimonio poético de ese drama nacional en su poemario Las cruces del olvido (2001. Ya había publicado antes textos que se pueden considerar como poesía social: es el caso de Viaje a destiempo (1989 dedicado a las víctimas de la dictadura. Desde el texto apertural, Las cruces del olvido potencia la función de testimonio que la autora desea conceder a sus versos y el papel que éstos pueden desempeñar en la transmisión de una memoria colectiva. La voz de un joven desaparecido del «marzo paraguayo», el desdoblamiento que sufre y a través del cual evoca su entrada en la

  1. Carta del editor

    Directory of Open Access Journals (Sweden)

    José Sánchez Gutiérrez

    2018-01-01

    Full Text Available La comunicación científica en México vive enormes retos ante la carrera de adaptar sus formas de comunicación a las nuevas tecnologías. No es tarea fácil convencerse de abandonar el papel y la imprenta para apostar por el código abierto. Sin embargo, esto es apremiante debido al retraso que se lleva en comparación con otras regiones.  Un reto muy evidente ha sido comprender el acceso abierto, reconociendo que este permite mayor visibilidad a la ciencia y que ayuda a evitar el plagio.  Razón por la que nos alegra que a partir del número 37, Mercados y Negocios cuenta con el ISSN electrónico, además del impreso

  2. Carta del Editor

    OpenAIRE

    Luis Eladio Proaño

    2015-01-01

    Henos aquí con un nuevo número de RIESED. Después de casi un año de ver la luz, y como lo anticipábamos en la carta del editor que acompañaba al número fundacional, hacer una revista electrónica no ha sido una tarea sencilla. Un año más tarde no podemos sino confirmar esa opinión.Gracias al decidido trabajo de los autores, revisores y miembros del equipo editorial hemos podido hacerlo. El proceso de revisión de los artículos ha merecido un cuidado, dedicación y tiempo especiales, que hicieron...

  3. Sonidos del Silencio

    Directory of Open Access Journals (Sweden)

    Luz Rodríguez Carranza

    2009-12-01

    Full Text Available La novela ha muerto, afirmaba Alberto Moravia, popularizada, anexada y banalizada por el cine, la televisión, la prensa, la sicología y la sociología. Para Carlos Fuentes en cambio - quien cita a Moravia en 1969 – « lo que ha muerto es sólo la forma burguesa de la novela, el realismo » (17. Basta un viaje rápido por la red para verificar, sin embargo, que la víctima goza de buena salud y que no está confinada en la cultura de masas o en las ciencias sociales : el modelo realista del siglo XIX – y particularmente la creación de tipos representativos de una época, sean éstos promediales o excepcionales - constituye aún la principal preocupación de los escritores y críticos literarios del siglo XXI.

  4. del consumidor mexicano

    Directory of Open Access Journals (Sweden)

    Nadia Huitzilin Jiménez Torres

    2013-01-01

    Full Text Available Pese a que el 80% de la población del mundo vive en mercados emergentes y países en desarrollo, como México, la investigación sobre el consumidor de estos países ha sido insuficiente. El objetivo de este estudio es determinar el perfil del consumidor mexicano en función de variables psicosociológicas como el etnocentrismo, la apertura cultural, el patriotismo, el colectivismo y las características demográficas. Con este propósito se recogió la información de una muestra de 274 consumidores, se realizaron un análisis factorial de sus principales componentes y un análisis cluster con el cual se aglomeró a los individuos en tres grupos con diferentes perfiles psicosociológicos y demográficos.

  5. del noroeste murciano

    Directory of Open Access Journals (Sweden)

    Ma. Luz Tudela Serrano

    2006-01-01

    Full Text Available En la Región de Murcia se está realizando un esfuerzo por aumentar la producción de energías renovables en cumplimiento de los objetivos de Kyoto establecidos para España. Paralelamente, la percepción social acerca de las mismas preocupa cada vez más. En este trabajo, los ciudadanos opinan ante la necesidad de promover el uso e implantación de energías renovables en varias poblaciones afectadas del noroeste. Emplazamientos idóneos, la conservación de los valores naturales y paisajísticos del entorno y las necesidades socioeconómicas de la zona se suman a un uso racional de estas energías y un desarrollo tecnológico paralelo para alcanzar un desarrollo sostenible.

  6. Lo siniestro del enigma.

    Directory of Open Access Journals (Sweden)

    Victoria Eugenia Diaz.

    1999-11-01

    Full Text Available En "El nacimiento de la filosofía griega", Giorgio Colli nos muestra una faceta tenebrosa del enigma. El dios Apolo, de naturaleza ilimitada, insondable, caprichosa, plantea al hombre enigmas que lo enfrentan con el sufrimiento y con la muerte. Allí, Edipo se confronta con enigmas enviados por el dios en los que se pone en juego su propia existencia. Tiempo después, en el transcurrir del siglo XX, reaparece una nueva forma de este dios arbitrario y arrogante: el desaparecedor de personas, ese inmoderado que impone moderación, borra con su acto un cuerpo, una imagen, un nombre, y formula un nuevo enigma siniestro que enfrenta otra vez al hombre con el dolor y con la muerte.

  7. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Luis Eladio Proaño

    2015-01-01

    Full Text Available El aparecimiento del periodista digital y la educación superior en su formación, el cine indígena y la resistencia cultural, más los Grammy latinos, son temas protagónicos de este número. Se suman la prensa en el combate de piráticas corruptas, los errores de la comunicación del presidente URIBE en el referendo, el fútbol y las Relaciones Públicas en España, la libertad de prensa encarcelada, el Internet y la sociedad de la Información y México: profesiones emergentes para los comunicadores, completan la edición.

  8. Percepcion multisensorial del sabor

    Directory of Open Access Journals (Sweden)

    Charles Spence

    2010-12-01

    Full Text Available La investigación sobre la integración multisensorial de los estímulos auditivos, visuales y táctiles nos está ayudando a entender el funcionamiento de la percepción del sabor. Este conocimiento está teniendo ya un impacto sobre el diseño de alimentos y bebidas, desde los productos que compramos en un supermercado hasta aquellos que encontramos en los restaurantes con estrellas Michelin.

  9. Estado Nutricional del Yodo.

    Directory of Open Access Journals (Sweden)

    Hernando Vargas Uricoechea

    2015-06-01

    Full Text Available INTRODUCCIÓN: Los Desórdenes por Deficiencia de Yodo son un problema serio de salud pública, con cerca de 2 mil millones de personas a riesgo de padecerlos, pudiendo causar bocio neonatal, cretinismo, retardo mental, hipotiroidismo, entre otros. Estos desórdenes son aún prevalentes, y en algunos casos los esfuerzos para su erradicación se han traducido en aumento del riesgo de exceso poblacional de yodo y autoinmunidad tiroidea. En Colombia, se desconoce el estado real de yodo en la población. OBJETIVOS: Determinar la mediana de la yoduría en población escolar, y de los hábitos del consumo de sal, función y parámetros de autoinmunidad tiroidea, y cociente intelectual. MATERIALES Y MÉTODOS: Estudio basado en la comunidad, de corte transversal. Se evaluaron las variables sociodemográficas, la frecuencia de bocio y los niveles de TSH, anti-TPO, anti-Tg, anti-TSHR, yoduria, test de factor G de Cattell, y hábitos del consumo de sal. RESULTADOS: El consumo de sal promedio persona/día fue de 18,13 g. El 37,9% presentó bocio. 36,1% tenían un valor límite en el cociente intelectual. La mediana de yoduria fue de 510,3 μg/L. El 42,75% tuvo anti-TPO positivos, y el 2,87% anti-Tg positivos. El 10% presentó niveles de TSH elevados. CONCLUSIÓN: En escolares de zona urbana, hay un exceso en la mediana de yoduria, pudiendo explicarse por el alto consumo de sal. La alta prevalencia de autoinmunidad tiroidea y bocio, junto al alto nivel de la TSH, puede ser consecuencia del exceso en la ingesta de sal y de otros factores medioambientales/ hereditarios.

  10. El lenguaje del pensamiento

    Directory of Open Access Journals (Sweden)

    Alberto Andreu Marín

    2017-09-01

    Full Text Available ¿Somos capaces de interpretar las señales eléctricas que genera nuestro cerebro cuando estamos pensando? Lo que a priori parece ciencia ficción comienza a ser factible gracias a los avances recientes en técnicas de registro cerebral y en aprendizaje automático. Nos encontramos en el inicio de una nueva era en lo que al conocimiento del cerebro se refiere.

  11. Fundamentos del saber administrativo

    OpenAIRE

    Paola Podestá Correa; Juan Carlos Jurado Jurado

    2005-01-01

    El presente texto tiene por objetivo delimitar, de manera general, algunos de los conceptos más importantes del saber administrativo; en primera instancia, práctica administrativa y saber administrativo. Estos conceptos están ligados con los que en el texto se denominan fundamentos de la administración, estableciendo consensos sobre algunas expresiones comunes en el lenguaje administrativo, y contribuyendo a la comprensión de estos temas para los estudiantes de los primeros niv...

  12. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Jorge Aguirre

    2015-01-01

    Full Text Available La crisis de la prensa Argentina a efecto del mal manejo de la economía y las finanzas, ocupa el tema central. Pasa revista a tres temas de actualidad: El aumento de cobertura y difusión de la prensa gratuita; los esfuerzos de los "viejos" diarios por cambiar de apariencia y el caso del diario estadounidense TODAY que hace veinte años dio un cambio revolucionario en la forma de hacer periodismo diario. Se analizan también temas como: el "carisma" de los líderes actuales, los acuerdos entre los medios de comunicación y el gobierno de México para la difusión de planes y programas oficiales y el rol de los medios en el proceso de establecimiento del ALCA. Agrega el tema controversial sobre la Ley de radiodifusión privada, vigente desde la época de la dictadura pinochetista. En este mismo campo de la Radio otro artículo señala las normas para "contar las noticias" con impacto e interés.

  13. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Jorge Mantilla Jarrín

    2015-01-01

    Full Text Available En este número, el módulo Dibujos Animados, recoge las experiencias del primer curso realizado por el CIESPAL con apoyo de la UNICEF sobre la producción de programas educativos y culturales que utilizan este recurso como una opción comunicacional. Se trata de nuevas tecnologías aprovechadas en Cuba y que pueden ser aplicadas en nuestros países. El módulo relativo al medio ambiente habla del periodismo ecológico con importante desarrollo en América Latina, tema de actualidad que requiere preocupación por parte de los medios de comunicación. Incluye entrevistas a Gunter Grass y Jesús Polanco. Gabriel Alba adentra a los lectores en una novedosa forma de usar las computadoras. En el módulo Debate se trata la Economía, cultura y comunicación; La publicidad vía televisión, La evolución del merchandising en las novelas brasileñas ¿Exigir Ética solo al periodista?

  14. Los felinos del canciller

    Directory of Open Access Journals (Sweden)

    Marco Palacios

    1988-01-01

    Full Text Available En la introducción a una de las obras más influyentes de la historiografía colombiana de nuestros tiempos, el autor, Luis Ospina Vásquez, advierte ciertas dificultades inherentes al oficio de historiar la economía: "Otros aspectos del tema son difíciles de tratar por otros motivos: no se puede citar, entre las causas del difícil adelanto económico de cierta región nuestra, llamada por la generosidad de la naturaleza a una gran riqueza; el hecho de que en ella la política se haya reducido con frecuencia a una pugna entre grupos de hampones[...] Y en el supuesto de que se pudiera dar tratamiento adecuado a lo que, al fin y al cabo, es cosa tangible, no muy difícil de percibir y de describir, faltaría aun dar entrada a un elemento sumamente importante, pero este sí difícil de captar y de transmitir: la 'atmósfera', las 'atmósferas' sucesivas del país y sus regiones, elemento esencial en la historia de la evolución económica.

  15. El Museo del Oro

    Directory of Open Access Journals (Sweden)

    Efraín Sánchez Cabra

    2003-09-01

    Full Text Available El 22 de diciembre de 1939 el Banco de la República compró un objeto de oro de 777,7 gramos de peso y 23,5 centímetros de altura que dio origen al Museo del Oro. Era un poporo quimbaya, pieza maestra de la orfebrería prehispánica. Un objeto bello bello que levanta su bruñido vientre globular y su cuello coronado por cuatro cuerpos esféricos sobre una exquisita base de filigrana fundida, y parece flotar en un espacio propio. Quien lo contempla no puede menos que asombrarse, deleitarse y sentir admiración por sus artífices. Detrás de la compra del poporo había una clara preocupación oficial por proteger una riqueza que comenzaba a entenderse como parte del patrimonio nacional. Esta motivación se pone de manifiesto en una serie de documentos relativos a su adquisición.

  16. Llanto del adulto

    Directory of Open Access Journals (Sweden)

    Alegría Majluf

    2013-09-01

    Full Text Available Se presentan los resultados de un primer estudio transcultural del llanto del adulto que comprende 30 países, entre los que se encuentra el Perú. Vingerhoets et al. (1997 de la Universidad de Tilburg, Holanda, analizan las causas, tendencia y frecuencia del llanto, emociones y sentimientos que inducen al llanto, diferencias y similitudes entre los países y los sexos. Los autores encuentran que las mujeres tienden a llorar con más frecuencia e intensidad que los varones, advirtiendo que en algunos países las mujeres establecen mayor relación entre la tendencia al llanto y el ciclo menstrual que en otros. The results of a first cross-cultural study on adult crying in 30 countries including Peru are presented. Vingerhoets et al. (1997 from the University of Tilburg have analyzed motives, tendencies and frequency of crying, emotions and feelings that provoke crying, as well as differences and similarities among countries and sexes. Results show that women have a tendency to cry more frequently and intensively than men. It has also been noted that, in certain countries, there is a link between crying in women and their monthly period.

  17. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Luis Eladio Proaño

    2015-01-01

    Full Text Available Artículo de fondo es un ejemplo de una campaña exitosa de Relaciones Públicas realizada para rescatar a Medellín para el turismo, ahora herida de muerte por el narcotráfico. Reinicia el tema sobre el cine, recordando el aniversario del nacimiento de Luis Buñuel. Y sobre el Nuevo Orden Internacional de la Información, Luis Ramiro Beltrán da respuesta a las múltiples interrogantes planteadas en la controversia surgida alrededor del tema. Se da a conocer cómo era el periódico de ayer, de hoy y del futuro frente al desafío de las nuevas tecnologías. Se señala el camino para hacer publicidad en Internet. El Internet y la radio nuevos actores para un mismo mercado. Y para los interesados en la investigación se trata cómo y cuándo hacer sondeos flash y se cierra con el lenguaje periodístico cuándo el dequeísmo es lícito.

  18. comportamiento del consumidor

    Directory of Open Access Journals (Sweden)

    Erico Rentería Pérez

    2006-01-01

    Full Text Available En este artículo se analiza el posicionamiento exitoso de los profesionales, particularmente los jóvenes, a partir de las nuevas realidades del mundo y del mercado laboral, así como la empleabilidad como constructo, estrategias posibles y, finalmente, una discusión sobre falacias y realidades de discursos sobre mercado de trabajo profesional. La reflexión se liga a dos investigaciones, y a redes de discusión en Brasil y Colombia, que reflexionan sobre las implicaciones y requerimientos estratégicos que marcan el ingreso o permanencia en el mercado de trabajo de profesionales jóvenes, y se reconoce que esto afecta a otros tipos de profesionales. La investigación de Rentería (2006ª sobre Empleabilidad arroja información sobre las dos primeras partes. La de Enríquez y Rentería (2006 sobre Estrategias de aprendizaje y empleabilidad informa sobre la tercera. Apoyan la discusión elementos de psicología y comportamiento del consumidor. Se discute la inclusión social y calidad de vida por el trabajo.

  19. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Luis Eladio Proaño

    2015-01-01

    Full Text Available Abre la revista una retrospectiva de la crisis económica, política y social en la que se precipitó Argentina (2001-2002 y el tratamiento que dieron los medios a esta situación. En opinión se describe el significado de los nuevos paradigmas de Internet como: interactividad, personalidad, multimedialidad, hipertextualidad, actualización, abundancia y mediación. Responde a la cuestión de ¿cómo y cuándo en la prensa latinoamericana sigue imperando la prensa amarilla? Recoge en un artículo los factores que más inciden en el éxito o fracaso de una campaña política. Aborda la implantación de una nueva moneda única en la Unión Europea y sus incidencias. Destaca las consecuencias vividas por México tras el ataque terrorista del 11 de septiembre 2001 y analiza el tratamiento que los medios dan a las informaciones procedentes del Tercer Mundo en Europa. Contesta a la pregunta inquietante sobre las posibilidades del liberalismo económico para garantizar o contrarrestar la libertad de prensa y por último se aclara los mitos y realidades que se han tejido alrededor de Windows XP de Microsoft.

  20. Receptor GNSS multiantena para aplicaciones aeroespaciales

    OpenAIRE

    Cogo, Jorge; López La Valle, Ramón G.; Puga, Gerardo L.; Smidt, Javier A.; Díaz, Juan G.; García, Javier Gonzalo; Roncagliolo, Pedro Agustín; Muravchik, Carlos Horacio

    2013-01-01

    La determinación de la posición y velocidad del vehículo es una de las tareas críticas en las aplicaciones aeroespaciales como es el caso de aviones, satélites o cohetes. En los últimos años esta tarea se ha visto favorecida por el despliegue de los Sistemas de Navegación Global por Satélite (GNSS). Estos sistemas, utilizando como base una constelación de satélites que envían señales a la superficie terrestre, permiten que un usuario que cuente con un receptor adecuado pueda obtener esta info...

  1. Propofol pretreatment attenuates LPS-induced granulocyte-macrophage colony-stimulating factor production in cultured hepatocytes by suppressing MAPK/ERK activity and NF-κB translocation

    International Nuclear Information System (INIS)

    Jawan, Bruno; Kao, Y.-H.; Goto, Shigeru; Pan, M.-C.; Lin, Y.-C.; Hsu, L.-W.; Nakano, Toshiaki; Lai, C.-Y.; Sun, C.-K.; Cheng, Y.-F.; Tai, M.-H.

    2008-01-01

    Propofol (PPF), a widely used intravenous anesthetic for induction and maintenance of anesthesia during surgeries, was found to possess suppressive effect on host immunity. This study aimed at investigating whether PPF plays a modulatory role in the lipopolysaccharide (LPS)-induced inflammatory cytokine expression in a cell line of rat hepatocytes. Morphological observation and viability assay showed that PPF exhibits no cytotoxicity at concentrations up to 300 μM after 48 h incubation. Pretreatment with 100 μM PPF for 24 h prior to LPS stimulation was performed to investigate the modulatory effect on LPS-induced inflammatory gene production. The results of semi-quantitative RT-PCR demonstrated that PPF pretreatment significantly suppressed the LPS-induced toll-like receptor (TLR)-4, CD14, tumor necrosis factor (TNF)-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression. Western blotting analysis showed that PPF pretreatment potentiated the LPS-induced TLR-4 downregulation. Flow cytometrical analysis revealed that PPF pretreatment showed no modulatory effect on the LPS-upregulated CD14 expression on hepatocytes. In addition, PPF pretreatment attenuated the phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and IκBα, as well as the nuclear translocation of NF-κB primed by LPS. Moreover, addition of PD98059, a MAPK kinase inhibitor, significantly suppressed the LPS-induced NF-κB nuclear translocation and GM-CSF production, suggesting that the PPF-attenuated GM-CSF production in hepatocytes may be attributed to its suppressive effect on MAPK/ERK signaling pathway. In conclusion, PPF as an anesthetic may clinically benefit those patients who are vulnerable to sepsis by alleviating sepsis-related inflammatory response in livers

  2. Liver myeloid-derived suppressor cells expand in response to liver metastases in mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T

    Science.gov (United States)

    Burga, Rachel A.; Thorn, Mitchell; Point, Gary R.; Guha, Prajna; Nguyen, Cang T.; Licata, Lauren A.; DeMatteo, Ronald P.; Ayala, Alfred; Espat, N. Joseph; Junghans, Richard P.; Katz, Steven C.

    2015-01-01

    Chimeric antigen receptor modified T cell (CAR-T) technology, a promising immunotherapeutic tool, has not been applied specifically to treat liver metastases (LM). While CAR-T delivery to LM can be optimized by regional intrahepatic infusion, we propose that liver CD11b+Gr-1+ myeloid-derived suppressor cells (L-MDSC) will inhibit the efficacy of CAR-T in the intrahepatic space. We studied anti-CEA CAR-T in a murine model of CEA+ LM and identified mechanisms through which L-MDSC expand and inhibit CAR-T function. We established CEA+ LM in mice and studied purified L-MDSC and responses to treatment with intrahepatic anti-CEA CAR-T infusions. L-MDSC expanded three-fold in response to LM and their expansion was dependent on GM-CSF, which was produced by tumor cells. L-MDSC utilized PD-L1 to suppress anti-tumor responses through engagement of PD-1 on CAR-T. GM-CSF, in cooperation with STAT3, promoted L-MDSC PD-L1 expression. CAR-T efficacy was rescued when mice received CAR-T in combination with MDSC depletion, GM-CSF neutralization to prevent MDSC expansion, or PD-L1 blockade. As L-MDSC suppressed anti-CEA CAR-T, infusion of anti-CEA CAR-T in tandem with agents targeting L-MDSC is a rational strategy for future clinical trials. PMID:25850344

  3. β-Galactomannan and Saccharomyces cerevisiae var. boulardii modulate the immune response against Salmonella enterica serovar Typhimurium in porcine intestinal epithelial and dendritic cells.

    Science.gov (United States)

    Badia, Roger; Brufau, M Teresa; Guerrero-Zamora, Ana Maria; Lizardo, Rosil; Dobrescu, Irina; Martin-Venegas, Raquel; Ferrer, Ruth; Salmon, Henri; Martínez, Paz; Brufau, Joaquim

    2012-03-01

    Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that causes inflammation, necrosis, and diarrhea in pigs, as well as being an important source of food-borne diseases in humans. Probiotics and prebiotics are promising alternatives to antibiotics to control and prevent intestinal infections. The present work investigated a recently developed β-galactomannan (βGM) prebiotic compared to the proven probiotic Saccharomyces cerevisiae var. boulardii on porcine ileum intestinal epithelial cells (IECs) of the IPI-2I line and monocyte-derived dendritic cells (DCs) cocultured in vitro with Salmonella. We observed that both S. cerevisiae var. boulardii and βGM inhibited the association of Salmonella with IECs in vitro. Our data indicated that βGM has a higher ability than S. cerevisiae var. boulardii to inhibit Salmonella-induced proinflammatory mRNA (cytokines tumor necrosis factor alpha [TNF-α], interleukin-1α [IL-1α], IL-6, and granulocyte-macrophage colony-stimulating factor [GM-CSF] and chemokines CCL2, CCL20, and CXCL8) and at protein levels (IL-6 and CXCL8). Additionally, βGM and S. cerevisiae var. boulardii induced some effects on DCs that were not observed on IECs: βGM and S. cerevisiae var. boulardii showed slight upregulation of mRNA for TNF-α, GM-CSF, and CCR7 receptor on porcine monocyte-derived dendritic cells (DCs). Indeed, the addition of βGM or S. cerevisiae var. boulardii on DCs cocultured with Salmonella showed higher gene expression (mRNA) for TNF-α, GM-CSF, and CXCL8 compared to that of the control with Salmonella. In conclusion, the addition of βGM inhibits Salmonella-induced proinflammatory profiles in IECs but may promote DC activation, although associated molecular mechanisms remain to be elucidated.

  4. Effect of Interlukin-1β on proliferation of gastric epithelial cells in culture

    Directory of Open Access Journals (Sweden)

    Beales Ian LP

    2002-04-01

    Full Text Available Abstract Background Helicobacter pylori is the main risk factor for the development of non-cardia gastric cancer. Increased proliferation of the gastric mucosa is a feature of H. pylori infection. Mucosal interkeukin-1β production is increased in H. pylori infection and IL-1β genotypes associated with increased pro-inflammatory activity are risk factors for the development of gastric cancer. The effect of IL-1β on gastric epithelial cell proliferation has been examined in this study. Methods AGS cells were cultured with IL-1β. DNA synthesis was assed by [3H]thymidine incorporation and total viable cell numbers by MTT assay. Results IL-1β dose dependently increased DNA synthesis and cell numbers. The enhanced proliferation was blocked by interleukin-1 receptor antagonist. Addition of neutralising antibody to GM-CSF reduced IL-1β-stimulated proliferation by 31 ± 4 %. GM-CSF alone significantly stimulated proliferation. Addition or neutralisation of IL-8 had no effect on basal or IL-1β-stimulated proliferation. The tyrosine kinase inhibitor genistein completely blocked IL-1β-stimulated proliferation and inhibition of the extracellular signal related kinase pathway with PD 98059 inhibited IL-1β stimulated proliferation by 58 ± 5 %. Conclusions IL-1β stimulates proliferation in gastric epithelial cells. Autocrine stimulation by GM-CSF contributes to this proliferative response. Signalling via tyrosine kinase activity is essential to the mitogenic response to IL-1β. The extracellular signal related kinase pathway is involved in, but not essential to downstream signalling. IL-1β may contribute to the hyperproliferation seen in H. pylori- infected gastric mucosa, and be involved in the carcinogenic process.

  5. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium.

    Science.gov (United States)

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B; Behrens, Sabine; Goode, Ellen L; Bolla, Manjeet K; Dennis, Joe; Dunning, Alison M; Easton, Douglas F; Wang, Qin; Benitez, Javier; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Fasching, Peter A; Haeberle, Lothar; Peto, Julian; Dos-Santos-Silva, Isabel; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marmé, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Nielsen, Sune F; Nordestgaard, Børge G; González-Neira, Anna; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Fagerholm, Rainer; Dörk, Thilo; Bogdanova, Natalia V; Mannermaa, Arto; Hartikainen, Jaana M; Van Dijck, Laurien; Smeets, Ann; Flesch-Janys, Dieter; Eilber, Ursula; Radice, Paolo; Peterlongo, Paolo; Couch, Fergus J; Hallberg, Emily; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Schumacher, Fredrick; Simard, Jacques; Goldberg, Mark S; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Winqvist, Robert; Grip, Mervi; Andrulis, Irene L; Glendon, Gord; García-Closas, Montserrat; Figueroa, Jonine; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Eriksson, Mikael; Hall, Per; Li, Jingmei; Cox, Angela; Cross, Simon S; Pharoah, Paul D P; Shah, Mitul; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Ademuyiwa, Foluso; Ambrosone, Christine B; Swerdlow, Anthony; Jones, Michael; Chang-Claude, Jenny

    2016-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry.

  6. Efecto del tramadol en la motilidad del ciego en dos equinos sanos (estudio preliminar

    Directory of Open Access Journals (Sweden)

    Anastasia Cruz-Carrillo

    2012-07-01

    Full Text Available El tramadol (analgésico opioide atípico es utilizado ampliamente en humanos y, en menor proporción, en animales, por falta de productos comerciales de uso veterinario. Es un analgésico eficaz que produce efectos adversos suaves, en comparación con los opioides típicos. Se propone su uso como alternativa en el manejo del dolor en equinos, a partir de la hipótesis de que al estimular los receptores opioides de manera suave, los efectos adversos en los equinos deben ser menores. Así, el objetivo del presente trabajo fue determinar el efecto del tramadol en la motilidad de la musculatura lisa de la base del ciego en equinos sanos. Se utilizaron tres equinos, a los cuales, mediante intervención quirúrgica, se les colocaron dos electrodos en la base del ciego, y se exteriorizaron sus extensiones por la pared abdominal, para conectarlas a un equipo de registro electromiográfico que permitió la valoración de la actividad intestinal 15 días después de colocados los electrodos y después de aplicar 1,2 mg de tramadol/kg de peso. Se comprobó que después de aplicar el tramadol hubo un descenso leve de la intensidad de las contracciones musculares, los sonidos intestinales estuvieron presentes, no hubo atonía, cólico ni estreñimiento. Adicionalmente, se comprobó su gran eficacia analgésica y la ausencia de cualquier efecto adverso. Se concluye que bajo las condiciones aquí planteadas, el tramadol no deprimió la motilidad del ciego en equinos sanos, aunque disminuyó la intensidad de las contracciones musculares en el ciego.

  7. Inestabilidad compleja del codo

    Directory of Open Access Journals (Sweden)

    Héctor Gabriel Díaz Carrillo

    2014-08-01

    Full Text Available La inestabilidad compleja del codo es de reciente descripción y controversial en sus resultados; es el estado que se deriva del daño estructural y funcional, producido por la incongruencia de las superficies articulares y las estructuras ligamentosas que estabilizan el codo. Se realizó un estudio descriptivo prospectivo, en el período comprendido entre enero de 2011 y abril de 2013, en una muestra no probabilística de ocho pacientes (diez codos, seleccionados según criterios de inclusión y exclusión. Los objetivos fundamentales del estudio fueron: la actualización de conocimientos para el manejo de la enfermedad y la caracterización de los resultados obtenidos en los afectados por esta dolencia que fueron operados en el Hospital Dr. Ernesto Guevara de la Serna de la provincia de Las Tunas. Se analizaron los datos mediante técnicas estadísticas descriptivas y se realizó la evaluación clínica y radiográfica de los lesionados. El tratamiento se ejecutó según los hallazgos y consistió en: reparación ligamentosa, actuación sobre las partes óseas dañadas y colocación de osteosíntesis diversas. La edad promedio fue de 39,2 años y predominó el sexo masculino. A todos se les practicó reparación ligamentosa, siete cupulectomías y seis aplicaciones de cerclajes anti-distractores. Existieron dos reluxaciones y una sepsis local. La amplitud de movimientos fue aceptable dentro del rango compatible, con una buena función ergonómica; de acuerdo a las comparaciones bibliográficas actualizadas que se realizaron. La fijación y reparación de los estabilizadores del codo brindan buenos resultados funcionales. La sistematización en el manejo de la enfermedad, la detección de complicaciones y el arsenal terapéutico disponible son factores a tener en cuenta

  8. Nuevos usos del cemento

    Directory of Open Access Journals (Sweden)

    Páez Balaca, A.

    1977-04-01

    Full Text Available In this article, the evolution of the different systems of transporting and storing submarine oil and its by-products (petroleum gas and natural gas, is dealt with stressing the importance of the use of concrete boats. Due to the high cost of oil pipelines, we have passed from tanks built on land to prestressed concrete tanks which can be berthed at great depths or anchored to the bottom to keep them afloat, it being possible to unmoor them for transferring them. Transporting and storing liquated gas leads US to see the advantages of prestressed concrete over steel, as the latter becomes brittle at low temperatures, whereas the former's strength increases. The different forms and possible sections are analyzed, stressing the great importance of the solution of the double concrete hull with pearlite insulation. Finally, a study is made of «light concretes », not the classical types used as thermal and acoustic insulation, but the semi-heavy ones made with expanded clay, high quality sand and P-450 cement, which technique is not yet as developed in Spain at might be wished.En este artículo se trata la evolución de los distintos sistemas de transporte y almacenamiento del petróleo submarino y sus derivados (gas de petróleo y gas natural, resaltando la importancia del uso de barcos de hormigón. Debido al gran coste de los oleoductos, se ha pasado de los tanques construidos en tierra firme a los depósitos de hormigón pretensado que pueden estar fondeados a gran profundidad o anclados al fondo para mantenerlos flotantes, existiendo la posibilidad de poder desamarrarlos para su traslado. El transporte y almacenamiento del gas licuado nos hace ver las ventajas del hormigón pretensado sobre el acero, pues éste se vuelve quebradizo a bajas temperaturas, mientras aquél aumenta su resistencia. Se analizan las diferentes formas y secciones posibles, destacando la gran importancia de la solución del doble casco de hormigón con

  9. Enfermedad Diverticular del Colon

    Directory of Open Access Journals (Sweden)

    Gonzalo López Escobar

    1991-06-01

    Full Text Available

    Los divertículos del colon han sido reconocidos por varios observadores desde hace más de un siglo, pero en su mayor parte se trataba de casos aislados, hoy se la considera como la enfermedad del siglo XX, la de la era moderna y de los países industrializados y de avanzada tecnología (5,18,33.

    Según el diccionario de la Real Academia Española (11, divertículo, del latín, diverticulum, quiere decir desviación de un camino; y desde el punto de vista anatómico, apéndice hueco y terminado en fondo de saco. (Gráfica No. 1.

    Goligher (17 lo define como la “posada al borde del camino, probablemente un lugar, a menudo, de mala reputación”.

    Historia

    Según Hackford (18, el proceso fué descrito brevemente por Littre a comienzos del siglo XVIII; pero se le atribuye a Cruveilhier la primera descripción como proceso patológico en 1849, quien, además, mencionó: “encontramos, no rara vez, en el sigmoide, entre las bandas de fibras musculares longitudinales, una serie de pequeños tumores piriformes oscuros, que están formados por hernias de la mucosa a través de brechas en la capa muscular” (17.

    Fleischman en 1815 hizo la primera observación de la enfermedad y empleó el término divertículo (45.

    Rokitansky en 1.849, habló de una enfermedad adquirida y consideró que su causa consistía en la constipación (45.

    Virchowen 1853 describió la perisigmoiditis (45.

    En 1859 Sidney Jones informó de una fístula colo-vesical debida a diverticulitis (5,45.

    Loomis en 1870 describe una peritonitis como resultante de una diverticulitis (45.

    En 1877 Ball describió la anatomía patológica de la enfermedad y presentó dos casos de fístula colovesical debidas a diverticulitis (9. Cripps en 1.888 popularizó la colostomía de desviación como tratamiento para la fístula colovesical(18...

  10. Assays for calcitonin receptors

    International Nuclear Information System (INIS)

    Teitelbaum, A.P.; Nissenson, R.A.; Arnaud, C.D.

    1985-01-01

    The assays for calcitonin receptors described focus on their use in the study of the well-established target organs for calcitonin, bone and kidney. The radioligand used in virtually all calcitonin binding studies is 125 I-labelled salmon calcitonin. The lack of methionine residues in this peptide permits the use of chloramine-T for the iodination reaction. Binding assays are described for intact bone, skeletal plasma membranes, renal plasma membranes, and primary kidney cell cultures of rats. Studies on calcitonin metabolism in laboratory animals and regulation of calcitonin receptors are reviewed

  11. Max Weber o el enigma emocional del origen del capitalismo

    OpenAIRE

    EDUARDO BERICAT ALASTUEY

    2001-01-01

    Se analiza el trabajo clave de Max Weber, La ética protestante y el espíritu del capitalismo, desde la perspectiva de la Sociología de las Emociones. Aunque la inclusión de las emociones de los fenómenos sociales es clave para entender la idea de Weber sobre el dogma de la predestinación, los sociólogos han trivializado el papel de la emoción. Tras detallar la creencia de Weber en que el espíritu del capitalismo parte del conocimiento de que el destino del hombre está predeterminado (la ética...

  12. Sobre el significado del descubrimiento del gen FOXP2

    OpenAIRE

    Longa Martínez, Víctor Manuel

    2006-01-01

    El reciente descubrimiento del gen FOXP2 ha ofrecido la primera evidencia clara de la base genética del lenguaje, mostrando una correlación inequívoca desde la perspectiva genética entre una versión mutada de F0XP2 y los trastornos lingüísticos de diferente tipo sufridos por una familia inglesa, conocida como KE. El objetivo central del presente trabajo es discutir diferentes aspectos relacionados con tal descubrimiento; especialmente, la discusión del significado de FOXP2 con ...

  13. Competitividad sectorial internacional. Caso: sector del cuero y del calzado

    Directory of Open Access Journals (Sweden)

    Diana Carolina Villegas Álvarez

    2007-01-01

    Full Text Available El presente escrito se origina en un trabajo de investigación cuya pretensión fue indagar sobre el nivel de competitividad internacional (C.I, del sector del cuero y del calzado colombiano, mediante la aplicación de indicadores que, a partir de la información estadística de las variables de comercio exterior permiten establecer ciertas relaciones que dan cuenta de la importancia del producto en los mercados de los países de la Comunidad Andina de Naciones (CAN, seleccionados para la comparación.

  14. Posible efecto de dos presiones parciales de oxígeno en la vascularización del saco vitelino y la alantoides de embriones de pollo (Gallus domesticus) y en la expresión de VEGF y su receptor FLK-1 (KDR)

    OpenAIRE

    Acosta Virgüez, Edwin

    2011-01-01

    Con el objetivo de establecer el posible efecto de dos diferentes alturas en el peso embrionario y en la vascularización de las membranas extraembrionarias, se incubaron embriones de pollo a 355 y 1378msnm, y el día 3 y 4 de incubación, lo mismo que en el día 6 y 7 de incubación: se midió el peso del embrión y de las membranas extraembrionarias (día 3 y 4: saco vitelino - día 6 y 7 corioalantoides); se estimó el área vascular media, el porcentaje capilar y el área capilar media del saco vitel...

  15. La impronta del nuevo mundo

    Directory of Open Access Journals (Sweden)

    Rodrigo Lagos Vergara

    1992-05-01

    Full Text Available Cuando nos aprontamos a conmemorar el quinto centenario del Nuevo Mundo, cabe hacer algunas reflexiones acerca de nuestro continente a la luz del lenguaje propio de las artes y la arquitectura a través del tiempo. Hablamos del Nuevo Mundo en la medida que aceptamos, por una parte, la concepción del nuevo espacio generado a partir del encuentro de dos culturas, la precolombina americana y la propiamente europea llegada principalmente a través de España, y, por otra parte, aceptando también que el nuevo continente resulta ser la pieza clave que ayuda definitivamente a configurar un nuevo cosmos que revela al mundo su otro extremo y aquella parte que manifiesta la totalidad en la certeza de que la tierra es un planeta.

  16. Angiotensin type 2 receptor (AT2R) and receptor Mas

    DEFF Research Database (Denmark)

    Villela, Daniel; Leonhardt, Julia; Patel, Neal

    2015-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striki...

  17. Efectos colaterales del voto preferente

    Directory of Open Access Journals (Sweden)

    Luis Diego Brenes Villalobos

    2012-07-01

    Full Text Available El artículo describe la multiplicidad de potenciales efectos que la implementación del voto preferente podría acarrear en el ordenamiento jurídico y el sistema de partidos. La primera parte del análisis se dirige a caracterizar y definir el voto preferencial. En segunda instancia, el estudio comprenderá la revista de los efectos colaterales del voto preferente como modalidad de votación.

  18. El movimiento del software libre

    OpenAIRE

    Prudencio Óscar Mochi Alemán

    2002-01-01

    El objetivo de este trabajo es describir el surgimiento y desarrollo del movimiento de software libre. Para ello se analizan algunas características importantes que dan cuenta del origen y desarrollo del mismo, así como de sus momentos más críticos y sus tensiones, sus desafíos y sus retos. Otra de las grandes inquietudes de este trabajo, es intentar descifrar cómo el movimiento del software libre y Linux, en su versión más conocida, sobrevivieron y se afirmaron hasta llegar a ...

  19. Analisi del decadimento $W -> \\tau \

    CERN Document Server

    Coscetti, Simone

    Questo lavoro di tesi si e' svolto nell'ambito dell'esperimento CMS a LHC, ed in particolare verte sullo studio delle strategie di identificazione off-line del leptone tau, atteso tra i prodotti di decadimento del bosone di Higgs, cosi' come di altre particelle previste in altri modelli teorici. Il canale utilizzato per testare la procedura di identificazione del tau e' il decadimento semileptonico del bosone vettore W. Infine, sulla base dei risultati ottenuti viene presentata una stima quantitativa della sezione d'urto di produzione pp-> W + X

  20. El pie del adulto mayor

    OpenAIRE

    Parodi García, José Francisco

    2005-01-01

    Acta Médica Peruana es una publicación del Colegio Médico del Perú El estudio del pie y sus patologías es un capítulo muy importante de la Geriatría. Las patologías del pie no escapan las características comunes de muchos síndromes geriátricos como son el ser asumidos como "normales para la edad", ser poco valorados, menospreciados, no tratados, con gran impacto sobre la salud en general y la calidad de vida.

  1. El maestro del Pavo Real

    OpenAIRE

    Montalvo Martín, Francisco J

    2013-01-01

    Este trabajo pretende hacer una primera aproximación al Maestro del Pavo Real, un platero barcelonés del siglo XIX que usó como marca personal la silueta de un pavo real visto de frente con la cola desplegada y todo ello dentro de un círculo. Este trabajo pretende hacer una primera aproximación al Maestro del Pavo Real, un platero barcelonés del siglo XIX que usó como marca personal la silueta de un pavo real visto de frente con la cola desplegada y todo ello dentro de un círculo.

  2. LIDERAZGO VISIONARIO: CENTRO DEL CONOCIMIENTO

    Directory of Open Access Journals (Sweden)

    Rafael Pérez Uribe

    2013-07-01

    Full Text Available El gestor del conocimiento es el ser humano. En el mundo como en las empresas es el centro de la destrucción y la creación del conocimiento. Por esta razón en las empresas se deben generar los escenarios adecuados para revertir el conocimiento de las personas y convertirlo en patrimonio de las organizaciones. El papel del líder es vital para la construcción de escenarios adecuados para que los trabajadores se conviertan en auténticos gestores del «knowledge» y esto permita que las organizaciones sean entes permanentes de aprendizaje continuo.

  3. TLX: An elusive receptor.

    Science.gov (United States)

    Benod, Cindy; Villagomez, Rosa; Webb, Paul

    2016-03-01

    TLX (tailless receptor) is a member of the nuclear receptor superfamily and belongs to a class of nuclear receptors for which no endogenous or synthetic ligands have yet been identified. TLX is a promising therapeutic target in neurological disorders and brain tumors. Thus, regulatory ligands for TLX need to be identified to complete the validation of TLX as a useful target and would serve as chemical probes to pursue the study of this receptor in disease models. It has recently been proved that TLX is druggable. However, to identify potent and specific TLX ligands with desirable biological activity, a deeper understanding of where ligands bind, how they alter TLX conformation and of the mechanism by which TLX mediates the transcription of its target genes is needed. While TLX is in the process of escaping from orphanhood, future ligand design needs to progress in parallel with improved understanding of (i) the binding cavity or surfaces to target with small molecules on the TLX ligand binding domain and (ii) the nature of the TLX coregulators in particular cell and disease contexts. Both of these topics are discussed in this review. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

  5. Ginkgolides and glycine receptors

    DEFF Research Database (Denmark)

    Jaracz, Stanislav; Nakanishi, Koji; Jensen, Anders A.

    2004-01-01

    Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown ...

  6. adrenergic receptor with preeclampsia

    African Journals Online (AJOL)

    User

    2011-05-09

    May 9, 2011 ... due to a post- receptor defect (Karadas et al., 2007). Several polymorphisms have ... the detection of the Arg16Gly polymorphism, overnight digestion at. 37°C with 10 U ..... DW, Wood AJ, Stein CM (2004). Beta2-adrenoceptor ...

  7. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    1984-01-01

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

  8. Las aristas del racismo

    Directory of Open Access Journals (Sweden)

    Fredy Rivera Vélez

    2000-01-01

    Full Text Available En el presente trabajo se estudia un ámbito que normalmente se esquiva y se enmascara: Las prácticas racistas. Esta evasión del tema se da en diferentes planos discursivos, y es una práctica, cada vez más frecuente en América Latina, pues aquí se hace de la integración étnica uno de los ejes centrales de la construcción de sus relaciones identitarias y políticas. Se propone, entonces, este trabajo develar la naturaleza y el movimiento de prácticas racistas presentes no sólo discursivamente, en la práctica política, en la práctica laboral, sino que también están presente en nuestra vida cotidiana, bajo nuevas formas y contenidos que se distancian del racismo tradicional e incorpora una nueva gramática racista, una suerte de racismo moderno, no basado en el fenotipo o características físicas como elemento central, sino en un racismo basado en la diferencia cultural, lo cual plantea un plano más excluyente, pues en este planteamiento el “objeto de racismo” no es un objeto de racismo limitado, como en el racismo tradicional, en el cual siempre es utilizado por quien practica el racismo; en el racismo contemporáneo se pretende una ruptura completa y una exclusión total del otro.

  9. Etiche del paesaggio

    Directory of Open Access Journals (Sweden)

    Massimo Venturi Ferriolo

    2015-11-01

    Full Text Available L’etica riflette sui rapporti fra uomo e ambiente. Indaga l’azione dell’uomo. Svela la sua visione della vita e il mondo possibile e accoglie in sé un complesso di norme morali e di costume che identificano un preciso comportamento nella vita di relazione. Si riferisce all’agire dell’individuo in una struttura sociale che lo comprende. Siamo alla ricerca di un’essenza del paesaggio indipendente dalla mera pittura, dalla rappresentazione, dall’immagine sentimentale: dalla natura sia ideale che reale. Prendere coscienza della cosa in sé, anche nei suoi aspetti ideali, significa comprenderne la complessità. Possiamo leggere quindi ogni paesaggio come realtà etica, risultato dell'operosità dell'uomo nella natura, ambito complessivo della vita: nel significato peculiare di progetto del mondo umano, che parte da lontano, da quando l'uomo ha incominciato a trasformare il proprio ambiente naturale per creare i luoghi dell'abitare, modellati con la mano e con lo spirito. La conoscenza dei paesaggi in tutta la loro complessità, a partire dal mondo antico, diventa quindi un nostro obiettivo. Questo significa superare, se non addirittura rovesciare, alcuni luoghi comuni consolidati e storicizzati: la teoria secondo la quale il paesaggio, nella sua dimensione estetica, sarebbe un'invenzione della modernità; il collegamento tra la moderna pittura di paesaggio e la nascita dei concetti estetici; la confusione tra natura e paesaggio, frequente nelle concezioni ecologico- ambientaliste; la tesi lessicale della nascita della coscienza del paesaggio, legata all'esistenza di una parola specifica che lo indichi. 

  10. del paradigma comprensivo

    Directory of Open Access Journals (Sweden)

    María Luisa Bacarlett Pérez

    2008-01-01

    Full Text Available A partir de la distinción planteada por von Wright en su texto ya clásico Explicación y comprensión, se analiza la obra de Giambattista Vico (1668-1744 a la luz de su crítica desarrollada hacia Descartes y la distinción que realiza en tre "crítica" y "tópica". No es aventurado decir que en la propuesta viquiana la actividad propia de la tópica, ligada al uso del lenguaje, la retórica y la elocuencia, se acerca más aquello que von Wright ubica dentro del "paradigma comprensivo"; mientras que la crítica, identificada con el método cartesiano, privilegia la abstracción, la deducción lógica y el análisis matemático; es decir, todo aquello ligado al conocimiento de la naturaleza. La gran diferencia en tre tópica y crítica radica, al final, en el criterio de verdad propio de cada perspectiva: mientras la crítica encuentra la verdad en la exterioridad del mundo natural, en algo que los hombres no hacen; en cambio, la única forma de verdad en el terreno de la tópica es como "verdad hecha" o "verum factum"; es decir, la verdad que nosotros mismos hacemos como agentes históricos, lingüísticos, creadores de cultura, de vida política y social.

  11. Canales iónicos TRP y DEG/ENAC en órganos sensitivos del pez cebra

    OpenAIRE

    Viña Fernández, Eliseo

    2016-01-01

    En los vertebrados la capacidad para detectar y discriminar entre estímulos del entorno, y del medio interno, se consigue gracias a órganos sensoriales y receptores sensitivos dispersos por todo el cuerpo que dependen de la activación de canales iónicos para transducir los estímulos específicos en señales eléctricas. El presente trabajo de tesis se inscribe en una línea de investigación desarrollada en el Grupo SINPOS del Departamento de Morfología y Biología Celular de la Universidad d...

  12. La era del youtuber

    OpenAIRE

    Sánchez Arufe, Irene

    2017-01-01

    En el trabajo se analizan los cambios que ha provocado y la recuperación que ha tenido la red social YouTube en la sociedad actual, poniendo como antecedentes la aparición de Internet y el auge de las nuevas redes sociales. También se examinan la figura del youtuber como la creación de una nueva profesión y los aspectos económicos y sociales de este nuevo trabajo. Grado en Publicidad y Relaciones Públicas

  13. El desarrollo del emprendedor

    OpenAIRE

    Arco Juan, Francisco Javier del

    2010-01-01

    En este trabajo pretendemos abordar el desarrollo de las competencias y de las cualidades del emprendedor. Para ello analizaremos como mediante el trabajo en equipo, el liderazgo y la toma de decisiones a la hora de elaborar un Plan de Negocio, el alumno desarrollo todas estas competencias básicas. Además, por supuesto, de la capacidad de emprender un negocio a través de las herramientas básicas para la puesta en marcha de un negocio. No data (2010) UEM

  14. Peter Carravetta, Del postmoderno.

    Directory of Open Access Journals (Sweden)

    Alessandro Carrera

    2010-08-01

    Full Text Available Peter Carravetta, professor of “Italian and Italian American Studies” at SUNY Stony Brook, with an Italian and American education, has put together in his massive Del postmoderno possibly the most complete critical review so far of American academic production from the 1970s to the present. “Postmodern” is the key word of the cultural turn that took place between the 1950s and the 1970s only to meet its death, in Carravetta’s opinion, on September 11, 2001, when the shortlived illusion that h...

  15. A favor del Plagio

    OpenAIRE

    Manuel Arranz

    2007-01-01

    Yo no tengo nada contra el plagio. Ustedes, como lectores, seguramente tampoco. Bueno, tal vez prejuicios. Es lógico que los tengan con tanto artículo condenándolo. Hasta ahora, que yo sepa, nadie ha escrito para defenderlo. Los que sí tienen algo, parece ser, son los autores. Una minoría al fin y al cabo. Ya sé que hay que respetar el derecho de las minorías, pero el asunto del plagio, como tantos otros, deberíamos examinarlo con más detalle, y preguntarnos, por ejemplo, ¿por qué se molestan...

  16. El mundo del postfordismo.

    OpenAIRE

    Lipietz, Alain

    2012-01-01

    La crisis de la relación salarial fordista ha conducido a diferentes regímenes salariales aún en bloques continentales integrados. Característica que se suma a la transformación jerárquica de las economías mundiales ocasionadas por el avance competitivo de los nuevos países industrializados y por la concentración de las relaciones económicas internacionales por bloques continentales. Tales son las características básicas del mundo económico internacional posterior a la guerra fría.Este artícu...

  17. emergencia del trabajo liberado

    Directory of Open Access Journals (Sweden)

    Rocío Gómez Z.

    2008-01-01

    Full Text Available Este ensayo sugiere que habría una inestimable conexión entre el compromiso subjetivo y emocional de los jóvenes usuarios de Internet, que invierten tiempo y deseo en realizar un conjunto variado de obras menores (correos electrónicos, imágenes de sí mismos en Facebook, trozos de música, mantenimiento de la bitácora en la Red, y los malestares del bienestar urbano. Estas obras menores encarnan y objetivan las demandas de trabajo liberado -frecuentemente reprimidas, pospuestas, administradas o reguladas-, que algunos de los nuevos repertorios tecnológicos canalizan y movilizan vigorosamente.

  18. Funciones sociales del folclore

    Directory of Open Access Journals (Sweden)

    Alberto Londoño Álvarez

    1969-07-01

    Full Text Available Con el objeto de estudiar los principales aspectos sociológicos del folclore, empecemos con uno de los problemas más significativos, cual es el análisis de sus funciones que cumple en una sociedad. se trata de un asunto perteneciente al sociólogo, quien, con el propósito de mostrar al folclórogo, que su investigación no es única, porque se refiere a un hecho que pertenece al grupo de los fenómenos sociales.

  19. Trastorno del espectro autista

    OpenAIRE

    Mendoza Mendoza, María Yésica

    2012-01-01

    Se explica qué es el autismo, sus causas, tipos, síntomas, tratamiento, detección temprana, técnicas y programas específicos de intervención. A continuación, se analiza el resultado de unos cuestionarios pasados a los padres que tienen hijos con autismo para identificar y conocer el impacto de dicho trastorno en los miembros que conviven con el paciente diagnosticado de autismo y otras comorbilidades asociadas: ansiedad, presión psicológica y trastornos del estado de ánimo

  20. Les Malalties dels cereals

    OpenAIRE

    Puiggrós i Jové, Josep Maria

    1989-01-01

    En aquest treball es fa una descripció de les principals malalties dels cereals que han estat trobades a Catalunya. Agrupant-les segons ataquin la fulla i espiga: oïdi, rovells, septòries, Rhynchosporium, Helminthosporium, i virus; al coll i tija: Cercosporella, Ophiobolus, Rhizoctbnia i Fusarium o bé les que vénen de la llavor: carbons, càries i Helminthospbrium. A part de la descripció, hom fa esment de les observacions efectuades els darrers anys en els diferents indrets de...

  1. La inutilidad del etnocentrismo

    OpenAIRE

    Vanegas Betancourth, Paula C.

    2017-01-01

    El etnocentrismo como filosofía de poder en el mundo occidental. Ha evitado el exaltamiento de las mezclas culturales como opción de vida. Dándole a las minorías un lugar en los suburbios del conocimiento y de la ciencia. La exclusión de las fuentes de conocimiento primitivo por el hombre contemporáneo. Le permite la sensación de dominio sobre el mismo hombre y sobre la naturaleza. La industrialización le permitió al hombre. Como lo menciona David Dickson: « El supuesto dominio sobre la natur...

  2. Catàleg dels Miridae (Heteroptera) del Massís del Garraf

    OpenAIRE

    Goula Goula, Marta

    1989-01-01

    Per a la redacció d'aquest catàleg, s'aporten dades d'observació pròpia al llarg dels anys 1980-1984, així com les troballes publicades per CUNI (1889a,1889b,1889c,1891) i per RIBES (1978a,1978b,1980,1984). Totes aquestes observacions s'han fet en localitats del Massis del Garraf, que será objecte d'una curta descripció.

  3. Olfactory Receptor Database: a sensory chemoreceptor resource

    OpenAIRE

    Skoufos, Emmanouil; Marenco, Luis; Nadkarni, Prakash M.; Miller, Perry L.; Shepherd, Gordon M.

    2000-01-01

    The Olfactory Receptor Database (ORDB) is a WWW-accessible database that has been expanded from an olfactory receptor resource to a chemoreceptor resource. It stores data on six classes of G-protein-coupled sensory chemoreceptors: (i) olfactory receptor-like proteins, (ii) vomeronasal receptors, (iii) insect olfactory receptors, (iv) worm chemoreceptors, (v) taste papilla receptors and (vi) fungal pheromone receptors. A complementary database of the ligands of these receptors (OdorDB) has bee...

  4. LAS NEURONAS DEL SEPTUM LATERAL MODIFICAN LA ACTIVIDAD DE LAS NEURONAS DEL NUCLEO TUBEROMAMILAR DEL HIPOTALAMO

    OpenAIRE

    FARIAS RODRIGUEZ, PAULA ANDREA; FARIAS RODRIGUEZ, PAULA ANDREA

    2012-01-01

    El septum lateral (SL), es un núcleo del cerebro anterior, que, procesa la información sensorial afectiva procedente del hipocampo y dirige sus respuestas, importantes para la supervivencia, hacia las zonas del hipotálamo importantes para la motivación, como lo es el núcleo tuberomamilar del hipotálamo (TMN). El TMN contiene las neuronas histaminérgicas en el cerebro, la cual relacionamos con la vigilia y alerta en conductas motivadas y así puede dirigir y reforzar el comportamiento. El TM...

  5. La superación del modelo del ángel del hogar:

    OpenAIRE

    Hurtado Muñoz, Mónica

    2013-01-01

    La Tesis Doctoral titulada "La superación del modelo del "ángel del hogar". Recuperación de la escritora Leonor Canalejas y Fustegueras (1869-1945)" aborda, en primer lugar, un análisis sociológico de las circunstancias que rodearon a la mujer española en el cambio de siglo en el ámbito social y educativo, en un intento de esclarecer las características propias del contexto en el que la mujer accede a la intelectualidad en general y a la literatura en particular. Esta parte concluye que la cr...

  6. Cytokine production but lack of proliferation in peripheral blood mononuclear cells from chronic Chagas' disease cardiomyopathy patients in response to T. cruzi ribosomal P proteins.

    Directory of Open Access Journals (Sweden)

    Silvia A Longhi

    2014-06-01

    Full Text Available BACKGROUND: Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC. It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC stimulated with P2β, the C-terminal portion of P0 (CP0 proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells. CONCLUSIONS/SIGNIFICANCE: Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T

  7. Recent origin and spread of a common Lithuanian mutation, G197del LDLR, causing familial hypercholesterolemia: positive selection is not always necessary to account for disease incidence among Ashkenazi Jews

    NARCIS (Netherlands)

    Durst, R.; Colombo, R.; Shpitzen, S.; Avi, L. B.; Friedlander, Y.; Wexler, R.; Raal, F. J.; Marais, D. A.; Defesche, J. C.; Mandelshtam, M. Y.; Kotze, M. J.; Leitersdorf, E.; Meiner, V.

    2001-01-01

    G197del is the most prevalent LDL receptor (LDLR) mutation causing familial hypercholesterolemia (FH) in Ashkenazi Jew (AJ) individuals. The purpose of this study was to determine the origin, age, and population distribution of G197del, as well as to explore environmental and genetic effects on

  8. RASGOS GEOGRÁFICOS DEL VALLE DEL RIO AGRIO INFERIOR.

    Directory of Open Access Journals (Sweden)

    Celia Torren

    1993-12-01

    Full Text Available El presente artículo es una síntesis del trabajo "Rasgos Geográficos del Valle del Río Agrio Inferior, el cual es un estudio de base para el conocimiento de la geografía de la región: - apoyando el esfuerzo que está realizando la población del área para lograr una identidad propia y una definitiva integración al contexto provincial; - aportando al proyecto "Rescate Arqueológico en Quili Malal, Neuquén" (subsidiado por CONICET y UNESCO, cuya dirección está a cargo de la profesora Susana Rodríguez de la U.N.C., a través de la confección del mapa geomorfológico del área; y - contribuyendo a los estudios que resultan necesarios ante la construcción de una obra hidroeléctrica de la magnitud de "El Chihuido I", emprendimiento que será llevado a cabo por Agua y Energía eléctrica de la Nación. Los límites del área estudiada fueron establecidos teniendo en cuenta el área del valle inferior del Río Agrio que será completamente inundada por el futuro embalse de la represa "El Chihuido I", a emplazarse 5,5 Km aguas abajo de la confluencia de los ríos Agrio y Neuquén. Además de esta área de afectación directa se tomó también una zona de perilago estrechamente vinculada a la anterior. De esta manera los límites este y oeste quedaron establecidos por la confluencia de los ríos antes mencionados y la localidad de Bajada del Agrio, respectivamente.

  9. del cuerpo femenino

    Directory of Open Access Journals (Sweden)

    Betina Hillesheim

    2005-01-01

    Full Text Available Este artículo discute cómo las prácticas de salud dirigidas a las mujeres construyen determinadas significaciones sobre la salud y el cuerpo femenino, comprendiendo que las prácticas en salud producen determinadas formas de ser, vivir y sentir, y constituyen modos de ser mujer y de ser hombre. Se presentan los datos de una investigación desarrollada en un servicio académico de salud, con mujeres que se realizaron exámenes de prevención de cáncer de útero y mama, entre mayo y diciembre del 2002. La recolección de datos se realizó mediante observaciones de las prácticas de la salud y entrevistas con las usuarias del servicio. En términos teóricos, el punto de referencia fueron los estudios feministas, especialmente autores(as cuyas teorizaciones son postestructuralistas. Se espera que este estudio contribuya con la reflexión sobre las prácticas de salud dirigidas a las mujeres, posibilitando una ampliación sobre lo que se entiende por femenino y, dando espacio a otras formas de ser y de estar en el mundo, además de aquellas que el discurso hegemónico sobre mujeres propone como adecuadas.

  10. Fundamentos del metodo cientifico

    Directory of Open Access Journals (Sweden)

    Badii, M. H.

    2004-01-01

    Full Text Available El objetivo de esta obra no radica en realizar una búsqueda exhaustiva de la literatura en el tema, sino, sentar las bases del método científico, notando los aspectos filosóficos e éticos de la ciencia. Se presentan los conceptos y definiciones fundamentales relacionados con la metodología de la investigación científica. Se maneja el concepto de la toma de los datos válidos como un requisito básico en cualquier trabajo científico. Se pone a disposición del lector un modelo denominado el ECOEE que es una herramienta poderosa para establecer puntos de comparación e discusión entre los resultados de diferentes trabajos científicos. Finalmente, ofrece unas sugerencias de que hacer o no hacer en cuanto a realizar un trabajo de investigación.

  11. RECUERDOS DEL SIGLO XX

    Directory of Open Access Journals (Sweden)

    ASUNCIÓN LAVRIN

    2011-10-01

    Full Text Available Este ensayo hace una revisión de conceptos clave en la educación de la mujer en Hispanoamérica, en la primera mitad del siglo XX, y el debate sobre la educación superior de la mujer. También analiza las ideas de Gabriela Mistral para la educación femenina en su Lectura para mujeres, y las compara con las de la escritora mexicana Rosario Castellanos. Finalmente, hace un llamado por nuevos modelos educativos para la mujer de siglo XXI.Este ensayo hace una revisión de conceptos clave en la educación de la mujeren Hispanoamérica, en la primera mitad del siglo XX, y el debate sobre laeducación superior de la mujer. También analiza las ideas de Gabriela Mistralpara la educación femenina en su Lectura para mujeres, y las comparacon las de la escritora mexicana Rosario Castellanos. Finalmente, hace unllamado por nuevos modelos educativos para la mujer de siglo XXI.

  12. Incorrecciones del habla infantil

    Directory of Open Access Journals (Sweden)

    María del Pino LECUONA NARANJO

    2009-11-01

    Full Text Available En el presente trabajo se pretende dar una visión de algunos rasgos característicos del lenguaje infantil, centrándonos especialmente en el estudio de los niños de 4 a 6 años de edad. Es pues, su finalidad fundamental la descripción y análisis de los rasgos que se pueden observar en la expresión verbal de los preescolares. Las diversas peculiaridades que van a ser objeto de examen se refieren a la emisión de incorrecciones de carácter fonético, morfológico y semántico. El análisis unificado de estos tres factores responde a la consideración de que todos surgen como consecuencia de un proceso de simplificación lingüística originado por un estado inconcluso de desarrollo del lenguaje.

  13. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Jorge Jarrín Mantilla

    2015-01-01

    Full Text Available Comunicación y Género, acopia trabajos que vinculan a la mujer y la comunicación y sus esfuerzos por no ser consideradas inferiores. Del libro a la pantalla, acerca a algunas reflexiones sobre el proceso que lleva del libro a la pantalla por la polémica que despierta la adaptación de las novelas, puesto que muchos señalan que la trama se ve desfigurada. Se agregan varios temas sobre el cine. En "Días de Radio", se plantea el que a pesar de la censura y los problemas económicos que deben enfrentar, las radios populares de América Latina, siguen ganando espacios, de su desarrollo depende una mayor profundización de la democracia. Tema de debate es Estrategias comunicativas en Chiapas y Haití. Se añaden dos entrevistas a un caricaturista brasileño y a un corresponsal de guerra muy prestigiado.

  14. Gerencia del Siglo XXI

    Directory of Open Access Journals (Sweden)

    John Orlando Crissien Castillo

    2013-07-01

    Full Text Available El cambio es más rápido que nunca, la tecnología genera nuevos modelos gerenciales, los mercados se abren, el paradigma de la competitividad y la productividad. Los gerentes modernos estamos expuestos a muchas presiones generadoras de estrés; hecho que, según la OMS (Organización Mundial de la  alud, está entre las tres enfermedades que cobran más muertes en el mundo. EL campo de juego gerencial ha cambiado: por ende la gerencia del siglo XXI requiere un perfil de administrador-gerente diferente. Este nuevo gerente se debe tornar líder y administrador. Las cosas se administran, la gente se lidera, se gerencia. Por esto el gerente líder del siglo XXI se debe formar, capacitar, entrenar en aquellas habilidades-competencias requeridas por este nuevo entorno. Por tal razón debe generar dos sets de competencias: las de gerente integral y el desarrollo de la capacidad directiva.

  15. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Luis Eladio Proaño

    2015-01-01

    Full Text Available Refiere el Informe Nacional de Brasil sobre el Diagnóstico de la Comunicación en América Latina en el que se analizan los más importantes medios de comunicación de ese país. En el artículo de opinión se reflexiona sobre los cambios que sufre la comunicación política en la región como resultado de nuevos protagonistas con nuevos mensajes como: Hugo Chávez, Venezuela, Bucarám, Ecuador y Fujimori, Perú. Describe dos noticias que han llamado la atención: la desinformación en la campaña electoral de los Estados Unidos y el peculiar sistema de comunicación del Presidente Chávez para mantener la popularidad. En cultura para la imagen periodística impresa o Infografía muestra los esfuerzos que la prensa diría del mundo entero hace para competir en cuanto a imagen con la televisión. Se trata la elaboración de los guiones cinematográficos y en Comunicación Institucional se responde a cómo a solucionar los problemas de un banco desde Argentina.

  16. El Gobierno del mal menor

    DEFF Research Database (Denmark)

    Agustin, Oscar Garcia

    2012-01-01

    El Gobierno no aspira a ser bueno ni malo. Se conforma con ser el Gobierno del mal menor, cuyas medidas drásticas y poco populares están destinadas a salvar a los ciudadanos del desastre que no ha llegado todavía pero podría llegar....

  17. Tratamiento del paciente con artrosis

    Directory of Open Access Journals (Sweden)

    Francisco Vargas Negrín

    2014-01-01

    Full Text Available El manejo terapéutico del paciente con artrosis tiene como objetivo disminuir la sintomatología dolorosa e inflamatoria, mejorar la capacidad funcional del paciente y la aplicación de intervenciones terapéuticas eficaces y lo más seguras posibles. Un enfoque centrado en el paciente implica su participación activa en el diseño del plan terapéutico y en la toma de decisiones informadas oportunas en todas las etapas de la enfermedad. La educación terapéutica, la actividad física y el ejercicio terapéutico junto con el control de peso, en caso de sobrepeso u obesidad, constituyen el núcleo central del tratamiento. Los autocuidados individuales y por los familiares son fundamentales en el control del día a día del paciente. El uso de terapias físicas, ayudas técnicas (bastón, etc. y de fármacos tipo analgésicos simples, opioides y antiinflamatorios tiene evidencias demostradas en el control del dolor, mejora la funcionalidad y la calidad de vida del paciente y una clara recomendación de uso en el tratamiento de la artrosis. La cirugía conservadora y la de reemplazo articular se indican en los casos en los que no se logran los objetivos terapéuticos en casos concretos.

  18. El Derecho universal del Trabajo

    Directory of Open Access Journals (Sweden)

    Héctor-Hugo Barbagelata

    2014-01-01

    Full Text Available La idea de un derecho universal del trabajo no es nueva, en realidad es más antigua quela legislación del trabajo y por lo tanto, más antigua que la propia rama del derecho que estudia estas cuestiones.Sí, son nuevos los avances que con ese objetivo se han ido registrando desde fines del siglo pasado.I- Introducción.- II Antecedentes.- II Constitucionalización e internacionalización.- IV Principios y criterios de interpretación del bloque de constitucionalidad.- A Criterio fundado en las condiciones del Estado Social de Derecho; B Principio de complementariedad e interdependencia de todas las normas sobre derechos humanos; C Primacía de la disposición más favorable a la persona humana; D Criterio resultante del principio de progresividad.; E Principio de irreversibilidad o de no regresión. F Principio de autoejecución y autoaplicación..- V Conflictos entre los derechos fundamentales .- VI.- Los principios filosóficos: a La Justicia social ; b La especificidad del trabajo humano; c Reafirmación de la dignidad de la persona humana; VII Conclusiones. 

  19. Taquicardias supraventriculares. Estado del arte

    Directory of Open Access Journals (Sweden)

    Jairo Alfonso Gándara Ricardo

    2016-01-01

    El tratamiento de las taquicardias supraventriculares dependerá del estado hemodinámico del paciente, el cual definirá el requerimiento de terapia eléctrica o tratamiento médico. Se debe hacer una selección adecuada de los pacientes que requieren estudio electrofisiológico y ablación.

  20. Prostaglandin Receptor Signaling in Disease

    Directory of Open Access Journals (Sweden)

    Toshiyuki Matsuoka

    2007-01-01

    Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

  1. The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

    Science.gov (United States)

    Keegan, A D; Pierce, J H

    1994-02-01

    Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

  2. Meeting report: nuclear receptors

    DEFF Research Database (Denmark)

    Tuckermann, Jan; Bourguet, William; Mandrup, Susanne

    2010-01-01

    The biannual European Molecular Biology Organization (EMBO) conference on nuclear receptors was organized by Beatrice Desvergne and Laszlo Nagy and took place in Cavtat near Dubrovnik on the Adriatic coast of Croatia September 25-29, 2009. The meeting brought together researchers from all over...... the world covering a wide spectrum from fundamental mechanistic studies to metabolism, clinical studies, and drug development. In this report, we summarize the recent and exciting findings presented by the speakers at the meeting....

  3. Neurotransmitter receptor imaging

    International Nuclear Information System (INIS)

    Cordes, M.; Hierholzer, J.; Nikolai-Beyer, K.

    1993-01-01

    The importance of neuroreceptor imaging in vivo using single photon emission tomography (SPECT) and positron emission tomography (PET) has increased enormously. The principal neurotransmitters, such as dopamine, GABA/benzodiazepine, acetylcholine, and serotonin, are presented with reference to anatomical, biochemical, and physiological features. The main radioligands for SPECT and PET are introduced, and methodological characteristics of both PET and SPECT presented. Finally, the results of neurotransmitter receptor imaging obtained so far will be discussed. (orig.) [de

  4. Thyroid Stimulating Hormone Receptor

    Directory of Open Access Journals (Sweden)

    Murat Tuncel

    2017-02-01

    Full Text Available Thyroid stimulating hormone receptor (TSHR plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases.

  5. Notas del Consejo Editorial

    Directory of Open Access Journals (Sweden)

    Fernando Serpa Florez

    1990-08-01

    Full Text Available

    Merecida Distinción
    Complacidos registrados la señalada distinción de que fue objeto en Hiroshima, Japón, durante la celebración del IX Congreso Mundial de la Organización Internacional a Médicos para la Prevención de la Guerra Nuclear (lPPNW el Académico Honorario Alberto Cárdenas Escovar quien recibió el Premio Albert Schweitzer, en reconocimiento a la meritoria labor que ha cumplido en el campo internacional de la medicina.

    Fernando Serpa Flórez

    Breves de la Academia
    En el número anterior de nuestra revista, por involuntaria omisión no se incluyeron dos señalados acontecimientos, que nos apresuramos a subsanar en la presente edición. Se trata del ingreso a la Corporación de dos distinguidos y muy apreciados Miembros de nuestro Instituto, el Académico correspondiente Joaquín Silva, Profesor de Cirugía y eminente maestro de numerosas generaciones médicas, quien disertó en forma erudita y ponderada sobre el tema “Los albores de la Medicina y Cirugía”. Así mismo tomó posesión como Miembro de Número el actual Presidente del Capítulo de los Santanderes de la Academia Nacional de Medicina, ex-decano de la Escuela de Medicina de la Universidad Industrial de Santander y notable escritor y psiquiátra doctor Roberto Serpa Flórez, quien presentó su libro sobre medicina y enfermedades tropicales en Colombia en la primera mitad de este siglo que, en forma interesante y amena, desarrolló alrededor de la biografía de su padre, el también Académico de Número profesor Roberto Serpa Novoa.

  6. Caracterización del potencial de abuso del flunitracepam

    OpenAIRE

    Martí de la Llave, Cecilia

    1997-01-01

    Con el presente estudio se pretende caracterizar el potencial de abuso del flunitracepam. La pauta de administración del flunitracepam está ajustada para alcanzar concentraciones máximas plasmáticas similares entre los dos regímenes de administración del fármaco activo, aunque a diferente velocidad; con la dosis única se alcanza la concentración máxima plasmática más rápidamente que con la dosis dividida. Cuando el voluntario recibe el fármaco activo a dosis única toma cinco cápsulas que ...

  7. Del Charco del Agua Amarga (Alcañiz

    Directory of Open Access Journals (Sweden)

    Tomás MAIGI

    2009-10-01

    Full Text Available En agosto de 1947, habiendo llegado a la excelentísima Diputación Provincial de Teruel rumores de recientes deterioros en el friso pintado del abrigo rupestre del "Charco del Agua Amarga", nos fué requerida oficialmente, por dicha Corporación, la presentación de un informe sobre la realidad de los hechos expuestos, así como el planeamiento de las medidas adecuadas para salvaguardar en forma eficaz, en el futuro, las referidas pinturas.

  8. Calidad del servicio de taxis del municipio Maracaibo

    Directory of Open Access Journals (Sweden)

    Joheni A. Urdaneta G.

    2011-05-01

    Full Text Available El presente trabajo tiene como objetivo describir la calidad del servicio de los taxis en el municipio Maracaibo, ya que los mismos forman parte del sistema de transporte urbano de la ciudad, y es un servicio público fundamental para la convivencia de la sociedad; para lograr este objetivo se realizó una adaptación del modelo SERVPERF, diseñando un instrumento tipo cuestionario, con 32 ítems en 6 dimensiones, adecuado a las características propias del servicio de taxi, con la finalidad de confirmar que los ítems de los instrumentos se correspondían con las dimensiones adaptadas se aplicó la técnica de análisis factorial resultando un nuevo instrumento con 24 ítems en 3 dimensiones. Se utilizó la escala de Likert con tres (3 alternativas de respuesta. La investigación es de tipo descriptiva y aplicada, bajo diseño no experimental de tipo transeccional descriptiva y de campo. La población quedó conformada por los usuarios de las líneas de taxis del municipio Maracaibo. Se aplicó muestreo aleatorio por conglomerado. La confiabilidad del instrumento se midió a través del coeficiente alfa de Cronbach resultando de 0,82 lo cual se considera aceptable. Los resultados revelan que la calidad del servicio de taxis del municipio Maracaibo es mediana por lo tanto este servicio es susceptible a mejoras, las cuales son necesarias para elevar la calidad de vida de los marabinos. Este resultado se obtuvo con el instrumento originalmente adaptado de 32 ítems y con el cuestionario resultante del análisis factorial, de 24 ítems; esto confirma lo apropiado de esta técnica, ya que se redujo el número de ítems y de las dimensiones originalmente adaptadas y no se encontraron diferencias significativas en los resultados con ambos instrumentos; de esta manera se puede medir la calidad del servicio de taxis en el municipio Maracaibo a través de las dimensiones: confiabilidad del servicio, socialización y responsabilidad.

  9. DE LA SOCIEDAD DEL CONOCIMIENTO A LA SOCIEDAD DEL RIESGO

    OpenAIRE

    Abdala Cardona, Alejandro

    2013-01-01

    El tiempo en el que vivimos: el siglo XXI, presenta a la vez, retos y exigencias al conjunto global de los habitantes del mundo, puesto que, no solo se nos presenta la actualidad como aquella coyuntura histórica en los que el cambio de los acontecimientos gira en torno al rol central del conocimiento, sino también, en torno al potencial que dicho conocimiento trae tras de sí; es decir, el presente siglo impone al conjunto de personas el rótulo de "sociedad del conocimiento" donde se puede enc...

  10. Historia del desarrollo institucional turístico del Meta

    Directory of Open Access Journals (Sweden)

    Ramón Vergel

    2002-11-01

    el primer plan de desarrollo turístico departamental, se comienza a visualizar diferentes tipologías de turismo que se podían desarrollar como el Ecoturismo y a trabajar en pro de ello. Surge luego el segundo Plan Sectorial del Meta visualizando al turismo como producto. Posteriormente se realiza un Estudio Exploratorio sobre el Potencial Turístico del Meta y la promoción turística del departamento comienza a surgir con la participación en ferias y vitrinas turísticas importantes logrando así fijar un mercado turístico: Bogotá.

  11. Perfil del director hospitalario

    Directory of Open Access Journals (Sweden)

    Gabril Pontón Laverde

    1990-04-01

    Full Text Available RESUMEN El hospital, sin importar su tamaño, es una empresa de servicios con una importante función social que trabaja dentro de las características administrativas y económicas generales, toda vez que actúa dentro de un  SISTEMA ABIERTO con los componentes clásicos de una demanda cíclica de servicios de salud, que requiere de una organización con personas, materiales y equipos que trabajan para dar respuesta a esa carencia y que produce resultados que benefician a la comunidad. Tienen un efecto de retroalimentación (Feed – back con base con las experiencias, expectativas y nuevas demandas de servicios y que trabajan dentro de una comunidad precisa, como parte integrante de un sistema mayor, al cual beneficia y fortalece con sus resultados y del que depende para su supervivencia.

  12. Los presupuestos del Concurso

    Directory of Open Access Journals (Sweden)

    Línea de Investigación “De la Crisis Empresarial

    2006-01-01

    Full Text Available Este escrito es el resultado de uno de los proyectos de investigación adelantados por el Departamento de Derecho Comercial de la Universidad Externado de Colombia. En el se hace una aproximación histórica a los presupuestos para acceder a los trámites concursales en Perú, Argentina y España, analizándolos desde los puntos doctrinal, académico y legal.Así mismo, es parte integrante de un trabajo más amplio que pretende elaborar un documento contentivo del tratamiento que se da a los presupuestos concursales a nivel mundial.En este orden de ideas, nos permitimos presentar un análisis minucioso de la legislación de los citados países iberoamericanos.

  13. cuarto del siglo XX

    Directory of Open Access Journals (Sweden)

    José Antonio Nieto Calmaestra

    2005-01-01

    Full Text Available Los últimos 25 años del siglo XX han supuesto un sustancial cambio en el modelo de crecimiento de la población andaluza. Así, mientras la caída de la fecundidad y la estabilización de las tasas de mortalidad han contribuido a un progresivo retroceso de la vitalidad natural, la masiva emigración de antaño ha dado paso al papel de Andalucía como incipiente foco de inmigración y al creciente protagonismo de movimientos internos de relocalización de la población. Desde el punto de vista territorial estas afirmaciones quedan matizadas por los notables contrastes que se producen entre los distintos ámbitos que conforman la región y que contraponen al medio rural con el urbano, al litoral con el interior o a las grandes ciudades con sus periferias.

  14. del caribe colombiano

    Directory of Open Access Journals (Sweden)

    José Amar A.

    2006-01-01

    Full Text Available La investigación indagó acerca de la construcción de conceptos económicos en una muestra de 50 estudiantes universitarios, residentes en una ciudad multifinanciera de la región Caribe colombiana. Para conocer las conceptualizaciones se aplicó una entrevista en profundidad que permitió indagar sobre la función, valor y circulación del dinero y la emisión y acuñación monetaria. Se encontró que sólo el 24% de los jóvenes universitarios alcanza el nivel de pensamiento económico inferencial, y no hay diferencias significativas de acuerdo con el programa académico al que pertenecen. Los resultados indican que los jóvenes presentan un desfase en cuanto a nivel de pensamiento económico, de acuerdo con el contexto internacional.

  15. Avatares del paradigma conexionista

    Directory of Open Access Journals (Sweden)

    Asier Arias

    2012-02-01

    Full Text Available Hace ahora un año que falleciera David Everett Rumelhart, conexionista pionero y editor junto con James Lloyd McClelland de la llamada “biblia del Procesamiento Distribuido en Paralelo” (PDP. Al mismo tiempo, los dos volúmenes de la referida biblia celebraban su vigésimo quinto cumpleaños. También uno de los padres de la inteligencia artificial, John McCarthy, que bautizara de hecho la disciplina, nos abandonó el pasado mes de octubre a los 84 años. Estas tres efemérides nos sirven de pretexto para un breve recorrido por las derivas y obstáculos a los que se ha enfrentado el llamado paradigma conexionista desde su puesta en escena como alternativa al cognitivismo clásico.

  16. El reordenamiento del mundo

    Directory of Open Access Journals (Sweden)

    Antonio Pasquali

    2015-01-01

    Full Text Available Se publica la propuesta de marco histórico y proyección de futuro de Antonio Pasquiali, en nuestra opinión, es útil referente contextualizado para los ensayos y estudios de caso sobre la formación del comunicador profesional. La evolución reciente de la filosofía, la ciencia y la tecnología llevan a Pasquali a afirmar que la humanidad se encamina lentamente hacia la reformulación global de la moral de la intersubjetividad, y a replantear desde sus cimientos el contrato social que concierne a la comunicación social mediática.

  17. Beneficios del descanso peritoneal

    Directory of Open Access Journals (Sweden)

    Jesús Lucas Martín Espejo

    Full Text Available Introducción: Valorar si el descanso peritoneal, de al menos un día semanal, ha supuesto mejoras en la rehabilitación de los pacientes y el impacto clínico que puede suponer. Nos planteamos además cuantificar el beneficio económico. Material y Método: Se realizó un estudio longitudinal, retrospectivo, descriptivo. De los pacientes atendidos en nuestra unidad desde el 1 de enero de 2014 al 31 de diciembre de 2014, se estudiaron los pacientes que cumplieran todo el año de seguimiento y que no procedieran de otras técnicas de depuración como la hemodiálisis o trasplante renal. La muestra de estudio estuvo compuesta por 40 pacientes, de los que 21 tuvieron prescrito al menos 1 día semanal de descanso peritoneal y 19 pacientes sin descanso. Se recogieron las siguientes variables al inicio del periodo de estudio y a los 12 meses: Variables demográficas, variables relacionadas con el estado de volumen, datos clínicos relacionados con la técnica, se pasó una encuesta de satisfacción a todos los pacientes estudiados, y se recogieron los importes del coste mensual de cada tipo de tratamiento. Resultados: Las diferencias iniciales entre los grupos, eran esperables ya que son los valores en los cuales se ha basado la prescripción del día de descanso. La exposición a la glucosa, al comienzo y al final fue menor en el grupo con descanso. Al año, no se encontró diferencias en los parámetros estudiados. Una encuesta de satisfacción nos reveló a que dedican los pacientes el día de descanso y los que no lo tienen a que lo dedicarían. Conclusiones: El descanso peritoneal no ha supuesto una peor evolución de los parámetros clínicos estudiados al año de seguimiento, cumpliendo las recomendaciones de adecuación de diálisis de las guías clínicas. La exposición a la glucosa, aun sin llegar a ser significativa por la duración del estudio, ha sido menor en el grupo con descanso. El día de descanso ha facilitado a los pacientes

  18. Carta del editor

    Directory of Open Access Journals (Sweden)

    Oscar Mauricio Covarrubias-Moreno

    2014-05-01

    Full Text Available Henos aquí con un nuevo número de RIESED. Después de casi un año de ver la luz, y como lo anticipábamos en la carta del editor que acompañaba al número fundacional, hacer una revista electrónica no ha sido una tarea sencilla. Un año más tarde no podemos sino confirmar esa opinión.Gracias al decidido trabajo de los autores, revisores y miembros del equipo editorial hemos podido hacerlo. El proceso de revisión de los artículos ha merecido un cuidado, dedicación y tiempo especiales, que hicieron necesario demorar unos días la fecha de publicación de este tercer número. Asumimos un compromiso con la calidad y estamos convencidos que esa es la única posibilidad de éxito para una revista científica. El contenido y nivel de los artículos disponibles servirá sin duda como incentivo para que los investigadores deseen publicar sus aportes en RIESED.Agradezco especialmente a la Dra. Gloria Rosique Cedillo, Editora Invitada y Coordinadora de este tercer número, así como al investigador César Nicandro Cruz-Rubio, Editor Asociado, apreciados colegas con quienes he tenido el privilegio de trabajar a lo largo de estos meses, y cuya dedicación y esmero han hecho posible RIESED 3.Por otra parte, derivado de nuestro proyecto editorial informo a ustedes de la creación de la Cátedra RIESED. Educación y Sociedad. Esta Cátedra es una iniciativa que la Universidad del Desarrollo Empresarial y Pedagógico ha impulsado en estrecha colaboración con el Grupo de Investigación en Gobierno Administración y Políticas Públicas (GIGAPP del Instituto Universitario de Investigación Ortega y Gasset (IUIOG, Fundación Ortega – Marañón; así como, con la Academia Internacional de Ciencias Político Administrativas y Estudios de Futuro A.C.La Cátedra está concebida como un espacio de diálogo y reflexión interdisciplinario sobre las diferentes temáticas abordadas en RIESED. En el marco de esta iniciativa académica, se invita a los miembros

  19. Memoria del mal

    Directory of Open Access Journals (Sweden)

    Semprún, Jorge

    2011-06-01

    Full Text Available In May 2003 the twelfth edition of the «Aranguren Conferences» was held. Jorge Semprún gave three keynote speeches titled «Kant and the Maquis’ rucksack», «The radical evil and the Buchenwald latrines» and «Literature and memory of the evil: from Sartre to Paul Ricoeur», all of them grouped under the generic denomination Memory of Evil. The thread running through the three speeches was Semprún’s experience as a political deportee at Buchenwald concentration camp, so close to the Weimar camp of Schiller and Goethe. There, he could experience the radical evil, but also the brotherhood through the antifascist resistance groups who coordinated the various clandestine political groups at the camp. This experience helped him review some of the philosophical readings he had done as a philosphy student at the Sorbonne, as well as those readings he took an interest in following the end of the war. In this way, Semprún went over various authors (Immanuel Kant, André Malraux, Edmund Husserl, Jacques Maritain, Martin Heidegger, Karl Marx, Hannah Arendt, Jean Paul Sartre, Paul Ricoeur or Primo Levi arguing their relationship with the issue of Evil.

    En mayo de 2003 se celebró la duodécima edición de las «Conferencias Aranguren». Jorge Semprún dictó tres conferencias magistrales tituladas «Kant y la mochila del maquis», «El mal radical y las letrinas de Buchenwald» y «Literatura y memoria del mal: de Sartre a Paul Ricoeur», agrupadas todas ellas bajo el título genérico de Memoria del mal. El hilo conductor de las tres intervenciones fue la experiencia de Semprún como deportado político en el campo de concentración de Buchenwald, tan cercano al Weimar de Schiller y Goethe. Allí pudo experimentar el mal radical, pero también la fraternidad, a través de los grupos de resistencia antifascista que coordinaban en el campo los distintos grupos políticos clandestinos. Esta experiencia le sirvió para repasar las lecturas

  20. [Feminismos del siglo XXI

    Directory of Open Access Journals (Sweden)

    M. Xosé Agra

    2013-07-01

    Full Text Available ¿Qué soluciones políticas podemos encontrar para las nuevas formas de subjetividad? ¿Cómo debe la teoría feminista interpretar la voluntad de romper los límites y, al mismo tiempo, la necesidad de normalidad? Los pensadores posmodernos son escépticos respecto de las nociones tradicionales de identidad; los límites que definen al sujeto no sólo construyen sino que también excluyen. Debemos oponernos a las interpretaciones dominantes de normalidad y aceptar otras posibles alternativas a los modelos tradicionales. Necesitamos ir más allá del binario sistema sexo/género y de la orientación sexual y mantener una mentalidad abierta, persiguiendo una filosofía de la libertad.

  1. La materialidad del sonido

    Directory of Open Access Journals (Sweden)

    Esteban Manuel Stepanian Taracido

    2012-04-01

    Full Text Available La investigación sobre los procesos de producción sonora en la crea-ción de obras audiovisuales afectan, en términos generales, a cuestio-nes exclusivamente tecnológicas. Para valorar su rendimiento expresi-vo en la construcción del discurso es imprescindible que, de forma paralela, esta investigación se aborde también desde la perspectiva de la realización audiovisual.Para ello es necesario asumir que los conceptos básicos en los que se fundamenta el desarrollo tecnológico no han de ser necesariamente esenciales en los estudios que se plantean desde puntos de vista creati-vos.En particular es oportuno someter a examen el concepto de fidelidad y reivindicar las posibilidades emotivas, e incluso significantes, de formatos de producción sonora hoy en desuso.

  2. La democracia del futuro

    Directory of Open Access Journals (Sweden)

    Rodrigo Borja

    2015-01-01

    Full Text Available El desarrollo logrado por la informática, la microelectrónica y en general las nuevas tecnologías de la información, hace que del zoon politikon aristotélico se pase al homo digitalis posmoderno, de una "democracia restringida" a una telecracia: en el siglo XXI. El autor vaticina que el voto se hará vía computadores desde casa a través de éstos, los gobernantes podrán tener una relación directa con los gobernados, las consultas populares serán más frecuentes, las implicaciones para los regímenes democráticos serán enormes y es en torno a ellas que reflexiona el autor

  3. Valor social del anciano

    Directory of Open Access Journals (Sweden)

    Luna Torres Bertha

    1997-11-01

    Full Text Available

    The old age is been surrounded bymisteries, myths and prejuidices. The concepts and the valoration of the ancient man, have been contradictory. In different places and in many cultural moments, the old man has been taken from the glory to the scorn. The actual world scrolls the ancient in a very fast rhythm; the social changes have generayed conditions of disadvantajes for that group of the population, difficulting even more the process of growing old, that in fact has a lot of limitations. Its important that a lot of professionals from many institutions involved with this important cause, join the work developed by geriatrics and gerontologics;  soin this way we can restore the social values of the ancient, who deserves a peacefull old age in compensation with his participation in the job of building a better society. Only in this way, the fear to grow old will be lost.

    La vejez se ha visto rodeada de tabúes, mitos y prejuicios. Han sido contradictorios los conceptos y la valoración del anciano, quien en lugares y momentos culturales ha estado desde ensalzado hasta despreciado. El mundo actual, desplaza al geronte a ritmo acelerado; los cambios sociales han generado condiciones de marginalidad para ese sector de población, dificultando aun más el proceso de envejecer, que de hecho tiene limitaciones. Es por eso importante que al trabajo que desarrollan geriatras y gerontólogos se sumen otros profesionales y un sinnúmero de entidades; en aras de eliminar prejuicios y rescatar el valor social del anciano, quien por su legado merece un ocaso, que compense su aporte y participación en la construcción de la sociedad, solo así se perderá el miedo a envejecer.

     

  4. Para aprender del pasado

    Directory of Open Access Journals (Sweden)

    Esquivel Valverde, Lidier

    2004-05-01

    Full Text Available Este texto reflexiona sobre la importancia de reconocer el valor que tiene el conocimiento de los eventos del pasado, como fuentes importantes de lecciones aprendidas. Inicia presentando ejemplos de sucesos históricos en Japón y cómo estos han sido utilizados de forma positiva en los procesos de educación en niños y adultos. Posteriormente presenta la realidad de Costa Rica, donde a nivel de la población existe un desconocimiento de hechos históricos sobre el tema, al propiciarse su olvido u ocultamiento. Finalmente, los autores exponen sobre un programa del Área de Prevención de la Comisión Nacional de Prevención de Riesgos y Atención de Emergencias, quienes se han dedicado de distribuir reseñas históricas breves de los principales eventos en el país This text reflects about the importance of recognizing the value of knowing past events as important sources for lessons learned. It starts including examples of historical events in Japan and how they have been used positively in the educational processes for children and adults. Lately, it includes the reality in Costa Rica. The population does not know about historical events on the topic because they have been forgotten or not shared. Finally, the authors refer to a program of the Prevention Area of the National Commission of Risk Prevention and Emergency Response that has dedicated to distribute brief historical reviews about the main events in the country

  5. Discurso del Presidente Entrante

    Directory of Open Access Journals (Sweden)

    Gilberto Rueda Pérez

    1994-09-01

    Full Text Available

    Santafé de Bogotá, D.C., 17 de mayo de 1994

    Señoras y señores:

    Estoy profundamente conmovido y emocionado, al escuchar los elogiosos comentarios de quienes me precedieron en el uso de la palabra, pues, aunque inmerecidos, naturalmente me enorgullecen sobremanera.

    Quiero, antes de iniciar mi discurso, agradecer a la noble Academia de la Lengua, a su presidente doctor Jaime Posada y a los miembros de su Junta Directiva, la generosa hospitalidad en este precioso auditorio que contribuye a dar realce a esta sesión solemne.

    Muchas Gracias.

    Deseo manifestar, que los conceptos que vaya emitir, reflejan mi pensamiento y por tanto, de ellos soy responsable. No pretendo con ellos criticar, ni mucho menos ofender, a personas o instituciones, son más que todo reflexiones, que me llevan a propuestas de trabajo para el futuro y espero que así sean percibidas y analizadas por esta distinguida audiencia.

    El día 3 de enero de 1873, el joven médico Abraham Aparicio, reunió en su residencia, en las primeras horas de la fría noche santafereña, a sus colegas Manuel Plata Azuero, Nicolás Osario, Liborio Zerda, Leoncio Barreta y Evaristo García, con el propósito de crear una sociedad científica, para el estudio y adelanto de las ciencias médicas y naturales, así como para solidarizar al cuerpo médico y darle unidad al ejercicio profesional en el país. Así nació la Sociedad de Medicina y Ciencias Naturales que posteriormente sería elevada a la categoría de Academia Nacional de Medicina, por la Ley 71 de 22 de noviembre de 1890.

    Sin embargo, bien vale la pena rememorar los orígenes aún más remotos, de esta insigne institución.

    El 29 de diciembre de 1816, el Dr. Pablo Fernández de la Reguera, médico cirujano, químico y boticario mayor del ejército expedicionario, inspector de los hospitales, en comunicación dirigida al Sr. Brigadier Don Juan Sámano, Gobernador militar y político de la

  6. Carta del Editor

    Directory of Open Access Journals (Sweden)

    Blasco Fernando Checa Montúfar

    2015-01-01

    Full Text Available En "El laberinto de la ciberred" se habla de los beneficios y problemas que caracteriza el caos existente en la telaraña cibernética. Ahora el cibernauta puede acceder a una inimaginable oferta de información multimedia. Este caos garantiza libertades, pero presenta enormes limitaciones para quienes no tienen acceso a la tecnología, particularmente en países de América Latina, carentes de Políticas de Comunicación que generen condiciones para un uso intensivo, extensivo y democrático de la ciberred. En el tema “La televisión por cable" relacionado con la cultura visual, multimediática, satelital, informática, televisionada, se señala que tiene como soporte a la más antigua nueva tecnología, la televisión por cable. Se trata de uno de los más grandes negocios disputados por los magnates nacionales y transnacionales de la comunicación que atraparon para el año 2000 a más de 20 millones de suscriptores de la televisión pagada. En esta entrega se presentan distintos acercamientos del perfil del ombudsman de prensa, las ventajas y límites de esta institución, su necesaria independencia, trasfondo ético, autonomía y otros aspectos que contribuirán a fortalecer mecanismos adecuados para controlar este "peligroso poder”

  7. Carta del editor

    Directory of Open Access Journals (Sweden)

    Simón Espinosa

    2015-01-01

    Full Text Available La autora relata la historia de las Relaciones Públicas y dice que surgieron y se desarrollaron para legitimar ante el público los intereses económicos y políticos de quienes detentan el poder. Se cuestiona sobre el por qué no aplicar las relaciones públicas, en organizaciones populares, para que mejoren su publicación y orienten sus propósitos de desarrollo. El tema que aborda las Políticas culturales en América Latina acopia un extracto de lo más trascendente de los ensayos del libro editado por Néstor García Canclini. Sobre la telenovela se afirma que esta ha llegado a ser uno de los instrumentos más importantes de la comunicación popular: por ella desfilan las identidades de las más variadas culturas brasileñas. Y en cuanto a la caricatura se relata lo que ocurrió en el Seminario taller " Caricatura y Periodismo", realizado el(9-11 de Nov.- 1987 en el CIESPAL. El estudio sobre el mercado del vídeo se ve dificultado por la imprecisión de los datos obtenidos. Los datos oficiales no siempre se aproximan a la realidad, pues el mercado de vídeo se instauró en América Latina partiendo de una lógica totalmente diversa de los equipos de sonido e imagen.

  8. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

    Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

  9. Los objetivos del desarrollo

    Directory of Open Access Journals (Sweden)

    Currie Lauchlin

    1993-12-01

    Full Text Available To broach the goals of development implies broaching the problem of economic growth in a critical manner. Not only the concept of growth but also the means of achieving it in practice should be questioned. Growth is not an end, it is a means of gaining access to development And development should not be understood as a goal, but as a permanent process of learning tending towards more control over the environment and greater levels of well-being. It is not a matter of increasing GNP linearly; development must occur, sustained growth that, without being a threat to mm or to our natural resources, can lead to the eradication of absolute and relati.ve poverty. The low rates of growth of the developing countries constitute structural problem that can /lot be reso1.ved by resorting to the neo-classical mechanisms of mobility, nor to the Keynesian formulas. These have served as a source of inspiration to the Harrod-lX:m3r·type models of growth which limit themselves to stimulating savings and ending unemployment by concentrating exclusively on the monetary demand. Getting OUt of the vicious circle of low growth implies eradicating poverty with respect into the immediateness of a direct attack on the problem. with respect to the developed counties, growth is starting to became harmful, and, given the prevalence of ostensible consumption and of pecuniary emulation, it is imperative to foment non-economic motivation that will permit the eradication of relative poverty.

    Abordar los objetivos del desarrollo implica abordar de manera crítica el problema del crecimiento econ

  10. Deslumbramientos del mercado

    Directory of Open Access Journals (Sweden)

    Monique Selim

    2006-07-01

    Full Text Available Con eje en los diferentes aspectos que adopta el actual proceso de mundialización de la lógica del mercado y expansión capitalista, aún en países socialistas, el presente artículo plantea la necesidad de una reflexión antropológica susceptible de articular el surgimiento de nuevas formas de dominación y representación simbólicas. Se discute el aparente efecto de unificación intelectual producido por la hegemonía del mercado respecto de hechos sociales heterogéneos dados en la historia reciente de las sociedades contemporáneas. Así, la renovada atracción que ejercen los nuevos escenarios sociales reconfigurados en virtud de las modalidades específicas de encarnación y operación de los procesos globalizantes, llama al estudio antropológico de las coyunturas. La autora despliega una interpretación del socialismo de mercado, conjunción -siempre en tensión- de un monopolio político estatal y una liberalización del mercado económico. En esta perspectiva se reubica el interés de una antropología del presente en relevar localmente, en este caso en Vietnam del Norte, la conformación de un nuevo mercado de demandas simbólicas, donde la reaparición de las prácticas culturales de comunicación con los antepasados expresa la necesidad de reunificación familiar y reconciliación con los muertos en la "larga guerra".Tendo como eixo os aspectos diferentes que adota o processo atual de mundialização da lógica do mercado e de expansão capitalista, até mesmo nos países socialistas, este artigo propoe a necessidade de uma reflexão antropológica capaz de articular o aparecimento de novas formas de dominação e de representação simbólica. Discute-se o efeito de superfície de unificação intelectual causado pela hegemonia do mercado em fatos sociais diversos em sociedades contemporâneas. Assim, a atração renovada de novos fatos sociais pelos modos específicos de incorporação e operação de processos de globaliza

  11. La legitimidad del derecho penal

    Directory of Open Access Journals (Sweden)

    Francisco Bernate-Ochoa

    2010-03-01

    Full Text Available El interrogante sobre la legitimidad del derecho penal se ha convertido en un asunto medular dentro de los estudios contemporáneos sobre la materia, dado que hoy en día se reconoce que a partir de la solución a este interrogante teórico se puede asumir la tarea de construir un sistema. El panorama contemporáneo nos ofrece dos soluciones al respecto: por una parte, se sostiene que la legitimación del derecho penal emana de la Constitución, y se prescinde de una construcción sistémica del delito en aras de la obtención de consecuencias acordes con lo planteado en la Carta Política. Por otra, desde una propuesta -de corte normativista- se entiende que la legitimación del derecho penal debe encontrarse en la sociedad, y a partir del entendimiento de ésta se encuentra la necesidad de aquél, lo cual ejerce una influencia en la construcción del sistema del delito.

  12. Del internacionalismo al nacionalismo: rumbos del conflicto armado en Colombia

    Directory of Open Access Journals (Sweden)

    Mónica Zuleta P.

    2003-10-01

    Full Text Available Este ensayo tiene por propósito sugerir una interpretación del desarrollo del conflicto armado colombiano durante la última década del siglo XX mediante el uso de la concepción de poder de Michel Foucault. Ello con miras a presentar alternativas analíticas frente a la relación entre lo global y lo local donde se consideren algunas de las hipótesis contemporáneas sobre la cuestión del nacionalismo. El ensayo utiliza el término nacionalismo como sustantivo (lo que es en lugar de como adjetivo (lo que debe ser y ordena los conjuntos de acciones que, en torno al proyecto de lo nacional, han sido puestos en práctica por las guerrillas en Colombia.

  13. Gestión del riesgo del cambio (primera parte

    Directory of Open Access Journals (Sweden)

    Juan Pablo Zorrilla

    2007-07-01

    Full Text Available A partir de la desaparición del sistema Bretton-Woods, y la libre flotación del tipo de cambio, el mundo se volvió más susceptible a todo tipo de riesgos. El presente artículo pretende explicar a los gestores financieros o empresarios interesados en el tema de instrumentos financieros derivados, a conocer lo más relevante y necesario acerca del uso de futuros sobre el tipo de cambio, instrumento útil para cubrir riesgos derivados del tipo de cambio para las empresas que se dedican a importar, exportar o para protegerse de un crédito otorgado en moneda extranjera.

  14. Calidad del software: camino hacia una verdadera industria del software

    Directory of Open Access Journals (Sweden)

    Saulo Ernesto Rojas Salamanca

    1999-07-01

    Full Text Available El software es quizá uno de los productos de la ingeniería que más ha evolucionado en muy poco tiempo, pasando desde el software empírico o artesanal hasta llegar al software desarrollado bajo los principios y herramientas de la ingeniería del software. Sin embargo, dentro de estos cambios, las personas encargadas de la elaboración del software se han enfrentado a problemas muy comunes: unos debido a la exigencia cada vez mayor en la capacidad de resultados del software, debido al permanente cambio de condiciones lo que aumenta su complejidad y obsolescencia; y otros, debido a la carencia de herramientas adecuadas y estándares de tipo organizacional encaminados al mejoramiento de los procesos en el desarrollo del software. Hacia la búsqueda de mecanismos de solución de estos últimos problemas se orienta este artículo...

  15. Perspectivas del derecho procesal constitucional

    OpenAIRE

    Hernández-Villarreal, Gabriel-Angel

    2007-01-01

    Este texto recoge las ponencias que participaron en el Foro Internacional de Derecho Procesal Constitucional, que con gran éxito se realizó en el mes de junio de 2005, en las aulas de la Universidad Colegio Mayor de Nuestra Señora del Rosario de Bogotá; razón por la cual contiene el fruto maduro de las investigaciones realizadas por algunos de los más notables exponentes del derecho procesal constitucional en América del Sur. El lector de esta obra se encontrará con riguroso trabajo sobre alg...

  16. Contabilidad del impuesto sobre beneficios

    OpenAIRE

    Luceño Martínez, Haizea

    2017-01-01

    Este Trabajo Fin de Grado pretende dar una explicación al tratamiento contable del Impuesto de Sociedades. Siendo un impuesto que hay que contabilizar, pero que se calcula siguiendo criterios fiscales, lleva a tener que realizar ajustes que tendrán su repercusión contable. El punto de partida no es otra que la norma de registro y valoración 13ª del PGC, que versa sobre cómo hay que proceder a contabilizar el Gasto por Impuesto de Sociedades, que se compone tanto del Gasto por Impuesto Co...

  17. Flavivirus Entry Receptors: An Update

    Directory of Open Access Journals (Sweden)

    Manuel Perera-Lecoin

    2013-12-01

    Full Text Available Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell surface and primary receptor(s that bind to virions and direct them to the endocytic pathway. Here, we present the currently available knowledge regarding the flavivirus receptors described so far with specific attention to C-type lectin receptors and the phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM and TYRO3, AXL and MER (TAM. Their role in flavivirus attachment and entry as well as their implication in the virus biology will be discussed in depth.

  18. Entrenamiento funcional del core: eje del entrenamiento inteligente

    Directory of Open Access Journals (Sweden)

    Iván Dario Pinzón Ríos

    2015-06-01

    Full Text Available Antecedentes: La evolución del entrenamiento físico busca la optimización de la salud y el bienestar, como piedra angular de todo programa de ejercicio. El Entrenamiento Funcional (EF es recomendable para optimizar el control postural del core, mejorando el balance y la ejecución de actividades de la vida diaria.  Objetivo: Revisar la definición, elementos constitutivos, características e implicaciones del EF del core en el movimiento corporal humano (MCH y la salud desde la perspectiva del fisioterapeuta. Metodología: Se incluyeron artículos en inglés y español de las bases Pubmed, Scielo y Ebsco; adicionalmente se incluyeron fuentes electrónicas e impresas y libros. Resultados: 56 documentos cumplieron los criterios de inclusión. La definición más adoptada de EF fue entrenar con un propósito buscando obtener un efecto positivo en la aptitud física. Las implicaciones del EF en el MCH, se relacionan con la ganancia y mejoría de la estabilidad. La propuesta de EF enfocada a las actividades de la vida diaria incluye fases que permiten adquirir la estabilidad hasta lograr el desarrollo de movimiento que demanden más agilidad. En la planificación del EF se deben estructurar los procesos a ejecutar considerando el criterio de funcionalidad. Para organizar la sesión del EF, el fisioterapeuta cuenta con tres maneras de planificar la sesión: globales, por hemisferios y por grupos musculares. Conclusión: La fundamentación teórica sobre el EF permite al fisioterapeuta comprender y determinar cómo esta modalidad de intervención repercute de manera positiva sobre el desempeño funcional y calidad de vida de los sujetos.

  19. Aspectos Hardware y Software del microprocesador 68000

    OpenAIRE

    Alcaraz Martínez, Raúl

    2009-01-01

    INTRODUCCIÓN AL 68000.ORGANIZACIÓN INTERNA DEL 68000. PROGRAMACIÓN DEL 68000 EN LENGUAJE ENSAMBLADOR. ORGANIZACIÓN EXTERNA DEL 68000. EXCEPCIONES. PROGRAMACIÓN DE LA VÍA 6522. PROGRAMACIÓN DE LA DUART 68681 PARA COMUNICACIÓN SERIE. EVOLUCIÓN DEL 68000

  20. La finalidad del proceso

    Directory of Open Access Journals (Sweden)

    Iván Alfonso Cordero Gutiérrez

    2011-07-01

    Full Text Available Resumen:El tipo de Estado que Colombia asumió desde 1991 (Estado Social de Derecho, implica que el cumplimiento de los fines estatales se comparten con la población, generando de esta forma grados de responsabilidad respecto a las cargas asumidas por ellos y el Estado para la materialización de los objetivos planteados. La satisfacción de las necesidades básicas de la población como unode los fines esenciales del Estado Social de Derecho, no escapa a este esquema, lo que determina la colaboración armónica no sólo entre las entidades y organismos del Estado sino de este, complementado con la población. Una de las necesidades básicas de la población, se refiere a la posibilidad de resolver sus conflictos haciendo uso de los mecanismos que para tal efecto tiene a su disposición, utilizando las formas de Auto tutela, Autocomposición, híbridas y de Heterocomposiciòn, que el Estado autoriza,de acuerdo a los lineamientos propios de cada mecanismo, respecto a las materias que componen los derechos sustanciales que se debaten en la relación conflictiva. Dentro de estos mecanismos de solución de conflictos, la heterocomposiciòn presenta uno llamado el proceso jurisdiccional, en donde un tercero investido de poderes específicos ejerce la jurisdicción y toma la decisión respecto al conflicto, después del agotamiento de etapas sucesivas y preclusivas que garantizan la efectiva participación, ejercicio y defensa de los derechos fundamentales y sustanciales de las partes, generando una mayor garantía de legalidad respecto a la decisión generada por ese tercero investido de plena Jurisdicción (el Juez. Por ser el proceso jurisdiccional el mecanismo más idóneo por su garantismo reglado y tecnificado, debe ser protegido, fortalecido y preferente respecto a los denominados equivalentesjurisdiccionales pues con estos el Estado pretende desplazar la competencia al momento de la resolución de los conflictos, generando un