Search results for "ERAS"
showing 10 items of 4431 documents
Change in expression of MGMT during maturation of human monocytes into dendritic cells.
2005
Dendritic cells (DCs) maturated from monocytes play an important role in the immune system, not only in defense against conventional infections but also in cancer rejection. Because of the central role of DCs in tumor host defense it is highly important that DCs as well as the progenitor cell population are protected during cancer therapy. Since most anticancer drugs target DNA, the DNA repair capacity is most importance for the response of DCs and their precursor cells. Here, we studied the expression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) in monocytes obtained from peripheral blood of healthy donors and DCs maturated from monocytes (moDCs). We show that MG…
Transgenic systems in studies on genotoxicity of alkylating agents: critical lesions, thresholds and defense mechanisms
1998
Abstract Transgenic systems, both cell lines and mice with gain or loss of function, are being used in order to modulate the expression of DNA repair proteins, thus allowing to assess their contribution to the defense against genotoxic mutagens and carcinogens. In this review, questions have been addressed concerning the use of transgenic systems in elucidating critical primary DNA lesions, their conversion into genotoxic endpoints, low-dose effects, and the relative contribution of individual cellular functions in defense. It has been shown that the repair protein alkyltransferase (MGMT) is decisive for protection against methylating and chloroethylating compounds. Protection pertains also…
Assessment of mechanisms driving non-linear dose-response relationships in genotoxicity testing.
2014
In genetic toxicology, risk assessment has traditionally adopted linear dose-responses for any compound that causes genotoxic effects. Increasing evidence of non-linear dose-responses, however, suggests potential cellular tolerance to low levels of many genotoxicants with diverse modes of action. Such putative non-linear dose-responses need to be substantiated by strong mechanistic data that identifies the mechanisms responsible for the tolerance to low doses. This can be achieved by experimental demonstration of cytoprotective mechanisms and by providing experimental support for the existence of tolerance mechanisms against low dose effects. By highlighting key experiments into low dose me…
MGMT: Key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents
2007
O(6)-methylguanine-DNA methyltransferase (MGMT) plays a crucial role in the defense against alkylating agents that generate, among other lesions, O(6)-alkylguanine in DNA (collectively termed O(6)-alkylating agents [O(6)AA]). The defense is highly important, since O(6)AA are common environmental carcinogens, are formed endogenously during normal cellular metabolism and possibly inflammation, and are being used in cancer therapy. O(6)AA induced DNA damage is subject to repair, which is executed by MGMT, AlkB homologous proteins (ABH) and base excision repair (BER). Although this review focuses on MGMT, the mechanism of repair by ABH and BER will also be discussed. Experimental systems, in wh…
Mismatch G-T binding activity and MSH2 expression is quantitatively related to sensitivity of cells to methylating agents
1998
To elucidate mechanisms involved in alkylating drug resistance, Chinese hamster cells resistant to methylating agents have been generated upon transfection with human DNA. Here it is shown that these Chinese hamster ovary (CHO) variants exhibit the tolerance phenotype: they are alkyltransferase deficient (Mex-), cross-resistant to 6-thioguanine, exhibit reduced G-T binding (MutS alpha) activity and express the mismatch repair protein MSH2 at a significantly lower level than the corresponding control. By comparing wild-type cells with different tolerant strains that show gradual differences in resistance to methylating agents, it was shown that both the G-T binding activity and the amount of…
Effective treatment of allergic airway inflammation with Helicobacter pylori immunomodulators requires BATF3-dependent dendritic cells and IL-10
2014
The prevalence of allergic asthma and other atopic diseases has reached epidemic proportions in large parts of the developed world. The gradual loss of the human indigenous microbiota has been held responsible for this trend. The bacterial pathogen Helicobacter pylori is a constituent of the normal gastric microbiota whose presence has been inversely linked to allergy and asthma in humans and experimental models. Here we show that oral or i.p. tolerization with H. pylori extract prevents the airway hyperresponsiveness, bronchoalveolar eosinophilia, pulmonary inflammation, and Th2 cytokine production that are hallmarks of allergen-induced asthma in mice. Asthma protection is not conferred by…
Rapid identification of minor histocompatibility antigen HA-1 subtypes H and R using fluorescence-labeled oligonucleotides
2000
Acknowledgments: We thank Brigitte Schuch and Karola Schmidt for excellent technical assistance. This work was supported by a grant of the Deutsche Krebshilfe (Nr. 70-2427 and Nr. 70-2428). Abstract: Donor-recipient disparitiy of the minor histocompatibility antigen HA-1 is relevant for the development of graft-versus-host disease after HLA-matched sibling allogeneic bone marrow transplantation in HLA-A*0201-positive individuals. Two different alleles of HA-1 with a single amino acid polymorphism have been identified. Here we describe a time- and cost-efficient method for HA-1 typing of genomic DNA, using site-specific hybridization probes with the LightCycler. This method was compared with…
Estudio de los factores ambientales que afectan a la conducta de actividad física en niños y niñas en edad preescolar
2017
Introducción: La actividad física es una conducta de salud que conlleva múltiples beneficios para la población. En niños y niñas de preescolar, la realización de actividad física conlleva una mejora de la adiposidad corporal, salud ósea, desarrollo de habilidades motoras, salud psicosocial, desarrollo cognitivo y aspectos de la salud cardiometabólica. La realización de dicha actividad va a depender de varios factores, entre los que se encuentran factores ambientales, así como el tiempo en el que pasan los niños y niñas en el contexto escolar. Objetivo general: Conocer y analizar los factores, sobre todo ambientales, que influyen en la conducta de actividad física de los niños y niñas en eda…
The Global Boundary Stratotype Section and Point (GSSP) for the base of the Pliensbachian Stage (Lower Jurassic), Wine Haven, Yorkshire, UK
2006
14 pages; International audience; Following votes by the Pliensbachian Working Group, the Jurassic Subcommission and the International Commission on Stratigraphy, IUGS ratified the proposed Global Boundary Stratotype Section and Point (GSSP) for the base of the Pliensbachian Stage (Lower Jurassic) at the base of bed 73b in the Wine Haven section, Robin Hood's Bay, Yorkshire Coast, UK. This level contains the characteristic ammonite association Bifericeras donovani Dommergues and Meister and Apoderoceras sp. Complementary data include: a) Strontium-isotope stratigraphy, based on analysis of belemnites which yield a calcite 87Sr/86Sr ratio for the boundary level of 0.707425 and data supportin…
Fuciniceras paradoxus nov. sp. (Harpoceratinae, Ammonitina) du Domérien portugais. Réflexion sur le sens taxonomique d’un assemblage paradoxal de car…
2002
A new ammonite (Fuciniceras paradoxus) is described here. This Lower Domerian species is based on a recently revised collections which came from the Maria Pares section (Rabacal area, South of Coimbra, Portugal). Curiously, shell of F. paradoxus bears both diagnostic traits for the genus Protogrammoceras SPATH (e.g. acute ogival ventral area) and Fuciniceras HAAS (e.g. angulirursiradiate rib). Thus, the new species can be viewed as a morphological puzzle and as a challenge for taxonomists. The amazing collection of morphological traits previously suspected as highly improbable because of biomechanical constraints (1) confirms the inadequacy of the traditional use of the genera Protogrammoce…