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  • 1
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    Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-08-23
    Description: Helicobacter pylori (Hp) vacuolating cytotoxin VacA induces cellular vacuolation in epithelial cells. We found that VacA could efficiently block proliferation of T cells by inducing a G1/S cell cycle arrest. It interfered with the T cell receptor/interleukin-2 (IL-2) signaling pathway at the level of the Ca2+-calmodulin-dependent phosphatase calcineurin. Nuclear translocation of nuclear factor of activated T cells (NFAT), a transcription factor acting as a global regulator of immune response genes, was abrogated, resulting in down-regulation of IL-2 transcription. VacA partially mimicked the activity of the immunosuppressive drug FK506 by possibly inducing a local immune suppression, explaining the extraordinary chronicity of Hp infections.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gebert, Bettina -- Fischer, Wolfgang -- Weiss, Evelyn -- Hoffmann, Reinhard -- Haas, Rainer -- New York, N.Y. -- Science. 2003 Aug 22;301(5636):1099-102.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max von Pettenkofer-Institut fur Hygiene und Medizinische Mikrobiologie, LMU Munchen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12934009" target="_blank"〉PubMed〈/a〉
    Keywords: Apoptosis ; Bacterial Proteins/pharmacology/*physiology ; Bacterial Toxins/pharmacology ; Calcineurin/metabolism ; Calcineurin Inhibitors ; Cyclins/metabolism ; Cytotoxins/pharmacology ; DNA-Binding Proteins/genetics/metabolism ; G1 Phase ; Gene Expression Regulation ; HeLa Cells ; Helicobacter pylori/genetics/*pathogenicity ; Humans ; Interleukin-2/genetics/metabolism ; Jurkat Cells ; *Lymphocyte Activation ; NFATC Transcription Factors ; *Nuclear Proteins ; Oligonucleotide Array Sequence Analysis ; S Phase ; Signal Transduction ; T-Lymphocytes/*immunology/*microbiology/physiology ; Tacrolimus/pharmacology ; Transcription Factors/genetics/metabolism ; Transcription, Genetic ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1 (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-10-18
    Description: We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hacein-Bey-Abina, S -- Von Kalle, C -- Schmidt, M -- McCormack, M P -- Wulffraat, N -- Leboulch, P -- Lim, A -- Osborne, C S -- Pawliuk, R -- Morillon, E -- Sorensen, R -- Forster, A -- Fraser, P -- Cohen, J I -- de Saint Basile, G -- Alexander, I -- Wintergerst, U -- Frebourg, T -- Aurias, A -- Stoppa-Lyonnet, D -- Romana, S -- Radford-Weiss, I -- Gross, F -- Valensi, F -- Delabesse, E -- Macintyre, E -- Sigaux, F -- Soulier, J -- Leiva, L E -- Wissler, M -- Prinz, C -- Rabbitts, T H -- Le Deist, F -- Fischer, A -- Cavazzana-Calvo, M -- New York, N.Y. -- Science. 2003 Oct 17;302(5644):415-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM Unit 429, Cedex 15, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14564000" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Clinical Trials as Topic ; Clone Cells/physiology ; DNA-Binding Proteins/*genetics ; Gene Expression Regulation ; Gene Transfer Techniques ; Genetic Therapy/*adverse effects ; *Genetic Vectors ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/physiology ; Humans ; Infant ; LIM Domain Proteins ; Leukemia-Lymphoma, Adult T-Cell/*etiology ; Metalloproteins/*genetics ; Mutagenesis, Insertional ; Promoter Regions, Genetic ; Proto-Oncogene Proteins ; Proto-Oncogenes ; Receptors, Interleukin-2/genetics ; Retroviridae/*genetics/physiology ; Severe Combined Immunodeficiency/*therapy ; T-Lymphocytes/*physiology ; Transcription, Genetic ; Virus Integration ; Virus Replication
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
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