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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of biomedical science 3 (1996), S. 365-378 
    ISSN: 1423-0127
    Keywords: Retroviral vectors ; Gene therapy ; Stem cells ; Transcription ; Silence ; Inactivation ; Integration site ; Position effects ; Methylation ; Primer-binding site
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Although retroviral vector systems have been found to efficiently transduce a variety of cell types in vitro, the use of vectors based on murine leukemia virus in preclinical models of somatic gene therapy has led to the identification of transcriptional silencing in vivo as an important problem. Extinction of long-term vector expression has been observed after implantation of transduced hematopoietic cells as well as fibroblasts, myoblasts and hepatocytes. Here we review the influence of vector structure, integration site and cell type on transcriptional silencing. While down-regulation of proviral transcription is known from a number of cellular and animal models, major insight has been gained from studies in the germ line and embryonal cells of the mouse. Key elements for the transfer and expression of retroviral vectors, such as the viral transcriptional enhancer and the binding site for the tRNA primer for reverse transcription may have a major influence on transcriptional silencing. Alterations of these elements of the vector backbone as well as the use of internal promoter elements from housekeeping genes may contribute to reduce transcriptional silencing. The use of cell culture and animal models in the testing and improvement of vector design is discussed.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 261 (1968), S. 225-238 
    ISSN: 1432-1912
    Keywords: Iron Deficiency ; Iron Absorption ; Iron Complexes ; Rat ; Eisenmangel ; Eisen-Resorption ; Eisenkomplexe ; Ratte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. Die Retention von freiem und komplexgebundenem 59Fe-Eisen wurde 6 Tage nach Verabreichung mit der Schlundsonde bei normalen und anämischen Ratten in einer Ganztiermeßanlage bestimmt. 2. Anämische Ratten nahmen fünfmal mehr Eisen auf als normale Tiere, wenn ionisiertes Eisen angeboten wurde. Alle geprüften Komplexbildner vermindern die gesteigerte Eisen-Retention anämischer Ratten. Bezogen auf die Werte der anämischen Gruppe (=100%) wurde die Retention durch EDTA um 87%, durch Citronensäure um 40%, durch Ascorbinsäure um 32% und durch Nicotinhydroxamsäure um 31% herabgesetzt. 3. In Gegenwart von Komplexbildnern ist die Eisen-Retention anämischer Tiere bei Citronensäure 8,7, von EDTA 6,3, von Nicotinhydroxamsäure 3,7 und von Ascorbinsäure 2,7 mal höher als bei normalen.
    Notes: Summary 1. In normal and anemic rats, the retention of free and complex-bound 59Fe-iron was measured with a whole body counter 6 days after its oral administration. 2. If the iron is administered in the ionic form to iron-deficient rats they show a retention of iron 5 times greater than that of normal animals. The increased iron retention of anemic rats is diminished by all complexing agents tested. EDTA reduced it by 87%, citric acid by 40%, ascorbic acid by 32% and nicotine hydroxamic acid by 31%. 3. When the iron is combined with citric acid its retention by iron-deficient rats was 8.7 times increased in comparison to normal rats, with EDTA 6.3 times, with nicotine hydroxamic acid 3.7 and with ascorbic acid 2.7 times.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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