42 research outputs found

    Amplification of specific DNA sequences correlates with multi-drug resistance in Chinese hamster cells

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    Mammalian cells selected for resistance to certain cytotoxic drugs frequently develop cross-resistance to a broad spectrum of other drugs unrelated in structure to the original selective agent. This phenomenon constitutes a major problem in cancer chemotherapy. Multi-drug resistance arises from decreased intracellular drug accumulation, apparently due to an alteration of the plasma membrane. The observation of double minute chromosomes or homogeneously staining regions in some of the multi-drug-resistant cell lines suggests that gene amplification underlies this phenomenon. We have used the technique of DNA renaturation in agarose gels to detect, compare and clone amplified DNA sequences in Adriamycin- and colchicine-resistant sublines of Chinese hamster cells. We show that both Adriamycin- and colchicine-resistant cells contain amplified DNA fragments, some of which are amplified in both of these independently derived cell lines. Furthermore, loss of the multi-drug resistance phenotype on growth in the absence of drugs correlates with the loss of amplified DNA. These results strongly suggest that the DNA sequences which are amplified in common in multi-drug-resistant cell lines include the gene(s) responsible for a common mechanism of multi-drug resistance in these cells. We have cloned one of the commonly amplified DNA fragments and show that the degree of amplification of this fragment in the cells correlates with the degree of their drug resistance

    Breaking the wave: The contested legitimation of an alien organizational form

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    Organizational forms imbued with values of modernity – that is, rationality, efficiency and equity – diffuse rapidly around the world. Nonetheless, when sustained by beliefs, norms and regulations contrasting with those prevalent in the receiving country, their adoption may be delayed, and within-country legitimation may not proceed smoothly. We study the diffusion of multiplex cinemas – a form conceived in the US and attuned to the cinema-as-commerce logic – across Europe, where the cinema-as-art logic prevails. Our findings reveal that the cultural meanings embodied by multiplexes shaped the founding rates of this organizational form in three ways. First, countries with larger normative and regulative distance from the US retarded the adoption of the first multiplex. Second, camouflaged entries and, at increasing density, opposition from local interest groups were observed. Third, the embodiment of global cultural scripts of progress and modernity allowed multiplexes to overcome local opposition. The normative distance of the country from the US amplified the fluctuating dynamics of within-country legitimacy. A new specification of density-dependent legitimation is presented to model the cultural-cognitive legitimacy of rationalized but alien organizational forms
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