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  • 1
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Objective To identify counselling requirements, we reviewed the frequency and type of non-trisomy 21 chromosome abnormalities found at amniocentesis after maternal serum screening for Down's syndrome.Design The study involved a review of the cytogenetic results of amniocenteses performed because of a raised maternal serum screening risk.Setting The maternal serum screening and amniocenteses were performed at hospitals in the Yorkshire region.Sample 1715 amniocenteses were performed as a result of a raised maternal serum screening risk for the period 1990 to 1993.Methods The cytogenetic results were classified into the main categories of numerical and structural chromosomal abnormalities.Main outcome measures The nature and frequency of abnormal cytogenetic results were identified in which parental samples were required in order to determine if the abnormal finding was de novo or familial and/or for which specialist genetic counselling was required.Results Sixty-nine pregnancies of 1715 amniocenteses were identified with a chromosomal abnormality (4.0%): 35 (2.0%) with trisomy 21 and 34 (2.0%) with another chromosomal abnormality. For 20 of these 34 abnormalities, parental karyotypes were required and in 29 of the 34 specialist genetic counselling was required.Conclusions Women undergoing maternal serum screening and, in particular, those proceeding to amniocentesis, should be informed that there is an equal chance that a chromosomal abnormality other than trisomy 21 will be found at amniocentesis, the nature of which usually requires parental samples and specialist counselling.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Our aim was to identify the biochemical defect responsible for the inability of highly growth autonomous human tumor cells to proliferate in culture medium devoid of methionine, but containing homocysteine and 5-methyltetrahydrofolic acid. We have adopted the terms “homocysteine-responsive” and “homocysteine-nonresponsive” to describe cells which can or cannot proliferate in methionine-free homocysteine-supplemented medium. Using a panel of genetically related homocysteine-responsive and -nonresponsive human melanoma cell lines, the results from a number of experiments indicate that acquisition of the “homocysteine-nonresponsive phenotype” is associated with the reduced intracellular accumulation of methyl-cobalamin, a critical cofactor of the methionine synthase enzyme. When in vitro methionine synthase assays were performed in the presence of exogenously added methyl-cobalamin, specific methionine synthase activity in extracts obtained from homocysteine-responsive cells was only twofold greater than that observed with extracts prepared from homocysteine-nonresponsive cells. However, when exogenous methyl-cobalamin was omitted from the enzyme assays, methionine synthase activity in extracts derived from homocysteine-nonresponsive cells was dramatically reduced, compared with the small decrease observed with homocysteine-responsive cell extracts. Compared with their homocysteine-responsive counterparts, homocysteine-nonresponsive cells exhibited increased levels of cobalamin efflux and decreased intracellular accumulation of methyl-cobalamin. There was a clear relationship between the abilities of these related melanoma cell lines to proliferate in methionine-free homocysteine-supplemented medium, and the extent of cobalamin loss and capacity of exogenously added methyl-cobalamin to stimulate in vitro methionine synthase activity. These results indicate a link between alterations in the intracellular trafficking and/or metabolism of cobalamin and the increased growth autonomy of human melanoma cells.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 141 (1989), S. 675-681 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Our aim was to determine if the selection of human tumor cells with enhanced anchorage-independent growth capacity was associated with alterations in methionine auxotrophy. Cells with an increased ability to form colonies on soft agarose were selected from human melanoma (MeWo) and neuroepithelioma (SK-N-MC) cell lines. In contrast to their respective parental lines, a high proportion of the agarose-selected variants were completely unable to proliferate in methionine-free medium containing its immediate precursor homocysteine. The variants exhibited no significant change in their total DNA 5-methylcytosine content and showed no stimulation of either RNA or DNA synthesis upon the addition of homocysteine when the cells were cultured in methionine-free medium. These variants were unable to synthesize [3H]S-adenosylmethionine from [3H]adenine and homocysteine. The failure to detect the accumulation of [3H]S-adenosylmethionine in these variant lines was not likely due to the enhanced turnover of S-adenosylmethionine but rather to a reduced ability to synthesize methionine from homocysteine and 5-methyltetrahydrofolic acid. These results support our hypothesis that alterations in the metabolism of methionine and/or intracellular transmethylating activities may contribute to, or be associated with, the autonomous growth of malignant human tumor cells.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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