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Articles by R. J Ward
Total Records ( 2 ) for R. J Ward
  F Lallemand , R. J Ward and P. De Witte

Aims: The possible interaction between nicotine and ‘binge drinking’ in eliciting changes in behavioural patterns of ‘binge drinking’ rats as well as nucleus accumbens (NAc) glutamate levels has been investigated in these present studies. Methods: Adult or adolescent male and female rats received ethanol, 2 g/kg or 3 g/kg, by gavage in a ‘binge drinking’ regimen (3 times/day over a 6 h period, for 2 days followed by 5 days of abstinence) combined with or without nicotine, 0.3 g/kg, for either a 5-week (adult) or a 4-week (adolescent) period. Motor activity was then assessed for a period of 60 min after three further doses of ethanol or water. In addition, the NAc glutamate level was assayed in each group for 1 h after the first gavage regimen with ethanol, 2 g/kg or 3 g/kg, or water. Results: Adult female rats showed greater sensitivity to each ethanol dose (2 g/kg and 3 g/kg) than the adult male rats, their motor activity decreasing during the first and third ‘binge’. In contrast, in male adult rats, the sedative effects of ethanol were reduced, particularly after the third binge when no significant changes in the locomotor activity were apparent between the ethanol-administered male rats and controls. Adolescent rats did differ in their response to ethanol in comparison with adult rats. It was noteworthy that in young female adolescent rats, given 2 g/kg ethanol, motor activity was enhanced, thereby indicating that adolescent female rats are less sensitive to the sedative effects of ethanol at specific doses. In addition, male and female adolescent rats showed little change in locomotor activity in comparison with controls during the third ‘binge administration’ possibly indicating that tolerance to such alcohol doses was occurring. Nicotine administration did prevent the decrease in locomotor activity after ethanol administration during the first binge regimen in both male and female adolescents as well as adult female rats. However, after the third binge, such alcohol-induced changes in motor activity were not so well defined in the female adult rats that now showed significant decreases in motor activity. In contrast, adolescent male and female rats still showed similar motor activity to that of the controls. No clear association between the NAc glutamate extracellular content and locomotor activity was discernible in either adult or adolescent rats in these present studies. However, chronic nicotine administration markedly reduced the elevated basal glutamate content in the ‘binge drinking female’ adult rats. Conclusions: These studies have shown clear and distinct differences, with respect to both sensitivity and tolerance, in adult and adolescent male and female rats, which could be modified by supplementation with nicotine.

  R. J Ward , L Lee , K Graham , T Satkunendran , K Yoshikawa , E Ling , L Harper , R Austin , E Nieuwenhuis , I. D Clarke , C. c Hui and P. B. Dirks

Subpopulations of tumorigenic cells have been identified in many human tumors, although these cells may not be very rare in some types of cancer. Here, we report that medulloblastomas arising from Patched-1–deficient mice contain a subpopulation of cells that show a neural precursor phenotype, clonogenic and multilineage differentiation capacity, activated Hedgehog signaling, wild-type Patched-1 expression, and the ability to initiate tumors following allogeneic orthotopic transplantation. The normal neural stem cell surface antigen CD15 enriches for the in vitro proliferative and in vivo tumorigenic potential from uncultured medulloblastomas, supporting the existence of a cancer stem cell hierarchy in this clinically relevant mouse model of cancer. [Cancer Res 2009;69(11):4682–90]

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