By C J H Kelnar; et al

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30 Freeman JV, Cole TJ, Chinn S, et al. Cross-sectional stature and weight reference curves for the UK, 1990. Arch Dis Child 1995; 73: 17–24. 31 Wright CM, Corbett SS, Drewett RF. Sex differences in weight in infancy and the British 1990 national growth standards. BMJ 1997; 313: 513–14. 32 Cole TJ, Freeman JV, Preece MA. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Stat Med 1998; 17: 407–29. 33 Tanner JM, Buckler JM.

34–36 It is not yet known how cytochrome c manages to cross the mitochondrial outer membrane, but it is clear that the Bcl-2 family is intimately involved in the regulation of this process. Bcl-2 family proteins are divided into two groups, one that suppresses apoptosis including several identified members, and one that promotes apoptosis comprising more than ten known proteins. 36,42 This knowledge has formed the basis of novel therapeutic targets in cancer therapy. 43 The basic idea behind this hypothesis is that a certain concentration of survival factor is needed at the tissue level to prevent activation of the apoptotic suicide program of the constituent cells.

15 The physiological relevance of in vitro growth factors on growth regulation in vivo has been challenged by data accumulating from gene deletion experiments in mice. For some growth factors, gene disruption in knock-out mice has produced the expected growth disturbances, whereas elimination of other peptide growth factors has not shown any growth failure in vivo. 17 On the contrary, removal of TGF-α has failed to show any systemic growth reduction in vivo18 and EGF, one of the archetypes of peptide growth factors, still awaits disclosure of its growth function in vivo.

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