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As development proceeds from the embryonic to fetal stages, cardiac energy demands increase substantially, and oxidative phosphorylation of ADP to ATP in mitochondria becomes vital. Relatively little, however, is known about the signaling mechanisms regulating the transition from anaerobic to aerobic metabolism that occurs during the embryonic period. The main objective of this study was to test the hypothesis that adrenergic hormones provide critical stimulation of energy metabolism during embryonic/fetal development. We examined ATP and ADP concentrations in mouse embryos lacking adrenergic hormones due to targeted disruption of the essential dopamine β-hydroxylase (Dbh) gene. Embryonic ATP concentrations decreased dramatically, whereas ADP concentrations rose such that the ATP/ADP ratio in the adrenergic-deficient group was nearly 50-fold less than that found in littermate controls by embryonic day 11.5. We also found that cardiac extracellular acidification and oxygen consumption rates were significantly decreased, and mitochondria were significantly larger and more branched in adrenergic-deficient hearts. Notably, however, the mitochondria were intact with well-formed cristae, and there was no significant difference observed in mitochondrial membrane potential. Maternal administration of the adrenergic receptor agonists isoproterenol or l-phenylephrine significantly ameliorated the decreases in ATP observed in Dbh-/- embryos, suggesting that α- and β-adrenergic receptors were effective modulators of ATP concentrations in mouse embryos in vivo. These data demonstrate that adrenergic hormones stimulate cardiac energy metabolism during a critical period of embryonic development.

Two cases of primary adenosquamous carcinomas of the sigmoid colon and rectum are presented. Clinical features and pathologic findings of both primary and metastatic lesions are reported (including immunohistochemistry and electron microscopy). We emphasize that the presence of a metastatic squamous tumor in a patient with an unknown primary does not exclude the possibility of colonic carcinoma. Comparison with other reports in the American medical literature indicates that these are very aggressive tumors that may have a worse prognosis than the more common form of colonic adenocarcinoma. Furthermore, the squamous component, in particular, may have a greater potential for metastasizing and can do so as an undifferentiated-appearing carcinoma. In view of this, the authors suggest that very poorly differentiated areas within colonic adenocarcinomas should be very carefully evaluated by means of immunoperoxidase stains and/or electron microscopy in an attempt to identify squamous features.

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