1. The earliest components of the developing innervation of the rabbit intestine to be detected in this study were the cholinergic excitatory and the intrinsic inhibitory innervation. These developed simultaneously in the rabbit at 17 days of gestation. Both were also present in the mouse by the 16th day of gestation. Responsiveness of rabbit tissue to exogenous acetylcholine appeared together with the advent of a functional cholinergic innervation. Since excitatory responses were potentiated by eserine, the tissue was probably able to inactivate acetylcholine through hydrolysis mediated by cholinesterase. Early relaxant responses resisted blockade by adrenergic neurone blocking agents and by antagonists active at alpha- and beta-adrenoceptors.2. The development of the adrenergic innervation lagged far behind that of the other two components. Specific uptake of noradrenaline in the rabbit was detected for the first time at the 21st day of gestation and stores of noradrenaline could not be detected histochemically until 26-28 days. However, relaxant responses to stimulation of the perivascular sympathetic supply, such as characterize adult tissues, had not yet developed by the time of birth. Relaxation in response to perivascular stimulation could be seen 30 days after birth.3. Morphologic studies indicated that the longitudinal layer of smooth muscle was very primitive when an effective innervation was established. Although contractile, the cells were still myoblasts. Neural elements also appeared primitive. Thus considerable morphological maturation follows the development both of a functioning contractile machinery and innervation in the foetal gut.4. This study helps establish that the intrinsic inhibitory innervation of the gut is not adrenergic.

Acetylcholine↗

PubMed1973

Glucocorticoid-binding proteins in human acute lymphoblastic leukemic blast cells.

The first known step in steroid hormone action is the association of the steroid with specific cytoplasmic steroid-binding proteins (SBP). Using a competitive binding assay, we detected, quantified, and partially characterized such a SBP in cytosol from glucocorticoid-sensitive human lymphoblastic leukemic blasts. The affinity of steroids for the SBP was directly related to their known killing potency. For example, steroids without glucocorticoid effect such as androstenedione, etiocholanolone, and tetrahydrocortisol were unable to displace radiolabeled dexamethasone from the SBP in the binding reaction. The dose-response curve for in vitro inhibition of [(3)H]thymidine uptake in leukemic blasts correlated closely with the binding affinity of glucocorticoids to the SBP, providing additional support for an essential physiologic role for SBP in steroid action. SBP activity was either greatly diminished or absent in glucocorticoid-resistant cells. Six patients who intially had SBP in their blasts and were responsive to combinations of drugs including glucocorticoids no longer had SBP activity detectable at a time when they no longer responded to combinations of drugs including glucocorticoids. In vitro [(3)H]thymidine uptake was not inhibited by steroids in leukemic blast cells lacking SBP activity. Other patients who had received some antileukemic therapy including glucocorticoids and who still had SBP in their leukemic blasts, were still responsive to drug combinations that included glucocorticoids. This appears to be the first study demonstrating glucocorticoid receptors in a human tissue.

Androstenedione↗

PubMed1972

Variation in tyrosine aminotrasferase induction in HTC cell clones.

Examination of tyrosine aminotransferase induction in many HTC cell subclones revealed a wide and unstable distribution of inducibility. The instability of this phenotype cannot easily be explained by classical mutation rates. These observations may be important in interpreting certain cell fusion experiments.

Carcinoma, Hepatocellular↗

PubMed1972