Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure.

Craniofacial malformations are among the most frequent congenital birth defects in humans; cleft palate, that is inadequate fusion of the palatal shelves, occurs with an annual incidence of 1 in 700 to 1 in 1,000 live births among individuals of European descent. The secondary palate arises as bilateral outgrowths from the maxillary processes, and its formation depends on the coordinated development of craniofacial structures including the Meckel's cartilage and the mandible. Cleft lip and palate syndromes in humans are associated with polymorphisms in the gene (TGFA) encoding transforming growth factor-alpha (TGF-alpha), an epidermal growth factor receptor (EGFR) ligand made by most epithelia. Here we have characterized craniofacial development in Egfr-deficient (Egfr-/-) mice. Newborn Egfr-/- mice have facial mediolateral defects including narrow, elongated snouts, underdeveloped lower jaw and a high incidence of cleft palate. Palatal shelf explants from Egfr-/- mice fused, but frequently had residual epithelium in the midline. In addition, morphogenesis of Meckel's cartilage was deficient in cultured mandibular processes from Egfr-/- embryos. The secretion of matrix metalloproteinases (MMPs) was diminished in Egfr-/- explants, consistent with the ability of EGF to increase MMP secretion and with the decreased MMP expression caused by inhibition of Egfr signalling in wild-type explants. Accordingly, inactivation of MMPs in wild-type explants phenocopied the defective morphology of Meckel's cartilage seen in Egfr-/- explants. Our results indicate that EGFR signalling is necessary for normal craniofacial development and that its role is mediated in part by its downstream targets, the MMPs, and may explain the genetic correlation of human cleft palate with polymorphisms in TGFA.     

Influence of alpha-MSH and ACTH on cortical bone remodelling in hypophysectomized rats.

Hypophysectomy increases both periosteal resorption and endosteal apposition along the femur diaphysis in rat. Administration of alpha-MSH decreased the periosteal resorption but had no effect on the endosteal apposition. ACTH had only minor effects on the endosteum. Thus, alpha-MSH and ACTH, in the doses used, have different effects on cortical bone in rat. The effect of alpha-MSH on cortical bone could be an effect of the hormone alone or by its stimulation of other factors.     

Control of the hypothalamus-pituitary-adrenal axis in young and older rats injected with thyroxine.

Administration of T4 on alternate weeks for 30 weeks at a dosage which does not alter body weight depresses basal serum corticosterone levels in older rats (575 days), but not in young animals (260 days). Similar serum corticosterone response to HPA axis stimulation occurs regardless of age or T4 injection.     

Mechanisms of heterotypic immunity against canine distemper.

Hep-2 cells infected with measles virus (MV) for as short as 6 h became refractory to superinfection with canine distemper virus (CDV) but not to vesicular stomatitis virus (VSV). The exact mechanism of such interference is unknown but probably occurs after virus attachment and penetration. These results verify the suggestion that virus interference may be a mechanism of heterotypic protection against canine distemper.     

Effects of aresenite and oxamate on the in vitro functional activity of estrogen-dominated rate uterine horns.

Arsenite but not oxamate produce in vitro a distinct depression of estrogen-dominated uterine motility, both in the absence of substrate as well as in the presence of exogenous glucose or lactate. The addition of oxamate to preparations suspended in a medium with lactate as the sole external substrate ameliorates the depression of uterine motility elicited by arsenic.     

Relationship between the pentose phosphate shunt and methemoglobin reductase activity in human erythrocytes: Effect of aging on methemoglobin reductase activity.

The increase in methemoglobin reductase activity in human erythrocytes upon incubation with inosine, phosphate, pyruvate occurs only in the presence of methylene blue. No difference in activity of the methemoglobin reductases was observed between enzyme extracts of fresh cells and aged cells.     

An adrenergic participation subserving a positive inotropism and chonotropism of prostacyclin on isolated rat atria.

The effects of prostacyclin (PGI2) on the contractile frequency and on the isometric developed tension of spontaneously beating or paced isolated rat atria were explored. PGI2 enhanced frequency and contractile tension, both effects being blocked by the presence of propranolol, or following a pretreatment with 6-OHDopamine.