Identification and ontogenesis of beta-adrenergic receptors in fetal and neonatal rabbit myocardium

In adult animals, beta-adrenergic receptors are involved in the regulation of myocardial contractility and heart rate. Their properties in the fetal and early neonatal period have not been adequately investigated. We have directly characterized beta-adrenergic receptors in rabbit fetal and neonatal myocardial membranes by a radioligand binding assay utilizing 125I-hydroxybenzylpindolol (I-HYP), a potent, non-specific, beta-adrenergic antagonist, I-HYP binding sites were detected as early as the 21st day of gestation (term 31 days). The binding was rapid, saturable and reversible. The dissociation constant, KD, as determined by Scatchard plots, ranged from 30 pM to 50 pM. There was a progressive increase in the density of the receptor sites with advancing gestation. Competition studies with beta-agonists and antagonists showed that the order of potency in inhibiting I-HYP binding was consistent with a beta 1-subtype of beta-adrenergic receptors. We conclude that the progressive increase in density of beta-adrenergic receptors in rabbit fetal myocardium parallels similar maturational processes occurring in other tissues with advancing gestation. It may also account for the reported developmental changes in fetal myocardial contractility.     

Bromoacetylcholine as an affinity label of the acetylcholine receptor from Torpedo californica

Bromoacetyl[methyl-³H]choline is a highly specific label for the reduced acetylcholine binding site on the acetylcholine receptor from $\text{Torpedo californica}$. Only one of two binding sites per receptor monomer is susceptible to labeling. The labeled site is on the α chain of the receptor.     

Career preferences of doctors graduating in 1974.

Questionnaires were sent to all 2348 doctors who had graduated from medical schools in England, Scotland, and Wales in 1974 asking about their career preferences. Most were in their second preregistration post, and the response rate was 86-1%. The most popular first choice of career was general practice (665 of the responders; 32-9%), followed by medicine (454; 22-5%), surgery (321; 15-9%), and paediatrics (129; 6-4%). Only 507 of the responders (25-1%), however, stated that their preference was "definite". First choices differed widely between men and women graduates and between graduates of different medical schools.     

Mitral stenosis with posterior diastolic movement of posterior leaflet.

The echocardiographic diagnosis of mitral stenosis depends in part on the demonstration of abnormal posterior leaflet movement to distinguish it from other conditions that similarly affect anterior leaflet motion. In mitral stenosis the posterior leaflet has been shown to move anteriorly in diastole rather than in the normal posterior direction. A patient presented with clinical evidence of moderate mitral stenosis. The anterior leaflet echo was typical but the posterior leaflet showed posterior diastolic movement. At catheterization moderate mitral stenosis was confirmed. To our knowledge this is the first report of the echocardiographic demonstration of posterior diastolic movement of the posterior mitral leaflet in documented mitral stenosis.     

The effect of cycloheximide upon polyribosome stability in two yeast mutants defective respectively in the initiation of polypeptide chains and in messenger RNA synthesis

Summary The effect of cycloheximide upon protein synthesis, RNA metabolism, and polyribosome stability was investigated in the parent and in two temperature-sensitive mutant yeast strains defective respectively in the initiation of polypeptide chains and in messenger RNA synthesis. Cycloheximide at high concentrations (100 g/ml) severely inhibits but does not completely stop protein synthesis (Fig. 1); the incorporation of ¹⁴C-amino acids into polyribosome-associated nascent polypeptide chains continues at a slow but measurable rate (Figs. 2 and 3). Polyribosome structures are stable in the parent strain at 36° whether or not cycloheximide is present (Fig. 5). However, in Mutant ts^- 136, a mutant defective in messenger as well as in stable RNA production, polyribosomes decay at the restrictive temperature (36° C) at the same rate whether or not cycloheximide is present (Fig. 5). Thus the maintenance of polyribosome structures is dependent upon the continued synthesis of messenger RNA even under conditions of extremely slow polypeptide chain elongation. In mutant ts^- 187, a mutant defective in the initiation of polypeptide chains, all of the polyribosomes decay to monoribosomes within 2 minutes after a shift to the restrictive temperature; cycloheximide completely prevents this decay demonstrating that this mutant is capable of continued messenger RNA synthesis at 36° C. Consistent with these observations is the fact that a newly synthesized heterogeneously sedimenting RNA fraction continues to enter polyribosomes in the presence of cycloheximide whereas the entrance of newly synthesized ribosomal RNA is severely inhibited (Figs. 7, 8, 9). The decay or lack of decay of polyribosomes at the restrictive temperature is, therefore, a rapid and discriminating test for the analysis of mutants defective in macromolecule synthesis. Mutants which exhibit a decay of polyribosomes in the presence of cycloheximide are likely to be defective directly or indirectly in the synthesis of messenger RNA whereas mutants in which decay is prevented or slowed by cycloheximide are likely to be defective in some factor required for the association of ribosomes and messenger RNA.