Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1

The sphingolipid metabolite sphingosine-1-phosphate (SPP) has been implicated as a second messenger in cell proliferation and survival. However, many of its biological effects are due to binding to unidentified receptors on the cell surface. SPP activated the heterotrimeric guanine nucleotide binding protein (G protein)-coupled orphan receptor EDG-1, originally cloned as Endothelial Differentiation Gene-1. EDG-1 bound SPP with high affinity (dissociation constant = 8.1 nM) and high specificity. Overexpression of EDG-1 induced exaggerated cell-cell aggregation, enhanced expression of cadherins, and formation of well-developed adherens junctions in a manner dependent on SPP and the small guanine nucleotide binding protein Rho.     

Relationship between internal calcium and outward current in mammalian ventricular muscle; a mechanism for the control of the action potential duration?

In sheep and calf ventricular bundles, increasing the internal calcium by increasing the frequency of voltage-clamping to plateau range potentials increased the time-independent outward current. This effect was more marked with higher [Ca]o, and was reduced if the Ca current blockers Verapamil or D 600 were used. 2. If the internal Ca was increased by the addition of cyanide and reduction of external sodium the outward current was also increased. The frequency-dependent increase in outward current also occurred in this Na-poor (12 mM) solution. 3. Tension measurement on the ventricular bundles showed that a Na-free solution with cyanide did not cause a contracture. On changing from Tyrode to a Na-free solution containing cyanide, and on changing back to Tyrode there was a potentiation of the twitch. 4. In Na-poor solution with cyanide, although no contracture was found, ECa was less positive, suggesting that under these circumstances Ca accumulates at the inner side of the membrane, but not around the myofibrils. 5. The prolongation of the action potential in Cl-free solution is frequency-dependent. A greater prolongation is seen at lower frequencies suggesting that Cl current is relatively more important for repolarization at lower frequencies of stimulation. 6. It is suggested that calcium at the inner side of the membrane sets the level of the background outward current. A feed-back mechanism on this basis is proposed for the control of the action potential duration. Various factors that could influence this basic mechanism are discussed.     

Placental proteins and steroid hormones in the soluble fraction of human syncytiotrophoblast plasma membrane

Placental protein 5 (PP5), pregnancy-specific glycoprotein (SP1), pregnancy-associated alpha 2-glycoprotein (SP3) and chorionic gonadotrophin could not be demonstrated in appreciable molar quantities in the soluble fraction from microvillous plasma membrane preparations isolated from the syncytiotrophoblast of full-term human placentae. However, progesterone, total oestriol and placental lactogen may have some association with this membrane.     

The management of diabetes in the elderly

It appears inevitable that with increased longevity, the management of the elderly diabetic will place even greater demands on hospital services. It seems reasonable to adopt a more liberal attitude to the regulation of control of diabetes in the elderly than in younger patients. However, the view that diabetes in the elderly is always mild can be dangerously misleading. A significant number of elderly diabetics develop ketoacidosis or other serious forms of metabolic disturbance, and in these patients the mortality is high. Cardiovascular disease and peripheral vascular disease are major problems in the elderly, the former being the main cause of death. For best results, it is desirable that management of diabetes not be isolated from management of other, coexisting disorders, but rather that it be considered as part of the overall patient problem. As Malins pointed out, we should think in terms of diabetics rather than diabetes.     

Linkage group V in the Syrian hamster: cardiomyopathy and lethal gray

It was shown that the cm and Lg genes, which are relatively closely linked, are not linked with markers in any of the four established linkage groups in the Syrian hamster. Therefore, the linkage between these two genes constitutes a new linkage group, LGV.