Evidence for a circulating sodium transport inhibitor in essential hypertension.

The active sodium transport of white cells and red cells obtained from patients with essential hypertension was impaired. Incubating white cells from normotensive subjects in serum obtained from patients with essential hypertension caused an impairment in sodium transport in the white cells of normotensive subjects similar to that found in the white cells of hypertensive patients. The impairment in sodium transport was due to a fall in the ouabain-sensitive component of the total sodium efflux rate constant. These results show that the serum of patients with essential hypertension contains a substance which influences sodium transport and that it has ouabain-like activity. They also suggest that it is this substance which causes the impairment in sodium transport in the leucocytes of patients with essential hypertension. These findings support the hypothesis that the rise in blood pressure in patients with essential hypertension is due to an increased concentration of a circulating sodium transport inhibitor which is continuously correcting a tendency for sodium retention by the kidney.     

Evidence for a raised concentration of a circulating sodium transport inhibitor in essential hypertension.

A cytochemical technique that measures the ability of plasma to stimulate guinea-pig renal glucose-6-phosphate dehydrogenase (G6PD) activity in vitro, which is a marker of its ability to inhibit Na+-K+-adenosine-triphosphatase (Na+-K+-ATPase), was used in 19 patients with essential hypertension and 23 normotensive, healthy subjects. The ability of plasma to stimulate G6PD was significantly greater in the hypertensive patients when they were taking their normal sodium diet than in the normotensive subjects, and was significantly correlated with blood pressure. The ability of plasma to stimulate G6PD was inversely correlated with plasma renin activity in the hypertensive patients and increased with age and sodium intake in the normotensive subjects. These results support the hypothesis that essential hypertension, and also perhaps the increase in blood pressure with age in communities that consume large quantities of salt, is in part due to an increase in a circulating concentration of an inhibitor of Na+-N+-ATPase.     

Cardiac mechanics at the cellular level.

The active mechanical properties of heart muscle are load, length, and time-dependent. The capability for investigating cardiac mechanisms at the cellular level may help to distinguish between those properties of the myocardium which arise from myocardial cells and those which arise from the tissue architecture and extracellular matrix of connective fibers. We present here, for the first time, a general approach for subjecting single heart cells to isometric, isotonic, afterloaded, or physiological loading sequences, while obtaining on-line measures of cell force and length. This approach has been implemented and tested on freshly dissociated, adult frog ventricular myocytes. Examples are presented for each of the four loading sequences.     

Turnover of polyadenylated messenger RNA in fission yeast. Evidence for the control of protein synthesis at the translational level.

Polyadenylated RNA was isolated from fission yeast (Schizosaccharomyces pombe) total RNA using oligo(dT)-cellulose, and was studied as a model for messenger RNA. The half-life of poly adenylated RNA was measured by two independent methods. (a) The rate of labelling of polyadenylated RNA during incubation of cells with [5-3H]uridine was measured. A half-life of 40-45 min was found by comparing the experimental data with theoretical curves calculated for labelling of RNAs with various half-lives. The influence of precursor-pool specific activity on RNA labelling kinetics is considered. (b) Cells were labelled with [5-3H]uridine then further RNA synthesis was inhibited by addition of 8-hydroxyquinoline. The rate of loos of radioactivity from polyadenylated RNA indicated a half-life of 50 min. The half-life found by these two methods is about one-third of the cell doubling time, and is much longer than previous estimates by indirect methods of yeast messenger RNA half-life. Both experimental methods provided evidence for the existence of tas a half-life of 40-50 min; a much smaller population is probably turning over more rapidly. After inhibition of RNA synthesis by 8-hydroxyquinoline, the rate of total protein synthesis declined much more rapidly than the polyadenylated RNA content of the cells. However, 60 min after inhibition of RNA synthesis there was a small rise in the rate of portein synthesis. These data are interpreted as evidence for mechanisms controlling protein synthesis which operate at the level of messenger RNA translation.     

Evidence for a circulating endogenous Na+-K+ pump inhibitor in low-renin hypertension

It is now more than 10 years since we suggested that an endogenous Na+,K+-ATPase inhibitor might participate in the genesis of certain forms of ren hypertension. Although the question is not yet fully resolved, there has been much activity in the area. We here review that activity. In 1980 we reported that supernatant of boiled plasma from dogs with one-kidney, one wrapped hypertension reduces Na+-K+ pump activity when applied to an artery from another animal. Since then, we and a number of other investigators have described Na+-K+ pump inhibitory activity in the plasma of animals and humans with hypertension, particularly the low-renin varieties. The activity results from a heat-stable small molecule, but the chemical structure of the molecule is unknown. It appears to be released from the hypothalamus in response to pulmonary vascular distension and to act on blood vessels via electrogenic depolarization. Although it may be sufficient by itself to raise pressure, it may be most effective when superimposed on vascular smooth muscle cells that are abnormally permeable to Na+. Efforts to determine the chemical structure of the agent or agents should be intensified.     

Advanced technologies for studying circulating tumor cells at the protein level

Metastasis is the main cause of cancer death. As the tumor progresses, cells from the primary tumor site are shed into the bloodstream as circulating tumor cells (CTCs). Eventually, these cells colonize other organs and form distant metastases. It is therefore imperative that we gain a better understanding of the biological characteristics of CTCs for development of novel treatment modalities to minimize metastasis-associated cancer deaths. In recent years, rapid developments in technologies for the study of CTCs have taken place. We now have a variety of tools for the isolation and examination of CTCs which were not available before. This review introduces some commonly used protein markers in CTC investigations and summarizes a few advanced technologies which have been successfully applied for studying CTC biology at the protein level.     

Thyroid hormone action at the cellular level

Thyroid hormones influence numerous physiological and biochemical functions. The expression of the hormonal effects involves several events. The interaction of T3 with nuclear receptors, and the stimulation of mRNA production appears to be a major step. Extranuclear binding of thyroid hormones could account for early responses. Plasma membrane receptors may play a role in the cellular uptake of T3 and the stimulation of amino acids and sugar transport. A direct control of oxidative phosphorylation through binding of T3 to mitochondrial binding sites has been proposed. The role of cytosolic binding proteins remains unclear. The understanding of the mode of action of thyroid hormones requires a better knowledge of the molecular events occurring at the nuclear level, and the relation between the nuclear and extranuclear binding sites in the hormonal expression.