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Biomedical subjects

N M Cohen

Publications and source records attributed to N M Cohen.

At least 37 records · Page 2Linked to original sources

Calcium current in isolated neonatal rat ventricular myocytes.

1. Calcium currents (ICa) from neonatal rat ventricular heart muscle cells grown in primary culture were examined using the 'whole-cell' voltage-clamp technique (Hamill, Marty, Neher, Sakmann & Sigworth, 1981). Examination of ICa was limited to one calcium channel type, 'L' type (Nilius, Hess, Lansman & Tsien, 1985), by appropriate voltage protocols. 2. We measured transient and steady-state components of ICa, and could generally describe ICa in terms of the steady-state activation (d infinity) and inactivation (f infinity) parameters. 3. We observed that the reduction of ICa by the calcium channel antagonist D600 can be explained by both a shift of d infinity to more positive potentials as well as a slight reduction of ICa conductance. D600 did not significantly alter either the rate of inactivation of ICa or the voltage dependence of f infinity. 4. The calcium channel modulator BAY K8644 shifted both d infinity and f infinity to more negative potentials. Additionally, BAY K8644 increased the rate of inactivation at potentials between +5 and +55 mV. Furthermore, BAY K8644 also increased ICa conductance, a change consistent with a promotion of 'mode 2' calcium channel activity (Hess, Lansman & Tsien, 1984). 5. We conclude that, as predicted by d infinity and f infinity, there is a significant steady-state component of ICa ('window current') at plateau potentials in neonatal rat heart cells. Modulation of the steady-state and transient components of ICa by various agents can be attributed both to specific alterations in d infinity and f infinity and to more complicated alterations in the mode of calcium channel activity.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Autonomous control of phosphatidylinositol turnover by histamine and acetylcholine receptors in the N1E-115 neuron-like cell line.

Histamine was found to stimulate the turnover of phosphatidylinositol (PI) in cultures of neuron-like NE-115 cells. Turnover was measured by increased production of [3H]inositol phosphates (breakdown) and by accelerated incorporation of 32P into PI (resynthesis). Data were consistent with hydrolysis of polyphosphoinositides being the initial event in receptor-stimulated PI turnover. This response to histamine desensitized within 10 min. Receptor systems for histamine and acetylcholine were tested for possible interactions: PI turnover in response to dual stimulation was approximately equal to the sum of the individual responses while prior desensitization of the acetylcholine receptor system had no effect on subsequent stimulation of the histamine receptor system. These results are consistent with the hypothesis that components of acetylcholine and histamine receptor systems responsible for PI turnover are autonomously organized and regulated. and regulated.

Carbachol↗

Receptor-mediated increases in phosphatidylinositol turnover in neuron-like cell lines.

Muscarinic receptors found in the N1E-115 mouse neuroblastoma cell line were tested for their ability to mediate stimulation of phosphatidylinositol (PI) turnover. This study was facilitated by the development of a new solvent system (acetone:butanol:acetic acid:water, 3:5:1:1) for the rapid and consistent separation of PI by one-dimensional thin-layer chromatography. Cholinergic stimulation caused as much as a 680% increase in the incorporation of 32P into PI. Enhanced incorporation of 32P into PI could be measured as early as 4 min after stimulation began. By 20 min, the rate of incorporation by stimulated cells had decreased to that of unstimulated cells, indicating desensitization. The magnitude of the response was dependent on the extent of receptor occupancy, and the response elicited by a saturating dose of carbamylcholine was blocked completely by 10(-7) M atropine, a specific muscarinic antagonist. Chronic stimulation, known to cause a loss of receptor binding sites, led to a 90% decrease in the maximum response even after a 40-min withdrawal period. Replacement of Na+ ions in the medium with choline or K+ severely impaired the ability of the cells to incorporate added 32P into PI (90 and 50%, respectively). Removal of the putative second messenger Ca2+ for short periods of time by the addition of excess EGTA did not alter either basal or muscarinic-stimulated PI turnover.

Acetylcholine↗

British Regional Heart Study: cardiovascular risk factors in middle-aged men in 24 towns.

The British Regional Heart Study seeks to define risk factors for cardiovascular disease, to examine their interrelationships, and to explain the geographic variations in cardiovascular disease in Britain. A clinical survey of men aged 40-59 in 24 British towns was carried out and preliminary data from the survey analysed. On a town basis cardiovascular mortality was associated with mean systolic blood pressure and the prevalence of heavy cigarette smoking and heavy alcohol consumption. No such association was seen for body mass index or mean serum total cholesterol or high-density-lipoprotein cholesterol concentration. Cigarette smoking and alcohol intake and, to a less degree, systolic blood pressure were related to the social class (percentage of manual workers) of a town, and these factors may determine to some extent the increased risk of cardiovascular disease in manual workers. Blood pressure in individual subjects was affected predominantly by age, body mass index, and alcohol intake. Body mass index appeared to affect blood pressure to a greater extent than alcohol intake and did so with a consistent and positive linear trend. Nevertheless, the differences between towns in mean blood pressure readings appeared to be more closely associated with variations in the prevalence of heavy drinking than with variations in body mass index. Alcohol intake and body mass index explained only a part of the striking differences between towns in mean blood pressure readings, and some important "town"factors remained unexplained.

Adult↗

Cross-sectional-type weight reference values for village children under five years in Lesotho.

Cross-sectional-type reference values for weight attained are described for village children under five years in rural Lesotho (formerly Basutoland). Weight measurements derive from observations on 1317 children attending an Under-Fives clinic; it is estimated that 60-70% of the children under five in the catchment area were represented. 4585 weighings on boys and 4826 weighings for girls are included in the analysis. Figures of weight-for-age of boys and girls are given separately as centile distributions suitable for use on Growth Charts. Lesotho 50 centile approximates to 3 centile of British children and slightly exceeds 80% Harvard standard. Weight attained for age is similar, in both sexes, to reports from other less-priviledged urban and rural areas, emphasizing the relative importance of environmental as compared to genetic influences in determining weight-for-age in early childhood. It is suggested that the construction of locally-derived growth reference values is both appropriate and practicable.

Age Factors↗

Proteins and insulin release: a dual role of amino-acids and intestinal hormones.

In two subjects concurrent infusion of amino-acids and the hormones secretin and pancreozymin provoked much higher plasma insulin levels than did administration of amino-acids or hormones individually. It is suggested that this may be a physiological phenomenon, augmenting the release of insulin from the pancreas after a meal containing protein.

Adult↗