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Biomedical subjects

S K Sharpless

Publications and source records attributed to S K Sharpless.

At least 19 recordsLinked to original sources

Techniques for the chronic cannulation of the jugular vein in mice.

The use of chronic intravenous cannulae implanted in the jugular vein of mice utilizing techniques previously developed for larger rodents is discussed. Two cannula designs and a chronic infusion chamber are illustrated. Cannula insertion depths for mice of three strains and various body weights, and estimates of operative mortality and cannula durability are given.

Animals↗

Electrophysiological responses to ethanol, pentobarbital, and nicotine in mice genetically selected for differential sensitivity to ethanol.

Cortical electroencephalographic (EEG) changes induced by ethanol (4.3 and 1.4 g/kg, ip), pentobarbital (50 and 16 mg/kg), and nicotine (1.0 g/kg) were examined in long-sleep (LS) and short-sleep (SS) mice that were genetically selected for differential sleep times induced by a hypnotic dosage of ethanol. Ethanol (4.3 g/kg) caused EEG changes that paralleled the behavioral differences, whereas no differences between selected lines were observed following the activating dose (1.4 g/kg). Data support the notion that the known difference in ethanol sleep times is due not to greater SS sensitivity to ethanol activation but rather to greater LS sensitivity to ethanol hypnosis. No differences between selected lines were observed following 50 mg/kg pentobarbital, which again parallels previous behavioral data. The SS mice were more responsive to pentobarbital activation (16 mg/kg). Nicotine more severely reduced EEG power and heart rate in LS mice; a continuous iv infusion of nicotine elicited a distinct pattern of behavioral stereotypy for each selected line, with more profound motor and reflex depression in LS mice. The lines do not differ in rate of nicotine metabolism, hence they must differ in central nervous system sensitivity to nicotine. Thus, lines of mice selectively bred for differential sensitivity to ethanol also display marked differences in electrophysiological and behavioral responses to nicotine.

Animals↗

Activating and anesthetic effects of general depressants.

The long-sleep (LS) and short-sleep (SS) lines of mice were derived by selective breeding with respect to ethanol sleep time. We found that in current generations LS mice also have longer sleep times than SS mice to trichloroethanol and paraldehyde. Two subsequent experiments tested our hypothesis that mice that are relatively insensitive to the hypnotic effects of depressant drugs might be relatively activated by low doses of these drugs. Both experiments failed to support the hypothesis. First, although SS mice were more activated than LS mice by subhypnotic doses of paraldehyde, the lines did not differ in the degree of activation produced by low doses of trichloroethanol. Second, among mice from a genetically heterogeneous population (HS), there was no relation between the degree of activation induced by a low dose of ethanol and sensitivity to the hypnotic effects of a higher dose.

Animals↗

Inhibition of acoustic priming in mice.

Mice of the C57BL/6J strain can be made susceptible to audiogenic seizures by a process known as acoustic priming. Acoustic priming can be blocked when the animals are injected either with puromycin or with puromycin aminonucleoside before the application of the priming stimulus. Cycloheximide, diphenylhydantoin, and d-amphetamine had little effect on priming-induced audiogenic seizures in these animals. All of these drugs, however, when given in combination with puromycin reversed in the protective action of puromycin against audiogenic seizures. Puromycin administered to 19-day-old mice increased susceptibility to electroconvulsive seizures when the animals were tested at 22 days of age. It is suggested that puromycin is able to block priming-induced audiogenic seizures by producing abnormal electrical activity in the brain or through an interference with normal neurohumoral transmission by incomplete peptides.

Acoustic Stimulation↗

A pressure vessel model for nerve compression.

This paper suggests that compression block in nerve can be better interpreted in terms of a pressure vessel model for nerve fiber distension that the more common models based upon tubes with more or less rigid walls. In this model resistance to compression is due to the elasticity of the cell membrane at locations where displaced intracellular fluid tends to distend it. Because the stresses in pressure vessels increase with the size of the vessel, the theory predicts that the percentage deformation should be larger in larger diameter fibers.

Mathematics↗

Supersensitivity-like phenomena in the central nervous system.

The are numerous supersensitivity-like changes in the central nervous system associated with denervation and disuse. There is little evidence, however, for increases in postjunctional sensitivity exactly parallel to that which occurs in disused effector organs. As we learn more about the mechanisms responsible for supersensitivity in effector organs, it becomes evident that the operation of such mechanisms in neurons may have reverberations in all spheres of cellular function, including transmitter release and energy control as well as receptor function.

Acetylcholine↗

Reversible differential block of saphenous nerve by cold.

1. This report is concerned with the question of whether the alpha and delta groups of myelinated A fibres show conduction failure at different temperatures.2. The experiments were done on cat saphenous nerve in vitro. Stimuli were applied to both ends of the nerve and biphasic recordings were taken adjacent to an 11 mm segment of nerve, whose temperature was varied. Before cooling commenced, the stimuli were adjusted so that the action potential which passed through the cold zone and was recorded, collided with the action potential initiated at the opposite end of the nerve.3. Upon cooling the nerve, it was always observed that the delta peak of the action potential which had been previously occluded by collision reappeared at a temperature at which the alpha peak remained occluded.4. The reappearance of the delta peak was reversible upon warming the nerve and was not affected by increasing the interstimulus interval.5. The mean temperature for reappearance of the delta peak was 13.5 degrees C, for reappearance of the alpha peak, 5.3 degrees C.6. In any given nerve, the blocking temperature was replicable and was dependent on the temperature of the cooled segment rather than the gradient between that segment and the remainder of the nerve.7. We conclude that in cat saphenous nerve, the delta group of myelinated A fibres shows conduction failure at a higher temperature than does the alpha group.

Action Potentials↗