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D W Townsend

Publications and source records attributed to D W Townsend.

48 records · Page 3Linked to original sources

A multicompartment model of vitamin B6 metabolism.

The shape of the labelling curve for urinary pyridoxic acid following a single dose of labelled pyridoxine can be most easily described by a two compartment model. However, the usefulness of such a model is limited because the two pools have no physiological identity; the model does not describe the many metabolic interconversions associated with vitamin B6 metabolism; and the predictions of the total size of the vitamin B6 pool are not consistent with data from direct measurements. Therefore, we have been using the Simulation, Analysis, and Modelling program (SAAM) developed at the National Cancer Institute to develop an improved model. Since the SAAM 29 program is limited to 25 pools, only a few of the many tissue vitamin B6 pools could be included. Muscle and liver were chosen because they contain 80 to 90% of the vitamin B6 in the body. Plasma and erythrocytes were selected because of their importance in transport. This review traces the development of the model to its current stage and shows comparisons between the predictions of the model and a variety of data from the literature. At this point the emphasis has been on describing metabolism in rats because the most detailed kinetic data available were obtained from rats. The predictions of the current model do not match all available observations. However, the results are sufficiently encouraging to warrant continued development.

Animals↗

Plasma catecholamines associated with hypothalamically-elicited flight behavior.

Hypothalamic sites were selected which elicited flight (escape) behavior in the freely moving cat. Sympatho-adrenal (SA) activation was determined by measuring the levels of norepinephrine (NE) and epinephrine (E) in bilateral adrenolumbar and peripheral venous plasma following stimulation of these 29 hypothalamic sites in 18 anesthetized cats. Heart rate (HR) and mean arterial pressure (MAP) were continuously monitored to permit comparisons between SA and cardiovascular (CV) activation. The most frequent SA response was a bilateral increase in the output of NE and E from the adrenal medulla greater than or equal to 10 ng/min. Increases in MAP during hypothalamic stimulation were significantly correlated with bilateral increases in both adrenal CAs, while increases in HR were significantly correlated with increases in peripheral venous NE. The data suggest that hypothalamic regions which elicit flight behavior overlap with regions that activate the adrenal medullary and CV systems. The SA activation that accompanied hypothalamically-elicited escape is compared to SA activation associated with hypothalamically-elicited affective defense.

Adrenal Medulla↗

Plasma catecholamines associated with hypothalamically-elicited defense behavior.

Sympatho-adrenal (SA) activation was determined by measuring levels of norepinephrine (NE) and epinephrine (E) in bilateral adrenal venous and peripheral venous plasma of 20 anesthetized cats following stimulation of medial hypothalamic sites. Hypothalamic sites were selected that elicited affective defense behavior in the freely moving cat. Fifty-eight percent of these hypothalamic sites elicited a bilateral increase greater than or equal to 10 ng/min in the output of both adrenal catecholamines (CAs); these increases were greater from the gland ipsilateral to the side of stimulation. Other SA responses included both preferential increases or decreases in either NE or E. Under baseline conditions, an average of 67% of the NE in the peripheral venous plasma was contributed by the sympathetic noradrenergic nerves; hypothalamic stimulation at "defense" sites increased the contribution to 75%. The data suggest that hypothalamic regions that elicit defense behaviour may overlap with regions that activate the adrenal medullary and sympathetic nervous systems.

Adrenal Medulla↗

Increases in blood flow from the adrenal gland following medial hypothalamic stimulation in the cat.

Medial hypothalamic sites previously shown to elicit either flight or defense were stimulated in the anesthetized cat. The rate of blood flow from the adrenolumbar (AL) vein ipsilateral to the side of stimulation was measured, as well as the adrenal output of norepinephrine and epinephrine (E). Stimulation at nearly 15% of the hypothalamic sites increased ipsilateral AL venous flow more than 20% over baseline rates. These sites also significantly increased heart rate, mean arterial pressure, and output of E from the ipsilateral adrenal gland. These observations suggest that hypothalamic sites where stimulation increased AL venous flow may overlap with regions that selectively mediate the release of E from the adrenal medulla.

Adrenal Glands↗

Dopa oxidase activity in human hair bulbs measured by high-performance liquid chromatography.

A method for measuring the dopa oxidase (DO) activity of human hair bulb tyrosinase has been developed and the results of this method have been compared with the tyrosine hydroxylase (TH) activity of hair bulb tyrosinase for brown-, black-, blond-, and red-haired subjects. The method takes advantage of the rapid trapping of dopaquinone by cysteine with the subsequent formation of cysteinyldopas which can be measured by high-performance liquid chromatography. 5-S-Cysteinyldopa (5SCD) and 2-S-cysteinyldopa (2SCD) were detected in the reaction products. Formation of 5SCD correlated with the TH activity over the full range of hair colors and enzyme activity, while 2SCD appeared to be formed nonenzymatically. The absolute amount of 2SCD was constant for each individual but did not correlate with hair color or TH activity. The formation of 5SCD was linear for 60 min while most of the 2SCD was formed within seconds and did not change with time. White hair bulbs which demonstrated no TH activity formed 2SCD, but not 5SCD. We conclude that tyrosinase activity can be quantitated in human hair bulbs by this method, and that TH and DO are coordinate functions of tyrosinase over a broad range of hair color and enzyme activity.

Catechol Oxidase↗

The questionable relation between cochlear pigmentation and noise-induced hearing loss.

Some evidence has suggested that susceptibility to noise-induced hearing loss may be inversely proportional to the amount of melanin in the cochlea. However, published data have not been consistent in demonstrating this relation, and some results may be contaminated by lack of genetic control in experimental animals. In this investigation, noise-induced hearing loss was evaluated in pigmented and albino C57BL/6J mice that differed only in their ability to produce melanin. Surface-recorded electric responses to sound were used to assess auditory sensitivity. Results indicated no difference between the two groups either in pre-exposure thresholds or in magnitude of noise-induced threshold shift.

Animals↗

Modelling vitamin B6 metabolism in rodents (review).

Several improvements have been incorporated into a previously described compartmental model of vitamin B6 metabolism in order to expand the application of the model to non-steady state conditions such as growing animals and differing vitamin B6 intakes. A function which describes the growth of rats receiving various vitamin B6 intakes has been developed. The turnover rates for enzymatic reactions have been written in a form which responds to changes in substrate concentration. The predictions of the model are in reasonable agreement with several sets of data from the literature. Further refinement of the model is in progress.

Animals↗