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Biomedical subjects

D S Miller

Publications and source records attributed to D S Miller.

At least 217 records · Page 12Linked to original sources

Development of brush-border membrane hexose transport system in chick jejunum.

Hexose transport was characterized in jejunal slices and brush-border membrane (BBM) vesicles from chicks of several ages (range: 2 days before hatch to 21 days after hatch). With slices, initial rates of 0.1 mM 3-O-methyl-D-glucose transport were low in --2-, and 0-day chicks, increasing to maximal levels 2-7 days after hatching; rates declined to adult levels over the next 2 wk. Phlorizin did not inhibit uptakes in --2- or 0-day slices. In contrast, about 80% of the uptakes in tissue from 2-day or older chicks was phlorizin inhibitable. The apparent Kt for phlorizin-sensitive transport was the same in slices from 2- (maximal transport rates) and 21-day (minimal posthatch rates) chicks; the apparent Vmax was 2.5 times greater in 2-day slices. With BBM vesicles, initial rates of Na-dependent D-glucose transport and maximal overshoot levels were greater in 2-day vesicles than in 21-day vesicles. As in slice experiments, Kt values were the same in the two preparations, but Vmax values were 1.4 times higher in the 2-day preparation.

Aging↗

Heavy metal inhibition of p-aminohippurate transport in flounder renal tissue: sites of HgCl2 action.

p-Aminohippurate (PAH) uptake by teased flounder renal tubules was concentrative, Na-dependent, dependent on aerobic metabolism and inhibited by competitor organic anions and ouabain. Dose-response data for ouabain inhibition of PAH transport and tubule Na,K-adenosine triphosphatase (ATPase) activity were identical. In ouabain-treated tubules, reductions in PAH uptake correlated with alterations in total tissue Na and K even though both were not affected during the first 5 to 10 min of ouabain exposure. No such delay was found with HgCl2 and, as with ouabain, reductions in transport correlated well with alterations in tissue Na and K. Tissue respiration data indicated that low concentrations of HgCl2 rapidly affected the Na,K-ATPase. With higher HgCl2 concentrations, intracellular metabolic sites appeared to be affected. Transport studies with ouabain-poisoned tubules and plasma membrane vesicles indicated that the energetically uncoupled PAH carrier(s) were affected by HgCl2, but carrier sensitivities to Hg were lower than for the Na,K-ATPase. The data indicate that HgCl2 inhibits PAH transport primarily by reducing ion gradients that drive PAH transport. Both inhibition of Na,K-ATPase and increases in membrane permeability to Na and K appear to be involved.

Aminohippuric Acids↗

HgCl2 inhibition of nutrient transport in teleost fish small intestine.

Mediated D-glucose and cycloleucine uptakes by killifish intestinal slices and everted sacs were reduced in a dose- and time-dependent manner by HgCl2 exposure, but nonmediated components of nutrient uptake were not affected. Transport processes in intestinal slices from sea water and fresh water-adapted fish exhibited identical sensitivities to HgCl2. The inhibitory effects of mucosal plus serosal exposure (slices) were no greater than the effects of mucosal exposure alone (sacs), indicating that primary inhibitory sites were on the brush border membrane of the tissue. One- to 5-min slice exposures (which caused substantial inhibition of nutrient transport) did not affect cellular water or electrolyte levels (indirect measures of Na,K-adenosine triphosphatase activity). With brush border membrane vesicles from killifish and flounder small intestine, HgCl2 affected only the Na-dependent component of D-glucose up-take. Vesicle Na permeability was not increased by HgCl2 exposure. Kinetic studies with killifish slices and flounder vesicles indicated that both Km and Vmax for glucose transport were affected by HgCl2. Taken together, these findings indicate that HgCl2 blocks intestinal nutrient transport by interacting directly with brush border membrane transport proteins; the kinetic data indicate that multiple sites on these proteins are probably affected.

Amino Acids↗

A new member of the team? Extending the role of the nurse in British primary care.

533 (77.3%) of a random sample of 690 general practitioner (GP) principals in Britain replied to a postal questionnaire about the appropriateness of nurses undertaking, after suitable training and under the supervision of a doctor, but on their own, certain clinical tasks (history taking, examination, diagnosis, and advice on treatment) in general practice. Those who replied were representative of British GPs. Two-thirds were in favour of the extended role and were prepared to delegate clinical tasks to a nurse. Their opinion was unaffected by whether or not they had worked with or observed the work of medical auxiliaries. 65% of those in favour would prefer to work with a woman. The characteristics most significantly associated with acceptance of this new role for the nurse were: doctors aged less than 50 years and practices in which regular formal meetings took place between doctors, nurses, and other practice staff.

Age Factors↗

Effects of 2-deoxy-D-glucose on multi-unit activity of the hypothalamus in rats.

Multi-unit activity was recorded from the diencephalon of unanesthetized, immobilized female rats. Less than 50% of the recording sites in the hypothalamus showed changes in the level of multi-unit activity to changes in the level of glucose utilization induced by injection of 2-deoxy-D-glucose (2-DG). It was also not possible to specificy an area within the hypothalamus in which there was a concentration of recording sites which consistently responded to 2-DG. Relatively large amplitude, long duration changes in multi-unit activity levels were also observed in the optic tract, suggesting that 2-DG induced a widespread cellular metabolic response to glucoprivation which may not have been related to the regulation of feeding.

Animals↗

The measurement of food and energy intake in man-an evaluation of some techniques.

A dietary survey was carried out on an Antarctic base over a period of 6 to 12 months on twelve individuals. Three methods of determining individual food and energy intake were used-weighing and recording of food as eaten in combination with food tables, dietary recall, and bomb calorimetry of duplicate meals. Use of weighed food intakes and food composition tables underestimated energy intake by 7% when compared to analysis of duplicate meals by bomb calorimetry. One week was found to be the most practical period over which intake should be measured to determine "habitual" food intake.

Adult↗

The measurement of daily energy expenditure--an evaluation of some techniques.

An energy balance survey was conducted on an Antarctic base on 12 individuals for periods varying between 6 and 12 months. Energy expenditure was estimated using two activity/dairy card techniques and mean 24-hr heart rate used in conjunction with a variety of derived heart rate/energy expenditure regression equations. The accuracy of the various techniques was determined by comparison with estimates obtained using energy intakes and changes in body fat. No method of measuring energy expenditure was accurate enough to predict fat gain or loss. Errors in individuals were large and random but the mean error in the estimation of energy expenditure of the community was reasonable. When using the dairy card there was no difference between using measured values for energy costs of specific activities and using values taken from the literature. Using heart rate was no less accurate than the diary card if energy expenditure was predicted from a regression line derived from heart rate and log energy expenditure, and the technique was more acceptable to the subjects.

Adipose Tissue↗

A longitudinal study of body weight and body fat changes in Antarctica.

Body weight and body fat changes (calculated from skinfold thickness) that occurred in a male population spending a year on an Antarctic base are described. There was a marked individual variation in patterns of weight and fat changes between seasons but mean values for the whole community showed little change over the year. Combining skinfold and body weight measurements revealed probable individual differences in fat gain or loss with weight gain and loss, but the role of changes in total body water or fat-free mass could not be determined. The possibility of combining long-term measurements of body fat and energy intake to provide an estimate of energy expenditure is discussed.

Adipose Tissue↗

PAH transport in rock crab (Cancer irroratus) urinary bladder.

Crab urinary bladder appears to possess several morphological and functional similarities to vertebrate renal proximal tubule. Sections of intermolt rock crab bladder accumulated PAH by a process that was concentrative (60 min tissue-to-medium ratio (T/M) for 10 microM PAH averaged 24), Na dependent, powered by glycolytic metabolism, and inhibitable by other organic anions. Initial section uptakes exhibited saturation kinetics and a double-reciprocal plot of uptake vs. concentration yielded a single line with a Km of 70 microM and a Vmax of 5 nmol . mg tissue-1 . h-1. Chlorophenol red and bromocresol green (BCG) competitively inhibited PAH uptake. When bladder sheets were mounted in a flux chamber, they exhibited a large, net lumen-to-serosa (L leads to S) flux of 10 microM PAH that was abolished by 1 mM BCG. The small unidirectional S leads to L flux was not BCG-inhibitable. Bladder sheets exhibited PAH T/M greater than 1 after luminal, but not serosal, exposure. BCG only reduced bladder sheet T/M after luminal exposure. The data are consistent with uphill, Na-dependent, and carrier-mediated entry of PAH at the luminal membrane and nonmediated exit at the serosal membrane.

Aminohippuric Acids↗

HgCl2 inhibition of D-glucose transport in jejunal tissue from 2 day and 21 day chicks.

Chick jejunal slices that were exposed to HgCl2 exhibited markedly reduced uptakes of D-glucose. The carrier-mediated (phloridzin inhibitable), but not diffusive, component of uptake was affected by Hg. Within each age group, I50 values (concentration of HgCl2 causing 50% inhibition of mediated transport) for slices (mucosal plus serosal exposure) and sacs (mucosal exposure only) were nearly identical; values for brush border membrane vesicles were slightly lower (increased sensitivity). For each preparation, I50 values for 2 day chicks were consistently lower than corresponding values for 21 day chicks. Taken together, these data indicate that the jejunal brush border membrane is a site of HgCl2 action and that membrane sites in tissue from 2 day chicks are more sensitive to Hg than similar sites in tissue from 21 day chicks.

Age Factors↗

Teleost kidney in evaluation of xenobiotic toxicity and elimination.

The unique anatomy of the marine teleost kidney and the development of techniques to take advantage of that anatomy are discussed and several examples of their use to study xenobiotic excretion and toxicity are documented. These include: 1) characterization of renal organic anion transport, the system that mediates excretion of many such compounds and their metabolites; 2) assessment of the relative roles of transport, metabolism, and plasma binding in xenobiotic excretion; 3) examination of the morphological aspects of cellular injury; and 4) analysis of subcellular sites of heavy metal toxicity. Also presented are applications of new techniques in membrane physiology to the study of the effects of xenobiotics. It is suggested that continued application of the comparative approach, as exemplified by the use of the marine teleost kidney, will provide powerful and versatile tools for investigation of fundamental biological processes and the interactions of foreign compounds with those processes.

Animals↗

The relative importance of genetics and diet in determining adipocyte number and size in the periovarian fat pad of the rat.

Seven types of rat were fed either stock diet, wheat diet, or a high-fat diet for 98 days. Little difference was found for any parameter between rats fed the wheat and stock diets, but compared to rats fed the stock diet, body weight was 9 per cent higher in the rats fed the high-fat diet, and body-fat proportion was 31 per cent higher. The adipocytes contained 32 per cent more fat and were present in 42 per cent greater number. The extent of dietary-induced difference depended on the strain, but in any case was a much less important determinant of adipocyte number than the genetic differences already existing in the rats. When the extreme groups of Zucker-obese and wild rats were excluded, the diet assumed greater importance in determining adipocyte size and number.

Adipose Tissue↗

Pathways of cycloleucine transport in killifish small intestine.

By using blocking concentrations of competitors, i.e., concentrations of other neutral amino acids that cause maximal inhibition, cycloleucine transport into slices or everted sacs of killifish (fundulus heteroclitus) small intestine could be partitioned into three pathways. One is apparently not mediated, a second is inhibited by all neutral amino acids tested (component 1), and a third, is inhibited by alpha-aminocarboxylic acids (component 2), but not by beta-alanine or taurine. Both mediated pathways were Na dependent, and each yielded a linear double reciprocal plot of initial slice uptake vs. cycloleucine concentration. Apparent Kt and Vmax values for component 1 were 0.03 mM and 33 pmol/mg tissue per 3 min, respectively; corresponding values for component 2 were 0.12 mM and 28 pmol/mg tissue per 3 min. Additional experiments with an intestinal brush border membrane vesicle preparation indicate that these mediated components reflect true differences in carrier specificity rather than the differential effects of inhibitors on metabolism or on the Na gradient that drives cycloleucine transport.

Amino Acids↗

Energy balances in obese mice.

According to most existing theories, the regulation of energy balance is achieved by control of energy intake. This study was undertaken to find out whether there was control of energy output as well. Food intake, energy balance and the feed efficiency of weanling female mice made obese with injections of gold-thioglucose and monosodium glutamate indicate that the obesity is primarly due to an increased energetic efficiency, and suggest that the hypothalamus plays a role in controlling energy output. In the case of treatment with MSG, a relative obesity was observed, i.e. an increase in body fat without any change in body weight. This indicates that the CNS centres for the regulation of body weight and body fat are probably not the same. It is suggested that MSG obesity will be a suitable model for comparative studies of body weight and the regulation of fat content. It is concluded that chemically induced obesity is due more to a lower metabolic rate than to an elevated food intake.

Animals↗