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F A Wilson

Publications and source records attributed to F A Wilson.

67 records · Page 4Linked to original sources
PubMed1975

Thiamine transport across the rat intestine. I. Normal characteristics.

The characteristics of normal thiamine transport across the intestine were studied in rats using intact intestinal loops and everted jejunal segments. In vivo studies with [35-S]-thiamine hydrochloride revealed, in all segments of small intestine, saturation kinetics for low thiamine concentrations (0.06 to 1.5 muM), but a linear relationship between high concentrations (2 to 560 muM) and absorption. Moreover, in vitro studies of net transmural flux using everted jejunal sacs demonstrated movement of [14-C]-thiamine hydrochloride against a concentration gradient only when low, but not when high, thiamine concentration was used, so that the serosal to mucosal ratio became significantly greater than the initial value of one. Pyrithiamine, 2 muM, dinitrophenol, 200 muM, norethylmaleimide, 100 muM, and ouabain, 10 muM, reduced the net transmural flux of 0.2 muM thiamine. In contrast, these inhibitors had no effect on 20 muM thiamine. When unidirectional flux across the jejunum was measured, saturation kinetics was again demonstrated for low thiamine concentrations. This phenomenon, however, was abolished by the addition of pyrithiamine, which exerted competitive inhibition on thiamine absorption. Anoxia and sodium lack reduced intestinal uptake of 0.5 muM thiamine to 58% and 74% of normal, respectively, but did not affect uptake of 50 muM thiamine. Lowering the marked with low thiamine concentrations (O10, 1.648) than with high concentration (Q10, 1.127). Stirring of the water layer reduced Km to 59% of unstirred value, while Vmax and permeability coefficient remained unchanged. Finally, movement of low concentration thiamine against an electrical gradient was observed under conditions of electrical short circuiting and zero potential difference. In contrast, no such effect was seen with high concentrations. These studies suggest that there exists in the rat a dual system of intestinal thiamine transport. At low concentrations, thiamine is absorbed by an active process; at high concentrations, transport across the intestine is largely a passive movement.

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PubMed1975

Thiamine transport across the rat intestine. II. Effect of ethanol.

We have previously investigated the normal characteristics of thiamine intestinal transport in rats and found that a very low concentrations (0.06 to 2.0 muM) thiamine transport is a saturable, carrier-mediated, active process while at high concentrations (greater than 2.0 muM) transport proceeds by simple diffusion. The present studies were undertaken to characterize the effect of ethanol on thiamine transport. Intact isolated loops were used to measure rates of 35S-thiamine hydrochloride absorption into the circulation in vivo, and everted jejunal segments to measure net transmural flux, unidirectional uptake, and cellular exit of 14C-thiamine hydrochloride in vitro. Intragastric administration of ethanol (50 to 750 mg. per 100 grams of weight) reduced absorption of low thiamine concentration in vivo to 65.44 per cent of control value. A similar inhibition was noted after intravenous ethanol. Once attained, the inhibition of thiamine absorption was not related to the ethanol dose or to ethanol concentration in the blood or in the intestinal lumen; this inhibition was reversible. In contrast, ethanol did not affect absorption of high concentrations of thiamine. These findings were confirmed by the in vitro results. In transmural flux studies, the movement of low, but not high, thiamine concentration against a concentration gradient was inhibited by ethanol, so that the normal serosal/mucosal ratio of 1.5 was reduced to 1.0. Ethanol did not affect unidirectional uptake into the mucosa of either low or high thiamine concentrations, but blocked cellular exit of low thiamine concentrations from the cells into the serosal compartment. Exit of high thiamine concentrations was not affected. Ouabain, like ethanol, markedly reduced cellular exit but did not influence uptake of low thiamine concentrations. The present studies suggest that ethanol adversely affects the active, but not the passive, component of thiamine transport. Moreover, ethanol appears to block thiamine exit from the cells but does not affect cellular uptake of thiamine. The similarity to ouabain action suggests that ethanol may impair active thiamine transport by inhibiting Na-K ATPase activity.

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PubMed1972

Characterization of bile acid absorption across the unstirred water layer and brush border of the rat jejunum.

We have examined the rate-limiting steps involved in bile acid absorption across the unstirred water layer and lipid cell membrane of the jejunal mucosa. Uptake of the polar bile acid taurocholate is limited solely by the cell membrane since this compound permeates the unstirred water layer more rapidly than the lipid cell membrane and stirring does not enhance uptake. With less polar bile acids which permeate the cell membrane relatively more rapidly, however, the unstirred water layer does exert resistance to mucosal uptake of these compounds. That the unstirred water layer is even more rate limiting to uptake from micellar solutions is indicated by the facts that the rate of bile acid absorption from such solutions is lower than from corresponding monomer solutions, stirring markedly enhances uptake from micellar solutions while increases in viscosity of the incubation media depress uptake and expansion of the micelle size further depresses absorption rates. We also have examined the important question of whether the micelle crosses the brush border intact once it reaches the aqueous-lipid interface. The observations that the calculated permeation rate of the micelle should be extremely low, the rate of mucosal cell uptake plateaus at a constant value when the critical micelle concentration is reached at the aqueous-lipid interface, and the different components of a mixed micelle are taken up at different rates indicate that uptake of the intact micelle does not occur; rather, bile acid absorption must be explained in terms of monomers in equilibrium with the micelle. Finally, after correction of the permeability coefficients of the various bile acids for the unstirred layer resistance the incremental partial molar free energy of solution of the hydroxyl group in the brush border membrane was calculated to equal -6126 cal.mole(-1) indicating that passive diffusion of these compounds occurs through a very polar region of the cell membrane.

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PubMed1972

Determination of unidirectional uptake rates for lipids across the intestinal brush border.

An in vitro method is presented which measures valid, unidirectional uptake rates for lipids across the intestinal brush border. This method combines analysis by a newly devised, double isotope counting system for solubilized tissue with the use of a nonabsorbable marker to correct gross uptake determinations for contamination by adherent mucosal fluid. Of seven markers, only [(3)H]inulin measured adherent mucosal fluid volumes as much as 20% greater than the other markers. Diffusion of the nonabsorbable marker, as well as of the compound being studied, into the unstirred layer made the time course of uptake critically important. The time lag for diffusion of marker invalidates the use of 1-min incubation periods; however, a linear time course of uptake that intercepts essentially at zero was found for taurocholate and octanoate for periods of from 2 to 5 min. Working within this critical time period with jejunum, it was shown that tissue dry weight was an appropriate measure of the amount of tissue and that uptake rates for taurocholic, octanoic, and lauric acids were linear with respect to concentration. Tissue binding of compounds was not significant. The results demonstrate that careful use of the described method yields accurate measurement of unidirectional uptake rates of lipids across the brush border that are of critical importance in defining the characteristics of membrane penetration and the rate-limiting steps in fat and sterol absorption.

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PubMed1971

Unstirred water layers in intestine: rate determinant of fatty acid absorption from micellar solutions.

Bile acid and fatty acid uptake from micellar solutions by intestinal cells fails to reflect the incremental free energy changes expected for permeation that is rate limited by cell membranes. However, altering the size of the diffulsing particle or the thickness of tle unstirred water layer does change uptake. These observations show that the unstirred water layer is rate limiting for intestinal absorption of lipids from micellar solutions.

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PubMedDate not supplied

Face-selective neurons during passive viewing and working memory performance of rhesus monkeys: evidence for intrinsic specialization of neuronal coding.

The functional organization of prefrontal cortex (PFC) is a central issue in cognitive neuroscience. Previous physiological investigations have often failed to reveal specialization within the PFC. However, these studies have generally not been designed to examine this issue. Methodological issues such as statistical criteria for specificity, the number of neurons sampled, the extent of cortex sampled, and the number, location and nature of the stimuli used are among the variables that need to be considered in evaluating the results of studies on functional localization. In the present study, we have examined neurons in macaque monkeys trained to fixate while viewing visual stimuli, including faces, or to use them as memoranda on a working memory task. Visual responses of over 1500 neurons were recorded throughout a wide expanse of the PFC (areas 12, 9, 46, 8 and 45). Neurons were considered selective for faces if the best response to a face was over twice as strong as that to any of a wide variety of non-face stimuli. Full electrode track reconstructions in three monkeys revealed in each that neurons which met this criterion were concentrated almost exclusively in three distinct subregions within the projection region of the temporal lobe visual areas. We further show that for all neurons, the most visually selective neurons (for faces, objects or color patterns) were also the most concentrated in the temporal lobe recipient PFC. Similar face selectivity, regional specialization, and delay or delay-like activity were observed in monkeys whether trained on memory tasks or not, which suggests that these are naturally occurring properties of prefrontal neurons. These results confirm neuronal and regional specialization for information processing in PFC and elucidate how heretofore unexamined experimental variables have a strong influence on the detection of regional specialization.

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PubMedDate not supplied

Cortical and subcortical structures involved in recognition memory: neurophysiological and anatomical studies.

Recordings of neuronal activity were made in cortical and subcortical structures of monkeys performing visual recognition memory tasks in which the novelty/familiarity of the stimuli was varied. A population of neurons with memory-like activity was recorded in a periventricular region at the border of the anterior thalamus and dorsal hypothalamus. These neurons responded with decreases in firing rate to novel stimuli and increases in firing rate to the same stimuli when they were familiar. The calculated memory spans of these neurons ranged from 7 to hundreds of intervening trials. The afferent connections of this region were traced by an injection of HRP into the periventricular region. Retrogradely labeled cells were observed in the ventromedial prefrontal cortex, the ventromedial temporal cortex, amygdala, medial thalamus and supramammillary region. Recordings were then made in the hippocampus and ventromedial temporal cortex. A population of neurons in the ventromedial temporal cortex responded maximally to the first presentation of a stimulus, reflecting the novelty or recency of the stimulus presentation. In contrast, such neurons were not observed in the CA fields or subiculum of the hippocampal formation. These studies suggest that a system of brain structures involving the temporal cortex and periventricular region provide one mechanism whereby monkeys are able to recognise and respond to visual stimuli differing in their novelty and familiarity.

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