PubMed Health⌕ Search

Biomedical subjects

F A Wilson

Publications and source records attributed to F A Wilson.

At least 37 records · Page 2Linked to original sources

Neuronal responses related to reinforcement in the primate basal forebrain.

In the present study neurones recorded in the substantia innominata, the diagonal band of Broca and a periventricular region of the basal forebrain responded differentially to stimuli signalling the availability of fruit juice or saline obtained by making lick responses in two different visual discrimination tasks. The activity of certain neurones reflected the rewarding nature of stimuli used to signal the availability of juice in the tasks, responding to the sight and delivery of both foods and syringes used to deliver juice in tests in which behavioural responses were irrelevant. The activity of other neurones reflected aversion, responding to task stimuli signalling availability of saline and to syringes used to deliver saline to the mouth. In another task an auditory cue that signalled the availability of juice elicited neuronal responses. These neurones also responded to a tone cue used to signal the onset of the trial, and during certain mouth and arm movements which the monkey used to obtain reinforcement. The responses of these differential neurones were similar in most respects in all 3 regions of the basal forebrain. Thus these neurones respond to a range of visual and auditory stimuli that monkeys have learned can be used to obtain reinforcement, but not on the basis of sensory properties such as shape or colour of the stimuli. We conclude that the reinforcement-related nature of the neuronal signal from the basal forebrain could be used to facilitate processing in cortical regions, optimising the functioning of sensory, motor and association cortices, thus increasing the probability of responding appropriately to learned environmental contingencies. We suggest that the properties of these neurones are due to afferent inputs from ventromedial regions of the prefrontal and temporal cortices and amygdala.

Action Potentials↗

Neuronal responses related to the novelty and familarity of visual stimuli in the substantia innominata, diagonal band of Broca and periventricular region of the primate basal forebrain.

This study examined correlates of memory processes in neuronal activity recorded from the substantia innominata, the diagonal band of Broca and the periventricular region or the basal forebrain of monkeys performing recognition and/or visual discrimination tasks. Two types of neurons were found that responded differentially to stimuli on the basis of their novelty or their familiarity. Neurons (5/572) in the periventricular region rostral to the thalamus and caudal to the anterior commissure responded to familiar stimuli with increases in firing rate. Neurons in the substantia innominata (16/1058) and in the diagonal band (14/489) responded maximally to novel stimuli, with smaller responses to reappeared presentations of these stimuli. The properties of these two types of neurons were similar in three respects: (1) the magnitude of the differential response to novel and familiar presentations of stimuli were largest for stimuli presented on successive trials, and were attenuated for stimuli that had not been seen for some intervening trials; (2) both types of neurons responded to highly familiar stimuli as if they were novel if they had not been recently seen; (3) both types responded to two- and three-dimensional stimuli; and were recorded in rhesus monkeys trained on the recognition tasks and in untrained cynomolgus monkeys. An injection of HRP into the periventricular region of one monkey resulted in retrograde labeling of ventromedial regions of the prefrontal, cingulate and temporal cortices, of the amygdala, medial thalamus, supramammillary region of the midbrain. These data indicate that information about the novelty, familiarity or recency of presentation of visual stimuli is reflected in the responses of some basal forebrain neurons. Neurons in the substantia innominata and diagonal band of Broca could not be distinguished using the battery of applied tests, suggesting functional mechanisms common to both regions. The results of the anatomical experiment suggest that ventromedial limbic cortical and subcortical regions projecting to or through the periventricular region may be important for the transmission of information about visual stimuli and for memory function.

Action Potentials↗

Learning and memory is reflected in the responses of reinforcement-related neurons in the primate basal forebrain.

Certain basal forebrain neurons encode the learned reinforcement value of objects: they respond differentially to visual stimuli that signal availability of fruit juice (positively reinforcing) or saline (negatively reinforcing) obtained by lick responses in visual discrimination tasks. In this report we describe the rapid, learning-related changes in the responses of these neurons during the acquisition and reversal of the reinforcement contingency of a visual discrimination reversal task. The same neurons also responded differentially to novel and familiar stimuli in 2 recognition memory tasks, in which monkeys applied the learned rule that lick responses to novel stimuli elicited saline and responses to familiar stimuli elicited juice. These differential responses to novel and familiar stimuli thus reflected the reinforcement value of the stimuli. A single presentation of a novel or a familiar stimulus was sufficient to elicit a differential response which was maintained even when the stimulus had not been seen recently. The maintenance of the differential response indicates that these neurons are influenced by a durable memory for the stimuli, estimated to be 30 trials on average. These differential neurons were recorded in the substantia innominata, the diagonal band of Broca, and a periventricular region of the basal forebrain. The responses of the reinforcement-related neurons in these 3 regions were similar in most respects. These results support the conclusion that basal forebrain neurons respond to sensory stimuli that, through learning of different contingencies, signal the availability of reinforcement. We suggest that the properties of learning and memory reflected in these neuronal responses are due to afferent pathways from ventromedial regions of the prefrontal and temporal cortices and the amygdala, and that the responses of these neurons provide an enabling mechanism that facilitates the operation of diverse cortical regions in which specific sensory, motor, or mnemonic functions take place.

Animals↗

Identification and comparison of bile acid-binding polypeptides in ileal basolateral membrane.

Bile acid-binding polypeptides were examined using basolateral membrane vesicles and enterocytes isolated from rat ileum. The uptake of a photolabile taurocholate derivative, (7,7,-azo-3 alpha,12 alpha-dihydroxy-5 beta[3 beta-3H]cholan-24-oyl)-2- aminoethanesulfonate,7,7-azo-TC, in ileal vesicles preloaded with paraaminohippurate (PAH) was stimulated with respect to uptake in unpreloaded vesicles. The PAH-transstimulated uptake of 7,7-azo-TC was inhibited by taurocholate and vice versa. Irradiation of membrane vesicles in the presence of 7,7-azo-TC irreversibly inhibited PAH-transstimulated taurocholate uptake. Photoaffinity labeling of basolateral membrane vesicles directly with [3H] 7,7-azo-TC and separation of proteins by SDS-PAGE revealed incorporation of radioactivity into several polypeptides. Photoaffinity labeling of vesicles in the presence of taurocholate inhibited the labeling of 54,000 and 59,000 mol. wt. polypeptides. The efflux of taurocholate from ileal enterocytes was cis-inhibited by 7,7-azo-TC and transstimulated by PAH. Irradiation of enterocytes in the presence of 7,7-azo-TC inhibited taurocholate efflux greater than the presence of 7,7-azo-TC in the dark. When enterocytes that were irradiated in the presence of [3H] 7,7-azo-TC were fractionated and the resultant basolateral membrane fraction was subjected to SDS-PAGE, incorporation of radioactivity into the 54,000 and 59,000 mol. wt. polypeptides was seen. In contrast, when the brush-border membrane fraction was subjected to SDS-PAGE, greatest incorporation of radioactivity was seen in the previously described 99,000 mol. wt. polypeptide. These studies suggest that 7,7-azo-TC shared transporters with natural bile acid and identified polypeptides that may be involved in bile acid transport across the basolateral membrane and differ from that seen in the brush-border membrane of the ileal epithelial cell.

Affinity Labels↗

Neuronal evidence that inferomedial temporal cortex is more important than hippocampus in certain processes underlying recognition memory.

Amnesia has been reported to result from combined damage to the amygdala, hippocampus and inferomedial temporal cortex in man and monkey. Evidence is presented that neuronal activity in the monkey inferomedial temporal cortex reflects memory for the previous occurrence of visual stimuli: 26 (15%) of 173 single units responded more strongly to first than to subsequent presentations of unfamiliar stimuli. No such responses were found for neurones recorded in the hippocampus and subicular cortex. The findings suggest that the inferomedial temporal cortex plays a central role in processes necessary for recognition memory.

Animals↗

Photoaffinity labeling studies of the rat renal sodium bile salt cotransport system.

The uptake of a photolabile taurocholate derivative, (7,7-azo-3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-aminoethanesulfonate, 7,7-azo-TC, into rat renal brush-border membrane vesicles was stimulated by Na+ and inhibited by taurocholate indicating an interaction with the Na+/bile salt cotransport system. Irradiation of membrane vesicles in the presence of 7,7-azo-TC inhibited Na+-dependent taurocholate uptake irreversibly. Photoaffinity labeling with [3H]7,7-azo-TC resulted in a predominant incorporation of radioactivity into a polypeptide with apparent molecular weight of 99,000. These results suggest that the proteins involved in Na+/bile salt cotransport are similar in renal and ileal brush-border membranes, but differ from those in hepatocytes.

Affinity Labels↗

An analysis of imaging studies and liver function tests to detect hepatic neoplasia.

A retrospective study was conducted to determine the sensitivity, specificity, and accuracy of scintigraphy, ultrasound, and CT scanning in conjunction with biochemical tests in the detection of liver neoplasia. Sixty-three patients with metastatic liver disease and 45 patients with nonmalignant liver disease received a total of 46 liver/spleen scans, 61 ultrasounds, and 49 CT scans. The sensitivities of liver/spleen scan, ultrasound, and CT scan were 72, 73, and 81%, respectively; the specificities were 86, 94, and 83%, respectively; and, the accuracies were 78, 84, and 82%, respectively. No statistically significant difference in specificity, sensitivity, or accuracy was seen between the three imaging studies. The serum alkaline phosphatase was significantly more accurate than total bilirubin and SGOT in detecting liver metastasis. However, 19 and 13% of the malignant and nonmalignant groups, respectively, had normal biochemical tests. The sensitivity, specificity, and accuracy of the imaging studies in the presence of an abnormal alkaline phosphatase, SGOT, or total bilirubin were not significantly different than in the presence of normal biochemical tests. These results suggest that other factors such as cost, reproducibility, and availability of skilled interpreters should be considered in the selection of imaging studies for the detection of neoplastic liver disease.

Alkaline Phosphatase↗

Dehydroascorbic acid and ascorbic acid transport systems in the guinea pig ileum.

The transport properties of dehydroascorbic acid and ascorbic acid in membrane vesicle preparations of guinea pig ileum were evaluated. Na-dependent transport of ascorbic acid in the brush-border membrane was confirmed, and an Na-independent mechanism was found in the basolateral membrane. The electrically neutral oxidized form of vitamin C is transported by an Na-independent mechanism at both cell surfaces. Transport of each substrate is saturable and exhibits cis-inhibition and trans-stimulation in the presence of structural analogues. Additional studies on ascorbate metabolism will be necessary to support a comprehensive model of intestinal handling of vitamin C.

Animals↗

Taurocholate transport by rat intestinal basolateral membrane vesicles. Evidence for the presence of an anion exchange transport system.

The transport of bile acid was studied in basolateral membrane vesicles isolated from rat small intestine. Taurocholate transport into an osmotically reactive intravesicular space was Na+ independent. The uptake of taurocholate in jejunal and ileal vesicles preloaded with sulfate was stimulated with respect to uptake in unpreloaded vesicles. Glycocholate inhibited the transstimulation of taurocholate uptake by sulfate. Sulfate and taurocholate uptake in ileal vesicles preloaded with bicarbonate was stimulated with respect to uptake in unpreloaded vesicles. Taurocholate inhibited the transstimulation of sulfate uptake by bicarbonate. When ileal vesicles were loaded with p-aminohippurate, an early transstimulation of taurocholate was found that exceeded equilibrium uptake, was insensitive to a K+ diffusion potential, and was cis-inhibited by taurocholate, glycocholate, pyruvate, p-aminohippurate, probenecid, chloride, sulfate, and bicarbonate. These data indicate the presence of an anion exchanger in intestinal basolateral membrane vesicles that may be involved in the exit of bile acids from the enterocyte.

Animals↗

Neurons in the amygdala of the monkey with responses selective for faces.

To investigate the functions of the amygdala in visual information processing and in emotional and social responses, recordings were made from single neurons in the amygdala of the monkey. A population of neurons (40 of more than 1000 recorded in 4 monkeys) was investigated which responded primarily to faces. These neurons typically (1) responded to some human or monkey faces, which were presented to the monkey through a large aperture shutter so that response latencies could be measured, or were simply shown to the monkey, (2) responded to 2-dimensional representations of these faces, as well as to real 3-dimensional faces, (3) had no responses or only small (less than half maximum) responses to gratings, simple geometrical, other complex 3-D stimuli, or to arousing and aversive stimuli, (4) had response latencies of 110-200 ms, (5) were located in the basal accessory nucleus of the amygdala, (6) responded differently to different faces, as shown by measures of d', and could thus over a population of such neurons code information useful for making different responses to different individuals, (7) could in some cases (9/11 tested) respond to parts of faces, and (8) in a few cases (4/19 tested) responded more to a face which produced an emotional response. A comparison made in three monkeys of the responses of these neurons with the responses of 77 neurons with face-selective responses recorded in the cortex of the superior temporal sulcus (STS) showed that the amygdaloid neurons had longer response latencies (110-200 compared to 90-140 ms), and were in some respects more selective in their responses to different faces. It is suggested that the deficits in social and emotional behavior produced by amygdala lesions could be due in part to damage to a neuronal system specialized in utilizing information from faces so that appropriate social and emotional responses can be made to different individuals.

Amygdala↗

Developmental maturation of D-glucose transport by rat jejunal brush-border membrane vesicles.

D-Glucose uptake into jejunal brush-border membrane vesicles was studied in suckling (2-wk-old), weanling (3-wk-old), and adolescent (6-wk-old) rats. The purity of the membrane vesicles from all age groups was validated by the finding that the specific activity of brush-border enzyme markers was severalfold greater in membrane vesicles compared with corresponding values in mucosal homogenate. D-Glucose uptake was inversely related to increasing medium osmolality, indicating that uptake of D-glucose was into the intravesicular space rather than binding. D-Glucose uptake was sodium dependent at all age groups; however, the initial uptake at 20 s was significantly greater in adolescent rats compared with suckling rats. The addition of valinomycin to KCl-preincubated vesicles in the presence of Na+ gradient resulted in a severalfold increase in D-glucose initial uptake over Na+ gradient alone, indicating that D-glucose uptake was electrogenic at all age groups. To delineate the mechanism for the decrease in the initial uptake in suckling rats, two experiments were performed: 1) an exchange tracer study that indicated the activity of D-glucose-Na+ transporters was similar in suckling and adolescent rats, and 2) a study that indicated 22Na uptake, as an indicator for Na+ permeability, was significantly greater in suckling rats compared with adolescent rats. These findings suggest that a Na+-dependent, electrogenic D-glucose uptake is already developed in the suckling period; however, because of the increased permeability to Na+, the Na+ gradient dissipates faster, resulting in a decrease in initial uptake.

Aging↗

Ontogenesis of taurocholate transport by rat ileal brush border membrane vesicles.

Developmental aspects of taurocholate transport into ileal brush border membrane vesicles were studied in 2-wk-old (suckling), 3-wk-old (weanling), and 6-wk-old (adolescent) rats. Taurocholate uptake (picomoles per milligram protein) into brush border membrane vesicles prepared from 2-wk-old rats was similar under Na+ and K+ gradient conditions (outside greater than inside). By contrast, uptake in 3- and 6-wk-old rats was significantly enhanced at 20 s, and at 1, 2, and 5 min of incubation in the presence of a Na+ gradient when compared with a K+ gradient incubation (P less than 0.05). Under isotope exchange conditions, a plot of active uptake velocity versus taurocholate concentration (0.10-1.0 mM) in 2-wk-old rat membrane vesicles was linear and approached the horizontal axis, suggesting the absence of active transport. However, similar plots in 3- and 6-wk-old rats described a rectangular hyperbola, indicating a Na+-dependent, saturable cotransport system. Woolf-Augustinsson-Hofstee plots of the uptake velocity versus concentration data from 3- and 6-wk-old rat brush border membrane vesicles yielded Vmax values that were not significantly different, 844 and 884 pmol uptake/mg protein per 120 s, respectively. The respective Km values were 0.59 and 0.66 mM taurocholate. The induction of an electrochemical diffusion potential by incubating K+-loaded vesicles with valinomycin did not significantly enhance taurocholate uptake in 2-, 3-, or 6-wk-old rat vesicle preparations. These data indicate that taurocholate transport into rat ileal brush border membrane vesicles is mediated by an electroneutral, sodium-coupled, cotransport system that is incompletely developed in the 2-wk-old suckling rat but fully developed by the time of weaning at 3 wk of age.

Aging↗

Effects of ethanol in vitro on rat intestinal brush-border membranes.

Ethanol, at concentrations found in the intestinal lumen after moderate drinking, has been shown to inhibit carrier-mediated intestinal transport processes. This inhibition could occur by direct interaction with membrane transporters, dissipation of the energy producing Na+ electrochemical gradient and/or nonspecific alteration of membrane integrity. The latter alteration may be reflected by changes in membrane fluidity, chemical composition or vesicular size. These possibilities were examined with studies in purified brush border membrane vesicles of rat intestine. Ethanol inhibited concentrative Na+-dependent D-glucose uptake in a dose-dependent manner. In contrast, ethanol did not inhibit concentrative D-glucose uptake under conditions of D-glucose trans-stimulation in the absence of a Na+ electrochemical gradient. Ethanol also inhibited initial, concentrative Na+-dependent taurocholic acid uptake, as well as equilibrium uptake. That ethanol exerted a dual effect on transport by increasing membrane conductance for Na+ while decreasing intravesicular space was supported by direct studies of Na+ uptake. Morphometric analysis confirmed that ethanol-treated membranes had a decreased intravesicular size when compared to untreated membranes. Finally, membrane fluidity measured by EPR showed that ethanol had a significant fluidizing effect without producing qualitative changes in membrane proteins, as determined by SDS gel electrophoresis. These results suggest that ethanol inhibits carrier-mediated transport by dissipation of the Na+ electrochemical gradient and alteration of membrane integrity rather than by direct interaction with membrane transporter.

Animals↗

Inhibition of bile salt transport in brush-border membrane vesicles from rat small intestine by photoaffinity labeling.

The uptake of photolabile bile acid derivative, (7,7-azo-3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24 oyl)-2-aminoethanesulfonate (7,7-azo-TC), was investigated in rat ileal brush-border membrane vesicles. The uptake of 7,7-azo-TC showed a transient vesicle to medium ratio greater than one in the presence of a Na+ gradient. The Na+-dependent uptake of 7,7-azo-TC was inhibited by taurocholate and vice versa. 130 microM 7,7-azo-TC inhibited Na+-dependent taurocholate uptake by 50%. The degree of inhibitory power on taurocholate uptake was taurodeoxycholate greater than cholate greater than 7,7-azo-TC. Photoaffinity labeling of membrane vesicles with 7,7-azo-TC irreversibly inhibited Na+-dependent taurocholate and D-glucose transport but not Na+-dependent L-alanine transport. Kinetic and photoaffinity labeling experiments indicate that this representative photoaffinity probe interacts with the ileal Na+, bile salt cotransporter and may be used to identify polypeptide components of this transport system.

Affinity Labels↗

Bile salt-binding polypeptides in brush-border membrane vesicles from rat small intestine revealed by photoaffinity labeling.

Photoaffinity labeling of small intestinal brush-border membrane vesicles with photolabile bile salt derivatives was performed to identify bile salt-binding polypeptides in these membranes. The derivatives used in this study were the sodium salts of 7,7-azo-3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acid, 3 beta-azido-7 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acid, their respective taurine conjugates, and (11 xi-azido-12-oxo-3 alpha, 7 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-aminoethanesulfonic acid. With ileal brush-border membrane vesicles, photoaffinity labeling resulted in the identification of 5 polypeptides with apparent molecular weights of 125,000, 99,000, 83,000, 67,000, and 43,000. The extent of labeling depended on the photolabile derivative employed. In jejunal brush-border membrane vesicles, polypeptides with apparent molecular weights of 125,000, 94,000, 83,000, 67,000, and 43,000 were labeled. The results indicate that the binding polypeptides involved in bile salt transport in ileal brush-border membrane vesicles are 1) similar with one exception to those concerned with bile salt transport in jejunal brush-border membranes, and 2) markedly different from those previously shown to be concerned with bile salt transport in plasma membranes of hepatocytes.

Affinity Labels↗

Acute variegate porphyria following a Scarsdale Gourmet Diet.

Symptoms of porphyria developed in a 34-year-old woman following 3 weeks of a low carbohydrate diet. Reversal of a comatose state was obtained following multiple infusions of hematin. The diagnosis of variegate porphyria was made from the pattern of quantitative urine and stool porphyrins and a plasma fluorescence that was maximal at 626 nm. This fluorescence wavelength maxima also was found in the plasma of two family members screened for latent porphyria.

Adult↗

Neuronal responses related to visual recognition.

To analyse the neural basis of long-term memory, recordings were made from single neurons in monkeys performing a visual recognition task of the type impaired in anterograde amnesia in man. Each visual stimulus was shown twice per day, once as novel, and after 0 to 17 other intervening items in the recognition task, on a second trial, as familiar, when the monkey could lick to obtain fruit juice if he recognized the stimulus correctly. At the anterior border of the thalamus, a population of neurons was found which responded to the stimuli only when they were familiar. The activity of these neurons was not related to lick responses. Further, in a different, visual discrimination, task, a number of these neurons were found to respond both to the familiar rewarded stimulus to which the monkey always licked, and to the familiar aversive stimulus to which he did not lick. This shows that in a reward association task these neurons respond on the basis of familiarity, providing evidence for a dissociation of recognition and associative memories. Analysis of the responses of these neurons in the continuous visual recognition task showed that the responses to familiar stimuli were time-locked to the onset and duration of the visual stimulation (brief exposures producing brief responses). The response latencies were in the range 100 to 200 ms. A 100 ms exposure of the stimulus was sufficient for the stimulus to be encoded, and a 100 ms exposure was also sufficient for a recognition related response. The magnitude of the neuronal response on trials with familiar stimuli decreased as the number of trials between the first (novel) and second (familiar) presentation of the same stimulus increased. The rate of this decay or 'forgetting' varied from cell to cell and was best described by an exponential function. Repeated exposure tended to slow the rate of forgetting, and two or three repeated presentations prolonged some cell 'memories' for more than 100 intervening trials. Although the majority of the neurons did not have such long 'memories', in that they responded as novel to stimuli seen on a preceding day, so that their responses could be related to recency but not to absolute recognition of ever having seen a stimulus before, 2 neurons did respond to stimuli which had not been seen for 24 h. The neurons showed some ability to respond to stimuli as familiar despite changes in viewing conditions and transformations such as 90 deg rotation. These findings indicate that the responses of these neurons at the anterior border of the thalamus are activated during recency or longer term recognition processing, both of which are impaired in anterograde amnesia in man. Measurement of the responses of these neurons, which appear to have access to memory mechanisms, has allowed parameters affecting such memory mechanisms to be investigated.

Amnesia↗

Anaerobic bacterial populations on normal and diseased human biopsy tissue obtained at colonoscopy.

Human epithelium was cultured to characterize differences in microbial populations between regions of normal colon and between polyps, inflammatory bowel disease, and cancer and their respective adjacent normal mucosa. Twenty-one patients (12 polyps, 5 inflammatory bowel disease, 4 cancer) underwent colonoscopy with anaerobic culture of mucosal biopsies from normal and diseased ascending, transverse, descending, and sigmoid colon. No differences for total number of organisms and recovery of species between ascending colon and other normal regions were seen except for sigmoid colon. Significant differences between polyps and adjacent normal tissue were seen for total number of organisms and recovery of genera and species. No significant differences in total number of organisms and recovery of genera were seen between cancer and inflammatory bowel disease and their respective adjacent normal tissue. The recovery of genera from polyps and normal tissue was Bacteroides greater than Fusobacterium greater than Clostridium greater than Eubacterium greater than Peptostreptococcus. These data suggest that (i) the total number of anaerobic organisms and species remained relatively constant, except for lower numbers in normal distal colon which were probably a result of the preparation for colonoscopy; (ii) polyp formation favored increased microbial colonization; and (iii) the increased number of organisms generally reflected those genera and species seen on adjacent normal mucosa.

Anaerobiosis↗