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Biomedical subjects

F J Smith

Publications and source records attributed to F J Smith.

At least 91 records · Page 5Linked to original sources
PubMed1986

Temporal evolution of altered islet neurotransmitter sensitivity after VMH lesion.

It has been suggested that increased insulin secretion after ventromedial hypothalamic (VMH) obesity is mediated by decreased sympathetic and increased parasympathetic neural input. The evolution of pancreatic islet adaptation was studied from 1 to 130 days after VMH lesion in rats by assessing the sensitivity of insulin secretion from incubated isolated islets to 10 mM glucose and selected acetylcholine and norepinephrine concentrations. Insulin secretion in response to glucose increased by 1 day, reaching a twofold plateau from 7 to 130 days. Sensitivity to norepinephrine increased by 1 day, whereas sensitivity to acetylcholine decreased by 2 days, and both remained altered up to 130 days. These data suggest that elevated plasma insulin concentrations characteristic of VMH obesity were associated with increased insulin secretion in response to glucose before decreased sensitivity to acetylcholine and concurrent with increased sensitivity to norepinephrine. We conclude that these compensatory responses, which shift the islet to a new operating point secondary to altered neural input, are essential to pancreatic adaptation in VMH obesity.

Acetylcholine↗
PubMed1986

Pancreatic adaptation in VMH obesity: in vivo compensatory response to altered neural input.

The objective of these studies was to determine the impact of enhanced insulin response to glucose (glucose responsiveness) and altered neurotransmitter sensitivity of the pancreatic islet previously observed after ventromedial hypothalamic (VMH) lesion on the glucose regulatory system in the whole animal. Female Wistar (220 g) rats received bilateral electrolytic VMH lesions and were implanted with cardiac and femoral cannulas under anesthesia. After recovery, experimental studies were conducted in 2-h-fasted lightly heparinized conscious rats. Plasma glucose declined at 1 and 2 wk after lesion and returned gradually to basal levels by 4 wk, whereas plasma insulin was elevated at 1 wk and remained elevated at 4.5 wk after lesion. Glucose responsiveness was increased threefold 1 wk after lesion. Acetylcholine sensitivity, measured by insulin response to an acetylcholine analogue, was decreased at 1, 2, and 4 wk after lesion, whereas norepinephrine sensitivity, measured by norepinephrine inhibition of the insulin response to intravenous glucose, was significantly increased 1 wk after VMH lesion. These studies suggest that the observed alterations at the level of the pancreatic islet led to a shift in the operating point of the glucose regulatory system of the whole animal and that changes in neurotransmitter sensitivity reflect a pancreatic adaptation subsequent to the establishment of enhanced glucose responsiveness. This shift in operating point may be secondary to altered neural input and may be essential to pancreatic and, thus, metabolic adaptation to the VMH lesion-induced obese state.

Acetylcholine↗
PubMed1985

On-line continuous measurement of blood glucose and meal pattern in free-feeding rats: the role of glucose in meal initiation.

Louis-Sylvestre and LeMagnen have suggested that the premeal decline in blood glucose is or reflects a signal for meal initiation in rats. In order to extend and test this hypothesis, a computer controlled system for continuously and concurrently measuring blood glucose and food intake in free-feeding rats was developed. In 18 experiments (with and without intravenous saline infusions), blood glucose declined about 12 minutes prior to meal onset. During 2-1/2 hours of observation, no decline in blood glucose and no meal occurred in 19 other experiments. In 7 experiments in which 10 percent glucose was infused IV to partially block the premeal decline (average blockade = 46.5%), the subsequent meal was significantly delayed. These results suggest that the pre-meal decline in blood glucose is not only correlated with but is also caudally related to meal onset. These studies suggest that the premeal decline in blood glucose is among the signals for meal initiation.

Animals↗
PubMed1985

Ovine wet carcass syndrome induced by water deprivation and subsequent overhydration: preliminary findings.

Two groups of 25 one-year-old Dorper rams were deprived of water for 52 h and then allowed free access to water for the last 18 h before they were slaughtered. One of these groups received a maize-meal and bone-meal lick containing 28,5% salt (sodium chloride) during the last 18 h period. A control group of 20 sheep received water throughout the experiment. The salt group had an average intake of 4,5 liters of water per animal in the 18 h rehydration period while the other water deprived group drank about 3,8 liters of water per animal. After being slaughtered, all the sheep in the salt group had typically wet and glistening carcasses, 18 of the other water deprived group had wet carcasses while none in the control group were affected. These results seem to indicate that the wet carcass syndrome is caused by overhydration after a period of dehydration and that salt intake during rehydration can exacerbate the condition.

Animal Husbandry↗
PubMed1984

Glucose responsiveness and acetylcholine sensitivity of pancreatic beta-cells after vagotomy.

The chronic effects of removal of parasympathetic neural input to the pancreas on in vitro insulin secretion were assessed. Groups of Wistar and Long-Evans rats received total subdiaphragmatic vagotomy or sham operation. Four to ten weeks later, after the return of food intake and body weight in the vagotomized groups to values similar to the sham-operated groups, pancreatic islets were isolated and statically incubated with selected concentrations of glucose and acetylcholine. Two experimental protocols were used. In the first experiment, insulin secretion in response to basal (5 mM) glucose was 59 +/- 15 (SE) and 65 +/- 13% greater in islets from the vagotomized Wistar and Long-Evans groups, respectively, than in the corresponding sham groups. The enhancement of insulin secretion by several doses of acetylcholine observed in islets from sham-operated groups was totally absent in islets from both vagotomized strains. In the second experiment, insulin secretion was determined in response to selected glucose concentrations by using islets from Wistar rats. An upward and leftward shift of the dose-response curve was observed in the vagotomized group causing 5 mM to become a stimulatory glucose concentration and increasing the stimulatory potency of 10 mM glucose. These results suggest that interruption of vagal input to pancreatic beta-cells may induce a compensatory increase in responsiveness to glucose and a functional suppression of acetylcholine receptors. These data provide further support for the hypothesis that vagal input plays a functionally important role in the control of insulin secretion and maintenance of acetylcholine sensitivity.

Acetylcholine↗
PubMed1983

Altered endocrine pancreatic function following vagotomy: possible behavioral and metabolic bases for assessing completeness of vagotomy.

Total vagotomy induces multiple alterations in the function of the endocrine pancreas. The temporal evolution of selected behavioral and pancreatic alterations following subdiaphragmatic vagotomy was investigated. Sustained modifications were observed in the circadian rhythm of plasma insulin, beta-cell responses to glucose and acetylcholine, whole system response to oral, but not intravenous, glucose and meal frequency. Transient alterations occurred in plasma insulin concentrations, peak glucose response to oral glucose, body weight, food intake, dark-phase meal size and light/dark food intake ratio. Since a major methodological problem in studies of the effects of vagotomy remains the assessment of the completeness of nerve section, the efficiency of several validation tests based on pancreatic alterations were investigated. Of these possible tests, the marked changes in the time-course of blood glucose following oral glucose administration and the in vivo assessment of acetylcholine sensitivity appear to be the most promising. Among other tests investigated, the water intake/100 g body weight and the stomach weight/body weight ratio had high efficiencies. It is recommended that a combination of objective tests, appropriate to the specific study, with varying degrees of invasiveness be used to assess the completeness of vagotomy.

Animals↗
PubMed1983

Odor-aversion learning in neonate rat pups: the role of duration of exposure to an odor.

Five experiments employed 2- and 10-day-old rat pups to examine the ontogeny of odor-aversion learning. When duration of exposure to the to-be-conditioned odor stimulus (CS) was long, Experiments 1 and 2 demonstrated substantial and similar aversions across the two ages regardless of whether the toxin unconditioned stimulus (US) occurred simultaneously with, immediately before, immediately after, or some time after the CS. These experiments, therefore, did not support the claim of Rudy and Cheatle (Ontogeny of Learning and Memory. Hillsdale, N.J.: Erlbaum (1979) ) that the 2-day old pup suffers a deficit in its learning about the relation between successively presented events. The remaining experiments showed, however, that the 2-day-old pups did not acquire an aversion to a briefly presented CS, that the failure to condition this CS was not due to its overshadowing by contextual cues, and that the 10-day-old pup did acquire an aversion to that CS. The experiments have revealed, therefore, that there are age-related differences in the rat pup's ability to learn about the relation between a briefly-presented CS and the effects of a US.

Animals↗
PubMed1983

Neural control of insulin secretion: interaction of norepinephrine and acetylcholine.

We have quantitatively characterized the interaction of several concentrations of norepinephrine and acetylcholine applied simultaneously on insulin secretion in response to an intermediate glucose concentration (10 mM) from statically incubated pancreatic islets isolated from normal rats. When either norepinephrine or acetylcholine were applied alone, insulin secretion was respectively inhibited or enhanced in a dose-dependent manner. When combinations of norepinephrine and acetylcholine were applied simultaneously to the islet, insulin secretion was enhanced, inhibited, or not affected. The net effects of the interaction of norepinephrine and acetylcholine on insulin secretion were not only a function of the concentration of each neurotransmitter but also the relative concentrations of both neurotransmitters. Analysis of these interaction data suggests that 1) insulin secretion is the result of a complex interaction between sympathetic and parasympathetic neural and metabolic inputs; 2) norepinephrine and acetylcholine modulate insulin secretion primarily by direct action on the beta-cell membrane; 3) insulin secretion is more sensitive to perturbations in norepinephrine concentration than acetylcholine concentrations under these experimental conditions; and 4) the autonomic nervous system has the potential to play a major role in the control of insulin secretion in response to glucose.

Acetylcholine↗
PubMed1983

Alteration of islet neurotransmitter sensitivity following ventromedial hypothalamic lesion.

Recent studies suggest that alterations in autonomic neural activity may mediate the obese state observed following ventromedial hypothalamic (VMH) lesion. To assess the role of these alterations in the increased glucose responsiveness of the beta-cell observed in this state, we have determined the sensitivity of insulin secretion to norepinephrine or/and acetylcholine in statically incubated pancreatic islets from rats 30-40 days after VMH lesion. In islets from VMH-lesioned rats compared with islets from sham-operated and intact rats, the acetylcholine dose-response curve was shifted down and to the right, indicating a decreased sensitivity, whereas the norepinephrine dose-response curve was translated to the left, indicating an increased sensitivity. The interaction profile, which summarizes combined neurotransmitter exposure on insulin secretion, was shifted in the direction of net inhibition. Thus it was concluded that, following VMH lesion, autonomic neurotransmitter sensitivity of the pancreatic beta-cell was altered. It is suggested that these alterations play a role in the adaptation of the beta-cell to the experimentally induced obese state.

Acetylcholine↗
PubMed1980

Location of the multivalent control site for the ilvEDA operon of Escherichia coli.

A strain of Escherichia coli K-12 containing a deletion extending from early in the ilvE gene toward the ilvG gene was shown to exhibit a higher expression of the downstream genes, ilvD and ilvA, than did an ilv+ strain. The elevated expression was under apparently normal ilv-specific control, however. The deletion was transferred to the ilv region of lamba h80dilv and shown by restriction endonuclease and heteroduplex analysis to extend through the deoxyribonucleic acid (DNA) shown, in the preceding paper (C. S. Subrahmanyam, G. M. McCorkle, and H. E. Umbarget, J. Bacteriol 142:547--555, 1980), to contain the ilvO determinant. The deletion was also transferred to an ilv-lac fusion strain and shown to cause an increase in beta-galactosidase formation while allowing retention of ilv-specific control. Transducing phages excised from these fusion strains with and without the ilvO determinant were compared. The phage carrying the ilvO+ determinant contained ilv DNA extending only into but not through the ilvG gene. It did not exhibit an ilv-specific control of beta-galactosidase formation. The phage carrying the deletion of ilvO but containing ilv DNA extending beyond the ilvG gene exhibited ilv-specific control of beta-galactosidase formation. It was concluded that the multivalently controlled ilv-specific promoter affecting ilv operon expression lies upstream from ilvG and that the ilvO region in the wild-type K-12 strain is a region of polarity preventing ilvG expression and reducing ilvEDA expression.

Coliphages↗
PubMed1979

Mutations affecting the formation of acetohydroxy acid synthase II in Escherichia coli K-12.

Genetic mapping experiments have established that two recently isolated valine-resistant mutants of the K-12 strain of Escherichia coli have lesions lying between ilvE and rbs. These lesions allowed expression of the ilvG gene, specifying the valine-insensitive acetohydroxy acid synthase (synthase II) and an increased expression of the ilvEDA operon. In this respect, they resembled an earlier described ilvO lesion that was reported to lie between ilvA and ilvC. All three lesions were cis-dominant in cis-trans tests. Reexamination of the earlier studied ilvO lesion revealed that it, too, lies between ilvE and rbs. Valine-sensitive derivatives with lesions presumed to be in ilvG were selected from each of the valine-resistant strains. In two of the valine-resistant strains, the ilvG mutations were on the rbs side of ilvO, indicating a gene order rbs-ilvG-ilvO-ilvE-ilvD-ilvA-ilvC. In one of the recently isolated valine-resistant stocks, however, the apparent ilvG mutation was found to be between ilvE and the aline resistance marker. This finding suggests that either ilvO and ilvG mutations are interspersed or there is another locus, ilvR, that behaves phenotypically like ilvO and which lies between ilvG and rbs.

Acetolactate Synthase↗
PubMed1978

Comparative effectiveness of directive vs. nondirective group therapist style on client problem resolution.

This study was designed to determine the utility of two newly developed self-report measures of group therapy effectiveness. Repeated administrations of these instruments indicated that group therapy was effective in inducing significant problem resolution and that these changes were stable on a 3-month follow-up. One of the measures also suggested that the nondirective style of therapy appeared to be more effective than the directive style. Results suggest that two self-report measures may be useful in studies designed to determine both the outcome as well as the process of group psychotherapy.

Adult↗
PubMed1977

Identification of subgroups of euthyroid graves's ophthalmopathy.

We attempted to determine if euthyroid Graves's ophthalmopathy is a single entity or a heterogeneous group of disorders. Activity of long acting thyroid stimulator protector occurred in 31 of 33 patients with Graves's hyperthyroidism but in only nine of 17 with euthyroid Graves's ophthalmopathy. Of the euthyroid patients, six had protector activity and thyroid non-suppressibility; firm goiters and high titers of thyroid antibodies were the rule in this group. We believe that these patients have three autoimmune diseases: Hashimoto's thyroiditis, Graves's thyroid disease and Graves's ophthalmopathy. Five euthyroid patients had no detectable protector activity or thyroid antibodies and had normal thyroid suppressibility; the thyroid was generally normal in size and consistence. These patients are interpreted as having "isolated" Graves's ophthalmopathy without any autoimmune thyroid disease. The remaining six patients showed dissociation between protector activity and thyroid non-suppressibility and cannot be classified as yet. Euthyroidism in Graves's ophthalmopathy may have more than one cause.

Autoantibodies↗
PubMed1977

The mental health administrator and evaluation.

The administrator is responsible for ensuring that evaluation is an integral part of mental health programs. To do this, several important factors such as staff resistance must be considered.

Administrative Personnel↗
PubMed1974

Field trials of calciferol combined with warfarin against wild house-mice (Mus musclus L.).

A combination of calciferol (vitamin D(2)) and warfarin, each at 0.025% in medium oatmeal bait, failed to control six of seven house-mouse (Mus musculus L.) populations infesting urban and farm buildings. In three further treatments with both calciferol and warfarin at 0.05% in dehusked canary seed bait plus 5% corn oil, mortality, estimated from the consumption of pre- and post-treatment census bait, ranged between 94.2 and 97.4%. Finally, among sixteen treatments done with calciferol at 0.1% and warfarin at 0.025% in various cereal baits, the best results (97.0-100%) were obtained in six treatments where the bait-base was whole canary seed; this was so whether the poison bait was applied directly or after a 3-day pre-baiting period. It is concluded that calciferol at 0.1% plus warfarin at 0.025% is an effective combination against house-mice, especially when used with whole canary seed. The role played by warfarin in the poison mixture needs to be investigated further.

Animals↗