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Biomedical subjects

B M King

Publications and source records attributed to B M King.

At least 37 records · Page 2Linked to original sources

Hyperinsulinemia in rats with obesity-inducing amygdaloid lesions.

Electrolytic lesions of the posterodorsal aspects of the medial division of the extended amygdala in female rats result in hyperphagia and excessive weight gain. In the present study, the effects of such lesions on plasma insulin, glucose, corticosterone, and adrenocorticotropic hormone were assessed during a period of food restriction and again after a 15-day period of food ad libitum. Compared with control animals, the rats with amygdaloid lesions were hyperinsulinemic under both conditions and gained substantially more weight when fed ad libitum. No difference between groups was observed for the other hormones. It is concluded that damage to the posterodorsal aspects of the medial amygdala results in a primary metabolic dysfunction that accounts, at least in part, for the overeating and excessive weight gain.

Amygdala↗

Changes in the telephone calling patterns of adolescent girls.

It is commonly believed that adolescent girls now call adolescent boys on a regular basis and this represents a change in behavior from previous generations. The purpose of this study was to test the hypothesis that during the last 40 years the incidence has increased. A sample of current students from a Southern urban commuter university was interviewed to determine their telephone use patterns. The changes in calling behavior among this sample indicates a transition period between a time when adolescent girls perceived their parents as disapproving of their calling boys (they placed few calls) to a time when adolescent girls perceived their parents as approving (they evidenced many such calls). Based on the current age of respondents, the transition period was calculated to be from 1964 to 1981. The results are discussed in relation to changes in adolescent female gender roles in the United States beginning in 1964.

Adolescent↗

Effect on food intake and body weight of lesions in and adjacent to the posterodorsal amygdala in rats.

Bilateral lesions centered in the posterodorsal amygdala of female rats resulted in hyperphagia and excessive weight gain. The brain damage extended posteriorly through the amygdalohippocampal area and into the ventral hippocampus and subiculum. Lesions centered in the ventral hippocampal formation had a less pronounced, although still significant, effect on body weight. Damage to large areas of the amygdala, including the anterior, basolateral, and corticomedial groups of nuclei, was without effect. A serial reconstruction of overlapping areas of destruction for both effective and ineffective lesions is presented.

Amygdala↗

Hyperphagia and obesity in female rats with temporal lobe lesions.

Damage to the temporal lobes in cats, dogs, and primates has long been known to result in hyperphagia and obesity, but research into the role of this area of the brain in feeding behavior has largely been neglected because of an inability to produce similar results in rats. The present study reports hyperphagia and obesity in female rats with small electrolytic lesions centered in the posterodorsal amygdala. Daily food intake more than doubled in the first few days after surgery and mean weight gain was more than four times that observed in animals with sham lesions during the first 26 days. The rats with lesions were not hyperresponsive to a switch in diets (lab chow to high-fat, and back). In all animals that gained abnormal amounts of weight, the posterior extent of the lesions extended through the amygdalohippocampal area into the ventral hippocampal formation. The results suggest that the temporal lobe is an important extrahypothalamic site for the regulation of food intake in rodents.

Animals↗

Abnormal weight gain in rats with amygdaloid lesions.

Marked weight gain was observed in female rats given small electrolytic lesions in the dorsal posterior portion of the amygdala. With a standard lab pellet diet, weight gains typically ranged between 20-30 g during the first 3 postoperative days, and between 60-100 g over the first 20 days. Rats with sham lesions generally gained only 5-15 g in 20 days. The results are consistent with much older studies that reported obesity in cats, dogs, and primates with lesions of the amygdala.

Amygdala↗

Level of corticosterone replacement determines body weight gain in adrenalectomized rats with VMH lesions.

Adrenalectomized female rats with lesions of the ventromedial hypothalamus or sham lesions were given SC implants of wax pellets or a fused mixture of corticosterone-cholesterol (40, 75, or 130% by weight). In animals with sham lesions, high dosages of corticosterone proved to be catabolic (r = -0.61 between plasma corticosterone and weight change). In marked contrast, animals with VMH lesions displayed substantial weight gains at all circulating levels of corticosterone, with a significant positive correlation (r = +0.48) between these two variables. It is concluded that: a) damage to the basomedial hypothalamus alters an organism's response to corticosterone at both ends of the dose-response curve, and b) both Type I and Type II corticosterone receptors in the brain play a role in hypothalamic obesity.

Adrenal Glands↗

Paraventricular hypothalamic obesity in rats: role of corticosterone.

The role of adrenal glucocorticoid hormones in the weight gain produced by lesions of the paraventricular nuclei was explored in two experiments. In the first experiment, female rats with PVN lesions were found to have normal a.m. plasma corticosterone concentrations and blunted, albeit still elevated, p.m. concentrations. Nighttime corticosterone levels were moderately correlated with plasma insulin levels. In the second experiment, adrenalectomy markedly suppressed weight gain in animals with very large PVN lesions (mean weight gain of 33.0 g/20 days compared to 137.6 g/20 days for PVN rats with sham adrenalectomies). In the ADX-PVN group, there was a +0.90 correlation between plasma corticosterone levels and weight gain. Administration of corticosterone restored the abnormal weight gain in ADX-PVN animals. It is concluded that the steroid receptors mediating this effect of corticosterone lie outside the hypothalamus.

Adrenalectomy↗

Sulfate transport in normal and cystic fibrosis fibroblasts.

The glycoconjugate component of cystic fibrosis (CF) epithelial secretions is abnormally sulfated. Previous studies have suggested that some but not all CF fibroblasts express this secondary defect. We tested the hypothesis that the major CF mutation (delta F508/delta F508) is correlated with elevated sulfate transport, by measuring the rates of saturable and nonsaturable [35S]SO4(2-) uptake in skin fibroblasts isolated from CF patients of known genotype. No significant differences were apparent between normal and CF fibroblasts.

Biological Transport↗

Ventromedial hypothalamic obesity: a reexamination of the irritative hypothesis.

The basic assumption of brain research utilizing lesions is that any observed changes in behavior or physiological responses must be the result of tissue destruction. Reynolds suggested 25 years ago that in the case of electrolytic ventromedial hypothalamic lesions, the observed hyperphagia and obesity were due instead to metallic ion deposits from the electrode tip irritating adjacent tissue. His "irritative hypothesis" was largely ignored after others reported obesity in rats given nonirritative (i.e., no deposits) VMH lesions. However, recent studies have shown that the experimental observations by both Reynolds and his critics were correct and that the early discrepancies were largely due to the sex of the animals used in the experiments. Obesity can be produced with nonirritative VMH lesions, but the weight gain is only about 60% of that observed with irritative VMH lesions and the animals do not display the characteristic lesion-induced elevations in basal insulin levels. A new combination ablation-irritative hypothesis is proposed in which electrolytic VMH lesion obesity is attributed in part to tissue ablation and in part to metallic ion deposits stimulating (rather than disinhibiting) vagally mediated insulin responses.

Animals↗

Lead in the placenta, membranes, and umbilical cord in relation to pregnancy outcome in a lead-smelter community.

As part of a cohort study of the effects of chronic exposure to lead on pregnancy outcome and child development, lead concentrations in the umbilical cord and placental tissues (body and membranes) from 9 late fetal deaths, 23 preterm births, and 18 births associated with premature rupture of the amniotic membranes were compared with the lead concentrations in the tissues obtained at 22 normal births. Modest elevations in lead concentration were found in the placental body of late fetal deaths (stillbirths) and preterm births as well as in the cord tissue associated with preterm births and premature rupture of membranes. The geometric mean lead concentration in the membranes from late fetal deaths was 2.73 micrograms/g of dry tissue (95% confidence limits 0.69-10.8), which was 3.5 times higher than the mean found in normal births (0.78 micrograms/g, 95% confidence limits 0.61-1.00). The concentration in the membranes of preterm births was also significantly high, being 1.24 micrograms/G (0.91-1.67). Low correlations of membrane and antenatal blood lead concentrations suggest that other factors in addition to exposure to environmental lead may influence the amount of lead accumulated in the placental membranes.

Chemical Industry↗

Hypothalamic obesity: comparison of radio-frequency and electrolytic lesions in weanling rats.

Female rats were subjected to radio-frequency or anodal electrolytic lesions of the ventromedial hypothalamus (VMH) when 28 days old. Blood samples for determination of basal plasma insulin and glucose levels were taken on postoperative day 30 (Experiment 1) and on day 10 (Experiment 2). Body weight and daily food intake of rats with either type of lesion did not differ from unoperated animals during the first 10 days, but rats with electrolytic lesions, unlike radio-frequency lesioned animals, displayed excess food intake and weight gain starting in the third postoperative week. Both types of lesions produced stunted linear growth and a higher than normal Lee Obesity Index. Only the rats with electrolytic VMH lesions were significantly hyperinsulinemic on postoperative day 30, with a mean plasma insulin level that was at least double that observed in unoperated or radio-frequency lesioned animals. On day 10, however, the animals with electrolytic lesions had markedly lower plasma insulin and glucose levels compared to the other two groups, which did not differ from one another. There was no apparent difference in the size of the lesions produced by the two techniques, and it is therefore concluded that some of the endocrine dysfunctions resulting from electrolytic VMH lesions are due to metallic ion deposits (stimulating adjacent tissue) rather than to tissue ablation.

Animals↗

Effects of clonidine on self-selection of nutrients.

A Richter cafeteria was used to probe the self-selection of separate macro- and micronutrients in animals injected with the alpha 2 agonist, clonidine. The most effective dose of clonidine (25 micrograms/kg) used by previous investigators with more limited nutrient offerings elicited increases in carbohydrate (1, 12, 36 hr) and vitamin A (36 hr) consumption, and decreases in salt consumption (1, 36 hr). Casein intake was depressed at 1 hour, but increased at 12 hr. A significant negative correlation between sucrose and oil intake lent statistical support to Richter's concept of "sucrose and oil burners." Other significant correlations indicated that physiological links between nutrients may underly their cooccurrence in an animal's diet.

Animals↗

Comparison of radio-frequency and electrolytic lesions of the paraventricular hypothalamic nucleus.

Radio-frequency and anodal electrolytic lesions of the paraventricular nucleus (PVN) were found to produce equal and dramatic increases in body weight in female rats. Neither of the groups with lesions had significantly elevated plasma insulin levels during a period of food restriction, but individual values varied greatly. Both groups displayed marked basal hyperinsulinemia after 30 days of food ad lib. It is concluded that radio-frequency and electrolytic PVN lesions produce similar obesity syndromes.

Animals↗

Glucocorticoids and hypothalamic obesity.

Recent studies have demonstrated a role for adrenal glucocorticoid hormones in the hyperphagia and obesity which follow lesions of the ventromedial hypothalamus (VMH). Although VMH lesions elevate morning plasma corticosterone levels, it is concluded that this contributes little to the development of obesity. More importantly, animals with VMH lesions appear to be hyperresponsive to very low levels of circulating glucocorticoids. The overeating and obesity are both prevented and reversed by either complete adrenalectomy or complete hypophysectomy (i.e., resulting in plasma corticosterone levels of less than 1.0 microgram/dl) and restored by dosages of glucocorticoids that have no effect on feeding behavior and weight gain in nonlesioned adrenalectomized animals. Mineralocorticoid hormones have no effect on hypothalamic obesity. Judging by the time course of effects on feeding behavior in VMH-damaged mice of a single intracerebroventricular injection of a low dose of glucocorticoid, which has no effect when administered intraperitoneally, it is concluded that glucocorticoids exert their effect centrally in a permissive, rather than a regulatory, manner. Stimulation of the neighboring paraventricular nuclei (PVN) with norepinephrine or neuropeptide Y produces a rapid feeding response which is also abolished by adrenalectomy and restored with administration of glucocorticoids. However, it is unlikely that the PVN is the site at which glucocorticoids exert their effect in animals with VMH lesions, for PVN lesions or knife-cuts, or combination VMH-PVN lesions, also result in hyperphagia and obesity. It is concluded that adrenal glucocorticoid hormones exert their permissive effects on feeding behavior at brain sites other than the medial hypothalamus. The septo-hippocampal complex is suggested as a possible site.

Animals↗

Alcaligenes piechaudii from chronic ear discharge.

A recently described bacterium, Alcaligenes piechaudii, was isolated repeatedly from the ear discharge of a diabetic man. This appears to be the first report of human infection in which there is clinical evidence of a pathogenic role for this species.

Alcaligenes↗

Radio-frequency vs. electrolytic VMH lesions: differential effects on plasma hormones.

Electrolytic lesions of the ventromedial hypothalamus (VMH) result in marked hyperphagia and obesity, but several studies have found the excess food intake and weight gain to be greatly reduced when lesions are produced by electrocauterization with radio-frequency current. Unlike electrolytic lesions, radio-frequency lesions leave few or no deposits of metallic ions that can potentially stimulate adjacent tissue. In the present experiment, weight gain and several endocrine responses previously associated with the VMH syndrome were compared in female rats given either electrolytic, radio-frequency, or sham VMH lesions. Both groups with VMH lesions became obese, but rats with radio-frequency lesions displayed only 63.2% of the weight gain of animals with irritative lesions (120.0 vs. 189.8 g in 20 days). Only rats with electrolytic lesions displayed elevated plasma insulin levels during an initial period of food restriction, but both groups with lesions were hyperinsulinemic when allowed to overeat. Plasma growth hormone levels were decreased by electrolytic lesions but unaffected by radio-frequency lesions. Morning corticosterone levels were elevated in both VMH groups, but only the rats with electrolytic lesions were found to have elevations in plasma adrenocorticotropin. It is concluded that some of the endocrine dysfunctions resulting from electrolytic VMH lesions are due to irritative stimulation rather than to tissue ablation.

Animals↗

Hypothalamic obesity: comparison of radio-frequency and electrolytic lesions in male and female rats.

Obesity-inducing lesions of the ventromedial hypothalamus (VMH) have generally been produced by passing anodal electrolytic current through a stainless steel electrode, which in addition to tissue ablation leaves deposits of metallic ions that might chronically irritate surrounding tissue. Although a few early investigators reported that nonirritative lesions (i.e., those that do not leave deposits) resulted in little or no obesity, their results were largely ignored when others observed substantial weight gain in animals after using the same techniques. The results of the present experiment suggest that these discrepancies were the result of a sex difference (the former group of studies all used male rats, while the latter group all used females). Male rats in the present study gained less than 80% of the weight gained by female rats regardless of lesion type, while rats with nonirritative radio-frequency lesions gained about 60% of the weight gained by rats with electrolytic lesions regardless of sex. Thus, female rats with radio-frequency lesions displayed substantial (albeit suppressed) weight gain, whereas male rats with identical lesions gained only slightly more weight than sham-lesioned controls. It is concluded that obesity resulting from electrolytic lesions of the VMH is due in part to tissue ablation and in part to chronic irritation (possibly of parasympathetic efferents mediating insulin release).

Animals↗

Nonirritative lesions of VMH: effects on plasma insulin, obesity, and hyperreactivity.

Obesity resulting from lesions of the ventromedial hypothalamus (VMH) has often been attributed to ablation-induced disinhibition of insulin release. However, lesion studies have generally employed electrolyzing anodal current with stainless steel electrodes, which results not only in tissue ablation but deposits of metallic ions that can chronically irritate surrounding tissue. The present study compared the effects of irritative and nonirritative VMH lesions on plasma insulin levels and obesity in female rats. Blood samples were obtained after a 4-h fast and 17 min after the initiation of a meal (6 ml of sweetened milk in 7 min) during a period when VMH rats were food restricted to the level of sham-operated animals and again when all animals were fed ad libitum. Irritative lesions (anodal electrolytic with stainless steel electrodes) caused heavy metallic ion deposition at the lesion site, marked obesity, and hyperinsulinemia both during food restriction and ad libitum feeding. Nonirritative lesions (cathodal electrolytic with platinum electrodes) resulted in no metallic ion deposition in seven of nine animals. These seven rats, which displayed 65% of the weight gain of animals with irritative lesions (significantly greater than sham rats), had significantly elevated insulin levels only under the postabsorptive condition during ad libitum feeding. In addition, only the animals with irritative lesions displayed emotional hyperreactivity to capture and handling. It is concluded that obesity produced by anodal electrolytic lesions with stainless steel electrodes is a result of both a destructive component resulting in hyperphagia with secondary hyperinsulinemia and an irritative component (accounting for up to 40% of the weight gain in female rats) resulting in basal hyperinsulinemia independent of hyperphagia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗