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Biomedical subjects

J W Kemnitz

Publications and source records attributed to J W Kemnitz.

At least 55 records · Page 3Linked to original sources

The effects of topical diazoxide on hair follicular growth and physiology of the stumptailed macaque.

Diazoxide, an anti-hypertensive agent, has diverse pharmacologic effects; hypertrichosis, hyperglycemia associated with suppression of insulin release, and elevation of serum levels of androgens. Taking advantage of the hypertrichotic side effects of diazoxide, we examined the effect of topical application of the drug on hair regrowth in the bald frontal scalp of stumptailed macaques (Macaca arctoides); we also monitored systemic side effects. Using 7 adult stumptails, we applied diazoxide (5% solution in a vehicle) topically on the bald frontal scalp, once a day, 5 days per week. Two of seven macaques had vehicle alone applied. Hair growth was monitored by photographic recording (once every month) and by sequential analysis of folliculograms from biopsied skin (once every 4 months). We also examined body weight, hematology, blood pressure, heart rate, serum levels of testosterone and dihydrotestosterone, and glucose tolerance for a 4-month period. All 5 diazoxide-treated animals showed thickening and maintenance of the frontal hair during the entire treatment period (16 months). Analysis of folliculograms showed progressive enlargement of hair follicular size and acceleration of its cyclic growth from telogen to anagen phase and prolongation of anagen phase in all treated animals. Controls showed no consistent progressive changes of follicular growth. None of the animals treated with diazoxide showed abnormal changes in physical growth, cardiovascular function, serum levels of androgens, glucose tolerance (including insulin levels), or hematology.

Alopecia↗

Effects of ovarian hormones on eating behaviors, body weight, and glucoregulation in rhesus monkeys.

The influences of ovarian hormones on food intake, taste preferences, and glucoregulation were examined in intact and ovariectomized rhesus monkeys. Intake of intact monkeys was lowest in the preovulatory stage of the cycle, when estrogen levels are elevated, and exogenous estradiol transiently suppressed food intake of ovariectomized monkeys in a dose-related manner, confirming previous observations. Progesterone treatment did not affect food intake when given alone, but it did attenuate the effect of estradiol when both hormones were given concurrently. Preferences for sweet solutions were not detectably influenced by chronic treatment with estradiol or progesterone, and compensatory responses to ingestion of sugar were unaltered by hormone treatment. Glucose tolerance tests did not reveal significant influences of ovarian hormones on glycemia, but insulin levels were elevated during periods of progesterone treatment. These results do not support the suggestion that fluctuations in caloric intake during the menstrual cycle are secondary to changes in taste preference or glucoregulation. However, possible changes in sweet preference and glucoregulation shortly after initiation of estrogen treatment, i.e., during the time of suppressed food intake, remain to be examined.

Animals↗

Effects of food restriction and adrenalectomy in rats with VMH or PVH lesions.

The effects of adrenalectomy in rats with ventromedial or paraventricular hypothalamic lesions have been studied in two experiments. Rats with ventromedial hypothalamic lesions or lesions in the paraventricular nucleus were allowed to gain weight for fourteen days at which time they were adrenalectomized. Before adrenalectomy, animals with VMH lesions ate more, gained significantly more weight than animals with lesions in the paraventricular nucleus, and both were significantly heavier and consumed more food than sham-operated controls. Following adrenalectomy, food intake decreased and both groups of lesioned animals lost weight. The animals with VMH lesions stabilized at weights above the control animals. Implantation of corticosterone enhanced weight gain and food intake in animals with lesions in either the paraventricular nucleus or the ventromedial hypothalamus. In the second experiment, one subgroup of rats with VMH lesions was adrenalectomized, and allowed to eat ad lib. Two other groups of sham-operated rats with VMH lesions served as controls. One group ate ad lib and one group was pair fed to the food intake of the adrenalectomized VMH-lesioned rats. Weight gain in the adrenalectomized VMH-lesioned rats and the pair-fed VMH-lesioned controls was similar and less than the VMH-lesioned rats eating ad lib. GDP binding to interscapular brown adipose tissue was related to the degree of weight gain, not to the presence of the VMH lesion. These data show that corticosterone is essential for the expression of obesity in both PVH- and VMH-lesioned rats. They also argue that the reduction in the activity of the sympathetic nervous system of VMH-lesioned rats as estimated by the GDP binding to mitochondria from brown adipose tissue is associated with hyperphagia.

Adipose Tissue, Brown↗

Obesity in male and female rhesus monkeys: fat distribution, glucoregulation, and serum androgen levels.

Obese (n = 8) and nonobese (n = 6) adult rhesus monkeys (Macaca mulatta) were assessed in terms of body size and distribution of body fat, glucose tolerance, and serum lipid, insulin, and androgen levels. The weights of the obese monkeys were more than 2 SD above the mean for their sex, while the nonobese monkeys averaged less than 0.25 SD from the mean. Obese males and females had excess body fat located predominantly in the abdominal region; abdominal circumference was highly correlated with total body fat, as estimated by the isotope dilution method (r = 0.98; P less than 0.001). Obese monkeys of both sexes had fasting hyperinsulinemia, greater insulin response to iv glucose administration, and marginally impaired glucose tolerance. Obese males had delayed maximal insulin response to glucose administration. Fasting serum triglycerides also were elevated in the obese monkeys (0.95 +/- 0.08 vs. 0.47 +/- 0.05 mmol/L; P less than 0.001). Obese males had lower serum dihydrotestosterone levels than nonobese males (3.1 +/- 0.7 vs. 5.6 +/- 0.4 nmol/L; P less than 0.01). Nonobese females had approximately 2-fold higher serum dehydroepiandrosterone sulfate levels than the other groups. We conclude that obese male and female rhesus monkeys have patterns of fat distribution and glucoregulatory abnormalities similar to those of humans with upper body obesity. The contribution of differences in androgen metabolism to the development of obesity and its complications in rhesus monkeys remain to be defined.

Adipose Tissue↗

Androgenic influences on body size and composition of adult rhesus monkeys.

The effects of daily treatment with testosterone propionate (TP, 2 mg/kg) and dihydrotestosterone propionate (DHTP, 2 mg/kg) were examined in rhesus monkeys in three experiments. In experiments 1 and 2, males and females gonadectomized in infancy, and female pseudohermaphrodites produced by prenatal exposure to TP or DHTP and gonadectomized postpubertally, were studied in conjunction with intact males (IM). The IM group was heavier in adulthood than the three gonadectomized groups, which did not differ in body weight from each other. Genetic males had greater crown-rump length than genetic females. Treatment of the gonadectomized groups with TP produced large increases in body mass (averaging approximately 50%) that were attributable to accretion of lean tissue. This effect did not differ significantly between males and females. In experiment 3, additional groups of males that had been castrated as infants were given daily injections with DHTP or oil. The DHTP treatment resulted in increases in body size that were not different from those seen following TP treatment. When TP and DHPT treatments were discontinued, body weights and dimensions reverted to base-line values. Increased body size induced by TP and DHTP was accomplished without reliable increases in food intake. Because testosterone (T) is metabolized to dihydrotestosterone (DHT), while DHT cannot be converted to T, these results show that both T and DHT are effective anabolic hormones in rhesus.

Aging↗

Dynamic and static phases of obesity following lesions in PVN and VMH.

The effect of electrolytic lesions in the ventromedial hypothalamus (VMH) and the paraventricular nucleus (PVN) has been compared during both the dynamic and static phase of weight gain. Hyperphagia and weight gain were greater in the VMH-lesioned rats than in the PVN-lesioned rats. Food intake increased at night after both lesions but increased in the daytime only in VMH-lesioned rats. During the dynamic phase of rapid weight gain, the diurnal pattern of corticosterone was blunted to a similar degree in both lesioned groups. The morning insulin concentrations were higher in both lesioned groups than in the sham-operated controls, but in the static phase only the VMH-lesioned rats had higher insulin levels. In the afternoon the insulin was higher in the VMH-lesioned rats than in either the sham-operated or PVN-lesioned rats. In the dynamic phase the weight of interscapular brown adipose tissue was significantly increased in the VMH-lesioned rats, but the specific GDP binding was depressed both in the morning and afternoon when compared with either the sham-operated or PVN-lesioned groups. In both the dynamic and static phases GDP binding was similar in sham-operated and PVN-lesioned animals. The differences in concentration of corticosterone in morning and afternoon were smaller in the lesioned groups than in the controls. These data are consistent with the hypothesis that animals with PVN lesions do not show the disturbances in food intake or in the autonomic nervous system that characterize the VMH-lesioned rats.

Adipose Tissue, Brown↗

Lateral hypothalamic lesions and fenfluramine increase thermogenesis in brown adipose tissue.

The effects of treatment with fenfluramine or electrolytic lesions in the lateral hypothalamus (LH) on binding of guanosine 5-diphosphate (GDP) by mitochondria from brown adipose tissue have been compared in 4 experiments. In 2 experiments the lesions were lateral to the anterior hypothalamic nucleus and in the other two they were lateral to the ventromedial hypothalamic nucleus. Binding of GDP to mitochondria was significantly increased 18 hours after an electrolytic lesion in either LH site. d,1-Fenfluramine, 20 mg/kg, also increased GDP binding in both acute experiments. In the other 2 experiments GDP binding was measured 11 days after the LH lesion or after 11 daily injections of fenfluramine. When the chronic lesions were lateral to the VMN, there was a transient drop in food intake and body weight. With more anterior lesions, body weight remained significantly lower than in sham-operated rats although food intake returned slowly to control levels. Fenfluramine-treated rats had lower body weights in both chronic experiments even after food intake returned to normal. GDP-binding to mitochondria from interscapular brown adipose tissue was elevated in both of the chronically-treated fenfluramine groups but was only increased in the LH-lesioned rats whose body weight remained below normal.

Adipose Tissue, Brown↗

Characteristics of spontaneous obesity in male rhesus monkeys.

Adult male rhesus monkeys representing a wide range of adiposity were characterized according to body dimensions, eating behaviors, and endocrinologic/metabolic indices. Body fat, located most prominently on the abdomen, ranged from 30 to 61% of body weight. Three groups were formed on the basis of body composition data: Very Obese (VO), Moderately Obese (MO) and Nonobese (N). These groups did not differ in food intake, preferences for sweet solutions, or compensatory changes in food intake following consumption of sugar solutions. Glucose tolerance was normal, but fasting insulin levels and insulin response to glucose loading increased with increasing adiposity. Fasting triglyceride levels were highly correlated with insulin values and body fat. It is concluded that some adult male rhesus monkeys develop obesity without obvious differences in eating behavior and that obese monkeys, like obese humans, are at risk for diabetes mellitus and its complications.

Animals↗

Comparison of ventromedial and paraventricular lesions in rats that become obese.

Lesions in the ventromedial hypothalamus (VMH) uniformly produced obesity, but lesions in the paraventricular nucleus (PVN) produced obesity in only half of the animals. The obesity in the PVN-lesioned animals was related to the extent of PVN damage and was attenuated by concurrent damage to the dorsomedial nucleus. Comparing the PVN-lesioned rats that became obese with the VMH-lesioned rats that showed comparable weight gain, revealed several differences. The nocturnal intake of food in rats eating ad libitum was lower in the VMH-lesioned rats. Glucose concentrations were also lower in the VMH-lesioned rats, whether eating ad libitum or pair fed. Insulin concentrations were higher in the fatter animals fed ad libitum regardless of the location of the lesion. After pair feeding the insulin values were lower in both VMH- and PVN-lesioned rats than in controls. The diurnal excursion of corticosterone was blunted by both hypothalamic lesions in rats fed ad libitum, but after pair feeding there was less distortion of the diurnal rhythm. These data show that the characteristics of obesity produced by PVN lesions differ from those resulting from VMH damage.

Animals↗

Fetal lung development in male and female nonhuman primates.

Indices of lung maturation were assessed in 58 rhesus fetuses at five gestational ages during the last trimester of nonhuman primate pregnancy to determine whether fetal sex influences lung maturation. In addition to analysis of whole lung phospholipids, glycogen, protein, DNA, and pressure-volume curves surfactant fraction phosphatidylcholine (PC) was quantitated following isolation by sucrose gradient centrifugation and a combination of predictors were assessed by all possible subsets regression to attain a composite "maturity index." For the total population, there was a uniform progression in physical growth characteristics, lung destensibility and stability and phospholipids with advancing gestation. The quantitative change in surfactant fraction PC concentration for both sexes was considerably greater than that observed for whole lung PC between 135 days gestation and term. Further, the increase in surfactant PC occurred in association with improving lung destensibility and deflation stability prior to maximum changes in the whole lung PC or disaturated PC concentration. There were no statistically discernible differences in biochemical or physiological assessment between sexes at any gestational age. These data in nonhuman primates suggest that documented differences in survival from the respiratory distress syndrome between males and females do not result from a discordance in lung maturation as a function of time throughout the last trimester of gestation.

Animals↗

Effect of vagotomy on serum insulin in rats with paraventricular or ventromedial hypothalamic lesions.

The effects of vagotomy on plasma glucose and insulin levels in rats with paraventricular nuclear (PVN) or ventromedial hypothalamic (VMH) lesions were measured during a constant glucose infusion. In one experiment, vagotomy was performed 50 min after the lesions, and in a second experiment, it was performed at the same time as the lesions. After the introduction of lesions in the PVN, there was a significantly greater rise in plasma glucose than in animals with either large or small VMH lesions, both of which had plasma glucose values similar to those in the sham-lesioned animals. The rise in insulin was greater in all three lesion groups than in the sham-operated animals. Although both plasma glucose and insulin had begun to decline before the vagotomy performed 50 min after lesioning, there was a further subsequent fall after vagotomy which was greater in the VMH-lesioned animals with large lesions than in rats with PVN lesions or small VMH lesions. In the sham-lesioned rats, there was no significant change in insulin or glucose after vagotomy. When the vagotomy and hypothalamic lesions were performed simultaneously, the glucose and insulin values in all groups were the same. The present experiments suggest that VMH and PVN exert different controls over pancreatic hormone secretion. The VMH lesions appear to remove an inhibitory effect on the vagus, with resultant hyperinsulinemia in the absence of hyperglycemia. The PVN-lesioned animals show a hyperglycemia which is abolished by vagotomy, suggesting that the PVN connects to vagal fibers which activate the glucagon secretory system in the alpha-cell of the pancreas.

Animals↗

Norepinephrine stimulates activity of brown adipose tissue in rhesus monkeys.

Brown adipose tissue biopsies were obtained from the axillary region of adult rhesus monkeys before and after a 30-min infusion of norepinephrine or vehicle. Binding of guanosine diphosphate (GDP) to brown adipose tissue mitochondria increased an average of 186 percent in response to norepinephrine, while vehicle infusion resulted in an average decrease of 35 percent. The results are consistent with unmasking and remasking of GDP binding sites and indicative of functional brown adipose tissue in adult primates.

Adipose Tissue, Brown↗

Brown adipose tissue from fetal rhesus monkey (Macaca mulatta): morphological and biochemical aspects.

Brown adipose tissue (BAT) from fetal rhesus monkeys microscopically resembled adult rodent BAT containing multiocular fat cells with numerous mitochondria. Mitochondrial carnitine palmitoyl transferase activity was lower than that in adult rodents and adenine nucleotide translocase activity was similar to that reported for rats. Rhesus monkey BAT mitochondria (BATM) possess an uncoupling protein that is characteristic of BAT as evidenced by the binding of [3H]GDP, the inhibition by GDP of the high Cl- permeability or rapid alpha-glycerol-3-phosphate oxidation. Electrophoretic analysis of BATM showed the presence of a 32,000 mol.wt protein which was enriched by procedures established for the isolation of BATM uncoupling protein.

Adipose Tissue, Brown↗

Developmental aspects of lung lipids.

From this review, it is evident that multiple maternal/fetal endogenous or completely exogenous factors have been associated with the complex process regulating fetal lung development. Recent in vitro experiments with human fetal lung explants are especially noteworthy and may establish a perspective for future research. Snyder et al (108) and Medelson et al (74) have found that lung explants from 16-22-week abortuses show differentiated type II cells and augmented PC synthesis within 4 days of culture, rather than the minimum 10- to 15-week period expected in utero. Such a phenomenon is reminiscent of the usual time for clinical recovery from uncomplicated RDS (34). Thus, although expression of the genes influencing lung surfactant phospholipid synthesis and related biochemical processes normally occurs relatively late in gestation, the potential for biochemical differentiation is clearly present in earlier stages. It appears then that the "programming" of the fetal lung for maturation is not absolute but may be altered under certain influences. Whether the advent of lung biochemical maturation occurs as a result of release from inhibition, as the human lung explant data imply, or occurs in response to stimuli, as suggested by exogenous corticosteroid effects, remains to be clarified and is a very challenging scientific problem. It will also be of great interest to define further other biochemical regulators, such as fibroblast pneumocyte factor, that may play an important role in fetal lung maturation.

Androgens↗

Changes in food intake during menstrual cycles and pregnancy of normal and diabetic rhesus monkeys.

Food intake of control and streptozotocin-diabetic rhesus monkeys was measured during menstrual cycles and pregnancy. Intake of control monkeys was lower at the time of ovulation than during other phases of the menstrual cycle. Intake of control monkeys was also low during most of pregnancy, but this was accompanied by normal fetal growth and net maternal weight gain. Diabetic monkeys ate more than controls in all conditions and their intake did not vary reliably according to reproductive status. It is suggested that (1) oestrogen normally inhibits food intake during menstrual cycles and pregnancy, (2) food energy is utilized more efficiently during pregnancy than during non-pregnant states, and (3) the influence of oestrogen on food intake is either attenuated by insulinopenia or is obscured by the hyperphagia typically exhibited by the diabetic monkeys.

Animals↗

Ovarian hormones influence brown adipose tissue.

Adult female rats were ovariectomized (OVX) or sham-operated and 4-5 weeks later OVX groups were treated with estradiol benzoate (EB), progesterone, both hormones, or the oil vehicle. All rats were sacrificed on the 4th day of hormone treatment following an overnight fast and a terminal meal. Interscapular brown adipose tissue (BAT) pads of EB-treated groups were heavier and contained more lipid than those of the other OVX groups. Lipid content of adipose tissue differed according to site (BAT less than inguinal less than parametrial = retroperitoneal), but only BAT exhibited differential responsiveness to hormonal treatments. There was also a trend for increased oxygen consumption by BAT from EB-treated rats. It is concluded that BAT may be involved in the process of increased energy expenditure by estrogen-treated rats.

Adipose Tissue, Brown↗