Biomedical subjects

J W Kemnitz

Publications and source records attributed to J W Kemnitz.

At least 37 records · Page 2Linked to original sources

PubMed1998

Colon cancer in aged captive rhesus monkeys (Macaca mulatta).

The age-related incidence of malignant neoplasia was surveyed from a total of 301 necropsy cases of rhesus monkeys ranging in age from 13-37 years performed in the Pathology Service Unit of the Wisconsin Regional Primate Research Center during the past 15 years. All our aged monkeys lived in indoor cages and were fed with monkey chow and supplemental fruits during the past decades. In this survey, we found a total of 51 malignant neoplasms, and among them 25 cases were colon cancer. The incidence of colon cancer increased with advancing age: 3.2% at 13-19 years, 9.2% at 20-25 years, 13.5% at 26-29 years, and 20.7% at 30-37 years. Most cancers were located in the cecum and transverse regions with a unicentric origin. Two multicentric cases were associated with chronic hypertrophic colitis. Precancerous polypous lesions were not found in all cases. Histologically, all cases were mucinous adenocarcinoma and had local invasion to the muscular wall. Metastasis to the mesenteric lymph nodes was found in only two cases. As in humans, colon cancer is a common outcome of aging in nonhuman primates.

Adenocarcinoma, Mucinous↗

PubMed1998

The effect of dietary restriction on body composition in adult male and female rhesus macaques.

Dietary restriction is the only intervention shown to increase maximal life span, and to retard the rate of aging in rodents. As part of a long-term randomized trial of the effects of a 20-30% dietary restriction (DR) on adult rhesus macaques, female (N = 30) and male (N = 16) monkeys were assessed at baseline and 6, 12 and 18 months, following randomization to control (C) or dietary restricted (R) groups, for body composition by dual-energy x-ray absorptiometry. At baseline, there were no significant differences between C and R groups in any body composition parameters measured. Males had significantly (p < 0.05) greater values at baseline than females for body weight (BW), body mass index (BMI), total body lean tissue mass (LTM), appendicular skeletal muscle mass (ASM), and total body bone mineral content (BMC). When analyzed longitudinally through 18 months of DR, C females had significantly increased BW, total body fat tissue mass (FTM), total body percent fat tissue mass (%FTM), LTM, ASM, BMC and abdominal fat tissue mass (AbFTM) relative to R animals. Male C animals had significantly increased BW, FTM, %FTM, BMC and AbFTM relative to R males. The primary effect of DR on body composition in these animals was on FTM.

Absorptiometry, Photon↗

PubMed1998

Energy expenditure, body composition, and glucose metabolism in lean and obese rhesus monkeys treated with ephedrine and caffeine.

The administration of ephedrine and caffeine (E+C) has been proposed to promote weight loss by increasing energy expenditure and decreasing food intake. We tested this hypothesis in six lean (4-9% body fat) and six mildly to moderately obese (13-44% body fat) monkeys studied during a 7-wk control period, an 8-wk drug treatment period, and a 7-wk placebo period. During the drug treatment period, the monkeys were given ephedrine (6 mg) and caffeine (50 mg) orally three times per day. At the end of each period, a glucose tolerance test was performed, energy expenditure was measured, and body composition was determined. Treatment with E+C resulted in a decrease in body weight in the obese animals (P = 0.06). This loss in weight was primarily the result of a 19% reduction in body fat. Drug treatment also resulted in a decrease in body fat in the lean group (P = 0.05). Food intake was reduced by E+C only in the obese group (P < 0.05). Nighttime energy expenditure was increased by 21% (P < 0.03) in the obese group and 24% (P < 0.01) in the lean group with E+C treatment. Twenty-four-hour energy expenditure was higher in both groups during drug treatment. E+C did not produce systematic changes in glucoregulatory variables, whereas plasma leptin concentrations decreased in both groups with drug treatment. Overall, these results show that E+C treatment can promote weight loss through an increase in energy expenditure, or in some individuals, a combination of an increase in energy expenditure and a decrease in food intake.

Animals↗

PubMed1998

Caloric restriction in rhesus monkeys reduces low density lipoprotein interaction with arterial proteoglycans.

Caloric restriction (CR) has been shown to retard aging processes in many species. We investigated effects of CR on plasma low density lipoproteins (LDL), a major risk factor for the age-associated process of atherosclerosis. Studies emphasized effects of CR on LDL composition and their interaction with arterial proteoglycans (PG). Rhesus monkeys were fed a control diet (n=13) or subjected to CR (n=12 fed 30% less calories) for > 5 years. Plasma LDL cholesterol concentrations were similar for control and CR groups (82+/-8 vs 72+/-6 mg/dL, mean+/-SEM). LDL was isolated by ultracentrifugation and HPLC. LDL particles from CR animals had a lower molecular weight (2.9+/-0.1 vs 3.2+/-0.1 g/micromol, p < .05) and were depleted in triglyceride (249+/-16 vs 433+/-49 mol/particle, p < .005) and phospholipid (686+/-20 vs 837+/-33 mol/particle, p <.001). Lower PG binding was measured for LDL from CR animals (10.1+/-0.8 vs 15.6+/-1.1 microg LDL cholesterol/microg PG, p <.005). This was associated with the lower triglycerides (r=.76, p < .0005) and phospholipids (r=.48, p < .01). Thus, a dietary intervention which may retard aging inhibits a proposed mechanism of atherogenesis.

Animals↗

PubMed1998

Different central and peripheral responses to leptin in rhesus monkeys: brain transport may be limited.

The purpose of this experiment was to determine the effect of leptin administration on food intake and energy expenditure in rhesus monkeys. Four adult male rhesus monkeys, cannulated in the left lateral cerebral ventricle, were used for all phases of this experiment. Food intake was measured following intracerebroventricular injections of vehicle or three doses (500 ng, 2 micrograms, and 22 micrograms) leptin. Leptin administration resulted in a dose-dependent decrease in food intake (P < 0.05), with food intake decreased by an average of 54% at 22 micrograms leptin. Energy expenditure was also measured at two intracerebroventricular doses of leptin. Energy expenditure was not different (P > 0.10) between placebo and leptin injections at either dose. Food intake was also measured following i.v. injection of 3 mg leptin. In this case, leptin did not alter (P > 0.10) food intake, despite increasing serum leptin levels by as much as 100-fold. These results suggest that leptin is a potent inhibitor of food intake in rhesus monkeys, but this effect requires elevation of leptin concentrations in the cerebrospinal fluid or critical brain sites. The transport system for movement of leptin across the blood-brain barrier may limit the influence of circulating leptin on food intake in monkeys.

Animals↗

PubMed1997

Energy expenditure of adult male rhesus monkeys during the first 30 mo of dietary restriction.

Energy expenditure, activity, and body composition were measured in 30 adult male rhesus monkeys used in a study having the long-term goal of determining the effects of moderate dietary restriction (DR) on aging. All animals were fed a defined diet, with the restricted animals maintained at approximately 70% of the caloric intakes of the controls. After 12 mo of DR, body fat mass of restricted monkeys was 33% less than that of controls (P = 0.004), whereas lean body mass differences were not present until after 24 mo. At the 24- and 30-mo assessments, nighttime energy expenditure was significantly reduced (P < 0.01) in the restricted compared with control monkeys after adjustment for lean body mass differences, whereas morning, afternoon, and total energy expenditure were not significantly different (P > 0.05). No significant differences (P > 0.05) in activity were noticed between treatment groups at any time point. DR resulted in a prolonged decrease in resting energy expenditure, which could contribute to the possible life-extending action of this treatment.

Animals↗

PubMed1996

Age and sex differences in body size and composition during rhesus monkey adulthood.

Body size and composition were measured in forty-one adult Rhesus monkeys (Macaca mulatta) in order to characterize changes that occur during later life for both genders. Data were obtained by traditional somatometric techniques and by dual-energy X-ray absorptiometry. Representative monkeys were chosen within six categories defined by age (Young Adult, 6-9 year-old; Middle Aged, 15-19 year-old; Older Adult, 26-30 year-old), and sex. Body weight and most external measures of body size were greater during middle age and later life than in young adulthood, as were body fat content and lean body mass. Females tended to have a higher percentage body fat than males in all age categories. Lean tissue mass was markedly greater in the two younger groups for both sexes, compared to older adults. Bone mineral content and density were higher in the males than the females, but differences in bone mineralization among age groups did not achieve statistical significance. Such data derived from adult nonhuman primates are useful for defining fundamental biological changes with age in these species, and have value as a comparative model for studies of human aging and age-related morbidity.

Adipose Tissue↗

PubMed1996

The effect of advancing age on bone mineral content of female rhesus monkeys.

Dual-energy X-ray absorptiometry (DXA) can be used to assess bone mass in nonhuman primates; however, the changes in bone mineral across the lifespan have not been well described. The purpose of this cross-sectional study was to evaluate the effect of maturation and subsequent aging on bone mineral content (BMC) and bone size (two dimensional bone area) in female rhesus monkeys at sites analogous to those commonly evaluated in humans. Total body (n = 178) and lumbar spine (n = 167) DXA scans were performed on female rhesus monkeys aged 2.8 to 34.6 years. Radius scans (n = 86) were performed on monkeys aged 9.7 to 34.6 years. Measurement precision was comparable to that reported for humans. At all sites, BMC was highly correlated with bone area (p = 0.0001), which was positively correlated with both body weight (p < or = 0.002) and age (p < or = 0.08). Total body and lumbar spine BMC and bone area increased with maturation (p < 0.0001) until age 11 and then remained stable with further advancing age. There was little change in total body and lumbar spine area-adjusted BMC across the lifespan. At the radial sites, there were no significant changes in BMC or bone area with age, but the area-adjusted BMC and the weight- and area-adjusted BMC declined in older animals (p < 0.05). In conclusion, the female rhesus monkey does not attain peak bone mass until age 11. Significant bone loss at later ages was observed only at radial sites.

Absorptiometry, Photon↗

PubMed1996

Effects of maternal dexamethasone therapy on fetal lung development in the rhesus monkey.

A large body of evidence demonstrates that antenatal glucocorticoids can accelerate fetal lung maturation. The purpose of this study was to delineate the optimal dose of dexamethasone and to determine whether a single- or multiple-injection regimen of the same total dexamethasone dosage was more effective in accelerating pulmonary development. Pregnant rhesus monkeys were injected with varying doses of dexamethasone or vehicle as either a single-bolus injection or as four separate injections, each spaced 12 hours apart. All maternal treatments were begun exactly 72 hours prior to delivery, and all fetuses were delivered by cesarean section at 135 +/- 1 days gestation. When a single injection of dexamethasone was used, fetal liver weight increased in a dose-related fashion. Fetal and maternal cortisol and fetal blood glucose concentrations were also influenced by increasing dexamethasone dosages. Fetal pulmonary phospholipids, however, were unchanged at all steroid doses examined. Multiple injections of dexamethasone generally produced more pronounced effects, even though the total dexamethasone dose remained the same. Thus, liver weight and fetal and maternal cortisol, glucose, and insulin levels were significantly influenced by the multiple administration of dexamethasone. In addition, total lung phosphatidylcholine, surfactant phosphatidylcholine, the surfactant-phosphatidylcholine-to-total-phosphatidylcholine ratio, and the surfactant-disaturated-phosphatidylcholine-to-total-lung-disaturated- phosphatidylcholine ratio were elevated after the multiple-injection regimen. A total dose of 0.5 mg dexamethasone/kg maternal body weight given in four separate injections appeared to produce the most beneficial results. These data suggest that low-dose, antenatal glucocorticoid treatment can effectively accelerate the biochemical maturation of the fetal lung.

Animals↗

PubMed1996

Reduced immune responses in rhesus monkeys subjected to dietary restriction.

Dietary restriction (DR) has emerged as a major paradigm in experimental gerontology. The effects of DR on rodents are numerous and include reduced rates of immunologic aging, delayed morbidity, and increases in longevity. The effects of DR on primate species remain largely unknown. We began a randomized trial of long-term, adult-onset DR in rhesus monkeys (Macaca mulatta) in 1989. This report describes some early differences in immunologic function after two to four years of DR. Peripheral blood mononuclear cells were studied for mitogen-induced proliferation, natural killer (NK) cell lysis, and expression of cell surface antigens. Antibody response to influenza vaccine and the number of peripheral blood lymphocytes were also measured. Unexpectedly, concanavalin A and pokeweed mitogen response measures were reduced in restricted monkeys compared to controls (p < or = .01). NK activity and antibody responses were also reduced (p < .05). Neither cell surface antigens nor peripheral blood lymphocyte counts appear affected by DR thus far.

Aging↗

PubMed1994

Dietary restriction increases insulin sensitivity and lowers blood glucose in rhesus monkeys.

Insulin sensitivity and glucose tolerance typically decline during later life. In a multidimensional randomized trial of the effects of dietary restriction started in adulthood on the processes of aging, we are studying insulin sensitivity and glucoregulation longitudinally in control (C, n = 15, fed a defined diet ad libitum for 6-8 h/day) and restricted (R, n = 15, fed 30% less than C) monkeys using the Modified Minimal Model method. Linear rates of change were calculated for individual animals through 30 mo of diet treatment and compared between treatment groups. Basal glucose, basal insulin, and insulin responses to glucose and tolbutamide increased for C and decreased for R animals (P < or = 0.002), whereas insulin sensitivity decreased for C and increased for R (P = 0.008). Glycosylated hemoglobin at 30 mo was marginally lower in R (P = 0.06) and was positively correlated with fasting plasma glucose (r = 0.508, P < 0.001). Insulin changes were significantly correlated with changes in adiposity (weight and abdominal circumference). Identification of the mechanisms through which these effects are achieved may aid in ameliorating glucose intolerance, insulin resistance, and associated illnesses in older persons.

Animals↗

PubMed1994

Pioglitazone increases insulin sensitivity, reduces blood glucose, insulin, and lipid levels, and lowers blood pressure, in obese, insulin-resistant rhesus monkeys.

The antidiabetic effects of pioglitazone hydrochloride were evaluated in 6 spontaneously obese, insulin-resistant rhesus monkeys. The animals were studied during six successive 2-wk treatment phases separated by 2-wk rest periods: two placebo phases; 0.3, 1.0, and 3.0 mg.kg-1 x day-1 pioglitazone hydrochloride phases; and a final placebo phase. During the second week of each treatment phase, serum insulin (immunoreactive insulin [IRI]), plasma glucose, and serum triglyceride (TG) levels were measured after an overnight fast and after a standardized meal. Blood pressure was measured and glucose tolerance tests (modified minimal model protocol) were performed a few days after the meal tests. Pioglitazone hydrochloride significantly improved fasting and postprandial levels of IRI, plasma glucose, and TG in a dose-related manner (P < 0.05). Fasting values during treatment with 3.0 mg.kg-1 x day-1 were reduced by 64% for IRI, 19% for plasma glucose, and 44% for TG compared with the placebo phase before treatment. Efficacy of pioglitazone hydrochloride was more marked for those animals with fasting hyperglycemia. Insulin sensitivity was increased by pioglitazone hydrochloride (P = 0.05), whereas glucose effectiveness and glucose disappearance rate were not detectably affected. Systolic and mean arterial blood pressures were significantly decreased by pioglitazone hydrochloride (P < 0.05). No toxic side effects of pioglitazone hydrochloride treatment were noted.

Animals↗

PubMed1993

Insulin levels, physical activity, and urinary catecholamine excretion of obese and non-obese rhesus monkeys.

The hypothesis that spontaneous obesity in rhesus monkeys is associated with abnormalities in energy expenditure was tested. Obese (n=7) and non-obese (n=5) monkeys were described in terms of body size and composition, food intake, and physical activity. Additionally, the relationships among fasting and stimulated insulin levels in serum, C-peptide levels in serum and urine, and urinary catecholamines were examined. Obese animals had primarily abdominal deposition of excess body fat, as indicated by markedly elevated abdominal circumferences and skin-fold thicknesses. Food intake did not differ between groups. Physical activity was much lower in the obese group. Obese monkeys had markedly higher serum insulin and C-peptide levels in the fasted state and in response to an intravenous glucose challenge. Urinary excretion of C-peptide and catecholamines was measured during successive 2-day periods of ad libitum feeding, food deprivation, and refeeding in order to examine potential differences between groups in sympathoadrenal activity and their relationship to insulin secretion. C-peptide excretion was greater for obese and decreased for both groups during food deprivation. Urinary dopamine (DA), norepinephrine (NE), and epinephrine (E) levels were significantly greater for obese animals in all conditions. DA excretion was lowest during deprivation and E excretion was lowest during refeeding, whereas NE excretion was relatively unaffected by feeding condition. The overall patterns of C-peptide and catecholamine excretion were qualitatively similar for both groups, and there were no reliable differences between obese and non-obese in their responses to the feeding manipulation. The results suggest that hyperinsulinemia associated with obesity in rhesus monkeys is linked to increased catecholamine secretion and a resistance to catecholaminergic action.

Adrenal Glands↗

PubMed1993

Dietary restriction of adult male rhesus monkeys: design, methodology, and preliminary findings from the first year of study.

Dietary restriction (DR) retards aging processes and extends maximum life span in rodents and in simpler animals. We initiated a study in 30 adults (8-14 years old) male rhesus monkeys to determine whether or not aging processes are retarded by adult-onset DR in a primate species and herein report results from the experiment's first year. Following a 3-6 month period when baseline data were obtained, 15 animals were assigned to a control group and given free access to a semipurified diet for 6-8 hours per day. The other 15 monkeys were fed the same diet but at 70% of their baseline intake levels predetermined individually. The animals are being evaluated semi-annually for body size and composition, physical activity, metabolic rate, glucose tolerance and insulin sensitivity, hematologic indices, immunologic function, and fingernail growth. Ocular function is assessed annually. The preliminary observations after one year are: (a) all monkeys appear to be in excellent health; (b) average body weights for controls increased by 9% while monkeys on DR did not gain weight; (c) monkeys on DR have less body fat than do control monkeys, whereas the amount of lean body mass has not been significantly influenced by DR; (d) there was a small but statistically significant reduction in physical activity for monkeys on DR relative to controls; and (e) DR has not overtly influenced the other measures. Control monkeys gradually reduced their voluntary levels of food intake during the first year of study, and food allotments to DR monkeys are being adjusted accordingly in order to reinstate the intended 30% difference between groups. These early data indicate that DR can be safely instituted in adult monkeys, but that longer term and/or more severe DR is required to determine if it is capable of influencing age-sensitive indices in long-lived primates.

Accommodation, Ocular↗

PubMed1993

Vulnerability of placental antibody transfer and fetal complement synthesis to disturbance of the pregnant monkey.

Maternal and fetal/infant antibody levels were assessed across pregnancy and at birth to evaluate the prenatal transmission of IgG in the rhesus monkey. Although some antibody was evident in the fetus by midpregnancy, the marked increase in IgG occurred primarily during the last two weeks of pregnancy. This delay until the end of pregnancy would result in low antibody titers in premature infants. In contrast, when gestation length was normal, the placental transfer of IgG was resistant to both dexamethasone treatment and a prolonged period of stress during pregnancy. This resiliency occurred despite an effect of prenatal stress on other aspects of infant development, including physical growth and the fetal synthesis of complement proteins.

Animals↗

PubMed1993

Obesity in free-ranging rhesus macaques.

Spontaneous obesity in free-ranging rhesus macaques (Macaca mulatta) was assessed in terms of body size, body fat distribution, endocrinological/metabolic indices, and social and familial factors. Eleven animals (six females, five males), or 7% of the adult population surveyed, were defined as obese on the basis of morphometric indices of adiposity > 2 s.d. above the mean for adults in this colony. The age of the obese animals ranged from 9-16 years; obese males were older than females (average 14 vs. 12 years), but this difference was not significant. Mean body weights for obese males and females were 14.1 +/- 0.5 and 13.5 +/- 0.7 kg, respectively. There were no gender differences in either the incidence of obesity or measures of body fat. Serum concentrations of cholesterol and testosterone were not significantly different between obese and nonobese monkeys. Serum triglyceride levels were somewhat higher in obese animals, but this difference was not significant. Glucose clearance was within normal limits in both obese and age- and sex-matched non-obese monkeys (> 2% per min). Although increased adiposity was significantly correlated with fasting insulin and the insulin response to glucose loading, differences between obese and non-obese animals in these values did not achieve significance. The incidence of obesity ranged from 0-20% among the eleven matrilines studied, and several primary familial relationships were observed within the obese sample. Most obese females were from a high ranking matriline whereas only one of the obese males was high ranking at the time of the survey.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Age- and gender-related changes in body size, adiposity, and endocrine and metabolic parameters in free-ranging rhesus macaques.

Normative age- and gender-related changes in body composition, serum lipids, testosterone, and insulin-like growth factor (IGF-1) were examined in the Cayo Santiago free-ranging rhesus macaques. In both adult males and females, body weights, crown-rump lengths, and circumference of the limbs were lowest in the oldest group (20+ years of age) as compared with other adult age classes. Body fat, as reflected in subcutaneous fatfold thickness and waist/thigh ratios, were higher in adult females than adult males. This gender dimorphism was first detectable among the 6-9 year old age group. Greatest body fat among females was observed in the 10-14 age group, whereas in males the highest values were observed in the 15-19 age group. Differences in body composition were also observed with respect to reproductive status. Although there were no gender differences in overall cholesterol levels, there were age-related differences between males and females, and only in males were cholesterol values positively related to adiposity. There were no age- or gender-related differences in triglyceride values, but levels were significantly higher in pregnant females in comparison with other reproductive states. Levels of testosterone were not significantly related to any morphometric parameter and values did not decrease significantly with age. Levels of IGF-1 exhibited a significant age-related decrease among adult males, and females had higher levels independent of age. The similarities between the present findings and human studies suggest that further studies in the free-ranging rhesus macaques would provide a bridge between studies of laboratory-housed primates and studies of human beings with respect to the etiology of obesity and life-history changes in body composition and endocrine and metabolic parameters.

Adipose Tissue↗

PubMed1990

Brain damage induced by prenatal exposure to dexamethasone in fetal rhesus macaques. I. Hippocampus.

Neurotoxic effects of prenatal administration of dexamethasone were examined in the fetal rhesus monkey brain at 135 and 162 days of gestation (term is 165 days). In an experimental design mimicking human clinical trials, dexamethasone was given intramuscularly to pregnant monkeys on day 132 (single injection with doses of 0.5, 5, or 10 mg/kg maternal body weight) or on days 132 and 133 (multiple injections at 12-h intervals with 0.125 x 4, 1.25 x 4, or 2.5 mg/kg x 4). The fetuses were delivered by caesarean section on day 135 or day 162 and hippocampal slices were prepared for evaluation. Light and electron microscopic observation revealed decreased numbers of pyramidal neurons in the hippocampal CA regions and of granular neurons in the dentate gyrus associated with degeneration of neuronal perikarya and dendrites. Axodendritic synaptic terminals of the mossy fibers in the CA3 hippocampal region showed pronounced degeneration. Degeneration was dose-dependent and multiple injections induced more severe damage than single injections of the same total dose. Even the lowest dose (0.5 mg/kg, which is similar to the dose used in human clinical trials) produced these changes. Degenerative changes induced by dexamethasone treatment (5 mg/kg) on days 132 and 133 were also clearly evident in fetuses studied at 162 days. Therefore, caution is recommended in the use of prenatal corticosteroids in premature deliveries.

Animals↗