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.

Cerebral amyloid angiopathy and plaques, and visceral amyloidosis in aged macaques.

In the present study, we report our extended data on the incidence of two types of cerebral amyloidosis (plaques and plaques associated with angiopathy) and visceral amyloidosis in late adult and aged captive rhesus monkeys (Macaca mulatta). In a total of 81 brains from animals ranging from 16 to 39 years old, beta-amyloid plaques were found in 38, 10 of which were associated with amyloid angiopathy. Brains from eight adults, 16 to 19 years, had no lesions. In aged groups, the rates were 20.8% in the 20- to 25-year group (24), 60.9% in the 26- to 31-year group (41), and 100% in the 33- to 39-year group (8). Twelve monkeys in these aged groups had an involvement of amyloidosis in either the liver, the adrenal, or the pancreatic islets, and 7 of 12 had amyloid plaques (5) and plaques associated with cerebral angiopathy (2). No neurofibrillary tangles were detected in these brain lesions. Amyloid in both plaques and cerebral angiopathy showed immunocytochemical crossreactivity with human amyloid beta (beta/A4) and precursor proteins (APP-A4), but visceral amyloid was negative. Ultrastructurally, amyloid initially appears as loose filaments in the perivascular or Disse space, and they further aggregate to produce dense interlacing bundles. Cerebral amyloid angiopathy associated with plaque appears to be a subclass of senile plaque lesions in aged monkeys as well as in aged humans, and it appears to have no pathogenetic correlation with visceral amyloidosis.

Estrogenic contributions to sexual differentiation in the female guinea pig: influences of diethylstilbestrol and tamoxifen on neural, behavioral, and ovarian development.

We administered the synthetic estrogen, diethylstilbestrol (DES), or the antiestrogen, tamoxifen, to pregnant guinea pigs and observed the consequences for sexual differentiation of their female offspring. Hormones were administered during the period when treatment of fetuses with testosterone influences the development of sex-related traits (approximately Days 30 to 65 of gestation). Ovarian function, masculine and feminine sexual behavior, and the structure of a sexually dimorphic neural region in the preoptic area were assessed in adulthood in hormone-exposed animals and in oil-treated and untreated controls. Prenatal exposure to DES dipropionate (DESDP) caused masculinization and defeminization. DESDP-treated females mounted more than control females, both without hormonal stimulation and when given testosterone propionate (TP) as adults. The sexually dimorphic neural region was also masculinized in these females. In regard to defeminization, they showed delayed vaginal opening, impaired progesterone (P) production, an absence of corpora lutea, and impaired lordosis and mounting responses to estradiol benzoate (EB) and P. Prenatal treatment with tamoxifen produced a complicated pattern of results. Tamoxifen-exposed females evidenced less masculine-typical behavior, showing diminished mounting without hormonal stimulation and in response to TP. However, they also showed delayed vaginal opening, enhanced P production, and impaired mounting in response to EB and P. Their lordosis behavior and the volume of the sexually dimorphic neural region were unaffected. These results suggest that estrogens play a substantial role in sexual differentiation in the guinea pig. High levels of estrogen promote masculine-typical development, and unusually low levels may impair some aspects of both masculine-typical and feminine-typical development.