Assessment of Blood Pressure in Irradiated Rhesus Macaques (Macaca mulatta).

There is increasing evidence that circulatory disease incidence and mortality is associated with radiation exposure. Wake Forest School of Medicine is home to a unique cohort of total-body irradiated macaques, some with evidence of vascular end-organ disease in the brain, kidney and heart. Because there is a link between high blood pressure and vascular disease in all these sites, we undertook a retrospective study to evaluate blood pressure and radiation in this cohort of animals. In this work, we utilized a cohort of nonhuman primates (rhesus macaques, Macaca mulatta) long-term survivors of high-dose total-body irradiation (1.1-8.5 Gy, N = 129) and controls (N = 37) to evaluate the effects of radiation on blood pressure and obesity. Subjects were between 3 and 22 years of age (median 9 years). Blood pressure (BP) was measured 1-14 years postirradiation (median 4 years). Subjects were sedated with a combination of ketamine HCl (15 mg/kg body weight, IM) and midazolam (0.1 mg/kg body weight, IM) and systolic, diastolic, and mean arterial pressures were measured using a high definition oscillometer. Obesity was defined by dual energy X-ray absorptiometry as a body fat percentage >35%. Statistical analysis of the collected data indicated significant increases in blood pressure with increasing age and obesity. However, radiation did not significantly alter blood pressure in irradiated animals relative to controls, radiation dose, or age of irradiation.

Parity and expression of epithelial histopathologic markers in breast tissue.

It is well established that pregnancies protect against breast cancer; however, the mechanism involved is not completely understood. We investigated the influence of parity on hormonal and proliferation markers in benign tissue from tumor blocks of breast cancer cases. Women with breast cancer were recruited from a case-control study nested within the Multiethnic Cohort study. Tissue microarrays of benign tissue cores were available for 159 participants. Immunostaining for estrogen receptor α (ERα) and ERß, progesterone receptor, human epidermal growth factor receptor 2 (Her2/neu), Ki-67, and proliferating cell nuclear antigen (PCNA) in epithelial tissue was evaluated by a pathologic expert. We applied logistic regression models to examine marker expression by parity (0, 1-2, and ≥3 live births with adjustment for age at diagnosis and BMI). Of the 159 women, 24 were nulliparous, 63 had one or two live births, and 72 had three or more live births. Inverse associations were observed between parity and expression of ERα (Ptrend=0.02) and PCNA (Ptrend=0.04). Among nulliparous women, 45.5% were ERα positive in contrast to 18.0 and 18.9% of women with one or two and at least three live births, respectively. The respective values for PCNA were 56.5, 44.3, and 31.1%. No associations were detected for ERß, progesterone receptor, Her2/neu, and Ki-67. The current findings suggest that pregnancies may protect against breast cancer by reducing susceptibility to estrogenic stimuli and proliferative activity as assessed by the expression of ERα and PCNA in breast tissue.

Cyclic morphological changes in the beagle mammary gland.

Interpretation of chemical-induced effects on the female beagle mammary gland can be difficult owing to the wide variation of normal glandular morphology. In this retrospective study, morphological features of the gland in four (proestrus, estrus, diestrus, and anestrus) phases of the cycle are described. The gland was quiescent (inactive) in proestrus and estrus. In diestrus, with the rise of progesterone, four (I-IV) distinct morphological changes were evident. In phase I, there was exuberant stromal and ductal proliferation. In phase II, there was early lobular development with branching ducts and alveolar proliferation. In phase III, there was an abundance of glandular tissue with large lobules containing secretory material, whereas phase IV had features of early regression, increased interlobular connective tissue, and eosinophilic secretions in distended ducts and acini. In early anestrus, ducts were distended, with eosinophilic secretions with alveolar regression, whereas regression was complete in late anestrus. Glandular morphology was slightly variable in the mammary chain within the same dog. Progesterone receptor expression was prominent in estrus and early diestrus, and peak estrogen receptor expression was noted in diestrus II. Expression of proliferation marker ki-67 was highest in diestrus I, followed by diestrus II. There was excellent concordance between the estrous stage and the glandular morphology.