Histopathological changes in the pancreas from a spontaneous hyperglycemic cynomolgus monkey.

Morphological and immunohistochemical examinations were carried out on the pancreas of a hyperglycemic 5-year-old male cynomolgus monkey. Body weight gradually decreased from 6 months before termination, accompanying a slight reduction in food consumption and anorexia for the last 2 days. The blood glucose level was markedly elevated when examined at termination. Histopathologically, in the exocrine pancreas, diffuse hyperplasia of centroacinar and intercalated duct cells and diffuse atrophy of acinar cells with sporadic apoptosis were observed, although most centroacinar and intercalated duct cells were proliferating cell nuclear antigen (PCNA)-positive in both the present case and age-matched control animals. In the endocrine pancreas, the islets tended to be hypertrophic, with an increase in insulin-positive cells in comparison with the age-matched control animals. PCNA-positive cells also tended to increase in the islets, although positive cells for phospho-histone H3, a marker for mitotic cells, were not detected in the endocrine and exocrine pancreas. Moreover, neither inflammation nor amyloidosis was noted in the islets. In conclusion, the present case probably suffered from early-stage type 2 diabetes mellitus, and it provides fundamental information concerning pancreatic histopathology under insulin-related derangement in monkeys.

Confining barriers for surface state electrons tailored by monatomic Fe rows on vicinal Au111 surfaces.

We fabricated monatomic Fe wires on vicinal Au(111) surfaces and found that decoration of step edges with Fe adatoms has a significant influence on the behavior of surface state electrons confined between regularly arranged steps. On a surface with Fe monatomic rows, angle-resolved photoemission spectra measured in the direction perpendicular to the steps shows parabolic dispersion, in contrast to one-dimensional quantum-well levels observed on a clean surface. Simple analysis using a one-dimensional Kronig-Penney model reveals potential barrier reduction from 20 to 4.6 eV A, suggesting an attractive nature of the Fe adatoms as scatterers.

Mechanisms of promotion and progression of preneoplastic lesions in hepatocarcinogenesis by DDT in F344 rats.

Time-related changes in potential factors involved in hepatocarcinogenesis by DDT were investigated in a 4-week and a 2-year feeding studies of p,p'-DDT with F344 rats. In the 4-week study with males at doses of 50, 160, and 500 ppm, cell proliferation and gap junctional intercellular communication (GJIC) were examined after 1, 2, 3, 7, 14, and 28 days. Cell proliferation was enhanced within 3 days at any dose level, but returned to normal after 7 days, whereas GJIC was inhibited throughout the study. In the 2-year study with both sexes at doses of 5, 50, and 500 ppm, cell proliferation, GJIC, enzyme induction, and oxidative stress were investigated after 26, 52, 78, and 104 weeks. Males and females showed an inhibition of GJIC and increases in P450 isozymes (CYP2B1 and CYP3A2) in a dose-dependent manner at all time points, but no significant change in cell proliferation. Lipid peroxide for males at 50 and 500 ppm and 8-hydroxydeoxyguanosine for both sexes at 500 ppm were elevated throughout the study. Histologically, eosinophilic foci and hepatocellular adenomas increased in males at 50 ppm and both sexes at 500 ppm. Hepatocellular carcinomas also developed in males at 500 ppm. These results indicate that DDT may induce eosinophilic foci as a result of oxidative DNA damage and leads them to neoplasms in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT.

Thymic atrophy induced by methoxychlor in rat pups.

The effect of Methoxychlor (MXC) on the thymus was examined in rat pups that were delivered from dams receiving MXC at a dietary concentration of 0 or 1500 ppm for a period from pregnancy to lactation. The pups of both sexes were euthanized on postnatal days (PNDs) 7, 14, and 21. Histologically, the thymus showed marked depletion of cortical lymphocytes on PND 7 and also had an increase in lymphophagocytosis in the cortical area on PNDs 14 and 21. Morphometrical analysis disclosed that both cortex and medulla of the thymus from treated pups were reduced in size, but the reduction was more evident in the cortex. A significant increase in transferase-mediated dUTP nick end labeling-positive cells was detected in the cortex area, corresponding to the presence of lymphophagocytosis. Flow cytometric analysis revealed a significant decrease in the double positive (CD3(int)CD4(+)CD8(+)) immature cells on PND 21. These results have suggested that MXC may impair maturation of thymic lymphocytes in rat pups, which results in enhancement of apoptosis leading to thymic atrophy during the postnatal period.