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ABSTRACT Historical control data on rabbit prenatal developmental toxicity studies, performed between 1994-2010, were obtained from 20 laboratories, including 11 pharmaceutical and chemical companies and nine contract laboratories, in Japan. In this paper, data were incorporated from a laboratory if the information was based on 10 studies or more. Japanese White rabbits and New Zealand White rabbits were used for prenatal developmental toxicity studies. The data included maternal reproductive findings at terminal cesarean sections and fetal findings including spontaneous incidences of morphological alterations. No noticeable differences between strains or laboratories were observed in the maternal reproductive and fetal developmental data. The inter-laboratory variations in the incidences of fetal external, visceral, and skeletal alterations seem to be due to differences in the selection of observation parameters, observation criteria, and classification of the findings, and terminology of fetal alterations. [ABSTRACT FROM AUTHOR]

We examined a 70-year-old woman in whom a pancreatic endocrine tumor with partial acinar cell differentiation had been diagnosed. She had neither endocrine nor exocrine symptoms. The tumor was located in the pancreatic tail and measured 12.5×9.5×8 cm. It had a capsule, was composed of multiple adhesion nodules, and was elastically soft, medullary, and yellowish white. The neoplastic cells had large, irregular, oval nuclei; prominent eosinophilic nucleoli; and abundant eosinophilic cytoplasm with many fine granules. The cells had proliferated in islet-like solid medullary, trabecular, acinar, and papillary patterns. Most neoplastic cells were strongly positive for synaptophysin. 10 to 25% of the neoplastic cells were positive for α1-antitrypsin. Neuroendocrine and zymogen granules were simultaneously observed in the cytoplasm of the same neoplastic cells at the ultrastructural level. The tumor may be considered an amphicrine tumor. [ABSTRACT FROM AUTHOR]

Mucinous cystic neoplasms (MCN) of the pancreas are mucin-producing cystic tumors with an ovarian-like stroma (OLS). In the present study MCN were obtained from 27 patients. These MCN were derived from 22 pancreas, three livers, spleen, and mesentery. MCN in various organs have common clinicopathological profiles, being unilocular or multilocular cystic tumors, with a fibrous capsule and lined by mucin-secreting epithelium associated with an underlying subepithelial OLS. The OLS showed strong positivity for α-smooth muscle actin (α-SMA) and vimentin and weak, focal positivity for desmin. Both estrogen receptors and progesterone receptors were expressed in the nuclei of OLS cells. In addition, 20 ovarian MCN and 13 normal ovaries were studied with particular attention to the stroma. The stroma of ovarian MCN was strongly immunopositive for α-SMA and vimentin and focally positive for desmin, whereas normal ovarian stroma was immunonegative for both α-SMA and desmin. The OLS of MCN mentioned here was similar to the septa of ovarian MCN but not to ovarian stroma. In conclusion, MCN in various organs should be lumped together as ‘extraovarian’ MCN. The OLS was identified on the basis of myofibroblastic proliferation both in response to neoplastic development and dependent on hormones. [ABSTRACT FROM AUTHOR]

Hermansky–Pudlak syndrome (HPS) is a hereditary disorder involving the sorting processes of intracellular organelles such as lysosomes of reticuloendothelial cells. Pale ear ( ep) mouse is known to have the HPS1 gene mutation, which is seen in patients with HPS and pulmonary fibrosis. As pulmonary fibrosis is not spontaneously observed in ep mice, we hypothesized that external stimuli are necessary for the genetic predisposition of its development. We used silica as the external stimulus to induce the alveolar macrophage-mediated inflammatory response and evaluated the pathological changes of the lung and biochemical analysis of collagenolytic lysosomal enzymes cathepsins L and B in ep mice. Treatment with silica induced the following: persistent accumulation of activated macrophages; delayed clearance of silica from alveolar spaces; and increased collagen fibers in alveolar tissues, which were shown with trichrome staining in ep mice. The comparison of bronchoalveolar lavage cells between the naïve ep and control mice revealed: decreased enzymatic activities but increased antigenic levels of cathepsins L and B, resulting in significantly lower ratios of activity to antigen; increased ceroid deposits and cathepsin L antigens in lysosomes; and no abnormal forms of cathepsins were detected. After silica instillation, activities of cathepsin L in the ep mice increased but ratios of activity to antigen were still significantly low. These phenomena induced by silica suggest that external stimuli bring forth fibrogenesis in the animal models or humans that have HPS1 gene mutation. [ABSTRACT FROM AUTHOR]