Platelet vacuoles in a dog with severe nonregenerative anemia: evidence of platelet autophagy.

A 13-year-old neutered male English Springer Spaniel was presented to The Ohio State University Veterinary Medical Center for evaluation of severe anemia. Upon blood smear review, approximately 50% of the platelets contained single to multiple variably sized clear vacuoles. Transmission electron microscopy of the platelets revealed hallmark features of autophagy, including membrane-lined vesicles and vacuoles containing membrane whorls and degrading organelles. While autophagy has been demonstrated in a wide range of eukaryotic cells for decades, reports of platelet autophagy are lacking. This case report illustrates atypical platelet vacuolation with electron microscopic features characteristic of autophagy.

Osseous metaplasia within a canine insulinoma.

An 11-year-old male castrated mixed-breed dog was presented for exercise intolerance, tetraparesis, and persistent hypoglycemia. Abdominal ultrasound examination revealed 2 nodules within the right limb of the pancreas. Cytology from one nodule was consistent with a carcinoma of neuroendocrine origin, with a primary differential diagnosis of insulinoma. Histologic evaluation and immunohistochemistry for synaptophysin and insulin confirmed the diagnosis of insulinoma. Additionally, there was a solitary nodule of mineralized compact bone composing approximately 60% of the mass. To the authors' knowledge, this is the first report of osseous metaplasia within an insulinoma (islet cell carcinoma).

Asthma/allergic airways disease: does postnatal exposure to environmental toxicants promote airway pathobiology?

UNLABELLED: The recent, dramatic increase in the incidence of childhood asthma suggests a role for environmental contaminants in the promotion of interactions between allergens and the respiratory system of young children. To establish whether exposure to an environmental stressor, ozone (O3), and an allergen, house dust mite (HDMA), during early childhood promotes remodeling of the epithelial-mesenchymal trophic unit (EMTU) of the tracheobronchial airway wall by altering postnatal development, infant rhesus monkeys were exposed to cyclic episodes of filtered air (FA), HDMA, O3, or HDMA plus O3. The following alterations in the EMTU were found after exposure to HDMA, O3, or HDMA plus O3: (1) reduced airway number; (2) hyperplasia of bronchial epithelium; (3) increased mucous cells; (4) shifts in distal airway smooth muscle bundle orientation and abundance to favor hyperreactivity; (5) interrupted postnatal basement membrane zone differentiation; (6) modified epithelial nerve fiber distribution; and (7) reorganization of the airway vascular and immune system. CONCLUSIONS: cyclic challenge of infants to toxic stress during postnatal lung development modifies the EMTU. This exacerbates the allergen response to favor development of intermittent airway obstruction associated with wheeze. And, exposure of infants during early postnatal lung development initiates compromises in airway growth and development that persist or worsen as growth continues, even with cessation of exposure.

Early postnatal exposure to allergen and ozone leads to hyperinnervation of the pulmonary epithelium.

Airway injury in infant monkeys exposed to ozone and/or house dust mite allergen (HDMA) is associated with a loss of epithelial innervation. In this study, we evaluated for persistence/recovery of the altered epithelial innervation. Thirty-day-old rhesus monkeys were exposed to repeated episodes of HDMA and/or ozone from 1 to 6 months of age and subsequently allowed to recover for 6 months in the absence of further ozone exposure and/or minimal HDMA challenge (sufficient to maintain allergen sensitization). At 1 year of age, nerve density in intrapulmonary airways was immunohistochemically evaluated using antibodies directed against protein gene product 9.5. Hyperinnervation and irregular epithelial nerve distribution was observed in both HDMA- and ozone-exposed groups; most prominent alterations were observed in animals exposed to HDMA plus ozone. Therefore, while adaptive mechanisms exist that re-establish epithelial innervation following cessation or diminution of exposure to HDMA and/or ozone, the recovery is associated with persistent proliferative mechanisms that result in hyperinnervation of the airways.