Down syndrome with transient myeloproliferative disorder (TMD) is often associated with perinatal liver fibrosis. The authors recently encountered an autopsy case of this disease with a characteristic severe perisinusoidal liver fibrosis. Osteopontin (OPN) is a molecule that plays an important role in diverse fibro-inflammatory diseases. The purpose of the present report was to examine the involvement of OPN in development of the Down syndrome-associated liver fibrosis. Histology indicated severe perisinusoidal fibrosis and ductular arrangements of hepatocytes in the liver. Appearance of atypical megakaryocytes in the liver, a feature of TMD associated with Down syndrome, was not evident. On immunohistochemistry expression of OPN was observed in hepatocytes often having ductular arrangements and infiltrating macrophages. In contrast, a small number of transforming growth factor-beta1 (TGF-beta1)-positive mononuclear cells were present in the liver. Numerous activated hepatic stellate cells (HSC) expressing alpha-smooth muscle actin (alpha-SMA) were seen in the perisinusoidal area. A recent report indicated that OPN could directly activate the HSC. Thus, it is suggested that OPN produced by hepatocytes and macrophages induces activation of the HSC, and leads to the development of perisinusoidal liver fibrosis.

ABSTRACT. A stillborn calf at 259 days of gestation was examined. The dam showed no clinical signs of disease, and the stillbirth was occurred sporadically and were characterized by focal necrosis surrounded by infiltration of the cells such as macrophages and multinucleated giant cells. The lesions were observed systemically. The hyphae were visible by Grocott's stain and they were positive by immunohistochemical stain using serum of a rabbit immunized with the isolated organism. The isolated bacteria were determined to be Nocardia farcinica by bacteriological and molecular analysis and we confirmed that the stillbirth was caused by infection with and proliferation of Nocardia farcinica. This is the first report of a bovine stillbirth caused by this organism.