大野 伸彦

Classic cerebellar anatomy is based on the characteristic array of lobes and lobules. However, there is substantial evidence to suggest that more fundamental architecture is built around arrays of parasagittal stripes, which encompass both the inputs and outputs of the Purkinje cells (PCs). Sphingosine kinase (SPHK) is an enzyme that converts sphingosine (Sph) into sphingosine-1-phosphate (SIP). Recent reports have indicated that ceramide, Sph, and SIP play a role in cell survival, growth, and differentiation in several cell types, including neurons. In this study, we examined the localization of SPHK in the mouse cerebellum by using immunohistochemistry. Anti-SPHK immunoreactivity appeared in the cerebellar molecular layer and the PC membranes. The staining pattern is striped. In the molecular layer, the staining pattern probably reflects dendritic spines and dendrites. By electron microscopy, peroxidase reaction product was deposited within dendrites especially along the plasma membranes near spines. Seen at higher magnification, the staining was in and near the postsynaptic complexes. By double immunostaining, the striped pattern of SPHK expression was shown to be identical to that revealed by anti-zebrin II, although the subcellular distribution within PC's is not. This is the first demonstration of the cerebellar compartmentation of an enzyme related to lipid metabolism, and as such, it provides an insight into the roles of SPHK and formation of SIP. The selective expression of SPHK in the zebrin II-immunoreactive PCs may explain their resistance to cell death when ceramide metabolism is disrupted, as in the acid sphingomyelinase knockout model of Niemann-Pick type A/B disease.

A 28-year-old woman had chief complaints of headache and a 40degreesC fever. At this time, findings indicative of inflammation including elevated CRP and increased WBC were observed, and E. coli was detected on blood and urine culture. As a result, the patient was diagnosed with pyelonephritis and sepsis. Furthermore, markedly increased hepatobiliary enzymes and elevated anti-mitochondrial antibody were confirmed. The administration of antimicrobial agents resulted in improvement of the pyelonephritis and sepsis and normalization of hepatobiliary enzyme and anti-mitochondrial antibody levels. It has been documented that the incidence of urinary tract infection is high among patients with primary biliary cirrhosis (PBC). The findings obtained from the present patient are of considerable interest in elucidating the mechanism of onset in PBC.

Protein 4.1 family proteins are thought to interact with membrane proteins and membrane skeletons. Immunohistochemical studies by light and electron microscopy were performed on mouse pancreas with a specific antibody against protein 4.1B. Specific protein 4.1B immunolabeling was observed on endocrine cells in the islets of Langerhans. Protein 4.1B localized along the plasma membranes facing adjacent cells. By immunoelectron microscopy, the immunolabeling of the cells was restricted to the cytoplasmic side just beneath their plasma membrane, including the membranes adjacent to neighboring cells, while the plasma membranes facing endothelial cells were not immunolabeled for protein 4.1B. The immunolocalization of E-cadherin was similar, if not identical, to that of protein 4.1B supporting the idea that protein 4.1B may be functionally interconnected with adhesion molecules. In a transgenic mouse model of pancreatic beta-cell carcinogenesis (Rip1Tag2), the loss of protein 4.1B expression coincided with the phenotypic transition from adenoma to carcinoma. Therefore, we propose a role of protein 4.1B as a connecting and/or signaling molecule between membrane architecture, cell adhesion, and tumor cell invasion in mouse pancreatic endocrine cells.