Organic solute carrier protein 1 (OSCP1) is a recently described human gene that facilitates the transport of various organic solutes into the cell, when expressed in frog eggs. In this study, we cloned a mouse ortholog of OSCP1 encoding 379 amino acid protein, with 94% homology to the human counterpart. The mouse OSCP1 mRNA was predominantly expressed in the testis, in which it was attributed to the spermatogenic cells, except the spermatogonia. Immunohistochemistry confirmed that OSCP1 protein is continuously expressed during spermatogenesis in a stage- and cell type-specific manner, in the leptotene spermatocytes at stage IX through step 15 spermatids. Subcellular fractionation of mouse testis homogenates indicated that OSCP1 is a 45-kDa cytosolic protein. Moreover, when green fluorescent protein-OSCP1 fusion constructs were transfected into cultured cells, the fluorescence localized evenly in the cytoplasm. These results suggest that mouse testis OSCP1 may indirectly mediate substrate uptake into meiotic and spermiogenic germ cells, within the cytosol.

Cholestasis is characterized by accumulation of toxic bile acids in the liver and associated with reduced detoxification capacity.1) Imbalanced mitochondrial energy production and hepatic levels of hydrophobic bile acid have been associated with enhancement in generation of reactive oxygen species (ROS) and oxidative damage in hepatocytes. 2,3) It is well known that farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily and plays an essential role in regulating bile acid, lipids and glucose homeostasis. 4,5) Owing to the absence of FXR expression, hepatic bile acid, lipids and glucose accumulate in Fxr-null mice, which results in mild cholestasis, steatosis and type 2 diabetes. 4,5) In addition to controlling the levels of bile acid, lipid and glucose, FXR also helps accelerate normal liver regeneration after 70% hepatectomy, which suggests that FXR also has a role in promoting liver growth after injury. 6) Increased bile acids stimulate liver regeneration, in which the function of the bile acid receptor FXR in mice is required. The hepatoprotective role of FXR is essential for maintaining the normal liver physiology and prevention of deleterious effects of bile acids.Indeed, it was reported that liver tumors spontaneously developed in aged Fxr-null mice. 7,8) These mice showed high levels of hepatic and serum bile acids, increased expression levels of cell cycle-related genes such as cyclin D and E, proinflammatory cytokine interleukin-1b, tumor necrosis factor-a and interleukin-6 (IL-6), and elevated b-catenin and c-myc levels, which are associated with tumorgenesis. One of general reasons for development of endogenous liver tumors is considered to be oxidative stress generation.9) These reports suggest that continuous generation of oxidative stress might occur in Fxr-null mice, and liver tumors would be developed. The relationship between the absence of FXR and generation of oxidative stress, however, has not been investigated yet. Moreover, it is not clear whether increased hepatic bile acid or triglyceride concentration is involved in the generation of oxidative stress.In the present study, we observed histopathological changes and measured the hepatic levels of oxidative stress markers such as 8-hydroxy-2Ј-deoxyguanosine (8OHdG), thiobarbituric acid-reactive substance (TBARS) and hydroperoxide. Then we compared the oxidative stress-related genes expression profiles and nuclear factor (erythroid-2 like) factor 2 (Nrf2) protein levels between wild-type and Fxr-null mice. We also tested whether the high level of hepatic bile acids might be involved in generation of hepatic oxidative stress in Fxr-null mice using cholic acid (CA) and an experimental hepatic bile acid lowering compound ME3738 (22b-methoxyolean-12-ene-3b,24(4b)-diol) that is not a radical scavenger. The major function of farnesoid X receptor (FXR) is to maintain bile acid and lipid homeostasis. Fxr-null mice, in which the levels of hepatic bile acid and lipid have been elevated, develop spontaneous liver tumors. We e...

ABSTRACT. Thirty-three cases of enzootic bovine leukosis (EBL) and 14 cases of sporadic bovine leukosis (SBL) were examined by immunohistochemistry using 6 monoclonal antibodies against leukocyte differentiation molecules of bovine leukocytes. There were 17 cases of B-1a cell type, 10 cases of B-1b cell type and 6 cases of B-2 cell type in EBL, and 5 cases originating from B cells (B-2 cell type) and 9 cases originating from immature T cells in SBL. The average age for the EBL cases of B-1a cell type was 8.6 years, B-1b cell type was 6.5 years, and of B-2 cell type was 4.5 years. In cases of SBL, immature T cell type patients were younger than B-2 ce ll type ones. The lymphoma originating from B cells differed from that originating from T cells in morphology. In T cell tumors, the nucleus of tumor cells was round, the edge of the cytoplasm obvious, and tumor cells were sporadically present and proliferated. When compared with T cells, the region among B cells was obscure. But, there was no relation between phenotype and the histologic classification of tumor cells. In EBL, beyond the lymph node, tumors of B-1a and B-1b types had developed in the heart and abomasum, and those of the B-2 type tended to occur in liver. In SBL, B-2 type and T type cells formed tumors in the liver, kidney, thymus, and one case of T-cell type tumor formed on the skin. We would like to propose a new classification of bovine leukosis as EBL, calf type B-cell lymphoma, juvenile T-cell lymphoma and skin type T-cell lymphoma.

Organic solute carrier partner 1 (OSCP1) is a mammalian, transporter-related protein that is able to facilitate the uptake of structurally diverse organic compounds into the cell when expressed in Xenopus laevis oocytes. This protein has been implicated in testicular handling of organic solutes because its mRNA expression is almost exclusive in the testis. However, in this study, we demonstrated significant expression of OSCP1 protein in mouse brain, the level of which was rather higher than that in the testis, although the corresponding mRNA expression was one-tenth of the testicular level. Immunohistochemistry revealed that OSCP1 was broadly distributed throughout the brain, and various neuronal cells were immunostained, including pyramidal cells in the cerebral cortex and hippocampus. However, there was no evidence of OSCP1 expression in glia. In primary cultures of cerebral cortical neurons, double-labeling immunofluorescence localized OSCP1 to the cytosol throughout the cell body and neurites including peri-synaptic regions. This was consistent with the subcellular fractionation of brain homogenates, in which OSCP1 was mainly recovered after centrifugation both in the cytosolic fraction and the particulate fraction containing synaptosomes. Immunoelectron microscopy of brain sections also demonstrated OSCP1 in the cytosol near synapses. In addition, it was revealed that changes in the expression level of OSCP1 correlated with neuronal maturation during postnatal development of mouse brain. These results indicate that OSCP1 may have a role in the brain indirectly mediating substrate uptake into the neurons in adult animals.

ABSTRACT. Four sheep were immunized with synthesized peptides, derived from bovine leukemia virus (BLV) envelope glycoprotein, encapsulated in mannan coated liposomes as adjuvant. On the seventh day after the immunization, the sheep were intradermally challenged with BLV antigen, or synthesized peptides. The areas challenged with antigen were increased skin thickness and biopsied sequentially for immunohistological examinations. Strong delayed-type hypersensitivity was induced in sheep immunized and challenged with peptides encapsulated in mannan-coated liposomes. The major phenotype of the infiltrating lymphocytes was CD5+ . The ratio of CD4 + to CD8 + cells was about 1:1.KEY WORDS: bovine leukemia virus, delayed-type hypersensitivity, mannan-coated liposome.