Three glutathione peroxidase homologs (YKL026C, YBR244W, and YIR037W/HYR1) were found in the Saccharomyces Genome Database. We named them GPX1, GPX2, and GPX3, respectively, and we investigated the function of each gene product. The gpx3⌬ mutant was hypersensitive to peroxides, whereas null mutants of the GPX1 and GPX2 did not show any obvious phenotypes. Glutathione peroxidase activity decreased approximately 57 and 93% in the gpx3⌬ and gpx1⌬/gpx2⌬/ gpx3⌬ mutants, respectively, compared with that of wild type. Expression of the GPX3 gene was not induced by any stresses tested, whereas that of the GPX1 gene was induced by glucose starvation. The GPX2 gene expression was induced by oxidative stress, which was dependent upon the Yap1p. The TSA1 (thiol-specific antioxidant) gene encodes thioredoxin peroxidase that can reduce peroxides by using thioredoxin as a reducing power. Disruption of the TSA1 gene enhanced the basal expression level of the Yap1p target genes such as GSH1, GLR1, and GPX2 and that resulted in increases of total glutathione level and activities of glutathione reductase and glutathione peroxidase. However, expression of the TSA1 gene did not increase in the gpx1⌬/gpx2⌬/gpx3⌬ mutant. Therefore, de novo synthesis and recycling of glutathione were increased in the tsa1⌬ mutant to maintain the catalytic cycle of glutathione peroxidase reaction efficiently as a backup system for thioredoxin peroxidase.All aerobic organisms use molecular oxygen for respiration or oxidation of nutrients to acquire the energy efficiently. Molecular oxygen is reduced to H 2 O through acceptance of four electrons. During the reduction of molecular oxygen, several reactive oxygen species are formed, i.e. acceptance of one, two, and three electrons to form, respectively, superoxide anion radical (O 2 . ), hydrogen peroxide (H 2 O 2 ), and hydroxyl radical (HO ⅐ ). These reactive oxygen species attack almost all cell components, DNA, protein, and lipid membrane, and they sometimes cause lethal damage to the cells. Among the reactive oxygen species, HO ⅐ as well as perhydroxyl radical (HOO ⅐ ) can extract bis-allylic hydrogen atom of unsaturated fatty acid (LH) to form lipid alkyl radical (L ⅐ ) (1). The L ⅐ is oxidized by molecular oxygen to generate a lipid peroxy radical (LOO ⅐ ), and the LOO ⅐ thus formed reacts with LH to give lipid hydroperoxide (LOOH) and L ⅐ . A radical chain reaction is then propagated. LOOH also belongs to the reactive oxygen species, and the occurrence of the LOOHs in biological membranes may be one of the major oxidative damages to the cells. (2). ␤-Carotene and tocopherol function as radical scavengers. Glutathione is also a major antioxidant in aerobic cells. However, it has been widely believed that microorganisms do not have peroxidases whose electron donor is glutathione. Microorganisms are believed to use cytochrome c as an electron donor for the peroxidase reaction (cytochrome c peroxidase). GPx has been thought to be evolutionarily acquired by mammals. However, we have demonstrated that ...

able because the patients is a poor surgical risk, TAE has To assess intrahepatic metastasis (IM) and multicenbeen considered the treatment of choice. However, the value tric occurrence (MO) after initial treatment of small heof TAE is limited if the small HCCs have intracapsular or patocellular carcinomas (HCC) ß 2 cm in diameter, we extracapsular invasion. performed clinical and pathological studies in 112 pa-PEIT has been shown to be highly effective in patients with tients who underwent percutaneous ethanol injection HCCs ß3 cm in diameter. with HCC were admitted to Ogaki Municipal Hospital, and 163 of the 750 were found to have an HCC ß2 cm in diameter. One hundred and twelve of these patients who had undergone PEIT or hepatic Hepatocellular carcinoma (HCC) is one of the most maligresection were selected for this retrospective study. All cases were nant neoplasms in Japan. Because of recent progress in the diagnosed histologically. Fifteen patients were diagnosed by specific development of new diagnostic modalities, the incidence of imaging diagnosis (histological confirmation was made by analysis detection of small HCCs has increased.1-4 Therapeutic ap-of specimens obtained at surgery) and 97 patients were diagnosed proaches to HCC also have progressed markedly in recent by percutaneous liver tissue core biopsy with ultrasound guidance. years through the development of hepatic resection, trans-The PEIT was performed according to previously published methcatheter arterial embolization, and percutaneous ethanol in-ods 24 in 82 patients who had not undergone surgery because of imjection therapy (PEIT). [5][6][7] The surgical resectability rate of paired liver function or who had requested this type of therapy.Briefly, after administration of a local anesthetic, the needle was HCC, however, has remained low, this is, because most pa- A 25 ). In this series, radical hepatectomy represented the removal of Received December 29, 1995; accepted September 25, 1996. all tumors from the liver. and/or helical with contrast medium were performed every 3 months.

able because the patients is a poor surgical risk, TAE has To assess intrahepatic metastasis (IM) and multicenbeen considered the treatment of choice. However, the value tric occurrence (MO) after initial treatment of small heof TAE is limited if the small HCCs have intracapsular or patocellular carcinomas (HCC) ß 2 cm in diameter, we extracapsular invasion. performed clinical and pathological studies in 112 pa-PEIT has been shown to be highly effective in patients with tients who underwent percutaneous ethanol injection HCCs ß3 cm in diameter. with HCC were admitted to Ogaki Municipal Hospital, and 163 of the 750 were found to have an HCC ß2 cm in diameter. One hundred and twelve of these patients who had undergone PEIT or hepatic Hepatocellular carcinoma (HCC) is one of the most maligresection were selected for this retrospective study. All cases were nant neoplasms in Japan. Because of recent progress in the diagnosed histologically. Fifteen patients were diagnosed by specific development of new diagnostic modalities, the incidence of imaging diagnosis (histological confirmation was made by analysis detection of small HCCs has increased.1-4 Therapeutic ap-of specimens obtained at surgery) and 97 patients were diagnosed proaches to HCC also have progressed markedly in recent by percutaneous liver tissue core biopsy with ultrasound guidance. years through the development of hepatic resection, trans-The PEIT was performed according to previously published methcatheter arterial embolization, and percutaneous ethanol in-ods 24 in 82 patients who had not undergone surgery because of imjection therapy (PEIT). [5][6][7] The surgical resectability rate of paired liver function or who had requested this type of therapy.Briefly, after administration of a local anesthetic, the needle was HCC, however, has remained low, this is, because most pa- A 25 ). In this series, radical hepatectomy represented the removal of Received December 29, 1995; accepted September 25, 1996. all tumors from the liver. and/or helical with contrast medium were performed every 3 months.

The human serine/threonine kinase Aurora-B is structurally related to the protein kinase Ipl1p from S cerevisiae and aurora from Drosophila melanogaster, which are key regulators of mitosis. The present study shows that human Aurora-B is activated by okadaic acid and forms complexes with the protein serine/threonine phosphatase type 1 (PP1) or PP2A, but not with PP5. These data identi®ed Aurora-B associated protein phosphatases as negative regulators of kinase activation. We then used a series of substrates based on a histone H3 phosphorylation site (residues 5 ± 15) to determine the substrate speci®city of human Aurora-B. We found that this enzyme is an arginine-directed kinase that can phosphorylate histone H3 at serines 10 and 28 in vitro, suggesting that human Aurora-B is a mitotic histone H3 kinase.