Self-consistent Skyrme-Hartree-Fock plus random phase approximation calculation of nuclear low-lying states in the mesh representation

筑波大学University of Tsukuba博士（理学）Doctor of Philosophy in ScienceThe nuclear mean-field theory has been one of the central theoretical tools in the nuclear physics. Especially self-consistent mean-field(SCMF) approach with effective　interactions such as Skyrme Hartree-Fock method has succeeded in describing the ground state properties of nuclei in a wide area of nuclear chart. Based on the success of the SCMF for the static properties, the SCMF method is attracting more and more attention in investigations of excited properties of nuclei. In this thesis, we propose efficient formulation for describing the low-lying states of deformed nuclei within a framework of the self-consistent Skyrme Hartree-Fock (SHF) plus random phase approximation (RPA). We consider only the case of even-even nuclei, which are spherical, axial and triaxial deformed. And we do not consider the pairing correlations in this thesis. We study the self-consistent RPA equation in the mixed configuration space of coordinates and hole orbitals. First, we derive the RPA equation in the mixed configuration space of coordinates and hole orbitals from the RPA equation in the particle-hole configuration space. We explain the treatment of the spurious state in the case of the RPA in the mixed configuration space. Secondly, we also derive the RPA equation in the mixed configuration space as the small amplitude limit of the time-dependent Hartree-Fock equation in the coordinate representation. This derivation is useful for studying the properties of the RPA equation under time-reversal. ･･･2003Includes bibliographical referencesdoctoral thesi

肝再生過程におけるHMGB2の肝細胞増殖と細胞サイズ制御への関与

宮崎大学博士（医学）2022年度doctoral thesi

Studies on the Process of Formation of Beech Forest (III) : Regeneration and Growth of National Seedlings in Beech Forest

departmental bulletin pape

The Effect of Estrogen on Hepatic Fat Accumulation during Early Phase of Liver Regeneration after Partial Hepatectomy in Rats

Fatty liver is common in men and post-menopausal women, suggesting that estrogen may be involved in liver lipid metabolism. The aim of this study is to be clear the role of estrogen and estrogen receptor alpha (ERα) in fat accumulation during liver regeneration using the 70% partial hepatectomy (PHX) model in male, female, ovariectomized (OVX) and E2-treated OVX (OVX-E2) rats. Liver tissues were sampled at 0–48 hr after PHX and fat accumulation, fatty acid translocase (FAT/CD36), sterol regulatory element-binding protein (SREBP1c), peroxisome proliferator-activated receptor α (PPARα), proliferative cell nuclear antigen (PCNA) and ERα were examined by Oil Red O, qRT-PCR and immunohistochemistry, respectively. Hepatic fat accumulation was abundant in female and OVX-E2 compared to male and OVX rats. FAT/CD36 expression was observed in female, OVX and OVX-E2 at 0–12 hr after PHX, but not in male rats. At 0 hr, SREBP1c and PPARα were elevated in female and male rats, respectively, but were decreased after PHX in all rats. The PCNA labeling index reached a maximum at 36 hr and 48 hr in OVX-E2 and OVX rats, respectively. ERα expression in OVX-E2 was higher than OVX at 0–36 hr after PHX. In conclusion, these results indicated that estrogen and ERα might play an important role in fat accumulation related to FAT/CD36 during early phase of rat liver regeneration.Citation: Srisowanna N, Choijookhuu N, Yano K, Batmunkh B, Ikenoue M, Nhat Huynh Mai N, Yamaguchi Y, Hishikawa Y. The Effect of Estrogen on Hepatic Fat Accumulation during Early Phase of Liver Regeneration after Partial Hepatectomy in Rats. Acta Histochem Cytochem. 2019 Aug 30;52(4):67-75. doi: 10.1267/ahc.19018. Epub 2019 Aug 27. PMID: 31592200; PMCID: PMC6773610

Prediction of Posthepatectomy Liver Failure Proposed by the International Study Group of Liver Surgery : Residual Liver Function Estimation With 99mTc-Galactosyl Human Serum Albumin Scintigraphy

PURPOSE: The International Study Group of Liver Surgery (ISGLS) proposed a definition and grading system for posthepatectomy liver failure (PHLF). We evaluated the usefulness of residual liver function estimation using Tc-99m-galactosyl human serum albumin (99mTc-GSA) for the prediction of PHLF. METHODS: Patients with liver tumors (n = 136) and scheduled for hepatectomy underwent 99mTc-GSA scintigraphy. Based on their imaging data, the maximal GSA removal rate (GSA R-max）was calculated by multicompartment analysis. We also calculated GSA R-max in the predicted residual liver (GSA-RL) whose volume was determined on computed tomography (CT) scans. We compared the age, gender, 15-min indocyanine green retention rate, albumin-, bilirubin-, hyaluronic acid-, and type 4 collagen level, the Child-Pugh classification, residual liver volume, residual liver percentage, GSA R-max, and GSA-RL in patients with/without PHLF. Uni- and multivariate logistic analyses were used for statistical assessments. RESULTS: Of 136 patients, 17 (12.5%) met the ISGLS criteria for PHLF (ISGLS-PHLF). There was a statistically significant difference in the age, albumin level, Child-Pugh classification, residual liver volume, residual liver percentage, GSA R-max, and GSA-RL between patients with/without PHLF. Based on multivariate analysis, GSA-RL and the residual liver volume were significant independent predictors of ISGLS-PHLF (p = 0.004 and p = 0.038, respectively). The odds ratio was 149423 for GSA-RL and 1.003 for the residual liver volume. CONCLUSION: GSA-RL calculated by 99mTc -GSA scintigraphy was the most useful independent predictor for ISGLS-PHLF.Citation: Mizutani, Y., Hirai, T., Nagamachi, S., Nanashima, A., Yano, K., Kondo, K., Hiyoshi, M., Imamura, N., & Terada, T. (2018). Prediction of Posthepatectomy Liver Failure Proposed by the International Study Group of Liver Surgery: Residual Liver Function Estimation With 99mTc-Galactosyl Human Serum Albumin Scintigraphy. Clinical nuclear medicine, 43(2), 77–81. https://doi.org/10.1097/RLU.000000000000191

The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells

Hepatoid adenocarcinoma (HAC) is a rare and aggressive gastrointestinal tract cancer that is characterized by hepatic differentiation and production of alpha-fetoprotein (AFP). Cisplatin is mainly used to treat HAC, but the efficacy is poor. Recently, the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), was approved as an anticancer agent. In this study, we investigated the anticancer effect of SAHA in combination with cisplatin in VAT-39 cells, a newly established HAC cell line. Cell viability and apoptosis were examined by MTT assay, flow cytometry and TUNEL assay. Expression of H3S10, cleaved caspase-3, Bax, and Bcl-2 were evaluated by immunohistochemistry and western blotting. AFP levels were examined in VAT-39 cells and culture medium. Combined treatment with cisplatin and SAHA efficiently inhibited cell proliferation and decreased cell viability. Apoptotic cells, but not necrotic cells, were significantly increased following the combined treatment, and an increase in the Bax/Bcl-2 ratio indicated that the combination of cisplatin and SAHA induced apoptosis through the mitochondrial pathway. VAT-39 cells treated with cisplatin and SAHA also partially lost their main characteristic of AFP production. We conclude that cisplatin and SAHA have a synergistic anticancer effect of inducing apoptosis, and that this combination treatment may be effective for HAC.Citation: Kyaw MTH, Yamaguchi Y, Choijookhuu N, Yano K, Takagi H, Takahashi N, Synn Oo P, Sato K, Hishikawa Y. The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells. Acta Histochem Cytochem. 2019 Feb 28;52(1):1-8. doi: 10.1267/ahc.18044. Epub 2019 Feb 23. PMID: 30923410; PMCID: PMC6434315

Spatiotemporal expression of HMGB2 regulates cell proliferation and hepatocyte size during liver regeneration

Liver regeneration is an extraordinarily complex process involving a variety of factors; however, the role of chromatin protein in hepatocyte proliferation is largely unknown. In this study, we investigated the functional role of high-mobility group box 2 (HMGB2), a chromatin protein in liver regeneration using wild-type and HMGB2-knockout (KO) mice. Liver tissues were sampled after 70% partial hepatectomy (PHx), and analyzed by immunohistochemistry, western blotting and flow cytometry using various markers of cell proliferation. In WT mice, hepatocyte proliferation was strongly correlated with the spatiotemporal expression of HMGB2; however, cell proliferation was significantly delayed in hepatocytes of HMGB2-KO mice. Quantitative PCR demonstrated that cyclin D1 and cyclin B1 mRNAs were significantly decreased in HMGB2-KO mice livers. Interestingly, hepatocyte size was significantly larger in HMGB2-KO mice at 36–72 h after PHx, and these results suggest that hepatocyte hypertrophy appeared in parallel with delayed cell proliferation. In vitro experiments demonstrated that cell proliferation was significantly decreased in HMGB2-KO cells. A significant delay in cell proliferation was also found in HMGB2-siRNA transfected cells. In summary, spatiotemporal expression of HMGB2 is important for regulation of hepatocyte proliferation and cell size during liver regeneration.Citation: Yano K, Choijookhuu N, Ikenoue M, Fidya, Fukaya T, Sato K, Lee D, Taniguchi N, Chosa E, Nanashima A, Hishikawa Y. Spatiotemporal expression of HMGB2 regulates cell proliferation and hepatocyte size during liver regeneration. Sci Rep. 2022 Jul 13;12(1):11962. doi: 10.1038/s41598-022-16258-4. PMID: 35831365; PMCID: PMC9279446

Extracellular Volume Fraction Calculated Using Contrast-Enhanced Computed Tomography as a Biomarker of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome: A Preliminary Histopathological Analysis

Background. Oxaliplatin (OX)-based chemotherapy induces sinusoidal obstruction syndrome (SOS) in the nontumorous liver parenchyma, which can increase the risk of liver resection due to colorectal liver metastasis (CRLM). The extracellular volume (ECV) calculated from contrast-enhanced computed tomography (CT) has been reported to reflect the morphological change of hepatic fibrosis. The present retrospective study aimed to evaluate the ECV fraction as a predictive factor for OX-induced SOS. Methods. Our study included 26 patients who underwent liver resection for CRLM after OX-based chemotherapy with a preoperative dynamic CT of appropriate quality. We investigated the relationship between the pathological SOS grade and the ECV fraction. Results. Overall, 26 specimens from the patients were graded with the SOS classification of Rubbia-Brandt et al. as follows: grade 0, n = 17 (65.4%); grade 1, n = 4 (15.4%); and grade 2, n = 5 (19.2%). No specimens showed grade 3 SOS. In a univariate analysis, the ECV fraction in grade 0 SOS was significantly lower than that in grade 1 + 2 SOS (26.3 ± 3.4% vs. 30.6 ± 7.0%; P = 0.025). The cutoff value and AUC value of the ECV fraction to distinguish between grades 0 and 1 + 2 were 27.5% and 0.771, respectively. Conclusions. Measurement of the ECV fraction was found to be a potential noninvasive diagnostic method for determining early-stage histopathological sinusoidal injury induced by OX-based chemotherapy.Citation: Kai K, Hamada T, Sato Y, Hiyoshi M, Imamura N, Yano K, Ikeda T, Ichihara A, Ogata S, Choijookhuu N, Hishikawa Y, Hosokawa A, Nanashima A. Extracellular Volume Fraction Calculated Using Contrast-Enhanced Computed Tomography as a Biomarker of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome: A Preliminary Histopathological Analysis. J Oncol. 2023 Feb 14;2023:1440257. doi: 10.1155/2023/144025