2018年09月, IBD and Liver: East Meets West, Posters of Distinction.　　　　　　　　　　　　　　　
Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver with steatosis.
Michitaka Ozaki

2015年05月, 北海道大学大学院保健科学研究院, 第7回北海道大学大学院保健科学研究院長賞　　　　　　　　　　　　　　　
尾崎 倫孝

2005年, ILTS 2005, Travel Award　　　　　　　　　　　　　　　
International Liver Transplantation Society.
尾崎 倫孝

2002年, ACT 2002, International Investigator Award (Dr. Lei Guo as awardee)　　　　　　　　　　　　　　　
American Congress of Transplantation
尾崎 倫孝

2001年, AST 2001, International Investigator Award　　　　　　　　　　　　　　　
American Society of Transplantation
尾崎 倫孝

2000年, Johns Hopkins University Department of Medicine, Research Fellow Investigator Award　　　　　　　　　　　　　　　
尾崎 倫孝

1999年, American Liver Foundation, Amgen Postdoctoral Research Fellowship Award　　　　　　　　　　　　　　　
尾崎 倫孝

1999年, Johns Hopkins University Department of Surgery, Transplant Research Award　　　　　　　　　　　　　　　
尾崎 倫孝

In vivo bioluminescence imaging revealed the change of the time window of BDNF expression in the brain elicited by a single bout of exercise following repeated exercise
Ryo Ikegami, Takahiro Inoue, Yasuyuki Takamatsu, Taichi Nishio, Mamoru Fukuchi, Sanae Haga, Michitaka Ozaki, Hiroshi Maejima
Neuroscience Letters, 137830, 137830, Elsevier BV, 2024年05月
研究論文（学術雑誌）

Temporal dynamics of brain BDNF expression following a single bout of exercise: a bioluminescence imaging study
Takahiro Inoue, Ryo Ikegami, Yasuyuki Takamatsu, Mamoru Fukuchi, Sanae Haga, Michitaka Ozaki, Hiroshi Maejima
Neuroscience Letters, 799, 137120, Elsevier BV, 2023年03月, ［査読有り］
英語, 研究論文（学術雑誌）

加齢マウス肝切除による持続性肝障害と肝再生不全のメカニズム　　　　　　　　　　　　　　　
尾崎倫孝, 芳賀早苗, 森田直樹
Organ Biology, 30, 2, 88, 94, 2023年

Analysis of anticipatory behavior formation mechanism induced by methamphetamine using a single hair.　　　　　　　　　　　　　　　
Riku Sato, Megumi Kanai, Yukina Yoshida, Shiori Fukushima, Masahiro Nogami, Takeshi Yamaguchi, Norio Iijima, Kenneth Sutherland, Sanae Haga, Michitaka Ozaki, Kazuko Hamada, Toshiyuki Hamada
Cells, 12, 654, 2023年

A real-time measurement system for gene expression rhythms from deep tissues of freely moving mice under light-dark conditions.
Mizuki Nakaya, Miho Wakamatsu, Hinaki Motegi, Ami Tanaka, Kenneth Sutherland, Masayori Ishikawa, Michitaka Ozaki, Hiroki Shirato, Kazuko Hamada, Toshiyuki Hamada
Biochemistry and biophysics reports, 32, 101344, 101344, 2022年12月, ［国際誌］
英語, 研究論文（学術雑誌）, Clock gene expression in most organs of the living body exhibits a diurnal rhythm synchronized with the external 24 h light-dark (LD) cycle via circadian pacemaker suprachiasmatic nucleus (SCN). Disturbances in clock gene expression due to desynchronization of clock gene expression of the external LD cycle are risk factors for developing various diseases. Measuring the in vivo clock genes expression rhythm for a long duration under LD conditions can greatly contribute to understand the pathogenic mechanism of the disease caused by the disturbance of the biological rhythm. However, it is presently difficult to continuously measure gene expression for a long duration under LD conditions. In present study, we succeeded in measuring Period1 (Per1) gene expression under LD conditions using ultraviolet (UV) light with filter cut the visible light range. In addition, we succeeded in measuring the kinetic change of liver Per1 gene expression during the process of desynchronization of behavioral rhythm from the LD cycle by chronic administration of methamphetamine (MAP). In the future, by using this system to measure clock gene expression rhythms of brain tissues such as SCN and peripheral tissues under LD conditions, it could contribute to understand the onset mechanism of diseases induced by the desynchronization mechanism of biological rhythm to the LD cycle.

The usefulness of measuring n-butyric acid concentration as a new indicator of blood decomposition in forensic autopsy.
Kotaro Matoba, Manabu Murakami, Emi Fujita, Shigeki Jin, Ryosuke Ogasawara, Tomoko Matoba, Akiko Takeuchi, Sanae Haga, Michitaka Ozaki, Hideki Hyodoh
Legal medicine (Tokyo, Japan), 57, 102071, 102071, 2022年04月15日, ［国際誌］
英語, 研究論文（学術雑誌）, In forensic medicine, although various alcohols have been reported as indicators of decomposition in collected blood, no studies have examined short-chain fatty acids as indicators. In this study, the blood n-butyric acid concentration was quantified, and the association between n-butyric acid and decomposition was investigated to determine whether the detection of n-butyric acid could be a new indicator of decomposition. Among the forensic autopsies performed from 2016 to 2018 in our laboratory, the cases were divided into decomposed (n = 20) and non-decomposed (n = 20) groups based on macroscopic findings. Blood samples collected at the time of autopsy were derivatized with 3-nitrophenylhydrazine hydrochloride after solid-phase extraction. The n-butyric acid concentration was measured using liquid chromatography-tandem mass spectrometry. In addition, ethanol and n-propanol were measured using a gas chromatography-flame ionization detector. There was a significant difference (p < 0.01) in the concentrations of n-butyric acid between the decomposed and non-decomposed groups (0.343 ± 0.259 [0.030-0.973] and 0.003 ± 0.002 [0.001-0.007] mg/mL, respectively). In the decomposed group, n-butyric acid was detected at high concentrations, even in cases where n-propanol was low. These results suggest that n-butyric acid is more likely to be an indicator of blood decomposition than n-propanol.

Period1 gene expression in the olfactory bulb and liver of freely moving streptozotocin-treated diabetic mouse.
Harumi Kanou, Kouki Nagasawa, Yuki Ishii, Aya Chishima, Juri Hayashi, Sanae Haga, Kenneth Sutherland, Masayori Ishikawa, Michitaka Ozaki, Hiroki Shirato, Kazuko Hamada, Toshiyuki Hamada
Biochemical and biophysical research communications, 560, 14, 20, 2021年06月30日, ［国際誌］
英語, 研究論文（学術雑誌）, Clock genes express circadian rhythms in most organs. These rhythms are organized throughout the whole body, regulated by the suprachiasmatic nucleus (SCN) in the brain. Disturbance of these clock gene expression rhythms is a risk factor for diseases such as obesity. In the present study, to explore the role of clock genes in developing diabetes, we examined the effect of streptozotocin (STZ)-induced high glucose on Period1 (Per1) gene expression rhythm in the liver and the olfactory bub (OB) in the brain. We found a drastic increase of Per1 expression in both tissues after STZ injection while blood glucose content was low. After a rapid expression peak, Per1 expression showed no rhythm. Associated with an increase of glucose content, behavior became arrhythmic. Finally, we succeeded in detecting an increase of Per1 expression in mice hair follicles on day 1 after STZ administration, before the onset of symptoms. These results show that elevated Per1 expression by STZ plays an important role in the aggravation of diabetes.

Stability of d-luciferin for bioluminescence to detect gene expression in freely moving mice for long durations.
Kanako Nakajima, Kazuko Hamada, Ryoga Ito, Yukina Yoshida, Kenneth Sutherland, Masayori Ishikawa, Michitaka Ozaki, Hiroki Shirato, Toshiyuki Hamada
Luminescence : the journal of biological and chemical luminescence, 36, 1, 94, 98, 2021年02月, ［国際誌］
英語, 研究論文（学術雑誌）, Circadian disturbance of clock gene expression is a risk factor for diseases such as obesity, cancer, and sleep disorders. To study these diseases, it is necessary to monitor and analyze the expression rhythm of clock genes in the whole body for a long duration. The bioluminescent reporter enzyme firefly luciferase and its substrate d-luciferin have been used to generate optical signals from tissues in vivo with high sensitivity. However, little information is known about the stability of d-luciferin to detect gene expression in living animals for a long duration. In the present study, we examined the stability of a luciferin solution over 21 days. l-Luciferin, which is synthesized using racemization of d-luciferin, was at high concentrations after 21 days. In addition, we showed that bioluminescence of Period1 (Per1) expression in the liver was significantly decreased compared with the day 1 solution, although locomotor activity rhythm was not affected. These results showed that d-luciferin should be applied to the mouse within, at most, 7 days to detect bioluminescence of Per1 gene expression rhythm in vivo.

生体分子機能を可視化する発光イメージングと応用技術　　　　　　　　　　　　　　　
尾崎倫孝, 小澤岳昌
OPTRONICS, 480, 12, 104, 110, 2021年

Mouse period1 gene expression recording from olfactory bulb under free moving conditions with a portable optic fibre device.
Ryoga Ito, Kazuko Hamada, Shigeru Kasahara, Yoshihiro Kikuchi, Kanako Nakajima, Kenneth Sutherland, Hiroki Shirato, Michitaka Ozaki, Masayori Ishikawa, Toshiyuki Hamada
Luminescence : the journal of biological and chemical luminescence, 35, 8, 1248, 1253, 2020年12月, ［国際誌］
英語, 研究論文（学術雑誌）, Because the disruption of circadian clock gene is a risk factor in many diseases such as obesity and cancer, it is important to monitor and analyzed the expression of the rhythm of the clock gene throughout the body over a long period of time. Although we previously reported on a new gene expression analysis system tracking a target position on the body surface of freely moving mice, the experimental apparatus required a large space. We have therefore developed an in vivo recording system using a portable photomultiplier tube (PMT) system attached to an optical fibre. Directly connecting the target area with the device, we could easily measure the photon counts in a very small space. However, little information is known about the characteristics of optical fibres when exposed to twisting/looping in association with a moving mouse and the effect of the surface of optical fibre. In the present study, we report on the characteristics of optical fibres to detect gene expression rhythm in freely moving mice. Using this portable optical device directly connected with a target area, we were able to measure the circadian rhythm of clock gene expression over a prolonged period in freely moving mice in a small space.

Double recording system of Period1 gene expression rhythm in the olfactory bulb and liver in freely moving mouse.
Kazuko Hamada, Akari Oota, Ryoga Ito, Shigeru Kasahara, Kanako Nakajima, Yoshihiro Kikuchi, Kenneth Sutherland, Masayori Ishikawa, Hiroki Shirato, Michitaka Ozaki, Toshiyuki Hamada
Biochemical and biophysical research communications, 529, 4, 898, 903, 2020年09月03日, ［国際誌］
英語, 研究論文（学術雑誌）, Clock genes express circadian rhythms in most organs. These rhythms are organized throughout the whole body, regulated by the suprachiasmatic nucleus (SCN) in the brain. Disturbance of these clock gene expression rhythms is a risk factor for diseases such as obesity and cancer. To understand the mechanism of regulating clock gene expression rhythms in vivo, multiple real time recording systems are required. In the present study, we developed a double recording system of Period1 expression rhythm in peripheral tissue (liver) and the brain. In peripheral tissue, quantification of gene expression in a steadily moving target was achieved by using a photomultiplier tube (PMT) attached to a tissue contact optical sensor (TCS). Using this technique, we were able to analyze circadian rhythms of clock gene expression over a prolonged period in the liver and olfactory bub (OB) of the brain. The present double recording system has no effect on behavioral activity or rhythm. Our novel system thus successfully quantifies clock gene expression in deep areas of the body in freely moving mice for a period sufficient to analyze circadian dynamics. In addition, our double recording system can be widely applied to many areas of biomedical research, as well as applications beyond medicine.

Sample preparation method with ultrafiltration for whole blood thiosulfate measurement.
Shigeki Jin, Manabu Murakami, Kotaro Matoba, Tomoko Matoba, Sanae Haga, Michitaka Ozaki, Akiko Takeuchi, Hideki Hyodoh
Legal medicine (Tokyo, Japan), 47, 101765, 101765, 2020年07月23日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Quantitative analysis of thiosulfate is useful for diagnosing hydrogen sulfide poisoning. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) enables more rapid and sensitive measurements than previous methodologies. As simple measurements of blood thiosulfate concentration are affected by the blood matrix, blood is used as the solvent to prepare the standard solution for calibration curve generation. Thus, a large amount of blood devoid of thiosulfate is required. We developed a preparation method by incorporating an ultrafiltration step to overcome this limitation and generate a calibration curve using a standard solution prepared with pure water. We used this improved method to investigate the stability of thiosulfate in refrigerated samples. To compare the effects of refrigeration, blood samples were prepared using the following two methods: one sample was treated with a 50-kDa exclusion ultrafiltration membrane and the other was not treated. The samples were stored at 4 °C, and then measured at 0, 3, 6, 24, 48, and 96 h. The incorporation of the ultrafiltration step in the measurement procedure enabled the quantification of thiosulfate, by plotting a calibration curve using a standard of pure water; it did not require a blood standard. Additionally, the reduction in whole blood thiosulfate concentration was within 10% during 2 days of refrigeration. Thus, the need for a large amount of blood to prepare the standard solution was resolved by the ultrafiltration step in test sample preparation. This method is useful to measure thiosulfate concentration and is not hindered by sample refrigeration for a few days.

Cellular and molecular mechanisms of liver regeneration: proliferation, growth, death and protection of hepatocytes.
尾崎 倫孝
Seminars in Cell and Developmental Biology, 100, 62, 73, 2020年04月, ［査読有り］, ［招待有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, 13762468

Extracts of bilberry (Vaccinium myrtillus L.) fruits improve liver steatosis and injury in mice by preventing lipid accumulation and cell death.　　　　　　　　　　　　　　　
尾崎 倫孝
Bioscience, Biotechnology, and Biochemistry, 83, 11, 2110, 2120, 2019年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Activation of caspase-3 during Chlamydia trachomatis-induced apoptosis at a late stage.　　　　　　　　　　　　　　　
尾崎 倫孝
Canadian Journal of Microbiology, 65, 135, 143, 2019年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Detection of necroptosis in ligand-mediated and hypoxia-induced injury of hepatocytes using a novel optic probe-detecting receptor-interacting protein (RIP)1/RIP3 binding
Sanae Haga, Akira Kanno, Takeaki Ozawa, Naoki Morita, Mami Asano, Michitaka Ozaki
Oncology Research, 26, 3, 503, 513, Cognizant Communication Corporation, 2018年, ［査読有り］
英語, 研究論文（学術雑誌）, Liver injury is often observed in various pathological conditions including posthepatectomy state and cancer chemotherapy. It occurs mainly as a consequence of the combined necrotic and apoptotic types of cell death. In order to study liver/hepatocyte injury by the necrotic type of cell death, we studied signal-regulated necrosis (necroptosis) by developing a new optic probe for detecting receptor-interacting protein kinase 1 (RIP)/RIP3 binding, an essential process for necroptosis induction. In the mouse hepatocyte cell line, TIB-73 cells, TNF-a/cycloheximide (T/C) induced RIP1/3 binding only when caspase activity was suppressed by the caspase-specific inhibitor z-VAD-fmk (zVAD). T/C/zVAD-induced RIP1/3 binding was inhibited by necrostatin-1 (Nec-1), an allosteric inhibitor of RIP1. The reduced cell survival by T/C/zVAD was improved by Nec-1. These facts indicate that T/C induces necroptosis of hepatocytes when the apoptotic pathway is inhibited/unavailable. FasL also induced cell death, which was only partially inhibited by zVAD, indicating the possible involvement of necroptosis rather than apoptosis. FasL activated caspase 3 and, similarly, induced RIP1/3 binding when the caspases were inactivated. Interestingly, FasL-induced RIP1/3 binding was significantly suppressed by the antioxidants Trolox and N-acetyl cysteine (NAC), suggesting the involvement of reactive oxygen species (ROS) in FasL-induced necroptotic cellular processes. H2O2, by itself, induced RIP1/3 binding that was suppressed by Nec-1, but not by zVAD. Hypoxia induced RIP1/3 binding after reoxygenation, which was suppressed by Nec-1 or by the antioxidants. Cell death induced by hypoxia/ reoxygenation (H/R) was also improved by Nec-1. Similar to H2O2, H/R did not require caspase inhibition for RIP1/3 binding, suggesting the involvement of a caspase-independent mechanism for non-ligand-induced and/or redox-mediated necroptosis. These data indicate that ROS can induce necroptosis and mediate the FasL- and hypoxia-induced necroptosis via a molecular mechanism that differs from a conventional caspase-dependent pathway. In conclusion, necroptosis is potentially involved in liver/hepatocyte injury induced by oxidative stress and FasL in the absence of apoptosis.

Photo-activatable akt probe: A new tool to study the akt-dependent physiopathology of cancer cells
Sanae Haga, Takeaki Ozawa, Naoki Morita, Mami Asano, Shigeki Jin, Yimin, Michitaka Ozaki
Oncology Research, 26, 3, 467, 472, Cognizant Communication Corporation, 2018年, ［査読有り］
英語, 研究論文（学術雑誌）, Akt is commonly overexpressed and activated in cancer cells and plays a pivotal role in cell survival, protection, and chemoresistance. Therefore, Akt is one of the target molecules in understanding characters of cancer cells and developing anticancer drugs. Here we examined whether a newly developed photo-activatable Akt (PA-Akt) probe, based on a light-inducible protein interaction module of plant cryptochrome2 (CRY2) and cryptochrome-interacting basic helix–loop–helix (CIB1), can regulate Akt-associated cell functions. By illuminating blue light to the cells stably transfected with PA-Akt probe, CRY2-Akt (a fusion protein of CRY2 and Akt) underwent a structural change and interacted with Myr-CIBN (myristoylated N-terminal portion of CIB1), anchoring it at the cell membrane. Western blot analysis revealed that S473 and T308 of the Akt of probe-Akt were sequentially phosphorylated by intermittent and continuous light illumination. Endogenous Akt and GSK-3b, one of the main downstream signals of Akt, were also phosphorylated, depending on light intensity. These facts indicate that photo-activation of probe-Akt can activate endogenous Akt and its downstream signals. The photo-activated Akt conferred protection against nutritional deprivation and H2O2 stresses to the cells significantly. Using the newly developed PA-Akt probe, endogenous Akt was activated easily, transiently, and repeatedly. This probe will be a unique tool in studying Akt-associated specific cellular functions in cancer cells and developing anticancer drugs.

Type XVII collagen coordinates proliferation in the interfollicular epidermis
Mika Watanabe, Ken Natsuga, Wataru Nishie, Yasuaki Kobayashi, Giacomo Donati, Shotaro Suzuki, Yu Fujimura, Tadasuke Tsukiyama, Hideyuki Ujiie, Satoru Shinkuma, Hideki Nakamura, Masamoto Murakami, Michitaka Ozaki, Masaharu Nagayama, Fiona M. Watt, Hiroshi Shimizu
ELIFE, 6, ELIFE SCIENCES PUBLICATIONS LTD, 2017年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Type XVII collagen (COL17) is a transmembrane protein located at the epidermal basement membrane zone. COL17 deficiency results in premature hair aging phenotypes and in junctional epidermolysis bullosa. Here, we show that COL17 plays a central role in regulating interfollicular epidermis (IFE) proliferation. Loss of COL17 leads to transient IFE hypertrophy in neonatal mice owing to aberrant Wnt signaling. The replenishment of COL17 in the neonatal epidermis of COL17-null mice reverses the proliferative IFE phenotype and the altered Wnt signaling. Physical aging abolishes membranous COL17 in IFE basal cells because of inactive atypical protein kinase C signaling and also induces epidermal hyperproliferation. The overexpression of human COL17 in aged mouse epidermis suppresses IFE hypertrophy. These findings demonstrate that COL17 governs IFE proliferation of neonatal and aged skin in distinct ways. Our study indicates that COL17 could be an important target of anti-aging strategies in the skin.

Evaluation and regulation cellular/organ functions by optic technology.
Michitaka Ozaki, Sanae Haga, Takeaki Ozawa, Naoki Morita, Toshiyuki Hamada
Organ Biology, 24, 2, 87, 91, 一般社団法人 日本臓器保存生物医学会, 2017年, ［査読有り］
英語, 研究論文（学術雑誌）, To develop an effective organ/cell preservation method and to monitor post-transplant graft function continuously and non-invasively, an innovative optic technology to visualize cell/organ function seems to be useful. We have developed some optic probes to visualize regulated cell death (apoptosis, necroptosis, pyroptosis), redox states and cellular stresses, pH and cellular antigens in deeper lesions of the organ. In the hepatic ischemia/reperfusion model of mice, we successfully imaged liver oxidative stress (by redox-sensitive GFP) and apoptosis (by caspase-3 activity) non-invasively and chronologically in a single mouse. We also developed a unique tool to visualize intracellular pH and succeeded in imaging dynamic changes of pH in a mouse posterior limb ischemia/reperfusion model. We are also developing the new devices for tissue/organ imaging. We are trying to monitor the optic signals chronologically and track the lesions in the body by developing light sensor and multiple CCD camera system, which can be used in endoscopic examination and surgical operation. It is still on a way, but this kind of technology will definitely provide a new avenue toward effective and non-invasive surgical therapy in the future.

Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver, especially with steatosis
Sanae Haga, Yimin, Michitaka Ozaki
BMC GASTROENTEROLOGY, 17, 1, 9, BIOMED CENTRAL LTD, 2017年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Liver injury and regeneration involve complicated processes and are affected by various physiopathological conditions. Surgically, severe liver injury after surgical resection often leads to fatal liver failure, especially with some underlying pathological conditions such as steatosis. Therefore, protection from the injury of hepatocytes and liver is a serious concern in various clinical settings.
Methods: We studied the effects of the farnesoid X receptor (FXR) on cell survival and steatosis in mouse hepatocytes (AML12 mouse liver cells) and investigated their molecular mechanisms. We next studied whether or not FXR improves liver injury, regeneration and steatosis in a mouse model of partial hepatectomy (PH) with steatosis.
Results: An FXR-specific agonist, GW4064, induced expressions of the p62/SQSTM1 gene and protein in AML12 mouse liver cells. Because we previously reported p62/SQSTM1 as a key molecule for antioxidation and cell survival in hepatocytes, we next examined the activation of nuclear factor erythroid 2-related factor-2 (Nrf2) and induction of the antioxidant molecules by GW4064. GW4064 activated Nrf2 and subsequently induced antioxidant molecules (Nrf2, catalase, HO-1, and thioredoxin). We also examined expressions of pro-survival and cell protective molecules associated with p62/SQSTM1. Expectedly, GW4064 induced phosphorylation of Akt, expression of the anti-apoptotic molecules (Bcl-xL and Bcl-2), and reduced harmful hepatic molecules (Fas ligand and Fas). GW4064 promoted hepatocyte survival, which was cancelled by p62/SQSTM1 siRNA. These findings suggest the potential relevance of the FXR-p62/SQSTM1 pathway for the survival and protection of hepatocytes. Furthermore, GW4064 induced the expression of small heterodimer partners (SHP) and suppressed liver X receptor (LXR)-induced steatosis in hepatocytes, expecting the in vivo protective effect of FXR on liver injury especially with steatosis. In the hepatectomy model of db/db mice with fatty liver, pre-treatment by GW4064 significantly reduced post-PH liver injury (serum levels of LDH, AST & ALT and histological study) and improved steatosis. The key molecules, p62/SQSTM1, Nrf2 and SHP were upregulated in fatty liver tissue by GW4064 treatment.
Conclusions: The present study is the first to demonstrate the relevance of FXR-p62/SQSTM1 and-SHP in the protection against injury of hepatocytes and post-PH liver, especially with steatosis.

Inflammatory responses increase secretion of MD-1 protein
Richard Thomas Jennings, Erdenezaya Odkhuu, Akina Nakashima, Naoko Morita, Toshihiko Kobayashi, Ikuko Yamai, Miyako Tanaka, Takayoshi Suganami, Sanae Haga, Michitaka Ozaki, Yasuharu Watanabe, Yoshinori Nagai, Kiyoshi Takatsu, Takane Kikuchi-Ueda, Isao Ichimonji, Yoshihiro Ogawa, Hidekazu Takagi, Tatsuya Yamazaki, Kensuke Miyake, Sachiko Akashi-Takamura
INTERNATIONAL IMMUNOLOGY, 28, 10, 503, 512, OXFORD UNIV PRESS, 2016年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Novel antibodies detect the increased level of soluble MD-1 during inflammation.Radioprotective 105 (RP105) is a type I transmembrane protein, which associates with a glycoprotein, MD-1. Monoclonal antibody (mAb)-mediated ligation of RP105/MD-1 robustly activates B cells. RP105/MD-1 is structurally similar to Toll-like receptor 4 (TLR4)/MD-2. B-cell responses to TLR2 and TLR4/MD-2 ligands are impaired in the absence of RP105 or MD-1. In addition to RP105/MD-1, MD-1 alone is secreted. The structure of MD-1 shows that MD-1 has a hydrophobic cavity that directly binds to phospholipids. Little is known, however, about a ligand for MD-1 and the role of MD-1 in vivo. To study the role of RP105/MD-1 and MD-1 alone, specific mAbs against MD-1 are needed. Here, we report the establishment and characterization of two anti-MD-1 mAbs (JR2G9, JR7G1). JR2G9 detects soluble MD-1, whereas JR7G1 binds both soluble MD-1 and the cell surface RP105/MD-1 complex. With these mAbs, soluble MD-1 was detected in the serum and urine. The MD-1 concentration was altered by infection, diet and reperfusion injury. Serum MD-1 was rapidly elevated by TLR ligand injection in mice. The quantitative PCR and supernatant-precipitated data indicate that macrophages are one of the sources of serum soluble MD-1. These results suggest that soluble MD-1 is a valuable biomarker for inflammatory diseases.

Development for the measurement of serum thiosulfate using LC-MS/MS in forensic diagnosis of H2S poisoning
Shigeki Jin, Hideki Hyodoh, Kotaro Matoba, Fei Feng, Akira Hayakawa, Katsuhiro Okuda, Keiko Shimizu, Sanae Haga, Michitaka Ozaki, Koichi Terazawa
LEGAL MEDICINE, 22, 18, 22, ELSEVIER IRELAND LTD, 2016年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Thiosulfate measurement is crucial to diagnosis of hydrogen sulfide (H2S) poisoning in forensic toxicology. Although GC-MS method is currently regarded as a standard thiosulfate measurement, it requires complicated sample preparation prior to analysis. This study presents a simple, rapid, and highly sensitive method for the quantitative analysis of serum thiosulfate by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This method is based on selected reaction monitoring and has high sensitivity with a lower quantification limit of 0.5 mu M. Precision and accuracy of this method meet the basic requirements for quantitative analysis (intra- and inter-day tests have a relative standard deviation of <= 10.4%;range of analytical recovery is 94.3-102.6%). On the measurements of serum thiosulfate by our developed method, a thiosulfate concentration as 57.5 mu M was detected clearly in the H2S poisoning case comparing to the non poisoning case in which only a trace amount of thiosulfate was observed. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Novel anti-inflammatory agent 3-[ (dodecylthiocarbonyl)-methyl]-glutarimide ameliorates murine models of inflammatory bowel disease
Nobuki Ichikawa, Kenichiro Yamashita, Tohru Funakoshi, Shin Ichihara, Moto Fukai, Masaomi Ogura, Nozomi Kobayashi, Masaaki Zaitsu, Tadashi Yoshida, Susumu Shibasaki, Yasuyuki Koshizuka, Yusuke Tsunetoshi, Masanori Sato, Takahiro Einama, Michitaka Ozaki, Kazuo Umezawa, Tomomi Suzuki, Satoru Todo
INFLAMMATION RESEARCH, 65, 3, 245, 260, SPRINGER BASEL AG, 2016年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective and design To examine the effect of 3-[ (dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G), a novel anti-inflammatory agent that inhibits lipopolysaccharide (LPS) activation of RAW264.7 macrophages, on murine models of colitis and RAW264.7 cells.
Materials and methods Colitis was induced by rectally infusing trinitrobenzenesulfonic acid (TNBS) (1.5 mg in 50 % ethanol) in BALB/c mice or orally administering 3 % dextran sulfate sodium (DSS) for 5 days in C57BL/6 mice. The severity of colitis was assessed after intraperitoneally injecting DTCM-G (40 mg/kg). The anti-inflammatory properties of DTCM-G and its mechanisms were investigated in LPS-stimulated RAW264.7 cells.
Results DTCM-G significantly ameliorated TNBS-induced colitis, according to the body weight loss, disease activity index, colonic obstruction, macroscopic colonic inflammation score, mucosal myeloperoxidase activity, and histopathology. Immunohistochemistry and isolated lamina propria mononuclear cells showed significantly reduced colonic F4/80(+) and CD11b(+) macrophage infiltration. DTCM-G significantly suppressed tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 messenger RNA expression in the colon and attenuated DSS-induced colitis, according to the disease activity index and histopathology. In RAW264.7 cells, DTCM-G suppressed LPS-induced TNF-alpha/IL-6 production and enhanced glycogen synthase kinase-3 beta phosphorylation.
Conclusions DTCM-G attenuated murine experimental colitis by inhibiting macrophage infiltration and inflammatory cytokine expression. Thus, DTCM-G may be a promising treatment for inflammatory bowel disease.

Long-term ex vivo and in vivo monitoring of tumor progression by using dual luciferases
Naoki Morita, Sanae Haga, Yoshihiro Ohmiya, Michitaka Ozaki
ANALYTICAL BIOCHEMISTRY, 497, 24, 26, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2016年03月, ［査読有り］
英語, 研究論文（学術雑誌）, We propose a new concept of tumor progression monitoring using dual luciferases in living animals to reduce stress for small animals and the cost of luciferin. The secreted Cypridina luciferase (CLuc) was used as an ex vivo indicator to continuously monitor tumor progression. On the other hand, the non-secreted firefly luciferase was used as an in vivo indicator to analyze the spatial distribution of the tumor at suitable time points indicated by CLuc. Thus, the new monitoring systems that use dual luciferases are available, allowing long-term bioluminescence imaging under minimal stress for the experimental animals. (C) 2015 Elsevier Inc. All rights reserved.

p62/SQSTM1を基軸とした新たな肝臓・肝細胞保護・機能維持メカニズム
尾崎 倫孝, 芳賀 早苗
Organ Biology, 23, 2, 168, 172, 一般社団法人 日本臓器保存生物医学会, 2016年
日本語, We have been investigating the mechanism of liver regeneration and injury for liver surgery and transplantation. We firstly studied, in normal liver, the central role of IL-6/Jak/STAT3 in post-PH mitotic response and protective mechanism from hepatocyte injury, and the essential role of PDK1/Akt in post-PH cell growth in case where mitotic response is impaired. In fatty liver, reduced expression of p62/SQSTM1 plays a crucial role in post-hepatectomy acute injury and delayed regeneration with enhanced oxidative stress- and death signal-mediated injury. Reduced expression of p62/SQSTM1 lead to FasL/Fas overexpression and suppressed antioxidant genes through Nrf-2 inactivation, which along with the hypo-responsiveness of Akt, caused post-hepatectomy necrotic/apoptotic liver injury and delayed regeneration. Our study importantly suggests the potential role of p62/SQSTM1 in protecting the liver from all kinds of injury, providing pro-survival property to hepatocytes/liver. Here, we report the pivotal roles of p62/SQSTM1 as a key player for cell/organ preservation, and the potential application for liver preservation and transplantation.

Mitochondrial delivery of Coenzyme Q(10) via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver
Yuma Yamada, Kohei Nakamura, Jiro Abe, Mamoru Hyodo, Sanae Haga, Michitaka Ozaki, Hideyoshi Harashima
JOURNAL OF CONTROLLED RELEASE, 213, 86, 95, ELSEVIER SCIENCE BV, 2015年09月, ［査読有り］
英語, 研究論文（学術雑誌）, We herein report on a mitochondrial therapeutic effect based on the delivery of coenzyme Q(10) (CoQ(10)), an anti-oxidant, to in vivo mitochondria using a MITO-Porter, a liposome-based mitochondrial delivery system that functions via membrane fusion. To evaluate the effects, we used a mouse liver ischemia/reperfusion injury (I/R injury) model, in which mitochondrial reactive oxygen species are overexpressed. We packaged CoQ(10) in the lipid phase of a MITO-Porter and optimized the mitochondrial fusogenic activities to produce the CoQ(10)-MITO-Porter. A histological observation of the carriers in the liver by confocal laser scanning microscopy was done and the accumulation of the carrier labeled with a radio isotope in the liver confirmed that the CoQ(10)-MITO-Porter was delivered to liver mitochondria via systemic injection. These analytical results permitted us to optimize the compositions of the CoQ(10)-MITO-Porter so as to permit it to efficiently accumulate in mouse liver mitochondria. Finally, we applied the optimized CoQ(10) -MITO-Porter to mice via tail vein injection, and hepatic I/R injury was then induced, followed by measuring serum alanine aminotransferase (ALT) levels, a marker of liver injury. We confirmed that the use of the CoQ(10)-MITO-Porter resulted in a significant decrease in serum ALT levels, indicating that in vivo mitochondrial delivery of the CoQ(10) via MITO-Porter prevents I/R injury in mice livers. This provides a demonstration of the potential use of such a delivery system in mitochondrial therapies. (C) 2015 Elsevier B.V. All rights reserved.

虚血再灌流臓器障害に関する基礎研究の進歩 基礎研究・移植再生 光イメージングによる虚血再灌流障害の動的・質的解析　　　　　　　　　　　　　　　
尾崎 倫孝, 芳賀 早苗, 野田 なつみ, 小澤 岳昌, 森田 直樹
日本外科学会定期学術集会抄録集, 115回, SY, 6, (一社)日本外科学会, 2015年04月
日本語

Growth Arrest and DNA Damage-Inducible 34 Regulates Liver Regeneration in Hepatic Steatosis in Mice
Yuka Inaba, Tomoko Furutani, Kumi Kimura, Hitoshi Watanabe, Sanae Haga, Yoshiaki Kido, Michihiro Matsumoto, Yasuhiko Yamamoto, Kenichi Harada, Shuichi Kaneko, Seiichi Oyadomari, Michitaka Ozaki, Masato Kasuga, Hiroshi Inoue
HEPATOLOGY, 61, 4, 1343, 1356, WILEY-BLACKWELL, 2015年04月, ［査読有り］
英語, 研究論文（学術雑誌）, The liver has robust regenerative potential in response to damage, but hepatic steatosis (HS) weakens this potential. We found that the enhanced integrated stress response (ISR) mediated by phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2) impairs regeneration in HS and that growth arrest and DNA damage-inducible 34 (Gadd34)-dependent suppression of ISR plays a crucial role in fatty liver regeneration. Although mice fed a high-fat diet for 2 weeks developed moderate fatty liver with no increase in eIF2 phosphorylation before 70% hepatectomy, they showed impaired liver regeneration as a result of reduced proliferation and increased death of hepatocytes with increased phosphorylation of eIF2 and ISR. An increased ISR through Gadd34 knockdown induced C/EBP homologous protein (CHOP)-dependent apoptosis and receptor-interacting protein kinase 3-dependent necrosis, resulting in increased hepatocyte death during fatty liver regeneration. Furthermore, Gadd34 knockdown and increased phosphorylation of eIF2 decreased cyclin D1 protein and reduced hepatocyte proliferation. In contrast, enhancement of Gadd34 suppressed phosphorylation of eIF2 and reduced CHOP expression and hepatocyte apoptosis without affecting hepatocyte proliferation, clearly improving fatty liver regeneration. In more severe fatty liver of leptin receptor-deficient db/db mice, forced expression of hepatic Gadd34 also promoted hepatic regeneration after hepatectomy. Conclusion: Gadd34-mediated regulation of ISR acts as a physiological defense mechanism against impaired liver regeneration resulting from steatosis and is thus a possible therapeutic target for impaired regeneration in HS. (Hepatology 2015;61:1343-1356)

p62/SQSTM1 Plays a Protective Role in Oxidative Injury of Steatotic Liver in a Mouse Hepatectomy Model
Sanae Haga, Takeaki Ozawa, Yuma Yamada, Naoki Morita, Izuru Nagashima, Hiroshi Inoue, Yuka Inaba, Natsumi Noda, Riichiro Abe, Kazuo Umezawa, Michitaka Ozaki
ANTIOXIDANTS & REDOX SIGNALING, 21, 18, 2515, 2530, MARY ANN LIEBERT, INC, 2014年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Aims: Liver injury and regeneration involve complicated processes and are affected by various physio-pathological factors. We investigated the mechanisms of steatosis-associated liver injury and delayed regeneration in a mouse model of partial hepatectomy. Results: Initial regeneration of the steatotic liver was significantly delayed after hepatectomy. Although hepatocyte proliferation was not significantly suppressed, severe liver injury with oxidative stress (OS) occurred immediately after hepatectomy in the steatotic liver. Fas-ligand (FasL)/Fas expression was upregulated in the steatotic liver, whereas the expression of antioxidant and anti-apoptotic molecules (catalase/MnSOD/Ref-1 and Bcl-2/Bcl-xL/FLIP, respectively) and p62/SQSTM1, a steatosis-associated protein, was downregulated. Interestingly, pro-survival Akt was not activated in response to hepatectomy, although it was sufficiently expressed even before hepatectomy. Suppression of p62/SQSTM1 increased FasL/Fas expression and reduced nuclear factor erythroid 2-related factor-2 (Nrf-2)-dependent antioxidant response elements activity and antioxidant responses in steatotic and nonsteatotic hepatocytes. Exogenously added FasL induced severe cellular OS and necrosis/apoptosis in steatotic hepatocytes, with only the necrosis being inhibited by pretreatment with antioxidants, suggesting that FasL/Fas-induced OS mainly leads to necrosis. Furthermore, p62/SQSTM1 re-expression in the steatotic liver markedly reduced liver injury and improved liver regeneration. Innovation: This study is the first which demonstrates that reduced expression of p62/SQSTM1 plays a crucial role in posthepatectomy acute injury and delayed regeneration of steatotic liver, mainly via redox-dependent mechanisms. Conclusion: In the steatotic liver, reduced expression of p62/SQSTM1 induced FasL/Fas overexpression and suppressed antioxidant genes, mainly through Nrf-2 inactivation, which, along with the hypo-responsiveness of Akt, caused posthepatectomy necrotic/apoptotic liver injury and delayed regeneration, both mainly via a redox-dependent mechanism. Antioxid. Redox Signal. 21, 2515-2530.

"光"を利用した新たな細胞・臓器保存法の開発
芳賀 早苗, 小澤 岳昌, 野田 なつみ, 尾崎 倫孝
Organ Biology, 21, 3, 42, 42, (一社)日本臓器保存生物医学会, 2014年10月
日本語

高血糖および脂肪化状態が肝虚血/再灌流傷害に及ぼす影響　　　　　　　　　　　　　　　
芳賀 早苗, 小澤 岳昌, 森田 直樹, 野田 なつみ, 尾崎 倫孝
日本生化学会大会プログラム・講演要旨集, 87回, [2P, 408], (公社)日本生化学会, 2014年10月
日本語

細胞・臓器移植における基礎的研究の最前線 光を応用した移植細胞機能・細胞環境のモニタリングと制御の試み
尾崎 倫孝, 芳賀 早苗, 野田 なつみ, 森田 直樹, 山田 勇磨, 小澤 岳昌
日本外科学会雑誌, 115, 臨増2, 168, 168, (一社)日本外科学会, 2014年03月
日本語

臓器保存 光学技術を応用した新たな臓器保存法、細胞・臓器移植法の開発
尾崎 倫孝, 芳賀 早苗, 森田 直樹, 野田 なつみ, 山田 勇馬, 小澤 岳昌
Organ Biology, 20, 3, 40, 40, (一社)日本臓器保存生物医学会, 2013年10月
日本語

Contribution of Toll-Like Receptor 2 to the Innate Response against Staphylococcus aureus Infection in Mice
Yimin, Masashi Kohanawa, Songji Zhao, Michitaka Ozaki, Sanae Haga, Guangxian Nan, Yuji Kuge, Nagara Tamaki
PLoS ONE, 8, 9, e74287, 2013年09月13日, ［査読有り］
英語, 研究論文（学術雑誌）, Staphylococcus aureus is a common pathogen that causes a wide range of infectious diseases. The function of TLRs, specifically TLR2, during S. aureus infection is still debated. In this study, we investigated the extent to which TLR2 contributes to the host innate response against the bacterial infection using TLR2-deficient mice. Intravenous inoculation with S. aureus resulted in all TLR2-deficient mice dying within 4 d, along with a high bacterial burden in the livers. However, histological examination showed the same degree of macrophage and neutrophil accumulation in the livers of infected TLR2-deficient mice as that in infected wild-type (WT) mice. TLR2-deficient mouse macrophages also showed normal phagocytic activity, although they failed to express CD36 that appeared on the surface of WT mouse cells upon challenge with heat-killed S. aureus. These data indicate that TLR2, as well as CD36, does not directly affect S. aureus clearance and that CD36 expression on macrophages depends on the presence of TLR2. In vivo infection with S. aureus caused significantly elevated production of TNF-α and IL-6 in the livers and blood of TLR2-deficient mice compared with those in WT mice, while the hepatic and serum levels of IL-10 decreased in these mice. In contrast, lower expression of IL-6 and IL-10, but not of TNF-α, at both the gene and protein levels was found in TLR2-deficient mouse macrophages compared to that in WT mouse cells, in response to challenge with heat-killed S. aureus. These findings suggest that the S. aureus-induced pro-inflammatory cytokine response is not dependent on macrophages and that TLR2 deficiency results in decreased IL-10 release by macrophages, which contributes to dysregulated cytokine balance, impaired bacterial clearance, and mouse death. Therefore, TLR2 possesses a protective function during S. aureus infection by regulating pro- and anti-inflammatory cytokine responses. © 2013 Yimin et al.

Efficacy of DHMEQ, a NF-κB inhibitor, in islet transplantation: II. Induction DHMEQ treatment ameliorates subsequent alloimmune responses and permits long-term islet allograft acceptance.
Watanabe M, Yamashita K, Kamachi H, Kuraya D, Koshizuka Y, Shibasaki S, Asahi Y, Ono H, Emoto S, Ogura M, Yoshida T, Ozaki M, Umezawa K, Matsushita M, Todo S
Transplantation, 96, 5, 454, 462, LIPPINCOTT WILLIAMS & WILKINS, 2013年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Background. Long-term graft deterioration remains a major obstacle in the success of pancreatic islet transplantation (PITx). Antigen-independent inflammatory and innate immune responses strengthen subsequent antigen-dependent immunity; further, activation of nuclear factor (NF)-kappa B plays a key role during these responses. In this study, we tested our hypothesis that, by the inhibition of NF-kappa B activation, the suppression of these early responses after PITx could facilitate graft acceptance.
Methods. Full major histocompatibility complex (MHC) Ymismatched BALB/c (H-2(d)) mice islets were transplanted into streptozotocin-induced diabetic C57BL/6 (B6: H-2(b)) mice. The NF-kappa B inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) was administered for either 3 or 14 days after PITx. To some PITx recipients, tacrolimus was also administered. Islet allograft survival, alloimmune responses, and in vitro effects of DHMEQ on dendritic cells (DCs) were assessed.
Results. With a vehicle treatment, 600 islet allografts were promptly rejected after PITx. In contrast, 3-day treatment with DHMEQ, followed by 2-week treatment with tacrolimus, allowed permanent acceptance of islet allografts. The endogenous danger-signaling molecule high mobility group complex 1 (HMGB1) was elevated in sera shortly after PITx, whereas DHMEQ administration abolished this elevation. DHMEQ suppressed HMGB1-driven cellular activation and proinflammatory cytokine secretion in mouse bone marrowYderived DCs and significantly reduced the capacity of DCs to prime allogeneic T-cell proliferation in vitro. Finally, the DHMEQ plus tacrolimus regimen reverted the diabetic state with only 300 islet allografts.
Conclusions. Inhibition of NF-kappa B activation by DHMEQ shortly after PITx suppresses HMGB1, which activates DCs and strengthens the magnitude of alloimmune responses; this permits long-term islet allograft acceptance, even in case of fewer islet allografts.

光応答性ルシフェラーゼによる生きた組織下でのpH時間変化モニタリング法の開発　　　　　　　　　　　　　　　
服部 満, 芳賀 早苗, 高倉 栄男, 尾崎 倫孝, 小澤 岳昌
日本分析化学会講演要旨集, 62年会, 42, 42, (公社)日本分析化学会, 2013年08月
日本語

Sustained accurate recording of intracellular acidification in living tissues with a photo-controllable bioluminescent protein
Mitsuru Hattori, Sanae Haga, Hideo Takakura, Michitaka Ozaki, Takeaki Ozawa
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110, 23, 9332, 9337, NATL ACAD SCIENCES, 2013年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Regulation of an intracellular acidic environment plays a pivotal role in biological processes and functions. However, spatiotemporal analysis of the acidification in complex tissues of living subjects persists as an important challenge. We developed a photo-inactivatable bioluminescent indicator, based on a combination of luciferase-fragment complementation and a photoreaction of a light, oxygen, and voltage domain from Avena sativa Phototropin1 (LOV2), to visualize temporally dynamic acidification in living tissue samples. Bioluminescence of the indicator diminished upon light irradiation and it recovered gradually in the dark state thereafter. The recovery rate was remarkably sensitive to pH changes but unsusceptible to fluctuation of luciferin or ATP concentrations. Bioluminescence imaging, taken as an index of the recovery rates, enabled long-time recording of acidification in apoptotic and autophagous processes in a cell population and an ischemic condition in living mice. This technology using the indicator is widely applicable to sense organelle-specific acidic changes in target biological tissues.

A Method for Intravital Monitoring of Human Cells Using a Far-Red Luminescent Probe in Graft-Versus-Host Disease Model Mice
Hongjiang Qiao, Riichiro Abe, Nao Saito, Yasuyuki Fujita, Inkin Hayashi-Ujiie, Gang Wang, Sanae Haga, Chun Wu, Yoshihiro Ohmiya, Michitaka Ozaki, Hiroshi Shimizu
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 133, 3, 841, 843, NATURE PUBLISHING GROUP, 2013年03月, ［査読有り］
英語

Immunosuppressive effects of DTCM-G, a novel inhibitor of the mTOR downstream signaling pathway
Susumu Shibasaki, Kenichiro Yamashita, Ryoichi Goto, Kenji Wakayama, Yusuke Tsunetoshi, Masaaki Zaitsu, Rumi Igarashi, Sanae Haga, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
Transplantation, 95, 4, 542, 550, 2013年02月27日, ［査読有り］
英語, 研究論文（学術雑誌）, Background: A newly developed compound, 3-[ (dodecylthiocarbonyl)methyl]- glutarimide (DTCM-G), has been shown to inhibit nuclear translocation of c-Fos/c-Jun in a murine macrophage cell line. Herein, we studied the immunosuppressive properties and potency of DTCM-G. METHODS: Using purified mouse T cells, the in vitro effects of DTCM-G on activation, cytokine production, proliferation, and cell cycle progression were assessed, and a possible molecular target of DTCM-G was investigated. In a BALB/c (H-2) to C57BL/6 (H-2) mouse heart transplantation model, transplant recipients were administered DTCM-G, a calcineurin inhibitor (tacrolimus), and a nuclear factor-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ). Treatment drugs were administered daily for 14 days after transplantation. Alloimmune responses were assessed in addition to graft survival time. RESULTS: After anti-CD3+anti-CD28 monoclonal antibody stimulation, DTCM-G significantly suppressed proliferation, interferon-γ production, and cell cycle progression of activated T cells but not CD25 expression or interleukin-2 production. These effects were accompanied by inhibition of 70-kDa S6 protein kinase phosphorylation, a downstream kinase of the mammalian target of rapamycin. The addition of tacrolimus and DHMEQ to DTCM-G resulted in a robust inhibition of T-cell proliferation. In vivo combination therapy of DTCM-G plus either tacrolimus or DHMEQ significantly suppressed alloreactive interferon-γ-producing precursors and markedly prolonged cardiac allograft survival. Furthermore, combination of all three agents markedly inhibited alloimmune responses and permitted long-term cardiac allograft survival. Conclusions: DTCM-G inhibits T cells by suppressing the downstream signal of mammalian target of rapamycin. DTCM-G in combination with tacrolimus and DHMEQ induces a strong immunosuppressive effect in vivo. © 2013 by Lippincott Williams &
Wilkins.

Stevens-Johnson syndrome/toxic epidermal necrolysis mouse model generated by using PBMCs and the skin of patients
Nao Saito, Naoya Yoshioka, Riichiro Abe, Hongjiang Qiao, Yasuyuki Fujita, Daichi Hoshina, Asuka Suto, Satoru Kase, Nobuyoshi Kitaichi, Michitaka Ozaki, Hiroshi Shimizu
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 131, 2, 434, +, MOSBY-ELSEVIER, 2013年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous reactions caused by drugs or infections and exhibiting widespread epidermal necrosis. Currently, there is no animal model that reproduces SJS/TEN symptoms.
Objective: We sought to develop a novel mouse model of SJS/TEN by using PBMCs and skin from patients who had recovered from SJS/TEN.
Methods: For our mouse model, patients' PBMCs were injected intravenously into immunocompromised NOD/Shi-scid, IL-2R gamma(null) (NOG) mice, followed by oral administration of a causative drug. Subsequently, to replace human skin, unaffected skin specimens obtained from patients who had recovered from SJS/TEN were grafted onto NOG mice, after which patient-derived PBMCs and the causative drug were applied.
Results: Mice injected with PBMCs from patients with SJS/TEN and given the causative drug showed marked conjunctival congestion and numerous cell death of conjunctival epithelium, whereas there were no symptoms in mice injected with PBMCs from patients with ordinary drug skin reactions. CD8(+) T lymphocyte-depleted PBMCs from patients with SJS/TEN did not elicit these symptoms. In addition, skin-grafted mice showed darkening of the skin-grafted areas. Cleaved caspase-3 staining showed that dead keratinocytes were more numerous in the skin-grafted mice than in the healthy control animals.
Conclusion: We have established a novel human-oriented SJS/TEN mouse model and proved the importance of CD8(+) T lymphocytes in SJS/TEN pathogenesis. The mouse model promises to promote diagnostic and therapeutic approaches. (J Allergy Clin Immunol 2013;131:434-41.)

Anoikis induction and inhibition of peritoneal metastasis of pancreatic cancer cells by a nuclear factor-κB inhibitor, (-)-DHMEQ.
Sato M, Nakanishi K, Haga S, Fujiyoshi M, Baba M, Mino K, Yimin, Niwa H, Yokoo H, Umezawa K, Ohmiya Y, Kamiyama T, Todo S, Taketomi A, Ozaki M
Oncology research, 21, 6, 333, 343, COGNIZANT COMMUNICATION CORP, 2013年, ［査読有り］
英語, 研究論文（学術雑誌）, The transcription factor nuclear factor-kappa B (NF-kappa B) plays a crucial role in pancreatic cancer (PC) progression. NF-kappa B is also involved in resistance to anoikis, a special type of apoptosis induced when cells are detached from the extracellular matrix or other cells. Anoikis resistance is related to the metastatic abilities of tumor cells; however, little is known about anoikis induction as it relates to inhibition of PC metastasis by NF-kappa B inhibitors. Here we used a specific NF-kappa B inhibitor, (-)-dehydroxymethylepoxyquinomicin (DHMEQ), to investigate anoikis induction and peritoneal metastasis suppression following NF-kappa B inhibition. We transduced Glue, a secretory form of luciferase, into a PC cell line, AsPC-1 (AsPC-1-Gluc), for our in vivo experiments. (-)-DHMEQ induced anoikis in AsPC-1-Gluc cells as measured by cell survival assays and flow cytometry. The DNA-binding activity of p65 was enhanced immediately after cell detachment from culture dishes in ELISA assays. Some antiapoptotic proteins such as cellular inhibitor of apoptotic protein-1 were consequently upregulated on Western blots. (-)-DHMEQ prevented this increase in p65 activity and the subsequent expressions of antiapoptotic molecules. In a murine xenograft model, anoikis-resistant PC cell lines tended to metastasize to the peritoneum more than anoikis-sensitive cells, suggesting a correlation between anoikis sensitivity and peritoneal metastasis. (-)-DHMEQ successfully inhibited peritoneal metastasis of AsPC-1-Gluc cells. We monitored metastasis inhibition by ex vivo chemiluminescent detection of Glue secreted from tumor cells into murine plasma and by in vivo imaging. Our results suggest that (-)-DHMEQ inhibited peritoneal dissemination by preventing anoikis resistance of PC cells.

Efficacy of DHMEQ, a NF-κB inhibitor, in islet transplantation: I. HMGB1 suppression by DHMEQ prevents early islet graft damage.
Kuraya D, Watanabe M, Koshizuka Y, Ogura M, Yoshida T, Asahi Y, Kamachi H, Nakamura T, Harashima H, Ozaki M, Umezawa K, Matsushita M, Yamashita K, Todo S
Transplantation, 96, 5, 445, 453, 2013年, ［査読有り］
英語, 研究論文（学術雑誌）, BACKGROUND: Pancreatic islet transplantation (PITx) is an attractive treatment option for restoring appropriate glucose homeostasis in type 1 diabetes patients. Although islet grafts can successfully engraft after PITx, large numbers of islet grafts are required mainly because immune reactions, including inflammation, destroy islet grafts. In these processes, nuclear factor (NF)-κB plays a central role. We hypothesized that the inhibition of NF-κB activation would ameliorate inflammatory responses after PITx and aid successful engraftment. METHODS: To test this hypothesis, a newly developed NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), was used on a syngeneic mouse PITx model. One hundred seventy-five islets from C57BL/6 (B6) mice were transplanted into streptozotocin-induced diabetic B6 mice. The recipient mice were administered DHMEQ for 1, 2, or 3 days after PITx. The underlying mechanisms of DHMEQ on islet graft protection were investigated in an in vitro coculture model of pancreatic islets and macrophages. RESULTS: With a vehicle treatment, only 11.1% of the islet-recipients achieved normoglycemia after PITx. In sharp contrast, DHMEQ treatment markedly improved the normoglycemic rate, which was associated with the suppression of serum high mobility group complex-1 (HMGB1) and proinflammatory cytokines, including tumor necrosis factor-α, monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, interleukin-1β, and interleukin-6, after PITx. In a murine macrophage-like cell line, DHMEQ inhibited HMGB1-driven activation and proinflammatory cytokine secretion and further prevented death isolated islets after coculture with these activated macrophages. CONCLUSIONS: Inhibition of NF-κB activation by DHMEQ after PITx reduces the HMGB1-triggered proinflammatory responses and results in engraftment of transplanted islets even with fewer islet grafts. Copyright © 2013 by Lippincott Williams &
Wilkins.

Rapid methods of detecting the target molecule in immunohistology using a bioluminescence probe
Chun Wu, Ke-Yong Wang, Xin Guo, Masanori Sato, Michitaka Ozaki, Shyohei Shimajiri, Yoshihiro Ohmiya, Yasuyuki Sasaguri
LUMINESCENCE, 28, 1, 38, 43, WILEY-BLACKWELL, 2013年01月, ［査読有り］
英語, 研究論文（学術雑誌）, We demonstrate a novel rapid direct detection method for immunohistochemistry, using a bioluminescent probe. An anti-CEA antibody-fused far-red bioluminescent protein can monitor the accumulation of this type of probe in tumour tissues. The bimodal spectrum (max=460 and 675nm) of this bioluminescent probe is extremely stable under different conditions of pH and ion concentration. The sensitivity of our bioluminescent labelling was at the same level of enzymatic labelling, e.g. peroxidase, as an indirect system. Our novel technique is simple and can shorten the pretreatment time of paraffin sections to around 30min. The utility of our bioluminescent labelling covers all imaging in vitro, in vivo and ex vivo, suggesting that our antibody-fused bioluminescent probe has the potential to detect tumour antigens with a high sensitivity in routine immune histological examinations. Copyright (c) 2012 John Wiley & Sons, Ltd.

Pathophysiological characteristics of melanoma in-transit metastasis in a lymphedema mouse model
Kohei Oashi, Hiroshi Furukawa, Hiroshi Nishihara, Michitaka Ozaki, Akihiko Oyama, Emi Funayama, Toshihiko Hayashi, Yuji Kuge, Yuhei Yamamoto
Journal of Investigative Dermatology, 133, 2, 537, 544, Nature Publishing Group, 2013年, ［査読有り］
英語, 研究論文（学術雑誌）, In-transit metastasis (ITM) is a unique manifestation of intralymphatic tumor dissemination, characterized by the presence of melanoma cells between the primary lesion and the draining regional lymph node basin that is clinically associated with poor prognosis. In this study, we aimed to establish an experimental animal model of melanoma ITM, as research progress in this field has been hampered by a lack of suitable experimental models. We reproduced melanoma ITM in a mouse hind limb by transplanting melanoma cells into the footpad of a mouse with lymphedema (LE). The tumor cells at the ITM site were highly proliferative, and mice with ITMs were more likely than control mice to develop distant lymph node and lung metastases. Peritumoral lymphatic vessels and tumor-associated blood vessels were increased in the primary tumor site of the LE mice. Our established ITM melanoma mouse model enabled us to clarify the molecular determinants and pathophysiology of ITM. This ITM model is also comparable to the unfavorable clinical behavior of melanoma ITM in humans and, moreover, underlined the importance of lymphangiogenic factors in the tumor dissemination through the lymphatic system. © 2013 The Society for Investigative Dermatology.

Xanthohumol Prevents Atherosclerosis by Reducing Arterial Cholesterol Content via CETP and Apolipoprotein E in CETP-Transgenic Mice
Hiroshi Hirata, Yimin, Shuichi Segawa, Moeko Ozaki, Naoyuki Kobayashi, Tatsuro Shigyo, Hitoshi Chiba
PLOS ONE, 7, 11, e49415, PUBLIC LIBRARY SCIENCE, 2012年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Xanthohumol is expected to be a potent anti-atherosclerotic agent due to its inhibition of cholesteryl ester transfer protein (CETP). In this study, we hypothesized that xanthohumol prevents atherosclerosis in vivo and used CETP-transgenic mice (CETP-Tg mice) to evaluate xanthohumol as a functional agent.
Methodology/Principal Findings: Two strains of mice, CETP-Tg and C57BL/6N (wild-type), were fed a high cholesterol diet with or without 0.05% (w/w) xanthohumol ad libitum for 18 weeks. In CETP-Tg mice, xanthohumol significantly decreased accumulated cholesterol in the aortic arch and increased HDL cholesterol (HDL-C) when compared to the control group (without xanthohumol). Xanthohumol had no significant effect in wild-type mice. CETP activity was significantly decreased after xanthohumol addition in CETP-Tg mice compared with the control group and it inversely correlated with HDL-C (%) (P<0.05). Furthermore, apolipoprotein E (apoE) was enriched in serum and the HDL-fraction in CETP-Tg mice after xanthohumol addition, suggesting that xanthohumol ameliorates reverse cholesterol transport via apoE-rich HDL resulting from CETP inhibition.
Conclusions: Our results suggest xanthohumol prevents cholesterol accumulation in atherogenic regions by HDL-C metabolism via CETP inhibition leading to apoE enhancement.

Dehydroxymethylepoxyquinomicin (DHMEQ), a novel NF-kappaB inhibitor, inhibits allergic inflammation and airway remodelling in murine models of asthma
K. Shimizu, S. Konno, M. Ozaki, K. Umezawa, K. Yamashita, S. Todo, M. Nishimura
CLINICAL AND EXPERIMENTAL ALLERGY, 42, 8, 1273, 1281, WILEY-BLACKWELL, 2012年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Background Dehydroxymethylepoxyquinomicin (DHMEQ) is a newly developed compound that inhibits nuclear factor kappa B activation and is reported to ameliorate animal models of various inflammatory diseases without significant adverse effects. Because nuclear factor jB is a transcription factor that plays a critical role in the pathophysiology of asthma, DHMEQ may be of therapeutic benefit in asthma.
Objective The purpose of this study was to evaluate the effects of DHMEQ on airway inflammation and remodelling in murine models of asthma.
Methods The BALB/c mice were sensitized and then challenged acutely or chronically with ovalbumin and administered DHMEQ intraperitoneally before each challenge. Inflammation of airways, lung histopathology and airway hyper responsiveness to methacholine challenge were evaluated. In addition, the effect of DHMEQ on production of cytokines and eotaxin-1 by murine splenocytes, human peripheral blood mononuclear cells and bronchial epithelial cells was investigated.
Results Airway hyper responsiveness was ameliorated in both acutely and chronically challenged models by treatment with DHMEQ. DHMEQ significantly reduced eosinophilic airway inflammation and levels of Th2 cytokines in bronchoalveolar lavage fluid in the acute model. It also inhibited parameters of airway remodelling including mucus production, peribronchial fibrosis and the expression of alpha-smooth muscle actin. Moreover, the production of Th2 cytokines from murine splenocytes and human peripheral blood mononuclear cells and the production of eotaxin-1 by bronchial epithelial cells were inhibited by DHMEQ.
Conclusions and Clinical Relevance These results indicate that DHMEQ inhibits allergic airway inflammation and airway remodelling in murine models of asthma. DHMEQ may have therapeutic potential in the treatment of asthma.

Successful transplantation of rat hearts subjected to extended cold preservation with a novel preservation solution
Kenji Wakayama, Moto Fukai, Kenichiro Yamashita, Taichi Kimura, Gentaro Hirokata, Susumu Shibasaki, Daisuke Fukumori, Sanae Haga, Mitsuru Sugawara, Tomomi Suzuki, Masahiko Taniguchi, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michitaka Ozaki, Toshiya Kamiyama, Satoru Todo
TRANSPLANT INTERNATIONAL, 25, 6, 696, 706, WILEY-BLACKWELL, 2012年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Since prolonged cold preservation of the heart deteriorates the outcome of heart transplantation, a more protective preservation solution is required. We therefore developed a new solution, named Dsol, and examined whether Dsol, in comparison to UW, could better inhibit myocardial injury resulting from prolonged cold preservation. Syngeneic heterotopic heart transplantation in Lewis rats was performed after cold preservation with UW or Dsol for 24 or 36 h. In addition to graft survival, myocardial injury, ATP content, and Ca2+ -dependent proteases activity were assessed in the 24-h preservation group. The cytosolic Ca2+ concentration of H9c2 cardiomyocytes after 24-h cold preservation was assessed. Dsol significantly improved 7-day graft survival after 36-h preservation. After 24-h preservation, Dsol was associated with significantly faster recovery of ATP content and less activation of calpain and caspase-3 after reperfusion. Dsol diminished graft injury significantly, as revealed by the lower levels of infarction, apoptosis, serum LDH and AST release, and graft fibrosis at 7-day. Dsol significantly inhibited Ca2+ overload during cold preservation. Dsol inhibited myocardial injury and improved graft survival by suppressing Ca2+ overload during the preservation and the activation of Ca2+ -dependent proteases. Dsol is therefore considered a better alternative to UW to ameliorate the outcome of heart transplantation.

Dendritic Cells Conditioned With NK026680 Prolong Cardiac Allograft Survival in Mice
Susumu Shibasaki, Kenichiro Yamashita, Yoshiki Yanagawa, Ryoichi Goto, Kenji Wakayama, Gentaro Hirokata, Yusuke Tsunetoshi, Masaaki Zaitsu, Rumi Igarashi, Sanae Haga, Michitaka Ozaki, Satoru Todo
TRANSPLANTATION, 93, 12, 1229, 1237, LIPPINCOTT WILLIAMS & WILKINS, 2012年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Background. Pharmacologically modulated dendritic cells (DCs) can potentially regulate alloimmune responses. We examined the characteristics of immunoregulatory DCs induced by a novel triazolopyrimidine derivative, NK026680, which has been previously shown to inhibit DC maturation.
Methods. DCs were generated from bone marrow progenitor cells from C57BL/6 (B6, H-2(b) haplotype) mice with granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4. DCs were cultured with allogeneic BALB/c (H-2(d)) splenocyte lysates with or without NK026680. DC functions were examined in vitro after stimulation of tumor necrosis factor alpha and in vivo by the intravenous injection of C3He/J (C3H, H-2(k)) DCs cultured with B6 cell lysates and NK026680 into C3H mice. Seven days later, DC-treated mice received B6 heart allografts, and graft survival and alloimmune responses were assessed.
Results. In NK026680-treated DCs (NK-DCs), significant inhibition of the up-regulation of surface activation markers (CD40, CD80, CD86, and major histocompatibility complex class II) and IL-12 p40 production was observed after stimulation of tumor necrosis factor alpha compared with that of control DCs. Furthermore, NK-DCs suppressed alloreactive T-cell proliferation. The modulation of NK-DCs was likely associated with the inhibition of phosphorylation of p38 mitogen-activated protein kinase and the up-regulation of indolamine 2,3-dioxygenase expression. Compared with both noninjected and control DC-injected mice, mice that received a single in vivo infusion of NK-DCs showed significant increases in splenocyte IL-10 production and the splenic CD4(+) IL-10(high) T-cell population 7 days after injection, a significantly increased splenic CD4(+)CD25(+)FoxP3(+) T-cell population 14 days after injection, and markedly prolonged cardiac allograft survival.
Conclusions. Ex vivo NK026680 conditioning allows DCs to acquire immunoregulatory properties that suppress alloimmune responses and prolong cardiac allograft survival.

Preoperative detection of circulating tumor cells in patients with colorectal carcinoma: Correlation with clinicopathologic variables and recurrence.
Hideyasu Sakihama, Nozomi Kobayashi, Tohru Funakoshi, Tatsushi Shimokuni, Shigenori Homma, Norihiko Takahashi, Akihiko Kataoka, Michitaka Ozaki, Toshiya Kamiyama, Akinobu Taketomi
JOURNAL OF CLINICAL ONCOLOGY, 30, 15, AMER SOC CLINICAL ONCOLOGY, 2012年05月, ［査読有り］
英語

Immunomodulatory effect of nuclear factor-κB inhibition by dehydroxymethylepoxyquinomicin in combination with donor-specific blood transfusion.
Goto R, Yamashita K, Aoyagi T, Ueki S, Uno M, Oura T, Kobayashi N, Igarashi R, Shibasaki S, Wakayama K, Hirokata G, Shibata T, Zaitsu M, Umezawa K, Ozaki M, Todo S
Transplantation, 93, 8, 777, 786, LIPPINCOTT WILLIAMS & WILKINS, 2012年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Background. Nuclear factor-kappa B (NF-kappa B) is a key molecule in alloimmune responses, however, its role in tolerance induction is not clear. We have previously reported that dehydroxymethylepoxyquinomycin (DHMEQ), a novel NF-kappa B inhibitor, prolongs cardiac allograft survival. In this study, we evaluated the immunomodulatory effects of DHMEQ when combined with a donor-specific blood transfusion (DST), and assessed whether the treatment induces tolerance in a mouse heart transplantation model.
Methods. DST (20 x 10(6) splenocytes) was given intravenously at day -7. DHMEQ (30 mg/kg/day) was administered intraperitoneally for 14 days after DST. Graft survival and histology were evaluated. The underlying mechanisms of immunomodulation by DST and DHMEQ treatments were investigated by assessing alloimmune responses after transplantation.
Results. In fully mismatched H2(d)-to-H2(b) heart transplants, DST alone prolonged allograft median survival time to 15 days, whereas when DST was combined with DHMEQ treatment, the graft median survival time was prolonged to 39.5 days. When the donor-recipient strain combination was reversed, that is, H2(b)-to-H2(d), heart transplants were accepted (>150 days survival) in more than 60% of recipients treated with a DST and DHMEQ, whereas control allografts were all rejected within 8 days. The combined therapy markedly inhibited immune responses by both the direct and indirect allorecognition pathways mainly attributed to promotion of activation-induced cell death and Treg generation.
Conclusions. Our results demonstrate the distinctive ability of NF-kappa B inhibition in combination with donor alloantigen to promote transplantation tolerance through multiple cellular mechanisms.

Bio-imaging of surgical stress: Dynamic analysis of liver oxidative stress and damage
Naoki Morita, Sanae Haga, Takeaki Ozawa, S. James Remington, Michitaka Ozaki
LUMINESCENCE, 27, 2, 143, 145, WILEY-BLACKWELL, 2012年03月, ［査読有り］
英語

A novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates inflammatory colonic injury in mice.
Funakoshi T, Yamashita K, Ichikawa N, Fukai M, Suzuki T, Goto R, Oura T, Kobayashi N, Katsurada T, Ichihara S, Ozaki M, Umezawa K, Todo S
Journal of Crohn's & colitis, 6, 2, 215, 225, OXFORD UNIV PRESS, 2012年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: In inflammatory bowel disease (IBD), gut inflammation is associated with the activation of nuclear factor kappa B (NE-kappa B), a key pro-inflammatory transcription factor.
Aim: To investigate the therapeutic potential of a novel, specific NE-kappa B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), we examined its effect on IBD using murine experimental colitis models.
Methods: The in vitro effect of DHMEQ was evaluated by inflammatory cytokine production and p65 immunostaining using HT-29 and RAW264.7 cells. The in vivo therapeutic effect of DHMEQ was studied in colitis induced by dextran sulphate sodium (DSS) and trinitrobenzenesulphonic acid (TNBS). In these, progression and severity of colitis was mainly assessed by the disease activity index (DAI), histopathology, cellular infiltration, and mRNA expression levels of proinflammatory cytokines in the colonic tissues.
Results: In RAW264.7 cells, DHMEQ significantly inhibited tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 production induced by LPS in a dose-dependent manner by blocking the nuclear translocation of NE-kappa B. In addition, DHMEQ inhibited IL-8 production induced by LPS in HT-29 cells. DHMEQ significantly ameliorated DSS colitis as assessed by DAI scores, colonic oedema, and histological scores. Immunohistochemistry revealed that DHMEQ inhibited colonic infiltration of nuclear p65(+) cells, CD4(+) lymphocytes, and F4/80(+) macrophages. mRNA expression levels of the pro-inflammatory cytokines, such as IL-1 beta, TNF-alpha, IL-6, IL-12p40, IL-17, and MCP-1 were also suppressed by DHMEQ administration. Furthermore, DHMEQ significantly ameliorated TNBS colitis as assessed by body-weight changes and histological scores.
Conclusion: DHMEQ ameliorated experimental colitis in mice. These results indicate that DHMEQ appears to be an attractive therapeutic agent for IBD. (C) 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

NK026680 inhibits T-cell function in an IL-2-dependent manner and prolongs cardiac allograft survival in rats
Susumu Shibasaki, Kenichiro Yamashita, Ryoichi Goto, Tetsu Oura, Kenji Wakayama, Gentaro Hirokata, Tomohiro Shibata, Rumi Igarashi, Sanae Haga, Michitaka Ozaki, Satoru Todo
TRANSPLANT IMMUNOLOGY, 26, 1, 42, 49, ELSEVIER SCIENCE BV, 2012年01月, ［査読有り］
英語, 研究論文（学術雑誌）, NK026680 is a triazolopyrimidine derivative that has been shown to inhibit dendritic cell maturation and activation. Here, we examined the immunosuppressive properties of NK026680 on T-cell function and assessed its immunosuppressive efficacy in an ACI (RT1(av1) haplotype) to Lewis (RT1(I)) rat heart transplantation model. The effects of NK026680 on T-cell proliferation, activation, and cytokine production were investigated in vitro. Heart transplant recipient rats were administered NK026680 daily for 14 days post-transplantation. In addition to graft survival time, alloimmune responses and graft histology at 4-10 days post-transplantation were assessed. NK026680 was found to inhibit proliferation, CD25 upregulation, IL-2 production, and cell cycle progression in alpha CD3/alpha CD28-stimulated murine T cells. These effects were likely due to suppression of the p38 mitogen-activated protein kinase pathway and the subsequent inhibition of p65, c-Fos, and to a lesser extent, c-Jun. Daily NK026680 treatment suppressed alloimmune responses, prevented cellular infiltration into allografts, and prolonged graft survival. The anti-rejection effects of NK026680 were enhanced by tacrolimus. In conclusion, NK026680 inhibits the activation of T cells and prolongs cardiac allograft survival in rats. These features make it a potential candidate immunosuppressant for the treatment of organ transplant patients in the future. (C) 2011 Elsevier B.V. All rights reserved.

α-fetoprotein, vascular endothelial growth factor receptor-1 and early recurrence of hepatoma.
Kamiyama T, Takahashi M, Nakanishi K, Yokoo H, Kamachi H, Kobayashi N, Ozaki M, Todo S
World journal of gastroenterology, 18, 4, 340, 348, BAISHIDENG PUBL GRP CO LTD, 2012年01月, ［査読有り］
英語, 研究論文（学術雑誌）, AIM: To investigate whether a-fetoprotein (AFP) and vascular endothelial growth factor receptor (VEGFR)-1 correlate with early recurrence of hepatoma/hepatocellular carcinoma (HCC).
METHODS: From 2000 to 2005, 114 consecutive patients with HCC underwent primary curative hepatectomy. The mean age was 60.7 (8.7) years and 94 patients were male. The median follow-up period was 71.2 mo (range: 43-100 mo). Immediately prior to commencing laparotomy, 5 nnL bone marrow was aspirated from the sternum and collected in citrate-coated test tubes. The initial 2 mL of bone marrow aspirate was discarded in each case. AFP mRNA and VEGFR-1 mRNA in the bone marrow and peripheral blood (BM- and PH-AFP mRNA and BM- and PH-VEGFR-1 mRNA, respectively) were measured by real-time quantitative reverse transcription polymerase chain reaction. As normal controls, VEGFR-1 mRNA in the bone marrow and peripheral blood was also measured in 11 living liver donors. These data were evaluated for any correlation with early recurrence, comparing clinical and pathological outcomes.
RESULTS: The cut-off value of the BM-AFP mRNA and PH-AFP mRNA level in patients with HCC was set at 1.92 x 10(-7) and zero, respectively, based on data from the controls. A total of 34 (29.8%) and six (5.4%) patients were positive for BM-AFP mRNA and PH-AFP mRNA, respectively. The BM-VEGFR-1 mRNA levels in all HCC patients were higher than those in the normal controls, and this was the case also for PH-VEGFR-1mRNA. The 25-percentile values for the BM- and PH-VEGFR-1 mRNA in HCC patients were used as the cut-off values for assigning the patients into two groups based on these transcript levels. The High group for BM- VEGFR-1 mRNA contained 81(71.1%) HCC cases and the Low group was assigned 33 (28.9%) patients. These numbers for PH-VEGFR-1mRNA were 78 (75.0%) and 26 (25.0%), respectively. HCC recurred in 80 patients; in the remnant liver in 48 cases, in the remnant liver and remote tissue in 20, and in the remote tissue alone in 12. BM-AFP nnRNA-positive cases showed a significantly higher rate of early recurrence (within 1 year of surgical treatment) compared with BM-AFP mRNA-negative patients (P = 0.0091). Patients were classified into four groups according to the level/status of their BM-VEGFR-1 and BM-AFP mRNA as follows: group A (n = 23), BM-VEGFR-1/BM-AFP mRNA = low/negative; group B (n = 57) high/negative; group C (n = 10)low/positive; group D (n = 24), high/positive. This classification was found to correlate with a recurrence of this disease within 1 year (P = 0.0228). The disease-free survival curve of group A was significantly better than that of groups B, C or D (P = 0.0437, P = 0.0325, P = 0.0225). No other classification (i.e., PH-VEGF-R1/BM-AFP, BM-VEGF-R1/PH-AFP, and PH-VEGF-R1/PH-AFP mRNA) showed such a correlation.
CONCLUSION: The evaluation of BM-AFP and BM-VEGFR-1 mRNA in patients with HCC may be a valuable predictor of disease recurrence following curative resection. (C) 2012 Baishideng. All rights reserved.

In Vivo Monitoring of Liver Damage Using Caspase-3 Probe
Michitaka Ozaki, Sanae Haga, Takeaki Ozawa
THERANOSTICS, 2, 2, 207, 214, IVYSPRING INT PUBL, 2012年, ［査読有り］
英語, 研究論文（学術雑誌）, Real-time monitoring of cellular and organ conditions improves our understanding of various physiopathological phenomena. Such monitoring is expected to provide important alternatives for clinical diagnosis and therapy. We have sought to show physiopathological changes of organs as well as cells. Here, we present an example of in vivo imaging of liver states using the luciferase-based caspase-3 optical probe. We examined dynamic changes of apoptosis (caspase-3 activity) of a mouse liver as well as those of liver cells, proving that the emitted signals reflected the biochemically evaluated apoptotic cell death. In live liver cell (AML 12) experiments, the optical probe for caspase-3 activity emitted signals in response to Fas-ligand, staurosporine and hypoxia/reoxygenation, demonstrating that the probe can measure cellular apoptosis quantitatively. We therefore applied this probe for mouse liver ischemia/reperfusion (I/R) and drug-toxicity to liver. By expressing the probe in a mouse liver adenovirally, we imaged liver caspase-3 activity (i.e. apoptotic damage) non-invasively and chronologically in the hepatic I/R model of mice. The duration of liver ischemia affected the post-ischemic caspase-dependent damage. Ischemia (up to 60 min) enhanced liver damage after reperfusion, but prolonged ischemia (90 min of ischemia) induced not apoptotic cell death but necrotic cell death. Direct observations of the changes of organ conditions elucidated the dynamism of organ function and damage. These technologies clearly possess clinical relevance. They are expected to provide a new diagnostic tool for various clinical settings in the future.

The molecular mechanism of liver injury/regeneration - An analysis by bio-imaging -
Michitaka Ozaki
Seikagaku, 84, 8, 685, 692, 2012年, ［査読有り］
日本語

CD40-CD154副刺激経路の遮断による、マウス同系膵島移植後早期グラフトロスの抑制
腰塚 靖之, 山下 健一郎, 渡辺 正明, 蔵谷 大輔, 小倉 正臣, 吉田 雅, 蒲池 浩文, 松下 通明, 尾崎 倫孝, 藤堂 省
移植, 46, 6, 616, 616, (一社)日本移植学会, 2011年12月
日本語

マウス膵島移植における新規AP-1阻害剤T-5224の免疫抑制効果
吉田 雅, 山下 健一郎, 渡辺 正明, 腰塚 靖之, 蔵谷 大輔, 小倉 正臣, 後藤 了一, 若山 顕治, 柴崎 晋, 蒲池 浩文, 尾崎 倫孝, 松下 通明, 塩沢 俊一, 広野 修一, 藤堂 省
移植, 46, 6, 612, 612, (一社)日本移植学会, 2011年12月
日本語

'Collagen vitrigel sheet' as a novel drug delivery bio-material
S. Haga, S. Haga, T. Takezawa, T. Ozawa, S. J. Remington, N. Morita, M. Ozaki
IFMBE Proceedings, 37, 1354, 1357, 2011年11月09日
英語, 研究論文（国際会議プロシーディングス）, Background/Aims. Ischemia/reperfusion (I/R)- induced injury is an acute injury mainly caused by surgical procedures. And HGF (hepatocyte growth factor) is known to protect against I/R-injury effectively. The sufficient dose of HGF must be topically delivered to the target organ to minimize the organ damage on surgery (reperfusion) and the dose of drug. For this purpose, we developed a novel technology for converting a fragile disk of the conventional type-I collagen gel into a strong and transparent 'vitrigel membrane', based on a concept for the vitrification of heat-denatured proteins. In the present study, we examined the efficacy of the newly designed 'HGF-containing collagen vitrigel sheet' as an effective drug delivery system in mouse liver I/R model. Materials and methods. Male C57Black6 mice were subjected to 60 min-liver ischemia (middle and left liver lobes) and reperfusion. Immediately after liver ischemia, the ischemic liver lobes were covered by collagen vitrigel sheet containing hHGF (3..g/ml). Reperfused liver injury was evaluated by biochemical/ histological methods and bio-imaging of hepatic oxidative stress (redox-sensitive GFP probe) and apoptosis (bioluminescent caspase-3 activity probe). Results. Collagen vitrigel sheet (containing hHGF) released hHGF until 96 hr in vitro and successfully delivered hHGF to the liver tissue suffering I/R. This effectively protected liver from I/R-induced injury. Blood biochemistry showed reduced levels of serum GOT/GPT/LDH, and liver histology revealed reduced necrotic area in the hHGF-treated liver. Oxidative stress and caspase-3 activity of the liver were examined by bioimaging, which revealed that hHGF delivered by vitrigel sheet significantly reduced oxidative stress and apoptotic cell death in the post-ischemic liver. Conclusions. hHGF-containing collagen vitrigel sheet protected liver from I/R-induced injury. Collagen vitrigel sheet may have good therapeutic potential in topical drug delivery in various clinical settings. © 2011 Springer-Verlag Berlin Heidelberg.

Co-Expression of Mesothelin and CA125 Correlates With Unfavorable Patient Outcome in Pancreatic Ductal Adenocarcinoma
Takahiro Einama, Hirofumi Kamachi, Hiroshi Nishihara, Shigenori Homma, Hiromi Kanno, Kenta Takahashi, Ayami Sasaki, Munenori Tahara, Kuniaki Okada, Shunji Muraoka, Toshiya Kamiyama, Yoshihiro Matsuno, Michitaka Ozaki, Satoru Todo
PANCREAS, 40, 8, 1276, 1282, LIPPINCOTT WILLIAMS & WILKINS, 2011年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives: Recent studies have shown that the high affinity of mesothelin-CA125 interaction might cause intracavitary tumor metastasis. We examined the clinicopathologic significance and prognostic implication of mesothelin and CA125 expression in pancreatic ductal adenocarcinoma.
Methods: Tissue samples from 66 pancreatic ductal adenocarcinomas were immunohistochemically examined. Proportion and intensity of constituent tumor cells with mesothelin and CA125 expression were analyzed and classified as high-level expression, defined as expression by more than 50% of tumor cells and/or moderate to strong staining, or low-level expression otherwise.
Results: A high level of mesothelin was correlated with a higher histological grade (P = 0.049) and the level of blood vessel permeation (P = 0.0006), whereas a high level of CA125 expression was correlated with a higher recurrence rate (P = 0.015). The expression of mesothelin was strongly correlated with that of CA125 (P = 0.0041). Co-expression of mesothelin and CA125 were associated with an unfavorable patient outcome (P = 0.0062).
Conclusions: This is the first report showing that co-expression of mesothelin and CA125 were in pancreatic ductal adenocarcinoma, and such co-expression is associated with a poor prognosis. Our finding suggests that co-expression of these two factors plays a significant role in the acquisition of aggressive clinical behavior.

AGE-ASSOCIATED P66SHC INDUCED REDOX-DEPENDENT LIVER DAMAGE AND IMPAIRED REGENERATION AFTER HEPATECTOMY IN AGED MICE
Michitaka Ozaki, Sanae Haga, Kaikobad Irani, Naoki Morita, Yoshimi Kaneshima, Takeaki Ozawa
HEPATOLOGY, 54, 686A, 687A, WILEY-BLACKWELL, 2011年10月, ［査読有り］
英語

A NOVEL COMPOUND, DTCM-GLUTARIMIDE MARKEDLY PROLONGS MURINE CARDIAC ALLOGRAFT SURVIVAL IN COMBINATION WITH DONOR SPECIFIC TRANSFUSION
Yusuke Tsunetoshi, Kenichiro Yamashita, Susumu Shibasaki, Ryoichi Goto, Kenji Wakayama, Masaaki Zaitsu, Rumi Igarashi, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
TRANSPLANT INTERNATIONAL, 24, 59, 60, WILEY-BLACKWELL, 2011年09月, ［査読有り］
英語

DTCM-GLUTARIMIDE SUPPRESSES IFN-gamma AND AMELIORATES CARDIAC ALLOGRAFT ARTERIOSCLEROSIS IN MICE
Masaaki Zaitsu, Kenichiro Yamashita, Susumu Shibasaki, Yusuke Tsunetoshi, Masaomi Ogura, Tadashi Yoshida, Kenji Wakayama, Gentaro Hirokata, Rumi Igarashi, Nozomi Kobayashi, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
TRANSPLANT INTERNATIONAL, 24, 267, 267, WILEY-BLACKWELL, 2011年09月, ［査読有り］
英語

Inhibition of macrophage activation and suppression of graft rejection by DTCM-glutarimide, a novel piperidine derived from the antibiotic 9-methylstreptimidone
Masatoshi Takeiri, Miyuki Tachibana, Ayumi Kaneda, Ayumi Ito, Yuichi Ishikawa, Shigeru Nishiyama, Ryoichi Goto, Kenichiro Yamashita, Susumu Shibasaki, Gentaro Hirokata, Michitaka Ozaki, Satoru Todo, Kazuo Umezawa
INFLAMMATION RESEARCH, 60, 9, 879, 888, SPRINGER BASEL AG, 2011年09月, ［査読有り］
英語, 研究論文（学術雑誌）, We have previously synthesized a novel piperidine compound, 3-[ (dodecylthiocarbonyl)methyl]glutarimide (DTCM-glutarimide), that inhibits LPS-induced NO production, and in the present research we studied further the anti-inflammatory activity of DTCM-glutarimide in a macrophage cell line and in mice bearing transplanted hearts.
Mouse macrophage-like RAW264.7 cells were employed for the evaluation of cellular inflammatory activity. DTCM-glutarimide was synthesized in our laboratory. The AP-1 activity was measured by nuclear translocation and phosphorylation. For the heart transplantation experiment, male C57BL/6 (H-2b) and BALB/c (H-2d) mice were used as donor and recipient, respectively. DTCM-glutarimide was administered intraperitoneally.
DTCM-glutarimide inhibited the LPS-induced expression of iNOS and COX-2 in macrophages; but, unexpectedly, it did not inhibit LPS-induced NF-kappa B activation. Instead, it inhibited the nuclear translocation of both c-Jun and c-Fos. It also inhibited LPS-induced c-Jun phosphorylation. Moreover, it inhibited the mixed lymphocyte reaction in primary cultures of mouse spleen cells; and furthermore, in mice it prolonged the graft survival in heart transplantation experiments.
The novel piperidine compound, DTCM-glutarimide, was found to be a new inhibitor of macrophage activation, inhibiting AP-1 activity. It also inhibited graft rejection in mice, and thus may be a candidate for an anti-inflammatory agent.

A Novel Anti-Inflammatory Agent, 3-[ (Dodecylthiocarbonyl)-Methyl]-Glutarimide, Ameliorates Murine Models of Inflammatory Bowel Disease
Nobuki Ichikawa, Kenichiro Yamashita, Tohru Funahashi, Shin Ichihara, Nozomi Kobayashi, Yasuyuki Koshizuka, Masaaki Zaitsu, Moto Fukai, Tomomi Suzuki, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
GASTROENTEROLOGY, 140, 5, S515, S515, W B SAUNDERS CO-ELSEVIER INC, 2011年05月, ［査読有り］
英語

Inhibition of nuclear factor-kappaB suppresses peritoneal dissemination of gastric cancer by blocking cancer cell adhesion
Kazuhiro Mino, Michitaka Ozaki, Kazuaki Nakanishi, Sanae Haga, Masanori Sato, Masaya Kina, Masato Takahashi, Norihiko Takahashi, Akihiko Kataoka, Kazuyoshi Yanagihara, Takahiro Ochiya, Toshiya Kamiyama, Kazuo Umezawa, Satoru Todo
CANCER SCIENCE, 102, 5, 1052, 1058, WILEY-BLACKWELL, 2011年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Currently, patients with peritoneal dissemination of gastric cancer must accept a poor prognosis because there is no standard effective therapy. To inhibit peritoneal dissemination it is important to inhibit interactions between extracellular matrices (ECM) and cell surface integrins, which are important for cancer cell adhesion. Although nuclear factor-kappa B (NF-kappa B) is involved in various processes in cancer progression, its involvement in the expression of integrins has not been elucidated. We used a novel NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), to study whether NF-kappa B blocks cancer cell adhesion via integrins in a gastric cancer dissemination model in mice and found that DHMEQ is a potent suppressor of cancer cell dissemination. Dehydroxymethylepoxyquinomicin suppressed the NF-kappa B activity of human gastric cancer cells NUGC-4 and 44As3Luc and blocked the adhesion of cancer cells to ECM when compared with the control. Dehydroxymethylepoxyquinomicin also inhibited expression of integrin (alpha 2, alpha 3, beta 1) in in vitro studies. In the in vivo model, we injected 44As3Luc cells pretreated with DHMEQ into the peritoneal cavity of mice and performed peritoneal lavage after the injection of cancer cells. Viable cancer cells in the peritoneal cavities were evaluated sequentially by in vivo imaging. In mice injected with DHMEQ-pretreated cells and lavaged, live cancer cells in the peritoneum were significantly reduced compared with the control, and these mice survived longer. These results indicate that DHMEQ could inhibit cancer cell adhesion to the peritoneum possibly by suppressing integrin expression. Nuclear factor-kappa B inhibition may be a new therapeutic option for suppressing postoperative cancer dissemination. (Cancer Sci 2011; 102: 1052-1058).

Molecular mechanisms of liver regeneration and protection for treatment of liver dysfunction and diseases
Masato Fujiyoshi, Michitaka Ozaki
JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES, 18, 1, 13, 22, SPRINGER TOKYO, 2011年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Liver regeneration is a necessary process that most liver damage depends on for recovery. Regeneration is achieved by a complex interactive network consisting of liver cells (hepatocytes, Kupffer cells, sinusoidal endothelial cells, hepatic stellate cells, and stem cells) and extrahepatic organs (thyroid gland, adrenal gland, pancreas, duodenum, and autonomous nervous system). The restoration of liver volume depends on hepatocyte proliferation, which includes initiation, proliferation, and termination phases. Hepatocytes are "primed" mainly by Kupffer cells via cytokines (IL-6 and TNF-alpha) and then "proliferation" and "cell growth" of hepatocytes are induced by the stimulations of cytokines and growth factors (HGF and TGF-alpha). Liver regeneration is achieved by cell proliferation and cell growth, where the IL-6/STAT3 and PI3-K/PDK1/Akt pathways play pivotal roles, respectively. IL-6/STAT3 pathway regulates hepatocyte proliferation via cyclin D1/p21 and protects against cell death by upregulating FLIP, Bcl-2, Bcl-xL, Ref1, and MnSOD. PI3-K/PDK1/Akt is known to be responsible for regulation of cell size via its downstream molecules such as mTOR in addition to being known for its survival, anti-apoptotic and anti-oxidative properties. Although the molecular mechanisms of liver regeneration have been actively studied, the mechanisms of liver regeneration must be elucidated and leveraged for the sufficient treatment of liver diseases.

p66(Shc) has a pivotal function in impaired liver regeneration in aged mice by a redox-dependent mechanism
Sanae Haga, Naoki Morita, Kaikobad Irani, Masato Fujiyoshi, Tetsuya Ogino, Takeaki Ozawa, Michitaka Ozaki
LABORATORY INVESTIGATION, 90, 12, 1718, 1726, NATURE PUBLISHING GROUP, 2010年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Liver regeneration involves complicated processes and is affected by various patho-physiological conditions. This study was designed to examine the molecular mechanisms underlying the aging-associated impairment of liver regeneration. Male C57BL/6J mice were used as young and aged mice (<10 weeks and >20 months old, respectively). These mice were subjected to 70% partial hepatectomy (PH). Liver regeneration and liver injury/stresses were evaluated chronologically after PH. Post-hepatectomy liver regeneration was markedly impaired in aged mice. Though the extent of hepatocyte proliferation in the regenerating liver was similar in aged and young mice, cell growth was absent in aged mice. Oxidative stress (OS) was observed immediately after hepatectomy, followed by marked apoptosis in aged mice. Signaling molecules regarding cell proliferation (mitogen-activated protein kinase, STAT3, p46/52(Shc)) and anti-oxidation (catalase, superoxide dismutase, Ref-1, glutathione peroxidase) were expressed/activated after hepatectomy in livers of both aged and young mice. Akt was not activated in aged-mouse liver, but its expression was similar to that in young mice. p66(Shc), known as an age-/oxidant-associated protein, was strongly phosphorylated. By knocking down p66(Shc), the impairment of liver regeneration was normalized. OS immediately after hepatectomy induced subsequent liver injury (apoptosis), and deletion of p66(Shc) suppressed both OS and hepatocyte apoptosis in the regenerating liver of aged mice. Though we need additional data in other animal models to fully understand the mechanism, p66(Shc) may have a pivotal function in the impairment of liver regeneration in aged mice by triggering OS and subsequent apoptosis. This data may provide a clue to understanding the mechanism underlying the association between aging and the impairment of liver regeneration. Laboratory Investigation (2010) 90, 1718-1726; doi:10.1038/labinvest.2010.119; published online 21 June 2010

Oxidative stress enhances granulocytic differentiation in HL 60 cells, an acute promyelocytic leukemia cell line
Tetsuya Ogino, Michitaka Ozaki, Akihiro Matsukawa
FREE RADICAL RESEARCH, 44, 11, 1328, 1337, INFORMA HEALTHCARE, 2010年11月, ［査読有り］
英語, 研究論文（学術雑誌）, This paper studied the effects of physiologically available oxidants on HL 60 differentiation induced by all-trans retinoic acid (ATRA) or dimethyl sulfoxide (DMSO). Hydrogen peroxide (15 mu M) and taurine chloramine (200 mu M) induced HL 60 differentiation, which was detected by CD11b expression and superoxide production. Cd11b and p67(phox) mRNA expression was also augmented by these oxidants. In contrast, reducing chemicals, such as dithiothreitol, 2,3-dimercapto-1-propanol and N-acetylcysteine inhibited CD11b expression. Notably, DMSO inhibited methionine sulfoxide reductase activity, induced heme oxygenase-1 (ho-1) mRNA and enhanced oxidant-induced cell death, which indicated that DMSO intensified oxidative stress. After the addition of oxidants, ho-1 expression preceded the cd11b expression. Vicinal dithiol-reactive phenylarsine oxide (50 nM) also increased CD11b expression induced by DMSO or ATRA. These observations suggested that oxidative stress enhanced granulocytic differentiation of HL 60 cells and that leukaemic cell differentiation was affected by cellular redox status.

Frequency and pattern of expression of the stem cell marker CD133 have strong prognostic effect on the surgical outcome of colorectal cancer patients
Shusaku Takahashi, Toshiya Kamiyama, Utano Tomaru, Akihiro Ishizu, Toshiyuki Shida, Mineji Osaka, Yutaka Sato, Yutaka Saji, Michitaka Ozaki, Satoru Todo
ONCOLOGY REPORTS, 24, 5, 1201, 1212, SPANDIDOS PUBL LTD, 2010年11月, ［査読有り］
英語, 研究論文（学術雑誌）, CD133 has been reported to be a cancer stem cell marker in colorectal cancer (CRC). The aim of this study was to examine the frequency and pattern of CD133 expression by immunohistochemical methods and evaluate their correlation with clinicopathological features, including patient survival (PS) and recurrence. Tissue specimens of 151 CRC patients who underwent surgical treatment for well-differentiated/moderately differentiated adenocarcinoma and stage I-IV tumors (TNM classification) were immunostained for analyzing CD133 expression. The frequency of CD 133 expression was 91.4% (138/151), and the pattern of expression was divided into membranous and cytoplasmic expression. Of the 151 patients, 136 (90.1%) showed membranous expression, whereas 44 (29.1%) showed cytoplasmic expression. Both expression patterns were seen in 42 (27.8%) patients. The frequency of CD133 overexpression (>50% of stained cells) was 27.2% (41/151); univariate analysis showed CD133 overexpression to be significantly associated with PS, but not recurrence, and multivariate analysis indicated it to be an independent prognostic factor. Multivariate analysis showed membranous overexpression (>50% of stained tumor cells on the membrane), which significantly correlated with histology and chemoresistance of recurrent and stage IV tumors, to be an independent prognostic factor for PS and recurrence. However, multivariate analysis did not indicate cytoplasmic expression, which significantly correlated with histology, lymph node metastasis, TNM stage and lymphatic invasion, as an independent prognostic factor for PS and recurrence. Our results demonstrated that evaluation of the frequency and pattern of CD133 expression is useful for predicting prognosis, recurrence, and chemosensitivity in CRC patients.

Donor Pretreatment with DHMEQ Improves Islet Transplantation
Tohru Takahashi, Shuichiro Matsumoto, Michiaki Matsushita, Hirofumi Kamachi, Yosuke Tsuruga, Hironori Kasai, Masaaki Watanabe, Michitaka Ozaki, Hiroyuki Furukawa, Kazuo Umezawa, Satoru Todo
JOURNAL OF SURGICAL RESEARCH, 163, 1, E23, E34, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2010年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Background. Currently, pancreatic islet transplantation to achieve normoglycemia in insulin-dependent diabetes mellitus (IDDM) requires two or more donors. This may be due to the inability to transplant functionally preserved and viable islets after isolation. Islets have already been subjected to various harmful stresses during the isolation process leading to apoptosis. One of the intracellular signaling pathways, the transcription factor nuclear factor-kappa B (NF-kappa B)-related pathway, is relevant to the mechanism of beta-cell apoptosis in isolated islets. We attempted to prevent islet apoptosis during isolation by a novel NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ).
Materials and Methods. DHMEQ was injected intra-peritoneally into donor mice 2 h prior to isolation. NF-kappa B activation, the functioning of isolated islets, apoptosis after isolation, and cytokine- and apoptosis-related genes were analyzed. After 160 equivalents of islets were transplanted into diabetic mice, graft survival and function were evaluated.
Results. Intra-islet NF-kappa B was activated immediately after isolation, and DHMEQ inhibited NF-kappa B activation without deterioration of islet function. DHMEQ significantly prevented apoptosis by inhibiting caspase 3/7 activities and down-regulated Bax, a proapoptotic gene. Donor pretreatment with DHMEQ significantly improved engraftment in syngeneic islet transplantation in mice, thus preserving insulin contents in the graft liver, as assessed by functional and histologic analyses.
Conclusions. DHMEQ is a promising agent in islet transplantation because it protects islets from apoptosis during isolation stress. Donor pretreatment with DHMEQ can significantly affect the success of islet engraftment. (C) 2010 Elsevier Inc. All rights reserved.

Signal transducer and activator of transcription 3 upregulates interleukin-8 expression at the level of transcription in human melanoma cells
Masahiro Oka, Masanobu Sakaguchi, Taro Okada, Hiroshi Nagai, Michitaka Ozaki, Toyo Yoshioka, Hiroshi Inoue, Naofumi Mukaida, Ushio Kikkawa, Chikako Nishigori
EXPERIMENTAL DERMATOLOGY, 19, 8, E50, E55, WILEY-BLACKWELL, 2010年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Many melanoma cells continuously produce interleukin-8 (IL-8). The involvement of signal transducer and activator of transcription 3 (STAT3) in the constant production of IL-8 in melanoma cells was examined. The level of IL-8 production correlated well with that of the phosphorylated (activated) STAT3 in six human melanoma cell lines. Introduction of the constitutively activated form of STAT3 (STAT3-C) into WM35 melanoma cells, that show low levels of IL-8 and phosphorylated STAT3, enhanced IL-8 production. Knockdown of STAT3 suppressed IL-8 production in WM1205Lu cells that contain a high level of IL-8 accompanied by STAT3 phosphorylation. Introduction of STAT3-C markedly increased the luciferase activity in WM1205Lu cells transfected with reporter vectors linked to the 5'-flanking region of the IL-8 gene from -546 to +44 base pair (bp) and from -272 to +44 bp, but not in cells expressing reporter plasmids from -133 to +44 bp and from -98 to +44 bp. These results indicate that the upregulation of IL-8 production is caused by constitutive STAT3 activation at the level of gene transcription in melanoma cells.

Cytoplasmic expression of CD133 is an important risk factor for overall survival in hepatocellular carcinoma
Ayami Sasaki, Toshiya Kamiyama, Hideki Yokoo, Kazuaki Nakanishi, Kanako Kubota, Hironori Haga, Michiaki Matsushita, Michitaka Ozaki, Yoshihiro Matsuno, Satoru Todo
ONCOLOGY REPORTS, 24, 2, 537, 546, SPANDIDOS PUBL LTD, 2010年08月, ［査読有り］
英語, 研究論文（学術雑誌）, CD133 antigen has been used to identify cancer stem cells in several solid tumor types, including hepatocellular carcinomas (HCCs). The aim of this study was to investigate whether the expression and subcellular localization of CD133 correlated with the clinicopathological factors, recurrence, and survival in HCC patients. Tissue specimens from 136 HCC patients who underwent curative primary hepatectomy between 2000 and 2005 were collected and immunohistochemically analyzed for CD133 expression. Positive immunohistochemical results and subcellular localization of CD133 were determined, and the correlation between CD133 expression and clinicopathological factors of HCC patients were evaluated. CD133-positive tumor cells were observed in 30 (22.1%) cases. Cytoplasmic and membranous expressions were observed in 22 (16.2%) and 20 (14.7%) of the CD133-positive cases, respectively. Positive cytoplasmic expression of CD133 was found to be associated with the overall survival of HCC patients, especially in stage III and IVA HCC patients (p=0.0092). Univariate analysis revealed that pre-operative serum albumin, alpha-fetoprotein (AFP) levels, tumor size, portal venous invasion, and cytoplasmic CD133 expression were important risk factors in HCC. Multivariate analysis revealed that among the factors related to tumor aggressiveness, cytoplasmic expression of CD133 showed the most significant association with overall survival, although the difference was not statistically significant (P=0.0681). Cytoplasmic expression of CD133 was a significant risk factor for the overall survival of HCC patients. Patients with stage III and IVA HCC showing positive cytoplasmic expression of CD133 are more likely to have a worse prognosis.

Topical application of dehydroxymethylepoxyquinomicin improves allergic inflammation via NF-kappa B inhibition
Riichiro Abe, Satoshi Kishino, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo, Hiroshi Shimizu
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 126, 2, 400, 403, MOSBY-ELSEVIER, 2010年08月, ［査読有り］
英語

Array comparative genomic hybridization analysis revealed four genomic prognostic biomarkers for primary gastric cancers
Nobumoto Tomioka, Keiko Morita, Nozomi Kobayashi, Mitsuhiro Tada, Tomoo Itoh, Soichiro Saitoh, Masao Kondo, Norihiko Takahashi, Akihiko Kataoka, Kazuaki Nakanishi, Masato Takahashi, Toshiya Kamiyama, Michitaka Ozaki, Takashi Hirano, Satoru Todo
CANCER GENETICS AND CYTOGENETICS, 201, 1, 6, 14, ELSEVIER SCIENCE INC, 2010年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Unlike the case with some other solid tumors, whole genome array screening has not revealed prognostic genetic aberrations in primary gastric cancer. Comparative genomic hybridization (CGH) using bacterial artificial chromosome (BAC) arrays for 56 primary gastric cancers resulted in identification of four prognostic loci in this study: 6q21 (harboring FOXO3A; previously FKHRL1), 9q32 (UGCG), 17q21.1 similar to q21.2 (CASC3), and 17q21.32 (HOXB3 through HOXB9). If any one of these four loci was deleted, the prognosis of the patient was significantly worse (P = 0.0019). This was true even for advanced tumors (stage IIIA, JIB, or IV, n = 39) (P = 0.0113), whereas only 1 of the 17 patients with less advanced tumors (stage IA, IB, or II; n = 17) died of disease after surgery. Multivariate analysis according to the status of four BACs or pathological stage based on the Japanese Classification of Gastric Carcinoma (stages IA, IB, and II vs. stages IIIA, IIIB, and IV) demonstrated that the BAC clone status was also an independent prognostic factor (P = 0.006). These findings may help predict which patients with malignant potential need more intensive therapy, or may point to new therapeutic approaches especially for advanced tumors. The parameter here termed the integrated genomic prognostic biomarker may therefore be of clinical utility as a prognostic biomarker. (C) 2010 Elsevier Inc. All rights reserved.

NF-κB阻害によるマウス膵島移植後早期グラフト傷害抑制効果
蔵谷 大輔, 蒲池 浩文, 渡辺 正明, 小倉 正臣, 吉田 雅, 腰塚 靖之, 中木村 繁, 山下 健一郎, 鈴木 友己, 尾崎 倫孝, 古川 博之, 松下 通明, 梅澤 一夫, 藤堂 省
移植, 45, 3, 289, 289, (一社)日本移植学会, 2010年06月
日本語

膵島移植におけるDHMEQ、tacrolimusの併用療法
渡辺 正明, 山下 健一郎, 蒲池 浩文, 小倉 正臣, 吉田 雅, 蔵谷 大輔, 腰塚 靖之, 中木村 繁, 鈴木 友己, 尾崎 倫孝, 古川 博之, 松下 通明, 梅澤 一夫, 藤堂 省
移植, 45, 3, 290, 290, (一社)日本移植学会, 2010年06月
日本語

マウス膵島移植における膵保存モデルの確立
中木村 繁, 蒲池 浩文, 渡辺 正明, 小倉 正臣, 吉田 雅, 蔵谷 大輔, 腰塚 靖之, 山下 健一郎, 鈴木 友己, 尾崎 倫孝, 古川 博之, 松下 通明, 藤堂 省
移植, 45, 3, 291, 291, (一社)日本移植学会, 2010年06月
日本語

A Novel NF-kappa B Inhibitor, DHMEQ, Ameliorates Inflammatory Colonic Injuries in Mice
Funakoshi Tohru, Yamashita Kenichiro, Ichikawa Nobuki, Fukai Moto, Suzuki Tomomi, Goto Ryoichi, Oura Tetsu, Kobayashi Nozomi, Katsurada Takehiko, Ozaki Michitaka, Umezawa Kazuo, Todo Satoru
GASTROENTEROLOGY, 138, 5, S410, 2010年05月, ［査読有り］

コラーゲンビトリゲル薄膜の特徴を活用した新しい細胞培養システムの開発
竹澤 俊明, 福田 真野, Mcintosh-Ambrose Winnette, 高 知愛, Elisseeff Jennifer, 芳賀 早苗, 尾崎 倫孝, 加藤 聖子, 王 碧昭, 内野 正, 西田 輝夫
薬学雑誌, 130, 4, 565, 574, (公社)日本薬学会, 2010年04月, ［査読有り］
日本語, 高密度のコラーゲン線維のゲルをガラス化工程を経て作製したコラーゲンビトリゲル(CV)は、薄膜状、糸状、管状など様々な形状に整形できる。このCV薄膜の特徴について述べ、これを用いた以下の細胞培養システムや薬物送達システムの開発を紹介した。1)眼刺激性および透過性試験用の角膜細胞培養システム、2)皮膚感作性試験用の皮膚細胞培養システム、3)血漿成分の濾過モデル用の腎糸球体細胞培養システム、4)肝障害を改善するための薬物送達システム。更に、このCVを創薬支援ツールとして展開することの有用性について述べた。

Immunosuppressive Effects of Regulatory Dendritic Cells Induced by NK026680.
Susumu Shibasaki, Kenichiro Yamashita, Ryoichi Goto, Kenji Wakayama, Gentaro Hirokata, Yusuke Tsunetoshi, Masaaki Zaitsu, Rumi Igarashi, Sanae Haga, Yoshiki Yanagawa, Michitaka Ozaki, Satoru Todo
AMERICAN JOURNAL OF TRANSPLANTATION, 10, 560, 561, WILEY-BLACKWELL PUBLISHING, INC, 2010年04月, ［査読有り］
英語

Effects of a Novel Immunosuppressive Agent, DTCM-Glutarimide Alone or in Combination with Donor Specific Transfusion in Mouse Cardiac Allo-Transplantation.
Yusuke Tsunetoshi, Kenichiro Yamashita, Susumu Shibasaki, Ryoichi Goto, Kenji Wakayama, Gentaro Hirokata, Masaaki Zaitsu, Shoko Kimura, Rumi Igarashi, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
AMERICAN JOURNAL OF TRANSPLANTATION, 10, 562, 562, WILEY-BLACKWELL PUBLISHING, INC, 2010年04月, ［査読有り］
英語

Heavy Water Containing Solution Ameliorates Cold Preservation Injury of the Rat Heart
Kenji Wakayama, Moto Fukai, Kenichiro Yamashita, Daisuke Fukumori, Mitsuru Sugawara, Susumu Shibasaki, Gentaro Hirokata, Masaaki Zaitsu, Yusuke Tsunetoshhi, Michitaka Ozaki, Satoru Todo
AMERICAN JOURNAL OF TRANSPLANTATION, 10, 494, 494, WILEY-BLACKWELL PUBLISHING, INC, 2010年04月, ［査読有り］
英語

DTCM-Glutarimide, a New Activator Protein-1 (AP-1) Inhibitor Ameliorates Chronic Allograft Vasculopathy in Mice
Masaaki Zaitsu, Kenichiro Yamashita, Susumu Shibasaki, Ryoichi Goto, Kenji Wakayama, Gentaro Hirokata, Shoko Kimura, Yusuke Tsunetoshi, Rumi Igarashi, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
AMERICAN JOURNAL OF TRANSPLANTATION, 10, 161, 162, WILEY-BLACKWELL PUBLISHING, INC, 2010年04月, ［査読有り］
英語

Amelioration of Experimental Autoimmune Uveoretinitis with Nuclear Factor-kappa B Inhibitor Dehydroxy Methyl Epoxyquinomicin in Mice
Daiju Iwata, Nobuyoshi Kitaichi, Akiko Miyazaki, Kazuya Iwabuchi, Kazuhiko Yoshida, Kenichi Namba, Michitaka Ozaki, Shigeaki Ohno, Kazuo Umezawa, Kenichiro Yamashita, Satoru Todo, Susumu Ishida, Kazunori Onoe
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 51, 4, 2077, 2084, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2010年04月, ［査読有り］
英語, 研究論文（学術雑誌）, PURPOSE. Experimental autoimmune uveoretinitis (EAU), a Th1/Th17 cell-mediated autoimmune disease induced in mice, serves as a model of human endogenous uveitis. In this model, proinflammatory cytokines and various stimuli activate the transcriptional factor, nuclear factor-kappa B (NF-kappa B), in the retina. The therapeutic effect of the NF-kappa B inhibitor, dehydroxy methyl epoxyquinomicin (DHMEQ), was examined on EAU.
METHODS. EAU was induced in B10.BR mice by K2 peptide immunization. DHMEQ (40 mg/kg/d) was administered daily by intraperitoneal injection. Clinical severity and histopathologic severity were assessed. Translocation of NF-kappa B p65 into the nucleus in EAU retina was assessed. T cells were collected from draining lymph nodes of the K2-immunized mice to examine antigen (Ag)-specific T-cell active responses and cytokine production in vitro.
RESULTS. Disease onset was significantly delayed in DHMEQ-treated mice (15.6 days) compared with untreated mice (12.6 days; P < 0.01). Histologic severity was significantly milder in DHMEQ-treated mice (score, 1.13) than in controls (score, 2.33; P < 0.05). DHMEQ suppressed the Ag-specific T-cell active responses and downregulated the productions of Th-1 type cytokines in vitro in a dose-dependent manner. Alternation was not observed in Th-2 type cytokines. Pretreatment of primed T cells or Ag-presenting cells with DHMEQ reduced T-cell activation and Th1/Th17 cytokine production. DHMEQ treatment suppressed the translocation of the NF-kappa B p65 subunit into the nuclei.
CONCLUSIONS. Systemic administration of DHMEQ suppressed NF-kappa B translocation in the retina, which might have reduced the inflammation of ocular tissues. DHMEQ-mediated regulation of NF-kappa B p65 could be a therapeutic target for the control of endogenous ocular inflammatory diseases. (Invest Ophthalmol Vis Sci. 2010; 51: 2077-2084) DOI:10.1167/iovs.09-4030

Development of Novel Cell Culture Systems Utilizing the Advantages of Collagen Vitrigel Membrane
Toshiaki Takezawa, Maya Fukuda, Winnette McIntosh-Ambrose, Ji-Ae Ko, Jennifer Elisseeff, Sanae Haga, Michitaka Ozaki, Kiyoko Kato, Pi-Chao Wang, Tadashi Uchino, Teruo Nishida
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 130, 4, 565, 574, PHARMACEUTICAL SOC JAPAN, 2010年04月, ［査読有り］
日本語, The white of an egg, rendered opaque by boiling, can be converted into a thin, transparent and rigid material like glass by evaporating the moisture. This phenomenon is known as the vitrification of heat-denatured proteins. We applied vitrification technology to a collagen gel and converted it into a rigid glass-like material. We attempted to rehydrate the glass-like material and succeeded in preparing a novel stable state of collagen gel that was a thin and transparent membrane with excellent gel strength and protein permeability. We called it "collagen vitrigel" because it was produced from the vitrification process of a traditional hydrogel. Further, a framework-embedded collagen vitrigel membrane that can be easily turned inside out with tweezers was prepared by inserting a nylon membrane ring in the collagen sol prior to the gelation, thereby allowing the membrane to function as a removable cell culture substratum. Different types of anchorage-dependent cells could be cultured on both surfaces of the substratum by the manipulation of two-dimensional cultures, and consequently a three-dimensional crosstalk model with paracrine effects from each cell type was reconstructed. Also, the collagen vitrigel membrane containing a bioactive molecule provided a drug delivery system (DDS) with sustainable release. In this review, we summarize the recent progress of applied studies using the collagen vitrigel membrane as follows: a corneal model for eye irritant and permeability tests, a skin model for sensitization test, a renal glomerular model for evaluating blood filtration, an endometrial model for developing a new treatment and a DDS of hepatocyte growth factor for improving liver disorder.

HEPATIC ISCHEMIA INDUCED IMMEDIATE OXIDATIVE STRESS AFTER REPERFUSION AND DETERMINED THE SEVERITY OF THE REPERFUSION-INDUCED DAMAGE. - IN VIVO DYNAMIC ANALYSIS OF LIVER OXIDATIVE STRESS AND DAMAGE
Michitaka Ozaki, Sanae Haga, S. James Remington, Naoki Morita, Takeaki Ozawa
HEPATOLOGY, 50, 4, 640A, 640A, JOHN WILEY & SONS INC, 2009年10月, ［査読有り］
英語

Hepatic Ischemia Induced Immediate Oxidative Stress after Reperfusion and Determined the Severity of the Reperfusion-Induced Damage
Sanae Haga, S. James Remington, Naoki Morita, Keita Terui, Michitaka Ozaki
ANTIOXIDANTS & REDOX SIGNALING, 11, 10, 2563, 2572, MARY ANN LIEBERT, INC, 2009年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Noninvasive evaluation of organ redox states provides invaluable information in many clinical settings. We evaluated a newly developed reduction/oxidation-sensitive green fluorescent protein (roGFP) probe that reports cellular redox potentials and their dynamic changes in live cells. On hypoxia/reoxygenation (H/R) of AML12 liver cells, roGFP indicated mild reduction during hypoxia, but immediate transient oxidation after reoxygenation. The roGFP probe confirmed the antioxidative effects of N-acetylcysteine, catalase, redox factor-1, and Mn-SOD/CuZn-SOD against H/R-induced cellular oxidative stress (OS). In a mouse liver ischemia/reperfusion (I/R) model, roGFP transduced by using an adenoviral vector revealed immediate reduction of the liver under ischemia, and two distinct peaks of OS: (a) early, observed within 60 min after reperfusion, similar to the in vitro study; and (b) later, at 24 h. The early peak levels paralleled the ischemic time up to 75 min and the postischemic liver injury (sGOT/GPT/LDH) in the later phase (6 and 24 h after I/R). The roGFP probe successfully indicated postischemic OS of the liver in living mice, accurately predicting postischemic liver injury. This probe may represent an effective OS marker indicating organ redox states and also predicting the damage/function. Antioxid. Redox Signal. 11, 2563-2572.

膵島移植におけるCD40-CD154副刺激経路の遮断効果
腰塚 靖之, 山下 健一郎, 渡辺 正明, 小倉 正臣, 吉田 雅, 蔵谷 大輔, 蒲池 浩文, 尾崎 倫孝, 古川 博之, 松下 通明, 藤堂 省
移植, 44, 総会臨時, 278, 278, (一社)日本移植学会, 2009年09月
日本語

マウス膵島移植におけるNF-κB阻害薬、DHMEQとtacrolimusの併用療法
渡辺 正明, 山下 健一郎, 尾崎 倫孝, 蒲池 浩文, 古川 博之, 松下 通明, 梅澤 一夫, 藤堂 省
移植, 44, 総会臨時, 278, 278, (一社)日本移植学会, 2009年09月
日本語

新規NF-κB阻害剤DHMEQによるマウス膵島移植早期グラフト障害抑制効果
蔵谷 大輔, 蒲池 浩文, 渡辺 正明, 腰塚 靖之, 山下 健一郎, 尾崎 倫孝, 古川 博之, 松下 通明, 梅澤 一夫, 藤堂 省
移植, 44, 総会臨時, 279, 279, (一社)日本移植学会, 2009年09月
日本語

In vivo far-red luminescence imaging of a biomarker based on BRET from Cypridina bioluminescence to an organic dye
Chun Wu, Kazuhiro Mino, Hidetoshi Akimoto, Makiko Kawabata, Koji Nakamura, Michitaka Ozaki, Yoshihiro Ohmiya
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106, 37, 15599, 15603, NATL ACAD SCIENCES, 2009年09月, ［査読有り］
英語, 研究論文（学術雑誌）, We aimed to develop a far-red luminescence imaging technology for visualization of disease specific antigens on cell surfaces in a living body. First, we conjugated a far-red fluorescent indocyanine derivative to biotinylated Cypridina luciferase. This conjugate produced a bimodal spectrum that has long-wavelength bioluminescence emission in the far-red region as a result of bioluminescence resonance energy transfer. To generate a far-red luminescent probe with targeting and imaging capabilities of tumors, we then linked this conjugate to an anti-human Dlk-1 monoclonal antibody via the biotin-avidin interaction. This far-red luminescent probe enabled us to obtain high-resolution microscopic images of live, Dlk-1-expressing Huh-7 cells without an external light source, and to monitor the accumulation of this probe in tumor-bearing mice. Thus this far-red luminescent probe is a convenient analytical tool for the evaluations of monoclonal antibody localization in a living body.

アレイCGHを用いた肝細胞癌の予後に関するゲノム異常領域の検討 既存の臨床病理学的因子との比較(Analysis of genomic abnormaity concerning with prognosis of hepatocellular carcinoma by array CGH)　　　　　　　　　　　　　　　
中西 一彰, 森田 桂子, 富岡 伸元, 神山 俊哉, 横尾 英樹, 高橋 将人, 尾崎 倫孝, 平野 隆, 藤堂 省
日本癌学会総会記事, 68回, 313, 313, 日本癌学会, 2009年08月
英語

マウスモデルにおける新規NF-kB阻害剤DHMEQの膵癌腹膜播種抑制効果(A novel NF-κB inhibitor DHMEQ suppressed pancreas cancer progression in a mouse model of peritoneal dissemination)　　　　　　　　　　　　　　　
佐藤 正法, 尾崎 倫孝, 中西 一彰, 渡邉 俊之, 三野 和宏, 芳賀 早苗, 横尾 英樹, 梅澤 一夫, 近江谷 克祐, 神山 俊哉, 藤堂 省
日本癌学会総会記事, 68回, 481, 481, 日本癌学会, 2009年08月
英語

Refractory Response to Growth Factors Impairs Liver Regeneration after Hepatectomy in Patients with Viral Hepatitis
Y. Umeda, H. Iwagaki, M. Ozaki, T. Ogino, T. Iwamoto, R. Yoshida, S. Shinoura, H. Matsuda, H. Sadamori, N. Tanaka, T. Yagi
HEPATO-GASTROENTEROLOGY, 56, 93, 971, 977, H G E UPDATE MEDICAL PUBLISHING S A, 2009年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Background/Aims: Liver regeneration after surgical resection is important. The present study was designed to understand the effect of background liver damage on the rate of liver tissue regeneration after hepatectomy and the mechanism of any defective regeneration.
Methodology: The subjects were 40 patients who underwent liver resection. They comprised 22 patients with chronic viral hepatitis-hepatocellular carcinoma (liver damage group) and 18 patients with hepatic metastases from colorectal cancer (normal liver group). Liver regeneration was evaluated by histopathological and immunohistochemical examination of the surgically resected tissue and by CT-scanning of the regenerated liver mass. The resected liver specimens were stained for c-met, gp-130 and nuclear factor-kappaB (NF-kappa B) proteins.
Results: Liver regeneration was significantly less in the liver-damage group than in the normal-liver group. Histopathological examination showed marked inflammatory cell infiltration in the liver-damage group. Expression of c-met, but not gp-130, was significantly higher on parenchymal cells of the liver-damage group than the normal-liver group. NF-kappa B expression in parenchymal liver cells was significantly higher than in non-parenchymal cells of the normal-liver group. In the liver-damage group, liver regeneration correlated negatively with the staining intensity of NF-kappa B protein in non-parenchymal cells. These findings suggest that non-parenchymal cells are constitutively activated in the damaged liver, probably explaining the refractoriness of hepatocytes to cytokine-induced proliferation after hepatectomy, in spite of increased receptor (c-met) expression.
Conclusions: The refractory response of injured hepatocytes to cytokines may explain the impaired postoperative liver regeneration in patients with damaged liver.

Autonomic Regulation of Liver Regeneration After Partial Hepatectomy in Mice
Osamu Ikeda, Michitaka Ozaki, Soichiro Murata, Ryota Matsuo, Yoritaka Nakano, Motonobu Watanabe, Katsuji Hisakura, Andriy Myronovych, Takuya Kawasaki, Keisuke Kohno, Nobuhiro Ohkohchi
JOURNAL OF SURGICAL RESEARCH, 152, 2, 218, 223, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2009年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Background/Aims. The autonomic vagus nerve is thought to play an essential role in liver regeneration since hepatic vagotomy delays hepatic DNA synthesis. However, how the parasympathetic vagus nerve is involved in liver regeneration remains obscure. Kupffer cells are located in liver sinusoids adjacent to hepatocytes and might regulate liver regeneration by releasing interleukin-6 (IL-6). The present study examines the role of the vagus nerve and how Kupffer cells are involved in parasympathetic nerve-mediated liver regeneration in mice.
Methods. We performed surgical vagotomy of the hepatic branch and then partial hepatectomy (PH); some mice received acetylcholine (ACh) agonist/antagonist before PH. We then evaluated liver regeneration and signal transducer and activator of transcription-3 (STAT3) activation. We also investigated whether ACh stimulates IL-6 release from Kupffer cells.
Results. Surgical vagotomy impaired liver regeneration. STAT3, which is activated by IL-6 after hepatectomy and plays a pivotal role in liver regeneration, was less activated in vagotomized mice after PH. Post-PH STAT3 activation was recovered by administering vagotomized mice with an ACh agonist. Furthermore, ACh stimulated IL-6 release in Kupffer cells in vitro.
Conclusion. The parasympathetic system (vagus nerve) contributes to liver regeneration after hepatectomy by stimulating IL-6 release from Kupffer cells followed by STAT3 activation in hepatocytes. (C) 2009 Elsevier Inc. All rights reserved.

新規NF-κB阻害剤(DHMEQ)のvitroにおける血中安定性の検討　　　　　　　　　　　　　　　
多田 緑, 佐藤 奈菜, 秋元 修, 渡邉 悦子, 望月 伸夫, 大野 恵子, 梅澤 一夫, 深井 原, 尾崎 倫孝, 古川 博之, 藤堂 省, 岸野 吏志
日本薬学会年会要旨集, 129年会, 4, 265, 265, (公社)日本薬学会, 2009年03月
日本語

In vivo bioluminescence imaging of bone marrow-derived cells in brain inflammation
Hidetoshi Akimoto, Hyuck Joon Kwon, Michitaka Ozaki, Kazunori Yasuda, Ken-ichi Honma, Yoshihiro Ohmiya
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 380, 4, 844, 849, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2009年03月, ［査読有り］
英語, 研究論文（学術雑誌）, It has been accepted that bone marrow cells infiltrate the brain and play important roles in neuroinflammation. However, there is no good tool for the visualization of these cells in living animals. In this study, we generated mice that were transplanted with GFP- or luciferase-expressing bone marrow cells, and performed in vivo fluorescence imaging (FLI) and in vivo bioluminescence imaging (BLI) to visualize the infiltrated cells. Brain inflammation was induced by intrahippocampal injection of lipopolysaccharide (LIPS). Immunohistochemical investigation demonstrated an increase in the infiltration of bone marrow cells into the hippocampus because of the LPS injection and differentiation of the infiltrated cells into microglia, but not into neurons or astrocytes. BLI, but not FLI, successfully detected an increase in signal intensity with the LPS injection, and the increase of BLI coincided with that of luciferase activity in hippocampus. BLI could quantitatively and continuously monitor bone marrow-derived cells in vivo. (C) 2009 Elsevier Inc. All rights reserved.

CXCL12/CXCR4抑制による転移抑制効果の検討 骨髄由来造血系前駆細胞とpermissive nicheの観点から
喜納 政哉, 小林 希, 上徳 ひろみ, 佐藤 正法, 三野 和宏, 崎浜 秀康, 横尾 英樹, 中西 一彰, 神山 俊哉, 尾崎 倫孝, 藤堂 省
日本外科学会雑誌, 110, 臨増2, 242, 242, (一社)日本外科学会, 2009年02月
日本語

高感度アレイCGHを用いた肝細胞癌の生物学的悪性度および予後に関するゲノム異常領域の検討
中西 一彰, 森田 桂子, 多田 光宏, 富岡 伸元, 神山 俊哉, 横尾 英樹, 高橋 将人, 尾崎 倫孝, 松下 通明, 藤堂 省, 平野 隆
日本外科学会雑誌, 110, 臨増2, 473, 473, (一社)日本外科学会, 2009年02月
日本語

Activation of c-Jun N-terminal kinase is essential for oxidative stress-induced Jurkat cell apoptosis by monochloramine
Tetsuya Ogino, Michitaka Ozaki, Mutsumi Hosako, Masako Omori, Shigeru Okada, Akihiro Matsukawa
LEUKEMIA RESEARCH, 33, 1, 151, 158, PERGAMON-ELSEVIER SCIENCE LTD, 2009年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Leukemic cell apoptosis may be enhanced by appropriate oxidative stress. We report here the mechanism of Jurkat cell apoptosis by monochloramine (NH(2)Cl), a neutrophil-derived oxidant. NH(2)Cl induced caspase-dependent apoptosis, which was preceded by cytochrome c and Smac/Diablo release from mitochondfia. Within 10 min of NH(2)Cl treatment, c-Jun N-terminal kinase (JNK) activation and elevation of cytosolic Ca(2+) were observed. JNK inhibitors (SP600125 or JNK inhibitor VIII) significantly suppressed the apoptosis as well as caspase cleavage and cytochrome c release. In contrast, Ca(2+) chelation by EGTA + acetoxymethyl-EGTA had no effects on apoptosis. Our results indicated that JNK activation contributed most importantly to the NH(2)Cl-induced apoptosis. (C) 2008 Elsevier Ltd. All fights reserved.

The Survival Pathways Phosphatidylinositol-3 Kinase (PI3-K)/Phosphoinositide-Dependent Protein Kinase 1 (PDK1)/Akt Modulate Liver Regeneration Through Hepatocyte Size Rather Than Proliferation
Sanae Haga, Michitaka Ozaki, Hiroshi Inone, Yasuo Okamoto, Wataru Ogawa, Kiyoshi Takeda, Shizuo Akira, Satoru Todo
HEPATOLOGY, 49, 1, 204, 214, JOHN WILEY & SONS INC, 2009年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Liver regeneration comprises a series of complicated processes. The current study was designed to investigate the roles of phosphoinositide-dependent protein kinase 1 (PDK1)-associated pathways in liver regeneration after partial hepatectomy (PH) using liver-specific Pdk1-knockout (L-Pdk1KO) and Pdk1/STAT3 double KO (L-DKO) mice. There was no liver regeneration, and 70% PH was lethal in L-Pdk1KO mice. Liver regeneration was severely impaired equally in L-Pdk1KO and L-DKO mice, even after nonlethal 30% PH. There was no cell growth (measured as increase of cell size) after hepatectomy in L-Pdk1KO mice, although the post-PH mitotic response was the same as in controls. As expected, hepatectomy did not induce hepatic Akt-phosphorylation (Thr308) in L-Pdk1KO mice, and post-PH phosphorylation of Akt, mammalian target of rapamycin (mTOR), p70 ribosomal S6 kinase (P70(S6K)), and S6 were also reduced. To examine the specific role of PDK1-associated signals, a "pif-pocket" mutant of PDK1, which allows PDK1 only to phosphorylate Akt, was used. Liver regeneration was recovered in L-Pdk1KO mice with a "pif-pocket" mutant of PDK1. This re-activated Akt in L-Pdk1KO mice liver and induced post-PH cell growth, without affecting cell proliferation. Further deletion of STAT3 (L-DKO mice) did not further deteriorate liver regeneration, although this certainly reduced post-PH mitotic response. These findings indicate that PDK1/Akt contribute to liver regeneration by regulating cell size. Regarding phosphatidylinositol-3 kinase (PI3-K), immediate upstream signal of PDK1, activation of PI3-K induced cell proliferation via STAT3 activation in the liver of L-Pdk1KO mice but did not improve impaired liver regeneration. This confirmed the pivotal role of PDK1 in liver regeneration and cell growth. Conclusion: PDK1/Akt-mediated responsive cell growth is essential for normal liver regeneration after PH, especially when cell proliferation is impaired. (HEPATOLOGY 2009;49:204-214.)

Taurine Chloramine: A Possible Oxidant Reservoir
Tetsuya Ogino, Tint Aung Than, Mutsumi Hosako, Michitaka Ozaki, Masako Omori, Shigeru Okada
Taurine 7, 643, 451, 461, SPRINGER, 2009年, ［査読有り］
英語, 研究論文（学術雑誌）, Taurine is abundant in polymorphonuclear leukocytes (PMNs) where it reacts with PMN-derived hypochlorous acid to form taurine chloramine (Tau-NHCl), a substance that does not readily cross the cell membrane. When PMNs were stimulated in PBS lacking taurine, extracellular oxidant concentration was low, but the concentration increased 3-4 fold when 15 mM taurine was added, indicating that taurine lowers oxidant levels inside the cell. When Tau-NHCl was added to Jurkat cells in suspension, its half life was about 75 min. In contrast, membrane-permeable ammonia mono-chloramine (NH(2)Cl) has a half life of only 6 min. Accordingly, NH(2)Cl oxidizes cytosolic proteins, such as I kappa B, and inhibits NF-kappa B activation, whereas Tau-NHCl exhibits no comparable effect. However, when NH(4)(+) was added to the medium, Tau-NHCl oxidizes I kappa B and inhibits NF-kappa B activation, probably through oxidant transfer to NH(4)(+) leading to NH(2)Cl formation. These results indicate that Tau-NHCl can serve as an oxidant reservoir, exhibiting either delayed oxidant effects or acting as an oxidant at a distant site.

選択的NFκB阻害剤DHMEQのDonor投与によるマウス膵島移植　　　　　　　　　　　　　　　
高橋 徹, 松本 秀一朗, 松下 通明, 敦賀 陽介, 渡辺 正明, 蔵谷 大輔, 腰塚 靖之, 中木村 繁, 蒲池 浩文, 佐藤 直樹, 尾崎 倫孝, 梅澤 一夫, 藤堂 省
人工臓器, 37, 2, S, 156, (一社)日本人工臓器学会, 2008年11月
日本語

Mutual modulation between interleukin-10 and interleukin-6 induced by Rhodococcus aurantiacus infection in mice
Yimin, Masashi Kohanawa, Michitaka Ozaki, Sanae Haga, Keiko Fujikawa, Songji Zhao, Yuji Kuge, Nagara Tamaki
MICROBES AND INFECTION, 10, 14-15, 1450, 1458, ELSEVIER SCIENCE BV, 2008年11月, ［査読有り］
英語, 研究論文（学術雑誌）, The interaction between interleukin-10 (IL-10) and interleukin-6 (IL-6) was investigated in the inflammatory response to Rhodococcus aurantiacus (R. aurantiacus) infection, in which both cytokines act as anti-inflammatory cytokines. Compared with wild-type (WT) counterparts, IL-6 gene-deficient (IL-6(-)/(-)) mice mounted a more robust production of IL-10 and tumor necrosis factor-alpha (TNF-alpha) during the initial phase of infection. Administration of anti-IL-10 antibody resulted in all the mice dying within 3 days post-infection as well as a further elevated TNF-alpha release. In vitro challenge of the macrophages from IL-6(-)/(-) and WT mice with heat-killed R. aurantiacus also showed similar results. Addition of exogenous IL-6 depressed IL-10 and TNF-alpha production by either IL-6(-)/(-) mice or IL-6(-)/(-) mouse macrophages. Likewise, WT mouse macrophages pretreated with anti-IL-10 or anti-IL-6 antibody exhibited increased production of TNF-alpha and IL-6 or IL-10 respectively. Moreover, neutralization of both IL-10 and IL-6 induced a further increase in TNF-alpha production by WT mouse cells. Overall, we conclude that IL-10 is a key element in protecting mice against mortality, and that IL-10 and IL-6 production are negatively regulated by each other although they are additive in suppressing TNF-alpha release in R. aurantiacus-infected mouse model. (C) 2008 Elsevier Masson SAS. All rights reserved.

マウス胃癌腹膜播種モデルにおける、新規NF-κB阻害剤DHMEQの腫瘍抑制効果の検討(A novel NF-κB inhibitor DHMEQ suppresses the expansion of gastric cancer in the mouse peritoneal dissemination model)　　　　　　　　　　　　　　　
三野 和宏, 中西 一彰, 喜納 政哉, 佐藤 正法, 芳賀 早苗, 横尾 英樹, 神山 俊哉, 梅澤 一夫, 尾崎 倫孝, 藤堂 省
日本癌学会総会記事, 67回, 183, 183, 日本癌学会, 2008年09月
英語

The novel NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin, prevents local and remote organ injury following intestinal ischemia/reperfusion in rats
Tomomi Suzuki, Kenichiro Yamashita, Wataru Jomen, Shinya Ueki, Takeshi Aoyagi, Moto Fukai, Hiroyuki Furukawa, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo
JOURNAL OF SURGICAL RESEARCH, 149, 1, 69, 75, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2008年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Background. Nuclear factor-kappa B regulates the expression of several genes involved in inflammation, the immune response, apoptosis, cell survival, and proliferation. Many of these same genes are activated during ischemia/reperfusion (I/R) injury. Here, we examined the anti-inflammatory efficacy of a newly developed nuclear factor-kappa B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), in the intestinal I/R injury model of rats.
Materials and methods. Intestinal ischemia was induced by occluding the superior mesenteric artery for 60 min. The experimental animals were divided into two groups: untreated group, control; treated group, DHMEQ-treated (20 mg/kg). DHMEQ were administered intraperitoneally at 60 min prior to clamping and 5 min prior to reperfusion. Animal survival rates, intestinal tissue blood flow, serum levels of tumor necrosis factor-alpha, and interleukin-6, and the histopathology of both the intestine and the lung were analyzed.
Results. The DHMEQ-treated animals exhibited higher values of intestinal tissue blood flow and suppression of tumor necrosis factor-alpha and interleukin-6 production, resulting in marked prolongation of their survival times. Histopathological findings obtained by examining tissues from control animals revealed severe intestinal mucosal damage and disruption of the lung alveolar architecture accompanied by hemorrhage and marked neutrophilic infiltration. These findings were significantly ameliorated in DHMEQ-treated animals.
Conclusion. DHMEQ effectively prevented both intestine and lung injuries in rat intestinal I/R models. This agent may possess a good potency for clinical application in various pathological settings including intestinal I/R and/or inflammatory acute lung injury. (c) 2008 Elsevier Inc. All rights reserved.

A simple and reliable method for determining plasma concentration of dehydroxymethylepoxyquinomicin by high performance liquid chromatography with mass spectrometry
Etsuko Watanabe, Nobuo Mochizuki, Hidetomo Ajima, Keiko Ohno, Mitsuhiro Shiino, Kazuo Umezawa, Moto Fukai, Michitaka Ozaki, Hiroyuki Furukawa, Satoru Todo, Satoshi Kishino
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 871, 1, 32, 36, ELSEVIER SCIENCE BV, 2008年08月, ［査読有り］
英語, 研究論文（学術雑誌）, We have developed a simple and reliable method for determining plasma concentration of dehydroxymethylepoxyquinomicin (DHMEQ), a new low molecular weight NF-kappa B inhibitor, using high performance liquid chromatography with mass spectrometry (LC-MS). An experiment of mass spectrometry with electrospray ionization in the negative ionization mode was performed to detect ion transitions at m/z 260.05 [M-H](-) for DHMEQ and 240.29 for mefenamic acid as an internal standard. The samples were purified using liquid-liquid extraction with ethyl acetate. The method yielded a standard curve which was linear for the concentration range of 0.1-125 ng/mL when 0.05 mL plasma was used. The correlation coefficients of all standard curves were greater than or equal to 0.999. The limit of detection was 50 pg/mL (signal/noise >3). Daily fluctuation of plasma standard curve was small. The intra- and inter-assay precision ranged from 2.84 to 4.76% (n = 6) and 2.91 to 7.03% (n = 6), respectively. The LC-MS technique described provides a simple and reliable liquid chromatographic method for the determination of DHMEQ level and for use in studies involving pharmacokinetics. (C) 2008 Elsevier B.V. All rights reserved.

Significant correlation between surgical stress of hepatectomy and changes in the serum levels of HGF, IL-6 and soluble Fas in patients with viral hepatitis
Naoto Gotohda, Hiromi Iwagaki, Michitaka Ozaki, Taira Kinoshita, Masaru Konishi, Toshio Nakagohri, Shinichiro Takahashi, Shinya Saito, Takahito Yagi, Noriaki Tanaka
HEPATO-GASTROENTEROLOGY, 55, 85, 1400, 1403, H G E UPDATE MEDICAL PUBLISHING S A, 2008年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Background/Aims: Liver damage after hepatectomy is still a serious concern. The present study was designed to clarify the relations between liver injury/surgical stress and cytokines after hepatectomy, in patients with viral hepatitis.
Methodology: Ten consecutive patients undergoing hepatectomy were studied, all with hepatocellular carcinoma due to viral hepatitis. Blood samples for interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), hepatocyte growth factor (HGF), soluble Fas (sFas), soluble Fas Ligand and soluble tumor necrosis factor receptor (sTNFR) assays were collected before the operation and at the end of the operation.
Results: There was a significant and positive correlation between the change in the serum level of HGF and preoperative liver function (ICG-R15). Notably, there were significant correlations between surgical stress and IL-6, HGF and sFas, but not sIL-6R and sTNFR. Furthermore, there was significant correlation between postoperative Ever function (total bilirubin, albumin) and HGF, IL-6.
Conclusions: There was a close relationship between surgical stress and HGF, IL-6 and sFas after hepatectomy in patients with viral hepatitis. It was useful for the evaluation of surgical stress of hepatectomy to estimate the serum level of HGF, IL-6 and sFas.

Deficient response of IL-6 impaired liver regeneration after hepatectomy in patients with viral hepatitis
Naoto Gotohda, Hiromi Iwagaki, Michitaka Ozaki, Taira Kinoshita, Masaru Konishi, Toshio Nakagohri, Shinichiro Takahashi, Shinya Saito, Takahito Yagi, Noriaki Tanaka
HEPATO-GASTROENTEROLOGY, 55, 85, 1439, 1444, H G E UPDATE MEDICAL PUBLISHING S A, 2008年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Background/Aims: Liver regeneration after surgical resection is still a serious concern. The present study is designed to understand the relations between liver injury/regeneration and cytokines after hepatectomy with viral hepatitis.
Methodology: Twenty-one consecutive patients undergoing liver resection were studied, which included two patients with biliary tract cancer, three patients with hepatic metastases from colorectal cancer, and sixteen patients with primary liver tumor. They were also divided into two groups according to the existence of chronic viral hepatitis: 10 patients with viral hepatitis and 11 patients without viral hepatitis.
Results: Viral hepatitis reduced pre-operative liver function (ICG-R15 and platelet count) with raised levels of sFas. Interestingly, this also reduced postoperative surge of IL-6, but not HGF, though they were equally at basal levels pre-operatively. Recovery of liver size, calculated with resected liver mass and volumetry with CT scan, was deteriorated in liver with viral hepatitis, but any difference of postoperative liver damage was observed between two groups.
Conclusions: Viral infection, somehow, increased sFas level pre-operatively, but does not influence the post-operative liver injury. Deficient response of IL-6, but not HGF, may be a major cause for poor liver regeneration after hepatectomy in patients with viral hepatitis independent from liver injury.

選択的NFkB阻害剤DHMDQのドナー投与によるマウス膵島肝内移植成績の改善効果
高橋 徹, 松本 秀一朗, 敦賀 陽介, 葛西 弘規, 細田 充主, 渡辺 正明, 古川 博之, 松下 通明, 藤堂 省, 尾崎 倫孝, 梅澤 一夫
北海道外科雑誌, 53, 1, 123, 124, 北海道外科学会, 2008年06月
日本語

選択的NFkB阻害剤DHMDQのドナー投与によるマウス膵島肝内移植成績の改善効果
高橋 徹, 松本 秀一朗, 松下 通明, 敦賀 陽介, 葛西 弘規, 渡辺 正明, 尾崎 倫孝, 古川 博之, 梅澤 一夫, 藤堂 省
日本外科学会雑誌, 109, 臨増2, 682, 682, (一社)日本外科学会, 2008年04月
日本語

臨床検体情報をどう治療へむすびつけるか? 血清中糖鎖の網羅的解析による肝細胞癌新規バイオマーカーの開発
横尾 英樹, 三浦 嘉晃, 神山 俊哉, 中西 一彰, 濱口 純, 工藤 岳秋, 古川 潤一, 中川 隆公, 田原 宗徳, 中馬 誠, 髭 修平, 篠原 康郎, 尾崎 倫孝, 多田 光宏, 松下 通明, 浅香 正博, 西村 紳一郎, 藤堂 省
日本外科学会雑誌, 109, 臨増2, 144, 144, (一社)日本外科学会, 2008年04月
日本語

Platelets strongly induce hepatocyte proliferation with IGF-1 and HGF in vitro
Ryota Matsuo, Nobuhiro Ohkohchi, Soichiro Murata, Osamu Ikeda, Yoritaka Nakano, Motonobu Watanabe, Katsuji Hisakura, Andriy Myronovych, Tomomi Kubota, Hisashi Narimatsu, Michitaka Ozaki
JOURNAL OF SURGICAL RESEARCH, 145, 2, 279, 286, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2008年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Background. It is well known that platelets have a thrombotic effect. However, platelets play an important role not only in hemostasis but also in wound healing and tissue regeneration. Platelets have been reported to accumulate in the liver and promote liver regeneration after an extended hepatectomy, but the mechanism is unclear. The present study was designed to clarify the mechanism by which platelets have a direct proliferative effect on hepatocytes in vitro.
Materials and methods. Hepatocytes obtained from male BALB/c mice by collagenase digestion and immortalized hepatocytes (TLR2) were used. To elucidate the mechanism of the proliferative effect of platelets, DNA synthesis of hepatocytes was measured under various conditions and the related cellular signals were analyzed. Chromatographic analysis was also performed to clarify which elements of platelets have mitogenic activity.
Results. DNA synthesis significantly increased in the hepatocytes cultured with platelets (P < 0.001). However, when the platelets and hepatocytes were separated, the platelets did not have a proliferative effect. Whole disrupted platelets, the supernatant fraction, and fresh isolated platelets had a similar proliferative effect, while the membrane fraction did not. After the addition of platelets, both Akt and extracellular signal-regulated kinases ERK1/2 were activated, but extracellular signal-regulated kinase STAT3 was not activated. Some mitogenic fractions were obtained from the platelet extracts by gel exclusion chromatography; the fractions were rich in hepatocyte growth factor and IGF-1.
Conclusions. Direct contact between platelets and hepatocytes was necessary for the proliferative effect. The direct contact initiated signal transduction involved in growth factor activation. Hepatocyte growth factor, vascular endothelial growth factor, and insulin-like growth factor-1, rather than platelet-derived growth factor, mainly contributed to hepatocyte proliferation. (C) 2008 Elsevier Inc. All rights reserved.

Identification of de novo STAT3 target gene in liver regeneration
Hui-Qi Zhang, Sanae Haga, Moto Fukai, Yuko Oikawa, Hiroshi Inoue, Wataru Ogawa, Arihiko Kano, Atsushi Maruyama, Xin-Yuan Fu, Satoru Todo, Shin Enosawa, Michitaka Ozaki
Hepatology Research, 38, 4, 374, 384, 2008年04月, ［査読有り］
英語, 研究論文（学術雑誌）, The process of liver regeneration is regulated by complex mechanisms. Although signal transducer and activator of transcription-3 (STAT3), a transcription factor which targets mainly mitotic genes, definitely plays an important role in liver regeneration, the exact roles of STAT3 are not completely understood. Aim: In this report, we tried to search for a new target of STAT3 involved in liver regeneration in mice. Methods: We generated liver-specific STAT3 knockout (L-S3KO) mice and a STAT3 knockout cell line of mouse origin. Using chromatin immunoprecipitation, we screened 12 genes to which STAT3 binds after partial hepatectomy (PH). Of these genes, we analyzed the S3-IE3 clone that is located on chromosome-3 and possesses STAT3 binding sites in it. Results: We showed that STAT3 binds to a specific site on S3-IE3, and that interleukin-6 (IL-6) stimulates its transcriptional activity. The mRNA and protein levels of the net gene, which is located downstream of S3-IE3, were negatively regulated in the control cells, but not in the STAT3 knockout cells after IL-6 stimulation. Similarly in in vivo mouse PH, the mRNA and protein levels of net were also negatively regulated after PH, but not in L-S3KO mice. Conclusion: The net gene is located downstream of a newly-recognized STAT3 binding site (S3-IE3) and negatively regulated after IL-6 stimulation and PH, although its role is still unclear. © 2007 The Japan Society of Hepatology.

Preventing hypoxia/reoxygenation damage to hepatocytes by p66(shc) ablation: Up-regulation of anti-oxidant and anti-apoptotic proteins
Sanae Haga, Keita Terui, Moto Fukai, Yuko Oikawa, Kaikobad Irani, Hiroyuki Furukawa, Satoru Todo, Michitaka Ozaki
JOURNAL OF HEPATOLOGY, 48, 3, 422, 432, ELSEVIER SCIENCE BV, 2008年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Background/Aims:Ischemia/reperfusion damage to the liver remains a serious concern in many clinical situations. Major mechanisms for this certainly include oxidative stress.
Methods:The effects of ablating the p66 isoform of ShcA (p66(shc)) on hypoxia/reoxygenation (H/R)-induced oxidative stress and cell injury in hepatocytes were investigated.
Results: Immediately after reoxygenation, AML12 cells were clearly under oxidative stress; many cells underwent apoptosis. However, knockdown of p66(shc) by specific RNAi markedly decreased cellular oxidative stress and H/R-induced apoptosis, as well as conferring resistance to H2O2 insult. These data suggest that prevention of apoptosis conferred by ablation of p66(shc) results from changed ROS-scavenging, but not inhibition of ROS generation. These data were also confirmed in fibroblasts from p66(shc) knockout mice. Anti-oxidant molecules, such as MnSOD and Ref-1 and the anti-apoptotic molecule Bcl-xL were up-regulated, and pro-apoptotic FLICE was down-regulated, by ablation of p66. Interestingly, catalase expression was not affected in p66(shc)-knockdown-AML12 cells although it is a major target in other cell types.
Conclusions: Our findings suggest that in hepatocytes, ablation of p66 A, is cytoprotective against H/R-induced oxidative stress, with MnSOD and Ref-1 playing critical roles, and with up-regulation of Bcl-xL and down-regulation of FLICE contributing jointly to preventing cells from undergoing oxidant-induced apoptosis. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

BlotGIycoABC (TM), an integrated glycoblotting technique for rapid and large scale clinical glycomics
Yoshiaki Miura, Megumi Hato, Yasuro Shinohara, Hiromitsu Kuramoto, Jun-ichi Furukawa, Masaki Kurogochi, Hideyuki Shimaoka, Mitsuhiro Tada, Kazuaki Nakanishi, Michitaka Ozaki, Satoru Todo, Shin-Ichiro Nishimura
MOLECULAR & CELLULAR PROTEOMICS, 7, 2, 370, 377, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2008年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Recent progress in mass spectrometry has led to new challenges in glycomics, including the development of rapid glycan enrichment techniques. A facile technique for exploration of a carbohydrate-related biomarker is important because proteomics research targets glycosylation, a posttranslational modification. Here we report an "all-in-one" protocol for high throughput clinical glycomics. This new technique integrates glycoblotting-based glycan enrichment onto the BlotGlycoABC(TM) bead, on-bead stabilization of sialic acids, and fluorescent labeling of oligosaccharides in a single workflow on a multiwell filter plate. The advantage of this protocol and MALDI-TOF MS was demonstrated through differentiation of serum N-glycan profiles of subjects with congenital disorders of glycosylation and hepatocellular carcinoma and healthy donors. The method also permitted total cellular glycomics analysis of human prostate cancer cells and normal human prostate epithelial cells. These results demonstrate the potentials of glycan enrichment/processing for biomarker discovery.

The roles of Jak/STAT3 and PI3-K/Akt pathways in liver injury and regeneration
Michitaka Ozaki
Seikagaku, 80, 5, 399, 408, 2008年, ［査読有り］
日本語

Surgical stress and tumor behavior: Impact of ischemia-reperfusion and hepatic resection on tumor progression
Michitaka Ozaki, Satoru Todo
LIVER TRANSPLANTATION, 13, 12, 1623, 1626, JOHN WILEY & SONS INC, 2007年12月, ［査読有り］
英語

Trpsl regulates proliferation and apoptosis of chondrocytes through Stat3 signaling
Hiroki Suemoto, Yasuteru Muragaki, Katsuhiro Nishioka, Misako Sato, Akira Ooshima, Shunji Itoh, Ikuji Hatamura, Michitaka Ozaki, Attila Braun, Erika Gustafsson, Reinhard Faessler
DEVELOPMENTAL BIOLOGY, 312, 2, 572, 581, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2007年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Mutations in the TRPSl gene lead to the tricho-rhino-phalangeal syndrome, which is characterized by skeletal defects and abnormal hair development. The TRPSl gene encodes an atypical member of the GATA-type family of transcription factors. Here we show that mice with a disrupted Trpsl gene develop a chondrodysplasia characterized by diminished chondrocyte proliferation and decreased apoptosis in growth plates. Our analyses revealed that Trpsl is a repressor of Stat3 expression, which in turn controls chondrocyte proliferation and survival by regulating the expression of cyclin Dl and Bcl2. Our conclusion is supported (i) by siRNA-mediated depletion of Stat3 in Trpsl-deficient chondrocytes, which normalized the expression of cyclin Dl and Bcl2, (ii) by overexpression of Trpsl in ATDC5 chondrocytes, which diminished Stat3 levels and increased proliferation and apoptosis, and (iii) by mutational analysis of the GATA-binding sites in the Stat3 gene, which revealed that their integrity is critical for the direct association with Trpsl and for Trpsl-mediated repression of Stat3. Altogether our findings identify Trpsl as a novel regulator of chondrocytes proliferation and survival through the control of Stat3 expression. (c) 2007 Elsevier Inc. All rights reserved.

Mechanism of impaired regeneration of fatty liver in mouse partial hepatectomy model
Hiroshi Murata, Takahito Yagi, Hiromi Iwagaki, Tetsuya Ogino, Hiroshi Sadamori, Hiroyoshi Matsukawa, Yuzoh Umeda, Sanae Haga, Noriaki Takaka, Michitaka Ozaki
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 22, 12, 2173, 2180, BLACKWELL PUBLISHING, 2007年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Background and Aim: The mechanism of injury in steatotic liver under pathological conditions been extensively examined. However, the mechanism of an impaired regeneration is still not well understood. The aim of this study was to analyze the mechanism of impaired regeneration of steatotic liver after partial hepatectomy (PH).
Methods: db/db fatty mice and lean littermates were used for the experiments. Following 70% PH, the survival rate and recovery of liver mass were examined. Liver tissue was histologically examined and analyzed by western blotting and RT-PCR.
Results: Of 35 db/db mice, 25 died within 48 h of PH, while all of the control mice survived. Liver regeneration of surviving db/db mice was largely impaired. In db/db mice, mitosis of hepatocytes after PH was disturbed, even though proliferating cell nuclear antigen (PCNA) expression (G1 to S phase marker) in hepatocytes was equally observed in both mice groups. Interestingly, phosphorylation of Cdc2 in db/db mice was suppressed by reduced expression of Wee1 and Myt1, which phosphorylate Cdc2 in S to G2 phase.
Conclusions: In steatotic liver, cell-cycle-related proliferative disorders occurred at mid-S phase after PCNA expression. Reduced expression of Wee1 and Myt1 kinases may therefore maintain Cdc2 in an unphosphorylated state and block cell cycle progression in mid-S phase. These kinases may be critical factors involved in the impaired liver regeneration in fatty liver.

Small liver graft regenerates through immediate increase of HGF and IL-6-possible involvement of sinusoidal tensile/shear stress in small liver graft
Takanori Oyama, Hiroshi Sadamori, Hiroyoshi Matsukawa, Hiroshi Murata, Yuzou Umeda, Yasuhiro Watanabe, Michitaka Ozaki, Hiromi Iwagaki, Noriaki Tanaka, Takahito Yagi
HEPATO-GASTROENTEROLOGY, 54, 79, 2078, 2083, H G E UPDATE MEDICAL PUBLISHING S A, 2007年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Background/Aims: The mechanisms whereby grafts in the recipients can be primed for regeneration following living donor liver transplantation (LDLT) are poorly understood. The present study was designed to understand the mechanism for post-transplant regeneration in small-for-size liver graft.
Methodology: Out of LDLT cases, we examined patients with end-stage liver cirrhosis and subsequent transplantation. A total of 16 patients were divided into 2 groups, group L (large graft) and group S (small graft). We examined the serum biochemical markers and cytokines preoperatively and postoperatively. We also carried out hemodynamic analysis by measuring the portal and arterial peak velocity.
Results: The differences in ages, preoperative bio-chemical markers and MELD score between the two groups were not statistically significant. Though differences in the preoperative levels of IL-6, sIL-6R and HGF were not significant between the two groups, IL-6 and HGF levels in group S significantly increased postoperatively. Immediate and significant increase of Vp max was also observed in group S. Two weeks after LDLT, the regeneration rate in group S was significantly higher than that in group L.
Conclusions: These findings may allow us to speculate that immediate increase of portal pressure, reflecting sinusoidal tensile/shear stress, accelerates liver regeneration through immediate induction of IL-6 and HGF.

新規低分子NF-κB阻害剤(DHMEQ)の高感度定量法の確立　　　　　　　　　　　　　　　
渡邉 悦子, 望月 伸夫, 大野 恵子, 椎野 三洋, 梅澤 一夫, 深井 原, 尾崎 倫孝, 古川 博之, 藤堂 省, 岸野 吏志
日本薬学会年会要旨集, 127年会, 3, 157, 157, (公社)日本薬学会, 2007年03月
日本語

SF-044-3 副交感神経のもつ肝再生制御メカニズムの解明(第107回日本外科学会定期学術集会)　　　　　　　　　　　　　　　
池田, 治, 村田, 聡一郎, 松尾, 亮太, 中野, 順隆, 渡辺, 基信, 久倉, 勝治, 尾崎, 倫孝, 大河内, 信弘
日本外科学会雑誌, 108, 2, 228, 社団法人日本外科学会, 2007年03月
日本語, 研究論文（学術雑誌）

Control of allograft rejection by applying a novel nuclear factor-kappa B inhibitor, dehydroxymethylepoxyquinomicin
Shinya Ueki, Kenichiro Yamashita, Takeshi Aoyagi, Sanae Haga, Tomomi Suzuki, Tomoo Itoh, Masahiko Taniguchi, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
TRANSPLANTATION, 82, 12, 1720, 1727, LIPPINCOTT WILLIAMS & WILKINS, 2006年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Background. Nuclear factor (NF)-kappa B plays a crucial role in lymphocyte activation, proliferation, and survival. We examined the immunosuppressive effect of a newly developed NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) in allotransplantation.
Methods. Purified C57BL/6 (H-2(b)) T cells were used for in vitro studies examining activation, proliferation, cytokine production and nuclear NF-kappa B and nuclear factor of activated T cells (NFAT) protein levels. A fully major histocompatibility complex incompatible BALB/c (H-2(d))-to-C57BL/6 mice cardiac transplantation model was utilized for in vivo studies. DHMEQ was given intraperitoneally to transplant recipients at a various dose starting from day 0. In some, DHMEQ was administered concomitantly with tacrolimus.
Results. DHMEQ significantly suppressed alpha CD3 + alpha CD28 monoclonal antibody-triggered T-cell proliferation, CD25/CD69 expressions, and both interleukin-2 and interferon (IFN)-gamma production in a dose-dependent fashion. DHMEQ blocked nuclear translocation of NF-kappa B but not NFAT in activated T cells. Combined treatment with DHMEQ and tacrolimus significantly suppressed T cell activation as compared to that of mono-therapy with either agent alone. Single DHMEQ treatment moderately prolonged cardiac allograft survival. Further, combination of DHMEQ plus tacrolimus markedly prolonged graft mean survival time (MST) to 59.5 days when compared to either DHMEQ (MST: 10 days) or tacrolimus (MST: 13 days) treatment alone. Such effect was associated with inhibition of mixed lymphocyte reaction against donor antigen, IFN-gamma producing splenocytes and graft cellular infiltration as examined at 5 and 12 days posttransplantation.
Conclusion. DHMEQ inhibits nuclear translocation of NF-kappa B but not NFAT inactivated T cells, and prolongs allograft survival. Blocking both NF-kappa B and NFAT by DHMEQ and tacrolimus induces potent immunosuppression, which may become a new modality in controlling allograft rejection.

Protective effects of nafamostat mesilate on liver injury induced by lipopolysaccharide in rats: Possible involvement of CD14 and TLR-4 downregulation on Kupffer cells
Hideaki Miyaso, Yoshinori Morimoto, Michitaka Ozaki, Sanae Haga, Susumu Shinoura, Yasuhiro Choda, Hiroshi Murata, Goutaro Katsuno, Kamul Huda, Hideo Takahashi, Noriaki Tanaka, Hiromi Iwagaki
DIGESTIVE DISEASES AND SCIENCES, 51, 11, 2007, 2012, SPRINGER, 2006年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Nafamostat mesilate (NM) is a synthetic protease inhibitor with various biological effects. To determine its effect on liver injury related to sepsis, we investigated the effects of NM on lipopolysaccharide (LPS)-induced liver injury. Wistar rats were allocated into two groups; the NM group underwent intraperitoneal NM administration 30 min before LPS administration, and the control group underwent PBS administration. Serum AST and ALT levels were significantly decreased in NM-treated rats. Reduced levels of TNF-alpha, IL-1 beta, and IFN-gamma were observed after LPS administration in NM-treated rats. No significant differences were observed in IL-6 levels between the NM and the control group. In contrast, HGF levels were significantly increased only in control rats. NM treatment decreased protein and mRNA levels of TLR-4 and CD14. Our data suggest that NM treatment has protective effects against LPS-induced hepatotoxicity through downregulation of TLR4 and CD14 in liver, which decreased TNF-alpha, IL-1 beta, and IFN-gamma production in liver.

抗癌剤耐性ヒト肝癌細胞株におけるN-結合型糖鎖の構造変化　　　　　　　　　　　　　　　
工藤 岳秋, 中川 裕章, 高橋 將人, 神山 直也, 濱口 純, 横尾 英樹, 中西 一彰, 中川 隆公, 尾崎 倫孝, 神山 俊哉, 出口 喜三郎, 西村 紳一郎, 藤堂 省
日本癌学会総会記事, 65回, 100, 100, 日本癌学会, 2006年09月
日本語

AFP mRNA detected in bone marrow by real-time quantitative RT-PCR analysis predicts survival and recurrence after curative hepatectomy for hepatocellular carcinoma
Toshiya Kamiyama, Masato Takahashi, Takahito Nakagawa, Kazuaki Nakanishi, Hirofumi Kamachi, Tomomi Suzuki, Tsuyoshi Shimamura, Masahiko Taniguchi, Michitaka Ozaki, Michiaki Matsushita, Hiroyuki Furukawa, Satoru Todo
ANNALS OF SURGERY, 244, 3, 451, 463, LIPPINCOTT WILLIAMS & WILKINS, 2006年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To determine whether detection of hepatocellular carcinoma (HCC) cells by real-time quantitative RT-PCR targeting of alpha-fetoprotein mRNA (AFP mRNA) before or after curative hepatectomy predicts HCC recurrence and patient survival.
Summary Background Data: The presence of cancer cells in peripheral blood and/or bone marrow in patients with malignant disease has been reported to correlate with outcome.
Methods: Between July 2000 and June 2005, 136 consecutive HCC patients underwent primary curative hepatectomy. Bone marrow aspirated preoperatively, and peripheral blood samples collected before and after operation were subjected to real-time quantitative RT-PCR analysis using AFP mRNA as a target molecule. Median follow-up was 23 months (range, 6-54 months). Patient survival (PS), disease-free survival (DFS), and clinicopathologic features were compared between patients with positive and negative AFP mRNA.
Results: Twenty-four patients died (22 from HCC). HCC recurred in 66 patients (hepatic in 37 [56.1%]; hepatic and remote in 17 [25.8%], and remote alone in 12 [18.2%]). Bone marrow was positive for AFP mRNA in 38 patients (27.9%) and negative in 98 (72.1%). One- and 3-year PS was 96.6% and 91.4%, respectively, with negative AFP mRNA versus 86.2% and 55.5%, respectively, with positive AFP mRNA (P < 0.0001). One- and 3-year DFS were 73.2% and 44.8%, respectively, with negative AFP mRNA versus 54.5% and 25.8%, respectively, with positive AFP mRNA (P = 0.0399). Portal vascular invasion, tumor size, multiple tumors, and tumor differentiation correlated with inferior PS and DFS on univariate analysis. On multivariate analysis, positive AFP mRNA was the most important risk factor for PS (P = 0.001) and DFS (P = 0.0165). In addition, positive AFP mRNA in peripheral blood after operation tended to predict reduced DFS.
Conclusion: AFP mRNA in the bone marrow and systemic circulation during the perioperative period predicts patient survival and recurrence after curative hepatic resection for HCC.

Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post-transplant liver injury and promotes regeneration in a 20% rat partial liver transplant model
KASM Huda, L Guo, S Haga, H Murata, T Ogino, M Fukai, T Yagi, H Iwagaki, N Tanaka, M Ozaki
TRANSPLANT INTERNATIONAL, 19, 5, 415, 423, BLACKWELL PUBLISHING, 2006年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Signal transducer and activator of transcription-3 (STAT3) is one of the most important transcription factors for liver regeneration. This study was designed to examine the effects of constitutively activated STAT3 (STAT3-C) on post-transplant liver injury and regeneration in a rat 20% partial liver transplant (PLTx) model by ex vivo adenoviral gene transfer. Adenovirus encoding the STAT3-C gene was introduced intraportally into liver grafts and clamped for 30 min during cold preservation. After orthotopic PLTx, liver graft/body weights and serum biochemistry were monitored, and both a histological study and DNA binding assay were performed. STAT3-C protein expression and its binding to DNA in the liver graft were confirmed by Western blotting and electrophoretic mobility shift assay (EMSA), respectively. This treatment modality promoted post-Tx liver regeneration effectively and rapidly. The serum levels of alanine aminotransferase/aspartate aminotransferase (AST/ALT) and bilirubin decreased in rats with STAT3-C. However, albumin (a marker of liver function) did not. Ex vivo gene transfer of STAT3-C to liver grafts reduced post-Tx injury and promoted liver regeneration. Thus, the activation of STAT3 in the liver graft may be a potentially effective clinical strategy for improving the outcome of small-for-size liver transplantation.

Monochloramine inhibits ultraviolet B-induced p53 activation and DNA repair response in human fibroblasts
Kazuhisa Hiramatsu, Tetsuya Ogino, Michitaka Ozaki, Shigeru Okada
Biochimica et Biophysica Acta - Molecular Cell Research, 1763, 2, 188, 196, 2006年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Monochloramine (NH2Cl) is one of the inflammation-derived oxidants, and has various effects on cell cycle, apoptosis and signal transduction. We studied the effects of NH2Cl on DNA repair response induced by ultraviolet B (UVB) irradiation in normal human diploid fibroblasts, TIG-1. TIG-1 irradiated with 20 mJ/cm2 UVB showed marked increase in thymine dimer, which decreased by about 50% after 24 h. This decrease in thymine dimer was significantly attenuated (P <
0.05) by the pretreatment of NH 2Cl (200 μM), which indicated DNA repair inhibition. UVB induced p53 phosphorylation at Ser15, Ser20 and Ser37, and p53 accumulation, and NH 2Cl also inhibited these changes. Consequently, UVB-induced increase in the downstream effectors of p53, namely p21Cip1 and Gadd45a, were almost completely inhibited by NH2Cl. Immunoprecipitation study indicated that the association of p53 and MDM2, an E3 ubiquitin ligase for p53, did not change substantially by NH2Cl and/or UVB. The phosphorylation of p53 (Ser15 and Ser37) by UVB is catalyzed by ATR (ataxia telangiectasia mutated and Rad3 related kinase), which works as DNA damage sensor, and ATR also phosphorylates checkpoint kinase 1(Chk1) at Ser345. NH2Cl also inhibited the phosphorylation of Chk1 (Ser345). As UVB-induced DNA damage is repaired by nucleotide excision repair (NER) in human cells, these findings indicated that NH2Cl inhibited NER through the inhibition of p53 phosphorylation and accumulation, and NH2Cl probably impaired DNA damage recognition and/or ATR activation. NH2Cl may facilitate carcinogenesis through the inhibition of NER that repairs DNA damages from various carcinogens. © 2005 Elsevier B.V. All rights reserved.

Monochloramine inhibits ultraviolet B-induced p53 activation and DNA repair response in human fibroblasts.
Hiramatsu K, Ogino T, Ozaki M, Okada S
Biochimica et biophysica acta, 1763, 2, 188, 196, 2006年02月, ［査読有り］

Naoto Gotohda, Hiromi Iwagaki, Michitaka Ozaki, Masaru Konishi, Toshio Nakagohri, Shinichiro Takahashi, Takahiro Yagi, Taira Kinoshita and Noriaki Tanaka. The role of a Protease Inhibitor against Hepatectomy. Hepato-Gastroenterology 53: 115-119, 2006　　　　　　　　　　　　　　　
2006年

Transduction of exogenous constitutively activated Stat3 into dispersed islets induces proliferation of rat pancreatic beta-cells
S Tsukiyama, M Matsushita, S Matsumoto, T Morita, S Kobayashi, H Tamura, H Kamachi, M Ozaki, S Todo
TISSUE ENGINEERING, 12, 1, 131, 140, MARY ANN LIEBERT INC, 2006年01月, ［査読有り］
英語, 研究論文（学術雑誌）, In vitro proliferation of functional islet mass/beta-cells by transduction of cell cycle regulatory genes has not been well documented due to the lack of either an effective method for gene transduction to islets or effective genes for beta-cell proliferation. Signal transducers and activators of transcription-3 (Stat3) are among the most important molecules for cell proliferation and for cell antiapoptosis. In this study, adenovirus-mediated gene transduction was performed on dispersed islet cells, and reaggregated islet mass functions, such as capabilities for reaggregation, proliferation, and glucose-stimulated insulin secretion (GSIS), were evaluated. The constitutively activated form of Stat3 (Stat3-C) was effectively transduced to most of the islet cells, even at a low density of adenovirus vector. There was no difference in the spontaneous reaggregation capability between Stat3-C transduced and control islet cells. BrdU incorporation in Stat3-C-transduced islet cells was significantly higher (2.8-fold) than that in the control cells, and it was significantly elevated (4-fold) by the addition of HGF in culture media. GSIS in Stat3-C-transduced islet cells was preserved to the level in controls by 5 days in culture. The results indicated that gene transduction into islet cells could be enhanced by first dispersing the cells. Stat3-C induced cell proliferation of beta-cells without loss of insulin secretion activity at the glucose challenge, and HGF enhanced the beta-cell proliferative activity of Stat3-C.

The role of a protease inhibitor against hepatectomy
N Gotohda, H Iwagaki, M Ozaki, M Konishi, T Nakagohri, S Takahashi, T Yagi, T Kinoshita, N Tanaka
HEPATO-GASTROENTEROLOGY, 53, 67, 115, 119, H G E UPDATE MEDICAL PUBLISHING S A, 2006年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Background/Aims: Nafamostat Mesilate (NM) is a synthetic serine protease inhibitor that is capable of inhibiting the various coagulation factors. To determine whether NM may also be useful in attenuating operative invasiveness, we investigated the effects of perioperative administration of NM on postoperative serum levels of proinflammatory cytokine IL-6 and hepatocyte growth factor (HGF).
Methodology: Thirty patients undergoing hepatectomy with hepatocellular carcinoma, biliary carcinoma and metastatic colorectal cancer were enrolled in this study. These patients were separated into two groups; high invasive group (resected liver volume: 1000cm(3) <) and less invasive group (resected liver volume: 1000cm(3) >). The high invasive group of 11 patients received perioperative administration of NM (G roup NM), while the less invasive group of 19 patients did not (Group C). Serum levels of IL-6, HGF and soluble IL-6 receptor (sIL-6R) were simultaneously measured on preoperative and postoperative day ('day 0', 'day 7').
Results: Serum IL-6 levels on day 0 were significantly elevated and returned to preoperative levels on day 7 in both groups, and the serum IL-6 level in Group NM on day 0 was significantly lower than that in Group C on day 0. Serum HGF levels on day 0 and day 7 were significantly higher in Group NM than those in Group C. Compared with healthy control subjects, the higher serum level of HGF on the preoperative day in all patients was attributable to tumor-burden. The sIL-6R levels on day 0 decreased in both groups, and their levels in Group NM were significantly lower than those in Group C, suggesting that increased synthesis of IL-6/sIL-6R complex which could accelerate liver regeneration.
Conclusions: These results suggested that perioperative administration of NM may attenuate surgical stress by decreasing production of proinflammatory cytokine IL-6, and may accelerate liver regeneration through stimulation with the IL-6/sIL-6R complex and possible involvement of increased production of HGF.

Tetsuya Ogino, Mutsumi Hosako, Kazuhisa Hiramatsu, Masako Omori, Michitaka Ozaki, Shigeru Okada. Oxidative modification of Ik-B by monochloramine inhibits tumor necrosis factor-alpha-induced NF-kB activation. Biochimica et Biophysica Acta (BBA) - Molec・・・
Tetsuya Ogino, Mutsumi Hosako, Kazuhisa Hiramatsu, Masako Omori, Michitaka Ozaki, Shigeru Okada
Biochimica et Biophysica Acta - Molecular Cell Research, 1746, 2, 135, 142, 2005年12月15日
英語, 研究論文（学術雑誌）, Tetsuya Ogino, Mutsumi Hosako, Kazuhisa Hiramatsu, Masako Omori, Michitaka Ozaki, Shigeru Okada. Oxidative modification of Ik-B by monochloramine inhibits tumor necrosis factor-alpha-induced NF-kB activation. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 15;1746:135-42.

Obstructive jaundice increases sensitivity to lipopolysaccharide via TLR4 upregulation: Possible involvement in gut-derived hepatocyte growth factor-protection of hepatocytes
H Miyaso, Y Morimoto, M Ozaki, S Haga, S Shinoura, Y Choda, H Iwagaki, N Tanaka
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 20, 12, 1859, 1866, BLACKWELL PUBLISHING, 2005年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Patients with obstructive jaundice are prone to sepsis after biliary tract surgery. The present study was designed to determine the effect of biliary obstruction on cytokine responses to lipopolysaccharide (LPS).
Methods: Wister rats were allocated into two groups; the BDL group underwent bile duct ligation, followed 2 weeks later by administration of LPS into the duodenum. The control group underwent sham operation, and similarly received enteral LPS. Specimens were collected serially, and applied for the assays.
Results: Serum aspartate aminotransferase and alanine aminotransferase levels were significantly increased in BDL rats. High tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6 levels in peripheral blood were observed 2 h after LPS administration in BDL rats. In contrast, no increases in both cytokines were noted in peripheral and portal blood in control rats. Baseline HGF levels in portal and peripheral blood in BDL rats were significantly higher than in control rats. LPS significantly increased hepatocyte growth factor (HGF) levels in portal blood and decreased in peripheral blood in BDL rats, but not in control rats. Immunohistochemical analysis revealed that BDL increased expressions of Toll-like receptor (TLR)4, CD14 and CD68 both in the small intestine and liver. Both TLR4 and CD14 mRNAs were upregulated in the small intestine and liver after LPS administration in BDL rats.
Conclusion: Obstructive jaundice and LPS stimulation induced TLR4 upregulation both in the liver and small intestine, which led to increased TNF-alpha and IL-6 production in liver and HGF production in the small intestine. The upregulation of TLR4 may lead to pathological and host defense reactions in obstructive jaundice complicated with Gram-negative bacterial infection. (C) 2005 Blackwell Publishing Asia Pty Ltd.

Oxidative modification of IkappaB by monochloramine inhibits tumor necrosis factor alpha-induced NF-kappaB activation.
Ogino T, Hosako M, Hiramatsu K, Omori M, Ozaki M, Okada S
Biochimica et biophysica acta, 1746, 2, 135, 142, 2005年12月, ［査読有り］

Compensatory recovery of liver mass by Akt-mediated hepatocellular hypertrophy in liver-specific STAT3-deficient mice
S Haga, W Ogawa, H Inoue, K Terui, T Ogino, R Igarashi, K Takeda, S Akira, S Enosawa, H Furukawa, S Todo, M Ozaki
JOURNAL OF HEPATOLOGY, 43, 5, 799, 807, ELSEVIER SCIENCE BV, 2005年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Background/Aims: Liver regeneration following hepatectomy is complicated and involves a variety of interacting factors. The present study was designed to study the roles of proliferation and hypertrophy of hepatocytes in liver regeneration following hepatectomy in liver-specific STAT3-knockout (LS3-KO) mice lacking mitogenic activity.
Methods: Partial hepatectomy was performed in LS3-KO and control mice. Liver regeneration was estimated by the liver weight, cell proliferation and cell size, and the related cellular signals were analyzed.
Results: Proliferation of hepatocytes following PH was markedly suppressed in LS3-KO mice with reduced cyclinD1 transcript. However, liver mass recovered sufficiently following PH in LS3-KO mice almost equal to that of control mice. Analysis of hepatocellular growth revealed that cell size following hepatectomy was significantly larger in LS3-KO mice than in control mice. Hepatectomy induced immediate but transient phosphorylation of Akt, p70(S6K), mTOR and GSK-3 beta in LS3-KO mice much more than in control mice. Additionally, adenoviral transfection of dominant negative mutant of Akt to control and LS3-KO mice led to insufficient liver regeneration following hepatectomy.
Conclusions: PI3-K/Akt-mediated responsive hepatocellular hypertrophy may be essential for liver regeneration following hepatectomy and sufficiently compensated liver regeneration even in STAT3-deficient liver, in which cell proliferation is impaired. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Kosei Maemura, Qizhi Zheng, Tatehiko Wada, Michitaka Ozaki, Sonshin Takao, Takashi Aikou, Gregory B Bulkley, Andrew S Klein, Zhaoli Sun. Reactive oxygen species are essential mediators in antigen presentation by Kupffer cells. Immunol Cell Biol 83 (4):・・・
Kosei Maemura, Qizhi Zheng, Tatehiko Wada, Michitaka Ozaki, Sonshin Takao, Takashi Aikou, Gregory B. Bulkley, Andrew S. Klein, Zhaoli Sun
Immunology and Cell Biology, 83, 4, 336, 343, 2005年08月
英語, 研究論文（学術雑誌）, Kosei Maemura, Qizhi Zheng, Tatehiko Wada, Michitaka Ozaki, Sonshin Takao, Takashi Aikou, Gregory B Bulkley, Andrew S Klein, Zhaoli Sun. Reactive oxygen species are essential mediators in antigen presentation by Kupffer cells. Immunol Cell Biol 83 (4): 336 - 343, 2005.

Reactive oxygen species are essential mediators in antigen presentation by Kupffer cells
K Maemura, QZ Zheng, T Wada, M Ozaki, S Takao, T Aikou, GB Bulkley, AS Klein, ZL Sun
IMMUNOLOGY AND CELL BIOLOGY, 83, 4, 336, 343, BLACKWELL PUBLISHING, 2005年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Kupffer cells (KC) act as APC in the liver and play a major role in the clearance of gut-derived antigens and pathogens entering the liver with portal venous blood. Antigen presentation by KC has been implicated in regulation of the local and systemic immune responses. In this study, modulation of KC antigen presentation by antioxidants and the role of reactive oxygen species (ROS) as essential mediators of antigen presentation in KC were investigated. Co-culture of KC with ovalbumin (OVA) antigens resulted in upstream intracellular endogenous ROS generation and increased expression of MHC class II and costimulator molecules, and consequent OVA-specific CD4(+) T-cell proliferation in response to antigen presentation by KC. Scavenging of KC ROS by antioxidants, or blocking of KC ROS generation by specific inhibitors of NADPH oxidase and/or xanthine oxidase, or by specific inhibitors of the mitochondrial electron transport chain, significantly decreased OVA-specific T-cell proliferation in response to antigen presentation by KC. Increased expression of MHC class II and costimulatory molecules in KC pulsed with OVA antigens was blocked by inhibiting ROS generation enzymatically. Intracellular endogenous ROS generation during antigen processing may therefore provide essential secondary signalling for KC antigen presentation.

Signal transducer and activator of transcription 3 alpha and specificity protein 1 interact to upregulate intercellular adhesion molecule-1 in ischemic-reperfused myocardium and vascular endothelium
XP Yang, K Irani, S Mattagajasingh, A DiPaula, F Khanday, M Ozaki, K Fox-Talbot, WM Baldwin, LC Becker
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 25, 7, 1395, 1400, LIPPINCOTT WILLIAMS & WILKINS, 2005年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective-Intercellular adhesion molecule-1 (ICAM-1) is upregulated rapidly on endothelial cells during ischemia reperfusion (I-R) and mediates tissue leukocyte accumulation. The ICAM-1 proximal promoter contains a signal transducer and activator of transcription (Stat) binding motif (gamma-interferon activation site [GAS] sequence), which flanks a specificity protein 1 (Sp1) binding site. We examined the roles of Stat and Sp1 in the regulation of ICAM-1 after myocardial I-R.
Methods and Results-Open-chest anesthetized rats underwent coronary artery occlusion for 35 minutes and reperfusion for 0 to 240 minutes. Stat became activated within 15 minutes after reperfusion, primarily in vascular endothelial cells; the activated Stat protein was identified as Stat3 (alpha-isoform). After phosphorylation on serine 727 (p-S727), Stat3 alpha was found in association with the transcriptional regulator Sp1, and the complex bound to an ICAM-1-GAS probe. ICAM-1 expression increased after I-R and lagged shortly behind Stat3 alpha activation. In cultured human umbilical vein endothelial (HUVE) cells, activation of Stat3 alpha after hypoxia-reoxygenation (H-R) was dependent on the small GTPase Rac1. Transfection of a dominant-negative Stat3 (Y705F) adenovirus or a GAS decoy oligonucleotide reduced ICAM-1 mRNA expression after H-R. Using a reporter gene transfected into HUVE cells, mutation of the GAS element in the ICAM-1 promoter resulted in reduced transcriptional activity after H-R. Sp1 coimmunoprecipitated with p-S727 Stat3 during H-R, and Sp1 or Stat3 alpha interfering RNA markedly reduced ICAM-1 mRNA expression.
Conclusion-The Sp1-Stat3 complex appears to play an important role in the upregulation of ICAM-1 transcription after reoxygenation or reperfusion.

Involvement of prostaglandin receptors (EPR2-4) in in vivo immunosuppression of PGE2 in rat skin transplant model
Y Fujimoto, H Iwagaki, M Ozaki, T Ogino, H Murata, DS Sun, H Sadamori, HK Takahashi, N Tanaka, T Yagi
INTERNATIONAL IMMUNOPHARMACOLOGY, 5, 7-8, 1131, 1139, ELSEVIER SCIENCE BV, 2005年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Prostaglandin E2 (PGE2) is known to modulate immune responses and is widely viewed as a general immunosuppressant. There have been recognized four receptors for PGE2 (EP1-EP4 receptor) so far, and EP2 and EN receptors are mainly involved in the immunosuppressive effect of PGE2 in vitro. In the present study we examined the in vivo immuno suppressive effects of selective EP receptor agonists using a high-responder rat skin transplantation model.
Materials and methods: Skin allografts from ACI donors were transplanted onto LEW recipients. Agents were injected everyday between day 0 and day 5 after skin transplantation at the dose of 300 mu g/kg subcutaneously. Survival of the skin allograft, histological changes and changes of the intragraft cytokine expressions were analyzed using the reverse transcription polymerase chain reaction (RT-PCR). We also assessed the mixed lymphocyte reaction (MLR) assay using splenocytes.
Results: PGE2 significantly prolonged allograft survival (18.8 +/- 1.5 days) compared with untreated control (14.8 +/- 0.8 days). EP2R+EP3R+EP4R agonists also prolonged allograft survival (18.0 +/- 1.0 days) although EP3R agonist or EP2R+EP4R agonists alone failed (15.5 +/- 0.7, 15.4 +/- 1.3 days, respectively). RT-PCR analysis in the skin grafts demonstrated IL-10 upregulation and IFN-gamma down-regulation in all groups except untreated control and EP2R agonist-treated groups. MLR was significantly reduced in groups of EP2R+EP4R agonists, EP2R+EP3R+EP4R agonists and PGE2, compared with untreated control.
Conclusions: The effect of PGE2 to prolong the survival of skin transplant requires the action of a combination of three receptors, i.e., EP2+EP3+EP4. (C) 2005 Elsevier B.V. All rights reserved.

The role of STAT3 in liver regeneration
Keita Terui, Michitaka Ozaki
Drugs of Today, 41, 7, 461, 469, 2005年07月, ［査読有り］
英語, Liver regeneration is a process in which the liver recovers its mass and function after injury due to various causes such as hepatectomy, virus infection and intoxication. This regeneration invokes a series of complex processes which may involve the actions of various cytokines, cell proliferation and cell growth. In response to cytokine stimuli, receptor-mediated signaling systems are activated, and many proteins are transcriptionally up-regulated to increase liver mass and improve liver function. In this review, we focus on the roles of signal transducer and activator of transcription-3 (STAT3) and its functions in mitogenic and other responses during liver regeneration following hepatectomy. We also describe newly discovered target genes of STAT3 and discuss their potential roles in liver regeneration after injury due to various causes. © 2005 Prous Science. All rights reserved.

Prolonged survival of donor-specific rat intestinal allograft by administration of bone-marrow-derived immature dendritic cells
DS Sun, H Iwagaki, M Ozaki, T Ogino, S Kusaka, Y Fujimoto, H Murata, H Sadamori, H Matsukawa, N Tanaka, T Yagi
TRANSPLANT IMMUNOLOGY, 14, 1, 17, 20, ELSEVIER SCIENCE BV, 2005年03月, ［査読有り］
英語, 研究論文（学術雑誌）, It has been reported that intraportal administration of donor antigens induced donor-specific hyporesponsiveness. We studied here the effects of transplantation of BM-derived immature dendritic cells (imDCs) and mature DCs (mDCs) via portal vein on rat small intestinal allograft survival. This study comprised four treatment groups: 1) untreated controls; 2) FK506 alone; 3) intraportal donor-specific BM-derived imDCs transplantation+FK506; 4) mDCs/Tx+FK506. Allograft survival was minimal in control group (5.2 +/- 0.8 days) and maximal in imDC+FK506 group (28.4 +/- 3.0 days). The rats in mDC+FK506 group showed systemic inflammatory reaction due to GVHR, and died within 10 days after transplantation. The in vitro MLR reaction using imDCs was also strongly inhibited both in direct and indirect recognition pathways. The impact of imDCs for the specific induction of transplant tolerance may suggest that immunization with donor-specific imDCs has therapeutic potential in organ transplantation. (c) 2004 Elsevier B.V. All rights reserved.

Xiao Ping Yang, Kaikobad Irani, Subhendra Mattagajasingh, Anthony DiPaula, Firdous Khanday, Michitaka Ozaki, Karen Fox-Talbot, William M. Baldwin, III, and Lewis C. Becker. Signal Transducer and Activator of Transcription 3{alpha} and Specificity Prote・・・　　　　　　　　　　　　　　　
2005年
Xiao Ping Yang, Kaikobad Irani, Subhendra Mattagajasingh, Anthony DiPaula, Firdous Khanday, Michitaka Ozaki, Karen Fox-Talbot, William M. Baldwin, III, and Lewis C. Becker. Signal Transducer and Activator of Transcription 3{alpha} and Specificity Protein 1 Interact to Upregulate Intercellular Adhesion Molecule-1 in Ischemic-Reperfused Myocardium and Vascular Endothelium. Arterioscl Throm Vas 25:1395-1400, 2005

Sanae Haga, Wataru Ogawa, Hiroshi Inoue, Keita Terui, Tetsuya Ogino, Rumi Igarashi, Kiyoshi Takeda, Shizuo Akira, Hiroyuki Furukawa, Satoru Todo, Shin Enosawa, Michitaka Ozaki*. Compensatory recovery of liver mass by Akt-mediated cellular hypertrophy i・・・　　　　　　　　　　　　　　　
2005年
Sanae Haga, Wataru Ogawa, Hiroshi Inoue, Keita Terui, Tetsuya Ogino, Rumi Igarashi, Kiyoshi Takeda, Shizuo Akira, Hiroyuki Furukawa, Satoru Todo, Shin Enosawa, Michitaka Ozaki*. Compensatory recovery of liver mass by Akt-mediated cellular hypertrophy in liver-specific STAT3-deficient mice. J Hepatol 43(5): 799-807, 2005.

Dong Sheng Sun, Hiromi Iwagaki, Michitaka Ozaki, Tetsuya Ogino, Satoshi Kusaka, Yoshimi Fujimoto, Hiroshi Murata, Hiroshi Sadamori, Hiroyoshi Matsukawa, Noriaki Tanaka, Takahito Yagi: Intraportal administration of bone-marrow-derived immature dendritic・・・　　　　　　　　　　　　　　　
2005年
Dong Sheng Sun, Hiromi Iwagaki, Michitaka Ozaki, Tetsuya Ogino, Satoshi Kusaka, Yoshimi Fujimoto, Hiroshi Murata, Hiroshi Sadamori, Hiroyoshi Matsukawa, Noriaki Tanaka, Takahito Yagi: Intraportal administration of bone-marrow-derived immature dendritic cells prolonged donor-specific rat intestinal allograft survival. Transpl Immunol 14: 17-20, 2005.

Frank Hoentjen, R. Balfour Sartor, Michitaka Ozaki, and Christian Jobin: Impaired STAT3 activation enhances LPS-induced NF-κB recruitment to the IL-12p40 promoter in IL-10 deficient mice. Blood 105: 689-696, 2005.　　　　　　　　　　　　　　　
2005年

Hideaki Miyaso, Yoshinori Morimoto, Michitaka Ozaki, Sanae Haga, Susumu Shinoura, Yasuhiro Choda, Hiromi Iwagaki and Noriaki Tanaka. Obstructive jaundice increases sensitivity to lipopolysaccharide via TLR4 upregulation: Possible involvement in gut-der・・・　　　　　　　　　　　　　　　
2005年
Hideaki Miyaso, Yoshinori Morimoto, Michitaka Ozaki, Sanae Haga, Susumu Shinoura, Yasuhiro Choda, Hiromi Iwagaki and Noriaki Tanaka. Obstructive jaundice increases sensitivity to lipopolysaccharide via TLR4 upregulation: Possible involvement in gut-derived hepatocyte growth factor-protection of hepatocytes. J Gastroen Hepatol 20 (12), 1859-1866, 2005.

Kenji Matsushita, Munekazu Yamakuchi, Craig N Morrell, Michitaka Ozaki, Brian O'Rourke, Kaikobad Irani, and Charles J Lowenstein Vascular endothelial growth factor regulation of Weibel-Palade body exocytosis: Blood 105: 207 - 214, 2005.　　　　　　　　　　　　　　　
2005年

Yoshimi Fujimoto, Hiromi Iwagaki, Michitaka Ozaki, Hiroshi Murata, Sun Dong Sheng, Hiroshi Sadamori, Hideo Kohka Takahashi, Masahiro Nishibori, Noriaki Tanaka, Takahito Yagi: Involvement of Prostaglandin receptors (EPR2-4) in in vivo immunosuppression ・・・　　　　　　　　　　　　　　　
2005年
Yoshimi Fujimoto, Hiromi Iwagaki, Michitaka Ozaki, Hiroshi Murata, Sun Dong Sheng, Hiroshi Sadamori, Hideo Kohka Takahashi, Masahiro Nishibori, Noriaki Tanaka, Takahito Yagi: Involvement of Prostaglandin receptors (EPR2-4) in in vivo immunosuppression of PGE-2 in rat skin transplant model. Int Immunopharmacol 11:1131-1139, 2005.

STAT3 regulates NF-kappa B recruitment to the IL-12p40 promoter in dendritic cells
F Hoentjen, RB Sartor, M Ozaki, C Jobin
BLOOD, 105, 2, 689, 696, AMER SOC HEMATOLOGY, 2005年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Interleukin-10-deficient (IL-10(-/-)) mice develop an IL-12-mediated intestinal inflammation in the absence of endogenous IL-10. The molecular mechanisms of the dysregulated IL-12 responses in IL-10(-/-) mice are poorly understood. In this study, we investigated the role of nuclear factor-kappa B (NF-kappaB) and signal transducers and activators of transcription 3 (STAT3) in lipopolysaccharide (LPS)-induced IL12p40 gene expression in bone marrow derived-dendritic cells (BMDCs) isolated from wild-type (WT) and IL-10(-/-) mice. We report higher IL-12p40 mRNA accumulation and protein secretion in LPS-stimulated BMDCs isolated from IL-10(-/-) compared with WT mice. LPS-induced NF-kappaB signaling is similar in IL-10(-/-) and WT BMDCs as measured by IkappaBalpha phosphorylation and degradation, ReIA phosphorylation and nuclear translocation. and NF-kappaB transcriptional activity, with no down-regulatory effects of exogenous IL-10. Chromatin immunoprecipitation demonstrated enhanced NF-kappaB (cRel, ReIA) binding to the IL-12p40 promoter in IL10(-/-) but not WT BMDCs. Interestingly, LPS induced STAT3 phosphorylation in WT but not IL-10(-/-) BMDCs, a process blocked by IL-10 receptor blocking antibody. Adenoviral gene delivery of a constitutively active STAT3 but not control green fluorescence protein (GFP) virus blocked LPS-induced IL-12p40 gene expression and cRel recruitment to the IL-12p40 promoter. In conclusion, dysregulated LPS-induced IL-12p40 gene expression in IL10(-/-) mice is due to enhanced NF-kappaB recruitment to the IL-12p40 promoter in the absence of activated STAT3.

Vascular endothelial growth factor regulation of Weibel-Palade-body exocytosis
K Matsushita, M Yamakuchi, CN Morrell, M Ozaki, B O'Rourke, K Irani, CJ Lowenstein
BLOOD, 105, 1, 207, 214, AMER SOC HEMATOLOGY, 2005年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Vascular endothelial growth factor (VEGF) not only regulates angiogenesis, vascular permeability, and vasodilation but also promotes vascular inflammation. However, the molecular basis for the proinflammatory effects of VEGF is not understood. We now show that VEGF activates endothelial cell exocytosis of Weibel-Palade bodies, releasing vasoactive substances capable of causing vascular thrombosis and inflammation. VEGF triggers endothelial exocytosis in part through calcium and phospholipase C-gamma (PLC-gamma) signal transduction. However, VEGF also modulates endothelial cell exocytosis by activating endothelial nitric oxide synthase (eNOS) production of nitric oxide (NO), which nitrosylates N-ethylmaleimide sensitive factor (NSF) and inhibits exocytosis. Thus, VEGF plays a dual role in regulating endothelial exocytosis, triggering pathways that both promote and inhibit endothelial exocytosis. Regulation of endothelial exocytosis may explain part of the proinflammatory effects of VEGF. (C) 2005 by The American Society of Hematology.

Stat3 confers resistance against hypoxia/reoxygenation-induced oxidative injury in hepatocytes through upregulation of Mn-SOD
K Terui, S Enosawa, S Haga, HQ Zhang, H Kuroda, K Kouchi, T Matsunaga, H Yoshida, JF Engelhardt, K Irani, N Ohnuma, M Ozaki
JOURNAL OF HEPATOLOGY, 41, 6, 957, 965, ELSEVIER SCIENCE BV, 2004年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Background/Aims: Hypoxia/reoxygenation (H/R) causes oxidative stress to the cell and induces apoptotic cell death. Signal transducer and activator of transcription-3 (Stat3) is one of the most important molecules involved in the initiation of liver development and regeneration, and has recently been shown to protect cells against various pathogens. In order to investigate the hepatoprotective effects of Stat3, we examined whether it protects against H/R-induced injury in primary hepatocytes.
Methods: Primary cultured hepatocytes were prepared from SD rats. Adenoviruses and cytokines were added 2 days and 1 h prior to the H/R insult, respectively. Hepatocytes and culture media were harvested for the assays before and after H/R insult.
Results: Interleukin-6 and cardiotropin-1, which may function mainly through Stat3 activation, protected cells from H/R-induced apoptosis. Adenoviral overexpression of the constitutively activated form of Stat3 (Stat3-C) reduced H/R-induced apoptosis as well as generation of reactive oxygen species (ROS) in hepatocytes. Interestingly, Stat3-C induced Mn-SOD, but not Cu/Zn-SOD, both at the protein and mRNA levels. Overexpression of Mn-SOD significantly reduced H/R-induced ROS and apoptosis by inhibiting redox-sensitive activation of caspase-3 activity.
Conclusions: Stat3 protects hepatocytes from H/R-induced cell injury at least partly by upregulating Mn-SOD and inactivating caspase-3. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The impact of portal infusion with donor-derived bone marrow cells and intracellular cytokine expression of graft-infiltrating lymphocytes on the graft survival in rat small bowel transplant model
N Mitsuoka, H Iwagaki, M Ozaki, SD Sheng, A Sadamori, H Matsukawa, Y Morimoto, J Matsuoka, N Tanaka, T Yagi
TRANSPLANT IMMUNOLOGY, 13, 3, 155, 160, ELSEVIER SCIENCE BV, 2004年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Intraportal administration of alloantigen is reported to reduce antigen-specific immune responses, although the underlying mechanisms for the reduced immunological reactions, especially those of the graft, are poorly understood. We examined intracellular cytokine production by graft-infiltrating lymphocytes (GILs) and peripheral blood lymphocytes (PBLs) to elucidate the underlying mechanisms of beneficial effects on intraportal infusion of donor cells in rat small bowel transplantation (SBT). Methods: Recipient rats (Lewis) were transplanted with small bowel from ACl rats. Tacrolimus (Tac) was injected daily from days 0 to 4. Bone marrow cells of ACI rats were infused via the portal or tail vein on the day of surgery. On day 5, both GILs and PBLs collected from SBT graft and peripheral blood, respectively, were analyzed for intracellular cytokine production of recipient-derived alphabeta-T cells. The Th1/ Th2 balance in each group was designated as the ratio of the percentage of GILs or PBLs staining positive for intracellular IL-4 or IFN-gamma, respectively. The total cell numbers of GILs from SBT graft were also counted. Results: Survival of recipients was markedly prolonged by the combination of Tac and donor-specific bone marrow infusion via the portal vein (DSBMI-PV-Tac) compared with the untreated control, Tac alone, or DSBM1 tail vein plus Tac. DSBM1-PV-Tac significantly decreased the total cell numbers of GILs and also induced remarkable Th2-type response in G1Ls. Conclusions: Our results indicate that DSBMI-PV-Tac decreased GILs and enhanced Th2-type response in SBT graft, both of which are associated with a significant prolongation of graft survival in SBT. (C) 2004 Elsevier B.V. All rights reserved.

Apurinic/apyrmidinic endonuclease 1 regulates endothelial NO production and vascular tone
BH Jeon, G Gupta, YC Park, B Qi, A Haile, FA Khanday, YX Liu, JM Kim, M Ozaki, AR White, DE Berkowitz, K Irani
CIRCULATION RESEARCH, 95, 9, 902, 910, LIPPINCOTT WILLIAMS & WILKINS, 2004年10月, ［査読有り］
英語, 研究論文（学術雑誌）, The dual-function protein apurinic/apyrmidinic endonuclease/redox factor-1 (APE1/ref-1) is essential for DNA repair and also governs the reductive activation of many redox-sensitive transcription factors. We examined the role of APE1/ref-1 in regulation of endothelium-dependent tone and systemic blood pressure. APE1/ref-1(+/-) mice have impaired endothelium-dependent vasorelaxation, reduced vascular NO levels, and are hypertensive. APE1/ref-1 upregulates H-ras expression and leads to H-ras-mediated, phosphoinositide-3 kinase/Akt kinase-dependent calcium sensitization of endothelial NO synthase (eNOS), stimulating NO production. The reducing property of APE1/ref-1 is essential for upregulation of H-ras and for the calcium sensitization of eNOS. These findings uncover a novel physiological role for APE1/ref-1 in regulating vascular tone by governance of eNOS activity and bioavailable NO.

Lei Guo, Sanae Haga, Shin Enosawa, Katsutoshi Naruse, Yasushi Harihara, Yasuhiko Sugawara, Masatoshi Makuuchi, Michitaka Ozaki: Improved Hepatic Regeneration With Reduced Post-Ischemic Injury By Redox Factor-1 Gene Transfer In A Rat Small Size-Liver Tr・・・
Lei Guo, Sanae Haga, Shin Enosawa, Katsutoshi Naruse, Yasushi Harihara, Yasuhiko Sugawara, Kaikobad Irani, Masatoshi Makuuchi, Michitaka Ozaki
American Journal of Transplantation, 4, 6, 879, 887, 2004年06月
英語, 研究論文（学術雑誌）, Lei Guo, Sanae Haga, Shin Enosawa, Katsutoshi Naruse, Yasushi Harihara, Yasuhiko Sugawara, Masatoshi Makuuchi, Michitaka Ozaki: Improved Hepatic Regeneration With Reduced Post-Ischemic Injury By Redox Factor-1 Gene Transfer In A Rat Small Size-Liver Transplant Model. Am J Transplant 4: 879- 887, 2004.

Improved hepatic regeneration with reduced injury by redox factor-1 in a rat small-sized liver transplant model
L Guo, S Haga, S Enosawa, K Naruse, Y Harihara, Y Sugawara, K Irani, M Makuuchi, M Ozaki
AMERICAN JOURNAL OF TRANSPLANTATION, 4, 6, 879, 887, BLACKWELL MUNKSGAARD, 2004年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Redox factor-1 (Ref-1) has been shown to function in a redox-dependent manner in the cell. This study was designed to examine the effects of Ref-1 on liver regeneration as well as protection against postischemic injury in a rat model of 20% partial liver transplantation. Adenovirus carrying the full length of Ref-1 gene was introduced into liver grafts by ex vivo perfusion via the portal vein during preservation. Liver graft weights were assessed, as well as graft histology, serum levels of alanine aminotransferase (ALT)/bilirubin, DNA binding activities of AP-1 and Stat3. Redox factor-1 successfully expressed in the liver graft, improved regeneration by promoting cell proliferation. Overexpression of Ref-1 protein also reduced post-transplant injury and inflammatory reactions in the grafts. The increased serum levels of ALT and bilirubin observed after transplantation were significantly reduced by Ref-1 overexpression. Furthermore, adenovirally overexpressed Ref-1 in mouse liver successfully promoted liver regeneration after simple partial hepatectomy. Interestingly, Ref-1 significantly increased DNA binding of Stat3, but not AP-1. Overexpressed Ref-1 effectively promoted graft regeneration and reduced postischemic injury in a small-sized liver transplantation model. The results of the present study may open a new avenue to clinical transplantation of disproportionately sized grafts in living-related liver transplantation.

Keita Terui, Shin Enosawa, Sanae Haga, Naomi Ohnuma, Michitaka Ozaki: Hypoxia/reoxygenation-induced, redox-dependent activation of STAT1 (signal transducer and activator of transcription 1) confers resistance to apoptotic cell death via hsp70 induction・・・
K Terui, S Haga, S Enosawa, N Ohnuma, M Ozaki
BIOCHEMICAL JOURNAL, 380, 203, 209, PORTLAND PRESS, 2004年05月
英語, 研究論文（学術雑誌）, Keita Terui, Shin Enosawa, Sanae Haga, Naomi Ohnuma, Michitaka Ozaki: Hypoxia/reoxygenation-induced, redox-dependent activation of STAT1 (signal transducer and activator of transcription 1) confers resistance to apoptotic cell death via hsp70 induction. Biochem J 380: 203-209, 2004.

Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo
H Inoue, W Ogawa, M Ozaki, S Haga, M Matsumoto, K Furukawa, N Hashimoto, Y Kido, T Mori, H Sakaue, K Teshigawara, SY Jin, H Iguchi, R Hiramatsu, D LeRoith, K Takeda, S Akira, M Kasuga
NATURE MEDICINE, 10, 2, 168, 174, NATURE PUBLISHING GROUP, 2004年02月, ［査読有り］
英語, 研究論文（学術雑誌）, The transcription factor, signal transducer and activator of transcription-3 (STAT-3) contributes to various physiological processes. Here we show that mice with liver-specific deficiency in STAT-3, achieved using the Cre-loxP system, show insulin resistance associated with increased hepatic expression of gluconeogenic genes. Restoration of hepatic STAT-3 expression in these mice, using adenovirus-mediated gene transfer, corrected the metabolic abnormalities and the alterations in hepatic expression of gluconeogenic genes. Overexpression of STAT-3 in cultured hepatocytes inhibited gluconeogenic gene expression independently of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), an upstream regulator of gluconeogenic genes. Liver-specific expression of a constitutively active form of STAT-3, achieved by infection with an adenovirus vector, markedly reduced blood glucose, plasma insulin concentrations and hepatic gluconeogenic gene expression in diabetic mice. Hepatic STAT-3 signaling is thus essential for normal glucose homeostasis and may provide new therapeutic targets for diabetes mellitus.

Keita Terui, Shin Enosawa, Sanae Haga, Hui Qi Zhang, Naomi Onuma, Michitaka Ozaki: Stat3 confers resistance against hypoxia/reoxygenation-induced oxidative injury in hepatocytes via Mn-SOD. J Hepatol 41: 957-965, 2004.　　　　　　　　　　　　　　　
2004年

Hiroshi Inoue, Wataru Ogawa, Michitaka Ozaki, Sanae Haga, Michihiro Matsumoto, Hiroyuki Mori, Kensuke Furukawa, Naoko Hashimoto, Yoshiaki Kido, Toshiyuki Mori, Hiroshi Sakaue, Kiyoshi Teshigawara, Shiyu Jin, Haruhisa Iguchi, Ryuji Hiramatsu, Delek Lero・・・　　　　　　　　　　　　　　　
2004年
Hiroshi Inoue, Wataru Ogawa, Michitaka Ozaki, Sanae Haga, Michihiro Matsumoto, Hiroyuki Mori, Kensuke Furukawa, Naoko Hashimoto, Yoshiaki Kido, Toshiyuki Mori, Hiroshi Sakaue, Kiyoshi Teshigawara, Shiyu Jin, Haruhisa Iguchi, Ryuji Hiramatsu, Delek Leroith, Kiyoshi Takeda, Shizuo Akira & Masato Kasuga: Role of Stat-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo. Nat Med 10(2): 168 -174, 2004.

Naoshi Mitsuoka, Hiromi Iwagaki, Michitaka Ozaki, Sun Dong Sheng, Hiroshi Sadamori, Hiroyoshi Matsukawa, Yoshinori Morimoto, Junji Matsuoka, and Noriaki Tanaka, Takahito Yagi: The impact of portal infusion with donor-derived bone marrow cells and intra・・・　　　　　　　　　　　　　　　
2004年
Naoshi Mitsuoka, Hiromi Iwagaki, Michitaka Ozaki, Sun Dong Sheng, Hiroshi Sadamori, Hiroyoshi Matsukawa, Yoshinori Morimoto, Junji Matsuoka, and Noriaki Tanaka, Takahito Yagi: The impact of portal infusion with donor-derived bone marrow cells and intracellular cytokine expression of graft-infiltrating lymphocytes on the graft survival in rat small bowel transplant model. Transpl Immunol 13: 155-160, 2004.

Measurement of In vivo oxidative stress regulated by the Rac1 GTPase
M Ozaki, K Irani
OXYGEN SENSING, 381, 184, 191, ACADEMIC PRESS INC, 2004年, ［査読有り］
英語

Stat3 protects against Fas-induced liver injury by redox-dependent and -independent mechanisms
S Haga, K Terui, HQ Zhang, S Enosawa, W Ogawa, H Inoue, T Okuyama, K Takeda, S Akira, T Ogino, K Irani, M Ozaki
JOURNAL OF CLINICAL INVESTIGATION, 112, 7, 989, 998, AMER SOC CLINICAL INVESTIGATION INC, 2003年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Signal transducer and activator of transcription-3 (Stat3) is one of the most important molecules involved in the initiation of liver development and regeneration. In order to investigate the hepatoprotective effects of Stat3, we examined whether Stat3 protects against Fas-mediated liver injury in the mouse. A constitutively activated form of Stat3 (Stat3-C) was adenovirally overexpressed in mouse liver by intravenous injection, and then a nonlethal dose of Fas agonist (Jo2) was injected intraperitoneally into the mouse (0.3 mug/g body wt). Stat3-C dramatically suppressed both apoptosis and necrosis induced by Jo2. In contrast, liver-specific Stat3-knockout mice failed to survive following Jo2 injection. Stat3-C upregulated expression of FLICE inhibitor protein (FLIP), Bcl-xL, and Bcl-2, and accordingly downregulated activities of FLICE and caspase-3 that were redox-independent. Interestingly, Stat3-C also upregulated the redox-associated protein redox factor-1 (Ref-1) and reduced apoptosis in liver following Jo2 injection by suppressing oxidative stress and redox-sensitive caspase-3 activity. These findings indicate that Stat3 activation protects against Fas-mediated liver injury by inhibiting caspase activities in redox-dependent and -independent mechanisms.

Hepatic reticuloendothelial system dysfunction after ischemia-reperfusion: Role of Rho-selectin-mediated neutrophil accumulation
N Sakamoto, ZL Sun, ML Brengman, K Maemura, M Ozaki, GB Bulkley, AS Klein
LIVER TRANSPLANTATION, 9, 9, 940, 948, W B SAUNDERS CO, 2003年09月, ［査読有り］
英語, 研究論文（学術雑誌）, The relationship between hepatic ischemia-reperfusion (I-R) and subsequent injury through neutrophil accumulation is well described. Although alterations in reticuloendothelial system (RES) function (specifically Kupffer cell function) after I-R have been delineated, the degree to which discrete components of RES function (phagocytosis and killing) are independently modulated under these conditions has not been quantified. A hepatic segmental I-R model was established in mice, in which blood supply to the left lateral lobe of the liver was occluded for 45 minutes, the liver was reperfused, and the laparotomy incision was closed. Experimental animals were pretreated with either vinblastin (1.5 mg/kg) to induce neutropenia or anti-P-selectin monoclonal antibody (mAb; 50 mug/mice) 4 days and 5 minutes before ischemia, respectively. We previously reported that after intravenous injection of chromium 51 (Cr-51) and iodine 125 (I-125) double-labeled Escherichia coli, hepatic Cr-51 levels could be used to reliably quantify hepatic phagocytic clearance (HPC) of bacteria from blood, whereas the subsequent release of 125(I) from the liver accurately paralleled hepatic bacterial killing efficiency (HKE). Using this double-label bacteria clearance assay, HPC and HKE were depressed after I-R, in association with hepatic neutrophil accumulation. Segmental I-R resulted in decreased HPC and HKE activity in both ischemic and nonischemic hepatic lobes. Depressions in HPC and HKE were attenuated by either vinblastin-induced neutropenia or blocking neutrophil adhesion to the hepatic endothelium with anti-P-selectin mAb. These findings support the hypothesis that I-R induces hepatic RES dysfunction, at least in part, through P-selectin-mediated neutrophil accumulation.

Inhibition of hypoxia/reoxygenation-induced oxidative stress in HGF-stimulated antiapoptotic siqnaling: role of P13-K and Akt kinase upon rac1
M Ozaki, S Haga, HQ Zhang, K Irani, S Suzuki
CELL DEATH AND DIFFERENTIATION, 10, 5, 508, 515, NATURE PUBLISHING GROUP, 2003年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Rac1-regulated reactive oxygen species (ROS) production has been implicated in apoptosis. In contrast, pleiotropic protein kinase At protects against apoptosis. However, the pro- and antiapoptotic mechanisms of rac1 and Akt, respectively, and the intersection between these mechanisms are incompletely understood. In a model of oxidative stress and apoptosis induced by hypoxia/reoxygenation (H/R) in primary hepatocytes, activation of the PI3-K Akt axis by the prosurvival hepatocyte growth factor (HGF) inhibited H/R-stimulated rac1 activation and intracellular ROS production, and suppressed apoptosis. Suppression of PI3-K or Akt activity abrogated the inhibitory effect of HGF on rac1 activity and rac1-regulated oxidative stress. Furthermore, constitutive activation of Akt or PI3-K in the absence of HGF was sufficient to phosphorylate rac1, inhibit rac1 activation, and suppress rac1-regulated ROS production. These findings demonstrate that growth factor-stimulated activation of PI3-K-Akt is necessary and sufficient to suppress intracellular oxidative stress and apoptosis by inhibiting activation of proapoptotic, prooxidative rac1 GTPase.

Tie-ing the antiinflammatory effect of angiopoietin-1 to inhibition of NF-kappa B
BH Jeon, F Khanday, S Deshpande, A Haile, M Ozaki, K Irani
CIRCULATION RESEARCH, 92, 6, 586, 588, LIPPINCOTT WILLIAMS & WILKINS, 2003年04月, ［査読有り］
英語

[Regenerative medicine in liver disease].
Ozaki M, Enosawa S, Suzuki S
Nihon rinsho. Japanese journal of clinical medicine, 61, 3, 498, 503, 2003年03月, ［査読有り］
日本語, In spite of dynamic increase of liver remnant mass after partial hepatectomy, liver regeneration is hard to induce under pathological condition. There are several approaches to achieve regenerative medicine for liver diseases, for instance, auxiliary partial orthotopic liver transplantation(APOLT), stem cell mobilization, and cytokine treatment. We propose here the fourth strategy, modification of intracellular signal transduction pathway. The regenerative cytokines, such as interleukin 6 and hepatocyte growth factor, drive several key molecules such as caspases, heat shock proteins, Bcl family, cyclin, etc, mediated by Stat molecules(signal transducers and activators of transcription). The transfection of constitutive active Stat3, which plays key roles in the signal cascade, resulted in similar cytological response to cytokine treatment. We describe possible strategy of liver regeneration from organ to molecular level.

Sanae Haga, Keita Terui, Hui Qi Zhang, Shin Enosawa, Wataru Ogawa, Hiroshi Inoue, Torayuki Okuyama, Kiyoshi Takeda, Shizuo Akira, Kaikobad Irani, Michitaka Ozaki:Stat3 protects against Fas-mediated liver injury in redox-dependent and -independent mecha・・・　　　　　　　　　　　　　　　
2003年
Sanae Haga, Keita Terui, Hui Qi Zhang, Shin Enosawa, Wataru Ogawa, Hiroshi Inoue, Torayuki Okuyama, Kiyoshi Takeda, Shizuo Akira, Kaikobad Irani, Michitaka Ozaki:Stat3 protects against Fas-mediated liver injury in redox-dependent and -independent mechanisms. J Clin Invest 112:989-998, 2003.

Byeong Hwa Jeon, Firdous Khanday, Shailesh Deshpande, Azeb Haile, Michitaka Ozaki, Kaikobad Irani: Tie-ing the antiinflammatory effect of antiopoietin-1 to inhibition of NF- B. Circ Res 92: 586-588, 2003.　　　　　　　　　　　　　　　
2003年

Michitaka Ozaki, Sanae Haga, Hui Qi Zhang, Kaikobad Irani, and Seiichi Suzuki. Inhibition of hypoxia/reoxygenation-induced and rac1-regulated oxidative stress in HGF-stimulated anti-apoptotic signaling: role of PI3-K and Akt kinase. Cell Death Differ 1・・・　　　　　　　　　　　　　　　
2003年
Michitaka Ozaki, Sanae Haga, Hui Qi Zhang, Kaikobad Irani, and Seiichi Suzuki. Inhibition of hypoxia/reoxygenation-induced and rac1-regulated oxidative stress in HGF-stimulated anti-apoptotic signaling: role of PI3-K and Akt kinase. Cell Death Differ 10: 508-515, 2003.

Sakamoto N, Sun Z, Brengman ML, Maemura K, Ozaki M, Bulkley GB, Klein AS: Hepatic reticuloendothelial system dysfunction after ischemia-reperfusion: role of P-selectin-mediated neutrophil accumulation. Liver Transplant 9(9): 940-8. 2003.　　　　　　　　　　　　　　　
2003年

Early infant kidneys as marginal donor sources: Histology and pathophysiology
T Kuroda, S Enosawa, M Endo, M Ozaki, N Morikawa, S Suzuki, H Amemiya
TRANSPLANTATION PROCEEDINGS, 34, 7, 2582, 2584, ELSEVIER SCIENCE INC, 2002年11月
英語, 研究論文（学術雑誌）

Overexpression of redox factor-1 protects against postischemic liver injury by reducing oxidative stress and NF-κB activity
Michitaka Ozaki, S. Haga, K. Irani, H. Amemiya, S. Suzuki
Transplantation Proceedings, 34, 7, 2640, 2642, 2002年11月
英語, 研究論文（国際会議プロシーディングス）

Overexpression of redox factor-1 protects against postischemic liver injury by reducing oxidative stress and NF-kappa B activity
M Ozaki, S Haga, K Irani, H Amemiya, S Suzuki
TRANSPLANTATION PROCEEDINGS, 34, 7, 2640, 2642, ELSEVIER SCIENCE INC, 2002年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Early infant kidneys as marginal donor sources: Histology and pathophysiology
T Kuroda, S Enosawa, M Endo, M Ozaki, N Morikawa, S Suzuki, H Amemiya
TRANSPLANTATION PROCEEDINGS, 34, 7, 2582, 2584, ELSEVIER SCIENCE INC, 2002年11月, ［査読有り］
英語, 研究論文（学術雑誌）

New strategy for preventing ischemia/reperfusion-induced organ injury and promoting regeneration: A novel trial for improving, transplant organ function by targeted regulation of cellular signals
M Ozaki
TRANSPLANTATION PROCEEDINGS, 34, 7, 2637, 2639, ELSEVIER SCIENCE INC, 2002年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Artificial mimicking of physiological active transport by a membrane co-cultured with two different cells: Hepatic origin HepG2 and renal origin PCTL-MDR
M Endo, S Enosawa, M Ozaki, S Tsuruoka, S Hiramatsu, K Kim, T Omasa, T Matsumura, T Aoki, Y Koyanagi, S Suzuki
ARTIFICIAL ORGANS, 26, 9, 806, 811, BLACKWELL PUBLISHING INC, 2002年09月, ［査読有り］
英語, 研究論文（学術雑誌）, We designed a membrane culture unit on which 2 different cell lines were co-cultured to achieve selective and active transport of toxins. Hepatic origin HepG2 and renal origin multidrug-resistant gene-transduced proximal convoluted tubular cell line (PCTL-MDR) were cultured on the opposite sides of an expanded polytetrafluoroethylene membrane. The activity of testosterone hydroxylation by original HepG2 was very low; however, the cytochrome P450 (CYP) 3A4-transduced recombinant HepG2 metabolized the substrate efficiently. Testosterone added into the outer medium was hydrolyzed by HepG2, and the metabolites were preferentially transported to the inner medium by PCTL-MDR. [H-3]-digoxin and [C-14]-inulin were added to the outer medium; the digoxin was transported from the outer to inner space through the cell monolayer but the inulin was not, suggesting that the membrane actively transported only the substrate of the channel protein, MDR. The cells were irradiated (10 Gy) to prevent a membrane leak due to overgrowth. The irradiation did not induce apoptosis but resulted in long-lasting membrane function without leakage. The membrane co-cultured with hepatic and renal origin cells will enable a novel hemofiltration system with selective and active transport activities.

Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis
P Angkeow, SS Deshpande, B Qi, YX Liu, YC Park, BH Jeon, M Ozaki, K Irani
CELL DEATH AND DIFFERENTIATION, 9, 7, 717, 725, NATURE PUBLISHING GROUP, 2002年07月, ［査読有り］
英語, 研究論文（学術雑誌）, The rac1 GTPase promotes oxidative stress through reactive oxygen species (ROS) production, whereas the DNA repair enzyme and transcriptional regulator redox factor-1 (ref-1) protects against cell death due to oxidative stimuli. However, the function of ref-1 in regulating intracellular oxidative stress, particularly that induced by rac1, has not been defined, We examined the role of ref-1 in vascular endothelial cell oxidative stress and apoptosis. Ref-1 was expressed in both the cytoplasm and nuclei of resting endothelial cells. Cytoplasmic ref-1 translocated to the nucleus with the oxidative trigger hypoxia/reoxygenation (H/R). Forced cytoplasmic overexpression of ref-1 suppressed H/R-induced oxidative stress (H2O2 production), NF-kappaB activation, and apoptosis, and also mitigated rac1-regulated H2O2 production and NF-kappaB transcriptional activity. We conclude that inhibition of oxidative stress is another mechanism by which ref-1 protects against apoptosis, and that this is achieved through modulation of cytoplasmic rac1-regulated ROS generation. This suggests a novel extra-nuclear function of ref-1.

Redox factor-1/APE suppresses oxidative stress by inhibiting activity of the rac1 GTPase
M Ozaki, S Suzuki, K Irani
FASEB JOURNAL, 16, 6, 889, +, FEDERATION AMER SOC EXP BIOL, 2002年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Oxidative stress triggered by many environmental and clinical insults results in cellular injury and death. The small GTPase rac1 promotes oxidative stress via the production of reactive oxygen species (ROS). In turn, the homeostatic response to such stress includes up-regulation of the dual function reducing protein/DNA repair enzyme APE/redox factor-1(ref-1). In this report we explore the function and relationship between ref-1 and rac1 in the setting of oxidative stress triggered by re-oxygenation/reperfusion. In a model of mouse hepatic ischemia/reperfusion (I/R), recombinant adenoviral overexpression of ref-1 resulted in suppression of reperfusion-stimulated oxidative stress, NF-kappaB induction, apoptosis, and acute injury, whereas down-regulation of endogenous ref-1 by adenoviral expression of antisense ref-1 led to an increase in these reperfusion-induced parameters. Ref-1 also mitigated ROS production induced by adenoviral expression of an active form of rac1. Finally, overexpression of ref-1 in primary hepatocytes suppressed reoxygenation-stimulated rac1 activity. This work demonstrates a novel function of ref-1 in inhibition of rac1 activity, and rac1-mediated oxidative stress and injury.

Michitaka Ozaki, Seiichi Suzuki, Kaikobad Irani. Redox factor-1/APE suppresses oxidative stress by inhibiting the rac1 GTPase. FASEB J 16: 889-890, 2002.　　　　　　　　　　　　　　　
2002年

レンチウイルスベクターをもちいたin vitroでの安定した遺伝子導入　　　　　　　　　　　　　　　
Organ Biology, 9, 285, 293, 2002年

P. Angkeow, S. Deshpande, B. Qi Y-X Liu, Y.C. Park, B. Jeon, M. Ozaki, K. Irani. Redox factor-1: An extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis. Cell Death Differ 9: 717-725, 2002.　　　　　　　　　　　　　　　
2002年

24. M.Ozaki: New Strategy For Preventing Ischemia / Reperfusion-Induced Organ Injury And Promoting Regeneration. - A Novel Trial For Improving Transplant Organ Function By Targeted Regulation Of Cellular Signals-. Transplant P 34: 2637-2639, 2002.　　　　　　　　　　　　　　　
2002年

Mitsufumi Endo, Shin Enosawa, Michitaka Ozaki, Shuichi Tsuruoka, Shinya Hiramatsu, Kazumi Kim, Takeshi Omasa, Toshiharu Matsumura, Tatsuya Aoki, Yasuhisa Koyanagi, Seiichi Suzuki. Artificial Mimicking of physiological active transport by a membrane co-・・・
Mitsufumi Endo, Shin Enosawa, Michitaka Ozaki, Shuichi Tsuruoka, Shinya Hiramatsu, Kazumi Kim, Takeshi Omasa, Toshiharu Matsumura, Tatsuya Aoki, Yasuhisa Koyanagi, Seiichi Suzuki
Artificial Organs, 26, 9, 806, 811, 2002年
英語, 研究論文（学術雑誌）, Mitsufumi Endo, Shin Enosawa, Michitaka Ozaki, Shuichi Tsuruoka, Shinya Hiramatsu, Kazumi Kim, Takeshi Omasa, Toshiharu Matsumura, Tatsuya Aoki, Yasuhisa Koyanagi, Seiichi Suzuki. Artificial Mimicking of physiological active transport by a membrane co-cultured with two different cells: hepatic origin HepG2 and renal origin PCTL-MDR. Artif Organs 26:806-811, 2002.

Targeted inhibition of the small GTPase protects against ischemia/reperfusion liver injury in mice
M Ozaki, S Deshpande, P Angkeow, J Bellan, CJ Lowenstein, MC Dinauer, P Goldschmidt-Clermont, S Suzuki, K Irani
TRANSPLANTATION PROCEEDINGS, 33, 1-2, 863, 864, ELSEVIER SCIENCE INC, 2001年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Ozaki M, Deshpande S, Angkeow P, Bellan J, Lowenstein CJ, Dinauer MC, Goldschmidt-Clermont P, Suzuki S and Irani K. Targeted inhibition of the small GTPase protects against ischemia/reperfusion liver injury in mice. Transplant P 33, 863-864. 2001.　　　　　　　　　　　　　　　
2001年

Rac1 regulates stress-induced, redox-dependent heat shock factor activation
M Ozaki, SS Deshpande, P Angkeow, S Suzuki, K Irani
JOURNAL OF BIOLOGICAL CHEMISTRY, 275, 45, 35377, 35383, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2000年11月, ［査読有り］
英語, 研究論文（学術雑誌）, The signaling pathway by which environmental stresses activate heat shock factors (HSFs) is not completely understood. We show that the small GTPase rad, and Rad-regulated reactive oxygen species (ROS) play an important role in stress-stimulated heat shock response. A dominant-negative allele of Rad (Rac1N17) inhibits the hypoxia/reoxygenation and sodium arsenite-induced transcriptional activity of HSF-1 and the transcription of heat shock protein 70. Rac1N17 also suppresses the production of intracellular ROS induced by hypoxia/reoxygenation or sodium arsenite. Moreover, direct suppression of intracellular ROS levels by antioxidants decreases stress-stimulated HSF activity. However, expression of a constitutively active mutant of Rad (Rac1V12) in the absence of extracellular stresses does not increase intracellular ROS levels or induce the heat shock response. These results show that Rad is a necessary but insufficient component of the stress-induced signaling pathway that leads to ROS production, activation of HSFs, and transcription of heat shock proteins.

cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors: potential role for nitrosylation
N Paolocci, UEG Ekelund, T Isoda, M Ozaki, K Vandegaer, D Georgakopoulos, RW Harrison, DA Kass, JM Hare
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 279, 4, H1982, H1988, AMER PHYSIOLOGICAL SOC, 2000年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Nitric oxide (NO) has concentration-dependent biphasic myocardial contractile effects. We tested the hypothesis, in isolated rat hearts, that NO cardiostimulation is primarily non-cGMP dependent. Infusion of 3-morpholinosydnonimine (SIN-1, 10(-5) M), which may participate in S-nitrosylation (S-NO) via peroxynitrite formation, increased the rate of left ventricular pressure rise (+dP/dt; 19 +/- 4%, P< 0.001, n = 11) without increasing effluent cGMP or cAMP. Superoxide dismutase (SOD; 150 U/ml) blocked SIN-1 cardiostimulation and led to cGMP elaboration. Sodium nitroprusside (10(-10)-10(-7) M), an iron nitrosyl compound, did not augment +dP/dt but increased cGMP approximately eightfold (P< 0.001), whereas diethylamine/ NO (DEA/NO; 10(-7) M), a spontaneous NO . donor, increased +dP/dt (5 +/- 2%, P< 0.05, n = 6) without augmenting cGMP. SIN-1 and DEA/NO +dP/dt increase persisted despite guanylyl cyclase inhibition with 1H-(1,2,4) oxadiazolo-( 4,3,-a) quinoxalin-1-one (10(-5) M, P< 0.05 for both donors), suggesting a cGMP-independent mechanism. Glutathione (5 x 10(-4) M, n = 15) prevented SIN-1 cardiostimulation, suggesting S-NO formation. SIN-1 also produced SOD-inhibitable cardiostimulation in vivo in mice. Thus peroxynitrite and NO donors can stimulate myocardial contractility independently of guanylyl cyclase activation, suggesting a role for S-NO reactions in NO/peroxynitrite-positive inotropic effects in intact hearts.

Rac1 inhibits TNF-alpha-induced endothelial cell apoptosis: dual regulation by reactive oxygen species
SS Deshpande, P Angkeow, JP Kuang, M Ozaki, K Irani
FASEB JOURNAL, 14, 12, 1705, 1714, FEDERATION AMER SOC EXP BIOL, 2000年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Reactive oxygen species (ROS) have been implicated as mediators of tumor necrosis factor-alpha (TNF) -induced apoptosis. In addition to leading to cell death, ROS can also promote cell growth and/or survival. We investigated these two roles of ROS in TNF-induced endothelial cell apoptosis. Human umbilical vein endothelial cells (HUVECs) stimulated with TNF produced an intracellular burst of ROS. Adenoviral-mediated gene transfer of a dominant negative form of the small GTPase Rad (Rac1N17) partially suppressed the TNF-induced oxidative burst without affecting TNF-induced mitochondrial ROS production. HUVECs were protected from TNF-induced apoptosis. Expression of Rac1N17 blocked TNF-induced activation of nuclear factor-kappa B (NF-kappa B), increased activity of caspase-3, and markedly augmented endothelial cell susceptibility to TNF-induced apoptosis. Direct inhibition of NF-kappa B through adenoviral expression of the super repressor form of inhibitor of kappa B alpha (I-kappa B S32/36A) also increased susceptibility of HUVECs to TNF-induced apoptosis. Rotenone, a mitochondrial electron transport chain inhibitor, suppressed TNF-induced mitochondrial ROS production, proteolytic cleavage of procaspase-3, and apoptosis. These findings show that Rad is an important regulator of TNF-induced ROS production in endothelial cells. Moreover, they suggest that Rad-dependent ROS, directly or indirectly, lead to protection against TNF-induced death, whereas mitochondrial-derived ROS promote TNF-induced apoptosis.

Inhibition of the Rac1 GTPase protects against nonlethal ischemia/reperfusion-induced necrosis and apoptosis in vivo
M Ozaki, SS Deshpande, P Angkeow, J Bellan, CJ Lowenstein, MC Dinauer, PJ Goldschmidt-Clermont, K Irani
FASEB JOURNAL, 14, 2, 418, 429, FEDERATION AMER SOC EXP BIOL, 2000年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Reperfusion of ischemic tissue results in the generation of reactive oxygen species that contribute to tissue injury. The sources of reactive oxygen species in reperfused tissue are not fully characterized. We hypothesized that the small GTPase Rac1 mediates the oxidative burst in reperfused tissue and thereby contributes to reperfusion injury. Zn an in vivo model of mouse hepatic ischemia/reperfusion injury, recombinant adenoviral expression of a dominant negative Rac1 (Rac1N17) completely suppressed the ischemia/reperfusion-induced production of reactive oxygen species and lipid peroxides, activation of nuclear factor-kappa B, and resulted in a significant reduction of acute liver necrosis, Expression of Rac1N17 also suppressed ischemia/reperfusion-induced acute apoptosis, The protection offered by Rac1N17 was also evident in knockout mice deficient for the gp91phox component of the phagocyte NADPH oxidase. This work demonstrates the crucial role of a Rac1-regulated oxidase in mediating the production of injurious reactive oxygen species, which contribute to acute necrotic and apoptotic cell death induced by ischemia/reperfusion in vivo. Targeted inhibition of this oxidase, which is distinct from the phagocyte NADPH oxidase, should provide a new avenue for in vivo therapy aimed at protecting organs at risk from ischemia/reperfusion injury.

Michitaka Ozaki, Shailesh S. Deshpande, Piamsook Angkeow, John Bellan, Charles J. Lowenstein, Mary C. Dinauer, Pascal J. Goldschmidt-Clermont and Kaikobad Irani: Inhibition of the Rac1 GTPase protects against non-lethal ischemia/reperfusion-induced nec・・・　　　　　　　　　　　　　　　
2000年
Michitaka Ozaki, Shailesh S. Deshpande, Piamsook Angkeow, John Bellan, Charles J. Lowenstein, Mary C. Dinauer, Pascal J. Goldschmidt-Clermont and Kaikobad Irani: Inhibition of the Rac1 GTPase protects against non-lethal ischemia/reperfusion-induced necrosis and apoptosis in vivo. FASEB J 14: 418-429, 2000.

N. Paolocci, U. E. G. Ekelund, T. Isoda, M. Ozaki, K. Vandegaer, D. Georgakopoulos, R. W. Harrison, D. A. Kass, and J. M. Hare. cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors: potential role for nitrosylation. Am J Physiol-・・・　　　　　　　　　　　　　　　
2000年
N. Paolocci, U. E. G. Ekelund, T. Isoda, M. Ozaki, K. Vandegaer, D. Georgakopoulos, R. W. Harrison, D. A. Kass, and J. M. Hare. cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors: potential role for nitrosylation. Am J Physiol-Heart C 279: H1982-H1988, 2000.

Michitaka Ozaki, Piamsook Angkeow, Shailesh S. Deshpande, Seiichi Suzuki and Kaikobad Irani: Rac1 regulates stress-induced, redox-dependent heat shock factor activation. J Biol Chem 275: 35377-35383, 2000.　　　　　　　　　　　　　　　
2000年

Shailesh S. Deshpande, Piamsook Angkeow, Jianping Huang, Michitaka Ozaki, and Kaikobad Irani: Rac1 Inhibits TNF- -Induced Endothelial Cell Apoptosis: Dual Regulation by Reactive Oxygen Species. FASEB J 14, 1705-1714, 2000.　　　　　　　　　　　　　　　
2000年

肝不全の外科　　　　　　　　　　　　　　　
2000年

Expression of Id1 results in apoptosis of cardiac myocytes through a redox-dependent mechanism
K Tanaka, JB Pracyk, K Takeda, ZX Yu, VJ Ferrans, SS Deshpande, M Ozaki, PM Hwang, CJ Lowenstein, K Irani, T Finkel
JOURNAL OF BIOLOGICAL CHEMISTRY, 273, 40, 25922, 25928, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 1998年10月, ［査読有り］
英語, 研究論文（学術雑誌）, We have constructed a recombinant adenovirus (Ad.Id1) that allows for efficient expression of the helix-loop-helix protein Idl, After infection with Ad.Id1, neonatal cardiac myocytes display a significant reduction in viability, which was proportional to the level of Idl expression, A similar effect was observed in adult myocytes, Morphological and biochemical assays demonstrated that Id1 expression resulted in myocyte apoptosis. In contrast, expression of Idl in endothelial cells, vascular smooth muscle cells, or fibroblasts did not affect the viability of these cells, Along with the induction of apoptosis, the expression of Idl in neonatal cardiac myocytes resulted in an increase in the level of intracellular reactive oxygen species. The source of these reactive oxygen species appears to be the mitochondria, Reducing the ambient oxygen concentration or treatment with a cell-permeant H2O2 scavenger prevented Id1-stimulated apoptosis in cardiac myocytes, These results suggest that the expression of Idl leads to the induction of apoptosis in cardiac myocytes through a redox-dependent mechanism.

Koichi Tanaka, John D.Pracyk, Kazuyo Takeda, Zu-Xi Yu, Victor J.Ferrans, Shailesh S.Deshpande, Michitaka Ozaki, Paul M.Hwang, Charles J.Lowenstein, Kaikobad Irani, Toren Finkel: Expression of Id1 results in apoptosis of cardiac myocytes through a redox・・・　　　　　　　　　　　　　　　
1998年
Koichi Tanaka, John D.Pracyk, Kazuyo Takeda, Zu-Xi Yu, Victor J.Ferrans, Shailesh S.Deshpande, Michitaka Ozaki, Paul M.Hwang, Charles J.Lowenstein, Kaikobad Irani, Toren Finkel: Expression of Id1 results in apoptosis of cardiac myocytes through a redox-dependent mechanism. J Biol Chem 273: 25922-25928, 1998.

Ascorbic acid prevents ischemia-reperfusion injury in the rat small intestine
Michio Nakamura, Michitaka Ozaki, Shohei Fuchinoue, Satoshi Teraoka, Kazuo Ota
Transplant International, 10, 2, 89, 95, 1997年03月
英語, 研究論文（学術雑誌）, Ischemia-reperfusion injury by free radicals and lipid peroxides is observed in various organs. Ascorbic acid (AsA) or glutathione (GSH) invarious doses (AsA:2, 0.5, 0.1 mmol/kg, GSH:2 mmol/kg) was intraperitoneally administered to male Wistar rats. The entire small intestines were resected just before ischemia, after ischemia, and after 20 min of reperfusion (n = 7-10 at each time point). At each time point, the specimens were subjected to assays of lipid peroxides, GSH, and glutaminase activity of the tissues
they were also examined histologically. In the AsA group, the production of lipid peroxides after reperfusion was significantly suppressed in a dose-dependent manner, and the ratio of oxidized GSH to total GSH was also significantly low. Tissue glutaminase activity decreased to a lesser extent, and the degree of injury was apparently less marked in the AsA group. This study indicates that AsA acts as an antioxidant against peroxidative tissue injury, possibly by scavenging radicals, preserving reduced GSH, and reducing the peroxidative reaction.

Ascorbic acid prevents ischemia-reperfusion injury in the rat small intestine
M Nakamura, M Ozaki, S Fuchinoue, S Teraoka, K Ota
TRANSPLANT INTERNATIONAL, 10, 2, 89, 95, SPRINGER VERLAG, 1997年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Ischemia-reperfusion injury by free radicals and lipid peroxides is observed in various organs. Ascorbic acid (AsA) or glutathione (GSH) in various doses (AsA:2, 0.5, 0.1 mmol/kg, GSH:2 mmol/kg) was intraperitoneally administered to male Wistar rats. The entire small intestines were resected just before ischemia, after ischemia, and after 20 min of reperfusion (n = 7-10 at each time point). At each time point, the specimens were subjected to assays of lipid peroxides, GSH, and glutaminase activity of the tissues; they were also examined histologically. In the AsA group, the production of lipid peroxides after reperfusion was significantly suppressed in a dose-dependent manner. and the ratio of oxidized GSH to total GSH was also significantly low. Tissue glutaminase activity decreased to a lesser extent, and the degree of in jury was apparently less marked in the AsA group. This study indicates that AsA acts as an antioxidant against peroxidative tissue injury, possibly by scavenging radicals, preserving reduced GSH, and reducing the peroxidative reaction.

Ebselen, a novel anti-oxidant compound, protects the rat liver from ischemia-reperfusion injury
M Ozaki, M Nakamura, S Teraoka, K Ota
TRANSPLANT INTERNATIONAL, 10, 2, 96, 102, SPRINGER VERLAG, 1997年03月, ［査読有り］
英語, 研究論文（学術雑誌）, The present study was designed to examine the in vivo effect of ebselen on reperfusion injury to the liver. Lipid peroxidation and glutathione (GSH) levels of the reperfused liver tissue, as well as hepatocellular damage (serum GOT, GPT, LDH: and histology) were examined. The production of thiobarbituric acid-reactive substance did not increase in the 60-min-reperfused liver tissue in the ebselen group. Ebselen completely suppressed the increase in lipid hydroperoxide production in the reperfused liver tissue. After the tissue GSH level was reduced by buthionine sulphoximine. ebselen failed to suppress the lipid peroxidation of the reperfused liver tissue. Serum levels of GOT CPT, and LDI-I, histological analysis, and the tissue level of GSH clearly showed that ebselen protects the reperfused liver tissue, both structurally and functionally, We conclude that ebselen's primary effect on ischemia-reperfusion injury may be due to a GSH-peroxidase-like effect and/or the inhibitor effect of leukocyte infiltration.

Michitaka Ozaki, Michio Nakamura, Satoshi Teraoka, Kazuo Ota: Ebselen, a novel anti-oxidant compound, protects against the hepatic ischemia-reoxygenation injury of the rats. Transplant Int 10:96-102, 1997.　　　　　　　　　　　　　　　
1997年

Preventive effects of ascorbic acid on the ischemia/reoxygenation injury in the rat small intestine.
Michio Nakamura, Michitaka Ozaki, Shohei Fuchinoue, Satoshi Teraoka, Kazuo Ota
Journal of Tokyo Women’s Medical College, 66, 11, 898, 907, 東京女子医科大学学会, 1996年, ［査読有り］
英語, 様々の臓器における虚血後再酸素化(ischemia/reoxygenation; I/R)時の細胞や機能の傷害は,発生する種々のフリーラジカルや,過酸化脂質によると考えられている.一方,アスコルビン酸(AsA)は,低濃度では過酸化を促進し,高濃度では逆に抑制することが知られている.ラット小腸においてI/R時の傷害の程度とAsAによる傷害抑制効果について生化学的,病理学的に検討した.AsAとグルタチオン(GSH)を,雄性Wistar系ラットに腹腔内投与し,60分後開腹,上腸間膜動脈を遮断し,全小腸を60分間虚血状態とした.再酸素化後20分で,全小腸を摘出して検索し,以下の結果をえた.AsA投与群では,過酸化脂質の産生は,有意に抑制され(LOOH Control: 26.30±1.98, AsA: 16.75±1.43 nmol/g tissue, p<0.01),また,glutaminase活性は,再酸素化後も有意に高く保たれ(Control: 0.41±0.04, AsA: 1.02±0.05μmol glutamate/h/mg tissue, p<0.05),組織傷害も軽微であった.また,還元型GSHレベルは,再酸素化後も高値に保たれた(Control:0.22±0.02, AsA:1.34±0.12μmol/g tissue, p<0.01).AsAは,ラット小腸において抗酸化剤として作用し,I/R傷害を軽減させることが明らかとなった.Ischemia/reoxygenation (I/R) injury is observed in various organs, where some free radicals and lipid peroxides are believed to play an important role. We examined the preventive effects of ascorbic acid (AsA), one of antioxidant agents, on the I/R injury of the rat small intestine. AsA or glutathione was intraperitoneally administered to male Wistar rats weighing 250～300 g after one-day fasting. The entire small intestine was resected at three different points, just before ischemia, after ischemia, and after 20 min of reoxygenation. The specimens were used for the assays of lipid peroxides, glutathione, and glutaminase activity and for histological examination. In AsA-treated group, the production of lipid peroxides after reoxygenation was significantly suppressed and the ratio of reduced form of glutathione to the total glutathione was also significantly high. Tissue glutaminase activity decreased to less extent, and the degree of injury by reoxygenation was apparently less marked in this AsA-treated group. AsA works as an antioxidant against the peroxidative tissue injury possibly by scavenging free radicals and reducing the peroxidative reaction. The effects of AsA are expected to be very useful in small bowel transplantation and various surgical procedures.

Donor criteria and technical aspects of procurement in combined pancreas and kidney transplantation from non-heart-beating cadavers
S Teraoka, T Babazono, O Tomonaga, S Sato, M Nakamura, H Ishida, T Hoshino, T Koike, M Abe, M Shinkai, H Haruguchi, S Hirotani, K Kitajima, M Akamatsu, M Ozaki, S Fujita, Y Nakagawa, Nakajima, I, T Kawai, S Fuchinoue, H Ohgawara, Y Ohmori, K Ota
TRANSPLANTATION PROCEEDINGS, 27, 6, 3097, 3100, APPLETON & LANGE, 1995年12月, ［査読有り］
英語, 研究論文（学術雑誌）

THE IN-VIVO CYTOPROTECTION OF ASCORBIC-ACID AGAINST ISCHEMIA REOXYGENATION INJURY OF RAT-LIVER
M OZAKI, S FUCHINOUE, S TERAOKA, K OTA
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 318, 2, 439, 445, ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS, 1995年04月, ［査読有り］
英語, 研究論文（学術雑誌）, The in vivo effects of ascorbic acid on the reoxygenated liver tissue were examined, with regard to the following effects: (i) the effects of scavenging radicals and/or reducing peroxidative reactions, and (ii) the effects of the chelation with low-molecular-weight iron and increasing its reactivity (radical production). Ascorbic acid is one of the water-soluble vitamins known to have various physiological effects involving both chelating and reducing properties at once. Lipid peroxidation of the reoxygenated liver tissue estimated by the production of TEARS (thiobarbituric acid-reactive substance) and LPO (lipid hydroperoxides) was suppressed effectively by the preischemic intraperitoneal administration of ascorbic acid. Ascorbic acid also showed this anti-oxidant effect in a dose-dependent manner. The analysis of the levels of ascorbic acid and glutathione of the liver tissue revealed that ascorbic acid works as an anti-oxidant probably by being oxydized finally to dehydroascorbic acid just after the reoxygenation. The latter was reduced to ascorbic acid again, coupled with the conversion of GSH to GSSG in the postischemic time course. The predominant effect of ascorbic acid on the reoxygenated liver tissue seems to be caused by the scavenging radicals and/or reducing peroxidative reactions, rather than by chelating iron and increasing its reactivity (radical production). Cellular integrity (estimated by the release of GOT, GPT, and LDH) and the energy state of the postischemic liver tissue (estimated by the tissue ATP level) were also well preserved by the administration of ascorbic acid. (C) 1995 Academic Press, Inc.

EFFECT OF RESCUE THERAPY USING FK-506 ON RELAPSING REJECTION AFTER COMBINED PANCREAS AND KIDNEY-TRANSPLANTATION
S TERAOKA, T BABAZONO, T KOIKE, M ABE, M KIMIKAWA, M SHINKAI, H HARUGUCHI, S HIROTANI, K KITAJIMA, M AKAMATSU, M OZAKI, S FUJITA, NAKAJIMA, I, T KAWAI, S FUCHINOUE, K OTA, O TOMONAGA, K YANO, Y TASAKA, Y OMORI
TRANSPLANTATION PROCEEDINGS, 27, 1, 1335, 1339, APPLETON & LANGE, 1995年02月, ［査読有り］
英語, 研究論文（学術雑誌）

S. Teraoka, T. Babazono, T.Koike, M.Abe, M.Kimikawa, M.Shinkai, H.Haruguchi, S.Hirotani, K.Kitajima, M.Akamatsu, M.Ozaki, S.Fujita, I.Nakagawa, T.Kawai, S.Fuchinoue, K.Ota, O.Tomonaga, K.Yano, Y.Tasaka and Y.Omori: Effect of rescue therapy using FK506 ・・・　　　　　　　　　　　　　　　
1995年
S. Teraoka, T. Babazono, T.Koike, M.Abe, M.Kimikawa, M.Shinkai, H.Haruguchi, S.Hirotani, K.Kitajima, M.Akamatsu, M.Ozaki, S.Fujita, I.Nakagawa, T.Kawai, S.Fuchinoue, K.Ota, O.Tomonaga, K.Yano, Y.Tasaka and Y.Omori: Effect of rescue therapy using FK506 on relapsing rejection after combined pancreas and kidney transplantation. Transplant P 27: 1335-1339, 1995.

Ozaki M, Fuchinoue S, Teraoka S, Ota K: The in vivo cytoprotection of ascorbic acid on the ischemia/reoxygenation injury of rat liver. Arch Biochem Biophys 318: 439-445, 1995.　　　　　　　　　　　　　　　
1995年

Protective effects of glycine and esterified γ-glutamylcysteine on ischemia/reoxygenation injury of rat liver
Michitaka Ozaki, Hisashi Ozasa, Shouhei Fuchinoue, Satoshi Teraoka, Kazuo Ota
Transplantation, 58, 6, 753, 755, 1994年09月27日
英語

PROTECTIVE EFFECTS OF GLYCINE AND ESTERIFIED GAMMA-GLUTAMYLCYSTEINE ON ISCHEMIA REOXYGENATION INJURY OF RAT-LIVER
M OZAKI, H OZASA, S FUCHINOUE, S TERAOKA, K OTA
TRANSPLANTATION, 58, 6, 753, 755, WILLIAMS & WILKINS, 1994年09月, ［査読有り］
英語

Mobilization ｏｆ low‐molecular‐weight iron and peroxidative damage during Ischemia and reoxygenation of the rat-liver.
Michitaka Ozaki, Shohei Fuchinoue, Satoshi Teraoka, Kazuo Ota
Transplantation Proceedings, 26, 2, 918, 921, ELSEVIER SCIENCE INC, 1994年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Michitaka Ozaki, Shohei Fuchinoue, Satoshi Teraoka, Kazuo Ota: Effects of deferrioxamine on lipid peroxidation of reoxygenated rat liver. Transplant P 26: 918-921, 1994.　　　　　　　　　　　　　　　
1994年

IRON RELEASE FROM HEMOSIDERIN AND PRODUCTION OF IRON-CATALYZED HYDROXYL RADICALS INVITRO
M OZAKI, T KAWABATA, M AWAI
BIOCHEMICAL JOURNAL, 250, 2, 589, 595, PORTLAND PRESS, 1988年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Michitaka Ozaki, Teruyuki Kawabata, Michiyasu Awai: Iron release from haemosiderin and production of iron catalysed hydroxyl radical in vitro. Biochem J 250: 589-595, 1988.　　　　　　　　　　　　　　　
1988年

CHARACTERISTICS OF HISTIOCYTIC LESIONS IN THE RETICULOENDOTHELIAL SYSTEM OF NZB MICE
Y SADAHIRA, M MORI, M OZAKI, M AWAI
ACTA PATHOLOGICA JAPONICA, 37, 11, 1719, 1729, BLACKWELL SCIENCE, 1987年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Yoshito Sadahira, Masayasu Mori, Michitaka Ozaki, Michiyasu Awai: Characteristics of histiocytic lesions in the reticuloendothelial system of NZB mice. Acta Pathologica Japonica 37: 1719-1729, 1987.　　　　　　　　　　　　　　　
1987年

肺結核症経過中皮膚の硬結性紅斑とImmunoblastic Lymphoadinopathy(Lukes)様リンパ節腫脹を続発した一剖検例　　　　　　　　　　　　　　　
倉敷中央病院年報(Ann Kurashiki Cent Hospital), 56, 27, 43, 1987年

Angioimmunoblastic Lymphadenopathy with Dysproteinemia(AILD)の組織像で発症したAdult T-cell Lynphoma-Leukemia(ATLL)の一剖検例　　　　　　　　　　　　　　　
倉敷中央病院年報(Ann Kurashiki Cent Hospital), 56, 91, 102, 1987年

Inhibition of cellular and animal inflammatory disease models by nf-κb inhibitor dhmeq
Jun Ma, Yuyang Zhang, Takeshi Sugai, Tetsuo Kubota, Hiroshi Keino, Magdy El-Salhy, Michitaka Ozaki, Kazuo Umezawa, Cells, 10, 9, 2021年09月01日
General inflammatory diseases include skin inflammation, rheumatoid arthritis, inflammatory bowel diseases, sepsis, arteriosclerosis, and asthma. Although these diseases have been extensively studied, most of them are still difficult to treat. Meanwhile, NF-κB is a transcription factor promoting the expression of many inflammatory mediators. NF-κB is likely to be involved in the mechanism of most inflammatory diseases. We discovered a specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), about 20 years ago by molecular design from a natural product. It directly binds to and inactivates NF-κB components. It has been widely used to suppress cellular and animal inflammatory disease models and was shown to be potent in vivo anti-inflammatory activity without any toxicity. We have prepared ointment of DHMEQ for the treatment of severe skin inflammation. It inhibited inflammatory cytokine expressions and lowered the clinical score in mouse models of atopic dermatitis. Intraperitoneal (IP) administration of DHMEQ ameliorated various disease models of inflammation, such as rheumatoid arthritis, sepsis, and also graft rejection. It has been suggested that inflammatory cells in the peritoneal cavity would be important for most peripheral inflammation. In the present review, we describe the synthesis, mechanism of action, and cellular and in vivo anti-inflammatory activities and discuss the clinical use of DHMEQ for inflammatory diseases., MDPI, 英語, 書評論文,書評,文献紹介等

17型コラーゲンは加齢による表皮の過増殖を抑制する　　　　　　　　　　　　　　　
渡邉 美佳, 夏賀 健, 西江 渉, 藤村 悠, 氏家 英之, 尾崎 倫孝, 清水 宏, 日本皮膚科学会雑誌, 128, 4, 607, 607, 2018年04月
(公社)日本皮膚科学会, 日本語

Regulatory action of toll-like receptor 2 in a non-alcoholic steatohepatitis mouse model
Min Yi, Masashi Kohanawa, Sanae Haga, Michitaka Ozaki, CYTOKINE, 100, 106, 106, 2017年12月
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 英語, 研究発表ペーパー・要旨（国際会議）

LC‐MS/MSを用いた血中チオ硫酸塩測定法の検討
神繁樹, 的場光太郎, 兵頭秀樹, 芳賀早苗, 尾崎倫孝, 質量分析総合討論会講演要旨集, 64th, 196, 2016年05月09日
日本語

Development of a New In Vivo Optical Probe for Biological Diagnosis and Therapy
Ozaki M, Ozawa T, Yamada Y, Nakao K, Minato N, Uemoto S, 2015年, ［査読有り］

PD-1-1 光を応用した移植細胞機能・細胞環境のモニタリングと制御の試み(PD-1 パネルディスカッション(1)細胞・臓器移植における基礎的研究の最前線,第114回日本外科学会定期学術集会)
尾崎 倫孝, 芳賀 早苗, 野田 なつみ, 森田 直樹, 山田 勇磨, 小澤 岳昌, 日本外科学会雑誌, 115, 2, 168, 168, 2014年03月05日
一般社団法人日本外科学会, 日本語

光学技術を応用した新たな臓器保存法、細胞・臓器移植法の開発.
尾崎倫孝, 芳賀早苗, 森田直樹, 野田なつみ, 小澤岳昌, Organ Biology, 21, 2, 171, 176, 2014年, ［査読有り］
In order to develop an effective organ/cell preservation method and to monitor/control post-transplant graft function continuously and non-invasively, an innovative optic technology to visualize/control cell/organ function seems to be useful. Recently, we have developed molecular probes to visualize redox states and cellular stresses, pH and cellular antigens in deeper lesions of the organ, and trying to activate intracellular key molecules by optical irradiation. In the hepatic ischemia/reperfusion model of mice, we successfully imaged liver oxidative stress and apoptosis by caspase-3 activity non-invasively and chronologically in a single mouse. We also developed a unique tool for visualizing intracellular pH and succeeded in imaging dynamic changes of pH in a mouse posterior limb ischemia/reperfusion model. Furthermore, we are now developing new tools to control intracellular molecules by blue light. We used plant-derived proteins to activate Akt/PKB molecule, essential for cell survival. By irradiating blue light, Akt in hepatocytes were phosphorylated(Ser and Thr)and activated. These tools will definitely provide a new avenue toward cell/organ transplantation in the future., 一般社団法人 日本臓器保存生物医学会, 日本語

死細胞誘導シグナルの可視化 (第1土曜特集 細胞死Update : 基礎から臨床までを俯瞰して) -- (多様な細胞死の実態)
小澤 岳昌, 尾崎 倫孝, 医学のあゆみ, 246, 5, 357, 363, 2013年08月03日
医歯薬出版, 日本語

A Method for Intravital Monitoring of Human Cells Using a Far-Red Luminescent Probe in Graft-Versus-Host Disease Model Mice (vol 133, pg 841, 2013)
Hongjiang Qiao, Riichiro Abe, Nao Saito, Yasuyuki Fujita, Inkin Hayashi-Ujiie, Gang Wang, Sanae Haga, Chun Wu, Yoshihiro Ohmiya, Michitaka Ozaki, Hiroshi Shimizu, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 133, 6, 1692, 1692, 2013年06月
NATURE PUBLISHING GROUP, 英語, その他

Bioluminescent imaging of hepatic caspase-3 activity in mice
Michitaka Ozaki, Sanae Haga, Takeaki Ozawa, FASEB JOURNAL, 27, 2013年04月
FEDERATION AMER SOC EXP BIOL, 英語, 研究発表ペーパー・要旨（国際会議）

PD-4-1 肝再生における分子メカニズムの解析(PD パネルディスカッション,第113回日本外科学会定期学術集会)
尾崎 倫孝, 芳賀 早苗, 井上 啓, 小川 渉, 小澤 岳彗, 日本外科学会雑誌, 114, 2, 236, 236, 2013年03月05日
一般社団法人日本外科学会, 日本語

細胞死誘導シグナルの　　　　　　　　　　　　　　　
2013年

カスパーゼ3活性化プローブによる肝傷害の生体イメージング
尾崎 倫孝, 芳賀 早苗, 小澤 岳昌, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 6, 253, 253, 2012年11月01日
日本語

SF-035-6 マージナル膵島移植におけるCD40-CD154副刺激経路遮断の効果(SF-035 サージカルフォーラム(35)膵 膵島移植,第112回日本外科学会定期学術集会)
腰塚 靖之, 山下 健一郎, 渡辺 正明, 蔵谷 大輔, 小倉 正臣, 吉田 雅, 蒲池 浩文, 松下 道明, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 113, 2, 332, 332, 2012年03月05日
一般社団法人日本外科学会, 日本語

SF-089-5 大腸癌の骨髄微小転移同定のpilot study : 病理組織学的因子との関係(SF-089 サージカルフォーラム(89)大腸 基礎-2(浸潤・転移),第112回日本外科学会定期学術集会)
崎浜 秀康, 小林 希, 下國 達志, 本間 重紀, 高橋 典彦, 片岡 昭彦, 神山 俊哉, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 113, 2, 2012年03月05日
一般社団法人日本外科学会, 日本語

SF-101-4 低温酸素化灌流による臓器修復は可能か? : ミトコンドリア機能と細胞内Ca2+の制御(SF-101 サージカルフォーラム(101)侵襲・再生,第112回日本外科学会定期学術集会)
深井 原, 若山 顕治, 山下 健一郎, 廣方 玄太郎, 谷口 雅彦, 古川 博之, 島田 慎吾, 小倉 正臣, 鈴木 友己, 嶋村 剛, 尾崎 倫孝, 神山 俊哉, 藤堂 省, 日本外科学会雑誌, 113, 臨時増刊号_2, 422, 422, 2012年03月05日
一般社団法人日本外科学会, 日本語

PS-144-5 マウス肝虚血再灌流モデルにおける硫化水素の肝保護効果(PS-144 肝 基礎-3,ポスターセッション,第112回日本外科学会定期学術集会)
島田 慎吾, 深井 原, 山下 健一郎, 鈴木 友己, 嶋村 剛, 尾崎 倫孝, 神山 俊哉, 藤堂 省, 日本外科学会雑誌, 113, 臨時増刊号_2, 779, 779, 2012年03月05日
一般社団法人日本外科学会, 日本語

胆管癌におけるMesothelin発現の免疫組織学的検討
川俣太, 蒲池浩文, 西原広史, 永生高広, 本間重紀, 宮崎将也, 田原宗徳, 尾崎倫孝, 松野吉宏, 神山俊哉, 藤堂省, 日本外科学会雑誌, 113, 臨増2, 389, 389, 2012年03月05日
(一社)日本外科学会, 日本語, その他

生体イメージング法による細胞・臓器のリアルタイム評価法の開発
芳賀 早苗, 尾崎 倫孝, Organ Biology, 19, 1, 29, 35, 2012年
The organ function and its regulatory mechanisms which are affected by various physiopathological conditions have been analyzed by molecular and biochemical methods. We have been working on developing various optical probes to visualize cellular and organ conditions/functions in vivo. An innovative technology is essential for imaging the biological functions, especially by using bioluminescence；for example, a novel highly transmittable and sensitive optic probe. We have, so far, developed some novel probes based on the unique bioluminescence theories. By applying these probes for biological systems, we succeeded to visualize the dynamic changes of liver injury and oxidative stress in mouse liver ischemia/reperfusion model by the caspase-3 activity probe and redox sensitive GFP probe, respectively. These novel bio-imaging techniques will definitely bring great possibility and potential impact for research and clinical medicine in the future., The Japan Society for Organ Preservation and Biology, 日本語

消化器癌に対する分子生物学の臨床応用(下部消化管) 大腸癌の循環腫瘍細胞同定を規定する因子　　　　　　　　　　　　　　　
崎浜 秀康, 小林 希, 藤好 真人, 下國 達志, 本間 重紀, 高橋 典彦, 片岡 昭彦, 尾崎 倫孝, 藤堂 省, 日本消化器外科学会総会, 66回, 269, 269, 2011年07月
(一社)日本消化器外科学会, 日本語

胃癌におけるMesothelin発現の免疫組織学的検討　　　　　　　　　　　　　　　
永生 高広, 本間 重紀, 蒲池 浩文, 西原 広史, 高橋 典彦, 片岡 昭彦, 神山 俊哉, 松野 吉宏, 尾崎 倫孝, 藤堂 省, 日本消化器外科学会総会, 66回, 458, 458, 2011年07月
(一社)日本消化器外科学会, 日本語

SF-002-5 新規化合物DTCM-Gを用いたマウス慢性拒絶反応抑制効果の検討(SF-002 サージカルフォーラム(2)移植-1,第111回日本外科学会定期学術集会)
財津 雅昭, 山下 健一郎, 柴崎 晋, 常俊 雄介, 若山 顕治, 廣方 玄太郎, 五十嵐 留美, 小林 希, 尾崎 倫孝, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 112, 1, 2011年05月25日
一般社団法人日本外科学会, 日本語

SF-003-2 新規化合物DTCM-Gの免疫抑制効果ならびにDSTとの併用効果の検討(SF-003 サージカルフォーラム(3)移植-2,第111回日本外科学会定期学術集会)
常俊 雄介, 山下 健一郎, 柴崎 晋, 後藤 了一, 若山 顕治, 廣方 玄太郎, 財津 雅昭, 五十嵐 瑠美, 尾崎 倫孝, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 112, 1, 2011年05月25日
一般社団法人日本外科学会, 日本語

PS-019-3 炎症性腸疾患モデルにおける新規化合物DTCM-Gの腸炎抑制効果に関する検討(PS-019 ポスターセッション(19)大腸:良性-4,第111回日本外科学会定期学術集会)
市川 伸樹, 山下 健一郎, 船越 徹, 吉田 雅, 小林 希, 腰塚 靖之, 財津 雅昭, 柴崎 晋, 常俊 雄介, 小倉 正臣, 深井 原, 市原 真, 尾崎 倫孝, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 112, 1, 2011年05月25日
一般社団法人日本外科学会, 日本語

PS-142-2 マウス同種膵島移植における新規AP-1阻害剤T-5224の免疫抑制効果(PS-142 ポスターセッション(142)膵臓:移植,第111回日本外科学会定期学術集会)
吉田 雅, 山下 健一郎, 渡辺 正明, 腰塚 靖之, 蔵谷 大輔, 小倉 正臣, 後藤 了一, 若山 顕治, 柴崎 晋, 蒲池 浩文, 尾崎 倫孝, 松下 通明, 藤堂 省, 日本外科学会雑誌, 112, 1, 751, 751, 2011年05月25日
一般社団法人日本外科学会, 日本語

PS-071-5 新規薬剤DTCM-Gの免疫抑制効果に関する検討(PS-071 ポスターセッション(71)移植,第111回日本外科学会定期学術集会)
柴崎 晋, 山下 健一郎, 後藤 了一, 若山 顕治, 常俊 雄介, 財津 雅昭, 五十嵐 瑠美, 芳賀 早苗, 尾崎 倫孝, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 112, 1, 627, 627, 2011年05月25日
一般社団法人日本外科学会, 日本語

SF-003-5 新規臓器保存液(FJ液)による肝冷保存再灌流障害の軽減 : FJ液の重要な成分(SF-003 サージカルフォーラム(3)移植-2,第111回日本外科学会定期学術集会)
旭 火華, 深井 原, 福森 大介, 若山 顕治, 山下 健一郎, 廣方 玄太郎, 芳賀 早苗, 田原 宗徳, 谷口 雅彦, 嶋村 剛, 鈴木 友己, 松下 通明, 古川 博之, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 112, 臨時増刊号_1・2, 340, 340, 2011年05月25日
一般社団法人日本外科学会, 日本語

PS-071-7 低温下で好気代謝を促進する新規臓器保存液の至適条件 : 低温酸素化灌流保存法への応用を目指した基礎的検討(PS-071 ポスターセッション(71)移植,第111回日本外科学会定期学術集会)
深井 原, 若山 顕治, 山下 健一郎, 福森 大介, 廣方 玄太郎, 芳賀 早苗, 谷口 雅彦, 嶋村 剛, 鈴木 友己, 尾崎 倫孝, 松下 通明, 古川 博之, 藤堂 省, 日本外科学会雑誌, 112, 臨時増刊号_1・2, 628, 628, 2011年05月25日
一般社団法人日本外科学会, 日本語

PS-118-2 ラット心冷保存同種異所性移植モデルにおける心エコーによる長期にわたる継続的な心機能の評価(PS-118 ポスターセッション(118)心臓:基礎,第111回日本外科学会定期学術集会)
若山 顕治, 深井 原, 山下 健一郎, 廣方 玄太郎, 福森 大介, 旭 火華, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 112, 臨時増刊号_1・2, 708, 708, 2011年05月25日
一般社団法人日本外科学会, 日本語

移植臓器の非侵襲的モニタリング法の開発
尾崎 倫孝, 芳賀 早苗, 森田 直樹, 深井 原, 藤堂 省, 小澤 岳昌, 近江谷 克裕, Organ Biology, 18, 1, 134, 140, 2011年
In order to develop an effective organ/cell preservation solution and to monitor graft function continuously and non-invasively, an innovative imaging technology to visualize cell/organ function is required. Recently, we developed molecular probes to visualize redox states and cellular stresses,and cellular antigens in deeper lesions of the organ. In the hepatic ischemia/reperfusion model of mice, we successfully imaged liver oxidative stress and apoptosis(by caspase-3 activity)noninvasively and chronologically in a single mouse. We are also trying to develop new tools to visualize ER stress and cellular antigens in deeper lesions. These tools will definitely provide a new avenue toward cell/organ transplantation in the future., The Japan Society for Organ Preservation and Biology, 日本語

MW8-3 アレルギー性気道炎症モデルにおけるDHMEQの効果(MW8 動物モデルを用いた喘息病態と治療法開発,ミニワークショップ,第60回日本アレルギー学会秋季学術大会)
清水 健一, 今野 哲, 清水 薫子, 谷口 菜津子, 伊佐田 朗, 高橋 歩, 服部 健史, 梅澤 一夫, 尾崎 倫孝, 藤堂 省, 西村 正治, アレルギー, 59, 9, 1352, 1352, 2010年10月30日
一般社団法人日本アレルギー学会, 日本語

新規化合物DTCM‐Gを用いたマウス慢性拒絶反応抑制効果の検討
財津雅昭, 山下健一郎, 柴崎晋, 常俊雄介, 若山顕治, 廣方玄太郎, 五十嵐留美, 小林希, 尾崎倫孝, 梅澤一夫, 藤堂省, 移植, 45, 320, 2010年10月
日本語

教室における新しい免疫抑制療法開発と免疫寛容誘導の試み
山下健一郎, 大浦哲, 渡辺正明, 鈴木友己, 宇野元博, 青柳武史, 今井敦, 柴崎晋, 後藤了一, 常俊雄介, 財津雅昭, 谷口雅彦, 嶋村剛, 尾崎倫孝, 古川博之, 藤堂省, 移植, 45, 161, 2010年10月
日本語

新規化合物DTCM‐Gの免疫抑制効果ならびにDSTとの併用効果の検討
常俊雄介, 山下健一郎, 柴崎晋, 財津雅昭, 後藤了一, 若山顕治, 廣方玄太郎, 五十嵐瑠美, 尾崎倫孝, 梅澤和夫, 藤堂省, 移植, 45, 279, 2010年10月
日本語

新規化合物NK026680を用いたex‐vivo誘導制御性樹状細胞の免疫抑制効果
柴崎晋, 山下健一郎, 若山顕治, 廣方玄太郎, 常俊雄介, 財津雅昭, 五十嵐瑠美, 芳賀早苗, 尾崎倫孝, 藤堂省, 移植, 45, 179, 2010年10月
日本語

MACS(Magnet cell sorting system)を用いた大腸癌患者の循環腫瘍細胞の同定(Detection of circulating tumor cells in colorectal cancer patients by magnet cell sorting system)　　　　　　　　　　　　　　　
崎浜 秀康, 小林 希, 佐々木 彩実, 本間 重紀, 高橋 典彦, 片岡 昭彦, 尾崎 倫孝, 藤堂 省, 日本癌学会総会記事, 69回, 334, 334, 2010年08月
日本癌学会, 英語

A Novel Anti-Inflammatory Agent, Dtcm-Glutarimide, Attenuates Experimental Colitis in Mice
Nobuki Ichikawa, Kenichiro Yamashita, Tohru Funakoshi, Susumu Shibasaki, Shin Ichihara, Moto Fukai, Tomomi Suzuki, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo, GASTROENTEROLOGY, 138, 5, S413, S413, 2010年05月
0, W B SAUNDERS CO-ELSEVIER INC, 英語, 研究発表ペーパー・要旨（国際会議）

Immunosuppressive Effect of DTCM-Glutarimide, a Novel AP-1 Inhibitor, on Allogeneic Islet Transplantation in Mice.
Tadashi Yoshida, Kenichiro Yamashita, Masaaki Watanabe, Yasuyuki Koshizuka, Daisuke Kuraya, Masaomi Ogura, Hirofumi Kamachi, Michitaka Ozaki, Michiaki Matsushita, Kazuo Umezawa, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 10, 230, 230, 2010年04月
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

A Novel Solution for Rat Liver Preservation Composed of Heavy Water and Swan Buffer; a Pilot Study
Daisuke Fukumori, Moto Fukai, Kenji Wakayama, Kenichiro Yamashita, Shinya Ueki, Mitsuru Sugawara, Sanae Haga, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 10, 496, 497, 2010年04月
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

CD40-CD154 Costimulation Blockade Plus NF-kappa B Inhibition Permits a Successful Single-Donor Islet Transplantation in Mice.
Yasuyuki Koshizuka, Kenichiro Yamashita, Masaaki Watanabe, Daisuke Kuraya, Masaomi Ogura, Tadashi Yoshida, Hirofumi Kamachi, Michiaki Matsushita, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 10, 46, 47, 2010年04月
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

Heavy Water (D2O) Universally Ameliorates Cold Preservation Injury: Precise Analyses of Cytoprotective Mechanisms In Vitro
Moto Fukai, Kenji Wakayama, Daisuke Fukumori, Kenichiro Yamashita, Mitsuru Sugawara, Sanae Haga, Ueki Gentaro Hirokata, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 10, 492, 493, 2010年04月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

SF-045-6 CD40Ig遺伝子組込みadenovirus vectorを用いたマウス膵島移植成績向上の試み(移植-5,サージカルフォーラム,第110回日本外科学会定期学術集会)
腰塚 靖之, 山下 健一郎, 渡辺 正明, 小倉 正臣, 吉田 雅, 蔵谷 大輔, 蒲池 浩文, 尾崎 倫孝, 古川 博之, 松下 道明, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 111, 2, 2010年03月05日
一般社団法人日本外科学会, 日本語

SF-045-7 マウス膵島移植におけるNF-κB阻害薬,DHMEQ,を用いたinduction療法の有用性 : 自然免疫-獲得免疫反応の抑制(移植-5,サージカルフォーラム,第110回日本外科学会定期学術集会)
渡辺 正明, 山下 健一郎, 蔵谷 大輔, 腰塚 靖之, 柴崎 晋, 小倉 正臣, 吉田 雅, 尾崎 倫孝, 蒲池 浩文, 古川 博之, 松下 通明, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 111, 2, 2010年03月05日
一般社団法人日本外科学会, 日本語

OP-090-3 炎症性腸疾患モデルに対するDTCM-glutarimideの効果に関する検討(小腸基礎-2,一般口演,第110回日本外科学会定期学術集会)
市川 伸樹, 山下 健一郎, 舩越 徹, 柴崎 晋, 深井 原, 尾崎 倫孝, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 111, 2, 2010年03月05日
一般社団法人日本外科学会, 日本語

OP-121-2 新規NF-κB阻害剤DHMEQによるマウス膵島移植後早期グラフト障害抑制効果(移植-3,一般口演,第110回日本外科学会定期学術集会)
蔵谷 大輔, 山下 健一郎, 渡辺 正明, 蒲池 浩文, 腰塚 靖之, 小倉 正臣, 吉田 雅, 尾崎 倫孝, 古川 博之, 松下 通明, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 111, 2, 2010年03月05日
一般社団法人日本外科学会, 日本語

OP-090-1 新規NF-kB阻害剤DHMEQの大腸炎モデルにおける炎症抑制作用(小腸基礎-2,一般口演,第110回日本外科学会定期学術集会)
舩越 徹, 市川 伸樹, 山下 健一郎, 深井 原, 鈴木 友己, 桂田 武彦, 後藤 了一, 大浦 哲, 小林 希, 尾崎 倫孝, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 111, 2, 2010年03月05日
一般社団法人日本外科学会, 日本語

WS-6-6 胃癌腹膜播種に対する,NF-κB抑制による治療戦略 : 腹膜との接着抑制を主眼に置いて(消化器癌腹膜転移の治療:基礎と臨床,ワークショップ(6),第110回日本外科学会定期学術集会)
三野 和宏, 中西 一彰, 芳賀 早苗, 馬場 基, 藤好 真人, 佐藤 正法, 横尾 英樹, 神山 俊哉, 尾崎 倫孝, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 111, 2, 166, 166, 2010年03月05日
一般社団法人日本外科学会, 日本語

WS-6-10 NF-κB制御による膵癌腹膜播種の抑制 : アノイキス誘導による新たな治療戦略(消化器癌腹膜転移の治療:基礎と臨床,ワークショップ(6),第110回日本外科学会定期学術集会)
佐藤 正法, 中西 一彰, 渡邉 俊之, 芳賀 早苗, 三野 和宏, 横尾 英樹, 梅澤 一夫, 近江谷 克裕, 神山 俊哉, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 111, 2, 167, 167, 2010年03月05日
一般社団法人日本外科学会, 日本語

OP-018-4 Magnet cell sorting(MACS) systemを用いた大腸癌の血中腫瘍細胞の同定(腫瘍マーカー-1,一般口演,第110回日本外科学会定期学術集会)
崎浜 秀康, 小林 希, 佐々木 彩実, 芳賀 早苗, 本間 重紀, 高橋 典彦, 片岡 昭彦, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 111, 2, 323, 323, 2010年03月05日
一般社団法人日本外科学会, 日本語

OP-051-1 肝細胞癌におけるCD133発現の臨床病理学的意義(腫瘍基礎-1,一般口演,第110回日本外科学会定期学術集会)
佐々木 彩実, 神山 俊哉, 横尾 英樹, 中西 一彰, 久保田 佳奈子, 羽賀 博典, 松下 通明, 尾崎 倫孝, 松野 吉宏, 藤堂 省, 日本外科学会雑誌, 111, 2, 369, 369, 2010年03月05日
一般社団法人日本外科学会, 日本語

SF-014-3 重水含有新規臓器保存液の開発 : ラット肝冷保存・単離再灌流モデルにおけるグラフト保護効果の検討(移植-3,サージカルフォーラム,第110回日本外科学会定期学術集会)
福森 大介, 深井 原, 山下 健一郎, 若山 顕治, 後藤 了一, 柴崎 晋, 廣方 玄太郎, 木村 鐘康, 常俊 雄介, 財津 雅明, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 古川 博之, 尾崎 倫孝, 松下 道明, 藤堂 省, 日本外科学会雑誌, 111, 臨時増刊号_2, 201, 201, 2010年03月05日
一般社団法人日本外科学会, 日本語

SF-014-4 重水含有新規臓器保存液のラット心冷保存・移植モデルにおけるグラフト保護効果(移植-3,サージカルフォーラム,第110回日本外科学会定期学術集会)
若山 顕治, 深井 原, 山下 健一郎, 福森 大介, 柴崎 晋, 廣方 玄太郎, 木村 鐘康, 財津 雅明, 常俊 雄介, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 古川 博之, 尾崎 倫孝, 松下 道明, 藤堂 省, 日本外科学会雑誌, 111, 臨時増刊号_2, 201, 201, 2010年03月05日
一般社団法人日本外科学会, 日本語

OP-119-2 NK026680を用いたRegulatory DCによる免疫抑制効果の検討(移植-1,一般口演,第110回日本外科学会定期学術集会)
柴崎 晋, 山下 健一郎, 若山 顕治, 廣方 玄太郎, 常俊 雄介, 財津 雅昭, 木村 鐘康, 五十嵐 瑠美, 芳賀 早苗, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 古川 博之, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 111, 臨時増刊号_2, 477, 477, 2010年03月05日
一般社団法人日本外科学会, 日本語

OP-152-2 重水含有新規臓器保存液の開発 : 効果の普遍性と保護作用メカニズムの検討(in vitro study)(移植-8,一般口演,第110回日本外科学会定期学術集会)
深井 原, 若山 顕治, 福森 大介, 山下 健一郎, 後藤 了一, 植木 伸也, 柴崎 晋, 廣方 玄太郎, 木村 鐘康, 常俊 雄介, 財津 雅明, 芳賀 早苗, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 古川 博之, 松下 通明, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 111, 臨時増刊号_2, 525, 525, 2010年03月05日
一般社団法人日本外科学会, 日本語

発現頻度・発現パターンから見た大腸癌における癌幹細胞マーカーCD133の臨床的意義についての検討　　　　　　　　　　　　　　　
高橋 周作, 神山 俊哉, 島田 信吾, 工藤 岳秋, 廣瀬 邦弘, 佐治 裕, 崎浜 秀康, 尾崎 倫孝, 外丸 詩野, 石津 明洋, 藤堂 省, 日本外科学会雑誌, 111, 臨増2, 372, 372, 2010年03月
(一社)日本外科学会, 日本語

生体イメージングをもちいたHGF含有コラーゲンビトリゲル薄膜による肝虚血/再灌流障害抑制効果の検討
芳賀早苗, 竹澤俊明, 山本智子, 小澤岳昌, 森田直樹, 藤好真人, 尾崎倫孝, 再生医療, 9, 304, 2010年02月05日
日本語

p66Shc Plays a Pivotal Role in Impaired Liver Regeneration in Aged Mice by a Redox-dependent Mechanism
Michitaka Ozaki, S. Haga, N. Morita, T. Ozawa, S. Todo, K. Irani, J. Remington, FREE RADICAL BIOLOGY AND MEDICINE, 49, S83, S83, 2010年
ELSEVIER SCIENCE INC, 英語, 研究発表ペーパー・要旨（国際会議）

DHMEQ, a New NF-kappa B Inhibitor, Suppresses Innate and Subsequent Allo-Immune Responses, and Permits a Long-Term Allogeneic Islet Engraftment Together with Tacrolimus
Masaaki Watanabe, Kenichiro Yamashita, Hirofumi Kamachi, Daisuke Kuraya, Yasuyuki Koshizuka, Susumu Shibasaki, Michitaka Ozaki, Kazuo Umezawa, Michiaki Matsushita, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 10, 3, 3, 2010年01月
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

コラーゲンビトリゲル薄膜の特徴を活用した新しい細胞培養システムの開発
竹澤 俊明, 福田 真野, Mcintosh-Ambrose Winnette, 高 知愛, ELISSEEFF Jennifer, 芳賀 早苗, 尾崎 倫孝, 加藤 聖子, 王 碧昭, 内野 正, 西田 輝夫, 薬学雑誌. 乙号, 130, 4, 565, 574, 2010年
The white of an egg, rendered opaque by boiling, can be converted into a thin, transparent and rigid material like glass by evaporating the moisture. This phenomenon is known as the vitrification of heat-denatured proteins. We applied vitrification technology to a collagen gel and converted it into a rigid glass-like material. We attempted to rehydrate the glass-like material and succeeded in preparing a novel stable state of collagen gel that was a thin and transparent membrane with excellent gel strength and protein permeability. We called it "collagen vitrigel" because it was produced from the vitrification process of a traditional hydrogel. Further, a framework-embedded collagen vitrigel membrane that can be easily turned inside out with tweezers was prepared by inserting a nylon membrane ring in the collagen sol prior to the gelation, thereby allowing the membrane to function as a removable cell culture substratum. Different types of anchorage-dependent cells could be cultured on both surfaces of the substratum by the manipulation of two-dimensional cultures, and consequently a three-dimensional crosstalk model with paracrine effects from each cell type was reconstructed. Also, the collagen vitrigel membrane containing a bioactive molecule provided a drug delivery system (DDS) with sustainable release. In this review, we summarize the recent progress of applied studies using the collagen vitrigel membrane as follows: a corneal model for eye irritant and permeability tests, a skin model for sensitization test, a renal glomerular model for evaluating blood filtration, an endometrial model for developing a new treatment and a DDS of hepatocyte growth factor for improving liver disorder., The Pharmaceutical Society of Japan, 日本語

Myocardial Protection With a Novel Organ Preservation Solution Containing Deuterium Oxide for Prolonged Cold Ischemia of the Heart
Kenji Wakayama, Moto Fukai, Kenichiro Yamashita, Daisuke Fukumori, Susumu Shibasaki, Gentaro Hirokata, Tetsu Oura, Ryoichi Goto, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo, CIRCULATION, 120, 18, S836, S836, 2009年11月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

組織再生に有用なコラーゲンビトリゲルを用いた新しい医薬学研究:肝虚血・再灌流後の肝障害抑制への応用
竹澤俊明, 芳賀早苗, 尾崎倫孝, Pharmaco-Hematologyシンポジウム講演要旨集, 10th, 25, 2009年06月19日
日本語

Effect of a Novel NF-kappa B Inhibitor, DHMEQ, On Dextran Sulfate Sodium-Induced Colitis in Mice
Tohru Funakoshi, Kenichiro Yamashita, Tomomi Suzuki, Moto Fukai, Nobuki Ichikawa, Takehiko Katsurada, Ryoichi Goto, Tetsu Oura, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo, GASTROENTEROLOGY, 136, 5, A404, A404, 2009年05月
W B SAUNDERS CO-ELSEVIER INC, 英語, 研究発表ペーパー・要旨（国際会議）

新しい細胞培養システムの開発とその創薬支援研究への応用 コラーゲンビトリゲル薄膜の特徴を活用した新しい細胞培養システムの開発　　　　　　　　　　　　　　　
竹澤 俊明, 福田 真野, Ambrose Winnette Mcintosh, 高 知愛, Elisseeff Jennifer H., 芳賀 早苗, 尾崎 倫孝, 加藤 聖子, 王 碧昭, 内野 正, 西田 輝夫, 日本薬学会年会要旨集, 129年会, 1, 179, 179, 2009年03月
(公社)日本薬学会, 日本語

SF-107-2 マウス膵島移植における選択的NFkB阻害剤DHMEQのDonor投与の効果(膵(移植1),サージカルフォーラム,第109回日本外科学会定期学術集会)
高橋 徹, 松本 秀一朗, 松下 通明, 敦賀 陽介, 渡辺 正明, 蔵谷 大輔, 腰塚 靖之, 中木村 繁, 蒲池 浩文, 尾崎 倫孝, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 110, 2, 2009年02月25日
一般社団法人日本外科学会, 日本語

SF-107-3 マウス膵島移植における新規NF-κB阻害薬Dehydroepoxyquinomycin(DHMEQ)の効果の検討(膵(移植1),サージカルフォーラム,第109回日本外科学会定期学術集会)
渡辺 正明, 山下 健一郎, 蒲池 浩文, 蔵谷 大輔, 腰塚 靖之, 中木村 繁, 後藤 了一, 松下 道明, 尾崎 倫孝, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 110, 2, 2009年02月25日
一般社団法人日本外科学会, 日本語

SF-111-2 マウス胃癌腹膜播種モデルを用いた,新規NFκB阻害剤DHMEQによる腫瘍抑制効果の検討(分子標的・遺伝子治療1,サージカルフォーラム,第109回日本外科学会定期学術集会)
三野 和宏, 中西 一彰, 芳賀 早苗, 喜納 政哉, 佐藤 正法, 横尾 英樹, 神山 俊哉, 尾崎 倫孝, 藤堂 省, 梅澤 一夫, 日本外科学会雑誌, 110, 2, 363, 363, 2009年02月25日
一般社団法人日本外科学会, 日本語

HP-090-6 胃癌腹膜播種モデルにおける新規NFκB阻害剤の腹膜への細胞接着抑制効果の検討(胃(分子標的・免疫療法),ハイブリッドポスター,第109回日本外科学会定期学術集会)
佐藤 正法, 三野 和宏, 中西 一彰, 芳賀 早苗, 上徳 ひろみ, 喜納 政哉, 横尾 英樹, 神山 俊哉, 梅澤 一夫, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 110, 2, 549, 549, 2009年02月25日
一般社団法人日本外科学会, 日本語

HP-189-4 Suboptimal graftの有効利用を目指した次世代の臓器保存液の開発(移植医療2,ハイブリッドポスター,第109回日本外科学会定期学術集会)
深井 原, 福森 大介, 若山 顕治, 山下 健一郎, 後藤 了一, 植木 伸也, 柴崎 晋, 大浦 哲, 廣方 玄太郎, 芳賀 早苗, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 松下 通明, 古川 博之, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 110, 臨時増刊号_2, 710, 710, 2009年02月25日
一般社団法人日本外科学会, 日本語

SF-068-6 新規薬剤NK026680の免疫抑制作用および効果の検討(移植治療・再生医療,サージカルフォーラム,第109回日本外科学会定期学術集会)
柴崎 晋, 山下 健一郎, 大浦 哲, 若山 顕治, 廣方 玄太郎, 柴田 智裕, 後藤 了一, 谷口 雅彦, 鈴木 知己, 嶋村 剛, 古川 博之, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 110, 臨時増刊号_2, 310, 310, 2009年02月25日
一般社団法人日本外科学会, 日本語

SF-068-1 DST+DHMEQによる免疫寛容誘導に対するTacrolimus併用の功罪(移植治療・再生医療,サージカルフォーラム,第109回日本外科学会定期学術集会)
後藤 了一, 山下 健一郎, 青柳 武史, 宇野 元博, 大浦 哲, 柴崎 晋, 廣方 玄太郎, 若山 顕治, 柴田 智裕, 五十嵐 瑠美, 渡辺 正明, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 古川 博之, 梅澤 一夫, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 110, 臨時増刊号_2, 309, 309, 2009年02月25日
一般社団法人日本外科学会, 日本語

新規開発臓器保存液を用いた心冷保存限界延長の試み
若山 顕治, 深井 原, 山下 健一郎, 後藤 了一, 植木 伸也, 福森 大介, 柴崎 晋, 大浦 哲, 廣方 玄太郎, 芳賀 早苗, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 松下 道明, 古川 博之, 尾崎 倫孝, 藤堂 省, 小野 太祐, 絹川 真太郎, 筒井 裕之, 菅原 満, 日本外科学会雑誌, 110, 臨増2, 709, 709, 2009年02月
(一社)日本外科学会, 日本語

新規開発臓器保存液を用いた心冷保存限界延長の試み
若山 顕治, 深井 原, 山下 健一郎, 後藤 了一, 植木 伸也, 福森 大介, 柴崎 晋, 大浦 哲, 廣方 玄太郎, 芳賀 早苗, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 松下 道明, 古川 博之, 尾崎 倫孝, 藤堂 省, 小野 太祐, 絹川 真太郎, 筒井 裕之, 菅原 満, 日本外科学会雑誌, 110, 臨増2, 709, 709, 2009年02月
(一社)日本外科学会, 日本語

Extended Preservation of Rat Hearts with Novel Organ Preservation Solution: Role of Actin Cytoskeleton and ATP Maintenance.
Kenji Wakayama, Moto Fukai, Kenichiro Yamashita, Daisuke Fukumori, Susumu Shibasaki, Gentaro Hirokata, Tomohiro Shibata, Tetsu Oura, Ryoichi Goto, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Michiaki Matsushita, Hiroyuki Furukawa, Michitaka Ozaki, Taisuke Ono, Mitsuru Sugawara, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 9, 491, 491, 2009年
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

NK026680, a Novel Triazolopyrimidine Derivative, for Allogeneic Islet Transplantation in Mice.
Yasuyuki Koshizuka, Kenichiro Yamashita, Masaaki Watanabe, Susumu Shibasaki, Daisuke Kuraya, Shigeru Nakakimura, Michitaka Ozaki, Hirofumi Kamachi, Michiaki Matsushita, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 9, 667, 667, 2009年
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

A Novel Triazolopyrimidine Derivative, NK026680 Inhibits T Cell Function, and Prolongs Cardiac Allograft Survival in Rats.
Susumu Shibasaki, Kenichiro Yamashita, Ryoichi Goto, Tetsu Oura, Kenji Wakayama, Gentaro Hirokata, Tomohiro Shibata, Rumi Igarashi, Sanae Haga, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 9, 660, 660, 2009年
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

Combined Treatment with a Nuclear Factor (NF)-kappa B Inhibitor, DHMEQ, and Tacrolimus Permits a Long-Term Allogeniec Islet Engraftment in Mice.
Masaaki Watanabe, Kenichiro Yamashita, Hirofumi Kamachi, Daisuke Kuraya, Yasuyuki Koshizuka, Shigeru Nakakimura, Michitaka Ozaki, Kazuo Umezawa, Michiaki Matsushita, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 9, 354, 354, 2009年
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

The Immunomodulatory Effect of NF-kappa B Blockade Is Augmented or Abrogated by NFAT Inhibition When Given with Donor-Specific Transfusion.
Ryoichi Goto, Kenichiro Yamashita, Shinya Ueki, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Hiroyuki Furukawa, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 9, 721, 721, 2009年
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

Prevention of Graft Failure Caused by IBMIR with a Novel NF-kappa B Inhibitor, Dehydroxymethylepoxyquinomicin (DHMEQ) after Intraportal Islet Transplantation in Mice.
Daisuke Kuraya, Hirofumi Kamachi, Masaaki Watanabe, Yasuyuki Koshizuka, Shigeru Nakakimura, Michitaka Ozaki, Kazuo Umezawa, Kenichiro Yamashita, Michiaki Matsushita, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 9, 355, 355, 2009年
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

Re-Evaluation of Heavy Water for Organ Preservation Solution; In Vitro Study.
Moto Fukai, Kenichiro Yamashita, Kenji Wakayama, Daisuke Fukumori, Ryoichi Goto, Sanae Haga, Gentaro Hirokata, Shigeru Nakakimura, Mitsuru Sugawara, Hirofumi Kamachi, Tomomi Suzuki, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michiaki Matsushita, Michitaka Ozaki, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 9, 581, 581, 2009年
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

Nuclear factor-kappa B inhibitor, dehydroxy methyl epoxyquinomicin ameliorates experimental autoimmune uveoretinitis (EAU) in mice　　　　　　　　　　　　　　　
Iwata, D, Kitaichi, N, Ebihara, A, Iwabuchi, K, Yoshida, K, Namba, K, Ozaki, M, Ohno, S, Umezawa, K, Yamashita, K, Todo, S, Ishida, S, Onoé, K, IOVS, in press, 2009年

NON-INVASIVE REALTIME MONITORING OF OXIDATIVE STRESS AND DAMAGE BY NEWLY DEVELOPED OPTICAL IMAGING PROBES IN MOUSE LIVER ISCHEMIA/REPERFUSION
Michitaka Ozaki, Sanae Haga, S. James Remington, Takeaki Ozawa, Yuko Oikawa, Satoru Todo, HEPATOLOGY, 48, 4, 640A, 640A, 2008年10月
JOHN WILEY & SONS INC, 英語, 研究発表ペーパー・要旨（国際会議）

Inhibition of NF-kappa B activation augments immunomodulatory effect of donor specific transfusion
Ryoichi Goto, Kenichiro Yamashita, Takeshi Aoyagi, Shinya Ueki, Motohiro Uno, Tetsu Oura, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Hiroyuki Furukawa, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 8, 403, 403, 2008年05月
BLACKWELL PUBLISHING, 英語, 研究発表ペーパー・要旨（国際会議）

A novel NF-kappa B inhibitor, DHMEQ, attenuates arterial vasculopathy.
Motohiro Uno, Kenichiro Yamashita, Tomohiro Shibata, Takeshi Aoyagi, Tetu Oura, Sanae Haga, Masaaki Watanabe, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 8, 343, 344, 2008年05月
BLACKWELL PUBLISHING, 英語, 研究発表ペーパー・要旨（国際会議）

Induction of immunosuppressive dendritic cells by a novel NF-kappa B inhibitor, DHMEQ
Takeshi Aoyagi, Kenichiro Yamashita, Yoshiki Yanagawa, Ryoichi Goto, Rumi Igarashi, Sanae Haga, Michitaka Ozaki, Kazunori Onoe, Kazuo Umezawa, Hiroyuki Furukawa, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 8, 483, 483, 2008年05月
BLACKWELL PUBLISHING, 英語, 研究発表ペーパー・要旨（国際会議）

A novel nuclear factor kappa B inhibitor, DHMEQ ameliorates development of obliterative bronchiolitis in heterotopic murine airway allo-transplantation.
Yuka Oshima, Motohiro Uno, Kenichiro Yamashita, Tomohiro Shibata, Tetu Oura, Masaaki Watanabe, Ryoichi Goto, Takeshi Aoyagi, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 8, 340, 340, 2008年05月
BLACKWELL PUBLISHING, 英語, 研究発表ペーパー・要旨（国際会議）

肝移植における虚血・再灌流障害のシグナル伝達機構
深井 原, 芳賀 早苗, 尾崎 倫孝, 臨床化学, 37, 2, 131, 140, 2008年04月30日
日本語

DP-121-4 生体イメージングに向けて新規開発した分子機能プローブの基礎的検討(第108回日本外科学会定期学術集会)
尾崎 倫孝, 芳賀 早苗, 及川 優子, 小澤 岳昌, 古川 博之, 藤堂 省, 日本外科学会雑誌, 109, 2, 586, 586, 2008年04月25日
一般社団法人日本外科学会, 日本語

SF-018-2 新規NFκB阻害剤DHMEQの動脈硬化抑制効果(第108回日本外科学会定期学術集会)
廣方 玄太郎, 宇野 元博, 山下 健一郎, 柴田 智裕, 後藤 了一, 青柳 武史, 大浦 哲, 渡辺 正明, 芳賀 早苗, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 古川 博之, 梅澤 一夫, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 109, 臨時増刊_2, 208, 208, 2008年04月25日
一般社団法人日本外科学会, 日本語

SF-022-2 新規NF-κB抑制剤DHMEQの閉塞性細気管支炎抑制効果(第108回日本外科学会定期学術集会)
渡辺 正明, 大島 有可, 宇野 元博, 柴田 智裕, 大浦 哲, 後藤 了一, 青柳 武史, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 古川 博之, 梅澤 一夫, 尾崎 倫孝, 山下 健一郎, 藤堂 省, 日本外科学会雑誌, 109, 臨時増刊_2, 213, 213, 2008年04月25日
一般社団法人日本外科学会, 日本語

SF-049-2 新規NF-κB阻害剤DHMEQの各種免疫担当細胞に対する効果(第108回日本外科学会定期学術集会)
大浦 哲, 山下 健一郎, 青柳 武史, 松本 秀一郎, 石戸谷 裕樹, 柳川 芳毅, 後藤 了一, 宇野元 博, 五十嵐 瑠美, 芳賀 早苗, 渡辺 正明, 柴田 智裕, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 古川 博之, 小野江 和則, 尾崎 倫孝, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 109, 臨時増刊_2, 247, 247, 2008年04月25日
一般社団法人日本外科学会, 日本語

DP-036-3 新規NF-kB阻害剤Dehydroxymethylepoxyquinomicin (DHMEQ)を用いた肝温阻血再灌流傷害軽減の試み(第108回日本外科学会定期学術集会)
深井 原, 尾崎 倫孝, 芳賀 早苗, 山下 健一郎, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 松下 通明, 古川 博之, 岸野 吏志, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 109, 臨時増刊_2, 416, 416, 2008年04月25日
一般社団法人日本外科学会, 日本語

DP-169-1 NF-kBおよびNFAT活性阻害とdonor specific transfuionによる免疫抑制効果(第108回日本外科学会定期学術集会)
後藤 了一, 山下 健一郎, 青柳 武史, 植木 伸也, 宇野 元博, 五十嵐 留美, 大浦 哲, 渡邊 正明, 柴田 智裕, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 古川 博之, 梅澤 一夫, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 109, 臨時増刊_2, 681, 681, 2008年04月25日
一般社団法人日本外科学会, 日本語

WS-3-6 血清中糖鎖の網羅的解析による肝細胞癌新規バイオマーカーの開発(第108回日本外科学会定期学術集会)
横尾 英樹, 三浦 嘉晃, 神山 俊哉, 中西 一彰, 濱口 純, 工藤 岳秋, 古川 潤一, 中川 隆公, 田原 宗徳, 中馬 誠, 髭 修平, 篠原 康郎, 尾崎 倫孝, 多田 光宏, 松下 通明, 浅香 正博, 西村 紳一郎, 藤堂 省, 日本外科学会雑誌, 109, 2, 2008年04月25日
一般社団法人日本外科学会, 日本語

TPA inhibits melanoma growth by inactivation of STAT3 through PKC-activated tyrosine phosphatase(s)
Masahiro Oka, Masanobu Sakaguchi, Naoko Sumita, Toshinori Bito, Toshiro Kageshita, Michitaka Ozaki, Ken-Ichi Sato, Yasuo Fukami, Chikako Nishigori, PIGMENT CELL & MELANOMA RESEARCH, 21, 2, 263, 263, 2008年04月
BLACKWELL PUBLISHING, 英語, 研究発表ペーパー・要旨（国際会議）

バイオイメージングに向けた光プローブの基礎的研究
芳賀 早苗, 及川 優子, 小澤 岳昌, 藤堂 省, 尾崎 倫孝, バイオイメージング, 16, 2, 161, 162, 2007年10月05日
日本語

酸化ストレス 細胞・臓器機能への影響とその制御 好中球由来のオキシダントによる細胞の機能修飾
荻野 哲也, Tin Aung Than, 大森 昌子, 寳迫 睦美, 平松 万尚, 尾崎 倫孝, 松川 昭博, 岡田 茂, Organ Biology, 14, 3, 213, 213, 2007年10月
(一社)日本臓器保存生物医学会, 日本語

P66SHC, an ageing protein, plays a pivotal role in post-hepatectomized liver regeneration in aged mice
Michitaka Ozaki, Sanae Haga, Tadahiro Osada, Yuko Oikawa, Hiroyuki Furukawa, Kaikobad Irani, Satoru Todo, HEPATOLOGY, 46, 4, 536A, 537A, 2007年10月
JOHN WILEY & SONS INC, 英語, 研究発表ペーパー・要旨（国際会議）

Donor pretreatment with a novel NF-kB inhibitor, DHMEQ can alleviate the graft damage in syngenic marginal islet transplantation
Tohru Takahashi, Shuichiro Matsumoto, Yosuke Tsuruga, Hironori Kasai, Masaaki Watanabe, Michitaka Ozaki, Hiroyuki Furukawa, Michiaki Matsushita, Kazuo Umezawa, Satoru Todo, XENOTRANSPLANTATION, 14, 5, 479, 479, 2007年09月
BLACKWELL PUBLISHING, 英語, 研究発表ペーパー・要旨（国際会議）

Effect of a novel NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin in combination with donor specific transfusion in mouse heart transplantation.
Ryoichi Goto, Kenichiro Yamashita, Takeshi Aoyagi, Motohiro Uno, Shinya Ueki, Tomoo Itoh, Tomomi Suzuki, Masahiko Taniguchi, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo, AMERICAN JOURNAL OF TRANSPLANTATION, 7, 324, 324, 2007年05月
BLACKWELL PUBLISHING, 英語, 研究発表ペーパー・要旨（国際会議）

高解像度アレイCGHによる胃癌の生物学的特性に関連するゲノム異常解析
富岡伸元, 森田桂子, 多田光宏, 野村克, 高橋典彦, 近藤正男, 片岡昭彦, 中西一彰, 高橋将人, 尾崎倫孝, 藤堂省, 平野隆, 日本外科学会雑誌, 108, 262, 2007年03月10日
日本語

WS-11-5 種々の病態における肝再生不全の要因 : 細胞内シグナル解析からみた問題点と対策(第107回日本外科学会定期学術集会)
尾崎 倫孝, 芳賀 早苗, 長田 忠大, 井上 啓, 小川 渉, 村田 宏, 岩垣 博巳, 古川 博之, 藤堂 省, 日本外科学会雑誌, 108, 2, 159, 159, 2007年03月10日
一般社団法人日本外科学会, 日本語

DP-061-1 新規NF-kB阻害剤"DHMEQ"の慢性拒絶反応抑制効果(第107回日本外科学会定期学術集会)
植木 伸也, 山下 健一郎, 青柳 武史, 鈴木 友己, 谷口 雅彦, 嶋村 剛, 梅澤 一夫, 古川 博之, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 108, 臨時増刊号_2, 449, 449, 2007年03月10日
一般社団法人日本外科学会, 日本語

創薬基盤としての公共的ヒト組織バンクを中心とした肝組織・細胞の研究利用システムの構築 18年度報告
絵野沢伸, 青木達哉, 安原一, 片岡一則, 大塚英典, 竹澤俊明, 落合孝広, 小林英司, 尾崎倫孝, 鈴木聡, 大和田哲男, 布施英一, 山田泰弘, 吉村勉, 榎本康弘, 池谷武志, 田向康人, 政策創薬総合研究重点研究報告書2 平成18年度, 989, 999, 2007年
日本語

創薬基盤としての公共的ヒト組織バンクを中心とした肝組織・細胞の研究利用システムの構築 総合研究報告
絵野沢伸, 青木達哉, 安原一, 片岡一則, 大塚英典, 竹澤俊明, 落合孝広, 小林英司, 尾崎倫孝, 鈴木聡, 大和田哲男, 布施英一, 小林弘幸, 山田泰弘, 吉村勉, 榎本康弘, 池谷武志, 田向康人, 澤田雅弘, 政策創薬総合研究重点研究報告書2 平成18年度, 979, 988, 2007年
日本語

慢性肝細胞障害の術後肝再生に及ぼす影響とその機序の臨床病理学的解析　　　　　　　　　　　　　　　
楳田 祐三, 八木 孝仁, 貞森 裕, 松川 啓義, 松田 浩明, 篠浦 先, 荻野 哲也, 尾崎 倫孝, 岩垣 博巳, 田中 紀章, 消化器と免疫, 42, 141, 145, 2006年04月
慢性肝障害を背景とする肝細胞癌と正常肝を背景とする転移性肝癌の肝切除例を対象とし,c-met/gp130/STAT/AKT/NF-κBをはじめとする肝再生シグナルにつき免疫組織学的検討を行い,あわせて両群の肝再生率,臨床病理学的諸因子を比較検討することによって,慢性肝障害における肝再生不良の機序を解析した.ウイルス性肝障害を背景とする肝細胞癌(D群)22例,正常肝を背景とする転移性肝癌群(N群)18例の肝切除症例を対象とした.手術侵襲(出血量,手術時間,肝切除量など)に差はなく,肝再生率は,D群で不良であった.シグナル蛋白の免疫染色では,D群の非癌部実質でc-metの優位な染色性,間質部でNF-κBの染色性の減弱を認めた.更に実質部NF-κB染色性と肝再生率に負の相関を認めた.慢性肝障害はc-met,NF-KBの不活性化が肝再生不良の原因となっている可能性が示唆された, 日本消化器免疫学会, 日本語

Prevention of liver ischemia/reperfusion-induced injury : from bench to clinics
尾崎 倫孝, 芳賀 早苗, 深井 原, 古川 博之, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 107, 2, 84, 84, 2006年03月05日
一般社団法人日本外科学会, 英語

異種移植に対する副刺激シグナル経路遮断による免疫抑制効果の臓器による違い
青柳 武史, 山下 健一郎, 植木 伸也, 華 南, 今井 敦, 鈴木 友己, 谷口 雅彦, 嶋村 剛, 尾崎 倫孝, 古川 博之, 藤堂 省, 日本外科学会雑誌, 107, 臨時増刊号_2, 235, 235, 2006年03月05日
一般社団法人日本外科学会, 日本語

ラット小腸虚血再灌流障害に対するNF-κB阻害薬(DHMEQ)の効果
鈴木 友己, 山下 健一郎, 深井 原, 嶋村 剛, 谷口 雅彦, 植木 伸也, 青柳 武史, 古川 博之, 尾崎 倫孝, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 107, 臨時増刊号_2, 408, 408, 2006年03月05日
一般社団法人日本外科学会, 日本語

NF-κB阻害剤,Dehydroxymethylepoxyquinomicinの免疫抑制作用
山下 健一郎, 植木 伸也, 青柳 武史, 鈴木 友己, 谷口 雅彦, 嶋村 剛, 古川 博之, 尾崎 倫孝, 梅澤 一夫, 藤堂 省, 日本外科学会雑誌, 107, 臨時増刊号_2, 453, 453, 2006年03月05日
一般社団法人日本外科学会, 日本語

虚血中の肝酸化ストレスが再灌流後の酸化ストレスを規定する
深井 原, 横田 良一, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 尾崎 倫孝, 古川 博之, 松下 通明, 藤堂 省, 日本外科学会雑誌, 107, 臨時増刊号_2, 632, 632, 2006年03月05日
一般社団法人日本外科学会, 日本語

CD40, CD154遺伝子欠損マウス心移植におけるカルシニューリン阻害の影響
植木 伸也, 山下 健一郎, 青柳 武史, 今井 敦, 鈴木 友己, 谷口 雅彦, 嶋村 剛, 尾崎 倫孝, 古川 博之, 藤堂 省, 日本外科学会雑誌, 107, 臨時増刊号_2, 710, 710, 2006年03月05日
一般社団法人日本外科学会, 日本語

安全な脂肪肝切除・移植にむけた基礎的研究 脂肪肝切除後肝不全(再生障害)の機序解析　　　　　　　　　　　　　　　
村田 宏, 八木 孝仁, 岩垣 博己, 貞森 裕, 松川 啓義, 篠浦 先, 藤本 善三, 楳田 祐三, 孫 冬生, 荻野 哲也, 藤堂 省, 田中 紀章, 尾崎 倫孝, 日本外科学会雑誌, 107, 臨増2, 311, 311, 2006年03月
(一社)日本外科学会, 日本語

A-15 STAT3の細胞保護作用を用いた再生医療への応用 : 低酸素再酸素化モデルにおける検討(小児外科としての発生学と再生医学)
照井 慶太, 尾崎 倫孝, 芳賀 早苗, 山田 慎一, 菱木 知郎, 黒田 浩明, 幸地 克憲, 松永 正訓, 吉田 英生, 大沼 直躬, 日本小児外科学会雑誌, 41, 3, 372, 372, 2005年05月20日
特定非営利活動法人日本小児外科学会, 日本語

アデノウイルスベクターを用いた単離膵内分泌細胞への Stat3遺伝子導入による膵β細胞増殖活性化の試み(第105回日本外科学会定期学術集会)
築山 周作, 松下 通明, 松本 秀一朗, 森田 恒彦, 小林 智, 田村 仁志, 蒲池 浩文, 尾崎 倫孝, 藤堂 省, 日本外科学会雑誌, 106, 0, 2005年04月05日
一般社団法人日本外科学会, 日本語

肝虚血再灌流傷害におけるSTAT3の細胞保護作用(第105回日本外科学会定期学術集会)
照井 慶太, 尾崎 倫孝, 芳賀 早苗, 絵野 沢伸, 黒田 浩明, 幸地 克憲, 松永 正訓, 吉田 英生, 大沼 直躬, 日本外科学会雑誌, 106, 0, 419, 419, 2005年04月05日
一般社団法人日本外科学会, 日本語

marginal liverの機能再生戦略と移植への応用 脂肪肝における再生障害の機序の解析　　　　　　　　　　　　　　　
村田 宏, 八木 孝仁, 岩垣 博己, 貞森 裕, 松川 啓義, 藤本 善三, 楳田 祐三, 孫 冬生, 荻野 哲也, 田中 紀章, 尾崎 倫孝, 日本外科学会雑誌, 106, 臨増, 215, 215, 2005年04月
(一社)日本外科学会, 日本語

慢性肝細胞障害の術後肝再生に及ぼす影響とその機序の臨床病理学的解析　　　　　　　　　　　　　　　
楳田 祐三, 八木 孝仁, 貞森 裕, 松川 啓義, 孫 冬生, 篠浦 先, 荻野 哲, 尾崎 倫孝, 岩垣 博巳, 田中 紀章, 日本外科学会雑誌, 106, 臨増, 540, 540, 2005年04月
(一社)日本外科学会, 日本語

門脈シェアストレスがSmall-for-size grafts移植後の肝再生に及ぼす影響の臨床的検討　　　　　　　　　　　　　　　
薬理と治療, vol. 32, S129-S136, 2005年

Immediate increase of portal pressure, reflecting sinusoidal shear stress, accelerated liver regeneration through increased production of IL-6 and HGF in small-for-size graft
Takanori Oyama, Takanori Oyama, Takahito Yagi, Hiroshi Sadamori, Hiroyoshi Matsukawa, Susumu Shinoura, Yoshimi Fujimoto, Hiroshi Murata, Aya Kunitomi, Yuuzou Umeda, Yasuhiro Watanabe, Michitaka Ozaki, Hiromi Iwagaki, Noriaki Tanaka, Japanese Pharmacology and Therapeutics, 32, 2004年12月01日
The mechanisms whereby grafts in the recipients can be primed for regeneration following living donor liver transplantation (LDLT) are poorly understood. In the liver transplantation from a living donor, we sometimes have the only option of using proportionally small graft for a patient due to the living donor's condition. Out of LDLT cases, we included cases which had end-stage liver cirrhosis and subsequent transplantation without acute rejection, infection and vascular complications. At the end, we were left with 8 cases from each group, total of 16 cases. Then they were divided into 2 groups, group L and group S. Group L had a graft-recipient ratio (G/R ratio) of 1.0 or higher while group S had G/R ratio of less than 1.0. There are three components in this study to measure. Firstly, we compared the serum levels of IL-6, soluble IL-6 receptor (sIL-6R) and hepatocyte growth factor (HGF), which play a role in the regulation of liver regeneration, preoperatively and postoperatively by ELISA. The concentrations of total bilirubin (T-Bil), C-reactive protein (CRP), prothrombin time (PT), albumin (Alb) and platelet count (PLT) were also measured. Finally, we carried out haemodynamic analysis by measuring the portal and arterial peak velocity (Vp max/Va max). The differences in age range, pre-operative T-Bil, PT and MELD score between the two groups were not statistically significant. Before the operation, no statistical differences in the levels of IL-6, sIL-6R and HGF were found between the two groups, however, at post-operative days, IL-6 and HGF levels in group S significantly increased while sIL-6R level was almost the same in both groups. Delayed production of CRP and increased Vp max were observed in group S. Two week after LDLT, the regeneration rate in group S was significantly higher than that in group L. In conclusion, the increase in post-operative IL-6 and HGF levels in group S suggested that production of IL-6 and HGF was required to promote the rapid liver regeneration and less IL-6 and HGF was used up due to proportionally smaller volume of available liver tissue. It is temptating to speculate that immediate increase of portal pressure, reflecting sinusoidal shear stress, accelerated liver regeneration through increased production of IL-6 and HGF.

肝糖新生におけるSTAT3の役割
井上 啓, 小川 渉, 尾崎 倫孝, 最新医学, 59, 12, 2614, 2619, 2004年12月
最新医学社, 日本語

Prostaglandin E2およびEP receptor agonistによる拒絶反応抑制効果の解析　　　　　　　　　　　　　　　
楳田 祐三, 藤本 善三, 八木 孝仁, 村田 宏, 孫 冬生, 尾崎 倫孝, 岩垣 博巳, 田中 紀章, 移植, 39, 総会臨時, 238, 238, 2004年07月
(一社)日本移植学会, 日本語

B-27 肝虚血再灌流傷害におけるSTAT3の細胞保護作用(一般口演 移植I)
照井 慶太, 尾崎 倫孝, 芳賀 早苗, 絵野沢 伸, 吉田 英生, 松永 正訓, 幸地 克憲, 黒田 浩明, 斎藤 武, 大沼 直躬, 日本小児外科学会雑誌, 40, 3, 420, 420, 2004年05月20日
特定非営利活動法人日本小児外科学会, 日本語

活性化Stat3(S3‐C)による劇症肝炎の抑制機序と治療への可能性
尾崎倫孝, 芳賀早苗, 照井慶太, 小川渉, 井上啓, 絵野沢伸, 肝臓, 45, Supplement 1, A75, 2004年04月30日
日本語

SF-093-1 肝再生おける細胞内シグナルの解析 : Stat3経路およびPI3-K/PDK/Akt経路の重要性
芳賀 早苗, 照井 慶太, 張 慧〓, 小川 渉, 井上 啓, 絵野沢 伸, 尾崎 倫孝, 日本外科学会雑誌, 105, 0, 299, 299, 2004年03月15日
一般社団法人日本外科学会, 日本語

肝虚血再潅流傷害におけるSTAT3の細胞保護作用
照井慶太, 尾崎倫孝, 芳賀早苗, 張慧ご, 菅沼靖之, 大沼直み, 絵野沢伸, 移植, 38, 247, 2003年10月
日本語

虚血再濯流傷害のシグナル伝達
尾崎 倫孝, 移植, 38, 3, 199, 207, 2003年06月10日
日本語

A-024 STAT3 の細胞保護作用を用いた再生医療への応用 : 肝の低酸素再酸素化モデルにおける検討
照井 慶太, 尾崎 倫孝, 芳賀 早苗, 張 慧き, 菅沼 靖之, 絵野沢 伸, 鈴木 盛一, 大沼 直躬, 日小外会誌, 39, 3, 106, 106, 2003年
特定非営利活動法人 日本小児外科学会, 日本語

低酸素再酸素化によるSTAT1のレドックス制御と肝細胞生存への影響
照井慶太, 尾崎倫孝, 芳賀早苗, 絵野沢伸, 鈴木盛一, 移植, 37, 269, 2002年09月
日本語

HGFによる肝虚血再潅流傷害抑制メカニズム : PI3-K/Akt/Racl pathwayによる細胞内活性酸素消去系
芳賀 早苗, 尾崎 倫孝, 長田 夕子, 鈴木 盛一, 日本外科学会雑誌, 103, 252, 252, 2002年03月10日
一般社団法人日本外科学会, 日本語

シグナル制御による臓器虚血再潅流傷害抑制の試み
尾崎 倫孝, 田中 秀明, 郭 雷, 芳賀 早苗, Irani Kaikobad, 鈴木 盛一, 日本外科学会雑誌, 103, 197, 197, 2002年03月10日
一般社団法人日本外科学会, 日本語

腎不全の外科-病態とマネジメント-<太田 和夫編>　　　　　　　　　　　　　　　
南江堂, 2000年

腎不全治療学 第一版<太田 和夫編>　　　　　　　　　　　　　　　
南江堂, 1997年

食道壁内に気管支性嚢胞を合併した血液透析患者の一例
石田 英樹, 尾崎 倫孝, 小池 太郎, 小山 一郎, 中島 一朗, 淵之上 昌平, 寺岡 慧, 阿岸 鉄三, 太田 和夫, 透析療法学会誌, 28, 6, 995, 998, 1995年
日本語

S. Teraoka, T. Babazono, O.Tomonaga, S.Sato, M.Nakamura, H.Ishida, T.Hoshino, T.Koike, M.Abe, M.Shinkai, H.Haruguchi, S.Hirotani, K.Kitajima, M.Akamatsu, M.Ozaki, S.Fujita, I.Nakagawa, T.Kawai, S.Fuchinoue, H.Ohgawara, Y.Omori, and K.Ota: Donor criteri・・・　　　　　　　　　　　　　　　
1995年
S. Teraoka, T. Babazono, O.Tomonaga, S.Sato, M.Nakamura, H.Ishida, T.Hoshino, T.Koike, M.Abe, M.Shinkai, H.Haruguchi, S.Hirotani, K.Kitajima, M.Akamatsu, M.Ozaki, S.Fujita, I.Nakagawa, T.Kawai, S.Fuchinoue, H.Ohgawara, Y.Omori, and K.Ota: Donor criteria and technical aspects of procurement in combined pancreas and kidney transplantation from non-heart-beating cadavers. Transplant P 27: 3097-3100, 1995.

肝虚血・再潅流初期の細胞傷害の機序（細胞内金属イオンの役割とキレート剤の役割） The mechanism of primary ischemia/reoxygenation injury from the aspect of iron chelation　　　　　　　　　　　　　　　
今日の移植, 8, 207, 211, 1995年

難治性腹水を有する透析患者に対する腹水ポンプの検討
春口 洋昭, 新開 真人, 赤松 真, 尾崎 倫孝, 小池 太郎, 阿部 正浩, 星野 智昭, 石田 英樹, 佐藤 純彦, 中村 道郎, 小山 一郎, 中島 一朗, 河合 達郎, 渕之上 昌平, 寺岡 慧, 阿岸 鉄三, 太田 和夫, 透析療法学会誌, 28, 8, 1135, 1141, 1995年
日本語

膵移植の現況と課題
寺岡慧, 今日の移植, 7, 139, 147, 1994年

膵腎複合移植の現況と将来の課題　　　　　　　　　　　　　　　
総合臨床, 43, 247, 254, 1994年

302 肝虚血・再潅流時のフリーラジカルによる組織障害の機序と障害の場に関する実験的考察(<特集>第41回日本消化器外科学会総会)
尾崎 倫孝, 淵之上 昌平, 寺岡 慧, 太田 和夫, 日本消化器外科学会雑誌, 26, 2, 527, 527, 1993年02月01日
一般社団法人日本消化器外科学会, 日本語

Michitaka Ozaki, Teruyuki Kawabata, Michiyasu Awai: Iron release from haemosiderin and production of iron catalysed hydroxyl radical in vitro in Medical Biochemical and Chemical aspects of free radicals. (O.Hayaishi, E.Niki, M.Kondo,T.Yoshikawa eds.) p・・・　　　　　　　　　　　　　　　
1989年
Michitaka Ozaki, Teruyuki Kawabata, Michiyasu Awai: Iron release from haemosiderin and production of iron catalysed hydroxyl radical in vitro in Medical Biochemical and Chemical aspects of free radicals. (O.Hayaishi, E.Niki, M.Kondo,T.Yoshikawa eds.) pp.149-152 Elsevier Science Publishers, B.V. Amsterdam, 1989.

経過中に皮膚の硬結性紅斑とImmunoblastic lymphoadenopathy(IBL)様リンパ節腫脹をきたした肺結核症の一剖検例　　　　　　　　　　　　　　　
臨床と剖検, 38, 73, 73, 1987年

Niemann-Pick病C型の一剖検例　　　　　　　　　　　　　　　
臨床と剖検, 37, 105, 105, 1986年

「移植のための臓器摘出と保存」　　　　　　　　　　　　　　　
尾崎 倫孝
シュプリンガー・ジャパン, 2012年, ［共著］

有酸素運動が脳内出血後の機能障害と脳由来神経栄養因子発現動態に与える影響 -生体発光イメージングを用いた検証-　　　　　　　　　　　　　　　
杉山拓也, 高松泰行, 芳賀早苗, 尾崎倫孝, 岡優一郎, 福地守, 前島洋
第29回日本基礎理学療法学会学術大会
2024年10月12日 - 2024年10月13日

低温ストレスに対する肝細胞応答の基礎的検討　　　　　　　　　　　　　　　
尾崎倫孝, 芳賀早苗, 森田直樹, 神繁樹, 的場光太郎
第31回肝細胞研究会, 2024年07月26日
2024年07月26日 - 2024年07月27日

Poly (ADP-ribose) polymerase (PARP)が制御する肝虚血再灌流傷害の新しい機序の探索　　　　　　　　　　　　　　　
芳賀早苗, 森田直樹, 神繁樹, 的場光太郎, 尾崎倫孝
第31回肝細胞研究会, 2024年07月26日
2024年07月26日 - 2024年07月27日

玄米米糠発酵食品（FBRA）による非アルコール性脂肪肝炎の予防効果　　　　　　　　　　　　　　　
根本英幸, 堀江裕紀子, 伊藤麻里, 芳賀早苗, 尾崎倫孝
第78回日本栄養・食糧学会大会
2024年05月24日 - 2024年05月26日

ストレスによる細胞・組織傷害と再生- 臨床的な視点で覗き見た基礎研究から思うこと -　　　　　　　　　　　　　　　
尾崎倫孝
大学院セミナー 旭川医科大学, 2024年02月28日

単回運動による生体脳BDNF発現の経時的変化：in vivo発光イメージングを用いた検証　　　　　　　　　　　　　　　
井上 貴博, 池上 遼, 高松 泰行, 福地 守, 芳賀 早苗, 尾崎 倫孝, 前島 洋
第28回日本基礎理学療法学会学術大会
2023年12月02日 - 2023年12月03日

脳出⾎が脳由来神経栄養因⼦の発現に与える影響 –⽣体発光イメージング技術を⽤いた検討–　　　　　　　　　　　　　　　
杉山拓也, 高松泰行, 芳賀早苗, 尾崎倫孝, 岡優一郎, 福地守, 前島洋
第28回日本基礎理学療法学会学術大会
2023年12月02日 - 2023年12月03日

がん細胞における光を利用したプログラム死誘導システム開発の試み　　　　　　　　　　　　　　　
芳賀 早苗, 森田 直樹, 小澤 岳昌, 尾崎 倫孝
第96回日本生化学会大会, 2023年11月01日, 日本語, ポスター発表
2023年10月31日 - 2023年11月02日

NIPTを受けるために遺伝カウンセリングを受けた人々の実態　　　　　　　　　　　　　　　
田中里佳, 尾崎倫孝, 荒木奈緒
第64回日本母性衛生学会総会・学術集会, 2023年10月14日
2023年10月13日 - 2023年10月14日

「光プローブをもちいた肝の酸化ストレスと傷害（プログラム細胞死）の観察と評価」 シンポジウム1 ［肝臓を視る、知る、創る］　　　　　　　　　　　　　　　
尾崎 倫孝, 芳賀 早苗, 森田 直樹, 小澤 岳昌
第28回肝細胞研究会（ハイブリッド開催 淡路夢舞台・Zoom）, 2021年09月10日

「肝虚血再灌流傷害進展における Poly（ADP-ribose）polymerase（PARP）依存性細胞死の解析」　　　　　　　　　　　　　　　
尾崎 倫孝, 芳賀 早苗, 浅野 真未, 菅野 憲, 小澤 岳昌, 森田 直樹
第27回肝細胞研究会（デジタル開催）
2020年12月15日 - 2020年12月16日

「時計遺伝子発現定量解析を用いた糖尿病発症機構解明」　　　　　　　　　　　　　　　
石井悠暉, 長沢光樹, 林珠理, 吉田幸那, 狩野晴美, 石川正純, 尾崎 倫孝, 浜田和子, 浜田俊幸
第64回日本薬学会 関東支部大会（デジタル開催）, 2020年09月19日

「生体リズムが乱れる過程をリアルタイムに解析するシステムの構築 ～病態モデルマウスを用いての検討～」　　　　　　　　　　　　　　　
長沢光樹, 石井悠暉, 林珠理, 吉田幸那, 狩野晴美, 石川正純, 尾崎 倫孝, 浜田和子, 浜田俊幸
第64回日本薬学会 関東支部大会（デジタル開催）, 2020年09月19日

「肝臓疾患モデルについて」 研究セミナー　　　　　　　　　　　　　　　
尾崎 倫孝
FBRA研究会 玄米酵素（株）本社4階会議室, 2020年09月18日

「様々な様式の細胞死は、慢性脂肪肝における遷延化した組織傷害に関与する可能性がある」　　　　　　　　　　　　　　　
芳賀 早苗, 森田 直樹, 小澤 岳昌, 尾崎 倫孝
第93回日本生化学会大会 （WEB開催）
2020年09月14日 - 2020年09月16日

Poly(ADP-ribose) polymerase plays a critical role in oxidative stress- and hypoxia/reoxygenation-induced programmed cell death in mouse liver cells.　　　　　　　　　　　　　　　
Michitaka Ozaki, Sanae Haga, Mami Asano, Naoki Morita
The Digital International Liver Congress 2020
2020年08月27日 - 2020年08月29日

「In vivo 長期間遺伝子発現定量解析におけるL-ルシフェリンのルシフェリン-ルシフェラーゼ反応阻害効果」　　　　　　　　　　　　　　　
中島 かな子, 伊藤 遼河, 菊池 祥裕, 狩野 晴美, 千島 綾, 太田 あかり, 石川 正純, 尾崎 倫孝, 浜田 和子, 浜田 俊幸
日本薬学会 第140年会 京都国際会議場（WEB開催）
2020年03月25日 - 2020年03月28日

「自由行動マウスの長期間遺伝子発現を検出するための機器製作」　　　　　　　　　　　　　　　
千島 綾, 狩野 晴美, 太田 あかり, 中島 かな子, 菊池 祥裕, 伊藤 遼河, 石川 正純, 尾崎 倫孝, 浜田 和子, 浜田 俊幸
日本薬学会 第140年会 京都国際会議場（WEB開催）
2020年03月25日 - 2020年03月28日

「PMT埋め込みマウスの長期間遺伝子発現解析」　　　　　　　　　　　　　　　
菊池 祥裕, 中島 かな子, 狩野 晴美, 千島 綾, 太田 あかり, 伊藤 遼河, 石川 正純, 尾崎 倫孝, 浜田 和子, 浜田 俊幸
日本薬学会 第140年会 京都国際会議場（WEB開催）
2020年03月25日 - 2020年03月28日

「自由行動マウスの中枢と末梢組織の遺伝子発現を長期間同時計測するシステム開発」　　　　　　　　　　　　　　　
伊藤 遼河, 菊池 祥裕, 中島 かな子, 狩野 晴美, 千島 綾, 石川 正純, 尾崎 倫孝, 浜田 和子, 浜田 俊幸
日本薬学会 第140年会 京都国際会議場（WEB開催）
2020年03月25日 - 2020年03月28日

「PARP が関与する肝傷害の意義」　　　　　　　　　　　　　　　
尾崎 倫孝
第32回日本肝臓医生物学研究会；LBSG-J（プロメテウスの会） 東京医科歯科大学 M&D タワー21階 大学院講義室, 2020年03月07日

Palmitate induces release of pro-inflammatory cytokines prior to cell death in mouse AML12 hepatocytes.　　　　　　　　　　　　　　　
Mami Asano, Sanae Haga, Shiina Itashiki, Sae Kamada, Aya Mikami, Michitaka Ozaki
CSH-Asia Liver, Biology, Diseases & Cancer, AWAJI (Awaji Yumebutai Conference Center), JAPAN
2019年12月09日 - 2019年12月12日

In vivo multi-recording system of clock gene expression in deep areas of the body using a photomultiplier tube.　　　　　　　　　　　　　　　
Kazuko Hamada, Ryoga Ito, Yoshihiro Kikuchi, Kanako Nakajima, Masayori Ishikawa, Michitaka Ozaki, Toshiyuki Hamada
Resonance Bio International Symposium, 2019年10月30日, 英語, シンポジウム・ワークショップパネル（公募）
［国際会議］

肝傷害および進展におけるPoly(ADP-ribose) polymerase-1(PARP1) の役割　　　　　　　　　　　　　　　
尾崎 倫孝
第31回日本肝臓医生物学研究会LBSG-J（プロメテウスの会）, 2019年10月12日, 日本語, シンポジウム・ワークショップパネル（指名）
［招待講演］, ［国内会議］

Fasリガンド/酸化ストレスによって引き起こされるプログラム細胞死の機序解析　　　　　　　　　　　　　　　
芳賀早苗, 森田直樹, 尾崎倫孝
第92回日本生化学会総会, 2019年09月18日, 日本語, ポスター発表
［国内会議］

非アルコール性脂肪肝炎に対するFBRAの抑制効果の検討　　　　　　　　　　　　　　　
尾崎 倫孝
第41回FBRA全国研究会, 2019年09月08日, 日本語, シンポジウム・ワークショップパネル（指名）
［招待講演］, ［国内会議］

肝虚血・再灌流、酸化ストレスと細胞死（臓器傷害）とその制御 -マウス肝における虚血再灌流傷害進展の分子機構 -　　　　　　　　　　　　　　　
尾崎 倫孝, 芳賀 早苗, 森田 直樹, 小澤 岳昌
第72回日本酸化ストレス学会学術集会, 2019年06月27日, 日本語, シンポジウム・ワークショップパネル（指名）
［招待講演］, ［国内会議］

脂肪肝における易傷害性メカニズム解析の基礎的研究　　　　　　　　　　　　　　　
芳賀早苗, 浅野真未, 森田直樹, 尾崎倫孝
第26回肝細胞研究会, 2019年05月23日, 日本語, ポスター発表
［国内会議］

The molecular mechanisms of oxidative stress, cell death and protection in liver/hepatocytes　　　　　　　　　　　　　　　
尾崎 倫孝
Invited Lecture at Dalian Medical University, 2018年12月07日, 英語, 公開講演，セミナー，チュートリアル，講習，講義等
［招待講演］, ［国際会議］

細胞・臓器の病態生理の時空間イメージングと研究・臨床への応用- 外科医が望むもの、そして今していること -　　　　　　　　　　　　　　　
尾崎倫孝, 芳賀早苗, 森田直樹, 浜田俊幸, 小澤岳昌
第16回医用分光学研究会, 2018年11月21日, 日本語, シンポジウム・ワークショップパネル（指名）
［招待講演］, ［国内会議］

「発光プローブによるプログラム細胞死（アポトーシス、ネクロプトーシス）動的解析の試み」　　　　　　　　　　　　　　　
芳賀 早苗, 菅野 憲, 小澤 岳昌, 森田 直樹, 浅野 真未, 伊 敏, 尾崎 倫孝
第27回日本Cell Death学会, 2018年
京都府立医科大学 図書館ホール、京都

「光による細胞生存能（Akt/PKB分子）制御に関する研究」　　　　　　　　　　　　　　　
芳賀 早苗, 小澤 岳昌, 森田 直樹, 伊 敏, 尾崎 倫孝
第91回日本生化学会, 2018年
国立京都国際会館、京都

「マウス脂肪肝モデルをもちいたビルベリーの予防効果に関する検討」　　　　　　　　　　　　　　　
芳賀 早苗, 伊 敏, 森田 直樹, 浅野 真未, 荘厳 哲哉, 尾崎 倫孝
第39会日本肥満学会, 2018年
神戸国際会議場、神戸

Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver with steatosis.　　　　　　　　　　　　　　　
Michitaka Ozaki, Sanae Haga, Yimi
IBD and Liver: East Meets West, 2018年
京都

「レドックスが制御するネクローシス型細胞死（ネクロプトーシス）の光プローブによる動的解析」　　　　　　　　　　　　　　　
芳賀 早苗, 菅野 憲, 小澤 岳昌, 森田 直樹, 浅野 真未, 尾崎 倫孝
第25回肝細胞研究会, 2018年
東京大学伊藤謝恩ホール、東京

「光プローブをもちいたプログラム細胞死（アポトーシス、ネクロプトーシス）の動的解析」　　　　　　　　　　　　　　　
尾崎 倫孝, 芳賀 早苗
第22回日本がん分子標的治療学会学術集会, 2018年
都市センターホテル、東京

「肝におけるレドックスバイオロジ−<制御と生理・病態> Redox Biology in Liver−regulation and physio-pathology ?」　　　　　　　　　　　　　　　
尾崎倫孝
MPO研究会, 2018年
北海道大学、札幌

Type XVII collagen suppresses interfollicular epidermal proliferation in neonatal and aged skin, and helps rejuvenate epidermis.　　　　　　　　　　　　　　　
Mika Watanabe, Ken Natsuga, Wataru Nishie, Giacomo Donati, Yu Fujimura, Tadasuke Tsukiyama, Hideyuki Ujiie, Michitaka Ozaki, Fiona M Watt, Hiroshi Shimizu
47th Annual ESDR Meeting, 2017年
オーストリア

Spatio-temporal imaging of cell/organ physio-pathology and its clinical application.　　　　　　　　　　　　　　　
Michitaka Ozaki, Sanae Haga, Toshiyuki Hamada, Takeaki Ozawa, Yuma Yamada
CIS Workshop 2017 “Innovative Bio-imaging toward Diagnosis and Therapy”, 2017年
北海道

脂肪化肝細胞・脂肪肝に対するビルベリーの効果とその機序の検討　　　　　　　　　　　　　　　
芳賀 早苗, 荘厳 哲哉, 伊 敏, 森田 直樹, 浅野 真未, 尾崎 倫孝
第24回肝細胞研究会, 2017年
旭川市民文化会館、旭川

肝核内受容体FXRはp62/SQSTM1およびSHPを経由して、それぞれ抗酸化・細胞保護効果、脂肪化抑制効果を示す　　　　　　　　　　　　　　　
尾崎 倫孝, 芳賀 早苗, 伊 敏
第24回肝細胞研究会, 2017年
旭川市民文化会館、旭川

マウス脂肪化肝細胞・脂肪肝に対するビルベリーの抑制効果の検討　　　　　　　　　　　　　　　
芳賀 早苗, 荘厳 哲哉, 伊 敏, 森田 直樹, 浅野 真未, 尾崎 倫孝
第38回日本肥満学会, 2017年
大阪国際会議場、大阪

肝細胞におけるレドックス依存性ネクロプトーシスの動態解析　　　　　　　　　　　　　　　
芳賀 早苗, 菅野 憲, 小澤 岳昌, 森田 直樹, 浅野 真未, 伊 敏, 尾崎 倫孝
ConBio2017, 2017年
神戸国際会議場、神戸

ビルベリー抽出物の糖尿病性網膜症発症・進行予防効果に関する基礎的研究　　　　　　　　　　　　　　　
浅野 真未, 芳賀 早苗, 柴崎 彩, 黒澤 和也, 荘厳 哲哉, 尾崎 倫孝
ConBio2017, 2017年
神戸国際会議場、神戸

カスパーゼ3プローブ発現細胞を用いたクラミジア感染宿主細胞内のアポトーシス制御機構の探索　　　　　　　　　　　　　　　
松尾 淳司, 芳賀 早苗, 大久保 寅彦, 中村 眞二, 小澤 岳昌, 尾崎 倫孝, 山口 博之
ConBio2017, 2017年
神戸国際会議場、神戸

Type XVII collagen regulates proliferation in the interfollicular epidermis.　　　　　　　　　　　　　　　
Mika Watanabe, Ken Natsuga, Yasuaki Kobayashi, Wataru Nishie, Giacomo Donati, Shotaro Suzuki, Yu Fujimura, Tadasuke Tsukiyama, Hideyuki Ujiie, Satoru Shinkuma, Masamoto Murakami, Michitaka Ozaki, Masaharu Nagayama, Fiona. M Watt, Hiroshi Shimizu
日本研究皮膚科学会 第42回年次学術大会・総会, 2017年
高知市文化プラザ かるぽーと、高知

Optical evaluation and monitoring of oxidative stress & damage in vivo.　　　　　　　　　　　　　　　
Sanae Haga, Takeaki Ozawa, Naoki Morita, Mami Asano, James Remington, Michitaka Ozaki
19th International Symposium on Bioluminescence & Chemiluminescence(ISBC2016)., 2016年
筑波

Long-term ex vivo and in vivo monitoring of tumor progression by using dual luciferases.　　　　　　　　　　　　　　　
Naoki Morita, Sanae Haga, Yoshihiro Ohmiya, Michitaka Ozaki
19th International Symposium on Bioluminescence & Chemiluminescence (ISBC2016)., 2016年
筑波

Function of Toll-like receptor 2 in the murine inflammatory response to Rhodococcus aurantiacus infection.　　　　　　　　　　　　　　　
Yimin, Masashi Kohanawa, Sanae Haga, Michitaka Ozaki
4th Annual Meeting of the International Cytokine and Interferon Society (ICIS) ．, 2016年
米国

ビルベリーによる非アルコール性脂肪肝炎(NASH)の予防に向けた基礎的検討」（ポスター）　　　　　　　　　　　　　　　
芳賀 早苗, 荘厳 哲哉, 森田 直樹, 浅野 真未, 尾崎 倫孝
第23回肝細胞研究会, 2016年
大阪大学中之島センター、大阪

ビルベリーの糖尿病性網膜症初期病変抑制効果の検討　　　　　　　　　　　　　　　
芳賀早苗, 荘厳哲哉, 森田直樹, 浅野真未, 尾崎倫孝
第89回日本生化学会大会, 2016年
仙台国際センター、仙台

光プローブをもちいた時空間的病態解析と積極的病態制御の試み　　　　　　　　　　　　　　　
尾崎 倫孝, 芳賀 早苗, 小澤 岳昌, 山田 勇磨
第71回日本消化器外科学会総会 特別企画「光エネルギーの医療への展開」（, 2016年
あわぎんホール、徳島

FXRを起点とした脂肪肝傷害抑制と 脂肪化改善の機序　　　　　　　　　　　　　　　
尾崎 倫孝, 芳賀 早苗, 森田 直樹
第25回日本肝臓医生物学研究会；LBSG-J（プロメテウスの会）, 2016年
ナスパニューオータニ、新潟

「光技術を用いた臓器・細胞機能評価と制御の可能性」　　　　　　　　　　　　　　　
尾崎倫孝, 芳賀早苗, 小澤岳昌, 森田直樹, 浜田俊幸
第43回日本臓器保存生物医学会学術集会, 2016年
東京薬科大学、東京

“光”を利用した肝細胞機能制御技術の開発　　　　　　　　　　　　　　　
芳賀 早苗, 小澤 岳昌, 森田 直樹, 野田 なつみ, 尾崎 倫孝
第22回肝細胞研究会 ポスターセッション6「創薬・新しい実験系の開発」, 2015年
米子コンベンションセンター、鳥取

統合的ストレス応答による脂肪肝再生障害の分子メカニズムの解明　　　　　　　　　　　　　　　
稲葉 有香, 芳賀 早苗, 尾崎 倫孝, 春日 雅人, 井上 啓
第22回肝細胞研究会 一般口演5「肝再生」, 2015年
米子コンベンションセンター、鳥取

種々の病態における肝臓ストレスの解析−生体イメージング法による動的解析の試み−　　　　　　　　　　　　　　　
尾崎倫孝
金沢大学脳・肝インターフェースメディシン研究センター研究セミナー, 2015年
金沢大学医学図書館十全記念スタジオ、金沢

肝における酸化ストレス、傷害と炎症　　　　　　　　　　　　　　　
尾崎倫孝
鳥取大学セミナー, 2015年
鳥取大学医学部、鳥取県

肝細胞（とくに脂肪化肝細胞）における酸化ストレスと細胞死について　　　　　　　　　　　　　　　
尾崎倫孝
第22回日本肝臓医生物学研究会；LBSG-J（プロメテウスの会）, 2015年
しいのき迎賓館3階セミナー室B、金沢

光イメージングによる虚血再灌流傷害の動的・質的解析　　　　　　　　　　　　　　　
尾崎倫孝
第115回日本外科学会定期学術集会, 2015年
名古屋国際会議場、名古屋

脂肪肝における肝切除後肝傷害・肝再生不全の機序について　　　　　　　　　　　　　　　
尾崎 倫孝, 芳賀 早苗, 小澤 岳昌, 森田 直樹, 井上 啓, 稲葉 有香
第22回肝細胞研究会, 2015年
米子コンベンションセンター、鳥取県

肝臓ストレスと生活習慣病　　　　　　　　　　　　　　　
尾崎倫孝
第46回北海道大学白菊会総会, 2015年
北海道大学 学術交流会館、札幌

核内受容体を介した肝細胞機能制御　　　　　　　　　　　　　　　
尾崎倫孝
第23回日本肝臓医生物学研究会；LBSG-J（プロメテウスの会）, 2015年
丸駒温泉旅館、千歳

光技術を応用した移植臓器（組織）のモニタリングと制御の試み　　　　　　　　　　　　　　　
尾崎 倫孝, 芳賀 早苗, 森田 直樹, 伊 敏, 菅野 憲, 小澤 岳昌
第51回日本移植学会総会, 2015年
ホテル日航熊本、熊本県

Development of a novel in vivo optic imaging technology for biological diagnosis and therapy. (生物学的診断と治療のための新たな生体光イメージング技術の開発)　　　　　　　　　　　　　　　
尾崎倫孝, 芳賀早苗, 森田直樹, 伊 敏, 山田勇磨, 小澤岳昌
第74回 日本癌学会学術総会, 2015年
名古屋国際会議場、名古屋

p62/SQSTM1 を基軸とした新たな肝臓・肝細胞保護・機能維持法の探索　　　　　　　　　　　　　　　
尾崎 倫孝, 芳賀 早苗, 森田 直樹, 伊 敏
第42回日本臓器保存生物医学会学術集会、シンポジウム, 2015年
いわて県民情報交流センター、岩手

種々の病態下における肝再生の分子機構 −増殖・成長と傷害−　　　　　　　　　　　　　　　
尾崎 倫孝
京都肝胆膵外科カンファランス（特別講演）, 2015年
芝蘭会館、京都

Application of an Optic Imaging Techology for Organ Transplantation “移植におけるイメージング技術の応用”　　　　　　　　　　　　　　　
Michitaka Ozaki
Harvard Medical School - Harvard University, 2014年
米国

Development of a New in vivo Optic Probe for Biological Diagnosis and Therapy. Session ? “New Technology for Innovative Medicine”,　　　　　　　　　　　　　　　
Michitaka Ozaki, Takeaki Ozawa, Yuma Yamada
The Uehara Memorial Foundation Symposium 2014 “INNOVATIVE MEDICINE” Basic Research and Development, 2014年
東京

新規分泌型発光プローブをもちいたマウス腫瘍の増殖モニタリング　　　　　　　　　　　　　　　
森田 直樹, 尾崎 倫孝
第18回日本がん分子標的治療学会学術集会, 2014年
仙台市情報産業プラザ（AER）、ホテルメトロポリタン仙台、仙台

p62/SQSTM1が制御する肝細胞障害機序の解析　　　　　　　　　　　　　　　
芳賀 早苗, 小澤 岳昌, 山田 勇磨, 森田 直樹, 野田 なつみ, 尾崎 倫孝
第21回肝細胞研究会, 2014年
東京医科歯科大学、東京

高血糖および脂肪化状態が肝虚血/再灌流傷害に及ぼす影響 Impact of high glucose and steatosis upon ischemia/reperfusion-induced liver injury in mouse.　　　　　　　　　　　　　　　
芳賀 早苗, 小澤 岳昌, 森田 直樹, 野田 なつみ, 尾崎 倫孝
第87回日本生化学会, 2014年
京都国際会議場、京都

光イメージング技術を用いた肝病態の解析　　　　　　　　　　　　　　　
尾崎 倫孝, 芳賀 早苗, 野田 なつみ, 森田 直樹, 小澤 岳昌
第21回肝細胞研究会 シンポジウム1「肝疾患の病態を制御するメカニズム」, 2014年
東京医科歯科大学、東京

肝臓のストレス応答（傷害と再生）について -脂肪肝からNASHへ-　　　　　　　　　　　　　　　
尾崎倫孝
国立病院機構福山医療センター オープンカンファレンス, 2014年
国立病院機構福山医療センター熊ヶ峰ホール、福山

“ 光” を利用した新たな細胞・臓器保存法の開発　　　　　　　　　　　　　　　
芳賀 早苗, 小澤 岳昌, 森田 直樹, 野田 なつみ, 尾崎 倫孝
第41回日本臓器保存生物医学会学術集会 平成25 年度日本臓器保存生物医学会奨励賞 受賞記念講演, 2014年
千里ライフサイエンスセンター、大阪

肝臓ストレスとストレス応答（傷害と再生）の分子機構の解析と動的理解の試み　　　　　　　　　　　　　　　
尾崎倫孝
第43回染色体工学研究セミナー, 2014年
鳥取大学染色体工学研究センター 臨床講義棟2階421講義室、鳥取県

p62/SQSTM1 plays a protective role from oxidative injury of steatotic liver in mouse hepatectomy model.　　　　　　　　　　　　　　　
Sanae Haga, Takeaki Ozawa, Naoki Morita, Yayoi Seki, Yuma Yamada, Yukari Yasuzaki, Kazuo Umezawa, Michitaka Ozaki
The 20th Annual Meeting of the Japanese Society for the Research of Hepatic Cells,Osaka．, 2013年
大阪（International Convention Center）

「光を応用した生物学的診断・治療法の開発」　　　　　　　　　　　　　　　
尾崎倫孝
上原記念生命科学財団特定研究「革新的医療を創生する医学研究」, 2013年
下田セントラルホテル、静岡

Bioluminescent imaging of hepatic caspase-3 activity in mice.　　　　　　　　　　　　　　　
Sanae Haga, Takeaki Ozawa, Michitaka Ozaki
第14回国際組織細胞化学会議, 2012年
京都（国立京都国際会館）

STAT3 plays a pivotal role in cell adhesion in mouse hepatocytes by regulating E-cadherin expression.　　　　　　　　　　　　　　　
Sanae Haga, Hiroshi Inoue, A.Kano, X.-Y.Fu, K.Terui, Michitaka Ozaki
25 th European Congress of Pathology., 2012年
Prague,Czech（Prague Congress Centre）

Bio-imaging of surgical stress: Dynamic analysis of liver oxidative stress and damage.　　　　　　　　　　　　　　　
Naoki Morita, Sanae Haga, Takeaki Ozawa, S. J. Remington, Michitaka Ozaki
17th International Symposium on Bioluminescence and Chemiluminescence(ISBC2012), 2012年
カナダ

Collagen Vitrigel Sheet’as a Novel Drug Delivery Bio-material.　　　　　　　　　　　　　　　
Sanae Haga, Toshiaki Takezawa, Takeaki Ozawa, James Remington, Naoki Morita, Michitaka Ozaki
5th European Conference of the International Federation for Medical and Biological Engineering., 2011年
Bdapest/Hungary（Bdapest Congress&World Trade Center）

Bio-imaging of Surgical Stresses-Dynamic Analyses of Liver Oxidative Stress and Damage.　　　　　　　　　　　　　　　
Michitaka Ozaki, Sanae Haga, Takeaki Ozawa, Naoki Morita, Yoshimi Kaneshima, J. Remington
5TH European Conference of the International Federation for Medical and Biological Engineering., 2011年
Bdapest/Hungary（Bdapest Congress&World Trade Center）

Age-associated p66Shc induced redox-dependent liver damage and impaired regeneration after hepatectomy in aged mice.　　　　　　　　　　　　　　　
Michitaka Ozaki, Sanae Haga, Kaikobad Irani, NaokiMorita, Yoshimi Kaneshima, Takeaki Ozawa
62th Annual meeting of AASLD．, 2011年
San Francisco/USA（Moscone West Convention Center）

Effects of a Novel Immunosuppressive Agent, DTCM?Glutarimide Alone or in Combination with Donor Specific Transfusion in Mouse Cardiac Allo?Transplantation.　　　　　　　　　　　　　　　
Yusuke Tsunetoshi, Kenichiro Yamashita, Susumu Shibasaki, Ryoichi Goto, KenjiWakayama, Gentaro Hirokata, Masaaki Zaitsu, Shoko Kimura, Rumi Igarashi, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
2010 American Transplant Congress (ATC)., 2010年
San Diego/USA

Immunosuppressive Effects of Regulatory Dendritic Cells Induced by NK026680.　　　　　　　　　　　　　　　
Susumu Shibasaki, Kenichiro Yamashita, Ryoichi Goto, Kenji Wakayama, Gentaro Hirokata, Yusuke Tsunetoshi, Masaaki Zaitsu, Rumi Igarashi, Sanae Haga, Yoshiki Yanagawa, Michitaka Ozaki, Satoru Todo
2010 American Transplant Congress (ATC)., 2010年
San Diego/USA

A Novel Solution for Rat Liver Preservation Composed of Heavy Water and Swan Buffer; a Pilot Study.　　　　　　　　　　　　　　　
Daisuke Fukumori, Moto Fukai, Kenji Wakayama, Kenichiro Yamashita, Shinya Ueki, Mitsuru Sugawara, Sanae Haga, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo
2010 American Transplant Congress (ATC)., 2010年
San Diego/USA

Heavy Water Containing Solution Ameliorates Cold Preservation Injury of the Rat Heart.　　　　　　　　　　　　　　　
Kenji Wakayama, Moto Fukai, Kenichiro Yamashita, Daisuke Fukumori, Mitsuru Sugawara, Susumu Shibasaki, Gentaro Hirokata, Masaaki Zaitsu, Yusuke Tsunetoshhi, Michitaka Ozaki, Satoru Todo
2010 American Transplant Congress (ATC)., 2010年
San Diego/USA

Heavy Water (D2O) Universally Ameliorates Cold Preservation Injury: Precise Analyses of Cytoprotective Mechanisms In Vitro.　　　　　　　　　　　　　　　
Moto Fukai, Kenji Wakayama, Daisuke Fukumori, Kenichiro Yamashita, Mitsuru Sugawara, Sanae Haga, Shinya Ueki, Gentaro Hirokata, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo
2010 American Transplant Congress (ATC)., 2010年
San Diego/USA

DTCM?Glutarimide, a New Activator Protein?1 (AP?1) Inhibitor Ameliorates Chronic Allograft Vasculopathy in Mice.　　　　　　　　　　　　　　　
Masaaki Zaitsu, Kenichiro Yamashita, Susumu Shibasaki, Ryoichi Goto, Kenji Wakayama, Gentaro Hirokata, Shoko Kimura, Yusuke Tsunetoshi, Rumi Igarashi, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
2010 American Transplant Congress (ATC)., 2010年
San Diego/USA

CD40?CD154 Costimulation Blockade Plus NF?κB Inhibition Permits a Successful Single?Donor Islet Transplantation in Mice.　　　　　　　　　　　　　　　
Yasuyuki Koshizuka, Kenichiro Yamashita, Masaaki Watanabe, Daisuke Kuraya, Masaomi Ogura, Tadashi Yoshida, Hirofumi Kamachi, Michiaki Matsushita, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo
2010 American Transplant Congress (ATC)., 2010年
San Diego/USA

Immunosuppressive Effect of DTCM?Glutarimide, a Novel AP?1 Inhibitor, onAllogeneic Islet Transplantation in Mice.　　　　　　　　　　　　　　　
Tadashi Yoshida, Kenichiro Yamashita, Masaaki Watanabe, Yasuyuki Koshizuka, Daisuke Kuraya, Masaomi Ogura, Hirofumi Kamachi, Michitaka Ozaki, Michiaki Matsushita, Kazuo Umezawa, Satoru Todo
2010 American Transplant Congress (ATC)., 2010年
San Diego/USA

A single infusion of the ex-vivo generated immuno-regulatory dendritic cells under a novel agent, NK026680 markedly prolongs cardiac allograft survival.　　　　　　　　　　　　　　　
Susumu. Shibasaki, Kenichiro Yamashita, Y. Yanagawa, Kenji Wakayama, Hirokata Gentaro, Yusuke Tsunetoshi, Masaaki Zaitsu, Rumi Igarashi, Sanae Haga, Michitaka Ozaki, Satoru Todo
XXIII International Congress of the Transplantation Society., 2010年
Vancouver/Canada

Heavy water containing organ preservation solution, Dsol, ameliorates graft survival and function of the rat hearts after extended cold preservation.　　　　　　　　　　　　　　　
Kenji Wakayama, Moto Fukai, Kenichiro Yamashita, Daisuke Fukumori, Susumu Shibasaki, Gentaro Hirokata, Masaaki Zaitsu, Yusuke Tsunetoshi, Mitsuru Sugawara, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo
XXIII International Congress of the Transplantation Society., 2010年
Vancouver/Canada

Important characteristics of heavy water (D2O) containing cold preservation solution.　　　　　　　　　　　　　　　
Moto Fukai, Daisuke Fukumori, Kenji Wakayama, Kenichiro Yamashita, Mitsuru Sugawara, Sanae Haga, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo
XXIII International Congress of the Transplantation Society., 2010年
Vancouver/Canada

Successful islet transplantation from a single-donor based on CD40-CD154 costimulation blockade plus NF-κB inhibition.　　　　　　　　　　　　　　　
Yasuyuki Koshizuka, Kenichiro Yamashita, Masayuki Watanabe, Daisuke Kuraya, Masaomi Ogura, Takashi Yoshida, Hirohumi Kamachi, Michiaki Matsushita, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo
XXIII International Congress of the Transplantation Society., 2010年
Vancouver/Canada

DTCM-glutarimide, a new activator protein-1 (AP-1) inhibitor ameliorates transplant vasculopathy in mice.　　　　　　　　　　　　　　　
Masaaki Zaitsu, Kenichiro Yamashita, Susumu Shibasaki, Ryoichi Goto, Krnji Wakayama, Hirokata Gentaro, Yusuke Tsunetoshi, Rumi Igarashi, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
XXIII International Congress of the Transplantation Society., 2010年
Vancouver/Canada

A novel immunosuppressive agent, DTCM-glutarimide markedly prolongs cardiac allograft survival in mouse when combined with Donor specific transfusion.　　　　　　　　　　　　　　　
Yusuke Tsunetoshi, Kenichiro Yamashita, Susumu Shibasaki, Ryoichi Goto, Kenji Wakayama, Gentaro Hirokata, Masaaki Zaitsu, Shoko Kimura, Rumi Igarashi, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
XXIII International Congress of the Transplantation Society., 2010年
Vancouver/Canada

Heavy water containing solution reduces injury of grafts subjected to extended cold preservation in an isolated perfused rat liver model.　　　　　　　　　　　　　　　
Daisuke Fukumori, Moto. Fukai, Kenji Wakayama, Kenichiro Yamashita, Mitsuru Sugawara, Hirokata. Gentaro, M. Zaitsu, Yusuke Tsunetoshi, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo
XXIII International Congress of the Transplantation Society., 2010年
Vancouver/Canada

The immune-regulatory function of ex-vivo modulated dendritic cells by a novel immunosuppressive agent, NK026680.　　　　　　　　　　　　　　　
Susumu Shibasaki, Kenichiro Yamashita, Yoshiki Yanagawa, Kenji Wakayama, Gentaro Hirokata, Yusuke Tsunetoshi, Masaaki Zaitsu, Rumi Igarashi, Sanae Haga, Michitaka Ozaki, Satoru Todo
14th International Congress of Immunology, 2010年
神戸

Analysis of genomic abnormal area concerning biological malignant potential and prognosis of hepatocellular carcinoma by high sensitive array CGH.　　　　　　　　　　　　　　　
Kazuaki Nakanishi, Keiko Morita, Mituhiro Tada, Nobumoto Tomioka, Toshiya Kamiyama, Hideki Yokoo, Masato Takahashi, Michitaka Ozaki, Michiaki Matushita, Satoru Todo, Takashi Hirano
2009 The American Hepato-Pancreato-Biliary Association annual meeting., 2009年
Miami/USA

The Immunomodulatory Effect of NF-κB Blockade Is Augmented or Abrogated by NFAT Inhibition When Given with Donor-Specific Transfusion.　　　　　　　　　　　　　　　
Ryoichi Goto, Kenichiro Yamashita, Shinya Ueki, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Hiroyuki Furukawa, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo
American Transplant Congress., 2009年
Boston/USA

NK026680, a Novel Triazolopyrimidine Derivative, for Allogeneic Islet Transplantation in Mice.　　　　　　　　　　　　　　　
Yasuyuki Koshizuka, Kenichiro Yamashita, Masaaki Watanabe, Susumu Shibasaki, Daisuke Kuraya, Shigeru Nakakimura, Michitaka Ozaki, Hirofumi Kamachi, Michiaki Matsushita, Satoru Todo
American Transplant Congress., 2009年
Boston/USA

A Novel Triazolopyrimidine Derivative, NK026680 Inhibits T Cell Function, and Prolongs Cardiac Allograft Survival in Rats.　　　　　　　　　　　　　　　
Susumu Shibasaki, Kenichiro Yamashita, Ryoichi Goto, Tetsu Oura, Kenji Wakayama, Gentaro Hirokata, Tomohiro Shibata, Rumi Igarashi, Sanae Haga, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo
American Transplant Congress., 2009年
Boston/USA

Prevention of Graft Failure Caused by IBMIR with a Novel NF-κB Inhibitor, Dehydroxymethylepoxyquinomicin (DHMEQ) after Intraportal Islet Transplantation in Mice.　　　　　　　　　　　　　　　
Daisuke Kuraya, Hirofumi Kamachi, Masaaki Watanabe, Yasuyuki Koshizuka, Shigeru Nakakimura, Michitaka Ozaki, Kazuo Umezawa, Kenichiro Yamashita, Michiaki Matsushita, Satoru Todo
American Transplant Congress., 2009年
Boston/USA

Combined Treatment with a Nuclear Factor (NF)-κB Inhibitor, DHMEQ, and Tacrolimus Permits a Long-Term Allogeniec Islet Engraftment in Mice.　　　　　　　　　　　　　　　
Masaaki Watanabe, Kenichiro Yamashita, Hirofumi Kamachi, Daisuke Kuraya, Yasuyuki Koshizuka, Shigeru Nakakimura, Michitaka Ozaki, Kazuo Umezawa, Michiaki Matsushita, Satoru Todo
American Transplant Congress., 2009年
Boston/USA

Re-Evaluation of Heavy Water for Organ Preservation Solution; In Vitro Study.　　　　　　　　　　　　　　　
Moto Fukai, Kenichiro Yamashita, Kenji Wakayama, Daisuke Fukumori, Ryoichi Goto, Sanae Haga, Gentaro Hirokata, Shigeru Nakakimura, Mitsuru Sugawara, Hirofumi Kamachi, Tomomi Suzuki, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michiaki Matsushita, Michitaka Ozaki, Satoru Todo
American Transplant Congress., 2009年
Boston/USA

Extended Preservation of Rat Hearts with Novel Organ Preservation Solution:Role of Actin Cytoskeleton and ATP Maintenance.　　　　　　　　　　　　　　　
Kenji Wakayama, Moto Fukai, Kenichiro Yamashita, Daisuke Fukumori, Susumu Shibasaki, Gentaro Hirokata, Tomohiro Shibata, Tetsu Oura, Ryoichi Goto, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Michiaki Matsushita, Hiroyuki Furukawa, Michitaka Ozaki, Taisuke Ono, Mitsuru Sugawara, Satoru Todo
American Transplant Congress., 2009年
Boston/USA

A novel NF-κB inhibitor DHMEQ could suppress peritoneal dissemination of gastric cancer by anti-tumor /-adhesive effects in mice.　　　　　　　　　　　　　　　
Kazuhiro Mino, Kazuaki Nakanishi, Sanae Haga, Masanori Sato, Masaya Kina, Hideki Yokoo, Toshiya Kamiyama, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo
ECCO 15 / ESMO 34 Multidisciplinary Congress, 2009年
Berlin/Germany

A novel NF-κBinhibitor DHMEQ suppressed peritoneal dissemination of pancreatic cancer in mouse xenograftmodel.　　　　　　　　　　　　　　　
Masanori Sato, M. Ozaki, K. Nakanishi, T. Watanabe, S. Haga, K. Mino, H. Yokoo, K. Umezawa, Y. Ohmiya, T. Kamiyama, S. Todo
ECCO 15 / ESMO 34 Multidisciplinary Congress, 2009年
Berlin/Germany

Hepatic ischemia induced immediate oxidative stress after reperfusion and determined the severity of the reperfusion-induced damage. ? in vivo dynamic analysis of liver oxidative stress and damage ?　　　　　　　　　　　　　　　
Sanae Haga, S. James Remington, Takeaki Ozawa, Naoki Morita, Keita Terui, Michitaka Ozaki
60th Annual meeting of AASLD., 2009年
Boston/USA

Heavy Water Reduced Cold Hypoxic Injury Of Cardiomyocytes.　　　　　　　　　　　　　　　
Moto Fukai, Kenichiro Yamashita, Kenji Wakayama, Daisuke Fukumori, Sanae Haga, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Taisuke Ono, Shintaro Kinugawa, Mitsuru Sugawara, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo
AHA2009-82nd Scientific Sessions of the American Heart Association., 2009年
Orlando/USA

Myocardial protection with a novel organ preservation solution containing deuterium oxide for prolonged cold ischemia of the heart.　　　　　　　　　　　　　　　
Kenji Wakayama, Moto Fukai, Kenichiro Yamashita, Daisuke Fukumori, Susumu Shibasaki, Gentaro Hirokata, Tetsu Oura, Ryoichi Goto, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo
AHA2009-82nd Scientific Sessions of the American Heart Association., 2009年
Orlando/USA

#1 molecular mechanism of liver injury, protection and regeneration, #2 bio-imaging of molecular functions and tumor by optic probes.　　　　　　　　　　　　　　　
Michitaka Ozaki
Japan-Denmark Joint Workshop on “Molecular Cancer Research, 2009年
東京

Bio-imagimg of Surgical Stress dynamic analysis of liver oxidative stress and damage.　　　　　　　　　　　　　　　
Michitaka Ozaki, Sanae Haga, Takeaki Ozawa, S. James Remington, Naoki Morita, Yoshihiro Ohmiya
Molecular Imaging for Systems Biology, 2009年
岡崎

.“The immunomodulatory effect of donor specific transfusion plus NF-kB blockade by utilizing a novel inhibitor, DHMEQ”　　　　　　　　　　　　　　　
Ryoichi Goto, Kenichiro Yamashita, Takeshi Aoyagi, Shinya Ueki, Rumi Igarashi, Motohiro Uno, Tetsu Oura, Masaaki Watanabe, Tomohiro Shibata, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
8th international conference, 2008年
Berlin/Germany

Inhibition of NF-kB Activation Augments Immunomodulatory Effect of Donor Specific Transfusion　　　　　　　　　　　　　　　
Goto R, Yamashita K, Aoyagi T, Ueki S, Uno M, Ohura T, Taniguchi M, Suzuki T, Shimamura T, Furukawa H, Umezawa K, Ozaki M, Todo S
Americn Transplant Congress 2011., 2008年
Berlin/Germany

A Novel NF-kappa B inhibitor, DHMEQ, Attenuates Arterial Vasculopathy.　　　　　　　　　　　　　　　
Uno M, Yamashita K, Shibata T, Aoyagi T, Ohura T, Haga S, Watanabe M, Umezawa K, Ozaki M, Todo S
Americn Transplant Congress 2010., 2008年
Toronto/Canada

A Novel Nuclear Factor kappa B inhibitor, DHMEQ Ameliorates Development of Obliterative Bronchiolitis in Heterotopic Murine Airway-Transplantation.　　　　　　　　　　　　　　　
Oshima Y, Uno M, Yamashita K, Shibata T, Aoyagi T, Umezawa K, Ozaki M, Todo S
Americn Transplant Congress 2009., 2008年
Toronto/Canada

Induction of Immunosuppressive Dendritic Cells by a Novel NF-kB inhibitor, DHMEQ.　　　　　　　　　　　　　　　
Takeshi Aoyagi, Kenichiro Ymashita, Y Yanagawa, Ryoichi Goto, Rumi Igarashi, Sanae Haga, Michitaka Ozaki, K Onoue, Kazuo Umezawa, Hiroyuki Furukawa, Satoru Todo
Americn Transplant Congress 2008., 2008年
Toronto/Canada

Effect of NF-FEB Inhibition by DHMEQ on Islet Transplantation in Mice.　　　　　　　　　　　　　　　
Masaaki Watanabe, Kenichiro Yamashita, Shuichiro Matsumoto, Yousuke Tsuruga, Thoru Takahashi, TetsuOura, Michitaka Ozaki, Kazuo Umezawa, Michiaki Matsushita, Satoru Todo
The Tranplantation Society2008, 2008年
Sydney/Australian

A novel NF-kB inhibitor, DHMEQ, Attenuates arterial Vasculopathy.　　　　　　　　　　　　　　　
Motohiro Uno, Kenichiro Yamashita, Tomohiro Shibata, Ryoichi Goto, Tetsu Oura, Masaaki Watanabe, Sanae Haga, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo
The Tranplantation Society2008, 2008年
Sydney/Australian

Inhibition of NF-kB and/or NFAT Activation Augments or Abrogates Immunomodulatory Effects of Donor Specific Transfusion.　　　　　　　　　　　　　　　
Ryoichi Goto, Kenichiro Yamashita, Ueki S, Masahiko Taniguchi, Tomomi Suzuki, Thuyoshi Shimamura, Hiroyuki Furukawa, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo
The Tranplantation Society2008, 2008年
Sydney/Australian

The Effect of DHMEQ, A Novel NF-kB Inhibitor on Development of Obliterative Bronchiolitis in Heterotopic Murine Airway Allo-transplantatin.　　　　　　　　　　　　　　　
Oshima Y, Uno M, Shibata T, Oura T, Watanabe M, Goto R, Umezawa K, Ozaki M, Yamashita K, Todo S
The Tranplantation Society2008, 2008年
Sydney/Australian

The Novel NF-EB Inhibitor, DHMEQ Prevents local and remote organ Injury Following Intestinal Ischemia/Reperfusion in Rats.　　　　　　　　　　　　　　　
Tomomi Suzuki, Kenichiro Yamashita, W Jomen, Shinya Ueki, Takeshi Aoyagi, Moto Fukai, Hiroyuki Furukawa, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo
The Tranplantation Society2008, 2008年
Sydney/Australian

Induction of Immunosuppressive Dendritic Cells by Novel Nuclear Factor-KappaB Inhibitor DHMEQ.　　　　　　　　　　　　　　　
Takeshi Aoyagi, Kenishiro Yamashita, R Yanagawa, Ryoichi Goto, Michitaka Ozaki, K Onoue, Kazuo Umezawa, Satoru Todo
The Tranplantation Society2008., 2008年
Sydney/Australian

Non-invasive realtime monitoring of oxidative stress and damage by newly developed optical probes in mouse liver ischemia/reperfusion.　　　　　　　　　　　　　　　
Michitaka Ozaki, Sanae Haga, S. James Remington, Takeaki Ozawa, Yuko Oikawa, Satoru Todo
AASLD annual meeting., 2008年
San Fransisco/USA

“Effect of A Novel NF-kB Inhibitor, Dehydroxymethylepoxyquinomicin in Combination with Dnonor Specific Transfusion in Mouse Heart Transolantation.”　　　　　　　　　　　　　　　
Goto R, Yamashita K, Aoyagi T, Uno M, Ueki S, Itoh T, Taniguchi M, Suzuki T, Shimamura T, Furukawa H, Ozaki M, Umezawa K, Todo S
American Transplant Congress, 2007年
San Francisco/USA

Donor pretreatment with a novel NF-kB inhibitor, DHMEQ can alleviate the graft damage in syngenic marginal islet transplantation.　　　　　　　　　　　　　　　
Takahashi T, Matsushita M, Matsumoto S, Tsuruga Y, Kasai H, Watanabe M, Ozaki M, Furukawa H, Umezawa K, Todo S
Joint congress of JSAO and IFAOaka, 2007年
Osaka

p66shc, an ageing protein, plays a pivotal role in post-hepatectomized liver regeneration in aged mice.　　　　　　　　　　　　　　　
Michitaka Ozaki, Sanae Haga, Tadahiro Osada, Yuko Oikawa, Hiroyuki Furukawa, Kaikobad Irani, Satoru Todo
AASLD annual meeting, 2007年
Boston/USA

Prevention of Intraportal Islet Graft Failure by a Novel NF-kB Inhibitor DHMEQ.　　　　　　　　　　　　　　　
Shuichiro Matsumoto, Michiaki Matsushita, Tohru Takahashi, Hironori Kasai, Yosuke Tsuruga, Hirofumi Kamachi, Michitaka Ozaki, Hiroyuki Furukawa, Kazuo Umezawa, Satoru Todo
World Transplant Congress, 2006年
Boston/USA

Control of allograft rejection by appling a novel NF-kB inhibitor, dehydroxymethylepoxyquinomicin.　　　　　　　　　　　　　　　
Kenichiro Yamashita, Shinya Ueki, Takeshi Aoyagi, Sanae Haga, Tomomi Suzuki, Masahiko Taniguchi, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
World Transplant Congress, 2006年
Boston/USA

A Novel NF-κB Inhibitor, Dehydroxymethylepoxyquinomicin Suppresses Donor Specific Memory/Effector Cells and Attenuates Development of Cardiac Allograft Vasculopathy.　　　　　　　　　　　　　　　
Shinya Ueki, Kenichiro Yamashita, Takeshi Aoyagi, Tomoo Itoh, Tomomi Suzuki, Masahiko Taniguchi, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michitaka Ozaki, Kazuo Umezawa, Satoru Todo
World Transplant Congress, 2006年
Boston/USA

PDK1/Akt pathway Plays a Critical Role in Liver Regeneration in Mouse Partial Hepatectomy Model.　　　　　　　　　　　　　　　
Michitaka Ozaki, Sanae Haga, Tadahiro Osada, Keita Terui, Hiroshi Inoue, Yasuo Okamoto, Wataru Ogawa, Hiroyuki Furukawa, Satoru Todo
FASEB Summer Research Conference., 2006年
Aspen/USA

James Remington, Michitaka Ozaki. Real-time monotoring of cellular redox states by newly developed redox-sensitive GFP probe.　　　　　　　　　　　　　　　
Sanae Haga, Rumi Igarashi, Hiroyuki Furukawa, Satoru Todo
International Symposia for Bioimaging 2006, 2006年
Kyoto

Ex vivo stat3 gene transfer prevents liver graft failure and elongates survival in rat fatty liver transplant model.　　　　　　　　　　　　　　　
Dong Sheng Sun, Tetsuya Ogino, Takahito Yagi, Hiroshi Sadamori, Hiroyoshi Matsukawa, Susumu Shinoura, Hiroshi Murata, Yuzo Umeda, Hiromi Iwagaki, Noriaki Tanaka, Michitaka Ozaki
ATC2005., 2005年
Seattle/USA

Ex vivo adenoviral gene transfer of constitutively activated stat3 reduced ischemia-reperfusion induced injury and promoted liver regeneration in 20% rat partial liver transplant model.　　　　　　　　　　　　　　　
Michitaka Ozaki, Sanae Haga, Lei Guo, Hiroyuki Furukawa, Michiaki Matsushita, Satoru Todo
11th International Liver Transplantation Society （ILTS） annual meeting, 2005年
Los Angeles/USA

Impaired Regeneration And Fatal Liver Failure After Resection Of Steatotic Liver By Cell Cycle Arrest.　　　　　　　　　　　　　　　
Hiroshi Murata, Takahito Yagi, Tetsuya Ogino, Hiroshi Sadamori, Hiroyoshi Matsukawa, Susumu Shinoura, Dong Sheng Sun, Yuzo Umeda, Hiromi Iwagaki, Noriaki Tanaka, Michitaka Ozaki
12th Congress Of The European Society For Organ Transplantation., 2005年
Geneva/Swiss

STAT3 Confers Resistance against Hyoxia/reoxygenation Injury in Hepatocytes via Mn-SOD.　　　　　　　　　　　　　　　
Keita Terui, Hiroaki Kuroda, Katsunori Kouchi, Tadashi Matsunaga, Hideo, Yoshida, Naomi Ohnuma, Sanae Haga, Shin Enosawa, Michitaka Ozaki
37th Annual Meeting of the Pacific Association of Pediatric Surgeons., 2004年
Seoul/Korea

Analysis of regulatory signals of liver regeneration -signals regulating hepatocellular proliferation and growth.　　　　　　　　　　　　　　　
Sanae Haga, Shin Enosawa, Keita Terui, Wataru Ogawa, Hiroshi Inoue, Michitaka Ozaki
2004 American Transplant Congress., 2004年
Boston/USA

Stat3 confers resistance against hypoxia/reoxygenation-induced oxidative injury in hepatocytes via mn-SOD.　　　　　　　　　　　　　　　
Keita Terui, Sanae Haga, Shin Enosawa, Naomi Onuma, Michitaka Ozaki
2004 American Transplant Congress., 2004年
Boston/USA

Improved Hepatic Regeneration With Reduced Injury By Redox Factor-1 in a Rat Small Size-Liver Transplant Model.　　　　　　　　　　　　　　　
Michitaka Ozaki, Lei Guo, Sanae Haga, Shin Enosawa, Katsutoshi Naruse, Yasushi Harihara, Yasuhiko Sugawara, Masatoshi Makuuchi, Kaikobad Irani
XX International Congress of The Transplantation Society.(, 2004年
Vienna/Austria

Constitutive activation of STAT3 confers resistance to liver against Fas-mediated liver injury: redox-dependent and ?independent mechanisms.　　　　　　　　　　　　　　　
Michitaka Ozaki, Sanae Haga, Wataru Ogawa, Hiroshi Inoue, Keita Terui, Shin Enosawa
55th Annual Meeting of the American Association for the Study of Liver Diseases., 2004年
Boston/USA

Novel targets of STAT3 and its clinical application.　　　　　　　　　　　　　　　
Michitaka Ozaki
University of Iowa., 2004年
Iowa city

Recent topics in redox-dependent signal regulation in liver. Invited lecture at Department of Cardiology.　　　　　　　　　　　　　　　
Michitaka Ozaki
Johns Hopkins University School of Medicine, 2004年
Baltimore

Ex Vivo Adenoviral Gene Transfer of Constitutively Activated Stat3 Reduced Ischemia-Reperfusion Induced Injury and Promoted Liver Regeneration in 20% Rat Partial Liver Transplant Model.　　　　　　　　　　　　　　　
Michitaka Ozaki, Lei Guo, Sanae Haga, Keita Terui, Hui Qi Zhang, Shin Enosawa, Seiichi Suzuki
2003 American Transplant Congress., 2003年
Washington D.C./USA

Constitutive Activation of Stat3 by Adenoviral Gene Transfer Confers Resistance to Liver Against Fas-Mediated Liver Injury: Caspase Inhibition and Redox-Dependent Mechanisms.　　　　　　　　　　　　　　　
Michitaka Ozaki, Sanae Haga, Hui Qi Zhang, Keita Terui, Wataru Ogawa, Hiroshi Inoue, Torayuki Okuyama, Kiyoshi Takeda, Shizuo Akira, Shin Enosawa, Seiichi Suzuki
6th Annual Meeting of the American Society of Gene Therapy., 2003年
Washington D.C./USA

Redox Regulation in Liver Injury.　　　　　　　　　　　　　　　
Michitaka Ozaki
International Meeting of the Society of Free Radical Research (SFRR)-Asia., 2003年
Seoul

Redox-dependent activation of Stat1 confers resistance against hypoxia/reoxygenation-induced apoptotic cell death in rat hepatocytes.　　　　　　　　　　　　　　　
Keita Terui, Michitaka Ozaki, Sanae Haga, Hui Qi Zhang, Shin Enosawa, Seiichi Suzuki
2002年
Redox Kyoto

Over-expressed redox factor-1 (REF-1) by ex vivo adenovirus-mediated gene transfer promotes liver regeneration with reduced liver injury in rat partial liver transplant model.　　　　　　　　　　　　　　　
Michitaka Ozaki, Lei Guo, Sanae Haga, Seiichi Suzuki
2002 American Transplant Congress., 2002年
Washington D.C./USA

Redox Gene Therapy in Liver Transplantation. (Grand Round Seminar)　　　　　　　　　　　　　　　
Michitaka Ozaki
Pittsburgh University Medical School, 2002年
Pittsburgh（USA）

Prevention of ischemia/reperfusion-induced liver injury by modulating redox sensitive signals. (Invited lecture)　　　　　　　　　　　　　　　
Michitaka Ozaki
International Symposium For Redox Signaling And Stress Diseases (Redox Kyoto 2002)., 2002年
Kyoto

Early infantile kidney as a marginal donation resource; histology and pathophysiology.　　　　　　　　　　　　　　　
Tatsuo Kuroda, Shin Enosawa, Mitsufumi Endo, Michitaka Ozaki, Nobuyuki Morikawa, Seiichi Suzuki, Hiroshi Amemiya
The 6th Congress of the International Society for Organ Sharing., 2001年
Nagoya

Overexpression of Redox Factor-1 protects against post-ischemic liver injury by reducing oxidative stress and NF-kB DNA binding activity.　　　　　　　　　　　　　　　
Michitaka Ozaki, Hiroshi Amemiya, Seiichi Suzuki
The 6th Congress of the International Society for Organ Sharing., 2001年
Nagoya

HGF protects hepatocytes against hypoxia/reoxygenation-induced cell death by reducing mitochondrial generation of reactive oxygen species through activation of PI3K-Akt pathway.　　　　　　　　　　　　　　　
Michitaka Ozaki, Yuko Nagata, Seiichi Suzuki
American Society of Transplantation 2001., 2001年
Chicago/USA

New strategy for preventing ischemia/ reperfusion-induced organ injury and promoting regeneration. ? a novel trial for improving transplanted graft function by targeted regulation of cellular signals-　　　　　　　　　　　　　　　
Michitaka Ozaki
The 6th congress of the international society for organ sharing, 2001年
名古屋

Adenovirally over-expressed redox factor-1(Ref-1) protects against post-ischemic liver injury by reducing oxidative stress and NF-kB DNA binding activity.　　　　　　　　　　　　　　　
Michitaka Ozaki, Kaikobad Irani, Seiichi Suzuki
American Society of Transplantation 2001, 2001年
Chicago（USA）

The novel protective mechanism of HGF -redox protection against hypoxia/reoxygenation-induced apoptosis-　　　　　　　　　　　　　　　
Michitaka Ozaki
Department of Medicine, Johns Hopkins University School of Medicine, 2001年
USA

Inhibition of the small GTPase, Rac1, protects against ischemia/reperfusion liver injury in mice.　　　　　　　　　　　　　　　
Ozaki M, Deshpande S, Angkeow P, Bellan J, Lowenstein CJ, Dinauer MC, Goldschmidt-Clermont P, Suzuki S, Irani K
18th International Congress of the Transplantation Society., 2000年
Rome/Itary

Inhibition of the small GTPase, Rac1, protects against reperfusion-induced liver injury by reducing intracellular reactive oxygen species and NF-kB DNA binding activity.　　　　　　　　　　　　　　　
Michitaka Ozaki, Shailesh S Deshpande, Piamsook Angkeow, John Bellan, Charles J Lowenstein, Mary C Dinauer, Pascal J Goldschmidt-Clermont, Seiichi Suzuki, Kaikobad Irani
International Hepato-Pancreatico-Biliary Association General Assembly 2000., 2000年
Brisbane/Australia

Inhibition of the small GTPase, Rac1, protects against post-ischemic liver injury by suppressing generation of intracellular reactive oxygen species and NF-kB binding activity.　　　　　　　　　　　　　　　
Michitaka Ozaki, Shailesh S Deshpande, Piamsook Angkeow, John Bellan, Charles J Lowenstein, Mary C Dinauer, Pascal J Goldschmidt-Clermont, Seiichi Suzuki, Kaikobad Irani
American Society of Transplantation General Meeting 2000, 2000年
Chicago（USA）

Anti-P selectin monoclonal antibldy protects against reticuloendothelial system dysfunction following hepatic ischemia/reperfusion.　　　　　　　　　　　　　　　
N Sakamoto, ML Bregman, K Maemura, ZL Sun, M Ozaki, GB Bulkley, AS Klein
Digestive Disease Week-USA, 1998年
New Orleans,LA/USA

Effects of an hepatic sinusoidal endothelial cell fraction on Kupffer cell antigen presentation.　　　　　　　　　　　　　　　
K Maemura, ZL Sun, N Sakamoto, M Ozaki, GB Bulkley, AS Klein
Digestive Disease Week-USA, 1998年
New Orleans,LA/USA

Immunomodulatory effects of Kupffer cells on antigen stimulated T-lymphocyte proliferation in vitro.　　　　　　　　　　　　　　　
ZL Sun, K Maemura, N Sakamoto, M Ozaki, GB Bulkley, AS Klein
Digestive Disease Week-USA., 1998年
New Orleans, LA（USA）

Iron release from haemosiderin and production of iron catalysed hydroxyl radical in vitro.　　　　　　　　　　　　　　　
M.Ozaki, T.Kawabata, M.Awai
The 4th Biennial General Meeting of the Society for Free Radical Research, 1987年
Kyoto

“光”を通じて今見えること、そして将来できること ?医療へそして日常へ-　　　　　　　　　　　　　　　
尾崎倫孝
北海道大学大学院保健科学研究院 公開講座2014「ようこそ！ヘルスサイエンスの世界へ」
北海道大学大学院保健科学研究院、札幌

生体リズムの乱れを超高感度で検出する組織密着型センサーの開発 ～疾患発症解明への応用を目指して～　　　　　　　　　　　　　　　
狩野晴美, 伊藤遼河, 浜田和子, 菊池祥裕, 中島かな子, 石川正純, 尾崎 倫孝, 浜田俊幸
第26回日本時間生物学会学術大会, 日本語, 口頭発表（一般）
［国内会議］

「肝再生・障害におけるJak/STAT3およびPI3K/PDK1/Aktの意義と機能解析」　　　　　　　　　　　　　　　
2005年

種々の原因による肝障害・肝再生のシグナル解析とその臨床応用への可能性　　　　　　　　　　　　　　　
2005年

「肝臓の虚血再還流障害、肝再生の病態・生理」 岡山大学・大学院特別講義　　　　　　　　　　　　　　　
2005年

教育講演「肝虚血・再潅流障害と再生の分子機構」　　　　　　　　　　　　　　　
2005年

急性肝不全の病態解明とSTAT3をターゲットとした治療の展望　　　　　　　　　　　　　　　
2005年

HCV肝硬変に対する生体肝移植の対策―IFN-beta術前投与とHCV再発の組織学的早期診断― 第40回日本移植学会総会 パネルディスカッション　　　　　　　　　　　　　　　
2004年

肝におけるSTAT3の制御と機能解析　　　　　　　　　　　　　　　
2004年

肝再生における細胞内シグナル伝達機構の解析とその治療への可能性 シンポジウム 第11回日本臓器保存生物医学会総会　　　　　　　　　　　　　　　
2004年

シグナル解析と臓器機能制御(肝疾患におけるシグナル解析とその治療への展望) 大阪市立大学大学院医学研究科 大学院特別講義　　　　　　　　　　　　　　　
2004年

シグナル解析と臓器機能制御(肝疾患におけるシグナル解析とその治療への展望)　　　　　　　　　　　　　　　
2004年

シグナル解析と臓器機能制御　　　　　　　　　　　　　　　
2003年

肝におけるSTAT3の新たなターゲットとその機能解析　　　　　　　　　　　　　　　
2003年

STAT3の新たなターゲットとその機能解析　　　　　　　　　　　　　　　
2003年

細胞内シグナル解析からみた保存液の条件　　　　　　　　　　　　　　　
2003年

STAT蛋白の臓器・細胞機能調節機構と移植・再生医療への応用 ―STAT蛋白をもちいた新しい治療戦略―、第38回日本移植学会 シンポジウム　　　　　　　　　　　　　　　
2002年

臓器虚血・再潅流傷害 －傷害抑制・再生促進のための新たな戦略－ 第38回日本移植学会 Pre-Congress Educational Program　　　　　　　　　　　　　　　
2002年

細胞内シグナル制御による肝傷害抑制および再生促進 第1回日本再生医療学会総会 シンポジウム1「21世紀の再生医療の現状とその実用化に向けて―肝臓」　　　　　　　　　　　　　　　
2002年

HGFによる肝虚血再潅流傷害抑制メカニズム（PI3-K/Akt/Rac1 pathwayによる細胞内活性酸素消去系）、第102回日本外科学会総会 サージカルフォーラム「HGF」　　　　　　　　　　　　　　　
2002年

Adenovirus vectorをもちいたex vivo Redox Factor-1 gene transductionによる移植肝再生促進、第102回日本外科学会総会 サージカルフォーラム「肝移植1」　　　　　　　　　　　　　　　
2002年

シグナル制御による臓器虚血再潅流傷害抑制の試み、第102回日本外科学会総会 サージカルフォーラム「虚血再潅流傷害3」　　　　　　　　　　　　　　　
2002年

移植遺伝子、蛋白治療 ―臓器傷害の抑制とすみやかな再生をめざして― 北海道大学第一外科特別セミナー　　　　　　　　　　　　　　　
2002年

外科領域における遺伝子、蛋白治療の展望 ―臓器傷害の抑制とすみやかな再生をめざして― 東京医科大学大学院特別講義　　　　　　　　　　　　　　　
2002年

移植遺伝子蛋白治療 移植臓器傷害の抑制とすみやかな再生をめざして、第37回日本移植学会 特別シンポジウム2「21世紀臓器移植のニューステージ」　　　　　　　　　　　　　　　
2001年

移植医療における臓器虚血・再潅流傷害抑制および再生促進にたいする新しい治療法の確立 - a novel trial for improving transplanted graft function by targeted regulation of cellular signals- 招待講演 神奈川県立小児医療センター　　　　　　　　　　　　　　　
2001年

「細胞内シグナル修飾による移植臓器機能制御の可能性」　　　　　　　　　　　　　　　
2001年

Redox regulation of signal transduction in the reperfused liver　　　　　　　　　　　　　　　
2000年

Redox Gene Therapy - 肝虚血再潅流障害克服への新たな展望 -、第7回日本臓器保存生物医学会総会 シンポジウム　　　　　　　　　　　　　　　
2000年

生体分子の熱操作と多次元細胞分析を実現する基盤技術の革新
科学研究費助成事業
2022年04月01日 - 2025年03月31日
小澤 岳昌, 塩谷 光彦, 尾崎 倫孝
日本学術振興会, 基盤研究(A), 東京大学, 22H00322

異なる特性をもつ二種類の光を利用した生体内深部組織の修復・再生法の開発
科学研究費助成事業
2021年04月01日 - 2024年03月31日
尾崎 倫孝, 小澤 岳昌, 森田 直樹, 芳賀 早苗
日本学術振興会, 基盤研究(B), 北海道大学, 21H02983

細胞内Ca2+と活性酸素が誘導するプログラム細胞死による肝虚血再灌流傷害の新展開
科学研究費助成事業
2020年04月01日 - 2024年03月31日
芳賀 早苗, 森田 直樹, 尾崎 倫孝
本研究は、虚血および再灌流時に肝細胞内で引き起こされる『活性酸素』, 『細胞内カルシウムイオン』, そして『（ネクローシス様）プログラム細胞死』に着目し、これまでの概念では説明しきれない肝傷害誘導機序の存在を明らかにすることを目的とする。この研究は、特に肝傷害の維持・拡大におおきく関わる、再灌流後中～後期の持続的な肝傷害をターゲットとし、新たな肝虚血再灌流傷害機構の解明に挑み、新たな標的分子・機序を導き出す意義を持つ。
本研究では、「ネクロプトーシス」、「パータナトス」など種々のネクローシス様プログラム細胞死等と、低酸素/再酸素化時に肝細胞内で引き起こされる様々なイベント、環境変化(①酸化ストレス、②細胞内カルシウムイオン(Ca2+)濃度―CaMKⅡ）の機序を段階的に進める計画である。
本年度は昨年度の研究成果を取りまとめるとともに、引き続き上記計画に則り研究を進めた。昨年度から着手している低酸素/再酸素化時の細胞内カルシウムイオン―CaMKⅡを介したネクロプトーシスの分子機序の解析を進め、この細胞死の機序や意義を解析した。これに関連して、ネクロプトーシスと他のプログラム細胞死との相互関係や相違についての解析も進めた。また、昨年度から取り掛かっている肝虚血/再灌流モデルにおける肝細胞死解析に関しては、ターゲットを抑制した条件での検討段階まで解析を進めた。また、各プログラム細胞死の重要性・機能性を検討するためのツールの開発に関して、事調査及び構想を固めることができた。
以上のように、本年度も肝細胞および生体肝で引き起こされる細胞死の機能性とその誘導機序について、基盤から応用までの検討を進めることができた。
日本学術振興会, 基盤研究(C), 北海道大学, 20K08299

薬理的神経制御を用いた新たな脳卒中運動療法の開発に対する生体脳イメージングの応用
科学研究費助成事業
2020年04月01日 - 2024年03月31日
前島 洋, 真先 敏弘, 榊間 春利, 高松 泰行, 芳賀 早苗, 尾崎 倫孝
昨年度までに得られた所見として、トレッドミル運動、或いはα5サブユニットを含むGABA受容体の特異的阻害薬L-655,708投与の単独介入による脳出血後の運動機能回復は限定的であるが、両者を組み合わせた介入により相乗的な回復効果が確認されていた。本年度は、これらの個体から採取した脳・脊髄サンプルの解析を進め、併用介入群に生じた可塑性修飾について検証を行った。L-655,708投与により大脳皮質運動野BDNF発現の増強が認められた。加えて、併用介入群の脊髄においては、 シナプスや軸索の可塑性に関与する分子マーカーの発現増強が認められた。このことから、併用介入群の効果的な機能回復には、脳内だけでなく脊髄における可塑性修飾も重要であることが示唆された。
脳におけるBDNF発現の生体イメージング計測を目的に、BDNFのプロモーター域に蛍発光酵素Luciferase遺伝子を挿入したBDNF-Luc Tgマウスを繁殖、飼育した。このTgマウスを対象に脳深部の発光の検知を可能とする発光基質AkaLumine-HCl (TokeOni)を腹腔内投与後、脳領域の発光を運動介入後に経時的に定量する一連の手法を開発した。この生体脳イメージングの手法を用いて、トレッドミル運動がBDNF発現に与える効果について検証を行った。単回のトレッドミル運動後４-8時間内において脳領域における発光、即ちBDNF発現が増強され、更に２週間のトレッドミル運動の継続することで運動後のより早いタイミングにBDNF発現増強が生じることを確認した。
一方、この生体脳イメージングを脳出血モデルに対して応用する際に、これまでのステレオタキシックシステムを用いた微量コラゲナーゼ注入によるモデル作成において、計測脳領域の皮膚処理が発光に影響を与える問題が生じ、術時における頭部の皮膚切開、縫合部位について検討を要することが示唆された。
日本学術振興会, 基盤研究(B), 北海道大学, 20H04048

ランタニド・ナノ粒子（LNP）を利用した癌細胞特異的光治療法の開発
科学研究費 挑戦的研究（開拓）
2019年 - 2022年
尾崎 倫孝
文部科学省, 研究代表者, 競争的資金

肝虚血・再灌流傷害における多段階多元的傷害進展のメカニズム解析
科学研究費 基盤研究（B）
2019年 - 2022年
森田 直樹
文部科学省, 競争的資金

生体分子の量と活性を測るオプトバイオ分析の創発　　　　　　　　　　　　　　　
科学研究費 基盤研究（A）
2019年 - 2022年
小澤 岳昌
文部科学省, 競争的資金

毒性関連ビッグデータを用いた人工知能による次世代型安全性予測手法の開発　　　　　　　　　　　　　　　
平成２９年度省エネ型電子デバイス材料の評価技術の開発事業（機能性材料の社会実装を支える高速・高効率な安全性評価技術の開発）
2017年 - 2021年
船津 公人
経済産業省, 競争的資金

意識下手術における聴覚刺激に伴う精神活動の可視化とストレスマネジメント方略　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｃ）
2017年 - 2020年
溝部佳代
文部科学省, 競争的資金

炎症誘導性の細胞死に着目した、慢性炎症性疾患の病態の解明と治療法の開発　　　　　　　　　　　　　　　
科学研究費 挑戦的萌芽研究
2017年 - 2020年
浅野真未
文部科学省, 競争的資金

時計遺伝子発現の自動定量化技術を用いた体内時計関連疾患発症機構解析システムの開発　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｂ）
2017年 - 2019年
浜田 俊幸
文部科学省, 競争的資金

分子イメージングを基軸とする生細胞内分子計測・光操作法の開発　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｓ）
2014年 - 2019年
小澤岳昌
文部科学省, 競争的資金

慢性肝疾患・肝障害を標的とした機能性食品スクリーニング法の開発　　　　　　　　　　　　　　　
イノベーション創出研究支援事業（スタートアップ研究補助金）
2016年 - 2017年
尾崎倫孝
北海道科学技術総合振興センター, 研究代表者, 競争的資金

肝臓代謝系を指標とした機能性食品等の機能性・安全性の解析法の開発　　　　　　　　　　　　　　　
2014年 - 2015年
尾崎倫孝
北海道科学技術総合振興センター, 研究代表者, 競争的資金

消化器癌の微小転移同定システムの臨床応用　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｃ）
2012年 - 2015年
崎浜秀康
文部科学省, 競争的資金

消化器癌におけるＭｅｓｏｔｈｅｌｉｎ分子発現の意義と癌悪性度との関係　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｃ）
2012年 - 2015年
蒲池浩文
文部科学省, 競争的資金

肝ストレスの動的解析による肝機能障害・予備能の評価
科学研究費 挑戦的萌芽研究
2012年 - 2014年
佐藤直樹
文部科学省, 競争的資金

光プローブを応用した生体イメージング法による画期的術中ライブ診断法の開発　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ａ）
2011年 - 2014年
尾崎倫孝
文部科学省, 研究代表者, 競争的資金

腹腔内転移のバイオイメージングと抑制物質の分子デザイン　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｂ）
2011年 - 2014年
梅澤一夫
文部科学省, 競争的資金

分子標的薬による新たな膵島移植法の開発：重症糖尿病の克服に向けた新戦略　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｂ）
2011年 - 2014年
山下健一郎
文部科学省, 競争的資金

細胞情報伝達に関わる蛋白質活性を可視化する発光プローブ分子の開発　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｂ）
2011年 - 2014年
森田直樹
文部科学省, 競争的資金

生体内分子をターゲットとした革新的バイオイメージング法による診断・治療法の開発
科学研究費 挑戦的萌芽研究
2012年 - 2013年
藤堂省
文部科学省, 競争的資金

光を応用した生物学的診断・治療法の開発　　　　　　　　　　　　　　　
第８回特定研究助成金
2011年 - 2013年
尾崎倫孝
上原記念生命科学財団, 研究代表者, 競争的資金

消化器癌におけるMesothelinおよびCA125発現の検討　　　　　　　　　　　　　　　
科学研究費 挑戦的萌芽研究
2011年 - 2012年
嶋村剛
文部科学省, 競争的資金

マウス肝移植における抗体プローブイメージング法を用いた拒絶反応の診断と病態解析　　　　　　　　　　　　　　　
科学研究費 挑戦的萌芽研究
2011年 - 2012年
細田充主
文部科学省, 競争的資金

新規分泌型発光デュアルプローブを用いたｉｎ ｖｉｖｏ での癌細胞上皮間葉移行解析　　　　　　　　　　　　　　　
科学研究費 挑戦的萌芽研究
2011年 - 2012年
片岡昭彦
文部科学省, 競争的資金

細胞死(オートファジー・アポトーシス)による肝再生制御メカニズムの解析
科学研究費 挑戦的萌芽研究
2011年 - 2012年
細田充主
文部科学省, 競争的資金

肝臓移植における重水を主体とした臓器保存液の開発　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ａ）
2010年 - 2012年
藤堂省
文部科学省, 競争的資金

光イメージングによる癌転移機構解明‐メラノーマがリンパから血流に入る瞬間を捉える-　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｂ）
2010年 - 2012年
古川洋志
文部科学省, 競争的資金

臓器ストレス測定法の開発と外科領域への応用
科学研究費 挑戦的萌芽研究
2010年 - 2011年
藤堂省
文部科学省, 競争的資金

大腸癌微小転移における癌幹細胞の役割　　　　　　　　　　　　　　　
科学研究費 挑戦的萌芽研究
2010年 - 2011年
崎浜秀康
文部科学省, 競争的資金

患者末梢血を用いた重症薬疹モデルマウスの作成および発症機序の解明　　　　　　　　　　　　　　　
厚生労働省科学研究費補助金（免疫アレルギー疾患等予防・治療研究事業）
2009年 - 2011年
阿部理一郎
厚生労働省, 競争的資金

迅速遺伝子解析による胆道閉鎖症細菌プロファイリングと胆管炎早期発見及び予後予測　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｃ）
2009年 - 2011年
岡田忠雄
文部科学省, 競争的資金

生体材料(コラーゲンビトリゲル)をもちいた新しい治療材料の開発　　　　　　　　　　　　　　　
科学研究費 挑戦的萌芽研究
2009年 - 2010年
古川博之
文部科学省, 競争的資金

分泌型光プローブによる生体内リポーターシステムの開発と腫瘍診断・治療法への応用　　　　　　　　　　　　　　　
科学研究費 挑戦的萌芽研究
2009年 - 2010年
尾崎倫孝
文部科学省, 研究代表者, 競争的資金

光プローブをもちいたバイオイメージングによる多角的診断・治療法の開発
科学研究費 基盤研究（Ａ）
2008年 - 2010年
尾崎倫孝
文部科学省, 研究代表者, 競争的資金

個別化医療の実現のための技術融合バイオ診断技術開発／染色体解析技術開発」に係る、がん組織バンクの構築とCGH解析　　　　　　　　　　　　　　　
NEDO独立行政法人新エネルギー・産業技術総合開発機構委託事業
2006年 - 2010年
藤堂省
経済産業省, 競争的資金

新規低分子NF-kB阻害剤による新たな免疫抑制療法の開発（06-44）　　　　　　　　　　　　　　　
平成１８年度保健医療分野における基礎研究推進事業
2006年 - 2010年
藤堂省
医薬基盤研究所, 競争的資金

新規分子機能プローブ開発による生体・臓器内分子機能診断への応用　　　　　　　　　　　　　　　
科学研究費 挑戦的萌芽研究
2008年 - 2009年
尾崎倫孝
文部科学省, 研究代表者, 競争的資金

転写因子NFkBをターゲットとした新しい薬剤流出ステントの開発　　　　　　　　　　　　　　　
科学研究費 挑戦的萌芽研究
2008年 - 2009年
藤堂省
文部科学省, 競争的資金

疾患早期診断のための糖鎖自動分析装置開発　　　　　　　　　　　　　　　
JST（先端計測分析技術・機器開発事業）
2007年 - 2009年
西村紳一郎
文部科学省, 競争的資金

新規NF-KB活性阻害剤(DHMEQ)の小腸虚血再灌流障害に対する治療効果　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｃ）
2007年 - 2008年
鈴木友巳
文部科学省, 競争的資金

CHIP-chip法/Oligofish法によるヒトがん組織の網羅的転写機能解析　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｃ）
2007年 - 2008年
中西一彰
文部科学省, 競争的資金

転写因子NF-KB制御による安全な肝臓移植法の開発　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ａ）
2006年 - 2008年
藤堂省
文部科学省, 競争的資金

高解像度アレイCGHによる胃癌のゲノム異常獲得形式と病理組織学的因子との統合解析　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｃ）
2006年 - 2008年
富岡伸元
文部科学省, 競争的資金

水素の動きを制御することにより阻血再灌流障害のシグナルを制御する試み　　　　　　　　　　　　　　　
科学研究費 挑戦的萌芽研究
2006年 - 2007年
深井原
文部科学省, 競争的資金

消化器外科領域における分子標的治療に向けた包括的基盤研究　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｂ）
2005年 - 2007年
尾崎倫孝
文部科学省, 研究代表者, 競争的資金

血小板を用いた新しい重症肝疾患に対する治療法の開発　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｂ）
2005年 - 2007年
大河内信弘
文部科学省, 競争的資金

新たに開発されたレドックス・プローブをもちいた新しい臓器機能評価法の開発　　　　　　　　　　　　　　　
科学研究費 萌芽研究
2005年 - 2006年
尾崎倫孝
文部科学省, 研究代表者, 競争的資金

遺伝子治療を用いた小腸移植の新しい戦略　　　　　　　　　　　　　　　
科学研究費 基盤研究（Ｂ）
2004年 - 2006年
古川博之
文部科学省, 競争的資金

アデノシン関連物質による臓器虚血再潅流障害の予防　　　　　　　　　　　　　　　
科学研究費 萌芽研究
2004年 - 2006年
藤堂省
文部科学省, 競争的資金

氷温域における臓器保存法の開発(飛躍的な保存時間の延長と機能回復にむけて)　　　　　　　　　　　　　　　
科学研究費 奨励研究（Ａ）
1998年 - 1999年
尾崎倫孝
文部科学省, 研究代表者, 競争的資金

移植を目的とした新しい臓器保存法の開発(アミノ酸,短鎖脂肪酸の効果について)　　　　　　　　　　　　　　　
科学研究費 奨励研究（Ａ）
1996年 - 1997年
尾崎倫孝
文部科学省, 研究代表者, 競争的資金

signal regulation of liver regeneration, liver transplantation from marginal donors, redox regulation of cellular signals　　　　　　　　　　　　　　　
競争的資金