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Embryonic stem cells develop into hepatocytes after intrasplenic transplantation in CCl_4-treated mice

World Journal of Gastroenterology 2007年第6期13卷 866-873页

作者： Kei Moriya Masahide Yoshikawa Ko Saito Yukiteru Ouji Mariko Nishiofuku noriko hayashi Shigeaki Ishizaka Hiroshi Fukui Division of Hepatology Third Department of Internal Medicine Nara Medical University 840 Shijo-cho Kashihara Nara 634-8521 Japan Division of Developmental Biology Department of Parasitology Nara Medical University 840 Shijo-cho Kashihara Nara 634-8521 Japan

AIM： To transplant undifferentiated embryonic stem （ES） cells into the spleens of carbon tetrachloride （CCl4）-treated mice to determine their ability to differentiate into hepatocytes in the liver. METHODS： CCh, 0.5 mL/kg body weight, was injected into the peritoneum of C57BL/6 mice twice a week for 5 wk. In group 1 （n = 12）, 1 × 10^5 undifferentiated ES cells （0.1 mL of 1 × 10^6/mL solution）, genetically labeled with GFP, were transplanted into the spleens 1 d after the second injection. Group 2 mice （n = 12） were injected with 0.2 mL of saline twice a week, instead of CCh, and the same amount of ES cells was transplanted into the spleens. Group 3 mice （n = 6） were treated with CCh and injected with 0.1 mL of saline into the spleen, instead of ES cells. Histochemical analyses of the livers were performed on post-transplantation d （PD） 10, 20, and 30. RESULTS： Considerable numbers of GFP-immunopositive cells were found in the periportal regions in group 1 mice （CCh-treated） on PD 10, however, not in those untreated with CCh （group 2）. The GFP-positive cells were also immunopositive for albumin （ALB）, alpha-1 antitrypsin, cytokeratin 18, and hepatocyte nuclear factor 4 alpha on PD 20. Interestingly, most of the GFP-positive cells were immunopositive for DLK, a hepatoblast marker, on PD 10. Although very few ES-derived cells were demonstrated immunohistologically in the livers of group 1 mice on PD 30, improvements in liver fibrosis were observed. Unexpectedly, liver tumor formation was not observed in any of the mice that received ES cell transplantation during the experimental period CONCLUSION： Undifferentiated ES cells developed into hepatocyte-like cells with appropriate integration into tissue, without uncontrolled cell growth.

关键词： Embryonic stem cells Hepatic differentiation Intrasplenic transplantation Carbon tetrachloride

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Promoted differentiation of cynomolgus monkey ES cells into hepatocyte-like cells by co-culture with mouse fetal liver-derived cells

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World Journal of Gastroenterology 2006年第42期12卷 6818-6827页

作者： Ko Saito Masahide Yoshikawa Yukiteru Ouji Kei Moriya Mariko Nishiofuku Shigehiko Ueda noriko hayashi Shigeaki Ishizaka Hiroshi Fukui Department of Gastroenterology and Hepatology Nara Medical University Kashihara Nara Japan Division of Developmental Biology Department of Parasitology Nara Medical University Kashihara Nara Japan

AIM: To explore whether a co-culture of cynomolgus monkey embryonic stem (cES) cells with embryonic liver cells could promote their differentiation into hepatocytes. METHODS: Mouse fetal liver-derived cells (MFLCs) were prepared as adherent cells from mouse embryos on embryonic d (ED) 14, after which undifferentiated cES cells were co-cultured with MFLCs. The induction of cES cells along a hepatic lineage was examined in MFLC- assisted differentiation, spontaneous differentiation, and growth factors (GF) and chemicals-induced differentiations (GF-induced differentiation) using retinoic acid, leukemia inhibitory factor (LIF), FGF2, FGF4, hepatocyte growth factor (HGF), oncostatin M (OSM), and dexamethasone. RESULTS: The mRNA expression of α-fetoprotein, albumin (ALB), α-1-antitrypsin, and hepatocyte nuclear factor 4α was observed earlier in the differentiating cES cells co-cultured with MFLCs, as compared to cES cells undergoing spontaneous differentiation and those subjected to GF-induced differentiation. The expression of cytochrome P450 7a1, a possible marker for embryonic endoderm-derived mature hepatocytes, was only observed in cES cells that had differentiated in a co-culture with MFLCs. Further, the disappearance of Oct3/4, a representative marker of an undifferentiated state, was noted in cells co-cultured with MFLCs, but not in those undergoing spontaneous or GF-induced differentiation. Immunocytochemical analysis revealed an increased ratio of ALB-immunopositive cells among cES cells co-cultured with MFLCs, while glycogen storageand urea synthesis were also demonstrated. CONCLUSION: MFLCs showed an ability to induce cES cells to differentiate toward hepatocytes. The co-culture system with MFLCs is a useful method for induction of hepatocyte-like cells from undifferentiated cES cells.

关键词： Primate embryonic stem cells Fetal liver Hepatic differentiation Co-culture

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“有些死者家人过来只是为找值钱的东西”

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商业周刊（中文版） 2018年第17期 68-72,74页

作者： Adam Minter noriko hayashi(摄影) 许诺(译) 《彭博观点》编辑部不详

韩京子（Jeongja Han，音泽）将抽屉里的笔和打火机等杂物倒进塑料垃圾袋里，一旁，她的客户正坐在凳子上看着她收拾。这位要求不透露姓名的女士（下文以“W女士”代称）今年五十四五岁，是位寡妇。几周前，她丈夫刚刚遭遇车祸去世，留... 详细信息

韩京子（Jeongja Han，音泽）将抽屉里的笔和打火机等杂物倒进塑料垃圾袋里，一旁，她的客户正坐在凳子上看着她收拾。这位要求不透露姓名的女士（下文以“W女士”代称）今年五十四五岁，是位寡妇。几周前，她丈夫刚刚遭遇车祸去世，留下她一个人清理他们这处宽敞的两居室公寓。这里位于东京市繁华的惠比寿一带，他们已经在这里住了30年。他们没有子女，没什么东西耍传给下一代继承或留作纪念，因此，她给韩京子的要求非常简单：“所有东西统统丢掉。”

关键词：死者垃圾袋打火机东京市女士

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Long-term outcome of percutaneous ethanol injection therapy for minimum-sized hepatocellular carcinoma

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World Journal of Gastroenterology 2008年第13期14卷 1997-2002页

作者： Miyuki Taniguchi Soo Ryang Kim Susumu Imoto Hirotsugu Ikawa Kenji Ando Keiji Mita Shuichi Fuki noriko Sasase Toshiyuki Matsuoka Masatoshi Kudo Yoshitake hayashi Department of Gastroenterology Kobe Asahi Hospital Kobe Japan Department of Radiology Osaka City University Medical School Osaka Japan Department of Gastroenterology Kinki University School of Medicine Osakasayama Japan Division of Molecular Medicine & Medical Genetics International Center for Medical Research and Treatment (ICMRT) Kobe University Graduate School of Medicine Kobe Japan

AIM： To evaluate long-term follow-up of minimum-sized hepatocellular carcinoma （HCC） treated with percutaneous ethanol injection （PEI）. METHODS： PEI was applied to 42 lesions in 31 patients （23 male and eight female） with HCC 〈 15 mm in diameter, over the past 15 years. RESULTS： Overall survival rate was 74.1% at 3 years, 49.9% at 5 years, 27.2% at 7 years and 14.5% at 10 years. These results are superior to, or at least the same as those for hepatic resection and radiofrequency ablation. Survival was affected only by liver function, but not by sex, age, etiology of Hepatitis B virus or Hepatitis C virus, α-fetoprotein levels, arterial and portal blood flow, histological characteristics, and tumor multiplicity or size. Patients in Chiid-Pugh class A and B had 5-, 7- and 10-years survival rates of 76.0%, 42.2% and 15.8%, and 17.1%, 8.6% and 0%, respectively （P = 0.025）. CONCLUSION： Treatment with PEI is best indicated for patients with HCC 〈 15 mm in Child-Pugh class A.

关键词： Percutaneous ethanol injection Interventional ablation Ultrasound Hepatocellular carcinoma Prognosi

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Wound Treatment Using Growth Factors

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Modern Plastic Surgery 2013年第3期3卷 108-112页

作者： Keisuke Okabe Ruka hayashi noriko Aramaki-Hattori Yoshiaki Sakamoto Kazuo Kishi Department of Plastic and Reconstructive Surgery Keio University Tokyo Japan

Treatment with growth factors is an effective method to promote wound healing. Several growth factors have been used in wound treatment, including basic fibroblast growth factor (bFGF) discovered in the 1970s, platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and bone morphogenetic protein (BMP). In 2001, Kaken Pharmaceutical Co., Ltd. launched Fiblast Spray in Japan. This product is a topical formulation containing recombinant human bFGF. It is used to treat decubitus ulcers and skin ulcers (burn ulcers and leg ulcers). There is increasing interest in its stimulatory effect on wound healing and its inhibitory effect on scar formation. Wound healing is a physiological phenomenon that involves a complex series of integrated cellular and biochemical responses, characterized by phases of hemostasis, inflammation, proliferation, and maturation. However, much of its detailed mechanism remains unknown. There have been many basic research studies on wound healing using cells and experimental animals. If findings can be used from such studies and clinical practice, development of even more effective treatments might be possible.

关键词： Wound Healing Growth Factors bFGF

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Angle of covered self-expandable metallic stents after placement is a risk factor for recurrent biliary obstruction

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World Journal of Hepatology 2022年第5期14卷 992-1005页

作者： Kojiro Tanoue Hirotsugu Maruyama Yuki Ishikawa-Kakiya Yosuke Kinoshita Kappei hayashi Masafumi Yamamura Masaki Ominami Yuji Nadatani Shusei Fukunaga Koji Otani Shuhei Hosomi Fumio Tanaka noriko Kamata Yasuaki Nagami Koichi Taira Toshio Watanabe Yasuhiro Fujiwara Department of Gastroenterology Osaka City University Graduate School of MedicineOsaka 545-8585Japan

BACKGROUND Studies have shown that covered self-expandable metallic stents(CSEMS)with a low axial forces after placement can cause early recurrent biliary obstruction(RBO)due to precipitating sludge *** To ascertain whether the angle of CSEMS after placement is a risk factor for RBO in unresectable distal malignant biliary obstruction(MBO).METHODS Between January 2010 and March 2019,261 consecutive patients underwent selfexpandable metallic stent insertion by endoscopic retrograde cholangiopancreatography at our facility,and 87 patients were included in this *** evaluated the risk factors for RBO,including the angle of CSEMS after placement as the primary *** measured the obtuse angle of CSEMS after placement on an abdominal radiograph using the SYNAPSE PACS *** also evaluated technical and functional success,adverse events,time to RBO(TRBO),non-RBO rate,survival time,cause of RBO,and reintervention procedure as secondary *** We divided the patients into two cohorts based on the presence or absence of *** angle of CSEMS after placement(per 1°and per 10°)was evaluated using the multivariate Cox proportional hazard analysis,which was an independent risk factor for RBO in unresectable distal MBO[hazard ratio,0.97 and 0.71;95%confidence interval(CI):0.94-0.99 and 0.54-0.92;P=0.01 and 0.01,respectively].For early diagnosis of RBO,the cut-off value of the angle of CSEMS after placement using the receiver operating characteristic curve was 130°[sensitivity,50.0%;specificity 85.5%;area under the curve 0.70(95%CI:0.57-0.84)].TRBO in the<130°angle group was significantly shorter than that in the≥130°angle group(P<0.01).CONCLUSION This study suggests that the angle of the CSEMS after placement for unresectable distal MBO is a risk factor for *** novel results provide pertinent information for future stent management.

关键词： Covered self-expandable metallic stents Recurrent biliary obstruction Malignant biliary obstruction Endoscopic retrograde cholangiopancreatography Angle Axial force

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Diagnosis and Treatment of Keloids and Hypertrophic Scars—Japan Scar Workshop Consensus Document 2018

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Burns & Trauma 2019年第1期7卷 356-395页

作者： Rei Ogawa Sadanori Akita Satoshi Akaishi noriko Aramaki-Hattori Teruyuki Dohi Toshihiko hayashi Kazuo Kishi Taro Kono Hajime Matsumura Gan Muneuchi Naoki Murao Munetomo Nagao Keisuke Okabe Fumiaki Shimizu Mamiko Tosa Yasuyoshi Tosa Satoko Yamawaki Shinichi Ansai Norihisa Inazu Toshiko Kamo Reiko Kazki Shigehiko Kuribayashi Department of Plastic Reconstructive and Aesthetic SurgeryNippon Medical School1-1-5 Sendagi Bunkyo-kuTokyo 113-8603Japan Department of Plastic Surgery Wound Repair and RegenerationFukuoka UniversityFukuoka 814-0180Japan Department of Plastic Surgery Nippon Medical School Musashikosugi Hospital1-396 KosugichoNakahara-kuKawasaki-shiKanagawa 211-8533Japan Department of Plastic and Reconstructive Surgery Keio University School of Medicine35 ShinanomachiShinjuku-kuTokyo 160-8582Japan Department of Plastic and Reconstructive Surgery Faculty of Medicine and Graduate School of MedicineHokkaido UniversityKita-15Nishi-7Kita-kuSapporo 060-8638Japan Department of Plastic Surgery Tokai University School of Medicine4-1-1 KitakanameHiratsukaKanagawa 259-1292Japan Department of Plastic and Reconstructive Surgery Tokyo Medical University6-7-1 NishishinjukuShinjuku-kuTokyo 160-0023Japan Department of Plastic and Reconstructive Surgery Osaka Saiseikai Nakatsu Hospital2-10-39 ShibataKita-kuOsaka 530-0012Japan Department of Plastic Reconstructive and Aesthetic SurgeryIwate Medical University School of Medicine19-1 UchimaruMoriokaIwate 020-8505Japan Department of Plastic Surgery Oita University Hospital1-1 IdaigaokaHasamamachiYufu-shiOita 879-5503Japan Department of Plastic Surgery Showa University Fujigaoka Hospital1-30 FujigaokaAoba-kuYokohamaKanagawaJapan Department of Plastic and Reconstructive Surgery Japanese Red Cross Fukui Hospital2-4-1 TsukimiFukui 918-8501Japan Division of Dermatology and Dermatopathology Nippon Medical School Musashikosugi Hospital1-396KosugichoNakahara-kuKawasaki-shiKanagawa 211-8533Japan Faculty of Pharmaceutical Sciences Teikyo Heisei University4-21-2 NakanoNakano-kuTokyo 164-8530Japan Wakamatsu-cho Mental and Skin Clinic 9-4 Wakamatsu-choShinjyuku-kuTokyo 162-0056Japan Department of Radiation Oncology Nippon Medical School HospitalTokyo 113-8603Japan

There has been a long-standing need for guidelines on the diagnosis and treatment of keloids and hypertrophic scars that are based on an understanding of the pathomechanisms that underlie these skin fibrotic *** is particularly true for clinicians who deal with Asian and African patients because these ethnicities are highly prone to these *** contrast,Caucasians are less likely to develop keloids and hypertrophic scars,and if they do,the scars tend not to be *** ethnic disparity also means that countries vary in terms of their differential diagnostic *** lack of clear treatment guidelines also means that primary care physicians are currently applying a hotchpotch of treatments,with uneven *** overcome these issues,the Japan Scar Workshop(JSW)has created a tool that allows clinicians to objectively diagnose and distinguish between keloids,hypertrophic scars,and mature *** tool is called the JSW Scar Scale(JSS)and it involves scoring the risk factors of the individual patients and the affected *** tool is simple and easy to *** a result,even physicians who are not accustomed to keloids and hypertrophic scars can easily diagnose them and judge their *** JSW has also established a committee that,in cooperation with outside experts in various fields,has prepared a Consensus Document on keloid and hypertrophic scar treatment *** guidelines are simple and will allow even inexperienced clinicians to choose the most appropriate treatment *** Consensus Document is provided in this *** describes(1)the diagnostic algorithm for pathological scars and how to differentiate them from clinically similar benign and malignant tumors,(2)the general treatment algorithms for keloids and hypertrophic scars at different medical facilities,(3)the rationale behind each treatment for keloids and hypertrophic scars,and(4)the body site-specific treatment protocols for these *** believe that t

关键词： Keloid Hypertrophic scars Pathological scars Guideline Pathology Surgery Radiotherapy Steroid Laser

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Nature:科学家鉴别出调节机体睡眠的两个关键基因

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现代生物医学进展 2017年第6期17卷 I0002-I0002页

作者： Hiromasa Funato, Chika Miyoshi, Tomoyuki Fujiyama, Takeshi Kanda, Makito Sato, Zhiqiang Wang, Jing Ma, Aya Ikkyu, Miyo Kakizaki, noriko Hotta-Hirashima, Satomi Kanno, Haruna Komiya, Fuyuki Asano, Takato Honda, Staci J. Kim, Kanako Harano, Hiroki Muramoto, Toshiya Yonezawa, Shinichi Miyazaki, Linzi Connor, Yu hayashi, Qinghua Liu, Joseph S. Takahashi Masashi Yanagisawa Hiromasa Funato Makito Sato Masashi Yanagisawa Shin Nakane, Jun Tomita Kazuhiko Kume Seiya Mizuno, Fumihiro Sugiyama Satoru Takahashi Vivek Kumar Joseph S. Takahashi Vivek Kumar Ikuo Miura, Tomohiro Suzuki Shigeharu Wakana Atsushi Watanabe Manabu Abe Kenji Sakimura Yu hayashi Qinghua Liu Joseph S. Takahashi Masashi Yanagisawa Masashi Yanagisawa International Institute for Integrative Sleep Medicine (WPI-IIIS) University of Tsukuba Tsukuba Ibaraki 305-8575 Japan Department of Anatomy Faculty of Medicine Toho University Ota-ku Tokyo 143-8540 Japan Department of Molecular Genetics University of Texas Southwestern Medical Center Dallas Texas 75390 USA Department of Neuropharmacology Graduate School of Pharmaceutical Sciences Nagoya City University Nagoya Aichi 467-8603 Japan Laboratory Animal Resource Center University of Tsukuba Tsukuba Ibaraki 305-8575 Japan Department of Neuroscience University of Texas Southwestern Medical Center Dallas Texas 75390 USA The Jackson Laboratory Bar Harbor Maine 04609 USA Technology and Development Team for Mouse Phenotype Analysis RIKEN Bioresource Center Tsukuba Ibaraki 305-0074 Japan Laboratory of Research Advancement National Center for Geriatrics and Gerontology Obu Aichi 474-8511 Japan Department of Cellular Neurobiology Brain Research Institute Niigata University Niigata 951-8585 Japan PRESTO Japan Science and Technology Agency Kawaguchi Saitama 332-0012 Japan Department of Biochemistry University of Texas Southwestern Medical Center Dallas Texas 75390 USA Howard Hughes Medical Institute University of Texas Southwestern Medical Center Dallas Texas 75390 USA Life Science Center Tsukuba Advanced Research Alliance University of Tsukuba Tsukuba Ibaraki 305-8575 Japan

近日，刊登在国际杂志Nature上的一项研究报告中，来自西南医学中心等机构的研究人员通过研究鉴别出了两个关键的核心基因，这两个基因能够帮助调节机体深度睡眠和做梦的水平，相关研究或为阐明相关的基因控制睡眠的网络提供新的线索。... 详细信息

近日，刊登在国际杂志Nature上的一项研究报告中，来自西南医学中心等机构的研究人员通过研究鉴别出了两个关键的核心基因，这两个基因能够帮助调节机体深度睡眠和做梦的水平，相关研究或为阐明相关的基因控制睡眠的网络提供新的线索。此前研究者通过对小鼠进行研究发现了能够控制机体快速眼动睡眠的基因，同时该基因还能够诱导深度睡眠。而第二个基因能够控制机体对快速眼动睡眠的需求量，相关研究为科学家们提供了一个关键的切入点来帮助解释睡眠工作的机制，同时研究者还鉴别出了治疗睡眠障碍的潜在靶点。

关键词：睡眠障碍核心基因科学家机体鉴别基因控制研究人员需求量

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