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Generation of insulin-producing β-like cells from human iPS cells in a defined and completely xeno-free culture system

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Journal of Molecular Cell Biology 2014年第5期8卷 394-408页

作者： Hussain Md. Shahjalal nobuaki shiraki Daisuke Sakano Kazuhide Kikawa Soichiro Ogaki Hideo Baba Kazuhiko Kume Shoen Kume Department of Stem Cell Biology Institute of Molecular Embryology and Genetics Kumamoto University Honjo 2-2-1 Chuo-Ku Kumamoto 860-0811 Japan Global-Center of Excellence (6-COE) Kumamoto University Honjo 2-2-1 Chuo-ku Kumamoto 860-0811 Japan Department of Pediatrics Graduate School of Medical Sciences Kumamoto University Honjo 1-1-1 Chuo-Ku Kumamoto 860-8556 Japan Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Honjo 1-1-1 Chuo-Ku Kumamoto 860-8556 Japan Department of Neuropharmacology Graduate School of Pharmaceutical Sciences Nagoya City University 3-1 Tanabe Street Mizuho Nagoya 467-8603 Japan Program for Leading Graduate Schools 'HIGO (Health Life Science Interdisciplinary and Glocal Oriented) Program ' Kumamoto University Honjo 2-2-1 Chuo-ku Kumamoto 860-0811 Japan

Human induced pluripotent stem （hiPS） cells are considered a potential source for the generation of insulin-producing pancreatic β-ceUs because of their differentiation capacity. In this study, we have developed a five-step xeno-free culture system to efficiently dif- ferentiate hiPS cells into insulin-producing cells in vitro. We found that a high NOGGIN concentration is crucial for specifically inducing the differentiation first into pancreatic and duodenal homeobox-1 （PDX1）-positive pancreatic progenitors and then into neurogenin 3 （NGN3）-expressing pancreatic endocrine progenitors, while suppressing the differentiation into hepatic or intestinal cells. We also found that a combination of 3-isobutyl-l-methylxanthine （IBMX）, exendin-4, and nicotinamide was important for the differentiation into insulin single-positive cells that expressed various pancreatic β-cell markers. Most notably, the differentiated cells contained en- dogenous C-peptide pools that were released in response to various insulin secretagogues and high levels of glucose. Therefore, our results demonstrate the feasibility of generating hiPS-derived pancreatic β-ceUs under xeno-free conditions and highlight their poten- tial to treat patients with type I diabetes.

关键词： diabetes pancreas ceil therapy hiPS ceils xeno-free differentiation β-cells

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Steroid-sparing strategies in the management of ulcerative colitis:Efficacy of leukocytapheresis

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World Journal of Gastroenterology 2012年第41期18卷 5833-5838页

作者： Manabu shiraki Takayuki Yamamoto Inflammatory Bowel Disease Center Yokkaichi Social Insurance Hospital Yokkaichi Mie 510-0016 Japan

Active ulcerative colitis （UC） is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Leukocytapheresis is a novel nonphar- macologic approach for active UC, in which leukocytes are mechanically removed from the circulatory system. Current data indicate that leukocytapheresis is effica- cious in improving response and remission rates with excellent tolerability and safety in patients with UC. Corticosteroid therapy remains a mainstay in the treat- ment of active UC, however, long-term, high doses of corticosteroids usually produce predictable and po- tentially serious side effects. If leukocytapheresis can spare patients from exposure to corticosteroids, the risk of steroid-induced adverse events should be mini- mized. This may be of great benefit to patients because severe side effects of steroids seriously impair health- related quality of life. In this article, we reviewed cur- rent evidence on whether leukocytapheresis can avoid or reduce the use of corticosteroids in the manage- ment of patients with UC. Several studies have shown that leukocytapheresis was effective for steroid-nafve patients with active UC. Furthermore, both short-term and long-term studies have demonstrated the steroid- sparing effects of leukocytapheresis therapy in patients with UC. Although the evidence level is not striking, theavailable data suggest that leukocytapheresis can avoid or reduce the use of corticosteroids in the management of UC. Large, well-designed clinical trials are necessary to more accurately evaluate the steroid-sparing effects of leukocytapheresis in the management of UC.

关键词： Corticosteroid Granulocyte and monocyteadsorptive apheresis Leukocytapheresis Steroid-naivepatients Steroid-sparing effect Ulcerative colitis

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Relative predictive factors for hepatocellular carcinoma after HBeAg seroconversion in HBV infection

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World Journal of Gastroenterology 2005年第43期11卷 6848-6852页

作者： Kazumoto Murata Kazushi Sugimoto Katsuya shiraki Takeshi Nakano the First Department of Internal Medicine

AIM： To determine the predictive factors for hepatocellular carcinoma （HCC） development in patients after spontaneous or therapeutic HBeAg seroconversion. METHODS： In 48 patients who seroconverted to anti- HBe positive during follow-up, the background factors for HCC development were analyzed. RESULTS： HCC was developed in six patients during follow-up （average follow-up after HBeAg seroconversion： 10.9±5.4 years）. The incidence of HCC evaluated by Kaplan-Meier analysis was significantly higher in patients with abnormal aspartate aminotransferase （AST〉 40 IU/L） level, lower platelet counts （PLT〈10×10^4/IJL）, lower albumin level （Alb〈30 g/L）, positive HBV-DNA or older age at seroconversion （〉40 years）. However, lower platelet count was the only predictive factor for HCC development shown by multivariate proportional-hazard analysis. CONCLUSION： Active hepatitis or advanced hepatitis at HBeAg seroconversion or progressive hepatitis even after HBeAg seroconversion would be the risk factors for HCC development. These predictive factors should be taken into account in determining the frequency of biochemical study or imaging studies for HCC surveillance.

关键词： HBeAg seroconversion Hepatocellularcarcinoma Predictive factors

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An anomaly in persistent right umbilical vein of portal vein diagnosed by ultrasonography

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World Journal of Gastroenterology 2005年第8期11卷 1179-1181页

作者： Shigeo Nakanishi Katsuya shiraki Kouji Yamamoto Mutsumi Koyama Takeshi Nakano First Department of Internal Medicine Matsusaka Central General Hospital of Medicine

AIM: To detect the anomaly in the persistent right umbilical vein (PRUV) of portal vein (PV) with deviation of the ligamentum tere and left-sided gallbladder. METHODS: A total of 5783 candidates for routine analysis were evaluated for hepatic vascular abnormalities by ultrasonography. RESULTS: Ten candidates (0.17%) had a portal vein anomaly with a rightward-deviated ligamentum tere. The blood-flow velocity in the PRUV of the portal vein (17.7±3.0 cm/s) of the 10 cases was similar to that of the right anterior portal trunk (17.6±4.1 cm/s). However, the vessel diameter of the PRUV (φ12.4±4.4 mm) was larger than the right anterior portal trunk (φ6.1?.9 mm). Therefore, flow volume in the anomalous portion (0.97±0.30 L/min) was more than that in the right anterior portal trunk (0.18±0.05 L/min). CONCLUSION: The anomaly plays an important role in intra-hepatic PV flow.

关键词： PV anomaly Persistent right umbilical vein Ultrasonography

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The right hepatic artery syndrome

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World Journal of Gastroenterology 2005年第19期11卷 3008-3009页

作者： Kazumi Miyashita Katsuya shiraki Takeshi Ito Hiroki Taoka Takeshi Nakano First Department of Internal Medicine Mie University School of Medicine TsuMie 514-8507Japan First Department of Surgery Mie University School of Medicine TsuMie 514-8507Japan

Various benign and malignant conditions could cause biliary obstruction. Compression of extrahepatic bile duct (EBD) by right hepatic artery was reported as a right hepatic artery syndrome but all cases were compressed EBD from stomach side. Our case compressed from dorsum was not yet reported, so it was thought to be a very rare case. We present here the first case of bile duct obstruction due to the compression of EBD from dorsum by right hepatic artery.

关键词： Right hepatic artery syndrome Obstructive jaundice Extrahepatic bile duct Right hepatic artery Endoscopic retrograde cholangiography Cholangioen-terostomy

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Portal hypertensive colopathy in patients with liver cirrhosis

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World Journal of Gastroenterology 2005年第20期11卷 3127-3130页

作者： Keiichi Ito Katsuya shiraki Takahisa Sakai Hitoshi Yoshimura Takeshi Nakano First Department of Internal Medicine Mie University School of Medicine 2-174 Edobashi Tsu Mie 514-8507Japan

AIM: In patients with liver cirrhosis and portal hypertension, portal hypertensive colopathy is thought to be an important cause of lower gastrointestinal hemorrhage. In this study, we evaluated the prevalence of colonic mucosal changes in patients with liver cirrhosis and its clinical significance. METHODS: We evaluated the colonoscopic findings and liver function of 47 patients with liver cirrhosis over a 6-year period. The main cause of liver cirrhosis was post-viral hepatitis (68%) related to hepatitis B (6%) or C (62%) infection. All patients underwent upper gastrointestinal endoscopy to examine the presence of esophageal varices, cardiac varices, and congestive gastropathy, as well as a full colonoscopy to observe changes in colonic mucosa. Portal hypertensive colopathy was defined endoscopically in patients with vascular ectasia, redness, and blue vein. Vascular ectasia was classified into two types: type 1, solitary vascular ectasia; and type 2, diffuse vascular ectasia. RESULTS: Overall portal hypertensive colopathy was present in 31 patients (66%), including solitary vascular ectasia in 17 patients (36%), diffuse vascular ectasia in 20 patients (42%), redness in 10 patients (21%) and blue vein in 6 patients (12%). As the Child-Pugh class increased in severity, the prevalence of portal hypertensive colopathy rose. Child-Pugh class B and C were significantly associated with portal hypertensive colopathy. Portal hypertensive gastropathy, esophageal varices, ascites and hepatocellular carcinoma were not related to occurrence of portal hypertensive colopathy. Platelet count was significantly associated with portal hypertensive colopathy, but prothrombin time, serum albumin level, total bilirubin level and serum ALT level were not related to occurrence of portal hypertensive colopathy. CONCLUSION: As the Child-Pugh class worsens and platelet count decreases, the prevalence of portal hypertensive colopathy increases in patients with liver cirrhosis. A colonoscopi

关键词： Portal hypertensive colopathy Liver cirrhosis

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Ge quantum dots light-emitting devices

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Frontiers of Optoelectronics 2012年第1期5卷 13-20页

作者： Jinsong XIA Takuya MARUIZUMI Yasuhiro shiraki Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhan 430074China Advance Research Laboratories Tokyo City UniversityTokyo 158-0082Japan

Si photonics becomes one of the research focuses in the field of photonics. Si-based light-emitting devices are one of the most important devices in this field. In this paper, we review the Si-based light-emitting devices fabricated by embedding Ge self-assembled quantum dots into optical microcavities. Ge self-assembled quantum dots emit light in the telecommunication wavelength range from 1.3 to 1.6 pro, for which Si is transparent. Ge self- assembled quantum dots were grown on silicon-on- insulator （SOI） by molecular beam epitaxy （MBE） in Stranski-Krastanov （S-K） mode. Then, electron beam lithography （EBL） was used to define the pattern of optical microcavities on the wafer. Finally, the pattern was transferred onto the Si/Ge slab by inductive coupled plasma （ICP） dry etching. Room-temperature photolumi- nescence （PL） was used to characterize the light-emitting properties of fabricated devices. The results showed that strong resonant light emission was observed in different optical microcavities. Significant enhancement of the intensity was obtained by the optical resonance. Based on the results of PL, we designed and fabricated current- injected light-emitting devices based on Ge self-assembled quantum dots in optical microcavities. Room-temperature resonant light emission was observed from Ge dots in a 3.8 μm microdisk resonator.

关键词： Si-based light-emitting devices Ge self-assembled quantum dots microcavities photonic crystal(PhC) microdisk

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Hydrocarbon-Degrading Bacteria and Paraffin from Polluted Seashores 9 Years after the Nakhodka Oil Spill in the Sea of Japan

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Acta Geologica Sinica(English Edition) 2006年第3期80卷 432-440页

作者： Kazue TAZAKI Hiroaki WATANABE Siti Khodijah CHAERUN Koichi shiraki Ryuji ASADA Graduate School of Natural Science and Technology Kanazawa University KakumaKanazawaIshikawa 920-1192Japan School of Life Sciences and Technology Institute of Technology Bandung Ganesa 10Bandung 40132Indonesia

Pollution of petroleum hydrocarbons, in particular oil spills, has attracted much attention in the past and recent decades. Oil spills influence natural microbial community, and physical and chemical properties of the affected sites. The biodegradation of hydrocarbons by microorganisms is one of the primary ways by which oil spill is eliminated from contaminated sites. One such spill was that of the Russian tanker the Nakhodka that spilled heavy oil into the Sea of Japan on January 2, 1997. The impact of the Nakhodka oil spill resulted in a viscous sticky fluid fouling the shores and affected natural ecosystems. This paper describes the weathering of hydrocarbon-degrading bacteria （genus Pseudomonas） and crystallized organic compounds from the Nakhodka oil spill-polluted seashores after nine years. The Nakhodka oil has hardened and formed crust of crystalline paraffin wax as shown by XRD analysis （0.422, 0.377, and 0.250 nm d-spacing） in association with graphite and calcite after 9 years of bioremediation. Anaerobic reverse side of the oil crust contained numerous coccus typed bacteria associated with halite. The finding of hydrocarbon-degrading bacteria and paraffin wax in the oil crust may have a significant effect on the weathering processes of the Nakhodka oil spill during the 9- year bioremediation.

关键词： bioremediation graphite halite heavy oil hydrocarbon-degrading bacteria paraffin wax,Pseudomonas the Nakhodka oil spill

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Hemodynamics in the portal vein evaluated by pulse wave Doppler ultrasonography in patients with chronic hepatitis C treated with interferon

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World Journal of Gastroenterology 2005年第3期11卷 396-399页

作者： Shigeo Nakanishi Katsuya shiraki Kouji Yamamoto Mutsumi Koyama Noboru Kimura Takeshi Nakano First Department of Internal Medicine Toshiba Corporation

AIM: To employ pulse wave Doppler ultrasonography to evaluate the changes in portal blood flow velocity in patients with chronic hepatitis C (CHC) receiving interferon (IFN) treatment. METHODS: The subjects in this study were 14 patients (13 men and l woman) with CHC who received IFN treatment. Portal blood flow velocity was measured in the vessels at the porta hepatis at four time points: before IFN administration (pre-IFN), 2 wk after the start of administration (wk 2), 24 wk after the start of administration (wk 24, i.e., the end of IFN administration), and 24 wk after the end of administration (wk 48). RESULTS: The patients with CHC in whom IFN treatment resulted in complete elimination or effective elimination of viruses showed a significant increase in portal blood flow velocity at the end of IFN treatment compared with that before IFN treatment. In contrast, when IFN was ineffective, no significant increase in portal blood flow velocity was observed at wk 24 or 48 compared with the pre-IFN value. In addition, the patients with CHC in whom IFN was ineffective showed significantly lower portal blood flow velocity values than control subjects at all measurement time points. CONCLUSION: Pulse wave Doppler ultrasonography is a noninvasive and easily performed method for evaluating the effects of IFN treatment in patients with CHC. This technique is useful for measuring portal blood flow velocity before and 24 wk after IFN administration in order to evaluate the changes over time, thus assessing the effectiveness of IFN treatment.

关键词： Chronic Hepatitis C Interferon Pulsed-wave Doppler ultrasonography Portal Vein Hemodynamics

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Churg-Strauss syndrome complicated by colon erosion, acalculous cholecystitis and liver abscesses

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World Journal of Gastroenterology 2005年第33期11卷 5248-5250页

作者： Msahiro Suzuki Kazuo Nabeshima Mitsukazu Miyazaki Hitoshi Yoshimura Shinsei Tagawa Katsuya shiraki Internal Medicine Mie Prefectual Shima Hospital Japan First Department of Internal Medicine University School of Medicine Tsu 514-8507 Japan

We report on a case of Churg-Strauss syndrome (CSS)with colon erosion, cholecystitis and liver abscesses. A 21-year-old woman with a history of bronchial asthma for 3 years was admitted with a complaint of abdominal pain. Laboratory findings included remarkable leukocytosis and eosinophilia, and a colonoscopy revealed erosion from the rectum to the ileocecal region. In addition, a colonic biopsy specimen showed necrotizing vasculitis and marked eosinophilic infiltration. On the basis of the clinical features and histopathological findings, she was diagnosed with CSS and subsequently treated with oral prednisolone,after which the eosinophilia and abdominal pain disappeared. However, on the 15th d in hospital she developed cholecystitis and liver abscesses. She was therefore treated with antibiotics and as a result went into clinical remission.

关键词： Churg-Strauss syndrome Cholecystitis Liverabscesses

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