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Clinical translation of bioartificial liver support systems with human pluripotent stem cell-derived hepatic cells

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World Journal of Gastroenterology 2017年第11期23卷 1974-1979页

作者： Ryoichi Sakiyama Brandon J Blau Toshio miki Department of Surgery Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033United States

There is currently a pressing need for alternative the-rapies to liver transplantation. The number of patients waiting for a liver transplant is substantially higher than the number of transplantable donor livers, resulting in a long waiting time and a high waiting list mortality. An extracorporeal liver support system is one possible approach to overcome this problem. However, the ideal cell source for developing bioartificial liver(BAL) support systems has yet to be determined. Recent advancements in stem cell technology allow researchers to generate highly functional hepatocyte-like cells from human pluripotent stem cells(h PSCs). In this mini-review, we summarize previous clinical trials with different BAL systems, and discuss advantages of and potential obstacles to utilizing h PSC-derived hepatic cells in clinical-scale BAL systems.

关键词： Artificial liver Clinical trial Hepatocytes Pluripotent stem cells Bioreactors

Gastro-esophageal reflux disease symptoms are more common in general practice in Japan

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World Journal of Gastroenterology 2007年第31期13卷 4219-4223页

作者： Toshiyasu Watanabe Yoshihisa Urita Motonobu Sugimoto Kazumasa miki Division of Gastroenterology and Hepatology Department of Internal Medicine Toho University School of Medicine Omori Hospital Tokyo Japan Division of Gastroenterology and Hepatology Department of Internal Medicine Toho University School of Medicine Omori Hospital Tokyo Japan Department of General Medicine and Emergency Care and Toho University School of Medicine Omori Hospital Tokyo Japan

To accurately assess the prevalence of GERD symptoms in general practice. METHODS： 4139 consecutive patients （2025 men and 2114 women with a mean age of 43 years）, who first attended the Outpatient Department of General Medicine and Emergency Care at Toho University Omori Hospital, were asked to respond to the F-scale questionnaire regardless of their chief complaints. The questionnaire is a self-report instrument, written in a simple and easy-to- understand language, containing 12 questions. RESULTS： Of 4139 subjects, 1554 patients （37.6%） were identified as GERD according to their F-scale score （〉 7）. However, there were only 45 consultations （1.1%） for typical GERD symptoms. Although GERD symptoms are common in adults of all ages, the prevalence of GERD was highest in the 20-29 years age group and the age group 70-79 years had the lowest prevalence for both males and females. CONCLUSION： Although there was a high rote indicating GERD in our primary care population, only 1.1% of outpatients attended our hospital with a chief complaint of GERD symptoms. Since about one-third of GERD patients are affected by atypical symptoms, general physicians need to be cautious about extrapolating these results to patients with a chief complaint other than typical GERD *** T, Urita Y, Sugimoto M, miki K. Gastro-esophagea reflux disease symptoms are more common in genera practice in Japan. World J Gastroenterol 2007; 13（31） 4219-4223

关键词： Gastroesophageal reflux disease (GERD) F-scale Questionnaire General practice

Smad3 phospho-isoform signaling in hepatitis C virus-related chronic liver diseases

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World Journal of Gastroenterology 2014年第35期20卷 12381-12390页

作者： Takashi Yamaguchi Katsunori Yoshida miki Murata Koichi Matsuzaki Department of Gastroenterology and Hepatology Kansai Medical University

The risk of hepatocellular carcinoma (HCC) development increases as hepatitis virus C (HCV)-related liver diseases progress, especially in patients with active inflammation. Insight into hepatic carcinogenesis have emerged from recent detailed analyses of transforming growth factor-β and c-Jun-N-terminal kinase signaling processes directed by multiple phosphorylated (phospho)-isoforms of a Smad3 mediator. In the course of HCV-related chronic liver diseases, chronic inflammation and host genetic/epigenetic alterations additively shift the hepatocytic Smad3 phospho-isoform signaling from tumor suppression to carcinogenesis, increasing the risk of HCC. Chronic inflammation represents an early carcinogenic step that provides a nonmutagenic tumor-promoting stimulus. After undergoing successful antiviral therapy, patients with chronic hepatitis C could experience a lower risk of HCC as Smad3 phospho-isoform signaling reverses from potential carcinogenesis to tumor suppression. Even after HCV clearance, however, patients with cirrhosis could still develop HCC because of sustained, intense carcinogenic Smad3 phospho-isoform signaling that is possibly caused by genetic or epigenetic alterations. Smad3 phospho-isoforms should assist with evaluating the effectiveness of interventions aimed at reducing human HCC.

关键词： Chronic inflammation c-Jun N-terminal kinase Hepatitis C virus Hepatocellular carcinoma Smad3 phospho-isoform signaling Transforming growth factor β

Linker phosphorylation of Smad3 promotes fibro-carcinogenesis in chronic viral hepatitis of hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第41期20卷 15018-15027页

作者： miki Murata Katsunori Yoshida Takashi Yamaguchi Koichi Matsuzaki Department of Gastroenterology and Hepatology Kansai Medical University

Epidemiological and clinical data point to a close association between chronic hepatitis B virus infection or chronic hepatitis C virus infection and development of hepatocellular carcinoma (HCC). HCC develops over several decades and is associated with fibrosis. This sequence suggests that persistent viral infection and chronic inflammation can synergistically induce liver fibrosis and hepatocarcinogenesis. The transforming growth factor-β (TGF-β) signaling pathway plays a pivotal role in diverse cellular processes and contributes to hepatic fibro-carcinogenesis under inflammatory microenvironments during chronic liver diseases. The biological activities of TGF-β are initiated by the binding of the ligand to TGF-β receptors, which phosphorylate Smad proteins. TGF-β type I receptor activates Smad3 to create COOH-terminally phosphorylated Smad3 (pSmad3C), while pro-inflammatory cytokine-activated kinases phosphorylates Smad3 to create the linker phosphorylated Smad3 (pSmad3L). During chronic liver disease progression, virus components, together with pro-inflammatory cytokines and somatic mutations, convert the Smad3 signal from tumor-suppressive pSmad3C to fibro-carcinogenic pSmad3L pathways, accelerating liver fibrosis and increasing the risk of HCC. The understanding of Smad3 phosphorylation profiles may provide new opportunities for effective chemoprevention and personalized therapy for patients with hepatitis virus-related HCC in the future.

关键词： Chronic viral hepatitis Transforming growth factor-β Smad3 Phosphorylation Fibro-carcinogenesis Hepatocellular carcinoma

Chronic atrophic gastritis detection with a convolutional neural network considering stomach regions

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World Journal of Gastroenterology 2020年第25期26卷 3650-3659页

作者： Misaki Kanai Ren Togo Takahiro Ogawa miki Haseyama Graduate School of Information Science and Technology Hokkaido UniversitySapporo 0600814HokkaidoJapan Education and Research Center for Mathematical and Data Science Hokkaido UniversitySapporo 0600812HokkaidoJapan Faculty of Information Science and Technology Hokkaido UniversitySapporo 0600814HokkaidoJapan

BACKGROUND The risk of gastric cancer increases in patients with Helicobacter pylori-associated chronic atrophic gastritis(CAG).X-ray examination can evaluate the condition of the stomach,and it can be used for gastric cancer mass ***,skilled doctors for interpretation of X-ray examination are decreasing due to the diverse of *** To evaluate the effectiveness of stomach regions that are automatically estimated by a deep learning-based model for CAG *** We used 815 gastric X-ray images(GXIs)obtained from 815 *** ground truth of this study was the diagnostic results in X-ray and endoscopic *** a part of GXIs for training,the stomach regions are manually annotated.A model for automatic estimation of the stomach regions is trained with the *** the rest of them,the stomach regions are automatically ***,a model for automatic CAG detection is trained with all GXIs for *** In the case that the stomach regions were manually annotated for only 10 GXIs and 30 GXIs,the harmonic mean of sensitivity and specificity of CAG detection were 0.955±0.002 and 0.963±0.004,*** By estimating stomach regions automatically,our method contributes to the reduction of the workload of manual annotation and the accurate detection of the CAG.

关键词： Gastric cancer risk Chronic atrophic gastritis Helicobacter pylori Gastric Xray images Deep learning Convolutional neural network Computer-aided diagnosis

Secondary pouchitis in a post-operative patient with ulcerative colitis,successfully treated by salvage surgery

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World Journal of Gastroenterology 2005年第43期11卷 6888-6890页

作者： Yuji Toiyama Toshimitsu Araki Shigeyuki Yoshiyama Chikao miki Masato Kusunoki The Second Department of Surgery

We report a case of secondary pouchitis, defined as a mucosal inflammatory lesion in the ileal reservoir provoked by pouch-related complication following total colectomy and pouch anal anastomosis, which was successfully treated by salvage surgery. A 20-year-old woman with ulcerative colitis developed acute severe bloody diarrhea following proctocolectomy, ileal pouchanal anastomosis and diverting ileostomy. She was diagnosed as having a secondary pouchitis mainly caused by a peripouch abscess and partly concerned with the abnormal pouch formation. The remnantrectum and ileal pouch were excised and ileal pouch-anal anastomosis and diverting ileostomy were *** postoperative course was uneventful with no sign of pouchitis. Salvage surgery may be indicated to treat secondary pouchitis when caused by surgery-related complications.

关键词： Ulcerative colitis Ileal pouch-anal anastomosis Secondary pouchitis Salvage operation

Epigenetic Regulation of Serotonin Transporter in Psychiatric Disorders

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Journal of Genetics and Genomics 2013年第7期40卷 325-329页

作者： Hiroko Sugawara miki Bundo Jun Ishigooka Kazuya Iwamoto Tadafumi Kato Laboratory for Molecular Dynamics of Mental Disorders RIKEN Brain Science Institute2-1 HirosawaWakoSaitama 351-0198Japan Department of Psychiatry Tokyo Women's Medical UniversityTokyo 162-8666Japan Department of Molecular Psychiatry Graduate School of MedicineUniversity of TokyoTokyo 113-8655Japan Department of Psychiatry.Tokyo Women's Medical University Tokyo 162-8666Japan

SLC6A4 （solute carrier family 6, member 4） gene encodes a serotonin transporter （5-hydroxytryptamine transporter, HTT）, which transports synaptic serotonin into presynaptic terminal. SLC6A4 is known to be the target of antidepressants such as selective serotonin reuptake inhibitors （SSRIs）. Inhibition of HTT increases synaptic serotonin concentration and thereby exerts antidepressant efficacy. A large number of genetic studies suggest the contribution of genetic variations of SLC6A4 to various psychiatric disorders. The most studied genetic variation, HTT-linked polymorphic region （HTTLPR）,

关键词： SLC Epigenetic Regulation of Serotonin Transporter in Psychiatric Disorders

Solution-based polycrystalline silicon transistors produced on a paper substrate

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npj Flexible Electronics 2017年第1期1卷 106-111页

作者： miki Trifunovic Paolo Maria Sberna Tatsuya Shimoda Ryoichi Ishihara Department of Electronic Components Technology and MaterialsDelft University of TechnologyBuilding 36Mekelweg 4Delft 2628 CDThe Netherlands School of Material and Science Japan Advanced Institute of Science and Technology1-1 AsahidaiNomiIshikawa 923-1292Japan

Printing of electronics is pursued as a low-cost alternative to conventional manufacturing *** addition,owing to relatively low process temperatures,flexible substrates can be used enabling novel *** flexible substrates,paper was found to be a particularly interesting candidate,since it has an order of magnitude lower price than low-cost polymer alternatives,and is *** ink materials,organic and metal-oxide semiconductors are thoroughly being investigated;however,they lack in electric performance compared to silicon in terms of device mobility,reliability,and energy *** recent years,liquid precursors for silicon were found and used to create polycrystalline silicon(poly-Si).However,fabrication of transistors on top of low-cost flexible substrates such as paper has remained an outstanding *** we demonstrate both p-channel and nchannel poly-Si thin-film transistors(TFTs)fabricated directly on top of paper with field-effect mobilities of 6.2 and 2.0 cm2/V s,*** fabrication challenges have been overcome by limiting the maximum process temperature to approximately 100℃,and avoiding liquid chemicals commonly used for etching and *** of poly-Si has been achieved by additive selective crystallization of the precursor film using an excimer *** work serves as a proof of concept,and has the potential to further improve device *** to the low-cost,biodegradable nature of paper,and the high performance,reliability,and energy efficiency of poly-Si TFTs,this work opens a pathway toward truly low-cost,low-power,recyclable applications including smart packages,biodegradable health monitoring units,flexible displays,and disposable sensor nodes.

关键词： polycrystalline film overcome

Gender differences in adolescent dry eye disease:a health problem in girls

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International Journal of Ophthalmology(English edition) 2018年第2期11卷 301-307页

作者： Masahiko Ayaki Motoko Kawashima miki Uchino Kazuo Tsubota Kazuno Negishi Department of Ophthalmology Keio University School of MedicineTokyoJapan.

AIM： To evaluate the signs and symptoms of dry eye disease（DED） in adolescents. METHODS： This was a cross-sectional, case-control study and outpatients aged 10 to 19y were recruited from six eye clinics of various practices and locations in Japan, and 253 non-DED subjects and 70 DED patients were enrolled. Participants were examined for DED-related signs. Patients were also interviewed to ascertain the presence or absence of six common DED-related symptoms： dryness, irritation, pain, eye fatigue, blurring, and photophobia. Main outcome measures were differences in signs and symptoms of dry eye disease between boys and ***： Of the 323 adolescents recruited, 70（21.7%） were diagnosed with DED. Significant differences between the non-DED and DED groups were found for short tear break-up time（BUT; ≤5s; P=0.000） and superficial punctate keratopathy（SPK; staining score ≥3; P=0.000）. Late adolescent girls reported fewer symptoms than late adolescent boys, although their DED-related signs were worse compared to other groups. The prevalence and severity of DED were similar in the Tokyo area compared with suburban and local areas but myopic errors were worse. CONCLUSION： We find that adolescents reported symptoms of DED similar to those found in adults, and the majority have short BUT-type DED. The prevalence and severity of DED in late adolescent girls is comparable with adults. Adolescents with DED are underserved and we believe that DED is a hidden but potentially serious health problem for this age group.

关键词： dry eye disease adolescence gender difference