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Mutations in carboxy-terminal part of E2 including PKR/eIF2αphosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b:Their correlation with response to interferon monotherapy and viral load

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World Journal of Gastroenterology 2006年第23期12卷 3722-3728页

作者： Koji Ukai Masatoshi Ishigami Kentaro Yoshioka Naoto Kawabe yoshiaki katano Kazuhiko Hayashi Takashi Honda Motoyoshi Yano Hidemi Goto Division of Gastroenterology Department of Internal MedicineNagoya University Graduate School of MedicineNagoyaJapan Division of Liver and Biliary Diseases Department of Internal MedicineFujita Health University School of MedicineAichiJapan

AIM： To study the amino acid substitutions in the carboxy （C）-terminal part of E2 protein and in the interferon （IFN） sensitivity determining region （ISDR） and their correlation with response to IFN and viral load in 85 hepatitis C virus （HCV）-lb-infected patients treated with IFN. METHODS： The C-terminal part of E2 （codons 617-711） including PKR/eIF2α phosphorylation homology domain （PePHD） and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy. RESULTS： The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to iFN or with viral load. The presence of substitutions in a N-terminal variable region （codons 617-641） in the C-terminal part of E2 was significantly correlated with both small viral load （33.9% vs 13.8%, P = 0.0394） and sustained response to iFN （25.0% vs 6.9 %, P = 0.0429）. Four or more substitutions in ISDR were significantly correlated with both small viral load （78.6% vs 16.2%, P 〈 0.0001） and sustained response to iFN （85.7% vs 2.9%, P 〈 0.0001）. In multivariate analysis, ISDR in nonstructural （NS） 5A （OR = 0.39, P 〈 0.0001） and N-terminal variable region （OR = 0.51, P = 0.039） was selected as the independentpredictors for small viral load, and ISDR （OR = 39.0, P 〈 0.0001） was selected as the only independent predictor for sustained response. CONCLUSION： The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.

关键词： E2 Genotype HCV Interferon ISDR NS5A PePHD PKR SVR

Clinical oncology for pancreatic and biliary cancers:Advances and current limitations

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World Journal of Clinical Oncology 2011年第5期2卷 217-224页

作者： Yoshiki Hirooka Akihiro Itoh Hiroki Kawashima Eizaburo Ohno Takuya Ishikawa Yuya Itoh Yosuke Nakamura Takeshi Hiramatsu Masanao Nakamura Ryoji Miyahara Naoki Ohmiya Masatoshi Ishigami yoshiaki katano Hidemi Goto Department of Endoscopy Nagoya University Hospital65Tsuruma-ChoShowa-KuNagoya CityAichi Prefecture 81-466-8550Japan Department of Gastroenterology Nagoya University Graduate School of Medicine65Tsuruma-ChoShowa-KuNagoya CityAichi Prefecture 81-466-8550Japan

In the early 2000s,the main stream of endoscopic ultrasonography(EUS)changed from a mechanical scanning method to electronic radial or linear scanning ***,useful applications in trans-abdominal ultrasonography came within reach of *** particular,contrast-enhanced EUS(CE-EUS)and EUS-elastography became cutting-edge diagnostic modalities for pancreatic *** type of pancreatic disorder has characteristic ***-EUS uses color Doppler flow imaging and harmonic imaging to classify pancreatic ***-elastography can assess tissue hardness by measuring its *** parameter appears to correlate with the malignant potential of the *** elasticity studies can provide information on both its pattern and *** former is the conventional method of morphological diagnosis,but it is restricted to observations made in a region of interest(ROI).The latter is an unbiased analysis that can be performed by image analysis software and is theoretically constant,regardless of the *** EUSfine needle aspiration(FNA)is also a very useful diagnostic tool,there are several *** EUS-FNA of pancreatic cystic lesions has marginal utility mainly due to low ***,in particular,endoscopists should keep this limitation in mind.

关键词： Contrast-enhanced endoscopic ultrasonography Endoscopic ultrasonography-elastography Endoscopic ultrasonography-fine needle aspiration Pancreatic cystic lesions Dissemination Track seeding Marginal utility for pancreatic cystic lesions of endoscopic ultrasonography-fine needle aspiration

Hedgehog signaling pathway as a new therapeutic target in pancreatic cancer

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World Journal of Gastroenterology 2014年第9期20卷 2335-2342页

作者： Hideya Onishi Mitsuo katano Department of Cancer Therapy and Research Graduate School of Medical Sciences Kyushu University Fukuoka 812-8582 Japan

Pancreatic cancer is one of the most aggressive and difficult cancers to *** numerous research efforts,limited success has been achieved in the therapeutic management of patients with this *** the current review,we focus on one component of morphogenesis signaling,Hedgehog(Hh),with the aim of developing novel,effective therapies for the treatment of pancreatic *** signaling contributes to the induction of a malignant phenotype in pancreatic cancer and is responsible for maintaining pancreatic cancer stem *** addition,we propose a novel concept linking Hh signaling and tumor hypoxic conditions,and discuss the effects of Hh inhibitors in clinical *** Hh signaling pathway may represent a potential therapeutic target for patients with refractory pancreatic cancer.

关键词： Hedgehog signaling pathway Pancreatic cancer Cancer stem cells Hypoxic condition Therapeutic target

Diabetic neuropathy research: from mouse models to targets for treatment

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Neural Regeneration Research 2019年第11期14卷 1870-1879页

作者： Vuong M. Pham Shinji Matsumura Tayo katano Nobuo Funatsu Seiji Ito Department of Medical Chemistry Kansai Medical UniversityHirakataOsakaJapan Singapore Institute for Neurotechnology (SINAPSE) National University of SingaporeSingapore Department of Anesthesiology Osaka Medical CollegeTakatsukiOsakaJapan

Diabetic neuropathy is one of the most serious complications of diabetes, and its increase shows no sign of stopping. Furthermore, current clinical treatments do not yet approach the best effectiveness. Thus, the development of better strategies for treating diabetic neuropathy is an urgent matter. In this review, we first discuss the advantages and disadvantages of some major mouse models of diabetic neuropathy and then address the targets for mechanism-based treatment that have been studied. We also introduce our studies on each part. Using stem cells as a source of neurotrophic factors to target extrinsic factors of diabetic neuropathy, we found that they present a promising treatment.

关键词： brain derived neurotrophic factor diabetes extrinsic factors nerve growth factor nerve regeneration neurotrophic factors non-obese type 2 diabetes phosphatase and tensin homolog stem cell streptozotocin

Current advances in humanized mouse models

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Cellular & Molecular Immunology 2012年第3期9卷 208-214页

作者： Ryoji Ito Takeshi Takahashi Ikumi katano Mamoru Ito Central Institute for Experimental Animals Kawasaki Japan

Humanized mouse models that have received human cells or tissue transplants are extremely useful in basic and applied human disease research. Highly immunodeficient mice, which do not reject xenografts and support cell and tissue differentiation and growth, are indispensable for generating additional appropriate models. Since the early 2000s, a series of immunodeficient mice appropriate for generating humanized mice has been successively developed by introducing the IL-2Rynull gene （e.g., NOD/SCID/7c＂uu and Rag2nu＂ycnun mice）. These strains show not only a high rate of human cell engraftment, but also generate well-differentiated multilineage human hematopoietic cells after human hematopoietic stem cell （HSC） transplantation. These humanized mice facilitate the analysis of human hematology and immunology in vivo. However, human hematopoietic cells developed from HSCs are not always phenotypically and functionally identical to those in humans. More recently, a new series of immunodeficient mice compensates for these disadvantages. These mice were generated by genetically introducing human cytokine genes into NODISCIDI？cn＂u and Rag2nulITcnUll mice. In this review, we describe the current knowledge of human hematopoietic cells developed in these mice. Various human disease mouse models using these humanized mice are summarized.

关键词： animal model immunodeficient mice immunology hematology humanized mice

Human PBMC-transferred murine MHC class I/II-deficient NOG mice enable long-term evaluation of human immune responses

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Cellular & Molecular Immunology 2018年第11期15卷 953-962页

作者： Tomonori Yaguchi Asuka Kobayashi Takashi Inozume Kenji Morii Haruna Nagumo Hiroshi Nishio Takashi Iwata Yuyo Ka Ikumi katano Ryoji Ito Mamoru Ito Yutaka Kawakami Division of Cellular Signaling Institute for Advanced Medical ResearchKeio University School of MedicineTokyo 160-8582Japan Department of Dermatology Yamanashi University School of MedicineYamanashi 409-3898Japan Department of Obstetrics and Gynecology Keio University School of MedicineTokyo 160-8582Japan Central Institute for Experimental Animals Kanagawa 210-0821Japan

Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune ***,when human peripheral blood mononuclear cells(PBMCs)are transferred into NOG(NOD/Shi-scid,IL-2rg null)mice,severe graft versus host disease(GVHD)hinders long term detailed *** of human PBMCs into newly developed murine MHC class I-and class II-deficient NOG(NOG-dKO;NOG-Iab,B2m-double-knockout)mice showed sufficient engraftment of human immune cells with little sign of *** with influenza vaccine resulted in an increase in influenza-specific human IgG Ab,indicating induction of antigen-specific B cells in the NOG-dKO *** with human dendritic cells pulsed with HLA-A2 restricted cytomegalovirus peptide induced specific cytotoxic T cells,indicating the induction of antigen-specific T cells in the NOG-dKO *** cell therapies(ACTs)using melanoma antigen recognized by T cells(MART-1)-specific TCR-transduced activated T cells showed strong tumor growth inhibition in NOG-dKO mice without any sign of GVHD accompanied by preferential expansion of the transferred MART-1-specific T *** using cultured human melanoma infiltrating T cells also showed anti-tumor effects against autologous melanoma cells in NOG-dKO mice,in which changes in human cancer phenotypes by immune intervention,such as increased CD271 expression,could be ***,NOG-dKO mice are useful tools for more detailed analysis of both the induction and effector phases of T-cell and B-cell responses for a longer period than regular NOG mice.

关键词： adoptive cell therapy humanized mouse vaccine

Rescue case of low birth weight infant with acute hepatic failure

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World Journal of Gastroenterology 2017年第40期23卷 7337-7342页

作者： Noriki Okada Yukihiro Sanada Taizen Urahashi Yoshiyuki Ihara Naoya Yamada Yuta Hirata Takumi katano Kentaro Ushijima Shinya Otomo Shujiro Fujita Koichi Mizuta Department of Transplant Surgery Jichi Medical University Department of Clinical Pharmacology Jichi Medical University Department of Pharmacy Jichi Medical University Department of Pediatrics Yokohama City University School of Medicine

We report a case involving a rescued low birth weight infant(LBWI) with acute liver failure. Case: The patient was 1594 g and 32^(3/7) gestational wk at birth. At the age of 11 d, she developed acute liver failure due to gestational alloimmune liver disease. Exchange transfusion and high-dose gamma globulin therapy were initiated, and body weight increased with enteral nutrition. Exchange transfusion was performed a total of 33 times prior to living donor liver transplantation(LDLT). Her liver dysfunction could not be treated by medications alone. At 55 d old and a body weight of 2946 g, she underwent LDLT using an S2 monosegment graft from her mother. Three years have passed with no reports of intellectual disability or liver dysfunction. LBWIs with acute liver failure may be rescued by LDLT after body weight has increased to over 2500 g.

关键词： Liver transplantation Acute liver failure Low birth weight infant Transplantable body weight Monosegment graft

Selective changes in the <i>α</i>-adrenoceptor-mediated contraction in the senescent rat urinary bladder

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Health 2012年第9期4卷 743-749页

作者： Tomomi Aita Akira Ishihata Akiko Yamada Yumi katano Division of Theoretical Nursing and Pathophysiology Yamagata University School of Medicine Yamagata Japan

The urinary bladder is innervated and functionally regulated by the autonomic nervous system. In order to elucidate the mechanism of functional changes in aged rat urinary bladder, we studied the influence of senescence on, 1) the α-adrenergic contractile response to phenylephrine in the urinary bladder body and trigone, 2) the muscarinic contractile response to carbachol in the body and trigone. The binding characteristics of [3H]quinuclidinyl benzilate (QNB) to muscarinic cholinoceptors were compared in young and aged bladder. Bladders from young (2 - 3 month-old) and aged (27 month-old) male Fischer 344 rats were isolated, cut into strips and mounted in the organ bath, then the developed tension was recorded. Histologically, the aged bladder did not show pathologic changes such as inflammation and hypertrophy. Carbachol-induced contraction in aged rat bladder was identical to that obtained in young rat. In the receptor binding assay, [3H]QNB maximal binding capacity and Kd value were not significantly changed in aged bladder. In contrast, a selective α-adrenergic agonist phenylephrine, elicited greater contractions both in the aged body and trigone than those in young rats. The augmentation of α-adrenoceptor-mediated contractions in aged bladder may induce urinary dysfunction such as voiding difficulty.

关键词： Bladder Smooth Muscle Aging α-Adrenoceptor Muscarinic Receptor

Pediatric living donor liver transplantation for congenital hepatic fibrosis using a mother's graft with von Meyenburg complex: A case report

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World Journal of Gastroenterology 2016年第44期22卷 9865-9870页

作者： Naoya Yamada Yukihiro Sanada Takumi katano Masahisa Tashiro Yuta Hirata Noriki Okada Yoshiyuki Ihara Atsushi Miki Hideki Sasanuma Taizen Urahashi Yasunaru Sakuma Koichi Mizuta Department of Transplant Surgery Jichi Medical University Department of Surgery Jichi Medical University

This is the first report of living donor liver transplantation(LDLT) for congenital hepatic fibrosis(CHF) using a mother's graft with von Meyenburg complex. A 6-year-old girl with CHF, who suffered from recurrent gastrointestinal bleeding, was referred to our hospital for liver transplantation. Her 38-year-old mother was investigated as a living donor and multiple biliary hamartoma were seen on her computed tomography and magnetic resonance imaging scan. The mother's liver function tests were normal and she did not have any organ abnormality, including polycystic kidney disease. LDLT using the left lateral segment(LLS) graft from the donor was performed. The donor LLS graft weighed 250 g; the graft recipient weight ratio was 1.19%. The operation and post-operative course of the donor were uneventful and she was discharged on post-operative day(POD) 8. The graft liver function was good, and the recipient was discharged on POD 31. LDLT using a graft with von Meyenburg complex is safe and useful. Long-term follow-up is needed with respect to graft liver function and screening malignant tumors.

关键词： Congenital hepatic fibrosis Von Meyenburg complex Living donor liver transplantation Pediatric liver transplantation