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A Revised Classification of Primary Iron Overload Syndromes

Journal of Clinical and Translational Hepatology 2024年第4期12卷 346-356页

作者： Yasuaki Tatsumi Motoyoshi Yano Shinya Wakusawa Hiroaki Miyajima Tetsuya Ishikawa Shinsaku Imashuku Atsuko Takano Wataru Nihei Ayako Kato Koichi Kato Hisao hayashi Kentaro Yoshioka kazuhiko hayashi Department of Medical Biochemistry Faculty of Pharmaceutical SciencesToho UniversityFunabashiJapan Department of Gastroenterology Yokkaichi Municipal HospitalYokkaichiJapan Department of Medical Technology Shubun UniversityIchinomiyaJapan Department of Medicine and Neurology Tenryu Kohseikai ClinicHamamatsuJapan Department of Gastroenterology and Hepatology Nagoya University Graduate School of MedicineNagoyaJapan Department of Laboratory Medicine Uji-Tokushukai Medical CenterUjiJapan Department of Medicine Saiseikai Takaoka HospitalTakaokaJapan Department of Medicine Aichi-Gakuin University School of PharmacyNagoyaJapan Department of Gastroenterology FNPS Meijo HospitalNagoyaJapan

Background and Aims:The clinical introduction of hepcidin25(Hep25)has led to a more detailed understanding of its relationship with ferroportin(FP)and divalent metal transporter1 in primary iron overload syndromes(PIOSs).In 2012,we proposed a classification of PIOSs based on the Hep25/FP system,which consists of prehepatic aceruloplasminemia,hepatic hemochromatosis(HC),and posthepatic FP disease(FP-D).However,in consideration of accumulated evidence on PIOSs,we aimed to renew the ***:We reviewed the 2012 classification and retrospectively renewed it according to new information on ***:Iron-loading anemia was included in PIOSs as a prehepatic form because of the newly discovered erythroferrone-induced suppression of Hep25,and the state of traditional FP-D was remodeled as the BIOIRON *** key molecules responsible for prehepatic PIOSs are low transferrin saturation in aceruloplasminemia and increased erythroferrone production by erythroblasts in iron-loading *** PIOSs comprise four genotypes of HC,in each of which the synthesis of Hep25 is inappropriately reduced in the *** Hep25 synthesis is adequate in posthepatic PIOSs;however,two mutant FP molecules may resist Hep25 differently,resulting in SLC40A1-HC and FP-D,*** phenotypes are diagnosed using laboratory tests,including circulating Hep25,followed by suitable *** sequencing of the candidate genes may be outsourced to gene centers when *** kits for the prevalent mutations,such as C282Y,may be the first choice for a genetic analysis of HC in ***:The revised classification may be useful worldwide.

关键词： Ethnicity Ferroportin Hemochromatosis Hepcidin25 Iron overload syndrome

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Transarterial chemoembolization for hepatocellular carcinoma: A review of techniques

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World Journal of Hepatology 2014年第12期6卷 844-850页

作者： Norihiro Imai Masatoshi Ishigami Yoji Ishizu Teiji Kuzuya Takashi Honda kazuhiko hayashi Yoshiki Hirooka Hidemi Goto Department of Gastroenterology and Hepatology Nagoya University Graduate School of Medicine Aichi 466-8560 Japan

Hepatocellular carcinoma(HCC)is one of the most common malignant diseases *** curative therapies,including resection,liver transplantation,and percutaneous ablation(percutaneous ethanol injection and radiofrequency ablation),are applicable for only a portion of the HCC population,transcatheter arterial chemoembolization(TACE)has been recognized as an effective palliative treatment option for patients with advanced *** is also used even for single HCCs in which it is difficult to perform surgical resection or locoregional treatment due to systemic co-morbidities or anatomical *** has become widely adopted in the treatment of *** using computed tomography-angiography,TACE is capable of performing diagnosis and treatment at the same ***,TACE plays an important role in the multidisciplinary treatment for HCC when combined with other *** this review,we first discuss the history of TACE,and then review the previous findings about techniques of achieving a locoregional treatment effect(liver infarction treatment,e.g.,ultra-selective TACE,balloon-occluded TACE),and the use of TACE as a drugdelivery system for anti-cancer agents(palliative,e.g.,platinum complex agents,drug-eluting beads)for multiple lesions.

关键词： Hepatocellular carcinoma Transcatheter arterial chemoembolization Balloon-occluded transcatheter arterial chemoembolization Drug-eluting bead

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Contribution of CD3 ε Epitope and Oxidative Type of Copper-Zinc Superoxide Dismutase to the Degeneration Processes of Cerebellar Purkinje Cells in Patients with Multiple System Atrophy-Cerebellar Type (MSA-C: Olivopontocerebellar Atrophy, OPCA): An Immunohistochemical Study

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World Journal of Neuroscience 2016年第4期6卷 310-324页

作者： Masako Kato Shinsuke Kato Kiyota Kato kazuhiko hayashi Division of Molecular Pathology Department of Pathology Tottori University Faculty of Medicine Yonago Japan Division of Neuropathology Department of Pathology Tottori University Faculty of Medicine Yonago Japan School of Medicine Hiroshima University Hiroshima Japan

Objective: This study aimed to investigate the contribution of CD3 epsilon (ε) epitope and oxidative type of copper-zinc superoxide dismutase to the degeneration processes of cerebellar Purkinje cells in patients with Multiple System Atrophy-Cerebellar type (MSA-C). Methods: This retrospective study was carried out on autopsy specimens of 17 patients with sporadic MSA-C and 10 normal individuals. Paraffin sections of autopsied cerebella and pontes were immunostained with polyclonal antibodies against CD3 ε epitope and oxidative modification to cysteine sulfonic acid of cys111 in human copper-zinc superoxide dismutase (Ox-SOD1). With respect to the areas of CD3-ε-epitope expression, the immunohistochemical study and the quantitative statistical analysis between the areas of CD3-ε-epitope expression in the surviving Purkinje cells of MSA-C patients and their disease duration were performed. Results: The cell bodies and dendritic arborization including primary, secondary, and tertiary dendrites of normal Purkinje cells were intensely immunostained by the antibody against CD3 ε epitope. Both the immunohistochemical study and the quantitative statistical analysis revealed that the areas positive for CD3 ε epitope disappeared in the order from tertiary dendrites, secondary dendrites, primary dendrites toward the cell bodies, along with the disease progression. In addition, Glial Cytoplasmic Inclusions (GCIs) and Neuronal Cytoplasmic Inclusions (NCIs) were strongly positive for CD3 ε epitope. The surviving Purkinje cells in MSA-C showed immunostaining by the anti-Ox-SOD1 antibody, although normal Purkinje cells did not. Conclusion: Based on the oxidative stress that the surviving Purkinje cells in MSA-C express Ox-SOD1, the functions of morphogenesis and morphological maintenance related to CD3-ε-epitope expression of the MSA-C Purkinje cells are impaired from the peripheral dendrites toward the cell bodies as the center of the Purkinje cell system. In addition,

关键词： CD3 Epsilon (ε) Epitope Glial Cytoplasmic Inclusion (GCI) Multiple System Atrophy Oxidative Stress Purkinje Cell

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Copper Accumulates in Hemosiderins in Livers of Patients with Iron Overload Syndromes

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Journal of Clinical and Translational Hepatology 2015年第2期3卷 85-92页

作者： Yukiya Ono Masatoshi Ishigami kazuhiko hayashi Shinya Wakusawa Hisao hayashi Kotaro Kumagai Natsuko Morotomi Tetsuji Yamashita Miwa Kawanaka Minemori Watanabe Hiroaki Ozawa Mayumi Tai Hiroaki Miyajima Kentarou Yoshioka Yoshiki Hirooka Hidemi Goto Department of Gastroenterology Nagoya University Graduate School of Medicine Nagoya Japan Department of Medical Laboratory Sciences Nagoya University Graduate School of Medicine Nagoya Japan Department of Medicine Aichi Gakuin University School of Pharmacy Nagoya Japan Digestive Disease and Lifestyle Related Disease Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan Department of Internal Medicine Moji Hospital Kitakyushu Japan Department of Medicine Yoshida Hospital Matsuyama Japan General Internal Medicine 2 Kawasaki Hospital Kawasaki Medical School Okayama Japan Department of Endocrinology and Diabetes Okazaki City Hospital Okazaki Japan Department of Pathology Okazaki City Hospital Okazaki Japan Department of Gastroenterology Fukushima Rohsai Hospital Fukushima Japan First Department of Medicine Hamamatsu University School of Medicine Hamamatsu Japan Department of Liver Biliary Tract and Pancreas Diseases Fujita Health University Toyoake Japan

In biology,redox reactions are essential and sometimes harmful,and therefore,iron metabolism is tightly regulated by *** the state of copper in iron overload syndromes remains unclear,we investigated whether copper metabolism is altered in these *** patients with iron overload syndromes participated in this *** clinical diagnoses were aceruloplasminemia (n=2),hemochromatosis (n=5),ferroportin disease (n=2),and receiving excess intravenous iron supplementation (n=2).Liver specimens were analyzed using a light microscope and transmission electron microscope equipped with an X-ray *** addition to a large amount of iron associated with oxygen and phosphorus,the iron-rich hemosiderins of hepatocytes and Kupffer cells contained small amounts of copper and sulfur,regardless of disease ***-dimensional imaging clearly showed that cuproproteins were distributed homogenously with iron complexes within *** stasis was unlikely in noncirrhotic *** enhanced induction of cuproproteins by excess iron may contribute to copper accumulation in *** conclusion,we have demonstrated that copper accumulates in hemosiderins in iron overload conditions,perhaps due to alterations in copper metabolism.

关键词： Aceruloplasminemia Cuproprotein induction Ferroportin disease Hemochromatosis Hemosiderin Iron copper interaction Iron overload syndromes

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Prevalence of nonalcoholic fatty liver disease and its association with age in patients with type 2 diabetes mellitus

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World Journal of Hepatology 2022年第6期14卷 1226-1234页

作者： Ryosuke Yamane Kentaro Yoshioka kazuhiko hayashi Yuko Shimizu Yuki Ito Komei Matsushita Michiyo Yoshizaki Go Kajikawa Taro Mizutani Atsuko Watarai Kosuke Tachi Hidemi Goto Department of Gastroenterology and Hepatology Federation of National Public Service Personnel Mutual Aid Associations Meijo HospitalNagoya 460-0001AichiJapan Center for Liver Diseases Federation of National Public Service Personnel Mutual Aid Associations Meijo HospitalNagoya 460-0001AichiJapan Department of Diabetes and Endocrinology Federation of National Public Service Personnel Mutual Aid Associations Meijo HospitalNagoya 460-0001AichiJapan

BACKGROUND Type 2 diabetes mellitus(T2DM)is a risk factor for nonalcoholic fatty liver disease(NAFLD).AIM To determine the prevalence and clinical correlates of NAFLD in a large cohort of patients with *** Four hundred thirty-seven participants with T2DM who consulted at Meijo Hospital from April 2019 to September 2020 and underwent computed tomography(CT)were *** mean age was 74±13 years,and 269 were *** attenuation minus splenic attenuation(CTL−S)less than 1 Hounsfield unit was considered fatty *** was defined as fatty liver in the absence of significant alcohol consumption and hepatitis virus infection.A multiple logistic regression was used to assess the independent factors associated with *** NAFLD was identified in 25.2%of the *** age(odds ratio[OR]=−0.945;95%confidence interval[CI]:0.922–0.969),higher hemoglobin levels(OR=1.501,95%CI:1.278–1.764),lower high-density lipoprotein(HDL)cholesterol levels(OR=0.971,95%CI:0.953–0.989),and the absence of dialysis(OR=0.109,95%CI:0.014–0.856)were independent predictors of *** NAFLD was detected with CT in 25.2%of the *** was associated with younger age,higher hemoglobin levels,lower HDL cholesterol levels,and an absence of dialysis.

关键词： Age Computed tomography Dialysis Hemoglobin Nonalcoholic fatty liver disease Type 2 diabetes mellitus

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Phenotypes and Chronic Organ Damage May Be Different among Siblings with Wilson's Disease

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Journal of Clinical and Translational Hepatology 2017年第1期5卷 27-30页

作者： Shinsuke Yahata Seitetsu Yung Mari Mandai Takakazu Nagahara Daisaku Kuzume Hiroshi Sakaeda Shinya Wakusawa Ayako Kato Yasuaki Tatsumi Koichi Kato Hisao hayashi Ryohei Isaji Yoji Sasaki Motoyoshi Yano kazuhiko hayashi Masatoshi Ishigami Hidemi Goto Division of Community Medicine and Career Development Kobe University Graduate School of Medicine2-1-5Arata-choHyogo-kuKobe 652-0032Japan Department of Gastroenterology Hyogo Prefectural Kakogawa Medical CenterKakogawaHyogoJapan Department of Gastroenterology and Hepatology Tottori Prefectural Kousei HospitalKurayoshiTottoriJapan Departments of Neurology and Gastroenterology Chikamori HospitalKochiJapan Medical Laboratory Sciences Nagoya University Graduate School of MedicineHigashi-kuNagoyaJapan Department of Medicine Aichi Gakuin University School of PharmacyChikusa-kuNagoyaJapan Department of Gastroenterology Konan Kosei HospitalTakaya-choKonanAichiJapan Department of Gastroenterology Yokkaichi Municipal HospitalYokkaichiMieJapan Department of Gastroenterology and Hepatology Nagoya University Graduate School of MedicineShowa-kuNagoyaJapan

Background and Aims:Cloning of ATP7B provided evidence that Wilson's disease is a hepatic copper toxicosis with a variety of extrahepatic *** siblings with the same genetic background and exposure to similar environmental factors may be a good model for the study of genotype-phenotype ***:Twenty-three affected siblings in 11 families were selected from a *** first phenotypes were determined according to the international *** final types of chronic organ damage were re-evaluated for life-long ***:Phenotypes were identical in 5 of the families and different in 6 of the *** acute hepatic phenotype H1 was found in 3 younger siblings and 1 older *** survived an acute episode of hemolysis with underlying chronic liver *** also presented complication with neurological *** neurological phenotype N1 with neuropsychiatric symptoms and hepatic disease was found in 2 aged siblings of 1 family,in an older sibling in 3 families and in the oldest sibling in 1 *** in siblings were mainly split by either H1 occurring in random order or age-dependent *** of chronic organ damage were identical in 8 of the families and different in 3 of the *** same combination of chronic liver disease was found in 6 families and chronic liver disease complicated with neurological disease in 2 *** organ damage in siblings was found when an older sibling was complicated by neurological *** was no reverse combination of a younger sibling being complicated by neurological disease in any of the ***:Phenotype combinations of siblings were mainly modified by externally-induced hemolytic episodes,while chronic organ damage in siblings was split by age-dependent neurological complications.

关键词： Hemolysis Liver disease Neurological disease Wilson's disease

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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

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Psychological potential field and human eye fixation on binary line-drawing images: A comparative experimental study

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Computational Visual Media 2020年第2期6卷 205-214页

作者： Naoyuki Awano Yuki hayashi Osaka University of Economics OsakaOsaka533-8533Japan Osaka Prefecture University SakaiOsaka599-8531Japan

Quantitatively evaluating the psychological and perceptual effects of objects is an important issue,but is difficult. In cognitive studies, the psychological potential field(PPF), which represents psychological intensities in vision and can be calculated by applying computational algorithms to digital images, may help with this issue. Although studies have reported using the PPF to evaluate psychological effects, such as impressions, detailed investigations on how the PPF represents psychological perception and its limitations have not yet been performed. Another relevant tool is the fixation map, which visualizes human eye fixations;this map is generated from actual measurements acquired by eye-tracking and does not represent psychological effects directly. Although the PPF and the fixation map are based on visual imaging, they have never been compared. In this paper, we do so for the first time, using psychological and perceptual properties of line-drawing images. The results demonstrate the difference between these methods, including their representation of different properties with respect to visual perception. Moreover, the similarity between the two methods highlights the possibility of assessing perceptual phenomena such as categorization and cognition of objects based on human vision.

关键词： psychological potential field(PPF) eye fixation eye-tracking visual perception line drawing

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Finite Abelian Groups of K3 Surfaces with Smooth Quotient

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Chinese Annals of Mathematics,Series B 2023年第1期44卷 99-162页

作者： Taro hayashi Faculty of Agriculture Kindai UniversityNakamaticho 3327-204NaraNara 631-8505Japan

The quotient space of a K3 surface by a finite group is an Enriques surface or a rational surface if it is *** groups where the quotient space are Enriques surfaces are *** this paper,by analyzing effective divisors on smooth rational surfaces,the author will study finite groups which act faithfully on K3 surfaces such that the quotient space are *** particular,he will completely determine effective divisors on Hirzebruch surfaces such that there is a finite Abelian cover from a K3 surface to a Hirzebrunch surface such that the branch divisor is that effective ***,he will decide the Galois group and give the way to construct that Abelian cover from an effective divisor on a Hirzebruch ***,he studies the same theme for Enriques surfaces.

关键词： K3 surface Finite Abelian group Abelian cover of a smooth rational surface

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Changes of integrin expression in rat hepatocarcinogenesis induced by 3′-Me-DAB

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World Journal of Gastroenterology 2000年第2期6卷 231-233页

作者： hayashi KeiKi Department of Pathology Okayarna UniversityJapan

AIM To investigate the expression of integrinsin rats liver during 3’-Me-DAB inducedhepatocarcinogenesis and to find out therelationship between integrins and liver *** The expressions of integrins α1,α2,α3 and α5 and epidermal keratin（EK）wereobserved by immunohistochemical PAP *** In the normal liver tissues,hepatocytes express integrins α1 and α5 and inthe bile duct epithlium,*** liver cirrhosis,hepatocytes highly express integrins α1,α2,α3and α5 and in hyperplastic bile duct epithelium,integrins α1,α5 and *** of integrinsα1,α2,α3 and α5 were obviously decreased in thepreneoplastic nodules and primary carcinomabut expressions of integrins α1 and α5 inmetastasis in the lung and diaphragma werehigher than those in primary *** Integrins α1 and α5 may play amajor role in chemically inducedhepatocarcinogenesis and metastasis in rats.

关键词： integrins 3′-Me-DAB liver neoplasm/chemically induced neoplasm metastasis rats

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