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1. Formation and evolution of carbonaceous asteroid Ryugu: Direct evidence from returned samples

Author

T. Nakamura, M. Matsumoto, K. Amano, Y. Enokido, M. E. Zolensky, T. Mikouchi, H. Genda, S. Tanaka, M. Y. Zolotov, K. Kurosawa, S. Wakita, R. Hyodo, H. Nagano, D. Nakashima, Y. Takahashi, Y. Fujioka, M. Kikuiri, E. Kagawa, M. Matsuoka, A. J. Brearley, A. Tsuchiyama, M. Uesugi, J. Matsuno, Y. Kimura, M. Sato, R. E. Milliken, E. Tatsumi, S. Sugita, T. Hiroi, K. Kitazato, D. Brownlee, D. J. Joswiak, M. Takahashi, K. Ninomiya, T. Takahashi, T. Osawa, K. Terada, F. E. Brenker, B. J. Tkalcec, L. Vincze, R. Brunetto, A. Aléon-Toppani, Q. H. S. Chan, M. Roskosz, J.-C. Viennet, P. Beck, E. E. Alp, T. Michikami, Y. Nagaashi, T. Tsuji, Y. Ino, J. Martinez, J. Han, A. Dolocan, R. J. Bodnar, M. Tanaka, H. Yoshida, K. Sugiyama, A. J. King, K. Fukushi, H. Suga, S. Yamashita, T. Kawai, K. Inoue, A. Nakato, T. Noguchi, F. Vilas, A. R. Hendrix, C. Jaramillo-Correa, D. L. Domingue, G. Dominguez, Z. Gainsforth, C. Engrand, J. Duprat, S. S. Russell, E. Bonato, C. Ma, T. Kawamoto, T. Wada, S. Watanabe, R. Endo, S. Enju, L. Riu, S. Rubino, P. Tack, S. Takeshita, Y. Takeichi, A. Takeuchi, A. Takigawa, D. Takir, T. Tanigaki, A. Taniguchi, K. Tsukamoto, T. Yagi, S. Yamada, K. Yamamoto, Y. Yamashita, M. Yasutake, K. Uesugi, I. Umegaki, I. Chiu, T. Ishizaki, S. Okumura, E. Palomba, C. Pilorget, S. M. Potin, A. Alasli, S. Anada, Y. Araki, N. Sakatani, C. Schultz, O. Sekizawa, S. D. Sitzman, K. Sugiura, M. Sun, E. Dartois, E. De Pauw, Z. Dionnet, Z. Djouadi, G. Falkenberg, R. Fujita, T. Fukuma, I. R. Gearba, K. Hagiya, M. Y. Hu, T. Kato, T. Kawamura, M. Kimura, M. K. Kubo, F. Langenhorst, C. Lantz, B. Lavina, M. Lindner, J. Zhao, B. Vekemans, D. Baklouti, B. Bazi, F. Borondics, S. Nagasawa, G. Nishiyama, K. Nitta, J. Mathurin, T. Matsumoto, I. Mitsukawa, H. Miura, A. Miyake, Y. Miyake, H. Yurimoto, R. Okazaki, H. Yabuta, H. Naraoka, K. Sakamoto, S. Tachibana, H. C. Connolly, D. S. Lauretta, M. Yoshitake, M. Yoshikawa, K. Yoshikawa, K. Yoshihara, Y. Yokota, K. Yogata, H. Yano, Y. Yamamoto, D. Yamamoto, M. Yamada, T. Yamada, T. Yada, K. Wada, T. Usui, R. Tsukizaki, F. Terui, H. Takeuchi, Y. Takei, A. Iwamae, H. Soejima, K. Shirai, Y. Shimaki, H. Senshu, H. Sawada, T. Saiki, M. Ozaki, G. Ono, T. Okada, N. Ogawa, K. Ogawa, R. Noguchi, H. Noda, M. Nishimura, N. Namiki, S. Nakazawa, T. Morota, A. Miyazaki, A. Miura, Y. Mimasu, K. Matsumoto, K. Kumagai, T. Kouyama, S. Kikuchi, K. Kawahara, S. Kameda, T. Iwata, Y. Ishihara, M. Ishiguro, H. Ikeda, S. Hosoda, R. Honda, C. Honda, Y. Hitomi, N. Hirata, T. Hayashi, M. Hayakawa, K. Hatakeda, S. Furuya, R. Fukai, A. Fujii, Y. Cho, M. Arakawa, M. Abe, Y. Tsuda, Tohoku University [Sendai], NASA Johnson Space Center (JSC), NASA, The University of Tokyo (UTokyo), Tokyo Institute of Technology [Tokyo] (TITECH), Institute of Space and Astronautical Science (ISAS), Japan Aerospace Exploration Agency [Sagamihara] (JAXA), ASU School of Earth and Space Exploration (SESE), Arizona State University [Tempe] (ASU), Planetary Exploration Research Center [Chiba] (PERC), Chiba Institute of Technology (CIT), Department of Earth, Atmospheric and Planetary Sciences [MIT, Cambridge] (EAPS), Massachusetts Institute of Technology (MIT), Nagoya University, Department of Earth and Planetary Science [Tokyo], Graduate School of Science [Tokyo], The University of Tokyo (UTokyo)-The University of Tokyo (UTokyo), Pôle Planétologie du LESIA, Laboratoire d'études spatiales et d'instrumentation en astrophysique = Laboratory of Space Studies and Instrumentation in Astrophysics (LESIA), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Guangzhou Institute of Geochemistry, Ritsumeikan University, Japan Synchrotron Radiation Research Institute [Hyogo] (JASRI), Institute of Low Temperature Science [Sapporo], Hokkaido University [Sapporo, Japan], Department of Earth, Environmental and Planetary Sciences [Providence], Brown University, The University of Aizu, University of Washington [Seattle], Osaka University, Kavli Institute for the Physics and Mathematics of the Universe [Tokyo] (Kavli IPMU), The University of Tokyo Institutes for Advanced Study (UTIAS), Japan Atomic Energy Agency, Goethe-University Frankfurt am Main, Department of Inorganic and Physical Chemistry, Ghent University, Universiteit Gent = Ghent University (UGENT), Institut d'astrophysique spatiale (IAS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Centre National d’Études Spatiales [Paris] (CNES), Department of Earth Sciences, Royal Holloway, University of London, Egham, Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Centre National d'Études Spatiales [Toulouse] (CNES)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France -Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France, Advanced Photon Source [ANL] (APS), Argonne National Laboratory [Lemont] (ANL)-University of Chicago-US Department of Energy, Kindai University, Kyushu University, Department of Earth and Atmospheric Sciences [Houston], University of Houston, Texas Materials Institute (TMI), University of Texas at Austin [Austin], Department of Geoscience, Virginia Tech, Blacksburg, VA, United States, National Institute for Materials Science (NIMS), Department of Earth Sciences [NHM London] (DES-NHM), The Natural History Museum [London] (NHM), Kanazawa University (KU), Graduate University for Advanced Studies [Hayama] (SOKENDAI), Division of Earth and Planetary Sciences [Kyoto], Kyoto University, Planetary Science Institute [Tucson] (PSI), Pennsylvania State University (Penn State), Penn State System, California State University [San Marcos] (CSUSM), Space Sciences Laboratory [Berkeley] (SSL), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Division of Geological and Planetary Sciences [Pasadena], California Institute of Technology (CALTECH), University of Shizuoka, Ehime University [Matsuyama, Japon], European Space Astronomy Centre (ESAC), Agence Spatiale Européenne = European Space Agency (ESA), KEK (High energy accelerator research organization), Hitachi, Ltd, Institute for integrated Radiation and Nuclear Science (KURNS), National Metrology Institute of Japan, National Institute of Advanced Industrial Science and Technology (AIST), Department of Physics, Rikkyo University, Tokyo, Japan Fine Ceramics Center (JFCC), Istituto di Astrofisica e Planetologia Spaziali - INAF (IAPS), Istituto Nazionale di Astrofisica (INAF), The Aerospace Corporation, Earth-Life Science Institute [Tokyo] (ELSI), University of Chinese Academy of Sciences [Beijing] (UCAS), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Photone Sciences, Deutsches Elektronen-Synchrotron (DESY), Graduate School of Life Science, University of Hyogo, International Christian University, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Center for Advanced Radiation Sources [University of Chicago] (CARS), University of Chicago, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Physique (ICP), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Graduate School of Information Science [Nagoya], Department of Natural History Sciences, Department of Earth and Planetary Sciences [Fukuoka], Graduate School of Advanced Science and Engineering [Higashi-Hiroshima], Hiroshima University, Rowan University, Lunar and Planetary Laboratory [University of Arizona] (LPL), University of Arizona, Kanagawa Institute of Technology, Marine Works Japan Ltd., Faculty of Science, Niigata University, National Astronomical Observatory of Japan (NAOJ), Department of Physics and Astronomy [Seoul], Seoul National University [Seoul] (SNU), Kochi University, Department of Planetology, Graduate School of Science, Graduate School of Science [Kobe], Kobe University-Kobe University, Kobe University, Supported by KAKENHI from the Japanese Society for Promotion of Science (JSPS), grants JP20H00188 and 19H05183 to T.N., JP19K14776 to M.M., 21K18645 to T.M. and K.S., JP20H00205 to A.Ts., M.M., A.M. and J.M., 17H06458 to K.F., Y.T., S.Y. and M.K., JP17H06459 to T.N., T.U., S.W., M.M., N.N., T.M., T.O., Y.S., N.S., and R.N., JP15H05695 to A.Ts. and K.U., 20H05846 to S.T., JP17H06457 to H.G., JP17H06458 to Y. T. and K. F., JP19H00726 to K.K., H. G., and T.M., JP21J13337 to K.A., and JP18H05456,JP20H00189 to K.S., 18H05463 to T.T., S.N., and S.W., 18H05460 to K.N. and T.O., 18H05464 to Y.M., 18H05457 to K.N., T.T., S.W., and Y.M., and JP18H05479 to M.U. Also supported by the JSPS Core-to-Core program ' International Network of Planetary Sciences', and from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (grants JPMXS0450200421 and JPMXS0450200521) to SS. A.K. acknowledges funding support from UK Research and Innovation (UKRI) grant MR/T020261/1. A.B. acknowledges funding support from NASA Emerging Worlds grant - 80NSSC18K0731. P.B. acknowledges funding from the European Research Council (ERC) under grant agreement no. 771691 (Solarys) and the CNES., and European Project: 771691,SOLARYS

Subjects
Multidisciplinary, [SDU]Sciences of the Universe [physics], Ryugu Hayabusa2 Carbonaceous asteroid Sample return
Abstract

Samples of the carbonaceous asteroid Ryugu were brought to Earth by the Hayabusa2 spacecraft. We analyzed 17 Ryugu samples measuring 1 to 8 millimeters. Carbon dioxide–bearing water inclusions are present within a pyrrhotite crystal, indicating that Ryugu’s parent asteroid formed in the outer Solar System. The samples contain low abundances of materials that formed at high temperatures, such as chondrules and calcium- and aluminum-rich inclusions. The samples are rich in phyllosilicates and carbonates, which formed through aqueous alteration reactions at low temperature, high pH, and water/rock ratios of

Published
2022
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2. Sequence analysis of the hepatitis C virus (HCV) core gene suggests the core protein as an appropriate target for HCV vaccine strategies

Author

W. M. McDonnell, Y. HitOmi, F. K. Askari, and A. A. Killeen

Subjects
Hepatitis C virus, Immunoblotting, Molecular Sequence Data, Population, Biology, medicine.disease_cause, Polymerase Chain Reaction, Sequence Homology, Nucleic Acid, Virology, Genotype, medicine, Amino Acid Sequence, education, education.field_of_study, Base Sequence, Sequence Homology, Amino Acid, Hepatology, Viral Core Proteins, Genetic Variation, Hepatitis C, Hepatitis C Antibodies, medicine.disease, Vaccine efficacy, Vaccination, Infectious Diseases, Immunology, Viral hepatitis, Vaccine failure
Abstract

Hepatitis C virus (HCV) is a major healthproblem with a prevalence of 1% in the United States population, and a significant percentage of infected patients progress to chronic liver disease and cirrhosis. Interferon therapy has demonstrated that the immune system can be modulated to alter the acute course of the disease, but long-term treatments remain elusive. Prevention of hepatitis C infection is therefore an important strategy to mitigate the impact of this disease. Initial attempts at vaccination have focused on recombinant envelope vaccines, which have shown an ability to protect against very low titre challenges of HCV in chimps. The need for vaccines capable of protecting against higher titre challenges has led to the search for alternative vaccine strategies. The most highly conserved structural protein in the HCV genome is the core protein, and vaccine strategies targeting the core protein have been proposed to increase vaccine efficacy. The variability of HCV core sequences and genotypes in the Ann Arbor patient population are not known, and the present study was undertaken to assess the theoretical feasibility of developing a HCV core vaccine by excluding promiscuous core (C) gene variability as a mechanism of vaccine failure. Results of nucleotide and deduced amino acid sequence analysis from 13 of 14 patients studied reveal a 93% nucleotide and 96.4% amino acid core sequence homology in the C gene regions studied. Genotype analysis revealed four of 14 to be type 1a and nine of 14 to be type 1b with one infection not being sufficiently characterized to determine genotype. These results demonstrate a sufficiently high degree of conservation of HCV core sequences in our patient population to permit design of a vaccine directed against core protein.

Published
1995
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3. Improvement of slab quality of ultra-low carbon steel in curved mold type continuous casting machines

Author

T. Nagahata, Y. Hitomi, and M. Asano

Subjects
Materials science, Carbon steel, Metallurgy, Nozzle, Metals and Alloys, engineering.material, Condensed Matter Physics, medicine.disease_cause, Pencil (optics), Continuous casting, Mold, Materials Chemistry, Slab, medicine, engineering, Physical and Theoretical Chemistry
Abstract

The casting speed of ULC-Ti steel in a curved mold type continuous casting machine used to be restricted by the formation of pencil pipe defects. These defects being caused by Ar bubbles at the immersion nozzle, a casting method without addition of Ar gas has been developed. With this method, casting speed could be raised and, at the same time, the occurrence of pencil pipe defects and phosphorous slivers reduced. The increase in alumina slivers could partly be compensated for by the higher casting speed made possible by the new casting method.

Published
1995
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4. High Efficiency Prokaryotic Expression and Purification of a Portion of the Hepatitis C Core Protein and Analysis of the Immune Response to Recombinant Protein in BALB/c Mice

Author

F. K. Askari, Y. HitOmi, W. M. McDonnell, and J R Baker

Subjects
Gene Expression Regulation, Viral, Recombinant Fusion Proteins, Hepatitis C virus, Molecular Sequence Data, Immunology, Population, Hepacivirus, medicine.disease_cause, law.invention, Mice, Maltose-binding protein, Antigen, law, Virology, Escherichia coli, medicine, Animals, Humans, Amino Acid Sequence, education, Glutathione Transferase, Mice, Inbred BALB C, education.field_of_study, Liver infection, Base Sequence, biology, Viral Core Proteins, 3T3 Cells, Hepatitis C, Hepatitis C Antibodies, Hepatitis B, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, Prokaryotic Cells, DNA, Viral, Recombinant DNA, biology.protein, Molecular Medicine, T-Lymphocytes, Cytotoxic
Abstract

Hepatitis C virus (HCV) produces chronic persistent liver infection in 1-2% of the U.S. population and is the leading cause of end stage liver disease in patients presenting for liver transplantation at our center. Efforts to cure persistent HCV infection are frequently unsuccessful, so the development of a HCV vaccine is a high priority. HCV envelope proteins are hypervariable so production of a recombinant surface antigen vaccine such as is available for hepatitis B is not likely to confer widespread, high level protective immunity. As the most highly conserved structural protein in the HCV genome, the core protein is one reasonable target for vaccine production. Presented here are data on the manufacture of recombinant core protein containing partial carboxy terminus deletions in an effort to increase the efficiency of core expression. The maltose binding protein (MBP) and glutathione S-transferase (GST) protein prokaryotic expression systems were used to study two different constructs, expressing the first 140 and 163 amino acids of the core region. Deletion of the 23 amino acids (aa) from aa141-163 led to a marked increase in the efficiency of protein production from1 to 3-4 mg/liter for both systems studied. Protein purification was accomplished using affinity chromatography (MBP) or inclusion body isolation (GST) as determined by SDS-PAGE gels and immunotransblot with HCV core protein-specific monoclonal antibody. Finally, the immune response to recombinant protein was assessed in BALB/c mice using a MBP HCV core fusion protein and an ELISA developed using GST HCV core protein as a target. In all mice of this strain, serum anti-HCV core antibody titer increased to 10(-4), two logs above background, following immunization in conjunction with Freund's complete adjuvant. These results represent an encouraging first step toward production of a core protein vaccine. Recombinant core protein is a useful tool to study the immune response to core protein and may be useful to further study the epidemiology and biology of the HCV virus.

Published
1995
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5. Increased systemic inflammatory interleukin-1ß and interleukin-6 during agitation as predictors of Alzheimer's disease

Author

T, Honma, K, Hatta, Y, Hitomi, Y, Kambayashi, Y, Hibino, T, Konoshita, and H, Nakamura

Subjects
Aged, 80 and over, Male, Interleukin-6, Dementia, Vascular, Incidence, Interleukin-1beta, Body Mass Index, Japan, Alzheimer Disease, Predictive Value of Tests, Hypertension, Diabetes Mellitus, Humans, Female, Biomarkers, Psychomotor Agitation, Aged
Abstract

Identification of biomarkers for Alzheimer's disease (AD) is important for its early diagnosis and prevention and a key in advancing our understanding of its pathophysiology. The aim of this study was to determine whether systemic inflammatory interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) as well as hypertension (HT), diabetes mellitus (DM), and body mass index (BMI) are predictors of AD.We performed a 10-year follow-up study on 133 elderly who were institutionalized in a nursing home. The associations of IL-1ß and IL-6 at both rest and agitation, as well as HT, DM, and BMI at baseline, were analyzed with the incidences of vascular dementia (VD) and AD during a 10-year follow-up period.The Kaplan-Meier method with log-rank test and Cox regression analyses for the total of 133 subjects showed significantly higher incidences of both VD and AD in subjects with DM or HT at baseline. Resting IL-1ß or IL-6 value, or agitation score, was not significantly associated with the subsequent development of VD or AD. The analyses of 40 subjects who had shown agitation at least once in the previous 3 months demonstrated that IL-1ß and IL-6 values at the agitation stage were significantly associated with AD, but not with VD.Our results indicate that systemic inflammatory IL-1ß and IL-6 at the agitation stage are risk factors for the development of AD, but not VD. Inflammatory mechanisms for AD seem to be causal and specific to the development of AD.

Published
2011

6. Rolling of Ni-based alloy (57Ni-15Cr 16Mo-3W) billets

Author

Y. Hitomi, A. Yamanaka, T. Nakayama, T. Katabuchi, K. Kobayashi, and M. Terunuma

Subjects
Materials science, Carbon steel, Bar (music), Metallurgy, Alloy, Metals and Alloys, engineering.material, Deformation (meteorology), Condensed Matter Physics, Forging, Materials Chemistry, engineering, Grain boundary, Physical and Theoretical Chemistry, Ingot, Stress concentration
Abstract

In Wakayama steel works of SMI, carbon steel and stainless steel billets are rolled by 2-stand 2-high reversing blooming mill.Ni-based alloy (57Ni-15Cr-16Mo-3W) billets have been produced by hot forging because of its high deformation resistance (from 3.5 t ingot to finished bar dia. 253 mm). Recently hot rolling of the alloy became possible. Two-heat rolling is used. The relatively low soaking temperature (1 230 °C) is applied for the first rolling to prevent a hot tear formation by a grain boundary remelting of the ingot due to segregation. After the first heat rolling, the intermediate bar is reheated at 1 250 °C to assure lower deformation resistance for the final rolling.Pass design and schedule are improved to reduce the amount of deformation at the final stages. The second bloomer housing design is modified to reduce stress concentration and to allow higher rolling load application.

Published
1992
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7. Contribution of the calcineurin signaling pathway to overload-induced skeletal muscle fiber-type transition

Author

M, Miyazaki, Y, Hitomi, T, Kizaki, H, Ohno, S, Haga, and T, Takemasa

Subjects
Male, Mice, Mice, Inbred ICR, Calcineurin, Calcineurin Inhibitors, Muscle Fibers, Skeletal, Animals, Muscle, Skeletal, Tacrolimus, Signal Transduction
Abstract

Skeletal muscle is highly adaptable, being capable of undergoing changes in its structural and functional properties in response to physiological stimuli. The fast-to-slow muscle fiber-type transition is evoked by increased motor nerve activity. Recently, the calcineurin (CaN) signaling pathway has been implicated in the transcriptional regulation of slow muscle fiber genes. Here we investigated the effect of treatment with a CaN-specific inhibitor, FK506, on skeletal muscle fiber-type transition in functionally overloaded muscles. The overloaded plantaris muscle showed fast-to-slow muscle fiber type transition, i.e., a decrease in myosin heavy chain (MHC) IIb, an increase in MHCIIa+d/x, and new expression of MHCI. In the FK506-administered group, however, overload-induced muscle fiber-type transition was completely prevented. We have demonstrated, therefore, that the CaN signaling pathway is required for fast-to-slow skeletal muscle fiber-type transition. Furthermore, we also confirmed that the protein expression levels of downstream effectors of CaN signaling exhibit a transient increase in the early phase of the overloaded condition.

Published
2004

8. Serum extracellular superoxide dismutase in pediatric patients with various diseases as judged by an ELISA

Author

T, Ookawara, N, Matsuura, T, Oh-ishi, M, Okazaki, T, Kizaki, K, Suzuki, Y, Hitomi, and H, Ohno

Subjects
Adult, Male, Adolescent, Superoxide Dismutase, Case-Control Studies, Child, Preschool, Humans, Infant, Disease, Enzyme-Linked Immunosorbent Assay, Child, Extracellular Space
Abstract

Extracellular superoxide dismutase (EC-SOD) concentration was measured in sera from 141 patients with 20 forms of infantile diseases including IDDM, SLE and epilepsy, 31 healthy children (controls), and 21 healthy young men by an enzyme-linked immunosorbent assay using a polyclonal antibody against human lung EC-SOD. Serum from patients with IDDM and fever of unknown origin had a significantly (p0.05) lower concentration of EC-SOD than control serum. Part of sera from patients with the seven forms of diseases (SLE, viral infections, epilepsy, nephrosis, hyperthyroidism, hepatic disease, and Reye syndrome), on the other hand, had a greatly high concentration of EC-SOD, albeit not statistically significant. This SOD isoenzyme profile appears to be specific to each pediatric disease.

Published
2001

9. Acetaldehyde production by non-pathogenic Neisseria in human oral microflora: implications for carcinogenesis in upper aerodigestive tract

Author

M, Muto, Y, Hitomi, A, Ohtsu, H, Shimada, Y, Kashiwase, H, Sasaki, S, Yoshida, and H, Esumi

Subjects
Mouth, Bacteria, Ethanol, Alcohol Dehydrogenase, Humans, Acetaldehyde, Aldehyde Dehydrogenase, Digestive System Neoplasms, Neisseria
Abstract

Many epidemiological studies have identified chronic alcohol consumption as a significant risk factor for cancer of the upper aerodigestive tract (UAT) in human. Although acetaldehyde, the first metabolite from ethanol by alcohol dehydrogenase (ADH), is regarded as a carcinogen, how systemic production of acetaldehyde particularly affects the UAT remains unclear. In our study, we searched for the regional source of acetaldehyde in UAT, especially the involvement of bacteria in the human normal oral microflora. Here we demonstrate that, among the bacterial species identified from the human oral cavity, genus Neisseria had extremely high ADH activity and produced significant amounts of acetaldehyde when cultured with medium containing ethanol in vitro. The ability to produce acetaldehyde was more than 100-fold higher than that produced by any other genera we studied. Furthermore, alcohol ingestion influences the bacterial composition of the oral microflora, resulting in an increased proportion of Neisseria. Although Neisseria present in normal oral microflora is generally non-pathogenic, these findings suggest that this microbe can be a regional source of carcinogenic acetaldehyde and thus potentially play an important role in alcohol-related carcinogenesis in human UAT.

Published
2000

10. Increased growth of Bifidobacterium and Eubacterium by germinated barley foodstuff, accompanied by enhanced butyrate production in healthy volunteers

Author

Atsushi Toyonaga, K Agata, Akira Andoh, Toru Nakamura, Tadao Bamba, Keiichi Mitsuyama, T Saiki, Yoshio Araki, Osamu Kanauchi, Yoshihide Fujiyama, Y Hitomi, and T Ishii

Subjects
Adult, Male, Lactobacillus casei, Bifidobacterium longum, ved/biology.organism_classification_rank.species, Germination, Butyrate, digestive system, fluids and secretions, Lactobacillus acidophilus, Genetics, Humans, Nutritional Physiological Phenomena, Eubacterium, Food science, Clostridium butyricum, Bifidobacterium, Bifidobacterium breve, biology, ved/biology, food and beverages, Hordeum, General Medicine, biology.organism_classification, Intestines, Butyrates, Food, Immunology, bacteria, Female
Abstract

Germinated barley foodstuff (GBF) derived from the aleurone and scutellum fractions of germinated barley mainly consists of low-lignified hemicellulose and glutamine-rich protein. GBF improves the proliferation of intestinal epithelial cells and defecation, through the bacterial production of short chain fatty acids (SCFA), especially butyrate. In this study we investigated the mechanism of production of butyrate by microflora in humans and in vitro. Daily administration of 9 g GBF for 14 successive days significantly increased fecal butyrate content. Fecal Bifidobacterium and Eubacterium were also significantly increased by GBF administration in healthy volunteers. Ten anaerobic micro-organisms selected from intestinal microflora were cultured in vitro in the medium containing GBF as a sole carbon source (GBF medium). After a 3-day incubation, 7 strains (Bifidobacterium breve, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus casei subsp. casei, Bacteroides ovatus, Clostridium butyricum, and Eubacterium limosum) lowered the medium pH producing SCFA. Eubacterium grown together with Bifidobacterium in GBF medium efficiently produced butyrate. On the other hand, GBF changed the intestinal microflora and increased probiotics such as Bifidobacterium in the intestinal tract. As a result, butyrate was produced by the mutual action of Eubacterium and Bifidobacterium. This butyrate is considered to enhance the proliferation of colonic epithelial cells.

Published
1999
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11. Germinated barley foodstuff increases fecal volume and butyrate production at relatively low doses and relieves constipation in humans

Author

Y Hitomi, Yoshihide Fujiyama, Osamu Kanauchi, Tsuyoshi Nakamura, Yoshio Araki, Keiichi Mitsuyama, Tadao Bamba, and T Saiki

Subjects
Adult, Dietary Fiber, Male, Constipation, Germination, Butyrate, Biology, Feces, Animal science, Genetics, medicine, Humans, Defecation, Maximum level, Short-chain fatty acid, Low dose, Hordeum, General Medicine, Butyrates, Immunology, Female, medicine.symptom
Abstract

Germinated barley foodstuff (GBF), derived from the aleurone layer, scutellum and germ of germinated barley, contains a large quantity of fermentable dietary fibers, especially hemicellulose. GBF was given to 9 healthy volunteers in a dose of 9 g of GBF per day for 10 consecutive days, and subsequently 18 g of GBF for another 10 days. As a control, no GBF was given for 3 days before administration of GBF (control period). Fecal weight, water content and short chain fatty acid content were measured before and during the last 3 days of each experimental period. Feeding of GBF significantly increased the fecal butyrate content as well as fecal weight at both dose-levels (9 and 18 g/day), compared with those during the control period. Daily administration of 9 g GBF induced the maximum level of defecation in humans. Relatively mild but chronic constipated volunteers (n = 16) were administered 9 g of GBF daily for 14 days. In this experiment, the condition of defecation (frequency, volume) was estimated by a questionnaire survey. GBF significantly improved defecation within a short period without severe adverse effects. No major abnormalities in laboratory findings were found in hematologic and urinary analyses. In conclusion, daily administration of 9 g GBF was effective for improving defecation in healthy but constipated humans. GBF is a highly safe and effective foodstuff for improving defecation.

Published
1998
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12. Evidence for monoclonal expansion of epithelial cells in ovarian endometrial cysts

Author

H, Jimbo, Y, Hitomi, H, Yoshikawa, T, Yano, M, Momoeda, A, Sakamoto, O, Tsutsumi, Y, Taketani, and H, Esumi

Subjects
Adult, Endometriosis, Cell Separation, Sequence Analysis, DNA, Middle Aged, Epithelium, Clone Cells, Ovarian Cysts, Receptors, Androgen, parasitic diseases, Humans, Female, Alleles, Cell Division, Research Article
Abstract

Ovarian endometrial cysts, one of the typical manifestations of endometriosis, are generated by the retention of cyclic hemorrhages and are classified as tumor-like lesions rather than neoplasms. Clonality analysis provides important information about the histogenesis and progression of neoplastic diseases. As it is generally accepted that most neoplasms are monoclonal in origin, however, the clonality of endometrial cysts remains uncertain. Using the human androgen receptor gene (HUMARA) as an X-linked polymorphic marker, we examined the clonal status of epithelial cells in endometrial cysts. We separated 21 fresh epithelial cell samples from 11 endometrial cysts and found that all were monoclonal in the methylation pattern of the HUMARA alleles. Moreover, in each of the five cysts from which epithelial cells were sampled from multiple and distant areas, the methylation patterns of all samples from a single cyst were identical. These data indicate that endometrial cysts are monoclonal in origin and suggest their neoplastic potentiality.

Published
1997

13. Complete correction of hyperbilirubinemia in the Gunn rat model of Crigler-Najjar syndrome type I following transient in vivo adenovirus-mediated expression of human bilirubin UDP-glucuronosyltransferase

Author

F K, Askari, Y, Hitomi, M, Mao, and J M, Wilson

Subjects
Genetic Vectors, Rats, Gunn, Gene Transfer Techniques, Gene Expression, Bilirubin, Genetic Therapy, Adenoviridae, Rats, Animals, Humans, Glucuronosyltransferase, In Situ Hybridization, Crigler-Najjar Syndrome, Hyperbilirubinemia
Abstract

Recombinant adenoviral vectors are useful for the in vivo expression of genes in hepatocytes. Adenoviral vectors deleted in E1a, E1b, and E3b were constructed and used to study in vivo expression of the major human bilirubin UDP-glucuronosyltransferase isoform (HUG Br1) under the transcriptional control of the cytomegalovirus (CMV) immediate-early promoter-enhancer (H5.010CMV hugBr1). As a control, a recombinant adenoviral vector containing the beta-galactosidase reporter gene driven by the CMV promoter-enhancer was employed (H5. 010CMVlacZ). Recombinant virus was expanded following exposure to E1 transcomplementing (293) cells and concentrated to t titer of approximately 10(13) particles per milliliter. A rat model for Crigler-Najjar syndrome type I deficient in HUG Br1 (ie the Gunn rat) was injected with 5 X 10(9) plaque-forming units (p.f.u.) via the portal vein of either H5.010CMVhugBr1 or H5. 010CMVlacZ. Rats from each set were killed at 3 days, 11 days and 22 days after infusion. Liver total cellular DNA, RNA and protein were analyzed for the transgene and the transgene product at the specified times. Analysis of livers by Southern blot hybridization demonstrates sequence-specific hybridization to adenoviral vector DNA, and Northern blot hybridization demonstrates sequence-specific hybridization to transgene-derived RNA. DNA levels peak at approximately one copy number at 3 days and decline over 22 days. RNA and Western blot analyses demonstrate overexpression of message and protein at 3 days, declining over 22 days. In virto functional assay for bilirubin glucuronosyl-transferase activity demonstrates overexpression of bilirubin UDP-glucurosyltransferase function. In situ hybridization of frozen sections to detect expressed mRNA using beta-galactosidasederived 35S-labeled riboprobes demonstrates adenovirus-derived transgene expression in hepatocytes. Significant drops in serum bilirubin levels were noted following expression of HUG Br1 but not beta-galactosidase. The drop in serum bilirubin correlates with the appearance of bilirubin glucuronides in bile. In summary, recombinant adenoviral vectors were used to demonstrate in vivo complementation of the genetic defect in Gunn rat livers with the HUG Br1 cDNA leading to a resolution of hyperbilirubinemia lasting approximately 7 weeks. These studies suggest that delivery of the HUG Br1 cDNA might provide a reasonable therapeutic benefit for Crigler-Najjar syndrome type I patients, as safe and efficacious gene delivery systems are developed.

Published
1996

14. [Clinical study of autologous blood transfusion in pregnant women]

Author

K, Kuromaki, S, Takeda, H, Seki, K, Kinoshita, Y, Hitomi, and H, Maeda

Subjects
Adult, Blood Transfusion, Autologous, Hemoglobins, Reticulocytes, Blood Preservation, Pregnancy, Postpartum Period, Humans, Female, Erythropoietin, Blood Coagulation Factors, Blood Cell Count
Abstract

The effect of autologous blood donation during the third trimester of pregnancy on the maternal circulation, the properties of blood collected in a phosplatebuffered citrate anticoagulant solution, and the clinical outcome of autologous blood donation and transfusion for pregnant women were investigated in this study. Thirty-four pregnant women with placenta previa or previous cesarean delivery underwent phlebotomies in an autologous transfusion program. Three hundred ml of blood was collected under the observation of fetal heart rate patterns and uterine contractions from 3 weeks prior to the planned date of cesarean section and a total of 900 ml of blood was stored. Electronic fetal monitoring tracings were all normal and changes in blood pressure and pulse rates were minimal during the blood donation. The decrease in hemoglobin after the removal of 900 ml of blood was only 0.6g/dl on average during the 3 weeks, since the concentration of erythropoietin in serum and the counts of reticlocyte increased in a few days after blood removal. But there were no significant changes in TAT levels in serum. Twelve out of 34 pregnant women received the autologous blood transfusion during or after cesarean delivery and the homologous transfusions were avoided. The results of this study suggested that autologous blood transfusion for pregnant women with a high incidence of blood loss at delivery, such as placenta previa or previous cesarean delivery was safe and advantageous in avoiding homologous blood transfusion.

Published
1994

15. Induction of HMG-CoA reductase and malic enzyme gene expressions by polychlorinated biphenyls in rat hepatocytes cultured on EHS-gel, not on Type I collagen

Author

Y. Hitomi, H. Oda, Akira Yoshida, Y. Suzuki, and T. Shibata

Subjects
Cytochrome, biology, Biochemistry, Chemistry, Gene expression, HMG-CoA reductase, Malic enzyme, biology.protein, Lipid metabolism, Reductase, Drug metabolism, Type I collagen
Abstract

Rat hepatocytes in primary culture have been used for studying growth and differentiation functions such as drug metabolism. In order to develop a culture system keeping high capacity of xenobiotics-responsiveness, effects of extracellular matrix (ECM) on gene expressions for cytochrome P-450 (P-450), 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase) and malic enzyme were investigated. The treatment of xenobiotics to animals induce HMG-CoA reductase and malic enzyme as well as cytochrome P-450s. The inductions of the expression of HMG-CoA reductase gene and malic enzyme gene by polychlorinated biphenyls (PCB) were observed in primary cultured rat hepatocytes. This showed that the effect of PCB on the gene expression relating lipid metabolism was direct to hepatocytes. The induction was observed only in hepatocytes cultured on Engelbreth-Holm-Swarm sarcoma basement membrane gel (EHS-gel), not on type I collagen (TIC), which is usually used for monolayer culture of hepatocytes. The induction of CYP2B1/2 (cytochrome P-450b/e) gene expression was also observed only in the cells cultured on EHS-gel. These results demonstrated that the culture on EHS-gel was better than the usual monolayer culture for investigating the effect of xenobiotics.

Published
1994
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16. Extinction of expression of the PU.1/Sfpi-1 putative oncogene encoding a B-cell- and macrophage-specific transcription factor in somatic cell hybrids

Author

Y, Hitomi, T, Yamada, and T, Oikawa

Subjects
DNA-Binding Proteins, B-Lymphocytes, Mice, Gene Expression Regulation, Macrophages, Retroviridae Proteins, Oncogenic, Animals, Oncogenes, Hybrid Cells, Methylation, Cells, Cultured, Transcription Factors
Abstract

Several examples of extinction of cell type-specific gene expression have been observed following fusion of different cell types. Possible mechanisms of the extinction include loss of transcriptional activators and acquisition of repressor factors responsible for cell type-specific gene expression. In this study, we demonstrated the extinction of expression of the PU.1/Sfpi-1 putative oncogene encoding a B-cell- and macrophage-specific transcription factor when plasmacytoma cells are fused with embryonal carcinoma (EC) cells. The hybrid cells retained most chromosome complements from both parental lines including chromosome 2 on which the PU.1 gene is located. Therefore, extinction of PU.1 gene expression in the hybrids is not likely the result of chromosome segregation but rather due to a transacting negative factor(s) present in EC cells. On the contrary, expression of the PU.1 mRNA in plasmacytoma cells was not extinguished upon cell fusion with T-lymphoma cells, although the parental T-lymphoma cells did not express PU.1 transcripts. Hence, T-lymphoma cells seemed to be permissive to PU.1 gene expression, while EC cells were repressive. These results suggest that PU.1 gene expression which positively regulates some B cell- and macrophage-specific gene expression is a target of negative regulatory mechanisms during cell differentiation, and the regulatory mechanisms repressing PU.1 gene expression is different between EC cells and T-cells.

Published
1993

17. Extinction of T cell receptor alpha-chain gene expression accompanied by loss of the lymphoid enhancer-binding factor 1 (LEF-1) in murine somatic cell hybrids

Author

K Shimizu, Y Hitomi, M Ohki, T Oikawa, and Toshiyuki Yamada

Subjects
Transcription, Genetic, Lymphoid Enhancer-Binding Factor 1, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Molecular Sequence Data, Biology, Hybrid Cells, Regulatory Sequences, Nucleic Acid, Lymphoma, T-Cell, Mice, Gene expression, T-Cell Receptor Alpha Chain, RNA Precursors, Animals, Nuclear protein, Enhancer, Gene, Molecular Biology, Base Sequence, T-cell receptor, Nuclear Proteins, Cell Biology, Fibroblasts, Molecular biology, DNA-Binding Proteins, Cell culture, Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, Lymphoid enhancer-binding factor 1, Transcription Factors, Research Article
Abstract

To investigate the presence of a negative regulatory factor(s) suppressing T-cell receptor alpha-chain (TCR alpha) gene expression in non-T cells, 10 independent cell hybrid clones were generated between mouse T-cell lymphoma EL4 cells (TCR alpha+/beta+) and mouse fibroblast B82 cells. These cell hybrids showed a typical fibroblastic morphology and retained an approximate sum of chromosome numbers derived from both parental cells. No transcripts of the TCR alpha gene were detected in the cell hybrids, although the presence of the rearranged TCR alpha allele from EL4 cells was confirmed. The possibility of involvement of nuclear proteins responsible for the activity of the TCR alpha gene enhancer in the extinction of TCR alpha gene expression in the cell hybrids was examined. Nuclear proteins which bind to the lymphoid enhancer-binding factor 1 (LEF-1) binding motif present in EL4 cells disappeared in the hybrid clones, whereas no significant change was observed in DNA-binding activity of nuclear proteins to a consensus cyclic AMP response element (CRE) and the Ets-1 binding motif between the parental cells and the cell hybrids. No transcripts of the LEF-1 gene were detected in the cell hybrids, despite the retention of the LEF-1 gene and murine chromosomes 3, on which the LEF-1 allele is located, from both parental cells. These results suggest that a trans-acting negative regulatory factor(s) present in fibroblasts suppresses LEF-1 gene expression and that suppression of LEF-1 may lead to the extinction of TCR alpha gene expression in the cell hybrids.

Published
1993

18. The effect of phlebotomy on serum erythropoietin levels in normal healthy subjects

Author

H, Maeda, Y, Hitomi, R, Hirata, H, Tohyama, J, Suwata, S, Kamata, Y, Fujino, and N, Murata

Subjects
Adult, Male, Hemoglobins, Reticulocytes, Reference Values, Iron, Humans, Erythropoiesis, Female, Erythropoietin, Blood Cell Count, Bloodletting, Follow-Up Studies
Abstract

We evaluated endogenous serum erythropoietin (Epo) levels in 14 normal subjects (eight males and six females) after a single 400-ml phlebotomy. The subjects were followed up for 56 days. The hemoglobin (Hb) values of both males and females decreased to a nadir on days 3 to 7 post-phlebotomy. Hb values gradually increased, but did not completely recover to pre-phlebotomy levels by day 56. Serum Epo levels increased after 6 h post-phlebotomy, to 20.1 +/- 5.4 (mU/ml) in males and 20.7 +/- 7.0 in females, from the pre-phlebotomy levels of 14.6 +/- 4.0 in males and 13.4 +/- 4.1 in females, respectively. Epo levels continued to increase to peak levels of 25.5 +/- 6.3 in males and 28.7 +/- 11.5 in females on days 7 to 14 and thereafter decreased until day 56. Thus, the Epo response to a 400-ml phlebotomy was relatively small in magnitude and was not sufficient to initiate a significant increase in erythropoiesis. This finding suggests that the administration of recombinant human erythropoietin (rHu-Epo) may be effective for the prompt correction of anemia induced by autologous blood donation and for increasing the volume of predonated autologous blood.

Published
1992

19. [Strategies for the isolation of tumor suppressor genes]

Author

N, Kuzumaki, H, Fujita, Y, Hitomi, and M, Leonhard

Subjects
Electrophoresis, Animals, Humans, Nucleic Acid Hybridization, Genes, Tumor Suppressor, Chromosome Deletion, Cloning, Molecular, Polymerase Chain Reaction
Published
1990

21. Activation and Apoptosis of Murine Peritoneal Macrophages by Acute Cold Stress

Author

T, Kizaki, K, Suzuki, Y, Hitomi, K, Iwabuchi, K, Onoé, H, Ishida, T, Izawa, L L, Ji, H, Ohno, and T, Kizkai

Subjects
Lipopolysaccharides, Male, Time Factors, Phagocytosis, Cell, Biophysics, Macrophage-1 Antigen, Apoptosis, CD18, In Vitro Techniques, Biology, Biochemistry, Mice, Stress, Physiological, Proto-Oncogene Proteins, medicine, Animals, RNA, Messenger, Molecular Biology, Cold stress, Chemistry, Cell Biology, Macrophage Activation, Protein-Tyrosine Kinases, Molecular biology, Cell biology, Cold Temperature, Mice, Inbred C57BL, src-Family Kinases, medicine.anatomical_structure, Integrin alpha M, CD18 Antigens, Macrophages, Peritoneal, biology.protein, DNA fragmentation, Tyrosine kinase, Homeostasis, Interleukin-1
Abstract

Effects of acute cold stress (5 degrees C for 24 h) on the functions of peritoneal macrophages and the mechanisms for controlling host homeostasis were investigated in mice. Phagocytic activity and expression of the cell surface adhesion molecule CD11b/CD18 were markedly increased in peritoneal exudate cells by acute cold stress. These alterations were attributable to an increased number and phenotypical changes of adherent cells from acute cold-stressed mice. On the other hand, a lipopolysaccharide-induced activity of src-family tyrosine kinase Fgr, an expression of interleukin-1beta (IL-1 beta) mRNA, and a bioactivity of IL-1 in the culture supernatants of adherent cells from acute cold-stressed mice were markedly lower than those from control mice. A time course study revealed that the number of adherent cells in peritoneal exudate cells was markedly increased in mice exposed to cold for 24 h but returned to normal numbers when mice were exposed to cold for 72 h. DNA fragmentation and Annexin-V(+) cells were observed in peritoneal exudate cells from acute-cold stressed mice. Thus, cold stress activated macrophages but these macrophages were destined to be eliminated by apoptosis.

Published
2001
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24. Association of aldehyde dehydrogenase 2 gene polymorphism with multiple oesophageal dysplasia in head and neck cancer patients.

Author

M, Muto, Y, Hitomi, A, Ohtsu, S, Ebihara, S, Yoshida, and H, Esumi

Abstract

BACKGROUND: Multiple occurrences of oesophageal dysplasia are frequently observed in head and neck cancer patients, and closely associated with alcohol consumption. Acetaldehyde, the first metabolite of ethanol, is thought to play an important role in the carcinogenesis of the upper aerodigestive tract. AIM: To investigate if genetic polymorphism in alcohol metabolising enzymes (ADH3, alcohol dehydrogenase 3; ALDH2, aldehyde dehydrogenase 2) is associated with oesophageal multiple dysplasia in head and neck cancer patients. METHODS: Thirty one consecutive patients with head and neck cancer were included in the study. Multiple oesophageal dysplasia was detected endoscopically as multiple Lugol voiding lesions (multiple LVL) using the Lugol dye staining method. The ADH3 and ALDH2 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Among the 31 patients with head and neck cancer, 17 had multiple LVL. Multiple LVL were closely associated with a second primary oesophageal carcinoma in head and neck cancer patients (odds ratio 60.7, 95% CI 5.6-659). Furthermore, the mutant ALDH2 allele was significantly more prevalent in patients with multiple LVL (65% v 29%; p<0.05) whereas no difference was observed in ADH3 polymorphism. CONCLUSIONS: The mutant ALDH2 allele appears to be a risk indicator for multiple LVL in head and neck cancer patients. Accumulation of acetaldehyde due to low ALDH2 activity may play a critical role in cancerous changes throughout the mucosa in the upper aerodigestive tract.

Published
2000

26. Comparison of proteases in normal and metaplastic human stomach mucosa

Author

Y, Hitomi, M, Niinobe, and S, Fujii

Subjects
Metaplasia, Gastric Mucosa, Stomach Neoplasms, Intestine, Small, Humans, Peptide Hydrolases
Abstract

The proteases in normal and metaplastic human stomach mucosa were examined by preparing zymograms of tissue extracts with tosyl-L-lysine-alpha-naphthyl ester and L-prolyl-L-phenylalanyl-L-arginine-alpha-naphthyl ester as substrates. With both substrates, the zymogram of metaplastic mucosa showed an additional band (Rf 0.64) not present with normal mucosa. This band was also observed with extracts of normal small intestine and cancerous stomach tissue. It disappeared on treatment of the preparations with leupeptin, but not with esterastin.

Published
1980

27. [Pseudoaneurysm of the left ventricle serially demonstrated from on-set using two-dimensional echocardiography: a case report]

Author

Y, Hitomi, H, Tsuneyoshi, K, Hara, K, Masuoka, T, Yamaguchi, R, Takanashi, K, Machii, M, Ikemura, K, Ishida, and H, Kawai

Subjects
Male, Echocardiography, Heart Ventricles, Myocardium, Humans, Heart Aneurysm, Aged, Follow-Up Studies
Abstract

A case of so-called pseudoaneurysm of the left ventricle without pericardial adhesion, serially demonstrated by two-dimensional echocardiography, was reported. A 76-year-old man developed congestive heart failure 10 hours after gastrectomy, and was diagnosed as having acute myocardial infarction. Two-dimensional echocardiography on the 21st day after onset revealed moderate pericardial effusion and an echo-free space in the posterolateral myocardium of the left ventricle. The echo-free space gradually expanded exteriorly and formed an aneurysm, which remained unchanged after the resolution of the pericardial effusion. Clinical diagnosis of pseudoaneurysm of the left ventricle was made by left ventriculography and coronary angiography. At autopsy, there was an aneurysm measuring 2.3 X 3.0 X 5.0 cm which communicated with the left ventricle via two small ostia, 5 mm each in diameter. There was a loose fibrous adhesion between the pericardium and the epicardium. The wall of the aneurysm consisted of organized fibrous tissue without any elements of the myocardium. Both myocardium and fibrous tissue were located at the junction of the left ventricular wall and the aneurysm. It is surmised that dissection of the infarcted myocardium expanded so greatly as to form an aneurysmal cavity, resulting in the formation of a so-called pseudoaneurysm of the left ventricle after fibrous changes of the outer wall in the infarcted myocardium. Therefore, this aneurysm might be termed a "dissecting" aneurysm of the left ventricle. The hypothesis that a pseudoaneurysm is derived from a localized hemopericardium should be reconsidered.

Published
1986

28. New synthetic substrate for kallikrein and its application

Author

S, Fujii, Y, Hitomi, K, Kimura, M, Ishii, M, Kurumi, and T, Aoyama

Subjects
Kinetics, Hydrolysis, Factor X, Factor Xa, Thrombin, Animals, Humans, Kallikreins, Fibrinolysin, Kidney, Oligopeptides, Pancreas, Substrate Specificity
Abstract

We developed a new synthetic substrate, Pro-Phe-Arg-alpha-naphthyl ester, for kallikrein. We found that this substrate had higher specificity and sensitivity for kallikrein and was applied for the preparation of zymogram and for the histochemical demonstration. With Pro-Phe-Arg-alpha-NE as substrate, the minimum detectable concentration of human urinary kallikrein was about 0.001 KU and then kallikrein could be determined with 25 microliter of human urine. We also found the possibility that occurring of abnormalities during pregnancy were predicted by the determination of urinary kallikrein of pregnants. Zymograms were prepared for various kinds of kallikrein using this substrate. The localization of kallikrein-like enzyme in rat kidneys was defined by the application this substrate for histochemistry. Moreover, cytochemical demonstrations of leucocytes in human blood were done using Ts-Lys-alpha-NE and Ac-Tyr-alpha-NE.

Published
1986

33. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Author

Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byan, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, MariaConsiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton VJ. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris DJ. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom JW. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch’ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya Mandal, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, Charles Millson, Cordell, H. J., Fryett, J. J., Ueno, K., Darlay, R., Aiba, Y., Hitomi, Y., Kawashima, M., Nishida, N., Khor, S. -S., Gervais, O., Kawai, Y., Nagasaki, M., Tokunaga, K., Tang, R., Shi, Y., Li, Z., Juran, B. D., Atkinson, E. J., Gerussi, A., Carbone, M., Asselta, R., Cheung, A., de Andrade, M., Baras, A., Horowitz, J., Ferreira, M. A. R., Sun, D., Jones, D. E., Flack, S., Spicer, A., Mulcahy, V. L., Byan, J., Han, Y., Sandford, R. N., Lazaridis, K. N., Amos, C. I., Hirschfield, G. M., Seldin, M. F., Invernizzi, P., Siminovitch, K. A., Ma, X., Nakamura, M., Mells, G. F., Mason, A., Vincent, C., Xie, G., Zhang, J., Affronti, A., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Azzaroli, F., Battezzati, P. M., Benedetti, A., Bragazzi, M., Brunetto, M., Bruno, S., Calvaruso, V., Cardinale, V., Casella, G., Cazzagon, N., Ciaccio, A., Coco, B., Colli, A., Colloredo, G., Colombo, M., Colombo, S., Cristoferi, L., Cursaro, C., Croce, L. S., Crosignani, A., D'Amato, D., Donato, F., Elia, G., Fabris, L., Fagiuoli, S., Ferrari, C., Floreani, A., Galli, A., Giannini, E., Grattagliano, I., Lampertico, P., Lleo, A., Malinverno, F., Mancuso, C., Marra, F., Marzioni, M., Massironi, S., Mattalia, A., Miele, L., Milani, C., Morini, L., Morisco, F., Muratori, L., Muratori, P., Niro, G. A., O'Donnell, S., Picciotto, A., Portincasa, P., Rigamonti, C., Ronca, V., Rosina, F., Spinzi, G., Strazzabosco, M., Tarocchi, M., Tiribelli, C., Toniutto, P., Valenti, L., Vinci, M., Zuin, M., Nakamura, H., Abiru, S., Nagaoka, S., Komori, A., Yatsuhashi, H., Ishibashi, H., Ito, M., Migita, K., Ohira, H., Katsushima, S., Naganuma, A., Sugi, K., Komatsu, T., Mannami, T., Matsushita, K., Yoshizawa, K., Makita, F., Nikami, T., Nishimura, H., Kouno, H., Ota, H., Komura, T., Nakamura, Y., Shimada, M., Hirashima, N., Komeda, T., Ario, K., Nakamuta, M., Yamashita, T., Furuta, K., Kikuchi, M., Naeshiro, N., Takahashi, H., Mano, Y., Tsunematsu, S., Yabuuchi, I., Shimada, Y., Yamauchi, K., Sugimoto, R., Sakai, H., Mita, E., Koda, M., Tsuruta, S., Kamitsukasa, H., Sato, T., Masaki, N., Kobata, T., Fukushima, N., Ohara, Y., Muro, T., Takesaki, E., Takaki, H., Yamamoto, T., Kato, M., Nagaoki, Y., Hayashi, S., Ishida, J., Watanabe, Y., Kobayashi, M., Koga, M., Saoshiro, T., Yagura, M., Hirata, K., Tanaka, A., Takikawa, H., Zeniya, M., Abe, M., Onji, M., Kaneko, S., Honda, M., Arai, K., Arinaga-Hino, T., Hashimoto, E., Taniai, M., Umemura, T., Joshita, S., Nakao, K., Ichikawa, T., Shibata, H., Yamagiwa, S., Seike, M., Honda, K., Sakisaka, S., Takeyama, Y., Harada, M., Senju, M., Yokosuka, O., Kanda, T., Ueno, Y., Kikuchi, K., Ebinuma, H., Himoto, T., Yasunami, M., Murata, K., Mizokami, M., Kawata, K., Shimoda, S., Miyake, Y., Takaki, A., Yamamoto, K., Hirano, K., Ichida, T., Ido, A., Tsubouchi, H., Chayama, K., Harada, K., Nakanuma, Y., Maehara, Y., Taketomi, A., Shirabe, K., Soejima, Y., Mori, A., Yagi, S., Uemoto, S., H, E., Tanaka, T., Yamashiki, N., Tamura, S., Sugawara, Y., Kokudo, N., Chalasani, N., Luketic, V., Odin, J., Chopra, K., Abecasis, G., Cantor, M., Coppola, G., Economides, A., Lotta, L. A., Overton, J. D., Reid, J. G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E. D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T. D., Padilla, M. S., Toledo, K., Widom, L., Wolf, S. E., Pradhan, M., Manoochehri, K., Ulloa, R. H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E. K., Salerno, W., Staples, J. C., Jones, M. B., Mitnaul, L. J., Sturgess, R., Healey, C., Yeoman, A., Gunasekera, A. V., Kooner, P., Kapur, K., Sathyanarayana, V., Kallis, Y., Subhani, J., Harvey, R., Mccorry, R., Rooney, P., Ramanaden, D., Evans, R., Mathialahan, T., Gasem, J., Shorrock, C., Bhalme, M., Southern, P., Tibble, J. A., Gorard, D. A., Jones, S., Mells, G., Mulcahy, V., Srivastava, B., Foxton, M. R., Collins, C. E., Elphick, D., Karmo, M., Porras-Perez, F., Mendall, M., Yapp, T., Patel, M., Ede, R., Sayer, J., Jupp, J., Fisher, N., Carter, M. J., Koss, K., Shah, J., Piotrowicz, A., Scott, G., Grimley, C., Gooding, I. R., Williams, S., Tidbury, J., Lim, G., Cheent, K., Levi, S., Mansour, D., Beckley, M., Hollywood, C., Wong, T., Marley, R., Ramage, J., Gordon, H. M., Ridpath, J., Ngatchu, T., Bob Grover, V. P., Shidrawi, R. G., Abouda, G., Corless, L., Narain, M., Rees, I., Brown, A., Taylor-Robinson, S., Wilkins, J., Grellier, L., Banim, P., Das, D., Heneghan, M. A., Curtis, H., Matthews, H. C., Mohammed, F., Aldersley, M., Srirajaskanthan, R., Walker, G., Mcnair, A., Sharif, A., Sen, S., Bird, G., Prince, M. I., Prasad, G., Kitchen, P., Barnardo, A., Oza, C., Sivaramakrishnan, N. N., Gupta, P., Shah, A., Evans, C. D., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Barclay, S. T., Mcdonald, N., Bathgate, A. J., Palmer, K., Dillon, J. F., Rushbrook, S. M., Przemioslo, R., Mcdonald, C., Millar, A., Tai, C., Mitchell, S., Metcalf, J., Shaukat, S., Ninkovic, M., Shmueli, U., Davis, A., Naqvi, A., Lee, T. J., Ryder, S., Collier, J., Klass, H., Cramp, M. E., Sharer, N., Aspinall, R., Ghosh, D., Douds, A. C., Booth, J., Williams, E., Hussaini, H., Christie, J., Mann, S., Thorburn, D., Marshall, A., Patanwala, I., Ala, A., Maltby, J., Matthew, R., Corbett, C., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Mitchison, H., Panter, S., Shearman, J., Bray, G., Roberts, M., Butcher, G., Forton, D., Mahmood, Z., Cowan, M., Ch'Ng, C. L., Rahman, M., Whatley, G. C. A., Wesley, E., Mandal, A., Jain, S., Pereira, S. P., Wright, M., Trivedi, P., Gordon, F. H., Unitt, E., Palejwala, A., Austin, A., Vemala, V., Grant, A., Higham, A. D., Brind, A., Mathew, R., Cox, M., Ramakrishnan, S., King, A., Whalley, S., Fraser, J., Thomson, S. J., Bell, A., Wong, V. S., Kia, R., Gee, I., Keld, R., Ransford, R., Gotto, J., Millson, C., Cordell H.J., Fryett J.J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S.-S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B.D., Atkinson E.J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M.A.R., Sun D., Jones D.E., Flack S., Spicer A., Mulcahy V.L., Byan J., Han Y., Sandford R.N., Lazaridis K.N., Amos C.I., Hirschfield G.M., Seldin M.F., Invernizzi P., Siminovitch K.A., Ma X., Nakamura M., Mells G.F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P.M., Benedetti A., Bragazzi M., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L.S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G.A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L.A., Overton J.D., Reid J.G., Shuldiner A., Beechert C., Forsythe C., Fuller E.D., Gu Z., Lattari M., Lopez A., Schleicher T.D., Padilla M.S., Toledo K., Widom L., Wolf S.E., Pradhan M., Manoochehri K., Ulloa R.H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E.K., Salerno W., Staples J.C., Jones M.B., Mitnaul L.J., Sturgess R., Healey C., Yeoman A., Gunasekera A.V., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J.A., Gorard D.A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M.R., Collins C.E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M.J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I.R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H.M., Ridpath J., Ngatchu T., Bob Grover V.P., Shidrawi R.G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M.A., Curtis H., Matthews H.C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M.I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N.N., Gupta P., Shah A., Evans C.D., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S.T., McDonald N., Bathgate A.J., Palmer K., Dillon J.F., Rushbrook S.M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T.J., Ryder S., Collier J., Klass H., Cramp M.E., Sharer N., Aspinall R., Ghosh D., Douds A.C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., Medical Research Council (MRC), LiveR North, Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tarocchi, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, Mells GF, PBC Consortia, Canadian PBC Consortium, Chinese PBC Consortium, Italian PBC Study Group, Japan-PBC-GWAS Consortium, US PBC Consortium, UK-PBC Consortium, and Calvaruso V. .

Subjects
Liver Cirrhosis, ALSPAC, ERN RARE-LIVER, Genomic co-localization, Network-based in silico drug efficacy screening, UK-PBC, 0301 basic medicine, Candidate gene, Genome-Wide Association Study, Humans, Liver Cirrhosis, Biliary, Italian PBC Study Group, LD SCORE REGRESSION, Japan-PBC-GWAS Consortium, Genome-wide association study, Locus (genetics), Disease, SUSCEPTIBILITY, PBC, Chronic liver disease, Bioinformatics, GENETIC ASSOCIATION, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, UK-PBC Consortium, Genotype, Medicine, Genetic association, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Biliary, Chinese PBC Consortium, 1103 Clinical Sciences, medicine.disease, PBC Consortia, 030104 developmental biology, Meta-analysis, ERN RARE LIVER, 030211 gastroenterology & hepatology, US PBC Consortium, Canadian PBC Consortium, business, Life Sciences & Biomedicine, Human
Abstract

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.

Published
2021

34. Designing Artificial Laccase Catalysts by Introducing Substrate Oxidation Metals into Oxygen-Reducing Metal-Organic Frameworks: Cu-Doped ZIF-67.

Author

Nakahara H and Hitomi Y

Abstract

Laccase, a multi-copper oxidase, is limited by its optimal temperature range and isolation costs. To overcome these challenges, we synthesized copper-doped zeolitic imidazolate framework-67 (Cu-doped ZIF-67) with 16 mol % Cu as an artificial laccase catalyst. The introduced Cu site acts as the phenol oxidation site, and Co-based ZIF-67 is the four-electron oxygen reduction site. Laccase also employs this division of oxidation and reduction sites. Cu-doped ZIF-67 demonstrated significant catalytic activity, superior to natural laccase, especially at elevated temperatures, and maintained stability across multiple reaction cycles. These findings suggest that Cu-doped ZIF-67 is a robust, reusable alternative for industrial applications requiring high thermal stability and efficient catalysis., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Published
2024
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35. A genome-wide association study identified PTPN2 as a population-specific susceptibility gene locus for primary biliary cholangitis.

Author

Hitomi Y, Ueno K, Aiba Y, Nishida N, Kono M, Sugihara M, Kawai Y, Kawashima M, Khor SS, Sugi K, Kouno H, Kohno H, Naganuma A, Iwamoto S, Katsushima S, Furuta K, Nikami T, Mannami T, Yamashita T, Ario K, Komatsu T, Makita F, Shimada M, Hirashima N, Yokohama S, Nishimura H, Sugimoto R, Komura T, Ota H, Kojima M, Nakamuta M, Fujimori N, Yoshizawa K, Mano Y, Takahashi H, Hirooka K, Tsuruta S, Sato T, Yamasaki K, Kugiyama Y, Motoyoshi Y, Suehiro T, Saeki A, Matsumoto K, Nagaoka S, Abiru S, Yatsuhashi H, Ito M, Kawata K, Takaki A, Arai K, Arinaga-Hino T, Abe M, Harada M, Taniai M, Zeniya M, Ohira H, Shimoda S, Komori A, Tanaka A, Ishigaki K, Nagasaki M, Tokunaga K, and Nakamura M

Subjects
Female, Humans, Male, Case-Control Studies, Japan, Polymorphism, Single Nucleotide, East Asian People genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Liver Cirrhosis, Biliary genetics, Protein Tyrosine Phosphatase, Non-Receptor Type 2 genetics
Abstract

Background and Aims: Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-nonspecific) and nonshared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC., Approach and Results: Protein tyrosine phosphatase nonreceptor type 2 ( PTPN2) was identified as a novel PBC susceptibility gene locus through GWAS and subsequent genome-wide meta-analysis involving 2181 cases and 2699 controls from the Japanese population (GWAS-lead variant: rs8098858, p = 2.6 × 10 -8 ). In silico and in vitro functional analyses indicated that the risk allele of rs2292758, which is a primary functional variant, decreases PTPN2 expression by disrupting Sp1 binding to the PTPN2 promoter in T follicular helper cells and plasmacytoid dendritic cells. Infiltration of PTPN2-positive T-cells and plasmacytoid dendritic cells was confirmed in the portal area of the PBC liver by immunohistochemistry. Furthermore, transcriptomic analysis of PBC-liver samples indicated the presence of a compromised negative feedback loop in vivo between PTPN2 and IFNG in patients carrying the risk allele of rs2292758., Conclusions: PTPN2 , a novel susceptibility gene for PBC in the Japanese population, may be involved in the pathogenesis of PBC through an insufficient negative feedback loop caused by the risk allele of rs2292758 in IFN-γ signaling. This suggests that PTPN2 could be a potential molecular target for PBC treatment., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Published
2024
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36. Relationship between the number of drugs used during percutaneous coronary intervention and adverse events in patients with chronic coronary syndrome: Analysis of CLIDAS database.

Author

Hitomi Y, Imai Y, Kuwabara M, Oba Y, Kabutoya T, Kario K, Makimoto H, Kohro T, Shiraki E, Akashi N, Fujita H, Matoba T, Miyamoto Y, Kiyosue A, Tsujita K, Nakayama M, and Nagai R

Abstract

Background: Polypharmacy is associated with an increased risk of adverse events due to the higher number of drugs used. This is particularly notable in patients with chronic coronary syndrome (CCS), who are known to use a large number of drugs. Therefore, we investigated polypharmacy in patients with CCS, using CLIDAS, a multicenter database of patients who underwent percutaneous coronary intervention., Method and Results: Between 2017 and 2020, 1411 CCS patients (71.5 ± 10.5 years old; 77.3 % male) were enrolled. The relationship between cardiovascular events occurring during the median follow-up of 514 days and the number of drugs at the time of PCI was investigated. The median number of drugs prescribed was nine. Major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke, heart failure, transient ischemic attack, or unstable angina, occurred in 123 patients, and all-cause mortality occurred in 68 patients. For each additional drug, the adjusted hazard ratios for MACE and all-cause mortality increased by 2.069 (p = 0.003) and 1.102 (p = 0.010). The adjusted hazard ratios for MACE and all-cause mortality were significantly higher in the group using nine or more drugs compared to the group using eight or fewer drugs (1.646 and 2.253, both p < 0.001)., Conclusion: This study showed that an increase in the number of drugs used for CCS may be associated with MACE and all-cause mortality. In patients with CCS, it might be beneficial to minimize the number of medications as much as possible, while managing comorbidities and using guideline-recommended drugs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Published
2024
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37. Identification of region-specific gene isoforms in the human brain using long-read transcriptome sequencing.

Author

Shimada M, Omae Y, Kakita A, Gabdulkhaev R, Hitomi Y, Miyagawa T, Honda M, Fujimoto A, and Tokunaga K

Subjects
Humans, Cerebellum, Sequence Analysis, RNA, Protein Isoforms genetics, Transcriptome, Brain
Abstract

In neurological and neuropsychiatric diseases, different brain regions are affected, and differences in gene expression patterns could potentially explain this mechanism. However, limited studies have precisely explored gene expression in different regions of the human brain. In this study, we performed long-read RNA sequencing on three different brain regions of the same individuals: the cerebellum, hypothalamus, and temporal cortex. Despite stringent filtering criteria excluding isoforms predicted to be artifacts, over half of the isoforms expressed in multiple samples across multiple regions were found to be unregistered in the GENCODE reference. We then especially focused on genes with different major isoforms in each brain region, even with similar overall expression levels, and identified that many of such genes including GAS7 might have distinct roles in dendritic spine and neuronal formation in each region. We also found that DNA methylation might, in part, drive different isoform expressions in different regions. These findings highlight the significance of analyzing isoforms expressed in disease-relevant sites.

Published
2024
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38. rs10924104 in the expression enhancer motif of CD58 confers susceptibility to human autoimmune diseases.

Author

Hitomi Y, Ueno K, Aiba Y, Nishida N, Kawai Y, Kawashima M, Khor SS, Takada S, Iwabuchi C, Nagasaki M, Tokunaga K, and Nakamura M

Subjects
Humans, Genetic Predisposition to Disease, Genome-Wide Association Study, Polymorphism, Single Nucleotide, CD58 Antigens metabolism, Autoimmune Diseases genetics, Lupus Erythematosus, Systemic genetics, Multiple Sclerosis genetics, Multiple Sclerosis metabolism
Abstract

CD58 plays roles in cell adhesion and co-stimulation with antigen presentation from major histocompatibility complex class II on antigen-presenting cells to T-cell antigen receptors on naïve T cells. CD58 reportedly contributes to the development of various human autoimmune diseases. Recently, genome-wide association studies (GWASs) identified CD58 as a susceptibility locus for autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), and primary biliary cholangitis (PBC). However, the primary functional variant and molecular mechanisms of susceptibility to autoimmune diseases in the CD58 locus were not clarified. Here, rs10924104, located in the ZNF35-binding motif within the gene expression regulatory motif, was identified as the primary functional variant for SLE, MS, and PBC among genetic variants showing stronger linkage disequilibrium (LD) with GWAS-lead variants in the CD58 locus. Expression-quantitative trait locus (e-QTL) data for each distinct blood cell type and in vitro functional analysis using the CRISPR/Cas9 system corroborated the functional role of rs10924104 in the upregulation of CD58 transcription by the disease-risk allele. Additionally, the strength of disease susceptibility observed in the CD58 locus could be accounted for by the strength of LD between rs10924104 and each GWAS-lead variant. In conclusion, the present study demonstrated for the first time the existence of a shared autoimmune disease-related primary functional variant (i.e., rs10924104) that regulates the expression of CD58. Clarifying the molecular mechanism of disease susceptibility derived from such a shared genetic background is important for understanding human autoimmune diseases and human immunology., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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39. Demographic history of Ryukyu islanders at the southern part of the Japanese Archipelago inferred from whole-genome resequencing data.

Author

Koganebuchi K, Matsunami M, Imamura M, Kawai Y, Hitomi Y, Tokunaga K, Maeda S, Ishida H, and Kimura R

Subjects
Humans, Japan epidemiology, Genome, Demography, East Asian People, Genetic Drift
Abstract

The Ryukyu Islands are located in the southernmost part of the Japanese Archipelago and consist of several island groups. Each island group has its own history and culture, which differ from those of mainland Japan. People of the Ryukyu Islands are genetically subdivided; however, their detailed demographic history remains unclear. We report the results of a whole-genome sequencing analysis of a total of 50 Ryukyu islanders, focusing on genetic differentiation between Miyako and Okinawa islanders. We confirmed that Miyako and Okinawa islanders cluster differently in principal component analysis and ADMIXTURE analysis and that there is a population structure among Miyako islanders. The present study supports the hypothesis that population differentiation is primarily caused by genetic drift rather than by differences in the rate of migration from surrounding regions, such as the Japanese main islands or Taiwan. In addition, the genetic cline observed among Miyako and Okinawa islanders can be explained by recurrent migration beyond the bounds of these islands. Our analysis also suggested that the presence of multiple subpopulations during the Neolithic Ryukyu Jomon period is not crucial to explain the modern Ryukyu populations. However, the assumption of multiple subpopulations during the time of admixture with mainland Japanese is necessary to explain the modern Ryukyu populations. Our findings add insights that could help clarify the complex history of populations in the Ryukyu Islands., (© 2023. The Author(s).)

Published
2023
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40. A Low Arginine/Ornithine Ratio is Associated with Long-Term Cardiovascular Mortality.

Author

Ishinoda Y, Masaki N, Hitomi Y, Taruoka A, Kawai A, Iwashita M, Yumita Y, Kagami K, Yasuda R, Ido Y, Toya T, Ikegami Y, Namba T, Nagatomo Y, Miyazaki K, Takase B, and Adachi T

Subjects
Male, Humans, Female, Middle Aged, Aged, Citrulline, Prognosis, Ornithine metabolism, Arginine, Hypertension
Abstract

Aims: The long-term prognostic value of the bioavailability of L-arginine, an important source of nitric oxide for the maintenance of vascular endothelial function, has not been investigated fully. We therefore investigated the relationship between amino acid profile and long-term prognosis in patients with a history of standby coronary angiography., Methods: We measured the serum concentrations of L-arginine, L-citrulline, and L-ornithine by high-speed liquid chromatography. We examined the relationship between the L-arginine/L-ornithine ratio and the incidence of all-cause death, cardiovascular death, and major adverse cardiovascular events (MACEs) in 262 patients (202 men and 60 women, age 65±13 years) who underwent coronary angiography over a period of ≤ 10 years., Results: During the observation period of 5.5±3.2 years, 31 (12%) patients died, including 20 (8%) of cardiovascular death, while 32 (12%) had MACEs. Cox regression analysis revealed that L-arginine/L-ornithine ratio was associated with an increased risk for all-cause death (unadjusted hazard ratio, 95% confidence interval) (0.940, 0.888-0.995) and cardiovascular death (0.895, 0.821-0.965) (p＜0.05 for all). In a model adjusted for age, sex, hypertension, hyperlipidemia, diabetes, current smoking, renal function, and log 10 -transformed brain natriuretic peptide level, cardiovascular death (0.911, 0.839-0.990, p=0.028) retained an association with a low L-arginine/ L-ornithine ratio. When the patients were grouped according to an L-arginine/L-ornithine ratio of 1.16, the lower L-arginine/L-ornithine ratio group had significantly higher incidence of all-cause death, cardiovascular death, and MACEs., Conclusion: A low L-arginine/L-ornithine ratio may be associated with increased 10-year cardiac mortality.

Published
2023
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41. Roles of DNA Target in Cancer Cell-Selective Cytotoxicity by Dicopper Complexes with DNA Target/Ligand Conjugates.

Author

Hata M, Ueno J, Hitomi Y, and Kodera M

Abstract

The DNA target/ligand conjugates (HL X , X = P n and M n , n = 1-3) were synthesized where various lengths of -CONH(CH 2 CH 2 O) n CH 2 CH 2 NHCO- linkers with a 9-phenanthrenyl (P) or methyl (M) terminal as DNA targets replace the methyl group of 2,6-di(amide-tether cyclen) -p -cresol ligand (HL). DNA binding, DNA cleavage, cellular uptake, and cytotoxicity of [Cu 2 (μ-OH)(L X )](ClO 4 ) 2 ( 1 X ) are examined and compared with those of [Cu 2 (μ-OH)(L)](ClO 4 ) 2 ( 1 ) to clarify roles of DNA targets. Upon reaction of 1 X with H 2 O 2 , μ-1,1-O 2 H complexes are formed for DNA cleavage. 1 P1 , 1 P2 , and 1 P3 are 22-, 11-, 3-fold more active for conversion of Form II to III in the cleavage of supercoiled plasmid DNA with H 2 O 2 than 1 , where the short P-linker may fix a dicopper moiety within a small number of base pairs to facilitate DNA double-strand breaks (dsb). This enhances the proapoptotic activity of 1 P1 , 1 P2 , and 1 P3 , which are 30-, 12-, and 9.9-fold cytotoxic against HeLa cells than 1 . DNA dsb and cytotoxicity are 44% correlated in 1 P1-3 but 5% in 1 M1-3 , suggesting specific DNA binding of P-linkers and nonspecific binding of M-linkers in biological cells. 1 P1-3 exert cancer cell-selective cytotoxicity against lung and pancreas cancer and normal cells where the short P-linker enhances the selectivity, but 1 M1-3 do not. Intracellular visualization, apoptosis assay, and caspase activity assay clarify mitochondrial apoptosis caused by 1 P1-3 . The highest cancer cell selectivity of 1 P1 may be enabled by the short P-linker promoting dsb of mitochondrial DNA with H 2 O 2 increased by mitochondrial dysfunction in cancer cells., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Published
2023
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42. A Single Intradermal Injection of Autologous Adipose-Tissue-Derived Stem Cells Rejuvenates Aged Skin and Sharpens Double Eyelids.

Author

Ichihashi M, Tanaka M, Iizuka T, Totsuka H, Tominaga E, Hitomi Y, Ando H, Nishikata T, and Mizutani KI

Abstract

Facial skin aging is the most visible manifestation of aging in the body. In this study, we aimed to rejuvenate aging skin via a one-time intradermal injection of autologous adipose-derived stem cells (ADSCs). Eight patients were enrolled for study. Photographs of patients taken immediately before and 1, 3, 6, and 12 months after ADSC injections were comparatively evaluated for visible skin manifestations. ADSCs were cultured from the abdominal-skin-derived subcutaneous fat tissue, and 1 × 108 cultured ADSCs were injected intradermally into the facial skin. Cultured myoblasts were incubated with the supernatant derived from ADSCs, and the effect was evaluated via glucose consumption and lactic acid production in the medium. Eight cases showed the shallowing and disappearance of wrinkles, including those of the glabella, lower eyelids, crow`s feet, and forehead and nasolabial grooves, a month to several months after treatment. Double eyelids became prominent, and facial pores significantly reduced in size. These effects lasted for over one year. Myoblasts cultured in the presence of an ADSC-derived exosome were activated compared to that of ADSCs cultured without supernatant. The result supports the role of muscle in ADSC skin rejuvenation. The present study first reports that a single intradermal administration of cultured ADSCs rejuvenates aged facial skin over the course of one year. Further, patients exhibited definite double eyelids and pore shrinkage, strongly indicating the active involvement of muscle, which was supported by an in vitro study. Our study also suggested the important role of biological factors delivered from injected stem cells, although the detailed mechanism of rejuvenation effects of ADSC skin injection remains to be clarified.

Published
2023
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43. Superoxide Dismutase-like Activity of Zeolitic Imidazolate Framework Nanoparticles Comprising Biomimetic Imidazolato-bridged CuZn Units.

Author

Nakahara H, Nomura A, Tokuda S, Okamura M, Fujisawa K, Koitaya T, Yoshida Y, Furukawa S, and Hitomi Y

Subjects
Copper chemistry, Biomimetics, Superoxide Dismutase chemistry, Zeolites chemistry, Nanoparticles
Abstract

Nanoparticles exhibiting enzymatic functions have garnered considerable attention due to their structural robustness and the profusion of active sites that can be introduced to a single nanosized particle. Here we report that nanosized mixed-metal zeolitic imidazolate frameworks (ZIFs) show a superoxide dismutase (SOD)-like catalytic activity. We chose a ZIF composed of copper and zinc ions and 2-methylimidazole, CuZn-ZIF-8, in which the Cu and Zn ions are bridged by an imidazolato ligand. This coordination geometry closely mimics the active site of CuZn superoxide dismutase (CuZnSOD). The CuZn-ZIF-8 nanoparticles exhibit potent SOD-like activity, attributed to their porous nature and numerous copper active sites, and also possess exceptional recyclability., (© 2023 Wiley-VCH GmbH.)

Published
2023
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44. Emergency Medical Team Response during the Hokkaido Eastern Iburi Earthquake 2018: J-SPEED Data Analysis.

Author

Yumiya Y, Chimed-Ochir O, Kayano R, Hitomi Y, Akahoshi K, Kondo H, Wakai A, Mimura S, Chishima K, Toyokuni Y, Koido Y, and Kubo T

Subjects
Humans, Japan epidemiology, Referral and Consultation, Earthquakes, Disasters, Natural Disasters
Abstract

Introduction: In the last ten years, Japan has experienced several large-scale earthquakes with devastating social and health impacts. Earthquakes directly and indirectly cause a variety of health problems. Further investigation is required to increase preparedness and preventive efforts. In response to the Hokkaido Eastern Iburi Earthquake on September 6, 2018, 32 Emergency Medical Teams (EMTs) employed the Japanese version of Surveillance in Post-Extreme Emergencies and Disasters (J-SPEED) as a national standard daily reporting template, gathering data on the number and type of health problems treated., Study Objective: The purpose of the study is to conduct a descriptive epidemiology study using the J-SPEED data to better understand the health problems during the earthquake disaster., Methods: Reported items in J-SPEED (Ver 1.0) form were analyzed by age, gender, and time to better understand the health issues that have arisen from the earthquake., Results: Most consultations (721; 97.6%) occurred between Day 1 and Day 13 of the 32-day EMT response. During the response period, disaster stress-related symptoms were the most common health event (15.2%), followed by wounds (14.5%) and skin diseases (7.0%)., Conclusion: The most often reported health event during the response period was stress-associated illnesses related to disasters, followed by wounds and skin conditions. The health consequences of natural disasters depend on diverse local environment and population. As a result, this initial study was hard to generalize; however, it is expected that data accumulated using the J-SPEED system in the future will strengthen and extend the conclusions.

Published
2023
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45. Novel HLA allele associations with susceptibility, staging, symptomatic state, autoimmune hepatitis and hepatocellular carcinoma events for primary biliary cholangitis in the Japanese population.

Author

Khor SS, Ueno K, Nishida N, Kawashima M, Kawai Y, Aiba Y, Hitomi Y, Nagasaki M, Nakamura M, and Tokunaga K

Subjects
Humans, HLA-DRB1 Chains genetics, Alleles, Genetic Predisposition to Disease, East Asian People, Haplotypes, Gene Frequency, Carcinoma, Hepatocellular genetics, Hepatitis, Autoimmune genetics, Liver Cirrhosis, Biliary genetics, Liver Neoplasms genetics
Abstract

Primary biliary cholangitis (PBC) is a rare autoimmune disease with a clear predisposition for human leukocyte antigen (HLA)-DR/DQ -associated loss of immune tolerance for the E2 component of the pyruvate dehydrogenase complex. Three-field-resolution HLA imputation of 1,670 Japanese PBC patients and 2,328 healthy controls was conducted using Japanese population-specific HLA reference panels. Eighteen previously reported Japanese PBC-associated HLA alleles were confirmed and extended to 3-field-resolution, including HLA-DRB1*08:03 to HLA-DRB1*08:03:02 , HLA-DQB1*03:01 to HLA-DQB1*03:01:01 , HLA-DQB1*04:01 to HLA-DQB1*04:01:01 and HLA-DQB1*06:04 to HLA-DQB1*06:04:01 . In addition, additional significant novel HLA alleles were identified, including 3 novel susceptible HLA-DQA1 alleles: HLA-DQA1*03:03:01 , HLA-DQA1*04:01:01 , HLA-DQA1*01:04:01 and 1 novel protective HLA-DQA1 allele, HLA-DQA1*05:05:01 . In addition, PBC patients carrying HLA-DRB1*15:01:01 and HLA-DQA1*03:03:01 would have a higher predisposition toward developing concomitant autoimmune hepatitis (AIH). Further, late-stage and symptomatic PBC shared the same susceptible HLA alleles of HLA-A*26:01:01 , HLA-DRB1*09:01:02 and HLA-DQB1*03:03:02 . Lastly, HLA-DPB1*05:01:01 was identified as a potential risk HLA allele for development of hepatocellular carcinoma (HCC) in PBC patients. In conclusion, we have extended the current knowledge of HLA allele associations to 3-field resolution and identified novel HLA allele associations with predisposition risk, staging, symptomatic state, and AIH and HCC events for Japanese PBC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khor, Ueno, Nishida, Kawashima, Kawai, Aiba, Hitomi, Nagasaki, Nakamura and Tokunaga.)

Published
2023
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46. Corrigendum to: "An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs" [J Hepatol 75 (2021) 572-581].

Author

Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, and Mells GF

Published
2023
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47. Macromolecular organic matter in samples of the asteroid (162173) Ryugu.

Author

Yabuta H, Cody GD, Engrand C, Kebukawa Y, De Gregorio B, Bonal L, Remusat L, Stroud R, Quirico E, Nittler L, Hashiguchi M, Komatsu M, Okumura T, Mathurin J, Dartois E, Duprat J, Takahashi Y, Takeichi Y, Kilcoyne D, Yamashita S, Dazzi A, Deniset-Besseau A, Sandford S, Martins Z, Tamenori Y, Ohigashi T, Suga H, Wakabayashi D, Verdier-Paoletti M, Mostefaoui S, Montagnac G, Barosch J, Kamide K, Shigenaka M, Bejach L, Matsumoto M, Enokido Y, Noguchi T, Yurimoto H, Nakamura T, Okazaki R, Naraoka H, Sakamoto K, Connolly HC Jr, Lauretta DS, Abe M, Okada T, Yada T, Nishimura M, Yogata K, Nakato A, Yoshitake M, Iwamae A, Furuya S, Hatakeda K, Miyazaki A, Soejima H, Hitomi Y, Kumagai K, Usui T, Hayashi T, Yamamoto D, Fukai R, Sugita S, Kitazato K, Hirata N, Honda R, Morota T, Tatsumi E, Sakatani N, Namiki N, Matsumoto K, Noguchi R, Wada K, Senshu H, Ogawa K, Yokota Y, Ishihara Y, Shimaki Y, Yamada M, Honda C, Michikami T, Matsuoka M, Hirata N, Arakawa M, Okamoto C, Ishiguro M, Jaumann R, Bibring JP, Grott M, Schröder S, Otto K, Pilorget C, Schmitz N, Biele J, Ho TM, Moussi-Soffys A, Miura A, Noda H, Yamada T, Yoshihara K, Kawahara K, Ikeda H, Yamamoto Y, Shirai K, Kikuchi S, Ogawa N, Takeuchi H, Ono G, Mimasu Y, Yoshikawa K, Takei Y, Fujii A, Iijima YI, Nakazawa S, Hosoda S, Iwata T, Hayakawa M, Sawada H, Yano H, Tsukizaki R, Ozaki M, Terui F, Tanaka S, Fujimoto M, Yoshikawa M, Saiki T, Tachibana S, Watanabe SI, and Tsuda Y

Abstract

Samples of the carbonaceous asteroid (162173) Ryugu were collected and brought to Earth by the Hayabusa2 spacecraft. We investigated the macromolecular organic matter in Ryugu samples and found that it contains aromatic and aliphatic carbon, ketone, and carboxyl functional groups. The spectroscopic features of the organic matter are consistent with those in chemically primitive carbonaceous chondrite meteorites that experienced parent-body aqueous alteration (reactions with liquid water). The morphology of the organic carbon includes nanoglobules and diffuse carbon associated with phyllosilicate and carbonate minerals. Deuterium and/or nitrogen-15 enrichments indicate that the organic matter formed in a cold molecular cloud or the presolar nebula. The diversity of the organic matter indicates variable levels of aqueous alteration on Ryugu's parent body.

Published
2023
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48. Samples returned from the asteroid Ryugu are similar to Ivuna-type carbonaceous meteorites.

Author

Yokoyama T, Nagashima K, Nakai I, Young ED, Abe Y, Aléon J, Alexander CMO, Amari S, Amelin Y, Bajo KI, Bizzarro M, Bouvier A, Carlson RW, Chaussidon M, Choi BG, Dauphas N, Davis AM, Di Rocco T, Fujiya W, Fukai R, Gautam I, Haba MK, Hibiya Y, Hidaka H, Homma H, Hoppe P, Huss GR, Ichida K, Iizuka T, Ireland TR, Ishikawa A, Ito M, Itoh S, Kawasaki N, Kita NT, Kitajima K, Kleine T, Komatani S, Krot AN, Liu MC, Masuda Y, McKeegan KD, Morita M, Motomura K, Moynier F, Nguyen A, Nittler L, Onose M, Pack A, Park C, Piani L, Qin L, Russell SS, Sakamoto N, Schönbächler M, Tafla L, Tang H, Terada K, Terada Y, Usui T, Wada S, Wadhwa M, Walker RJ, Yamashita K, Yin QZ, Yoneda S, Yui H, Zhang AC, Connolly HC Jr, Lauretta DS, Nakamura T, Naraoka H, Noguchi T, Okazaki R, Sakamoto K, Yabuta H, Abe M, Arakawa M, Fujii A, Hayakawa M, Hirata N, Hirata N, Honda R, Honda C, Hosoda S, Iijima YI, Ikeda H, Ishiguro M, Ishihara Y, Iwata T, Kawahara K, Kikuchi S, Kitazato K, Matsumoto K, Matsuoka M, Michikami T, Mimasu Y, Miura A, Morota T, Nakazawa S, Namiki N, Noda H, Noguchi R, Ogawa N, Ogawa K, Okada T, Okamoto C, Ono G, Ozaki M, Saiki T, Sakatani N, Sawada H, Senshu H, Shimaki Y, Shirai K, Sugita S, Takei Y, Takeuchi H, Tanaka S, Tatsumi E, Terui F, Tsuda Y, Tsukizaki R, Wada K, Watanabe SI, Yamada M, Yamada T, Yamamoto Y, Yano H, Yokota Y, Yoshihara K, Yoshikawa M, Yoshikawa K, Furuya S, Hatakeda K, Hayashi T, Hitomi Y, Kumagai K, Miyazaki A, Nakato A, Nishimura M, Soejima H, Suzuki A, Yada T, Yamamoto D, Yogata K, Yoshitake M, Tachibana S, and Yurimoto H

Abstract

Carbonaceous meteorites are thought to be fragments of C-type (carbonaceous) asteroids. Samples of the C-type asteroid (162173) Ryugu were retrieved by the Hayabusa2 spacecraft. We measured the mineralogy and bulk chemical and isotopic compositions of Ryugu samples. The samples are mainly composed of materials similar to those of carbonaceous chondrite meteorites, particularly the CI (Ivuna-type) group. The samples consist predominantly of minerals formed in aqueous fluid on a parent planetesimal. The primary minerals were altered by fluids at a temperature of 37° ± 10°C, about [Formula: see text] million (statistical) or [Formula: see text] million (systematic) years after the formation of the first solids in the Solar System. After aqueous alteration, the Ryugu samples were likely never heated above ~100°C. The samples have a chemical composition that more closely resembles that of the Sun's photosphere than other natural samples do.

Published
2023
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49. Noble gases and nitrogen in samples of asteroid Ryugu record its volatile sources and recent surface evolution.

Author

Okazaki R, Marty B, Busemann H, Hashizume K, Gilmour JD, Meshik A, Yada T, Kitajima F, Broadley MW, Byrne D, Füri E, Riebe MEI, Krietsch D, Maden C, Ishida A, Clay P, Crowther SA, Fawcett L, Lawton T, Pravdivtseva O, Miura YN, Park J, Bajo KI, Takano Y, Yamada K, Kawagucci S, Matsui Y, Yamamoto M, Righter K, Sakai S, Iwata N, Shirai N, Sekimoto S, Inagaki M, Ebihara M, Yokochi R, Nishiizumi K, Nagao K, Lee JI, Kano A, Caffee MW, Uemura R, Nakamura T, Naraoka H, Noguchi T, Yabuta H, Yurimoto H, Tachibana S, Sawada H, Sakamoto K, Abe M, Arakawa M, Fujii A, Hayakawa M, Hirata N, Hirata N, Honda R, Honda C, Hosoda S, Iijima YI, Ikeda H, Ishiguro M, Ishihara Y, Iwata T, Kawahara K, Kikuchi S, Kitazato K, Matsumoto K, Matsuoka M, Michikami T, Mimasu Y, Miura A, Morota T, Nakazawa S, Namiki N, Noda H, Noguchi R, Ogawa N, Ogawa K, Okada T, Okamoto C, Ono G, Ozaki M, Saiki T, Sakatani N, Senshu H, Shimaki Y, Shirai K, Sugita S, Takei Y, Takeuchi H, Tanaka S, Tatsumi E, Terui F, Tsukizaki R, Wada K, Yamada M, Yamada T, Yamamoto Y, Yano H, Yokota Y, Yoshihara K, Yoshikawa M, Yoshikawa K, Furuya S, Hatakeda K, Hayashi T, Hitomi Y, Kumagai K, Miyazaki A, Nakato A, Nishimura M, Soejima H, Iwamae A, Yamamoto D, Yogata K, Yoshitake M, Fukai R, Usui T, Connolly HC Jr, Lauretta D, Watanabe SI, and Tsuda Y

Abstract

The near-Earth carbonaceous asteroid (162173) Ryugu is expected to contain volatile chemical species that could provide information on the origin of Earth's volatiles. Samples of Ryugu were retrieved by the Hayabusa2 spacecraft. We measured noble gas and nitrogen isotopes in Ryugu samples and found that they are dominated by presolar and primordial components, incorporated during Solar System formation. Noble gas concentrations are higher than those in Ivuna-type carbonaceous (CI) chondrite meteorites. Several host phases of isotopically distinct nitrogen have different abundances among the samples. Our measurements support a close relationship between Ryugu and CI chondrites. Noble gases produced by galactic cosmic rays, indicating a ~5 million year exposure, and from implanted solar wind record the recent irradiation history of Ryugu after it migrated to its current orbit.

Published
2023
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50. Formation and evolution of carbonaceous asteroid Ryugu: Direct evidence from returned samples.

Author

Nakamura T, Matsumoto M, Amano K, Enokido Y, Zolensky ME, Mikouchi T, Genda H, Tanaka S, Zolotov MY, Kurosawa K, Wakita S, Hyodo R, Nagano H, Nakashima D, Takahashi Y, Fujioka Y, Kikuiri M, Kagawa E, Matsuoka M, Brearley AJ, Tsuchiyama A, Uesugi M, Matsuno J, Kimura Y, Sato M, Milliken RE, Tatsumi E, Sugita S, Hiroi T, Kitazato K, Brownlee D, Joswiak DJ, Takahashi M, Ninomiya K, Takahashi T, Osawa T, Terada K, Brenker FE, Tkalcec BJ, Vincze L, Brunetto R, Aléon-Toppani A, Chan QHS, Roskosz M, Viennet JC, Beck P, Alp EE, Michikami T, Nagaashi Y, Tsuji T, Ino Y, Martinez J, Han J, Dolocan A, Bodnar RJ, Tanaka M, Yoshida H, Sugiyama K, King AJ, Fukushi K, Suga H, Yamashita S, Kawai T, Inoue K, Nakato A, Noguchi T, Vilas F, Hendrix AR, Jaramillo-Correa C, Domingue DL, Dominguez G, Gainsforth Z, Engrand C, Duprat J, Russell SS, Bonato E, Ma C, Kawamoto T, Wada T, Watanabe S, Endo R, Enju S, Riu L, Rubino S, Tack P, Takeshita S, Takeichi Y, Takeuchi A, Takigawa A, Takir D, Tanigaki T, Taniguchi A, Tsukamoto K, Yagi T, Yamada S, Yamamoto K, Yamashita Y, Yasutake M, Uesugi K, Umegaki I, Chiu I, Ishizaki T, Okumura S, Palomba E, Pilorget C, Potin SM, Alasli A, Anada S, Araki Y, Sakatani N, Schultz C, Sekizawa O, Sitzman SD, Sugiura K, Sun M, Dartois E, De Pauw E, Dionnet Z, Djouadi Z, Falkenberg G, Fujita R, Fukuma T, Gearba IR, Hagiya K, Hu MY, Kato T, Kawamura T, Kimura M, Kubo MK, Langenhorst F, Lantz C, Lavina B, Lindner M, Zhao J, Vekemans B, Baklouti D, Bazi B, Borondics F, Nagasawa S, Nishiyama G, Nitta K, Mathurin J, Matsumoto T, Mitsukawa I, Miura H, Miyake A, Miyake Y, Yurimoto H, Okazaki R, Yabuta H, Naraoka H, Sakamoto K, Tachibana S, Connolly HC Jr, Lauretta DS, Yoshitake M, Yoshikawa M, Yoshikawa K, Yoshihara K, Yokota Y, Yogata K, Yano H, Yamamoto Y, Yamamoto D, Yamada M, Yamada T, Yada T, Wada K, Usui T, Tsukizaki R, Terui F, Takeuchi H, Takei Y, Iwamae A, Soejima H, Shirai K, Shimaki Y, Senshu H, Sawada H, Saiki T, Ozaki M, Ono G, Okada T, Ogawa N, Ogawa K, Noguchi R, Noda H, Nishimura M, Namiki N, Nakazawa S, Morota T, Miyazaki A, Miura A, Mimasu Y, Matsumoto K, Kumagai K, Kouyama T, Kikuchi S, Kawahara K, Kameda S, Iwata T, Ishihara Y, Ishiguro M, Ikeda H, Hosoda S, Honda R, Honda C, Hitomi Y, Hirata N, Hirata N, Hayashi T, Hayakawa M, Hatakeda K, Furuya S, Fukai R, Fujii A, Cho Y, Arakawa M, Abe M, Watanabe S, and Tsuda Y

Abstract

Samples of the carbonaceous asteroid Ryugu were brought to Earth by the Hayabusa2 spacecraft. We analyzed 17 Ryugu samples measuring 1 to 8 millimeters. Carbon dioxide-bearing water inclusions are present within a pyrrhotite crystal, indicating that Ryugu's parent asteroid formed in the outer Solar System. The samples contain low abundances of materials that formed at high temperatures, such as chondrules and calcium- and aluminum-rich inclusions. The samples are rich in phyllosilicates and carbonates, which formed through aqueous alteration reactions at low temperature, high pH, and water/rock ratios of <1 (by mass). Less altered fragments contain olivine, pyroxene, amorphous silicates, calcite, and phosphide. Numerical simulations, based on the mineralogical and physical properties of the samples, indicate that Ryugu's parent body formed ~2 million years after the beginning of Solar System formation.

Published
2023
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