Researchers Database

okuda hiroshi

    Mathematics Professor
Contact: okudahirjichi.ac.jp
Last Updated :2021/10/17

Researcher Information

URL

J-Global ID

Research Interests

  • ベイズの定理   ゲノム医療   数理遺伝学   Rh変異型   Rh genotyping法   組換え   Rh式血液型システム   分子進化   orthologous RH gene superfamily   染色体マッピング   塩基置換・gap   多型   RH superfamily   マイクロサテライト多型   自己免疫性溶血性貧血   ラットABOオーソログ   RH遺伝子   トランスジェニックラット   

Research Areas

  • Life sciences / Internal medicine - General
  • Natural sciences / Applied mathematics and statistics
  • Life sciences / Forensic medicine
  • Life sciences / Genetics
  • Life sciences / Genomics

Academic & Professional Experience

  • 2010/04 - Today  Jichi Medical UniversitySchool of Medicine教授
  • 2009/09 - 2010/03  Jichi Medical University
  • 2005/04 - 2009/08  Jichi Medical University
  • 2001/10 - 2005/03  Jichi Medical University
  • 2000/04 - 2001/09  Jichi Medical University
  • 1999/04 - 2000/03  Jichi Medical University
  • 1996/04 - 1999/03  Jichi Medical University
  • 1994/04 - 1995/03  国保智頭病院内科勤務
  • 1993/04 - 1994/03  鳥取県立中央病院内科勤務
  • 1991/04 - 1993/03  国保赤碕診療所勤務
  • 1989/04 - 1991/03  国保岩美病院内科勤務
  • 1988/04 - 1989/03  鳥取県立中部健康増進センター勤務
  • 1986/04 - 1988/03  鳥取県立中央病院勤務(初期研修)
  • - 1986/05  医師免許取得(1986年5月28日)
  • - 1986/03  Jichi Medical University

Published Papers

  • Sho Sugiyama, Yong Hwa Chong, Masayuki Shito, Manami Kasuga, Tsuyoshi Kawakami, Chihiro Udagawa, Hiroshi Aoki, Makoto Bonkobara, Shuichi Tsuchida, Atsushi Sakamoto, Hiroshi Okuda, Atsushi Nagai, Toshinori Omi
    LEGAL MEDICINE 15 (6) 303 - 309 1344-6223 2013/11 [Refereed][Not invited]
     
    To develop DNA markers for forensic analysis, we examined the hypervariable region 1 (HVR1) sequences of 447 pure-bred domestic dogs (Canis lupus familiaris) that had been bred and raised in Japan. HVR1 is a 660-bp stretch of mitochondrial (mt) DNA. Among the 447 HVR1 sequences examined, we identified 58 haplotypes from 47 single nucleotide polymorphisms (SNPs) and two insertion-deletion (InDel) polymorphisms. The haplotype diversity inferred from inter-breed analysis (N = 154, 88 breeds) was 0.929 +/- 0.011. Intra-breed analysis showed that the haplotype diversity of Golden Retrievers (N = 53), Labrador Retrievers (N = 67), Miniature Dachshunds (N = 61), Toy Poodles (N = 62), and Welsh Corgis (N = 50) was 0.624 +/- 0.052, 0.722 +/- 0.029, 0.922 +/- 0.010, 0.877 +/- 0.020, and 0.443 +/- 0.084, respectively. The results of this genotype analysis were used to construct a dataset consisting of dog mtDNA HVR1 sequences for use in forensic applications in Japan. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
  • 我が国で飼育されているイヌのmtDNA HV1ハプロタイプの検出(第1報)
    杉山 将, 鄭 英和, 市東 正幸, 河上 剛, 宇田川 智野, 近江 俊徳, 盆子原 誠, 奥田 浩, 土田 修一
    DNA多型 19 56 - 58 2011 [Not refereed][Not invited]
  • Maki Kumada, Munkhtulga Lkhagvasuren, Nanami Utsumi, Toshinori Omi, Takaya Gotoh, Toyomi Kamesaki, Hiroshi Okuda, Eiji Kajii, Sadahiko Iwamoto
    COMMUNITY GENETICS 11 (3) 150 - 159 1422-2795 2008 [Refereed][Not invited]
     
    Objective: The aim of the study was to investigate genetic heterogeneity among local Japanese populations. Methods: We performed a single nucleotide polymorphism (SNP) study of four demographically distinct local populations (population 1: a large city; population 2: isolated islands; populations 3 and 4: rural areas). Seventy SNPs in a region spanning 5 Mb of chromosome 17 known to be a candidate region for essential hypertension were genotyped and linkage disequilibrium analyses were performed. Results: Statistical analyses of SNP allele frequencies and haplotype distribution showed significant divergence among the populations, mostly between population 2 and the other populations. Pairwise D' declined with increasing population size, and smaller populations retained a high linkage disequilibrium. Conclusion: Population 2 is likely to have a different ancestry from the majority of the Japanese population, whereas the heterogeneity among the other populations may result from differences in population size or geographic background. Copyright (C) 2008 S. Karger AG, Basel.
  • An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension.
    Omi T, Kumada M, Kamesaki T, Okuda H, Munkhtulga L, Yanagisawa Y, Utsumi N, Gotoh T,Hata A, Soma M, Umemura S, Ogihara T, Takahashi N, Tabara Y,Shimada K, Mano H, Kajii E,Miki T,Iwamoto S.
    Eur J Hum Genet. 14 (12) 1295 - 1305 2006 [Refereed][Not invited]
  • H Suganuma, M Kumada, T Omi, T Gotoh, M Lkhagvasuren, H Okuda, T Kamesaki, E Kajii, S Iwamoto
    FEBS JOURNAL 272 (11) 2696 - 2704 1742-464X 2005/06 [Refereed][Not invited]
     
    The rhesus (Rh) blood group antigens are of considerable importance in transfusion medicine as well as in newborn or autoimmune hemolytic diseases due to their high antigenicity. We identified a major DNaseI hypersensitive site at the 5' flanking regions of both RHD and RHCE exon 1. A 34 bp fragment located at -191 to -158 from a translation start position, and containing the TCCCCTCCC sequence, was involved in enhancing promoter activity, which was assessed by luciferase reporter gene assay. A biotin-labelled 34 bp probe isolated an mRNA transporter protein, Aly/REF. The specific binding of Aly/REF to RH promoter in erythroid was confirmed by chromatin immunoprecipitation assay. The silencing of Aly/REF by siRNA reduced not only the RH promoter activity of the reporter gene but also transcription from the native genome. These facts provide second proof of Aly/REF as a transcription coactivator, initially identified as a coactivator for the TCR alpha enhancer function. Aly/REF might be a novel transcription cofactor for erythroid-specific genes.
  • ヒトおよびブタで同定された新規のPPARGスプライシングバリアント
    近江俊徳, ルハクワスレン ムンフトルガ, 熊田真樹, 後藤孝也, 亀崎豊実, 奥田浩, 梶井英治, 岩本禎彦
    DNA多型 13 263 - 265 2005 [Not refereed][Not invited]
  • ブタRhesus (RH)遺伝子のcDNAクローニング, マッピング, 多型性解析
    近江俊徳, 熊田真樹, 亀崎豊実, 奥田浩, 梶井英治, 岩本禎彦, Voegeli P, Stranzinger G, Neuenshwander S
    DNA多型 12 262 - 263 2004 [Not refereed][Not invited]
  • ラットABO ホモログの遺伝子重複とその多型
    岩本禎彦, 熊田真樹, 亀崎豊実, 奥田浩
    DNA 多型 11 38 - 41 2003 [Not refereed][Not invited]
  • Sadahiko Iwamoto, Toyomi Kamesaki, Maki Kumada, Toshinori Omi, Hiroshi Okuda, Tsuyoshi Hasegawa, Shinji Sakurai, Eiji Kajii
    Legal Medicine 5 (4) 246 - 250 1344-6223 2003 [Refereed][Not invited]
     
    We report a clinical mishap based on sample contamination of cytological specimens. Bronchial lavage fluid collected from three male patients was submitted to a pathological institute for cytological diagnosis and to the clinical laboratory in the hospital for tuberculosis screening. Cytological slides of two patients were diagnosed as lung adenocarcinoma and lobectomy was carried out on one patient. However, diagnosis of the surgical specimen was tuberculoma. To resolve the discrepancy, genome DNA was isolated from patients' blood, cytological slide glasses and the mycobacterial culture tubes. Analysis of mitochondrial hyper-variable sequence and microsatellite revealed sample contamination in the cytological slide of the tuberculoma patient. DNA from the mycobacterial culture tubes showed identical results with the cytological slides, suggesting that the contamination occurred at the bed-side. Preservation of part of cytological specimen will be a help to avoid dispute between pathological laboratory and hospital over responsibility of incident. © 2003 Elsevier Ireland Ltd. All rights reserved.
  • A novel mutation in the RHD gene in Japanese individuals with weak D, encoding an amino acid change in the 11th transmembranous domain of the RhD protein transmembranous portion of the RhD protein.
    Kamesaki T, Kumada M, Omi T, Okuda H, Iwamoto S, Takahashi J, Kimura K, Hirayama F, Kamata H, Obara K, Taniguchi M, Tani Y, Kajii E
    Vox Sang 84 141 - 141 2003 [Refereed][Not invited]
  • S Iwamoto, M Kumada, T Kamesaki, H Okuda, E Kajii, T Inagaki, D Saikawa, K Takeuchi, S Ohkawara, R Takahashi, S Ueda, S Inoue, K Tahara, Y Hakamata, E Kobayashi
    JOURNAL OF BIOLOGICAL CHEMISTRY 277 (48) 46463 - 46469 0021-9258 2002/11 [Refereed][Not invited]
     
    We cloned a rat ABO homologue and established human A- and B-transferase transgenic rats. A DNA fragment corresponding to exon 7 of the human ABO gene was amplified from Wistar rat genomic DNA and sequenced. Using the amplified fragments as a probe for Southern blotting, multiple hybridized bands appeared on both EcoRI- and BamHI-digested genomes of seven rat strains, which showed variations in the band numbers among the strains. Four cDNAs were cloned from a Wistar rat, three of which showed A-iransferase activity and one of which showed B-transferase activity. These activities were dependent on the equivalent residues at 266 and 268 of human ABO transferase. Wild Wistar rats expressed A-antigen in salivary gland, intestine, and urinary bladder tissue, but B-antigen was not stained in any organs studied, whereas a transcript from the ABO homologue with B-transferase activity was ubiquitous. Human A-transferase and B-transferase were transferred into Wistar rats. A-transgenic rats expressed A-antigen in ectopic tissue of the brain plexus, type II lung epithelium, pancreas, and epidermis. B-antigen in the B-transgenic rat was expressed in the same organs as A-transgenic rats. These results may shed light on the function and evolution of the ABO gene in primates.
  • 日本人Weak D 6例の分子遺伝学的解析
    亀崎豊実, 岩本禎彦, 奥田浩, 梶井英治, 高橋順子, 木村恵子, 平山文也, 谷慶彦, 鎌田博子, 小原健良, 谷口万里子
    DNA多型 10 186 - 190 2002 [Not refereed][Not invited]
  • The evolution and formation of RH genes.
    Okuda H, Kajii E
    Legal Medicine 4 139 - 155 2002 [Refereed][Not invited]
  • Isolation, characterization, and family study of a novel partial D named DTI affecting the fourth external loop of the RhD polypeptides.
    Omi T, Takahashi J, Seno T, Tanaka M, Hirayama F, Matsuo M, Ueda, N, Ohar R, Okuda H, Iwamoto S, Tani Y, Kajii E
    Transfusion 42 481 - 489 2002 [Refereed][Not invited]
  • T Kamesaki, S Iwamoto, M Kumada, T Omi, H Okuda, M Tanaka, J Takahashi, K Obara, T Seno, Y Tani, E Kajii
    VOX SANGUINIS 81 (4) 254 - 258 0042-9007 2001/11 [Refereed][Not invited]
     
    Background and Objectives Mutations detected in 161 weak D samples from Caucasians have been classified into 16 types. Because flow cytometry using monoclonal anti-D antibodies (mAbs) has shown that weak D red cells display type-specific antigen density, these mutations in transmembranous regions have been assigned weak D phenotypes. The present study attempts to confirm or refute this assignment. Materials and Methods We amplified DNA from four Japanese weak D samples using the polymerase chain reaction (PCR), and directly sequenced the amplified DNA. Using site-directed mutagenesis, we constructed three vectors expressing mutant RHDs - G212C, V270G (weak D type 1) and G358A (type 2) - in K562 cells. The expression of RhD antigens was examined by flow cytometry using mAbs. Results A new mutation resulting in a conversion at amino acid residue 212 (Gly to Cys) was detected in a Japanese weak D sample. K562 cells transduced with mutant RhD cDNA reacted weakly in a type-specific manner with mAbs. Conclusions The mutations - G212C (new weak D type), V270G (weak D type 1) and G358A (type 2) - in transmembranous regions had obvious effects on the D epitopes recognized by mAbs. The results of this study provide direct evidence that these mutations can account for weak D phenotypes.
  • S Iwamoto, T Kamesaki, T Oyamada, H Okuda, M Kumada, T Omi, J Takahashi, Y Tani, M Omine, E Kajii
    AMERICAN JOURNAL OF HEMATOLOGY 68 (2) 106 - 114 0361-8609 2001/10 [Refereed][Not invited]
     
    The specificity of autoantibodies in autoimmune hemolytic anemia (AlHA) has been studied using the serological procedure and immunoprecipitation technique with rare phenotype red cells. We attempted to analyze specificity using recombinant rhesus (Rh) blood group and band3 antigens expressed on erythroleukemic cell lines, KU812E. The autoantibody eluates were isolated by the acid elution procedure from the red cells of 20 ANA patients. The recombinant Rh antigens, RhD, cE, ce, CE, and chimera antigens CE-D and D-CE, were obtained by retroviral cDNA transduction into KU812E cells, and the cell line expressing the antigens was cloned. Band3 cDNA was also obtained and introduced into KU812E and cloned KU812 expressing RhcE. The reactivities of ANA eluates with recombinant Rh and band3 antigens were studied by flow cytometry. Fifteen eluates reacted with at least one of the RhcE, ce, or CE antigens, and four eluates reacted with RhD. Seven eluates with strong Rh specificity were studied further using chimera antigen. Five eluates showed reduced or lost reactivity, although two eluates reacted identically with the chimera antigens as wild type. These results indicated that conformational epitopes constituted by RhD or CE specific exofacial peptide loops are important for autoantibodies in most cases. Seven eluates reacted with band3, five exclusively, The coexpression study of RhcE and band3 did not enhance the expression of either antigen nor the reactivity with patient eluates, indicating that association of Rh and band3 was not involved in the appearance of autoantigen. Am. J. Hematol. 68:106-114, 2001. (C) 2001 Wiley-Liss, Inc.
  • Rh抗原発現制御メカニズムの解析
    梶井英治, 岩本禎彦, 小山田隆, 亀崎豊実, 奥田浩, 熊田真樹, 小峰光博
    厚生科学研究費補助金(特定疾患対策研究事業)特発性造血障害に関する研究班 平成12年度研究業績報告書 102 - 103 2001 [Not refereed][Not invited]
  • RH遺伝子の分子進化学的解析
    奥田浩, 菅沼弘, 津戸直樹, 熊田真樹, 亀崎豊実, 近江俊徳, 岩本禎彦,梶井英治
    DNA多型 9 220 - 225 2001 [Not refereed][Not invited]
  • S Iwamoto, H Suganuma, T Kamesaki, T Omi, H Okuda, E Kajii
    JOURNAL OF BIOLOGICAL CHEMISTRY 275 (35) 27324 - 27331 0021-9258 2000/09 [Refereed][Not invited]
     
    fRhesus-associated glycoprotein is a critical co-factor in the expression of rhesus blood group antigens. We identified and cloned an erythroid-specific major DNase I-hypersensitive site located about 10 kilobases upstream from the translation start site of the RHAG gene. A short core enhancer sequence of 195 base pairs that corresponded with the major hypersensitive site and possessed position- and orientation-independent enhancer activity in K562 cells. In vitro DNase I footprint analysis revealed four protected regions in the core enhancer; two GATA motifs, an Ets-like motif and an unknown motif. The GATA motifs bound GATA-1 and mutagenesis analysis revealed that the proximal one is critical for the enhancing activity. Homology plot analysis using the 5' sequence of the mouse RHAG gene revealed four homologous stretches and multiple insertions of repetitive sequences among them; four LINE/L1 and four Alu in the human and as well as one LINE/L1 and one LTR/MaLR in the mouse gene. The highly conservative enhancer region was flanked by SINE and LINE/L1 in both species. These results suggest that the 5'-flanking sequence of RHAG gene is a preferable target sequence for retroviral transposition and that the enhancer was inserted in the same manner, resulting in the acquisition of erythroid dominant expression.
  • H Okuda, H Suganuma, T Kamesaki, M Kumada, N Tsudo, T Omi, S Iwamoto, E Kajii
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 274 (3) 670 - 683 0006-291X 2000/08 [Refereed][Not invited]
     
    dWe determined the entire nucleotide sequences of all introns within the RHD and RHCE genes by amplifying genomic DNA using long PCR methods. The RND and RHCE genes were 57,295 and 57,831 bp in length, respectively. Aligning both genes revealed 138 gaps (insertions and deletions) below 100 bp, 1116 substitutions in all introns and all exons (coding region), and 5 gaps of over 100 bp. Homologies (%) between the RH genes were 93.8% over all introns and coding exons and 91.7% over all exons and introns. Various short tandem repeats (STRs) and many interspersed nuclear elements were identified in both genes. The proportions of Alu sequences in the RHD and RHCE genes were 25.9 and 25.7%, respectively and these Alu sequences were concentrated in several regions. We confirmed multiple recombinations in introns 1 and 2, Such multiple recombination, which probably arose due to the concentrations of Alu sequences and the high level of the homology (%), is one of most important factors in the formation and evolution of RH gene. The variability of the Rh system may be generated because of these features of RH genes. Apparent mutational hotspots and regions with low of K values (the numbers of substitutions per nucleotide site) caused by recombinations as well as true mutational hotspots may be found in human genome. Accordingly, in searching for and identifying single nucleotide polymorphisms (SNPs) especially in noncoding regions, apparent mutational hotspots and areas of low K values by recombination should be noted since the unequal distribution of SNPs will reduce the power of SNPs as genetic maker. Combining the complete sequences' data of both RH genes with serological findings will provide beneficial information with which to elucidate the mechanism of recombination, mutation, polymorphism, and evolution of other genes containing the RH gene as well as to analyze Rh variants and develop new methods of Rh genotyping. (C) 2000 Academic Press.
  • M Kato-Yamazaki, H Okuda, M Kawano, T Omi, T Iwamoto, T Ishimori, H Hasekura, E Kajii
    TRANSFUSION 40 (5) 617 - 618 0041-1132 2000/05 [Refereed][Not invited]
  • T Omi, H Okuda, S Iwamoto, E Kajii, J Takahashi, M Tanaka, Y Tani
    TRANSFUSION 40 (2) 256 - 258 0041-1132 2000/02 [Refereed][Not invited]
  • DVa(Partial D)表現型のエピトープマッピング
    近江俊徳,高橋順子,瀬尾たい子,田中光信,亀崎豊実,奥田浩,岩本禎彦,谷 慶彦,梶井英治
    DNA多型 8 203 - 206 2000 [Not refereed][Not invited]
  • H Okuda, H Fujiwara, T Omi, S Iwamoto, M Kawano, T Ishida, S Nomura, S Fukuhara, A Nagai, Ohya, I, E Kajii
    JOURNAL OF HUMAN GENETICS 45 (3) 142 - 153 1434-5161 2000 [Refereed][Not invited]
     
    In a family study of a Japanese propositus with the D-- phenotype, the serological data of her D-phenotype and those of her parents were discrepant. Gene analysis of the propositus showed a gross deletion of the RI-ICE gene and a new rearrangement of RHCE to yield the CE-D-CE hybrid. It was demonstrated that the hybrid CE-D-CE gene consisted of exon 1 from the RHCE gene, followed by exons 3 to 7 from the RHD gene and exons 8 to 10 from the RHCE gene. However, whether or not exon 2 of the RND or the RHCE gene was contained in the CE-D-CE gene remained unclear. Moreover, spacer analysis be tween both RN genes and the family study suggested that the D-- gene complex from the paternal and maternal sides consisted of only the CE-D-CE hybrid gene and a single RHD gene, respectively. For the purpose of confirming the parent-child relationship, a paternity test using DNA fingerprint and polymerase chain reaction (PCR) analysis at the D1S80 locus were performed, DNA fingerprints with two kinds of DNA minisatellite probes (33.15 and 33.6) confirmed that the parent-child relationship in the D-propositus was compatible. However, in the present case, at the D1S80 locus, the PCR product derived from the mother was lacking, thereby negating a parent-child relationship, it is probable that the RH genes and D1S80 locus exist in close proximity, because they are situated in chromosomes Ip 34.3-36.1 and Ip 36.1-36.3, respectively. These data suggested that at the stage of gametogenesis, both the RHCE gone and the D1S80 locus from the maternal side may have been deleted, thereby producing the D-- gene complex.
  • H Okuda, H Suganuma, N Tsudo, T Omi, S Iwamoto, E Kajii
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 263 (2) 378 - 383 0006-291X 1999/09 [Refereed][Not invited]
     
    Numerous variants of the Rh blood group system, discovered by Levine and Stetson in 1939, have been detected and more than forty antigens have been identified. By performing the molecular genetic analysis of the introns as well as the exons in both RH genes, it was elucidated that Rh variants were generated by gene conversion or recombination, deletions, or mutations. For understanding the generation of many Rh variants and Rh antigens in detail, it is necessary to analyze not only the RHCE and RHD genes but also the structure and the physical distance between both these RH genes. In order to achieve the aforesaid purpose, the spacer region between the RHD and RHCE genes were amplified by the long PCR method. Therefore the full spacer region was determined to be 12159 bp in length and contained the Alu consensus sequences and the putative CpG island. It was probable that the duplication of both RH genes occurred within about 12 kb region. Analysis of the spacer region provides new information for the research on the transcription-control region, the molecular evolution of RH genes, Rh variants, and the deletion of the RHD gene in Rh blood group system. (C) 1999 Academic Press.
  • H Fujiwara, H Okuda, T Omi, S Iwamoto, Y Tanaka, J Takahashi, Y Tani, H Minakami, S Araki, Sato, I, E Kajii
    HUMAN GENETICS 104 (4) 301 - 306 0340-6717 1999/04 [Refereed][Not invited]
     
    We identified simple-sequence repeat polymorphisms in intron 8 of the RHD and RHCE genes, both of which contained the 5-bp repeat unit (AAAAT)n. We analyzed the polymorphisms of this short tandem repeat (STR) in 104 Japanese RhD-positive and 124 RhD-negative (87 RHD gene negative and 37 nonfunctional RHD gene positive) donors by the polymerase chain reaction (PCR) and subsequent typing by electrophoresis and silver staining. We found five alleles (10, 11, 12, 13, and 14 repeats) in the RHD gene and four (7, 8, 9, and 10 repeats) in the RHCE gene. The Rh phenotypes were closely associated with polymorphisms of the STR. The Ce allele had 12 repeats in the RHD gene and 9 repeats in the RHCE gene at high frequency. The cE allele frequently had 10-12 repeats in the RHD gene and 10 repeats in the RHCE gene. The 10 repeats in the RHCE gene were identified exclusively in the 87 RHD gene-negative donors and 9 repeats were identified only in those with the RhC antigen. These results indicate that both haplotypes of dce and dcE arose from single RHD gene deletion and recombination events, respectively. In the 37 RhD-negative donors with a nonfunctional RHD gene, 12 repeats in the RHD gene and 9 repeats in the RHCE gene were frequently observed. Thus, the RhD-negative with a nonfunctional RHD gene combination might have arisen from the DCe haplotype via a mutation that abolished RHD gene expression. These findings suggest that the STR polymorphisms might shed light upon the molecular evolution of RH haplotypes.
  • T Omi, J Takahashi, N Tsudo, H Okuda, S Iwamoto, M Tanaka, T Seno, Y Tani, E Kajii
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 254 (3) 786 - 794 0006-291X 1999/01 [Refereed][Not invited]
     
    Within the Rh blood group, the partial D phenotype is a well known RhD variant, that induces Rh-incompatible blood transfusion and hemolytic diseases in the newborn. The partial D category D-Va phenotype (D-Va Kou.) results from a hybrid of RhD-CE-D transcript, We demonstrated a genomic organization of the hybrid RHD-CE-D gene leading to the D-Va phenotype, and showed that the D-Va gene were generated from gene conversion between the RHD and the RHCE genes in relatively small regions. This study also revealed that the presence of a new partial D associated with the D-Va phenotype, which we termed the D-Va-like phenotype, In this phenotype, five RHD-specific nucleotides were replaced with the corresponding RHCE-derived nucleotides on the exon 5 of the RHD gene. In addition, two variants of the mutated RHD genes at nucleotide 697 were revealed in the RhD variant samples. These results will provide useful information for future research into the diversification of the Rh polypeptides. (C) 1999 Academic Press.
  • Rh式---型とregulator typeのRhnull型の分子遺伝学的解析
    山崎 昌子, 奥田 浩, 河野 正樹, 近江 俊徳, 岩本 禎彦, 梶井 英治, 福田 さと子, 長谷川 倫子, 石森 崇平, 支倉 逸人.
    日本輸血学会雑誌 45 (6) 826 - 827 1999 [Refereed][Not invited]
  • S Iwamoto, M Yamasaki, M Kawano, H Okuda, T Omi, J Takahashi, Y Tani, M Omine, E Kajii
    INTERNATIONAL JOURNAL OF HEMATOLOGY 68 (3) 257 - 268 0925-5710 1998/10 [Refereed][Not invited]
     
    Rh blood group antigens are associated with non-glycosylated human erythrocyte membrane proteins encoded by two closely related genes, RHCE and RHD, and with a glycoprotein, a critical co-er;pressing factor encoded by the RH50 gene. The sequence analysis of RHCE transcripts has revealed that RhE/e and C/c serological phenotypes are associated with a nucleotide substitution in exon 5 and six substitutions in exons 1 and 2 of RHCE gene, respectively. Smythe et al, have shown that the full length transcript of RhcE gene expressed c and E antigens and the transcript of RhD gene expressed D and G antigens, using retroviral-mediated gene transduction into K562 cells. We performed an epitope analysis of Rh antigen by constructing retroviral gene coding six RH cDNAs, which contain RhcE, ce, CE and D cDNAs, and CE-D, D-CE chimera cDNAs. The cDNAs were introduced into KU812E cells and the expressed antigens were analyzed by flow cytometry. These studies revealed that the C/c and E/e associated substitutions actually participated in respective polymorphic epitopes. However, the C antigen was not detected on the KU812E cells introduced with CE cDNA, despite E antigen being expressed. The study with the chimera gene between CE and D cDNAs also indicated that the Rh epitopes were not constructed with short polymorphic exofacial peptide loops only but also with other peptide fragments and membrane components. Go-expression studies of Rh50 and RhD or cE gene in non-erythroid cells, 293, and expression studies of Rh50 in another erythroid cell, HEL, did not show any Rh antigens on the transduced cells, despite the Northern blot study showing both transcripts in the cells. It was suggested that at least a second co-expressing factor was needed to express RhCE or D antigens on the plasma membrane. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
  • Rh血液型システムにおけるRhD(-)ならびにD--表現型の分子遺伝学的背景に関する研究.(医学博士論文)
    奥田浩
    1998/05 [Refereed][Not invited]
  • M Kawano, S Iwamoto, H Okuda, S Fukuda, N Hasegawa, E Kajii
    ANNALS OF HUMAN GENETICS 62 107 - 113 0003-4800 1998/03 [Refereed][Not invited]
     
    Rh-null its a syndrome serologically characterized by the deficiency of all Rh antigens on human red blood cells. Rh-null is divided into two types: regulator and amorph. Recently, Cherif-Zahar et al. proposed:that the RHAG gene encoding the Rh50 glycoprotein is a candidate for inducing regulator type Rh-null. We investigated both the RH and RHAG genes in an Rh-null individual. The reticulocytes from the propositus had RHD, RHcE, and RHCe transcripts without any mutation. However, the sequence analysis of RHAG cDNA showed a deletion of 122 bp from nucleotide 946 to 1067. This deletion Tvas revealed to be due to a homozygous splicing mutation, which is a single base substitution at the consensus sequence of the splicing acceptor site (AG --> AT). The mutation appeared to break the 'GT-AG' splicing rule and to cause 122 bp exon skipping accompanied by a frameshift. This study confirms that the RHAG gene is the most likely candidate for the 'regulator' gene of Rh-null cases.
  • S Iwamoto, T Omi, M Yamasaki, H Okuda, M Kawano, E Kajii
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 243 (1) 233 - 240 0006-291X 1998/02 [Refereed][Not invited]
     
    The Rh blood group antigens are carried by two distinct but homologous membrane proteins encoded by two closely related genes, RHCE and RHD. Rh50 glycoprotein is the membrane protein tightly associated with Rh polypeptides and is critical for expression of Rh antigens. The amino acid sequence and predicted membrane topology of Rh50 glycoprotein are significantly homologous with those of the Rh proteins. Northern blot analysis of leukemic cell lines showed that expression of RH50 gene is restricted to cells with erythroid features. HEL and K562 cells showed a transcription levels ratio of 1 to 9.9 for Rh50, and 12.3 to 1 for Rh. The nucleotide sequence of 5' flanking region of RH50 gene and functional promoter assays also supported the erythroid-specific regulation of the gene, whereas the sequence had lower homology with the promoter sequence of RH genes. Seven GATAs, nine E-boxes, two CACCCs, one YY1, and one October motif were identified in the 1868bp 5' flanking sequence. The core promoter of RH50 gene was located within 68bp length from the translation start position, which included an inverse GATA motif, although obvious motifs for Sp1 or erythroid Kruppel-like factor were lacking. The inverse GATA motif was the target sequence of GATA-1 protein, and disruption of the motif abolished the transactivating activity of erythroid cells. These studies confirm the erythroid-specific expression of Rh antigens, but suggest distinct regulatory mechanisms for RH vs RH50 genes. (C) 1998 Academic Press.
  • リコンビナントRh抗原発現細胞を用いた抗赤血球自己抗体の特異性解析
    梶井英治, 亀崎豊実, 近江俊徳, 小山田隆, 奥田浩, 岩本禎彦
    厚生省特定疾患血液系疾患研究班・特発性造血障害分科会, 平成9年度研究業績報告書(分科会長 溝口秀昭) 68 - 69 1998 [Not refereed][Not invited]
  • へき地医療における突然死の発生状況ならびに背景因子に関する研究
    梶井英治, 岩本禎彦, 河野正樹, 奥田浩, 武富章, 津戸直樹
    平成9年度へき地住民の健康増進に関する研究等 (財団法人地域社会振興財団) 49 - 74 1998 [Not refereed][Not invited]
  • Partial D におけるRHD遺伝子の解析 : DFR表現型とVa表現型について
    近江 俊徳, 奥田 浩, 津戸 直樹, 岩本 禎彦, 梶井 英治, 田中 光信, 岡本 衣久代, 高橋 順子, 瀬尾 たい子, 中出 亮, 谷 慶彦, 柴田 弘俊, 田口 俊夫
    DNA多型 6 32 - 35 1998 [Not refereed][Not invited]
  • H Okuda, M Kawano, S Iwamoto, M Tanaka, T Seno, Y Okubo, E Kajii
    JOURNAL OF CLINICAL INVESTIGATION 100 (2) 373 - 379 0021-9738 1997/07 [Refereed][Not invited]
     
    Recent molecular studies on the Rh blood group system have shown that the Rh locus of each haploid RhD-positive chromosome is composed of two structural genes: RHD and RHCE, whereas the locus is made of a single gene (RHCE) on each haploid RhD-negative chromosome, We analyzed the presence or absence of the RHD gene in 130 Japanese RhD-negative donors using the PCR method, The RhD-negative phenotypes consisted of 34 ccEe, 27 ccee, 17 ccEE, 26 Ccee, 19 CcEe, 1 CcEE, and 6 CCee, Among them, 36 (27.7%) donors demonstrated the presence of the RHD gene, Others showed gross or partial deletions of the RHD gene, These results were confirmed by Southern blot analysis, Additionally, the RHD gene detected in the RhD-negative donors seemed to be intact through sequencing of the RhD polypeptide cDNA and the promoter region of RHD gene, The phenotypes of these donors with the RHD gene were CC or Cc, but not cc, It suggested that there is some relationship between the RHD gene and the RhC phenotypes in RhD-negative individuals, In Caucasian RhD-negative individuals, the RHD gene has not been found outside of the report of Hyland et al, (Hyland, C,A,, L,C, Welter, and A, Saul. 1994, Blood, 84:321-324), The discrepant data on the RHD gene in RhD-negative donors between Japanese and Caucasians appear to be derived from the difference of the frequency of RhD-negative and RhC-positive phenotypes. Careful attention is necessary for clinicians in applying RhD genotyping to clinical medicine.
  • 鳥取県漁村地域における胃疾患の疫学的および分子生物学的研究
    小谷和彦, 熊田真樹, 亀崎豊実, 渡辺賢司, 秋藤洋一, 中本周, 奥田浩, 岩本禎彦, 梶井英治
    平成8年度へき地住民の健康増進に関する研究等(財団法人地域社会振興財団) 117 - 143 1997 [Not refereed][Not invited]
  • 農山村及び漁村などへき地集団における溶血性貧血の分類とその発生機序に関する分子生物学的研究(Ⅱ)
    梶井英治, 岩本禎彦, 奥田浩, 石田暁宏, 渡辺賢司, 秋藤洋一, 長田憲一, 田中孝幸, 那須博司, 上本宗唯, 亀崎豊実
    平成8年度へき地住民の健康増進に関する研究等(財団法人地域社会振興財団) 91 - 116 1997 [Not refereed][Not invited]
  • Rh赤血球自己抗原の分子構造とエピトープ解析
    梶井英治, 岩本禎彦, 近江俊徳, 小山田隆, 奥田浩
    厚生省特定疾患血液系疾患研究班・特発性造血障害分科会, 平成8年度研究業績報告書(分科会長 溝口秀昭) 67 - 68 1997 [Not refereed][Not invited]
  • 各種RhvariantにおけるRhgenotypingとその問題点.DNA多型
    奥田浩, 河野正樹, 近江俊徳, 岩本禎彦, 田中光信, 瀬尾たい子, 大久保康人, 梶井英治
    DNA多型 5 126 - 130 1997 [Not refereed][Not invited]
  • Glycyrrhizin がLECラットの肝障害を防止する機序
    野見山 一生, 野見山 紘子, 亀田 直毅, 櫻井 弘, 辻 昭博, 岡山 明子, 梶井 英治, 岩本 禎彦, 奥田 浩, 政岡 俊夫, 和久井 信, 有薗 幸司
    Biomedical research on trace elements 8 (3) 89 - 90 1997 [Refereed][Not invited]
  • Dinucleotide repeat in the 3' franking region provides a clue for molecular evolution of Duffy gene.
    Li J, Iwamoto S,Sugimoto N, Okuda H, Kajii E
    Human Genet. 99 573 - 577 1997 [Refereed][Not invited]
  • M. Tanaka, T. Seno, H. Shibata, Y. Okubo, H. Okuda, E. Kajii, R. Utsumi
    Japanese Journal of Legal Medicine 51 (1) 32 - 38 0047-1887 1997 [Refereed][Not invited]
     
    The Rh blood group system has five major antigens D, C/c, and E/e. These antigens are encoded in RHD and RHCE genes. In this report, we describe a systemic method for RhC/c and RhE/e genotyping by PCR using allele-specific oligonucleotide primers (ASO-PCR). The ASO-PCR was carried out to determine the RhC/c and RhE/e genotypes in DNA samples from 513 Japanese donors. Genotypes of RhC, RhE, and Rhe were in full concordance with serological phenotypes in 511 donors. However, in two cases with the phenotype of ccdee, the C-specific ASO-PCR product was also detected in addition to the c- specific one. This method is simple and quite useful for the RhC/c and RhE/c genotyping, although further investigation on the 2 exceptional ccdee cases is needed.
  • S Iwamoto, JP Li, N Sugimoto, H Okuda, E Kajii
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 222 (3) 852 - 859 0006-291X 1996/05 [Refereed][Not invited]
     
    We have previously identified a novel first exon of Duffy gene and two inverse GATA motifs in the 600 bp 5' flanking region. The proximal GATA is positioned downstream from the start position of endothelium and upstream from that of erythroid. One base substitution (-365T-->C) was found in the proximal GATA motif from three black Fy(a-b-) individuals, and was regarded as a common polymorphic mutation in black Fy(a-b-) individuals. The upstream sequence of the novel first exon was inserted in the upstream of chloramphenicol acetyltransferase (CAT) gene and transfected in human erythroleukemia cell line (HEL) and human microvascular endothelial cells (HMvEC). The black type mutation abolished the CAT transcription in HEL cells but not in HMvEC. Deletion mutagenesis study revealed that the proximal GATA motif represent the erythroid regulatory core region for Duffy gene. Gel shift assay showed that the proximal GATA motif is the target sequence of GATA-1. These studies indicate that the black type mutation abolishes Duffy gene expression in erythroid but not in postcapillary venule endothelium, which is compatible with the Northern blot and immunohistochemical observation in black Fy(a-b-) individuals. (C) 1996 Academic Press, Inc.
  • 医師とABO式血液型.
    小谷和彦, 奥田浩, 小山田隆, 梶井英治, 池本卯典
    自治医大紀要 18 139 - 146 1995 [Refereed][Not invited]
  • IgG骨髄腫におけるIgG1値, IgG2値とZTT値の関連について.
    植木寿一, 秋藤洋一, 田中孝幸, 奥田浩, 松ノ谷真智子, 松本尚美, 石河健, 中本周他
    鳥取医学雑誌 21 290 - 293 1993 [Refereed][Not invited]
  • 急性リンパ性白血病の第二寛解期に同種骨髄移植を行った一例.
    田中孝幸, 植木寿一, 安東吾郎, 大谷恭一, 奥田浩, 加藤一吉 他
    鳥取医学雑誌 16 112 - 117 1988 [Refereed][Not invited]
  • 日本人のABO式およびMN式血液型表現型出現頻度と遺伝子頻度の再検討.
    奥田浩, 山本隆, 新鞍誠, 梶井英治, 土田修一, 池本卯典
    自治医大紀要 9 163 - 172 1986 [Refereed][Not invited]

Books etc

  • 医と知の航海(永井良三監修(自治医大総合教育 編))
    奥田浩 (Contributor医学を数学の言葉で考える)
    西村書店 2016
  • 南山堂医学大辞典(19版)
    奥田浩:相川直樹ら(編) (Contributor)
    南山堂 2006
  • リンパ節腫脹-悪性腫瘍によるもの(今月の治療 12:1169-1176)
    奥田浩, 梶井英治 (Contributor)
    総合医学社 2004
  • 赤血球の血液型(Medical Technology31:1455-1466)
    奥田浩, 梶井英治 (Contributor)
    医歯薬出版 2003
  • Rh式血液型の分子遺伝学(池田久實編集:輸血医学における分子生物学)
    梶井英治,奥田浩,近江俊徳,亀崎豊実,小山田隆,岩本禎彦 (Contributor)
    エフ・コピント富士書院 2001
  • 最新血液型学
    梶井英治編著, 岩本禎彦, 奥田浩著 (Contributor)
    南山堂 1998
  • 溶血性貧血(カレントテラピー14:13-17)
    奥田浩, 梶井英治 (Contributor)
    ライフメディコム 1996

Conference Activities & Talks

  • Establishment of learning support system in Jichi Medical University
    岡崎仁昭,武藤弘行,奥田浩,神田健史,石川鎮清
    第46回日本医学教育学会大会  2014
  • Introduction of an integrated science education for first-year medical students utilizing the dormitory at Jichi Medical University  [Not invited]
    松儀実広,原田三男,菊地元史,黒岩憲二,淺田義和,輿水崇鏡,奥田浩,遠藤仁司,野田泰子,岡崎仁昭
    第46回日本医学教育学会大会  2014
  • 医学部低学年生からの学生指導方法-自治医科大学Faculty development -  [Not invited]
    佐藤 正章,渥美 一弥,野田 泰子,松儀 実広,板井 美浩,奥田 浩,岡崎 仁昭
    第43回日本医学教育学会大会  2011/07
  • ゲノムが診療にもたらしたもの  [Invited]
    奥田浩
    医療法人相生会どうどうクリニック  2007/11
  • トルコ鞍部・下垂体出血によって受傷約2週間後に急変・死亡したと 推定される1例  [Not invited]
    坂本敦司,小山田隆,岩本禎彦,熊田真樹,後藤孝也,村田一素,奥田浩,梶井英治
    第91次日本法医学会総会  2007/05
  • 当部門における医療事故関連解剖事例の概要と医療過誤事案への取り組 み
    後藤孝也,熊田真樹,近江俊徳,小山田隆,亀崎豊実,奥田浩,岩本禎彦,坂本敦司
    第90次日本法医学会総会
  • 法医学部門における医療事故関連解剖事例の概要  [Not invited]
    後藤孝也, 熊田真樹, 近江俊徳, 小山田隆, ルハグワスレン ムンフトルガ, 宇津見七海, 亀崎豊実, 奥田浩, 岩本禎彦, 坂本敦司
    第4回自治医科大学シンポジウム  2005/09
  • Characterization of a novel variable number of tandem repeats(VNTR)polymorphism in CIAS1 gene.  [Not invited]
    Omi,T.,Kumada,M.,Okuda,H.,Kamesaki,T.,Kajii,E.,Sakamoto,A.,
    21th International society of forensic medicine  2005/09
  • PYAF1遺伝子の連鎖不平衡,ハプロタイプ解析  [Not invited]
    近江俊徳, 熊田真樹, ルハグワスレン ムンフトルガ, 後藤孝也, 亀崎豊実, 奥田浩, 梶井英治, 坂本敦司, 岩本禎彦
    第89次日本法医学会総会
  • モンゴルと日本人集団間における生活習慣病関連遺伝子多型の比較解析  [Not invited]
    ルハグワスレン ムンフトルガ, 熊田真樹, 近江俊徳, 後藤孝也, 亀崎豊実, 奥田浩, 梶井英治, 坂本敦司, 岩本禎彦
    第89次日本法医学会総会
  • ブタPPARgの遺伝子解析  [Not invited]
    近江俊徳, ルハグワスレンムンフトルガ, 熊田真樹, 後藤孝也, 亀崎豊実, 奥田浩, 梶井英治, 岩本禎彦
    日本DNA多型学会第13回学術集会  2004/12
  • 日本国内の人口統計学的背景の異なる集団間におけるハプロタイプブロックの比較解析  [Not invited]
    熊田真樹, ムンフトルガハグバスレン, 柳沢佳子, 近江俊徳, 後藤孝也, 亀崎豊実, 奥田浩, 梶井英治, 岩本禎彦
    日本人類遺伝学会第49回大会  2004/10
  • クームス陰性自己免疫性溶血性貧血患者における赤血球結合IgGサブクラス定量  [Not invited]
    亀崎豊実, 小山田隆, 熊田真樹, 近江俊徳, 奥田浩, 坂本敦司, 岩本禎彦, 梶井英治
    第66回46回日本血液学会・日本臨床血液学会回総会  2004/09
  • Angiotensin Vasopressin Receptor (AVR)-like 遺伝子のVNTR多型と遺伝子発現  [Not invited]
    近江俊徳, 熊田真樹, 亀崎豊実, 奥田浩, 梶井英治, 岩本禎彦
    第88 次日本法医学会総会  2004/06
  • 日本国内の人口統計学的背景の異なる集団間におけるハプロタイプブロックの比較解析  [Not invited]
    熊田真樹, 近江俊徳, 亀崎豊実, 奥田浩, 梶井英治, 岩本禎彦
    第88次日本法医学会総会  2004/06
  • ブタRhesus (RH)遺伝子のcDNAクローニング, マッピング, 多型性解析  [Not invited]
    近江俊徳, 熊田真樹, 亀崎豊実, 奥田 浩, 梶井英治, 岩本禎彦, Peter Vogeli, Gerald, Stranzinger, Stefan Neuenshwander
    日本DNA多型学会第12回学術集会  2003/11
  • 本態性高血圧症に対するヒト第17 番染色体長腕の疾患候補遺伝子領域におけるSNP 解析.  [Not invited]
    熊田真樹, 近江俊徳, 亀崎豊実, 奥田浩, 梶井英治, 岩本禎彦
    日本人類遺伝学会第48 回大会  2003/10
  • アンギオテンシンバソプレッシンレセプター様(AVP-like)遺伝子内に見出されたVNTR
    近江俊徳, 熊田真樹, 亀崎豊実, 奥田 浩, 梶井英治, 岩本禎彦
    第72 回日本法医学会関東地方会  2003/10
  • 抗Rh 抗体mimotope同定へのアプローチ  [Not invited]
    亀崎豊実, 小山田隆, 熊田真樹, 近江俊徳, 奥田浩, 岩本禎彦, 梶井英治
    第51回日本輸血学会総会  2003/05
  • RH 遺伝子発現調節領域結合タンパク質のプロテオーム解析  [Not invited]
    岩本禎彦, 奥田浩, 熊田真樹, 近江俊徳, 亀崎豊実, 梶井英治
    第87次日本法医学会総会  2003/04
  • 骨髄移植後の免疫性溶血性貧血における赤血球抗原の由来/STR多型による分析  [Not invited]
    亀崎豊実, 熊田真樹, 近江俊徳, 奥田浩, 岩本禎彦, 梶井英治
    第87次日本法医学会総会  2003/04
  • 医療機関内で集団発生した腸管出血性大腸菌感染症の剖検例  [Not invited]
    熊田真樹, 近江俊徳, 亀崎豊実, 奥田浩, 梶井英治, 岩本禎彦
    第87回次日本法医学会総会  2003/04
  • WNK4遺伝子におけるSNPスクリーニングとプロモータ領域のSNP(rSNP)の転写活性解析  [Not invited]
    熊田真樹, 岩本禎彦, 亀崎豊実, 近江俊徳, 奥田浩, 梶井英治
    日本人類遺伝学会第47回大会  2002/11
  • 覚醒剤中毒が疑われ,剖検にてびまん性心筋出血を認めた一例  [Not invited]
    亀崎豊実, 熊田真樹, 岩本禎彦, 奥田浩, 梶井英治
    第71回日本法医学会関東地方会  2002/10
  • ラットABOホモログの遺伝子重複とその多型  [Not invited]
    岩本禎彦, 熊田真樹, 亀崎豊実, 奥田浩, 梶井英治
    日本DNA多型学会第11回学術集会  2002/10
  • RH遺伝子間における塩基置換, gap, 組み換え領域のmapping解析  [Not invited]
    奥田浩, 熊田真樹, 亀崎豊実, 近江俊徳, 岩本禎彦, 高橋順子, 田中光信, 瀬尾たい子, 谷慶彦, 梶井英治
    第86次日本法医学会総会  2002/04
  • ラットABOホモログのクローニング  [Not invited]
    岩本禎彦, 奥田浩, 熊田真樹, 亀崎豊実, 梶井英治
    第86次日本法医学会総会  2002/04
  • 解離性大動脈瘤術後破裂肺穿破の一症例  [Not invited]
    熊田真樹, 亀崎豊実, 奥田浩, 岩本禎彦, 梶井英治
    第86次日本法医学会総会  2002/04
  • 自己免疫性溶血性貧血の自己抗原群mimotope の解析  [Not invited]
    梶井英治, 亀崎豊実, 小山田隆, 熊田真樹, 近江俊徳, 奥田浩, 岩本禎彦
    厚生労働科学研究費補助金(特定疾患対策研究事業)特発性造血障害に関する研究班(班長 小峰光博)および骨髄異形成症候群に対する新規治療法の開発に関する研究班(班長 平井久丸)平成15 年度第1 回 合同班会議総会  2002
  • 日本人Weak D 6例の分子遺伝学的解析  [Not invited]
    亀崎豊実, 熊田真樹, 近江俊徳, 奥田浩, 岩本禎彦, 高橋順子, 田中光信, 鎌田博子, 小原健良, 瀬尾たい子, 谷慶彦, 梶井英治
    日本DNA多型学会第10回学術集会  2001/11
  • パパニコロウ染色標本における細胞コンタミネーションの鑑別例  [Not invited]
    岩本禎彦, 亀崎豊実, 熊田真樹, 奥田浩, 梶井英治
    第70回日本法医学会関東地方会  2001/10
  • マウスRh1l遺伝子の塩基配列の決定とその構造解析  [Not invited]
    熊田真樹, 亀崎豊実, 奥田浩, 岩本禎彦, 梶井英治
    日本人類遺伝学会第46回大会  2001/10
  • A糖転移酵素遺伝子トランスジェニックラットの作製とA抗原の臓器発現  [Not invited]
    岩本禎彦, 亀崎豊実, 熊田真樹, 奥田浩, 袴田陽二, 小林英司, 梶井英治
    第49回日本輸血学会  2001/05
  • RHAG遺伝子解析  [Not invited]
    亀崎豊実, 岩本禎彦, 熊田真樹, 近江俊徳, 奥田浩, 高橋順子, 瀬尾たい子, 田中光信, 木村恵子, 中出亮, 平山文也, 谷慶彦, 山野孟, 梶井英治
    第49回日本輸血学会総会  2001/05
  • RHD遺伝子転写調節領域の機能解析  [Not invited]
    岩本禎彦, 菅沼弘, 奥田浩, 熊田真樹, 亀崎豊実, 梶井英治
    第85次日本法医学会総会  2001/04
  • Weak DにおけるD抗原活性の低下機序  [Not invited]
    亀崎豊実, 岩本禎彦, 熊田真樹, 高橋順子, 田中光信, 鎌田博子, 小原健良, 瀬尾たい子, 谷慶彦, 近江俊徳, 奥田浩, 梶井英治
    第85次日本法医学会総会  2001/04
  • 交通外傷後に発症し死亡した解離性大動脈瘤破裂の一例  [Not invited]
    熊田真樹, 亀崎豊実, 奥田浩, 岩本禎彦, 梶井英治, 徳留省悟
    第85次日本法医学会総会  2001/04
  • 抗赤血球自己抗体のmimotope 同定へのアプローチ  [Not invited]
    梶井英治, 亀崎豊実, 小山田隆, 熊田真樹, 近江俊徳, 奥田浩, 岩本禎彦
    厚生労働科学研究費補助金(特定疾患対策研究事業)特発性造血障害に関する研究班(班長 小峰光博)および骨髄異形成症候群に対する新規治療法の開発に関する研究班(班長 平井久丸)平成14 年度第2 回 合同班会議総会  2001
  • RH遺伝子の分子進化学的解析  [Not invited]
    奥田浩, 菅沼 弘, 津戸直樹, 熊田真樹, 亀崎豊実, 近江俊徳, 岩本禎彦, 梶井英治
    日本DNA多型学会第9回学術集会  2000/12
  • RHAG遺伝子DNaseI高感受性領域の転写調節活性  [Not invited]
    岩本禎彦, 亀崎豊実, 熊田真樹, 奥田浩, 梶井英治
    日本人類遺伝学会第45回大会  2000/10
  • Rh複合体構成遺伝子におけるヒトとマウスの比較遺伝学的解析  [Not invited]
    近江俊徳, 奥田浩, 亀崎豊実, 岩本禎彦, 梶井英治
    第48回日輸血学会総会  2000/05
  • 自己免疫性溶血性貧血における解離抗体とリコンビナント赤血球抗原との反応性  [Not invited]
    岩本禎彦, 亀崎豊実, 小山田隆, 近江俊徳, 奥田浩, 梶井英治
    第48回日本輸血学会  2000/04
  • RHAG遺伝子5'上流域の赤芽球特異的DNaseI高感受性領域の同定  [Not invited]
    岩本禎彦, 奥田浩, 山崎昌子, 近江俊徳, 梶井英治
    第84次日本法医学会総会  2000/04
  • 川崎病後の虚血心を伴った急死の一剖検例  [Not invited]
    亀崎豊実, 岩本禎彦, 奥田浩, 近江俊徳, 梶井英治
    第84次日本法医学会総会  2000/04
  • Weak D症例におけるRHD遺伝子発現量の解析  [Not invited]
    亀崎豊実, 岩本禎彦, 近江俊徳, 奥田浩, 田中光信, 高橋順子, 瀬尾たい子,谷慶彦, 梶井英治
    第48回日本輸血学会総会  2000/04
  • RH遺伝子座の全構造解析とその意義  [Not invited]
    奥田浩, 菅沼 弘, 津戸直樹, 亀崎豊実, 近江俊徳, 岩本禎彦, 梶井英治
    第84次日本法医学会総会  2000/04
  • 自己免疫性溶血性貧血の主要自己抗原Rhポリペプチドの発現制御機構に関する検討(マウスRhced遺伝子の塩基配列の決定とその構造解析)  [Not invited]
    梶井英治, 熊田真樹, 亀崎豊実, 小山田隆, 奥田浩, 岩本禎彦
    厚生科学研究費補助金(特定疾患対策研究事業)特発性造血障害に関する研究班(班長 小峰光博)および骨髄異形成症候群に対する新規治療法の開発に関する研究班(班長 平井久丸)平成13年度 第2回合同班会議総会  2000
  • RH遺伝子座におけるAlu配列の解析とその意義  [Not invited]
    奥田浩, 菅沼弘, 津戸直樹, 亀崎豊実, 近江俊徳, 山崎昌子, 岩本禎彦, 梶井英治
    日本人類遺伝学会第44回大会  1999/11
  • Rh weak D例の遺伝子解析  [Not invited]
    亀崎豊実, 近江俊徳, 奥田浩, 田中光信, 高橋順子, 瀬尾たい子, 谷慶彦, 岩本禎彦, 梶井英治
    第68回日本法医学会関東地方会  1999/10
  • 自己免疫性溶血性貧血について  [Not invited]
    梶井英治, 亀崎豊実, 小山田隆, 近江俊徳, 奥田浩, 岩本禎彦, 小峰光博
    厚生省特定疾患血液系疾患研究班・特発性造血障害に関する研究班, 平成11年度第1回班会議総会  1999/07
  • レトロウイルスベクターを用いたRHD遺伝子の発現解析  [Not invited]
    岩本禎彦, 奥田浩, 山崎昌子, 近江俊徳, 梶井英治
    第83次日本法医学会総会  1999/05
  • Amorph Rh alleleの分子遺伝学的解析  [Not invited]
    山崎昌子, 奥田浩, 近江俊徳, 河野正樹, 津戸直樹, 菅沼弘, 小山田隆, 岩本禎彦, 石森崇平, 支倉逸人, 梶井英治
    第83次日本法医学会総会  1999/05
  • 親子鑑定例に見い出されたvWAアリル21の同定  [Not invited]
    近江俊徳, 永井淳, 奥田浩, 岩本禎彦, 大谷勲, 梶井英治
    第83次日本法医学会総会  1999/05
  • RHAG遺伝子の発現調節機構の解析  [Not invited]
    岩本禎彦, 近江俊徳, 山崎昌子, 奥田浩, 梶井英治
    第47回日本輸血学会総会  1999/05
  • アリル特異的プライマーを用いたPCR法によるPartial D(Ⅵ)遺伝子型の同定法について  [Not invited]
    近江俊徳, 津戸直樹, 奥田浩, 岩本禎彦, 田中光信, 高橋順子, 谷慶彦, 瀬尾たい子, 梶井英治
    第47回日本輸血学会総会  1999/05
  • The sequence analysis of the spacer region between the RHD and RHCE genes.  [Not invited]
    Okuda H, Omi T, Iwamoto S, Kajii E
    6th Indo Pacific Congress on Legal Medicine and Forensic Sciences  1998/07
  • 新たに見い出されたDⅤa遺伝子とその構造  [Not invited]
    近江俊徳, 奥田浩, 津戸直樹, 岩本禎彦, 田中光信, 高橋順子, 瀬尾たい子, 中出亮, 谷慶彦, 冨田忠夫, 柴田弘俊, 村瀬隆治, 梶井英治
    第46回日本輸血学会総会  1998/05
  • RH遺伝子の多型解析による分子進化へのアプローチ  [Not invited]
    藤原寛行, 佐藤郁夫, 奥田浩, 近江俊徳, 岩本禎彦, 梶井英治
    第46回日本輸血学会総会  1998/05
  • RH遺伝子におけるイントロン構造の多様性について  [Not invited]
    奥田浩, 近江俊徳, 藤原寛行, 山崎昌子, 津戸直樹, 河野正樹, 岩本禎彦, 梶井英治
    第82次日本法医学会総会  1998/04
  • 僻地医療における検死状況の調査  [Not invited]
    奥田浩, 近江俊徳, 河野正樹, 津戸直樹, 小山田隆, 岩本禎彦, 梶井英治
    第82次日本法医学会総会  1998/04
  • Partial DにおけるRHD遺伝子  [Not invited]
    近江俊徳, 奥田浩, 津戸直樹, 岩本禎彦, 田中光信, 岡本衣久子, 高橋順子, 瀬尾たい子, 谷慶彦, 柴田弘俊, 梶井 英治
    日本DNA多型学会第5回学術集会  1997/12
  • 2つのRh血液型遺伝子(RHD及びRHCE)間をつなぐスペーサー領域の解析とその意義  [Not invited]
    奥田浩, 河野正樹, 近江俊徳, 山崎昌子, 藤原寛行, 岩本禎彦, 梶井英治
    日本人類遺伝学会第42回大会  1997/10
  • RHCe遺伝子とRHce遺伝子のハイブリッドが疑われる1例  [Not invited]
    津戸直樹, 近江俊徳, 奥田浩, 岩本禎彦, 田中光信, 高橋順子, 瀬尾たい子
    第66回日本法医学会関東地方会  1997/10
  • RHD, RHCE遺伝子の構造解析  [Not invited]
    奥田浩, 河野正樹, 山崎昌子, 津戸直樹, 岩本禎彦, 梶井英治
    第81次日本法医学会総会  1997/04
  • レトロウィルスベクターを用いたRHCE遺伝子の発現解析  [Not invited]
    岩本禎彦, 奥田浩, 梶井英治
    第81次日本法医学会総会  1997/04
  • Rhシステム血液型とD1S80型に不一致を認めた母子例  [Not invited]
    河野正樹, 奥田浩, 小山田隆, 岩本禎彦, 梶井英治
    第81次日本法医学会総会  1997/04
  • 各種Rh variantにおけるRh genotypingとその問題点  [Not invited]
    奥田浩, 河野正樹, 近江俊徳, 岩本禎彦, 田中光信, 瀬尾たい子, 大久保康人, 梶井英治
    日本DNA多型学会第5回学術集会  1996/12
  • RHCE遺伝子欠失とCE-D-CEハイブリッド遺伝子を認めた-D-の1例  [Not invited]
    奥田浩, 河野正樹, 石田萌子, 野村昌作, 福原資郎, 梶井英治
    日本人類遺伝学会第41回大会  1996/10
  • Rhnull 症候群におけるRH関連遺伝子の解析  [Not invited]
    岩本禎彦, 奥田浩, 梶井英治
    日本人類遺伝学会第41回大会  1996/10
  • チューインガム試料における血液型判定の可能性-genotypingを通して  [Not invited]
    奥田浩, 河野正樹, 岩本禎彦, 梶井英治
    第65回日本法医学会関東地方会  1996/10
  • RHD gene in RhD-negative Japanese donors.  [Not invited]
    Okuda H, Kawano M, Oyamada T, Iwamoto S, Tanaka M, Seno T, Okubo Y, Kajii E
    International Society for Forensic Haemogenetics, Hakone Symposium on DNA Polymorphisms  1996/08
  • RH遺伝子におけるイントロン4の構造解析とその意義  [Not invited]
    奥田浩, 河野正樹, 田中光信, 瀬尾たい子, 大久保康人, 梶井英治
    第80次日本法医学会総会  1996/04
  • 肝硬変の経過中, Torsarde de pointesをきたした一症例  [Not invited]
    奥田浩, 亀崎豊実, 徳山直美, 吉田泰之
    肝硬変研究会  1994/11
  • 造血器腫瘍に対するAra−CとG−CSFの併用療法の検討  [Not invited]
    奥田浩, 秋藤洋一, 植木寿一, 中本周
    第41回山陰血液同好会  1993/10
  • 溶血性貧血の一例  [Not invited]
    秋藤洋一, 奥田浩, 植木寿一, 中本周
    第11回鳥取血液研究会  1993/10
  • 高齢者の白血病治療の工夫  [Not invited]
    奥田浩, 秋藤洋一, 植木寿一, 中本周
    平成5年度鳥取県医師会秋季医学会  1993/10
  • 同種骨髄移植後,ヒトパルボウイルスB19が持続感染した一例  [Not invited]
    奥田浩, 田中孝幸, 秋藤洋一, 植木寿一
    第15回山陰感染症化学療法研究会  1993/06
  • CMMoLと思われる一例  [Not invited]
    奥田浩, 秋藤洋一, 植木寿一, 中本周 他
    第29回山陰血液同好会  1988/03
  • 病原大腸菌感染によると考えられる心合併症を伴った川崎病の一乳児例  [Not invited]
    奥田浩, 大谷恭一, 奈良井栄, 赤松由美子, 安東吾郎
    第18回山陰地区感染症懇話会集会  1987/06
  • 急性膵炎に続発したMOF症例の検討  [Not invited]
    奥田浩, 加藤一吉, 岸清志, 水本清
    山陰MOF研究会  1987/05
  • 電気水圧衝撃波による胆道鏡下砕石術の経験  [Not invited]
    岸清志, 加藤一吉, 山本洋之, 那須博司, 奥田浩
    第7回鳥取消化器疾患研究会  1987/02
  • 腸閉塞症状を呈した小児の結腸悪性リンパ種の一例  [Not invited]
    奥田浩, 加藤一吉, 山本洋之, 岸清志, 那須博司
    山陰外科集談会  1986/12
  • 多発性骨髄腫治療中に発症した急性骨髄性白血病の一例  [Not invited]
    奥田浩, 那須博司, 秋藤洋一, 塩宏, 田村公平, 植木寿一, 中本周
    第28回山陰血液同好会  1986/10
  • 十二指腸腫瘍の一例  [Not invited]
    奥田浩, 那須博司, 秋藤洋一, 宮崎博実, 田村公平, 岡本公男, 植木寿一, 佐藤 徹, 岸清志, 井上雅勝, 山本洋之, 加藤一吉, 中本周
    第6回鳥取消化器疾患研究会  1986/07

MISC

  • M Kumada, S Iwamoto, T Kamesaki, H Okuda, E Kajii  GENE  299-  (1-2)  165  -172  2002/10  [Not refereed][Not invited]
     
    The mouse genomic sequence of the region containing the gene Rhced, the orthologue to the human gene RH30, was determined to elucidate the structure of Rhced and its flanking regions and to compare these with the corresponding human genomic region. Two genes, Smpl and AK003528 (an orthologue of FLJ10747), flank Rhced. Neither sequences homologous to the characteristic nucleotide elements flanking the RHD gene in humans (rhesus boxes) nor an additional Rh gene were found within the mouse region sequenced. This result and that of a previous report demonstrate that this chromosomal region of the mouse comprises five genes (FLJI0747-RHCE-SMP1-NPD014-P29) that exhibit syntenic homology with the corresponding human region, which suggests that the RHD gene and rhesus boxes were inserted later. Evaluations of tissue distribution and subcellular localization of these genes indicate that the SMPI orthologue has a ubiquitous tissue distribution and cytoplasmic localization, whereas AK003528 is expressed slightly higher in testis with a strong subcellular localization in the nucleus. Despite the steady improvements in the draft sequence of the human genome, this study demonstrates the continuing benefits of comparative genetic analyses in increasing our understanding of human genomic structure. (C) 2002 Elsevier Science B.V. All rights reserved.
  • A糖転移酵素遺伝子トランスジェニックラットの作製とA抗原の臓器発現
    岩本 禎彦, 亀崎 豊実, 熊田 真樹, 奥田 浩, 袴田 陽二, 小林 英司, 梶井 英治  日本輸血学会雑誌  47-  (2)  200  -200  2001/04  [Not refereed][Not invited]

Awards & Honors

  • 2000/12 日本DNA多型学会 第2回DNA多型学会優秀研究賞
     RH遺伝子の分子遺伝学的解析 
    受賞者: 奥田 浩、菅沼 弘、津戸 直樹、熊田 真樹、亀崎 豊実、 近江 俊徳、岩本 禎彦、梶井 英治

Research Grants & Projects

  • Development of model animal to reveal the antibody production for ABO blood group antigens.
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2003 -2004 
    Author : IWAMOTO Sadahiko, KAMESAKI Toyomi, OKUDA Hiroshi, KUMADA Maki, OMI Toshinori, FUKUI Emiko
     
    Histo-blood group ABH antigens are important not only for blood transfusion but also for organ transplantation. To improve the clinical management of transplantation, we have established transgenic rats expressing human A-transferase and B-transferase gene. Wild Wistar rats expressed A-antigen in salivary gland, intestine, and urinary bladder tissue, but B-antigen was not stained in any organs studied. A-transgenic rats expressed A-antigen in ectopic tissue of the brain plexus, type II lung epithelium, pancreas, and epidermis. B-antigen in the B-transgenic rat was expressed in the same organs as A-transgenic rats. When small intestines of wild Wistar were transplanted into A- or B-trangenic rats, the grafts were rapidly rejected compared to the grafts from A- or B-transgenic rats into wild. The systemic expression of A- or B-antigens may have modified the terminal organization of sugar chain antenna and have stimulated the innate-immune system. We have cloned authologous genes of ABO transferase from Wistar rat, which consisted of three A-transferase and one B-transferase genes. These cDNAs were mapped on rats genome draft sequence. Rat chromosome 1 accommodates B-transferase gene and chromosome 3 encodes tandem arrayed three A-transferase copies. These facts indicated that the A- and B-transferase genes were established as paralogous genes in some mammals. Primates encode single ABO gene. If the ABO ancestral genes consisted of multicopy genes with A and B transferase activity like rats, they must donate or accept gene fragments from each other and may produce a locus composed of A-alleles and B-alleles. The multicopy genes may possibly gather and bundle into a single gene through unequal cross over. This estimation must be resolved by further genome projects in other mammals.
  • The analysis of Rh antigen (polypeptide) function and the molecular evolution of orthologous RH genes in various species.
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2003 -2004 
    Author : OKUDA Hiroshi, KAJII Eiji, IWAMOTO Sadahiko, KAMESAKI Toyomi, OMI Toshinoro, KUMADA Maki
     
    The Rh blood group discovered by Levine and Stetson is clinically one of the most important blood groups similar to ABO system. It is indicated that the Rh system was encoded on two genes termed RHCE and RHD, which are closely linked, highly homologous and consist of ten exons each. The RH genes are located in chromosome 1p 34.3-36.1. Many serological investigations have revealed and a lot of variants such as D--, partial D and antigens from forty up were identified. The RHD and RHCE genes totalled 57295 bp and 57831 bp in length, respectively. It is thought that multiple recombination (and/or gene conversion), nucleotide substitutions, small nucleotide gaps, replication slippage of microsatellite, large nucleotide gaps (due to Alu sequence) and the high level of the homology(%) between both RH genes is the important factors in the formation and evolution of both RH genes and Rh variants. We analyzed weakD phenotypes, which are Rh variant, and reported the molecular genetic background of them. Due to the findings obtained by the analysis of these Rh variants(weakD), we speculated the mechanism of the expression of Rh antigen(polypeptide). It is presumed that human Rh family (superfamily) consists of the RH (RHCE and RHD), RHAG (RH5O), RHBG and RHGK (RHCG) genes. It is speculated that Rh superfamily is associated with ammonium transporter by biochemical evidence and Genbank search. The RH, RHAG and RHBG/RHGK genes derived from ammonium transporter might have independently followed different evolutionary pathways by our phylogenetic tree analysis(the neighbor-joining method). By analyzing the orthologous RH gene superfamily in pig, we determined the porcine RH and RHBG genes are mapped in pig chromosomes 6q22-q23 and 4q21-q22, respectively.
  • The study on the mechanism of production of autoantibodies in autoimmune hemolytic anemia.
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2003 -2004 
    Author : KAMESAKI Toyomi, KUMADA Maki, OMI Toshinori, OKUDA Hiroshi, IWAMOTO Sadahiko, KAJII Eiji
     
    Rh polypeptides, especially RhCcEe, are the common autoantigens in autoimmune hemolytic anemia (AIHA). Rh blood group antigens and the autoantigens in AIHA are conformational antigens and constructed by six extracellular loops of Rh polypeptides. Identification of replica of autoantigen epitopes (mimotope) was performed by means of screening phage displayed random peptide library. 1.Identification of Rh mimotopes, reacting monoclonal anti-D antibody and/or anti-E antibody. 2.Identification of autoantigen mimotopes, reacting autoantibody from AIHA patients. 3.Six out of eight of the autoantibodies reacted the Rh mimotopes, therefore it is assumed that the Rh mimotopes might be included into autoantigen mimotopes. 4.These mimotopes will make it possible to identify and categorize autoantibodies in AIHA, to map epitopes of autoantigens on Rh peptides and to verify molecular mimicry between foreign antigens and Rh polypeptides as the etiology of autoantibodies in AIHA.
  • Further investigation on the Rh blood group system for the expression of the RH gene and the epitopes of the Rh antigens
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2001 -2002 
    Author : KAJII Eiji, KAMESAKI Toyomi, OKUDA Hiroshi, IWAMOTO Sadahiko, KUMADA Maki
     
    The mouse genomic sequence of the region containing the gene Rhced, the orthologue to the human gene RH30, was entirely determined and compared with the corresponding human genomic region. Two genes Smpl and AK003528 (an orthologue of FLJ10747), flank Rhced. Neither sequences homologous to the characteristic nucleotide elements flanking the RHD gene in human (rhesus boxes) nor an additional Rh gene were found within the mouse region sequenced. This result demonstrate that this chromosomal region of the mouse comprises five genes (FLJ10474-RHCE-SMP1-NPD014-P29) that exhibit syntenic homology with the corresponding human region, which suggests that the RHD gene and rhesus boxes were inserted later. The molecular characterization of weak D and partial D phenotypes was performed. The mutations - G212C (new weak D type), V270G (weak D type 1), and G358A (type 2) - in transmembranous regions had obvious effects on the D epitopes recognized by monoclonal anti-D antibodies. This result provide direct evidence that these mutations can account for weak D phenotypes. A novel partial D phenotype, termed DT1 was found. The DT1 phenotype affected the D polypeptide within the fourth external loop, resulting in a new RHD-CE (entire exon 5)-D hybrid gene. It is worth noting that P226, encoded by exon 5, is derived from E of RhCE in the DT1 polypeptide. The screening system for detecting the autoantigens in autoimmune hemolytic anemia (AIHA) was constructed by using several recombinant Rh antigens or band 3 protein-expressing KU812 cells. The autoantigens in twenty patients with AIHA were Rh-related ones in 15 cases and band 3 protein in 7 cases.
  • The molecular genetic analysis and its application of single nucleotide polymorphisms and microsatellite in both RH genes.
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2001 -2002 
    Author : OKUDA Hiroshi, KAMESAKI Toyomi, IWAMOTO Sadahiko, KAJII Eiji, OMI Toshinoro, KUMADA Maki
     
    The Rh blood group discovered by Levine and Stetson is clinically one of the most important blood groups. Many serological investigations have revealed and a lot of variants such as D-, partial D and antigens from forty up were identified. Studies during the 1980s confirmed that Rh antigens were polypeptides. Their cDNAs coding Rh polypeptides were cloned and compared with each phenotype. Investigations during the 1990s indicated that the Rh system was encoded on two genes termed RHCE and RHD, which are closely linked, highly homologous and consist of ten exons each. It is thought that multiple recombination (and/or gene conversion), nucleotide substitutions, small nucleotide gaps, replication slippage of microsatellite, large nucleotide gaps (due to Alu sequence) and the high level of the homology (%) between both RH genes is the important factors in the formation and evolution of both RH genes and Rh variants. We analyzed DTI (partial D), Rh_ and weakD, which are Rh variant, and reported the molecular genetic background of them. Due to the findings obtained by the analysis of these Rh variants (DTI(partial D), Rhmod and weakD), we speculated the mechanism of the expression of Rh antigen (polypeptide). The mouse genomic sequence of the region containing the gene Rhced, the orthologue to the human gene RH30, was determined to elucidate the structure of Rhced and its flanking regions and to compare these with the corresponding human genomic region. Due to the analysis of phylogenetic trees, it is supposed that the RHCE changes into the gene which acquire other function by positive selection and the RHD genes varies into pseudogene in process of time during evolution.
  • Establishment of transgenic rat expressing human A or B Transferase gene and cloning of rat paralogous genes equivalent of human histo-blood group ABO gene.
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2001 -2002 
    Author : IWAMOTO Sadahiko, KUMADA Maki, OKUDA Hiroshi, KAMESAKI Toyomi, KAJII Eiji
     
    Histo-blood group ABH antigens are important not only for blood transfusion but also for organ transplantation. To improve the clinical management of transplantation, development of ABO-mismatched animal models is desirable. Rats are more suitable for ordinary examination of organ transplantation because of the larger body size compared with mice. To evaluate the availability of rats as an animal model, we studied rat ABO homologue and established human A- and B-transferase transgenic rats. A DNA fragment corresponding to exon 7 of the human ABO gene was amplified from Wistar rat genomic DNA and sequenced. Using the amplified fragments as a probe for Southern blotting, multiple hybridized bands appeared on both EcoRI and BamHI digested genomes of seven rat strains, which showed variations in the band numbers among the strains. Four cDNAs were cloned from a Wistar rat, three of which showed A-transferase activity and one of which showed B-transferase activity. These activities were dependent on the equivalent residues at 266 and 268 of human ABO transferase. Wild Wistar rats expressed A-antigen in salivary gland, intestine, and urinary bladder tissue, but B-antigen was not stained in any organs studied, while a transcript from the ABO homologue with B-transferase activity was ubiquitous. Human A-transferase and B-transferase were transferred into Wistar rats. A-transgenic rats expressed A-antigen in ectopic tissue of the brain plexus, type II lung epithelium, pancreas, and epidermis. B-antigen in the B-transgenic rat was expressed in the same organs as A-transgenic rats. If the hominoid ABO ancestral genes consisted of multicopy genes with A and B transferase activity like rats, they must donate or accept gene fragments from each other and may produce a locus composed of A-alleles and B-alleles. This estimation must be resolved by further genome projects in rats and other mammals.
  • Molecular genetical analysis of the epitopes on Rh blood group antigen and establishment of genetic examination system in RH genes.
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B).
    Date (from‐to) : 1999 -2000 
    Author : KAJII Eiji, OMI Toshnori, OKUDA Hiroshi, IWAMOTO Sadahiko, KUMADA Maki, KAMESAKI Toyomi
     
    We determined the entire nucleotide sequences of both RHD and RHCE genes. Based on the data of these nucleotide sequences, we analyzed the genomic structure of both RH genes in detail. Various short tandem repeats (STRs) and many interspersed nuclear elements, for instance, Alu sequences were identified in both genes. By the alignment analysis of both RH genes, we confirmed multiple recombinations within 2〜3kb in introns 1 and 2. It was speculated that intron 2 in the RHCE (C) gene was produced by two recombinations between RHCE (c) and RHD genes and the following insertion of Alu-Sx. It was supported that Rh50 glycoprotein, which constituted the core of the Rh complex along with Rh polypeptide, showed the erythroid-specific expression. For the purpose of explaining the mechanism of the regulation for the expression in the RHAG gene, we identified and cloned an erythroid specific major DNaseI hypersensitive site (HS). HS located about 10kb upstream from the translation start site of the RHAG gene. A short core enhancer sequence of 195bp that corresponded with the major HS and possessed position- and orientation-independent enhancer activity in K562 cells. Homology plot analysis indicated that the enhancer region was conserved in human and mouse. The GATA motifs bound GATA-1 and mutagenesis analysis revealed that the proximal one is critical for the enhancing activity. In Rh blood system, molecular genetical analysis of various Rh variants smoothly developed. As for partial D variant, we were able to identify new type. Furthermore we proved that weak D variant possessed the qualitative and quantitative change of the RhD antigen.
  • Molecular cloning and variant analysis of the genes associated with Rh blood group antigens.
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 1998 -1999 
    Author : IWAMOTO Sadahiko, OMI Toshinori, KAJI Eiji, OKUDA Hiroshi
     
    Rhnull phenotypes, which lack all Rh antigens, were analyzed by molecular-genetic procedures and categorized into two groups by the genetic backgrounds; 'amorph type' results from abnormality of both RHCE and RHD genes and 'regulator type' results from abnormality of RH5O gene independent locus from RH. These results confirmed that Rh5O glycoprotein is an indispensable factor for the expression of Rh antigens on erythrocyte membrane. A erythroid cell line (KU812E) originally expressing Rh5O glycoprotein was transduced by retroviral vector encoding RhD or RhCE cDNAs. The cells transduced Rh cDNAs expressed the respective Rh antigens. On the contrary, non-erythroid cell line (HEK293) not expressing Rh5O glycoprotein failed to express Rh antigens on the plasma membrane despite the induction of both cDNAs of Rh and Rh5O. Immuno-electro-microscopic analysis of the induced cell lines revealed that the cell lines expressed Rh5O antigen on the cytoplasmic-organella membranes. It was suggested that non-erythroid cell lack the expression of erythroid specific factors other than Rh and Rh5O to express Rh antigens on the plasma membrane. Then, we have intended to induce further a human cDNA library established from bone marrow into the double transfected HEK293 and screen the induced cell stained by anti-Rh antibodies through cell-sorter. However, the cDNA clone which induce the expression of Rh antigens on the plasma membrane of non-erythroid is still under hunting. We also isolated the promoter region of RH50 gene and characterized it. Just 5' flanking sequence of RH5O gene has an inverse GATA motif which is critically involved in the erythroid specific promoter activity. An erythroid specific DNaseI hypersensitive site was identified in the further up-stream region, which also encoded an inverse GATA motif. These results support further the erythroid dominant expression of the RH5O gene.
  • The study on the nucleotide sequences of the RH genes and the Rh genotyping.
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 1997 -1998 
    Author : KAJII Eiji, KAWANO Masaki, OMI Toshinori, OKUDA Hiroshi, IWAMOTO Sadahiko
     
    The molecular analyses on the Rh blood group showed the following results. (1) The nucleotide sequences of RHD and RHCE genes were almost determined. (2) The nucleotide-sequencing of the spacer region between the RHD and RHCE genes was nearly finished. (3) We identified simple sequence repeat polymorphism in intron 8 of the RHD and RHCE genes, both of which contained the 5bp repeat unit, (AAAAT)n in loci. The polymorphisms of this short tandem repeat (STR) suggests that the RhD-negative with a non-functional RHD gene might have arisen from DCe haplotype via mutation, which abolished the RHD gene. Based on these findings, the STR polymorphisms may shed light upon the molecular evolution of RH haplotype. (4) We demonstrated a genomic organization of the hybrid RHD-CE-D gene leading to the D^ jthenotype, and showed that the D^ gene was generated from gene conversion between the RHD and RHCE genes in relatively small regions. This study also revealed that the presence of a new partial D associated with the D^ phenotype, which we termed the D^-like phenotype. (5) In a propositus with the Rhnull phenotype, the molecular analyses showed a deletion of 122bp in the RHAG-cDNA, which was revealed to be due to a homozygous splicing mutation. This result confirms that the RHAG gene is the most likely candidate for the regulator gene of Rhnufl cases. In a patient with myelodysplastic syndrome (MDS), the phenotype of the Rh system altered from D(+), C(+), c(+), E(+), e(+) to D(-), C(-), c(+), E(-), e(+) according to the progression of MDS.Its reason was demonstrated to be microdeletion containing the RHD and RHCE genes.
  • The study on the autoantigens and their epitopes of autoimmune hemolytic anemia.
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 1997 -1998 
    Author : KAJII Eiji, OMI Toshinori, OKUDA Hiroshi, IWAMOTO Sadahiko
     
    In autoimmune hemolytic anemia (AIHA), the determination of the epitopes of autoantigens directed with anti-red blood cells (RBC) autoantibodies is very important for revealing the mechanism in the failure of immunotolerance. We planed analysing the specificities of autoantibodies eluted from RBC of 21 AIHA patients. For the purpose of preparing panel cells, we constructed retroviral gene coding 4 Rh-cDNAs, which contain RhD, cE, ce, and CE, and introduced them into KU812E cells. All the Rh antigens other than RhC were confirmed to be expressed by flow cytometory. The reactivities of autoantihodies against these panel cells were examined by flow cytometory. The results showed specificities against the Rh polypeptides in 10 of 21 cases (47.6%). Nine of these 10 autoantibodies reacted with the RhC(c)E(e) polypeputide and three did with the RhD polypeptide. These data suggested that the RhC(c)E(e) polypeptide play an important role in pathogenesis of AIHA and that the epitopes directed with autoantibodies exist on the common region of the Rh polypeptides.
  • Human genetic analysis on the regulation of Duffy gene expression.
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 1995 -1996 
    Author : IWAMOTO Sadahiko, KAJII Eiji, OKUDA Hiroshi
     
    The genomic structure of Duffy gene has been shown not to be split by introns, even in its 5' and 3' untranslated regions. The genes of IL-8 receptors, which are the highly homologous genes of Duffy gene, are not split by introns within the coding regions but are split in the 5' untranslated regions. Then we reanalyzed the transcriptional start position by 5'-rapid amplification of cDNA ends (5'-RACE), and identified a novel first exon and spliced form mRNA that was predominant transcript in both erythroid and postcapillary venule endothelium. The 5' flanking region of the novel first exon was regarded as the transcription controlling unit for both tissues. However, the transcriptional start position in endotherium was 48 bases upstream from that of the erythroid cells. And the 48 bases included an inverted consensus binding site for the GATA transcription factor. We found homozygous one base substitution at the GATA motif in black individuals with Fy (a-b-) phenotype. The Fy (a-b-) individuals have been shown not to produce Duffy mRNA in the bone marrow, but to produce it in endothelial cells. The tissue-specific lacking of expression in Fy (a-b-) indicates that the transcription control of Duffy gene is under tight tissue-specific regulation. The 5' flanking region of the novel first exon was inserted in the upstream of CAT reporter gene and was analyzed the transcription controlling efficiency. The promotor sequence of Duffy positives efficiently transcribed the reporter gene in both erythroid and endothelial cells. When one base substitution of Duffy negatives was introduced in the GATA motif, the promotor activity in erythroid cells was completely diminished. These data clearly explain the erythroid specific disruption of Duffy gene expression in black type Fy (a-b-). The selective pressure other than Plasmodium vivax have to be studied in the future on the saving of Duffy glycoprotein along endothelial cells in Fy (a-b-) individuals and the fixing the phenotype in West Africa.


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