Graduate School of Medicine / School of Medicine, Faculty of Medicine

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Injection & Bioresponse

Legal Medicine

Legal medicine is essentially the application of scientific methods and techniques to matters involving the public: that covers a lot of ground. Every science from chemistry to medicine, from biology to statistics, from dentistry to anthropology, can be a forensic science if it has some applications to the law or public matter. Especially, our group has been focusing on human genetics, which is one of the important matters of legal medicine in Japan. We have performed researches on ABO blood group, which is one of the important genetic markers in human identification. Recently, we have succeeded to identify the erythroid cell-specific enhancer and found the deletion or impairment of the enhancer element in variant blood type Bm, developing valuable methods for the genetic diagnosis of Bm based on PCR analysis.

  • Staff
  • Research & education
  • Clinical Activities
  • Citizen Activities
  • Achievement
  • History

Staffs

Professor Yoshihiko KOMINATO, M.D., Ph. D.
Lecturer Rie SANO, M.D., Ph. D.
Assistant Professor Yoichiro TAKAHASHI,M.D., Ph. D.

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Research & Education

Research content

1) Fundamental studies on human ABO genes. We have studied the transcriptional regulation of the ABO genes with the identification of the erythroid cell-specific transcriptional regulatory element in the first intron, and found that the deletion or mutation of the element is associated with variant phenotype Bm
2) Fundamental studies on deoxyribonuclease I (DNase I). We have previously demonstrated that ischemia caused by acute myocardial infarction (AMI) induces an abrupt increase of serum DNase I activity. Therefore, we have investigated the transcriptional regulation of the DNASE1 with the demonstration of promoter and transcription factor involved in gene expression. Moreover, both elevated promoter activity and alternative splicing have been shown to play roles in hypoxia-induced up-regulation of DNASE1.
3) Postmortem computed tomography (CT). We have carried out postmortem CT prior to autopsies and validated the usefulness of the postmortem CT. We have tried to develop a new application of the postmortem CT to investigate the cause of death.

Business education

1) Course of forensic science involving lecture and practical exercise. We use an integrated curriculum including wide ranging matters from basic science to practical forensic pathology and the law relating to the practice of medicine.
2) Course of human genetics. We use an integrated curriculum based on wide ranging matters from basic molecular genetics to hereditary disorders.
3) Selective course of forensic sciences. We use a curriculum for personal identification based on the genetic markers in human blood.
4) Graduate school of medicine; lectures, exercises and seminars for forensic sciences. We use a curriculum for the scientific methods and techniques for personal identification based on the genetic markers including blood group antigens, isozyme patterns, and DNA polymorphisms in human blood, urine, semen, and saliva.

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Clinical Activities

Our department is not involved in clinical activity.

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Citizenship Activities

We perform autopsies more than one hundred a year, and we have several seminars on forensic pathology for medical doctors and policemen.

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Achievements

1.Sano R, Kuboya E, Nakajima T, Takahashi Y, Takahashi K, Kubo R, Kominato Y, Takeshita H, Yamao H, Kishida T, Isa K, Ogasawara K, Uchikawa M. A 3.0-kb deletion including an erythroid cell-specific regulatory element in intron 1 of the ABO blood group gene in an individual with the  Bm phenotype. Vox Sang, 108: 310-313, 2015.

2.Sano R, Nogawa M, Nakajima T, Takahashi Y, Takahashi K, Kubo R, Kominato Y, Yokohama A, Tsukada J, Yamao H, Kishida T, Ogasawara K, Uchikawa M. Blood group B gene is barely expressed in in vitro erythroid culture of  Bm-derived CD34+ cells without an erythroid cell-specific regulatory element. Vox Sang ,108: 302-309, 2015.

3.Tokue H, Takahashi Y, Hirasawa S, Awata S, Kobayashi S, Shimada T, Tokue A, Sano R, Kominato Y, Tsushima Y. Intestinal obstruction in a mentally retarded patient due to pica. Ann Gen Psychiatry, 14:22, 2015.

4.Murayama M, Takahashi Y, Sano R, Watanabe K, Takahashi K, Kubo R, Kuninaka H, Kominato Y. Characterization of five cases of suspected bathtub suicide. Leg Medcine, 13:576-578, 2015.

5.Fujihara J, Yasuda T, Iida R, Ueki M, Sano R, Kominato Y, Inoue K, Kimura-Kataoka K, Takeshita H.Global analysis of genetic variations in a 56-bp variable number of tandem repeat polymorphisms within the human deoxyribonuclease I gene. Leg Medcine,17:283-286, 2015.

6.Watanabe K, Takahashi Y, Sano R, Nakajima T, Kominato Y, Kobayashi S,  Shimada T, Takei H, Awata S, Hirasawa S. Brain fragility can be estimated by its putative signs on postmortem computed tomography. Legal Medcine, 17: 98-101, 2015.

7.Sano R, Takahashi Y, Nakajima T, Yoshii M, Kubo R, Takahashi K, Kominato Y, Takeshita H, Yasuda T, Tsuneyama H, Uchikawa M, Isa K, Ogasawara K: ABO  chimerism with a minor allele detected by the PNA-mediated PCR clamping method. Blood Transfusion, 12: 431-434, 2014.

8.Takahashi Y, Isa K, Sano R, Nakajima T, Kubo R, Takahashi K, Kominato Y, Michino J, Masuno A, Tsuneyama H, Ito S, Ogasawara K, Uchikawa M: Presence of nucleotide substitutions in transcriptional regulatory elements such as the erythroid cell-specific enhancer-like element and the ABO promoter in individuals with phenotypes A3 and B3, respectively. Vox Sang, 107:171-180, 2014.

9.Takahashi Y, Isa K, Sano R, Nakajima T, Kubo R, Takahashi K, Kominato Y, Tsuneyama H, Ogasawara K, Uchikawa M: Deletion of the RUNX1 binding site in the erythroid cell-specific regulatory element of the ABO gene in two individuals with the Am phenotype. Vox Sang, 106:167-175, 2014.

10.Takahashi Y, Sano R, Nakajima T, Kominato Y, Kubo R, Takahashi K, Ohshima N, Hirano T, Kobayashi S, Shimada T, Tokue H, Awata S, Hirasawa S, Ishige T: Combination of postmortem mass spectrometry imaging and genetic analysis reveals very long-chain acyl-CoA dehydrogenase deficiency in a case of infant death with liver steatosis. Forensic Sci Int, 244:e34-e37, 2014.

11.Ueki M, Kimura-Kataoka K, Takeshita H, Fujihara J, Iida R, Sano R, NakajimaT, Kominato Y, Kawai Y, Yasuda T: Evaluation of all non-synonymous single nucleotide polymorphisms (SNPs) in the genes encoding human deoxyribonuclease I and I-like 3 as a functional SNP potentially implicated in autoimmunity. FEBS J, 281:376-90, 2014.

12.Hata Y, Mori H, Tanaka A, Fujita Y, Shimomura T, Tabata T, Kinoshita K, Yamaguchi Y, Ichida F, Kominato Y, Ikeda N, Nishida N: Identification and characterization of a novel genetic mutation with prolonged QT syndrome in an unexplained postoperative death. Int J Legal Med, 128:105-115, 2014.

13.Murakami T, Tajika Y, Ueno H, Awata S, Hirasawa S, Sugimoto M, Kominato Y, Tsushima Y, Endo K, Yorifuji H: Integrated education of gross anatomy and CT radiology for current advances in medicine. Anat Sci Edu, 7:438-449, 2014.

14.Nakajima T, Sano R, Takahashi Y, Kubo R, Takahashi K, Kominato Y, Tsukada J, Takeshita H, Yasuda T, Uchikawa M, Isa K and Ogasawara K: Mutation of the GATA site in the erythroid cell-specific regulatory element of the ABO gene in a Bm subgroup individual. Transfusion, 53: 2917-2927, 2013.

15.Sano R, Hirasawa S, Awata S, Kobayashi S, Shimada T, Takei H, Takahashi Y and Kominato Y: Use of postmortem computed tomography to reveal acute subdural hematoma in a severely decomposed body with advanced skeletonization.Leg Med, 15: 32-34, 2013.

16.Takahashi Y, Sano R, Kominato Y, Takei H, Kobayashi S, Shimada T, Awata S and Hirasawa S: Usefulness of postmortem computed tomography for demonstrating cerebral hemorrhage in a brain too fragile for macroscopic examination. Journal of Forensic Radiology and Imaging, 1: 212-214, 2013.

17.Sano R, Nakajima T, Takahashi K, Kubo R, Kominato Y, Tsukada J, Takeshita H, Yasuda T, Ito K, Maruhashi T, Yokohama A, Isa K, Ogasawara K and Uchikawa M: Expression of ABO blood-group genes is dependent upon an erythroid cell-specific regulatory element that is deleted in persons with the Bm phenotype. Blood, 119: 5301-5310, 2012.

18.Kimura-Kataoka K, Yasuda T, Fujihara J, Toga T, Ono R, Otsuka Y, Ueki M, Iida R, Sano R, Nakajima T, Kominato Y, Kato H and Takeshita H: Genetic and expression analysis of SNPs in the human deoxyribonuclease II: SNPs in the promoter region reduce its in vivo activity through decreased promoter activity. Electrophoresis, 33: 2852-2858, 2012.

19.Soejima M, Fujimoto R, Agusa T, Iwata H, Fujihara J, Takeshita H, Minh TB, Trang PT, Viet PH, Nakajima T, Yoshimoto J, Tanabe S and Koda Y: Genetic variation of FUT2 in a Vietnamese population: identification of two novel Se enzyme-inactivating mutations. Transfusion, 52: 1268-1275, 2012.

20.Fujihara J, Takeshita H, Kimura-Kataoka K, Yuasa I, Iida R, Ueki M, Nagao M, Kominato Y and Yasuda T: Replication study of the association of SNPs in the LHX3-QSOX2 and IGF1 loci with adult height in the Japanese population; wide-ranging comparison of each SNP genotype distribution. Leg Med, 14: 205-208, 2012.

21.Takeshita H, Fujihara J, Ueki M, Iida R, Koda Y, Soejima M, Yuasa I, Kato H, Nakajima T, Kominato Y and Yasuda T: Nonsynonymous single-nucleotide polymorphisms of the human apoptosis-related endonuclease–DNA fragmentation factor beta polypeptide, endonuclease G, and Flap endonuclease-1–genes show a low degree of genetic heterogeneity. DNA Cell Biol, 31:36-42, 2012.

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History

Professor Shoei Iseki (1944‒1972) carried out the research on the genetic conversion of bacterial somatic antigen as well as the molecular structure of ABO blood group antigens, and was twice honored for the achievements of those studies by the Japan Academy, followed by application to the Novel Prize. Those studies were performed in cooperation with the succeeding professor Ken Furukawa (1972‒1995), who developed the biochemical and genetic studies on ABO blood group substances. The next professor Koichiro Kishi (1995‒2006), who worked with Shoei Iseki at Gunma University and the National Research Institute of Police Science in Japan for 18 years, established a novel research field “Urogenetics” in which DNases I and II were demonstrated as a new genetic marker, and carried out the research ranging from their molecular genetic basis to clinical applications. The present professor Yoshihiko Kominato (2006‒), who worked in the laboratory under one of Iseki’s colleagues at Toyama University for 16 years, has studied the transcriptional regulation of the ABO genes with the findings of cis/trans-elements and epigenetics, and demonstrated that the deletion or mutation of the enhancer is associated with variant phenotype Bm.