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Affiliation |
Graduate School of Medicine Doctorial Course in Medicine Public Health and Environmental Medicine Department of Forensic Science |
HORIOKA Kie
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Graduating School 【 display / non-display 】
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-2012.03
Hokkaido University Faculty of Health Care Graduated
Graduate School 【 display / non-display 】
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-2020.03
Asahikawa Medical College Graduate School, Division of Medicine Doctor's Course Completed
Campus Career 【 display / non-display 】
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2026.01-Now
Akita University Graduate School of Medicine Doctorial Course in Medicine Public Health and Environmental Medicine Department of Forensic Science Associate Professor
External Career 【 display / non-display 】
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2025.03
Akita University Graduate School of Medicine Associate Professor
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2020.02-2020.09
Karolinska Institutet Forensic Medicine Department of Oncology-Pathology Postdoctoral Researcher
Research Areas 【 display / non-display 】
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Life Science / Molecular biology
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Life Science / Forensics medicine
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Life Science / Human pathology
Research Achievements 【 display / non-display 】
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Wischnewsky spots relate to ketosis/ketoacidosis regardless of the cause of death - A systematic autopsy study.
Lasse Pakanen, Kie Horioka, Raimo Ketola, Pirkko Kriikku, Katja Porvari
Forensic science international 382 112870 - 112870 2026.02
Research paper (journal)
Wischnewsky spots are considered strongly associated with postmortem diagnosis of hypothermia with an unclear pathophysiology. Recent studies have suggested an association between Wischnewsky spots and diabetic ketoacidosis, yet no systematic data exist about Wischnewsky spots in other ketotic states besides hypothermia. To elucidate the pathogenesis of Wischnewsky spots, we studied their presence in relation to ketosis/ketoacidosis, glucose, urine catecholamines, and toxicological factors. We included all medicolegal autopsies (n = 1903) with an ancillary glucose metabolism assay in the database of Forensic Medicine Unit, Finnish Institute for Health and Welfare, Oulu, Finland in 2019-2023. Cases were divided into hypothermia deaths, diabetes-related deaths, alcohol-related deaths, and other causes of death. The presence and extent of Wischnewsky spots were estimated from the autopsy reports. Concentrations of β-hydroxybutyric acid (BHB), glucose, ethanol, acetone, isopropanol, urinary adrenaline and noradrenaline, and the presence of cyclooxygenase-1 inhibitors were assessed. Mean BHB concentrations were higher with sparse, moderate, or extensive Wischnewsky spots compared with those with no Wischnewsky spots documented. Odds ratios for Wischnewsky spots were 3.7 with BHB concentration ≥ 0.5 mmol/L, 3.6 with BHB concentration > 2.5 mmol/L, 4.8 with positive blood acetone, 3.6 with positive urine acetone, and 2.2 with adrenaline-noradrenaline ratio > 0.1876. Our findings showed a clear, concentration-dependent association between BHB concentration and the presence of Wischnewsky spots irrespective of the underlying cause of death. Our results indicate that Wischnewsky spots are linked to disturbances in glucose metabolism, not exclusively to hypothermia, highlighting the diagnostic importance of postmortem BHB measurement.
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Amphiregulin is overexpressed in human cardiac tissue in hypothermia deaths; associations between the transcript and stress hormone levels in cardiac deaths.
Katja Porvari, Kie Horioka, Helena Kaija, Lasse Pakanen
Annals of medicine 56 ( 1 ) 2420862 - 2420862 2024.12
Research paper (journal)
BACKGROUND: Amphiregulin (AREG) is a growth factor linked to cardioprotection and heart pathology during myocardial stress. Our aim was to investigate cardiac AREG expression, its potential as a postmortem hypothermia marker and its possible stress hormone dependency in different types of deaths. MATERIALS AND METHODS: Heart RNA was isolated from hypothermic, cardiac and non-cardiac deaths. Relative AREG mRNA levels and urine stress hormone concentrations were measured by qPCR and enzyme-linked immunosorbent assays from eight different death cause groups. Receiver operating characteristic curve was used to evaluate a cut-off point for AREG expression as a hypothermia marker. Regulatory elements were predicted by PROMO. RESULTS: The AREG mRNA levels were significantly higher in hypothermic deaths than in most cardiac and non-cardiac deaths. AREG expression indicated hypothermic deaths with nearly 70% sensitivity and specificity. However, high expression levels were also detected in non-ischaemic deaths. The highest concentrations of adrenaline and cortisol were detected in hypothermic deaths, while the highest noradrenaline concentrations associated with atherosclerotic heart disease (AHD) deaths with acute myocardial infarction and trauma deaths. There were no significant correlations between stress hormones and AREG mRNA in hypothermic and non-cardiac deaths, whereas moderate-to-high associations were detected in cardiac deaths. Putative response elements for cortisol and catecholamines were found in AREG. CONCLUSIONS: Severe hypothermia activates cardiac AREG expression practicable as a postmortem hypothermia marker. Cortisol and catecholamines may act as transcriptional modifiers of this gene, especially in long-term ischaemic heart disease. However, the exact role of these hormones in upregulation of AREG during hypothermia remains unclear.
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Biomarker patterns and mechanistic insights into hypothermia from a postmortem metabolomics investigation.
Albert Elmsjö, Liam J Ward, Kie Horioka, Shimpei Watanabe, Fredrik C Kugelberg, Henrik Druid, Henrik Green
Scientific reports 14 ( 1 ) 18972 - 18972 2024.08
Research paper (journal)
Postmortem metabolomics holds promise for identifying crucial biological markers relevant to death investigations and clinical scenarios. We aimed to assess its applicability in diagnosing hypothermia, a condition lacking definitive biomarkers. Our retrospective analysis involved 1095 postmortem femoral blood samples, including 150 hypothermia cases, 278 matched controls, and 667 randomly selected test cases, analyzed using UHPLC-QTOF mass spectrometry. The model demonstrated robustness with an R2 and Q2 value of 0.73 and 0.68, achieving 94% classification accuracy, 92% sensitivity, and 96% specificity. Discriminative metabolite patterns, including acylcarnitines, stress hormones, and NAD metabolites, along with identified pathways, suggest that metabolomics analysis can be helpful to diagnose fatal hypothermia. Exposure to cold seems to trigger a stress response in the body, increasing cortisol production to maintain core temperature, possibly explaining the observed upregulation of cortisol levels and alterations in metabolic markers related to renal function. In addition, thermogenesis seems to increase metabolism in brown adipose tissue, contributing to changes in nicotinamide metabolism and elevated levels of ketone bodies and acylcarnitines, these findings highlight the effectiveness of UHPLC-QTOF mass spectrometry, multivariate analysis, and pathway identification of postmortem samples in identifying metabolite markers with forensic and clinical significance. The discovered patterns may offer valuable clinical insights and diagnostic markers, emphasizing the broader potential of postmortem metabolomics in understanding critical states or diseases.
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Forensic application of three interstitial pneumonia markers: search for new pneumonia markers in dead bodies.
Keisuke Okaba, Go Inokuchi, Kie Horioka, Hirotaro Iwase, Hiroyuki Inoue, Ayumi Motomura, Namiko Ishii, Chihiro Moue, Takayuki Shiomi, Daisuke Yajima
International journal of legal medicine 2024.02
Research paper (journal)
In forensic cases, detailed identification of pneumonia is important. Our objective was to statistically determine the applicability of three interstitial lung disease (ILD) markers for forensic diagnosis using serum collected from dead bodies with various postmortem intervals (PMIs). We retrospectively analyzed the levels of postmortem serum Krebs von den Lungen-6 (KL-6) and pulmonary surfactant-associated proteins A and D (SP-A and SP-D) using 221 samples obtained during forensic autopsy at our facility from 2019 to 2023. We evaluated the diagnostic efficacy of ILD markers for various pneumonias against the pathological diagnosis, and examined the assessment of the severity of ILD. When comparing the ILD group with bacterial pneumonia (BP) versus the control group, there was a significant increase in KL-6 in the ILD group. When comparing the severe ILD (SILD) group with the mild ILD (MILD) group, there was a significant increase in KL-6 and SP-D in the SILD group. The optimal cutoff values for differentiating SILD were 607.0 U/mL for KL-6, 55.5 ng/mL for SP-A, and 160.0 ng/mL for SP-D, and the sensitivity/specificity (%) of KL-6, SP-A, and SP-D for SILD were 84.1/95.2, 55.6/85.7, and 66.7/74.6, respectively. This is the first study to examine KL-6 in postmortem serum in forensic medicine. By analyzing dead bodies with various PMIs, our results confirmed statistically that postmortem serum KL-6 specifically detects ILD, postmortem serum SP-A has high sensitivity to lung injury, and postmortem serum SP-D is potentially useful in assessing the severity of ILD.
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High titers of infectious SARS-CoV-2 in COVID-19 corpses.
Hisako Saitoh, Yuko Sakai-Tagawa, Sayaka Nagasawa, Suguru Torimitsu, Kazumi Kubota, Yuichiro Hirata, Kiyoko Iwatsuki-Horimoto, Ayumi Motomura, Namiko Ishii, Keisuke Okaba, Kie Horioka, Hiroyuki Abe, Masako Ikemura, Hirofumi Rokutan, Munetoshi Hinata, Akiko Iwasaki, Yoichi Yasunaga, Makoto Nakajima, Rutsuko Yamaguchi, Shigeki Tsuneya, Kei Kira, Susumu Kobayashi, Go Inokuchi, Fumiko Chiba, Yumi Hoshioka, Aika Mori, Isao Yamamoto, Kimiko Nakagawa, Harutaka Katano, Shun Iida, Tadaki Suzuki, Shinji Akitomi, Iwao Hasegawa, Tetsuo Ushiku, Daisuke Yajima, Hirotaro Iwase, Yohsuke Makino, Yoshihiro Kawaoka
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 129 103 - 109 2023.02
Research paper (journal)
BACKGROUND: The prolonged presence of infectious severe acute respiratory syndrome coronavirus (SARS-CoV-2) in deceased coronavirus disease 2019 (COVID-19) patients has been reported. However, infectious virus titers have not been determined. Such information is important for public health, death investigation, and handling corpses. AIM: The aim of this study was to assess the level of SARS-CoV-2 infectivity in COVID-19 corpses. METHODS: We collected 11 nasopharyngeal swabs and 19 lung tissue specimens from 11 autopsy cases with COVID-19 in 2021. We then investigated the viral genomic copy number by real-time reverse transcription-polymerase chain reaction and infectious titers by cell culture and virus isolation. RESULTS: Infectious virus was present in 6 of 11 (55%) cases, 4 of 11 (36%) nasopharyngeal swabs, and 9 of 19 (47%) lung specimens. The virus titers ranged from 6.00E + 01 plaque-forming units (PFU)/mL to 2.09E + 06 PFU/g. In all cases in which an infectious virus was found, the time from death to discovery was within 1 day and the longest postmortem interval was 13 days. CONCLUSION: COVID-19 corpses may have high titers of infectious virus after a long postmortem interval (up to 13 days). Therefore, appropriate infection control measures must be taken when handling corpses.
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A suicide case of liquid nicotine intoxication.
Ayumi Motomura, Hiroyuki Inoue, Namiko Ishii, Kie Horioka, Keisuke Okaba, Chihiro Moue, Ryuto Ohashi, Daisuke Yajima
Legal medicine (Tokyo, Japan) 68 102400 - 102400 2024.01
A man in his 50 s, who was found vomiting and in a disturbed state when the emergency medical team arrived, then went into cardiopulmonary arrest during transport and died without responding to resuscitation. The hospital initially suspected that the death may have been caused by internal causes, but since the deceased had previously been transported to the hospital in a suicide attempt, the hospital called police regarding suspicions of unnatural death. The police investigation revealed two empty bottles of nicotine liquid for e-cigarettes in his house and a search history of "nicotine suicide" on his cellphone. In a forensic autopsy, he was found to be highly obese, and abundant fat deposits were observed in his organs. A stent was placed in the aorta, but no abnormality was found. There was no obvious stenosis or obstruction in the coronary arteries. Drug screening using liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on cardiac blood, urine, and stomach contents collected at autopsy, which revealed the presence of some medical products such as aripiprazole, nicotine, and cotinine. Further quantitative testing revealed high concentrations of nicotine in all samples. The left and right femoral venous blood concentrations were above the lethal dose, suggesting that arrhythmia or respiratory failure due to nicotine intoxication was the cause of death. With the widespread use of e-cigarettes, high concentrations of nicotine are readily available, and case reports of serious nicotine addiction are increasing. It is important to always consider addiction when conducting forensic evaluations in the medical field.
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Forensic autopsy of COVID-19 cases (Report 2)-How one forensic institution handled the situation-
矢島大介, 本村あゆみ, 石井名実子, 堀岡希衣, 岡馬恵介, 井上博之
法医病理 30 ( 1 ) 2024
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Tumor-educated plateletsの蛋白質合成能の増強による肝発がん促進(Promotion of hepatocarcinogenesis by tumor-educated platelets with increased de novo protein synthesis capacity)
田中 宏樹, 堀岡 希衣, 後藤 正憲, 藤井 裕美子, 上小倉 佑機, 小川 勝洋, 西川 祐司
日本癌学会総会記事 ( (一社)日本癌学会 ) 82回 2057 - 2057 2023.09
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Post-traumatic cerebral infarction caused by thrombus in the middle cerebral artery.
Akira Hayakawa, Rie Sano, Yoichiro Takahashi, Haruki Fukuda, Takafumi Okawa, Rieko Kubo, Hiroyuki Takei, Takakazu Komatsu, Hiroyuki Tokue, Yusuke Sawada, Kiyohiro Oshima, Kie Horioka, Yoshihiko Kominato
Journal of forensic and legal medicine 93 102474 - 102474 2022.12
A woman in her 80s was found unconscious after being hit by a car while crossing a road. After admission to hospitals, computed tomography (CT) scans revealed traumatic brain injury (TBI), and the patient was treated symptomatically. However, despite improvement of TBI in CT images, she died unexpectedly. Postmortem CT demonstrated cerebral infarction in the territory of the right middle cerebral artery (MCA). Histopathological examination revealed lumen-obstructing thrombosis and intimal injury upstream of the thrombosis in the right MCA. These findings suggested that the intimal injury in the MCA had led to thrombus formation, and thromboembolism in the region distal to the injury leading to post-traumatic cerebral infarction (PTCI). Both postmortem CT and autopsy were able to reveal the final condition of the deceased, which had not been fully anticipated by the clinicians who had treated her after the accident. The longitudinal antemortem to postmortem course revealed by multiple CT images and the histopathological examination provided crucial clues to the pathogenesis of PTCI in this case.
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自己血小板を用いたドラッグデリバリーシステムの肝細胞癌に対するターゲティング効果
田中 宏樹, 堀岡 希衣, 後藤 正憲, 人見 淳一, 藤井 裕美子, 上小倉 佑機, 孟 玲童, 小川 勝洋, 西川 祐司
日本癌学会総会記事 ( (一社)日本癌学会 ) 80回 [J14 - 5] 2021.09
◆Original paper【 display / non-display 】
◆Other【 display / non-display 】
Grant-in-Aid for Scientific Research 【 display / non-display 】
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Grant-in-Aid for JSPS Fellows
Project Year： 2024.04 - 2027.03
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Development of a new diagnostic method for acute myocardial ischemia and search for diagnostic biomarkers
Grant-in-Aid for Scientific Research(C)
Project Year： 2025.04 - 2028.03
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Development of a new diagnostic method for acute myocardial ischemia and search for diagnostic biomarkers
Grant-in-Aid for Scientific Research(C)
Project Year： 2025.04 - 2028.03
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Grant-in-Aid for Scientific Research(C)
Project Year： 2025.04 - 2028.03
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Grant-in-Aid for Scientific Research(C)
Project Year： 2024.04 - 2027.03