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大学院医学系研究科（医学専攻等） 医学専攻 社会環境医学系 法医科学講座 |
職務経歴（学外） 【 表示 ／ 非表示 】
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2025年03月-継続中
秋田大学 大学院医学系研究科法医科学講座 准教授
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2023年01月-継続中
University of Oulu Department of Forensic Medicine Hypothermia group Postdoc Researcher
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2020年02月-2020年09月
Karolinska Institutet Forensic Medicine Department of Oncology-Pathology Postdoctoral Researcher
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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年02月
研究論文（学術雑誌）
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年12月
研究論文（学術雑誌）
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年08月
研究論文（学術雑誌）
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年02月
研究論文（学術雑誌）
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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Bioprotective role of platelet-derived microvesicles in hypothermia: Insight into the differential characteristics of peripheral and splenic platelets
Kie Horioka, Hiroki Tanaka, Keisuke Okaba, Shinnosuke Yamada, Akira Hayakawa, Namiko Ishii, Ayumi Motomura, Hiroyuki Inoue, Shuhei Takauji, Shotaro Isozaki, Katsuhiro Ogawa, Daisuke Yajima, Henrik Druid, Lasse Pakanen, Katja Porvari
Thrombosis Research ( Elsevier BV ) 223 155 - 167 2023年03月
研究論文（学術雑誌）
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Tozuka M.
Forensic Imaging ( Forensic Imaging ) 45 2026年06月
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Horioka K.
International Journal of Legal Medicine ( International Journal of Legal Medicine ) 139 ( 6 ) 3039 - 3049 2025年11月
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FATP1-mediated fatty acid uptake in renal tubular cells as a countermeasure for hypothermia
Horioka K.
Journal of Molecular Medicine ( Journal of Molecular Medicine ) 103 ( 4 ) 403 - 419 2025年04月
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Heat stroke-induced hepatic lipid dysregulation: histological and lipidomic insights
Deguchi T.
Medical Molecular Morphology ( Medical Molecular Morphology ) 59 ( 1 ) 34 - 41 2025年
Global warming has increased summer temperatures, leading to a rise in heat stroke-related deaths in Japan. Heat stroke disrupts the body's adaptation to high temperatures, often resulting in severe complications, including liver damage and even death. However, despite the increasing incidence, pathological autopsies remain rare, and the histological changes associated with heat stroke are poorly understood. In this study, we investigated the pathogenesis of heat stroke using a mouse model. Mice were exposed to 45 °C for 30 min and dissected immediately or 24, 48, and 72 h post-exposure. Histological analysis revealed significant lipid accumulation in hepatocytes surrounding the central vein at 24, 48, and 72 h. At 24 h, hepatocytes also exhibited features of early degeneration, including cytoplasmic lysis and chromatin condensation. Lipidomics analysis of liver tissue collected 24 h post-exposure demonstrated a marked increase in 27-hydroxycholesterol levels. These results indicate that heat stress rapidly disrupts hepatic lipid homeostasis, causing cellular damage and metabolic remodeling. The observed lipid accumulation, including elevated 27-hydroxycholesterol, may play dual roles in mediating inflammation and serving as a protective response. Our findings provide new insight into the pathogenesis of heat stroke-induced liver injury and suggest potential molecular targets for early diagnosis and intervention.
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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年01月
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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ヒト凍死体から解明する低体温症の脂質代謝機構：臨床応用に向けた法医学的アプローチ
国際共同研究加速基金(国際共同研究強化)
研究期間: 2025年 - 2027年 代表者: 堀岡 希衣
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低体温と脂質代謝の相互作用を探る： 寒冷ストレスの理解に向けた新たなアプローチ
特別研究員奨励費
研究期間: 2024年04月 - 2027年03月 代表者: 堀岡 希衣
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超急性期心筋虚血の新規診断法の開発および診断バイオマーカーの探索
基盤研究(C)
研究期間: 2025年04月 - 2028年03月 代表者: 早川 輝, 堀岡 希衣, 田中 宏樹, 高橋 遥一郎, 佐野 利恵, 窪 理英子, 大谷 真紀, 松尾 悠平
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超急性期心筋虚血の新規診断法の開発および診断バイオマーカーの探索
基盤研究(C)
研究期間: 2025年04月 - 2028年03月 代表者: 早川 輝, 堀岡 希衣, 田中 宏樹, 高橋 遥一郎, 佐野 利恵, 窪 理英子, 大谷 真紀, 松尾 悠平
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心筋細胞エネルギー代謝変化の視点から解明する低体温症における心筋保護機構
基盤研究(C)
研究期間: 2025年04月 - 2028年03月 代表者: 堀岡 希衣
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The biological significance of platelet activation and coagulation in hypothermia
提供機関: Karolinska Institutet The biological significance of platelet activation and coagulation in hypothermia
研究期間： 2022年07月 - 2023年07月
資金支給機関区分：その他