2024/06/18 更新

写真a

タカツカ ヒサカズ
高塚 尚和
TAKATSUKA Hisakazu
所属
教育研究院 医歯学系 医学系列 教授
医学部 医学科 教授
医歯学総合研究科 地域疾病制御医学専攻 地域予防医学 教授
職名
教授
外部リンク

学位

  • 博士(医学) ( 1998年3月   新潟大学 )

研究キーワード

  • 法医病理学

研究分野

  • ライフサイエンス / 応用生物化学

経歴

  • 新潟大学   医歯学総合研究科 地域疾病制御医学専攻 地域予防医学   教授

    2015年5月 - 現在

  • 新潟大学   医学部 医学科   教授

    2015年5月 - 現在

  • 新潟大学   医学部 医学科   准教授

    2009年11月 - 2015年5月

  • 新潟大学   医歯学総合研究科 地域疾病制御医学専攻 地域予防医学   准教授

    2009年11月 - 2015年5月

学歴

  • 富山医科薬科大学   医学部

    - 1992年3月

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    国名: 日本国

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所属学協会

 

論文

  • Bleeding-Source Exploration in Subdural Hematoma: Observational Study on the Usefulness of Postmortem Computed Tomography Angiography. 国際誌

    Kazuhisa Funayama, Akihide Koyama, Rieka Katsuragi-Go, Takashi Aoyama, Hiraku Watanabe, Naoya Takahashi, Hisakazu Takatsuka

    Diagnostics (Basel, Switzerland)   13 ( 13 )   2023年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In a few cases, postmortem computed tomography angiography (PMCTA) is effective in postmortem detection of cortical artery rupture causing subdural hematoma (SDH), which is difficult to detect at autopsy. Here, we explore the usefulness and limitations of PMCTA in detecting the sites of cortical arterial rupture for SDH. In 6 of 10 cases, extravascular leakage of contrast material at nine different places enabled PMCTA to identify cortical arterial rupture. PMCTA did not induce destructive arterial artifacts, which often occur during autopsy. We found that, although not in all cases, PMCTA could show the site of cortical arterial rupture causing subdural hematoma in some cases. This technique is beneficial for cases of SDH autopsy, as it can be performed nondestructively and before destructive artifacts from the autopsy occur.

    DOI: 10.3390/diagnostics13132286

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  • Detection and Morphological Analysis of Micro-Ruptured Cortical Arteries in Subdural Hematoma: Three-Dimensional Visualization Using the Tissue-Clearing Clear, Unobstructed, Brain/Body Imaging Cocktails and Computational Analysis Method. 査読 国際誌

    Kazuhisa Funayama, Kazuki Tainaka, Akihide Koyama, Rieka Katsuragi-Go, Natsumi Nishikawa-Harada, Ryoko Higuchi, Takashi Aoyama, Hiraku Watanabe, Naoya Takahashi, Hisakazu Takatsuka

    Diagnostics (Basel, Switzerland)   12 ( 11 )   2022年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    One of the causes of bleeding in subdural hematoma is cortical artery rupture, which is difficult to detect at autopsy. Therefore, reports of autopsy cases with this condition are limited and hence, the pathogenesis of subdural hematoma remains unclear. Herein, for the detection and morphological analysis of cortical artery ruptures as the bleeding sources of subdural hematoma, we used the tissue-clearing CUBIC (clear, unobstructed, brain/body imaging cocktails and computational analysis) method with light-sheet fluorescence microscopy and reconstructed the two-dimensional and three-dimensional images. Using the CUBIC method, we could clearly visualize and detect cortical artery ruptures that were missed by conventional methods. Indeed, the CUBIC method enables three-dimensional morphological analysis of cortical arteries including the ruptured area, and the creation of cross-sectional two-dimensional images in any direction, which are similar to histopathological images. This highlights the effectiveness of the CUBIC method for subdural hematoma analysis.

    DOI: 10.3390/diagnostics12112875

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  • PROS1 variant in sudden death case of pulmonary embolism caused by calcification in the inferior vena cava: The importance of postmortem genetic analysis. 国際誌

    Aya Miura, Kazuhisa Funayama, Hiromi Nyuzuki, Naoya Takahashi, Takuma Yamamoto, Akihide Koyama, Takeshi Ikeuchi, Hisakazu Takatsuka, Hajime Nishio

    Legal medicine (Tokyo, Japan)   55   102029 - 102029   2022年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A Japanese man in his 30s died suddenly. Postmortem computed tomography and autopsy revealed a pulmonary embolism from an organizing thrombus in the inferior vena cava as the cause of death. Genomic analysis of congenital thrombophilia-related genes (i.e., SERPINC1, PROC, PROS1, F2, F5, PLG, and MTHFR) revealed a heterozygous variant of PROS1 (p.A139V), which has been reported in patients with congenital protein S deficiency. After a genetic conference that included forensic pathologists, molecular scientists, genetic researchers, genetic clinicians, and clinical physicians, the results of the genetic analysis were explained to the family. Biochemical analyses of protein S (PS) activity and total PS antigen levels were performed with samples from the deceased's family and genetic analysis was not performed until clinical symptoms appear. Herein we demonstrate the importance of genetic background in cases of a sudden death due to pulmonary embolism.

    DOI: 10.1016/j.legalmed.2022.102029

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  • The usefulness of postmortem computed tomography angiography for subdural hematoma caused by rupture of the cortical artery: A report of two autopsy cases and a literature review. 国際誌

    Kazuhisa Funayama, Kazuki Harada, Akihide Koyama, Rieka Katsuragi-Go, Natsumi Nishikawa-Harada, Ryoko Higuchi, Takashi Aoyama, Hiraku Watanabe, Naoya Takahashi, Hisakazu Takatsuka

    Legal medicine (Tokyo, Japan)   53   101941 - 101941   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Acute subdural hematoma (SDH) occurs following severe head trauma with brain contusion or rupture of bridging veins. Conversely, SDH caused by rupture of a cortical artery without trauma or with minor trauma is also possible. Although over 150 cases of the latter SDH have been reported, they were predominantly diagnosed only during surgery, and therefore, no adequate histological evaluation has been performed. Therefore, essential etiology of this SDH type has remained unclear. In addition, the scarcity of autopsy cases may be attributed to arterial rupture being missed if the macroscopic findings are too minimal to detect during autopsy. Here, we describe two autopsy cases of SDH of cortical artery origin. Extravasation on postmortem computed tomography angiography and arterial leakage on macroscopic observation during autopsy facilitated detection of the ruptured artery and allowed detailed histological evaluation of the ruptured artery and adjacent dura mater. The etiology of arterial rupture is briefly described on the basis of histopathological findings in this study and the available literature.

    DOI: 10.1016/j.legalmed.2021.101941

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  • 【オートプシー・イメージング2021】臨床Aiと法医学Aiはパラレル!イメージング?

    高橋 直也, 高塚 尚和, 舟山 一寿

    Rad Fan   19 ( 3 )   57 - 60   2021年2月

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    記述言語:日本語   出版者・発行元:(株)メディカルアイ  

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  • Postmortem volume change of the spleen and kidney on early postmortem computed tomography: comparison with antemortem computed tomography. 査読

    Naoya Takahashi, Keisuke Yajima, Madoka Otaki, Yurina Yoshikawa, Ayumi Ishihara, Yuki Sato, Takeshi Higuchi, Hisakazu Takatsuka

    Japanese journal of radiology   37 ( 7 )   534 - 542   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: To clarify an early postmortem change, we investigated the volume changes of the spleen and kidney on postmortem CT compared with antemortem CT in the same patients. MATERIALS AND METHODS: We retrospectively evaluated the volumes of 56 spleens (56 cases) and 50 kidneys (25 cases) using antemortem and postmortem CT, which were performed within 168 min after death. We divided the cases of spleen analysis into a hemorrhagic group (n = 12) and a non-hemorrhagic group (n = 44). RESULTS: The volumes of the organs before and after death were 101.0 ± 70.9 (cm3, mean ± standard deviation) and 81.1 ± 57.8 in spleens, 120.3 ± 49.2 and 109.2 ± 39.2 in kidneys, respectively. Both spleens and kidneys shrank after death (p < 0.05). The volumes of spleens before and after death were 111 ± 66.5 and 67.5 ± 27.7 in the hemorrhagic group, and 98.2 ± 72.5 and 84.9 ± 63.3 in the non-hemorrhagic group, respectively. The median value of the ratio of postmortem splenic volume to antemortem volume in the hemorrhagic group (65.0%) was smaller than the one in the non-hemorrhagic group (90.5%) (p < 0.05). CONCLUSION: We demonstrated that spleens and kidneys significantly reduced in size after death. The rate of shrinkage of spleens in the hemorrhagic group significantly became larger than the one in the non-hemorrhagic group.

    DOI: 10.1007/s11604-019-00841-3

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  • An autopsy case of peliosis hepatis with X-linked myotubular myopathy. 査読 国際誌

    Kazuhisa Funayama, Hiroshi Shimizu, Hidetomo Tanaka, Izumi Kawachi, Ichizo Nishino, Kou Matsui, Naoya Takahashi, Akihide Koyama, Rieka Katsuragi-Go, Ryoko Higuchi, Takashi Aoyama, Hiraku Watanabe, Akiyoshi Kakita, Hisakazu Takatsuka

    Legal medicine (Tokyo, Japan)   38   77 - 82   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This report describes the autopsy case of a 4-year-old boy who died from hepatic hemorrhage and rupture caused by peliosis hepatis with X-linked myotubular myopathy. Peliosis hepatis is characterized by multiple blood-filled cavities of various sizes in the liver, which occurs in chronic wasting disease or with the use of specific drugs. X-linked myotubular myopathy is one of the most serious types of congenital myopathies, in which an affected male infant typically presents with severe hypotonia and respiratory distress immediately after birth. Although each disorder is rare, 12 cases of pediatric peliosis hepatis associated with X-linked myotubular myopathy have been reported, including our case. Peliosis hepatis should be considered as a cause of hepatic hemorrhage despite its low incidence, and it requires adequate gross and histological investigation for correct diagnosis.

    DOI: 10.1016/j.legalmed.2019.04.005

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  • Assessment of a simple method of heart weight estimation by postmortem computed tomography. 査読 国際誌

    Rei Ogawa, Naoya Takahashi, Takeshi Higuchi, Hiroyuki Shibuya, Motohiko Yamazaki, Norihiko Yoshimura, Hisakazu Takatsuka, Hidefumi Aoyama

    Forensic science international   296   22 - 27   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Measurement of heart weight is important when investigating cause of death, but there is presently no satisfactory method of heart weight estimation by postmortem computed tomography (PMCT). METHOD: We investigated 33 consecutive cases that underwent both PMCT and autopsy between February 2008 and June 2014. Heart and left ventricular (LV) weights were calculated by PMCT morphometry. We used a simple method to estimate LV weight: We assumed that LV was an ellipsoid and multiplied its volume on PMCT with myocardial specific gravity. We then compared the various heart and LV weights using linear regression. The calculated and estimated LV weights on PMCT were also compared. RESULTS: It was not possible to predict heart weight at autopsy from PMCT (R2 = 0.53). However, heart weight at autopsy could be accurately predicted from LV weight calculated by PMCT (R2 = 0.77). In addition, there was a strong correlation between the estimated and calculated LV weights by PMCT (R2 = 0.92). Heart weight at autopsy could also be accurately predicted using the PMCT-estimated LV weight (R2 = 0.72). CONCLUSION: Heart weight at autopsy could be accurately predicted using a simple method in which LV volume was assumed to be an ellipsoid on PMCT.

    DOI: 10.1016/j.forsciint.2018.12.019

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  • 【Multislice CT 2018 BOOK】Dual Energy CT オートプシー・イメージング(Ai)用Dual Energy CT使用の初期経験

    高橋 直也, 高塚 尚和, 舟山 一寿, 大澤 阿紋

    映像情報Medical   50 ( 8 )   85 - 89   2018年7月

  • 皮質動脈破綻による亜急性特発性硬膜下血腫の1例

    舟山 一寿, 原田 一樹, 高橋 直也, 青山 崇, 樋口 涼子, 渡辺 拓, 川井 桂, 高塚 尚和

    法医病理   23 ( 1 )   8 - 9   2017年7月

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    記述言語:日本語   出版者・発行元:日本法医病理学会  

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  • 皮質動脈破綻による急性硬膜下血腫の1例

    舟山 一寿, 原田 一樹, 高橋 直也, 樋口 涼子, 青山 崇, 渡辺 拓, 高塚 尚和

    日本法医学雑誌   71 ( 1 )   60 - 60   2017年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本法医学会  

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  • 皮質動脈破綻による亜急性特発性硬膜下血腫の1例

    舟山 一寿, 原田 一樹, 高橋 直也, 渡辺 拓, 川井 桂, 高塚 尚和

    日本法医学雑誌   70 ( 1 )   74 - 74   2016年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本法医学会  

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  • Changes in aortic shape and diameters after death: comparison of early postmortem computed tomography with antemortem computed tomography. 査読 国際誌

    Naoya Takahashi, Takeshi Higuchi, Yasuo Hirose, Haruo Yamanouchi, Hisakazu Takatsuka, Kazuhisa Funayama

    Forensic science international   225 ( 1-3 )   27 - 31   2013年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    PURPOSE: The purpose of this study is to evaluate the postmortem deformation of the aorta on postmortem computed tomography (CT) by comparison with the antemortem CT in the same patient. MATERIALS AND METHODS: A total of 58 non-traumatic patients without hemorrhagic events who underwent torso CT before and shortly after death were enrolled. Antemortem chest and abdominal CT were obtained in 44 cases and in 57 cases, respectively. The lengths of the major and minor axes of the ascending and descending thoracic aorta and the abdominal aorta were measured on both antemortem and postmortem CT in the same patient. To evaluate the shape of the aorta, the major axis-minor axis ratio (Ma-MiR) was calculated. Mean values of the diameters of the aorta and Ma-MiRs on postmortem CT were compared with those on antemortem CT using the Wilcoxon signed-rank test. We also evaluated the major and minor axes and Ma-MiRs on both antemortem and postmortem CT in two age groups: 65 years and under (n=13) and over 65 years (n=45). RESULTS: At each level tested, the aorta significantly shrank after death (p<0.001) (ascending thoracic aorta, descending thoracic aorta, and abdominal aorta: 38.5 mm × 33.5 mm, 28.0 mm × 25.9 mm, and 24.4 mm × 21.8 mm on antemortem CT, 30.0 mm × 26.2 mm, 24.4 mm × 20.7 mm, and 21.5 mm × 14.5 mm on postmortem CT, respectively). The postmortem Ma-MiRs significantly increased at the descending thoracic aorta and the abdominal aorta (p<0.001). The diameters of the aorta are longer in older cases at all levels on both antemortem and postmortem CT. The reduction rates were larger in younger cases than older cases at all levels. CONCLUSIONS: After death, the aorta shrunk at all levels, and became oval in shape in descending thoracic and abdominal aorta. The contraction was greater in younger cases than older cases. Investigators who interpret postmortem imaging should be aware of the postmortem deformation of the aorta.

    DOI: 10.1016/j.forsciint.2012.04.037

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  • 超音波画像診断装置(エコー)の死因診断への応用

    舟山 一寿, 高塚 尚和, 山内 春夫, 内ヶ崎 西作, 高橋 直也

    新潟県医師会報   ( 732 )   5 - 7   2011年3月

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    記述言語:日本語   出版者・発行元:新潟県医師会  

    2008年5月から2年4ヵ月間に超音波画像診断装置を用いて死因診断(死後エコー)を行った92例(検死41例、解剖51例)の死後エコーの状況と結果を報告した。外傷初期診療の超音波検査法FASTの6点に傍胸骨肋骨間操作を加えた計7点でecho free spaceの有無を判定し、死因との関連を推定した結果、92例中24例に1ヶ所以上のecho free spaceを認め、外傷死の約65%と非外傷死の約0.3%で死因との直接的関連を認めた。また、検死例におけるエコーガイド下穿刺では正確な部位からの採取が可能で、特に心腔や大血管を穿刺することで動静脈血の選択的採取が可能となり、死因推定の一助となった。死後エコーは検査そのものの制約や精度などに関して欠点を有するものの、非侵襲的に内部の形態的情報が得られるほかにも機動性という独自の利点があり、その有用性が示唆された。

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  • 超音波画像診断装置(エコー)を用いた死体の観察と死因診断への応用

    舟山 一寿, 内ヶ崎 西作, 高橋 直也, 須貝 壮朗, 西川 有紀子, 高塚 尚和, 山内 春夫

    日本法医学雑誌   64 ( 1 )   88 - 88   2010年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本法医学会  

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▶ 全件表示

MISC

  • Classification of Sphenoid Sinus Using Head Computed Tomography Images for Preliminary of Personal Identification(和訳中)

    Malkanthi Appu Gammahelage Chandani, Takahashi Naoya, Fuse Tomoya, Ohsawa Amon, Takatsuka Hisakazu, Higuchi Takeshi

    新潟大学保健学雑誌   17 ( 1 )   1 - 6   2020年3月

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    記述言語:英語   出版者・発行元:新潟大学医学部保健学科  

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  • Increased Susceptibility of Thymocytes to Apoptosis in Mice Lacking AIM, a Novel Murine Macrophage-derived Soluble Factor Belonging to the Scavenger Receptor Cysteine-rich Domain Superfamily.(共著)

    Journal of Experimental Medicine   189 ( 2 )   413 - 422   1999年1月

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  • Granuloma formation in scavenger receptor-deficient mice in response to BCG.(共著)

    Cells of the Hepatic Sinusoid   Vol.7, 243-244   243 - 244   1999年

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    記述言語:英語  

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  • Granuloma formation in scavenger receptor-deficient mice in response to BCG.(jointly worked)

    Cells of the Hepatic Sinusoid   Vol.7, 243-244   1999年

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  • Gene transduction into the liver - Present and perspective - Immunomodulation gene therapy for hepatic micrometastasis.(共著)

    Cells of the Hepatic Sinusoid   Vol.7, 272-277   272 - 277   1999年

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    記述言語:英語  

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  • Expression of macrophage colony-stimulating factor, scavenger receptors, and macrophage proliferation in the pregnant mouse uterus

    Y Kyaw, G Hasegawa, H Takatsuka, M Shimada-Hiratsuka, H Umezu, M Arakawa, M Naito

    ARCHIVES OF HISTOLOGY AND CYTOLOGY   61 ( 5 )   383 - 393   1998年12月

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    記述言語:英語   出版者・発行元:INT SOC HISTOLOGY & CYTOLOGY  

    During pregnancy, mouse uterine epithelial cells produce and secrete a large amount of macrophage colony-stimulating factor (M-CSF/CSF-1), Macrophages accumulate and proliferate in the undecidualized endometrium of the pregnant uterus. Observations showed that macrophages expressed scavenger receptor class A (type I and type II) and class C (macrosialin). Scavenger receptors appeared to be involved in the removal of apoptotic cells in the degenerated decidual tissue. The expression of class A and class C scavenger receptor mRNAs in the uterus of pregnant mice was elevated but the expression of class B scavenger receptor (CD36) mRNA was similar to that of non-pregnant mice. The expression of various cytokines and chemokines, including M-CSF, monocyte cheomattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1-alpha), was enhanced in the uterus of pregnant mice, suggesting that these molecules regulate macrophage chemotaxis and immunological function in the uterus. These findings imply that the pregnant uterus provides a microenvironment for the recruitment, differentiation, and proliferation of macrophages and the regulation of scavenger receptor and cytokine expression for a successful pregnancy.

    DOI: 10.1679/aohc.61.383

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  • Expression of Macrophage Colony-stimulating Factor, Scavenger Receptors, and Macrophage Proliferation in Pregnant Uterus of Mice.(共著)

    Archives of Histology and Cytology   61 ( 5 )   383 - 393   1998年12月

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  • Bone remodeling and macrophage differentiation in aged osteopetrosis (op) mutant mice defective in the production of macrophage colony-stimulating factor.(共著)

    Journal of Submicroscopic Cytology and Pathology   30 ( 2 )   239 - 247   1998年4月

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    記述言語:英語  

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  • Bone remodeling and macrophage differentiation in osteopetrosis (op) mutant mice defective in the production of macrophage colony-stimulating factor

    H Takatsuka, H Umezu, G Hasegawa, H Usuda, Y Ebe, M Naito, LD Shultz

    JOURNAL OF SUBMICROSCOPIC CYTOLOGY AND PATHOLOGY   30 ( 2 )   239 - 247   1998年4月

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    記述言語:英語   出版者・発行元:EDITRICE COMPOSITORI BOLOGNA  

    Mice homozygous for the osteopetrosis top) mutation are characterized by defective differentiation of osteoclasts, monocytes, and tissue macrophages due to a lack of functional macrophage colony-stimulating factor (M-CSF/CSF-1) activity. In young (4-6 week-old) op/op mice, the bone marrow cavities were filled with spongious Lone. In aged (50-72 week-old) op/op mice, the bone marrow cavities were markedly reconstructed and marrow hematopoiesis was expanded. Numbers of osteodasts and bone marrow macrophages in aged op/op mice were increased but most of the osteoclasts were mononuclear cells and showed poorly developed ruffled borders. Lysosomes of bone marrow macrophages were laden with abundant cry stalloid materials in aged op/op mice and aged littermate mice. However, such macrophages were not ob served in young op/op mice nor in young littermates. In contrast to the marked increase in numbers of osteoclasts and macrophages in the bone marrow the number of Kupffer cells in the liver did not increase in aged op/op mice. Kupffer cells in aged op/op mice did not show ultrastructural maturation with aging and contained a few crystalloid structures. M-CSF administration to aged op/op mice induced numerical increases in Kupffer sells and lysosomes in Kupffer cells, disappearance of crystalloid structures in lysosomes of Kupffer cells, and the development of ruffled border in osteoclasts. These findings indicate that M-CSF-independent mechanisms for macrophage and osteoclast development in aged op/op mice are restricted to bone marrow. M-CSF plays important roles in the differentiation of macrophage and osteoclast and the production and function of lysosomes.

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  • Expression of macrophage colony-stimulating factor and its receptor in hepatic granulomas of Kupffer-cell-depleted mice.(共著)

    American Journal of Pathology   150 ( 6 )   2047 - 2060   1997年6月

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    記述言語:英語  

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  • Expression of macrophage colony-stimulating factor and its receptor in hepatic granulomas of Kupffer-cell-depleted mice

    H Moriyama, T Yamamoto, H Takatsuka, H Umezu, K Tokunaga, T Nagano, M Arakawa, M Naito

    AMERICAN JOURNAL OF PATHOLOGY   150 ( 6 )   2047 - 2060   1997年6月

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    記述言語:英語   出版者・発行元:AMER SOC INVESTIGATIVE PATHOLOGY, INC  

    In mice administered with liposome-entrapped dichloromethylene diphosphonate, which depletes Kupffer cells, the size and the number of zymosan-induced granulomas in the liver were smaller than in untreated mice. The number of macrophage precursors, as detected by the monoclonal antibodies for macrophage precursors, increased after zymosan injection in both groups of mice, proliferated, and differentiated into macrophages. Expression of macrophage colony-stimulating factor (M-CSF), interleukin-1, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and interferon-gamma mRNA was enhanced in the stage of granuloma formation in the control mouse liver, whereas it was suppressed in Kupffer-cell-depleted mice. However, M-CSF mRNA expression was increased in the Kupffer-cell-depleted mice to form granulomas in the late stages. In situ hybridization demonstrated the expression of M-CSF mRNA and c-fms mRNA in Kupffer cells and monocyte-derived macrophages in the sinusoid and granulomas. The concentration of M-CSF in serum of zymosan-injected control mice was within normal range, but that of zymosan-treated or untreated Kupffer-cell-depleted mice was markedly elevated at day 1. These findings imply that Kupffer cells are indispensable for granuloma formation and produce various cytokines including M-CSF. The local production and consumption of M-CSF in the liver may play a crucial role in granulomtous inflammation.

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  • Macrophage differentiation and expression of macrophage colony stimulating factor in murine mikly spots and omentum after macrophage elimination.(共著)

    Journal of Leukocyte Biology   61 ( 4 )   436 - 444   1997年4月

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    記述言語:英語  

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  • Macrophage differentiation and expression of macrophage colony-stimulating factor in murine milky spots and omentum after macrophage elimination

    H Zhu, M Naito, H Umezu, H Moriyama, H Takatsuka, K Takahashi, LD Shultz

    JOURNAL OF LEUKOCYTE BIOLOGY   61 ( 4 )   436 - 444   1997年4月

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    記述言語:英語   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    To elucidate the differentiation mechanisms of macrophages in the murine omentum, we studied the repopulation of these cells and the expression of macrophage colony-stimulating factor (M-CSF) in the milky spots and omental tissues in mice depleted of macrophages following administration of liposome-encapsulated dichloromethylene diphosphonate (clodronate). The macrophages in the omentum were spindle or dendritic in shape, expressed several macrophage-specific antigens and Ia antigen, and phagocytized intraperitoneally injected carbon particles. In the milky spots, macrophages and macrophage precursors were detected, and the number of precursors increased after elimination of macrophages by intraperitoneal injection of liposome-encapsulated clodronate. Macrophage precursors in the milky spots proliferated, moved to the omentum, and transformed into dendritic-shaped macrophages. Expression of M-CSF mRNA extracted from the milky spots was markedly enhanced at 2 and 3 days after macrophage depletion. Localization of M-CSF protein and mRNA was observed iu the stromal cells of the milky spots. In osteopetrosis (op/op) mutant mice that are defective in the production of functional M-CSF omental macrophages were absent. These results indicate that M-CSF locally produced in the milky spots plays an important role in providing a microenvironment for development and differentiation of omental macrophages.

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  • Bone reconstruction and crystal storage in bone marrow macrophages of aged osteopetrosis (op) mice.(共著)

    Dendritic Cells   Vol.7, 43-46   1997年

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  • Bone reconstruction and crystal storage in bone marrow macrophages of aged osteopetrosis (op) mice.(jointly worked)

    Dendritic Cells   Vol.7, 43-46   1997年

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  • Liposome-encapsulated dichloromethylene diphosphonate induces macrophage apoptosis in vivo and in vitro.(共著)

    Journal of Leukocyte Biology   60 ( 3 )   337 - 344   1996年9月

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  • Liposome-encapsulated dichloromethylene diphosphonate induces macrophage apoptosis in vivo and in vitro

    M Naito, H Nagai, S Kawano, H Umezu, H Zhu, H Moriyama, T Yamamoto, H Takatsuka, Y Takei

    JOURNAL OF LEUKOCYTE BIOLOGY   60 ( 3 )   337 - 344   1996年9月

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    記述言語:英語   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Dichloromethylene diphosphonate (MDPCl(2)) encapsulated in multilamellar liposomes was selectively incorporated by macrophages, immediately transferred to lysosomes, then released from liposomes into lysosomes by enzymatic digestion of the Liposomal lipid layers. From 4 h after ingesting Liposome-encapsulated MDPCl(2) murine macrophages in vivo and in vitro acquired the ultrastructural features of apoptosis, such as condensed nuclear chromatin, nuclear fragmentation, cell shrinkage, and blebbing of the plasma membrane. Murine peritoneal macrophages and isolated rat Kupffer cells incubated in the medium containing liposome-encapsulated MDPCl(2) increased DNA fragmentation in a dose-dependent manner. Electrophoretic analysis of extracted DNA from the isolated Kupffer cells showed DNA fragmentation. Another diphosphonate, Alendronate (4-amino-1-hydroxy-butylidene-1,1- diphosphonate) had less potent macrophage cytotoxicity. However, MDPCl(2), Alendronate, and gadolinium chloride in solution were not cytotoxic to macrophages. These results implied that the intralysosomal accumulation of MDPCl(2) generates signals to induce macrophage apoptosis.

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  • マクロファージコロニー刺激因子(M-CSF/CSF-1)欠損マウス(op/op)を用いたマクロファージ分化機構の解析(共著)

    内藤 眞, 薄田 浩幸, 梅津 哉[他]

    新潟医学会雑誌   110巻1号 1-12項 ( 1 )   1 - 12   1996年

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    記述言語:日本語   出版者・発行元:新潟大学  

    "Osteopetrotic(OP/OP) mouse is an animal model for osteopetrosis and was demonstrated to be a mutation within the coding region of M-CSF gene itself. The OP/OP mouse serves as a model for investigating the differentiation mechanism of macrophage populations in the absence of functional M-CSF. The OP/OP mice also provide evidence to show the role of M-CSF in physiological and pathological conditions. The OP/OP mice are severely monocytopenic and show marked reduction and abnormal differentiation of tissue macrophages and osteoclasts. Most of these macrophages are ultrastructurally immature. Compared with the tissues of normal littermates, those of mutants contained about 30% of macrophages in many tissues, suggesting that the heterogeneity of macrophages is generated by their different dependency to M-CSF. In contrast, the numbers of dendritic cells in the epidermis and lymphoid apparatus of OP/OP mice were not reduced comparing to those in normal littermates, indicating that dendritic cells are an M-CSF-independent population. After daily M-CSF injection the numbers of monocytes, tissue macrophages, and osteoclasts showed remarkable increases and macrophages demonstrated morphological maturation. However, the numbers of macrophages in the ovary and uterus were not increased. After glucan injection hepatic granulomas in OP/OP mice were formed but smaller, less numerous, and more irregular in shape than those of normal littermates. Kupffer cells in the mutant mice exhibited an active proliferationcapacity, particularly just before the stage of granuloma foration. After administration of M-CSF, numbers of monocytes and Kupffer cells increased rapidly in OP/OP mice and granuloma formation was enhanced in these mice. These results indicate that M-CSF-independent Kupffer cells and M-CSF-dependent macrophage populations play an important role in granuloma formation. In conclusion, M-CSF is an important molecule for proliferation and differentiation of not only M-CSF-dependent macrophages but also M-CSF-independent macrophages inphysiological conditions. Furthermore, M-CSF is largely responsible for providing a microenvironment for generating macrophage heterogeneity in vivo. "

    CiNii Article

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    その他リンク: http://search.jamas.or.jp/link/ui/1996229042

  • Expression of Scavenger Receptors in macrophages and Endothelial Cells.(jointly worked)

    Niigata Medical Journal   Vol. 110(6), 216-220   1996年

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  • 《綜説》マクロファージコロニー刺激因子(M-CSF/CSF-1)欠損マウス(OP/OP) を用いたマクロファージ分化機構の解析

    内藤 眞, 薄田 浩幸, 梅津 哉[他]

    新潟医学会雑誌   Vol. 110(1), 1-12 ( 1 )   1 - 12   1996年

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    記述言語:日本語   出版者・発行元:新潟大学  

    "Osteopetrotic(OP/OP) mouse is an animal model for osteopetrosis and was demonstrated to be a mutation within the coding region of M-CSF gene itself. The OP/OP mouse serves as a model for investigating the differentiation mechanism of macrophage populations in the absence of functional M-CSF. The OP/OP mice also provide evidence to show the role of M-CSF in physiological and pathological conditions. The OP/OP mice are severely monocytopenic and show marked reduction and abnormal differentiation of tissue macrophages and osteoclasts. Most of these macrophages are ultrastructurally immature. Compared with the tissues of normal littermates, those of mutants contained about 30% of macrophages in many tissues, suggesting that the heterogeneity of macrophages is generated by their different dependency to M-CSF. In contrast, the numbers of dendritic cells in the epidermis and lymphoid apparatus of OP/OP mice were not reduced comparing to those in normal littermates, indicating that dendritic cells are an M-CSF-independent population. After daily M-CSF injection the numbers of monocytes, tissue macrophages, and osteoclasts showed remarkable increases and macrophages demonstrated morphological maturation. However, the numbers of macrophages in the ovary and uterus were not increased. After glucan injection hepatic granulomas in OP/OP mice were formed but smaller, less numerous, and more irregular in shape than those of normal littermates. Kupffer cells in the mutant mice exhibited an active proliferationcapacity, particularly just before the stage of granuloma foration. After administration of M-CSF, numbers of monocytes and Kupffer cells increased rapidly in OP/OP mice and granuloma formation was enhanced in these mice. These results indicate that M-CSF-independent Kupffer cells and M-CSF-dependent macrophage populations play an important role in granuloma formation. In conclusion, M-CSF is an important molecule for proliferation and differentiation of not only M-CSF-dependent macrophages but also M-CSF-independent macrophages inphysiological conditions. Furthermore, M-CSF is largely responsible for providing a microenvironment for generating macrophage heterogeneity in vivo. "

    CiNii Article

    CiNii Books

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    その他リンク: http://search.jamas.or.jp/link/ui/1996229042

  • Osteopetrotic (op/op) Mice: An animal model for investigating the biology of colony-stimulating factor-1 (CSF-1/M-CSF).(jointly worked)

    Acta Medica et Biologica   Vol.44(1), 1-11   1996年

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