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Your search keyword '"Arai, Nobutaka"' showing total 401 results
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401 results on '"Arai, Nobutaka"'

1. Conventional magnetic resonance imaging key features for distinguishing pathologically confirmed corticobasal degeneration from its mimics: a retrospective analysis of the J-VAC study

Author

Sakurai, Keita, Tokumaru, Aya M., Yoshida, Mari, Saito, Yuko, Wakabayashi, Koichi, Komori, Takashi, Hasegawa, Masato, Ikeuchi, Takeshi, Hayashi, Yuichi, Shimohata, Takayoshi, Murayama, Shigeo, Iwasaki, Yasushi, Uchihara, Toshiki, Sakai, Motoko, Yabe, Ichiro, Tanikawa, Satoshi, Takigawa, Hiroshi, Adachi, Tadashi, Hanajima, Ritsuko, Fujimura, Harutoshi, Hayashi, Kentaro, Sugaya, Keizo, Hasegawa, Kazuko, Sano, Terunori, Takao, Masaki, Yokota, Osamu, Miki, Tomoko, Kobayashi, Michio, Arai, Nobutaka, Ohkubo, Takuya, Yokota, Takanori, Mori, Keiko, Ito, Masumi, Ishida, Chiho, Idezuka, Jiro, Toyoshima, Yasuko, Kanazawa, Masato, Aoki, Masashi, Hasegawa, Takafumi, Watanabe, Hirohisa, Hashizume, Atsushi, Niwa, Hisayoshi, Yasui, Keizo, Ito, Keita, Washimi, Yukihiko, Kubota, Akatsuki, Toda, Tatsushi, Nakashima, Kenji, and Aiba, Ikuko

Published
2024
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5. mTORC2 links growth factor signaling with epigenetic regulation of iron metabolism in glioblastoma.

Author

Masui, Kenta, Harachi, Mio, Ikegami, Shiro, Yang, Huijun, Onizuka, Hiromi, Yong, William, Cloughesy, Timothy, Muragaki, Yoshihiro, Kawamata, Takakazu, Arai, Nobutaka, Komori, Takashi, Cavenee, Webster, Mischel, Paul, and Shibata, Noriyuki

Subjects
acetyl coenzyme A (acetyl-CoA), glioblastoma, glucose metabolism, histone acetylation, iron metabolism, mammalian target of rapamycin (mTOR), Active Transport, Cell Nucleus, Animals, Brain Neoplasms, Cell Line, Tumor, Cell Survival, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Glioblastoma, Histones, Humans, Immediate-Early Proteins, Intercellular Signaling Peptides and Proteins, Iron, Mechanistic Target of Rapamycin Complex 2, Metabolome, Mice, Neoplasm Transplantation, Promoter Regions, Genetic, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins c-akt, Pyruvate Dehydrogenase (Lipoamide), Signal Transduction
Abstract

In cancer, aberrant growth factor receptor signaling reprograms cellular metabolism and global gene transcription to drive aggressive growth, but the underlying mechanisms are not well-understood. Here we show that in the highly lethal brain tumor glioblastoma (GBM), mTOR complex 2 (mTORC2), a critical core component of the growth factor signaling system, couples acetyl-CoA production with nuclear translocation of histone-modifying enzymes including pyruvate dehydrogenase and class IIa histone deacetylases to globally alter histone acetylation. Integrated analyses in orthotopic mouse models and in clinical GBM samples reveal that mTORC2 controls iron metabolisms via histone H3 acetylation of the iron-related gene promoter, promoting tumor cell survival. These results nominate mTORC2 as a critical epigenetic regulator of iron metabolism in cancer.

Published
2019

7. Glucose-dependent acetylation of Rictor promotes targeted cancer therapy resistance

Author

Masui, Kenta, Tanaka, Kazuhiro, Ikegami, Shiro, Villa, Genaro R, Yang, Huijun, Yong, William H, Cloughesy, Timothy F, Yamagata, Kanato, Arai, Nobutaka, Cavenee, Webster K, and Mischel, Paul S

Subjects
Brain Disorders, Cancer, Brain Cancer, Rare Diseases, Genetics, Neurosciences, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Aetiology, Underpinning research, Acetates, Acetyl Coenzyme A, Acetylation, Amino Acid Sequence, Animals, Brain Neoplasms, Carrier Proteins, Cell Line, Tumor, Drug Resistance, Neoplasm, ErbB Receptors, Gene Expression Regulation, Neoplastic, Glioblastoma, Glucose, Humans, Mechanistic Target of Rapamycin Complex 2, Mice, Mice, SCID, Molecular Sequence Data, Multiprotein Complexes, Neoplasm Transplantation, Phosphatidylinositol 3-Kinases, Protein Structure, Tertiary, Proto-Oncogene Proteins c-akt, Rapamycin-Insensitive Companion of mTOR Protein, Sequence Homology, Amino Acid, Signal Transduction, TOR Serine-Threonine Kinases, mTORC2, Rictor acetylation, metabolic reprogramming, targeted therapy resistance, glioblastoma
Abstract

Cancer cells adapt their signaling in response to nutrient availability. To uncover the mechanisms regulating this process and its functional consequences, we interrogated cell lines, mouse tumor models, and clinical samples of glioblastoma (GBM), the highly lethal brain cancer. We discovered that glucose or acetate is required for epidermal growth factor receptor vIII (EGFRvIII), the most common growth factor receptor mutation in GBM, to activate mechanistic target of rapamycin complex 2 (mTORC2) and promote tumor growth. Glucose or acetate promoted growth factor receptor signaling through acetyl-CoA-dependent acetylation of Rictor, a core component of the mTORC2 signaling complex. Remarkably, in the presence of elevated glucose levels, Rictor acetylation is maintained to form an autoactivation loop of mTORC2 even when the upstream components of the growth factor receptor signaling pathway are no longer active, thus rendering GBMs resistant to EGFR-, PI3K (phosphoinositide 3-kinase)-, or AKT (v-akt murine thymoma viral oncogene homolog)-targeted therapies. These results demonstrate that elevated nutrient levels can drive resistance to targeted cancer treatments and nominate mTORC2 as a central node for integrating growth factor signaling with nutrient availability in GBM.

Published
2015

11. Expanded ischemic lesion due to herniation leads to axonal injury in a site remote to the primary lesion on autopsy brain with acute focal cerebral ischemia.

Author

Seki, Erika, Komori, Takashi, and Arai, Nobutaka

Subjects
CEREBRAL ischemia, HERNIA, AMYLOID beta-protein precursor, INTERNAL carotid artery, BRAIN damage, AUTOPSY
Abstract

Cerebral ischemia may lead to axonal injury not only at the site of the primary lesion but also in a region remote to the site of insult. In this study, we investigated the effect of herniation on the development of axonal injury at a site remote to the primary lesion during the acute phase of cerebral ischemia. We obtained postmortem brains of 13 cases with acute phase of unilateral cerebral infarction in the territory of the internal carotid artery or middle cerebral artery and seven controls. We classified the brain tissues into herniation and non‐herniation groups. Then we examined whether axonal and ischemic changes existed in the corpus callosum contralateral to the ischemic hemisphere and the upper pons. In the herniation group, we detected white‐matter lesions by Klüver‐Barrera staining, microglial loss by immunohistochemistry for ionized calcium‐binding adaptor molecule 1, and axonal injury by immunohistochemistry for amyloid precursor protein. However, none of the aforementioned findings were observed in the non‐herniation group. These findings suggest the existence of regional overlap in axonal and ischemic pathologies in remote regions in the presence of herniation. We concluded that herniation may play a significant role in the development of axonal and ischemic changes in the remote region. Our results suggest that axonal injury in a remote region may result from expanded ischemic lesions due to herniation. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Carbonyl stress-sensitive brain regions in the patient with treatment-resistant schizophrenia with a glyoxalase 1 frameshift mutation: Autopsy study

Author

Ishida, Hiroaki, primary, Miyashita, Mitsuhiro, additional, Oshima, Kenichi, additional, Kawakami, Ito, additional, Sekiyama, Kazunari, additional, Kounoe, Mai, additional, Seki, Erika, additional, Arai, Nobutaka, additional, Takizawa, Shunya, additional, Nagata, Eiichiro, additional, Itokawa, Masanari, additional, and Arai, Makoto, additional

Published
2022
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15. An autopsy case report of adult-onset Krabbe disease : Comparison with an infantile-onset case

Author

Sasaki, Miu, Ebata, Miori, 1000090757650, Tanei, Zen-ichi, Oda, Yoshitaka, Hamauchi, Akiko, Tanikawa, Satoshi, Sugino, Hirokazu, Ishida, Yusuke, Abe, Takenori, Arai, Nobutaka, Sako, Kazuya, 1000070261287, Tanaka, Shinya, Sasaki, Miu, Ebata, Miori, 1000090757650, Tanei, Zen-ichi, Oda, Yoshitaka, Hamauchi, Akiko, Tanikawa, Satoshi, Sugino, Hirokazu, Ishida, Yusuke, Abe, Takenori, Arai, Nobutaka, Sako, Kazuya, 1000070261287, and Tanaka, Shinya

Abstract

Krabbe disease is a lysosomal storage disease caused by a deficiency of the galactocerebrosidase (GALC) enzyme, which leads to demyelination of the central and peripheral nervous systems. Almost all patients with Krabbe disease are infants, and this is the first report of adult-onset cases that describe pathological findings. Here, we present two autopsy cases: a 73-year-old female and a 2-year-old male. The adult-onset case developed symptoms in her late thirties and was diagnosed by the identification of GALC D528N and L634S mutations and by T2-weighted magnetic resonance imaging; she had increased signal in the white matter along the pyramidal tract to the bilateral precentral gyrus, as well as from the triangular part to the posterior horn of the lateral ventricle. Microscopically, Kluver-Barrera staining was pale in the white matter of the precentral gyrus and occipito-thalamic radiation, and a few globoid cells were observed. The GALC mutations that were identified in the present adult-onset case do not completely inactivate GALC enzyme activity, resulting in focal demyelination of the brain.

Published
2022

16. Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu–Hakola disease: lesion staging and dynamic changes of axons and microglial subsets

Author

Oyanagi, Kiyomitsu, Kinoshita, Michiaki, Suzuki‐Kouyama, Emi, Inoue, Teruhiko, Nakahara, Asa, Tokiwai, Mika, Arai, Nobutaka, Satoh, Jun‐ichi, Aoki, Naoya, Jinnai, Kenji, Yazawa, Ikuru, Arai, Kimihito, Ishihara, Kenji, Kawamura, Mitsuru, Ishizawa, Keisuke, Hasegawa, Kazuko, Yagisita, Saburo, Amano, Naoji, Yoshida, Kunihiro, Terada, Seishi, Yoshida, Mari, Akiyama, Haruhiko, Mitsuyama, Yoshio, and Ikeda, Shu‐ichi

Published
2017
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27. Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73

Author

Hoshino, Masataka, Qi, Mei-ling, Yoshimura, Natsue, Miyashita, Tomoyuki, Tagawa, Kazuhiko, Wada, Yo-ichi, Enokido, Yasushi, Marubuchi, Shigeki, Harjes, Phoebe, Arai, Nobutaka, Oyanagi, Kiyomitsu, Blandino, Giovanni, Sudol, Marius, Rich, Tina, Kanazawa, Ichiro, Wanker, Erich E., Saitoe, Minoru, and Okazawa, Hitoshi

Subjects
Neurons -- Research, Gene expression -- Research, Huntington's chorea -- Risk factors, Neuroplasticity -- Research, Proteins -- Research, Genetic transcription -- Research, Genetic transcription -- Causes of, Biological sciences
Abstract

Transcriptional disturbance is implicated in the pathology of polyglutamine diseases, including Huntington's disease (HD). However, it is unknown whether transcriptional repression leads to neuronal death or what forms that death might take. We found transcriptional repression-induced atypical death (TRIAD) of neurons to be distinct from apoptosis, necrosis, or autophagy. The progression of TRIAD was extremely slow in comparison with other types of cell death. Gene expression profiling revealed the reduction of full-length yes-associated protein (YAP), a p73 cofactor to promote apoptosis, as specific to TRIAD. Furthermore, novel neuron-specific YAP isoforms (YAP[DELTA]Cs) were sustained during TRIAD to suppress neuronal death in a dominant-negative fashion. YAP[DELTA]Cs and activated p73 were colocalized in the striatal neurons of HD patients and mutant huntingtin (htt) transgenic mice. YAP[DELTA]Cs also markedly attenuated Htt-induced neuronal death in primary neuron and Drosophila melanogaster models. Collectively, transcriptional repression induces a novel prototype of neuronal death associated with the changes of YAP isoforms and p73, which might be relevant to the HD pathology.

Published
2006

28. High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer’s and Non-Alzheimer’s Disease Tauopathies

Author

Tagai, Kenji, primary, Ono, Maiko, additional, Kubota, Manabu, additional, Kitamura, Soichiro, additional, Takahata, Keisuke, additional, Seki, Chie, additional, Takado, Yuhei, additional, Shinotoh, Hitoshi, additional, Sano, Yasunori, additional, Yamamoto, Yasuharu, additional, Matsuoka, Kiwamu, additional, Takuwa, Hiroyuki, additional, Shimojo, Masafumi, additional, Takahashi, Manami, additional, Kawamura, Kazunori, additional, Kikuchi, Tatsuya, additional, Okada, Maki, additional, Akiyama, Haruhiko, additional, Suzuki, Hisaomi, additional, Onaya, Mitsumoto, additional, Takeda, Takahiro, additional, Arai, Kimihito, additional, Arai, Nobutaka, additional, Araki, Nobuyuki, additional, Saito, Yuko, additional, Trojanowski, John Q., additional, Lee, Virginia M.Y., additional, Mishra, Sushil K., additional, Yamaguchi, Yoshiki, additional, Kimura, Yasuyuki, additional, Ichise, Masanori, additional, Tomita, Yutaka, additional, Zhang, Ming-Rong, additional, Suhara, Tetsuya, additional, Shigeta, Masahiro, additional, Sahara, Naruhiko, additional, Higuchi, Makoto, additional, and Shimada, Hitoshi, additional

Published
2021
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34. Good interobserver and intraobserver agreement in the evaluation of the new ILAE classification of focal cortical dysplasias

Author

Coras, Roland, de Boer, Onno J., Armstrong, Dawna, Becker, Albert, Jacques, Thomas S., Miyata, Hajime, Thom, Maria, Vinters, Harry V., Spreafico, Roberto, Oz, Buge, Marucci, Gianluca, Pimentel, Jose, Mühlebner, Angelika, Zamecnik, Josef, Buccoliero, Anna Maria, Rogerio, Fabio, Streichenberger, Nathalie, Arai, Nobutaka, Bugiani, Marianna, Vogelgesang, Silke, Macaulay, Rob, Salon, Carolin, Hans, Volkmar, Polivka, Marc, Giangaspero, Felice, Fauziah, Dyah, Kim, Jang-Hee, Liu, Lei, Dandan, Wang, Gao, Jing, Lindeboom, Benjamin, Blümcke, Ingmar, and Aronica, Eleonora

Published
2012
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38. High-contrast in-vivo imaging of tau pathologies in Alzheimer’s and non-Alzheimer’s disease tauopathies

Author

Tagai, Kenji, primary, Ono, Maiko, additional, Kubota, Manabu, additional, Kitamura, Soichiro, additional, Takahata, Keisuke, additional, Seki, Chie, additional, Takado, Yuhei, additional, Shinotoh, Hitoshi, additional, Sano, Yasunori, additional, Matsuoka, Kiwamu, additional, Takuwa, Hiroyuki, additional, Shimojo, Masafumi, additional, Takahashi, Manami, additional, Kawamura, Kazunori, additional, Kikuchi, Tatsuya, additional, Okada, Maki, additional, Akiyama, Haruhiko, additional, Suzuki, Hisaomi, additional, Onaya, Mitsumoto, additional, Takeda, Takahiro, additional, Arai, Kimihito, additional, Arai, Nobutaka, additional, Araki, Nobuyuki, additional, Saito, Yuko, additional, Kimura, Yasuyuki, additional, Ichise, Masanori, additional, Tomita, Yutaka, additional, Zhang, Ming-Rong, additional, Suhara, Tetsuya, additional, Shigeta, Masahiro, additional, Sahara, Naruhiko, additional, Higuchi, Makoto, additional, and Shimada, Hitoshi, additional

Published
2020
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