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1. Digital detection of Alzheimer’s disease using smiles and conversations with a chatbot

Author

Takeshige-Amano, Haruka, Oyama, Genko, Ogawa, Mayuko, Fusegi, Keiko, Kambe, Taiki, Shiina, Kenta, Ueno, Shin-ichi, Okuzumi, Ayami, Hatano, Taku, Motoi, Yumiko, Kawakami, Ito, Ando, Maya, Nakayama, Sachiko, Ishida, Yoshinori, Maei, Shun, Lu, Xiangxun, Kobayashi, Tomohisa, Wooden, Rina, Ota, Susumu, Morito, Ken, Ito, Yoshitaka, Nakajima, Yoshihiro, Yoritaka, Asako, Kato, Tadafumi, and Hattori, Nobutaka

Published
2024
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2. Author Correction: Propagative α-synuclein seeds as serum biomarkers for synucleinopathies

Author

Okuzumi, Ayami, Hatano, Taku, Matsumoto, Gen, Nojiri, Shuko, Ueno, Shin-ichi, Imamichi-Tatano, Yoko, Kimura, Haruka, Kakuta, Soichiro, Kondo, Akihide, Fukuhara, Takeshi, Li, Yuanzhe, Funayama, Manabu, Saiki, Shinji, Taniguchi, Daisuke, Tsunemi, Taiji, McIntyre, Deborah, Gérardy, Jean-Jacques, Mittelbronn, Michel, Kruger, Rejko, Uchiyama, Yasuo, Nukina, Nobuyuki, and Hattori, Nobutaka

Published
2025
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4. Propagative α-synuclein seeds as serum biomarkers for synucleinopathies

Author

Okuzumi, Ayami, Hatano, Taku, Matsumoto, Gen, Nojiri, Shuko, Ueno, Shin-ichi, Imamichi-Tatano, Yoko, Kimura, Haruka, Kakuta, Soichiro, Kondo, Akihide, Fukuhara, Takeshi, Li, Yuanzhe, Funayama, Manabu, Saiki, Shinji, Taniguchi, Daisuke, Tsunemi, Taiji, McIntyre, Deborah, Gérardy, Jean-Jacques, Mittelbronn, Michel, Kruger, Rejko, Uchiyama, Yasuo, Nukina, Nobuyuki, and Hattori, Nobutaka

Published
2023
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5. Comparison of actionable alterations in cancers with kinase fusion, mutation, and copy number alteration.

Author

Suzuki, Shinsuke, Akahane, Toshiaki, Tanimoto, Akihide, Higashi, Michiyo, Kitazono, Ikumi, Kirishima, Mari, Nishigaki, Masakazu, Ikeda, Toshiro, Kanemitsu, Shuichi, Nakazawa, Junichi, Akahane, Erina, Nishihara, Hiroshi, Uozumi, Kimiharu, Yoshimitsu, Makoto, Ishitsuka, Kenji, and Ueno, Shin-ichi

Subjects
GENE fusion, CHIMERIC proteins, PROTEIN kinases, CARCINOGENESIS, KINASES
Abstract

Kinase-related gene fusion and point mutations play pivotal roles as drivers in cancer, necessitating optimized, targeted therapy against these alterations. The efficacy of molecularly targeted therapeutics varies depending on the specific alteration, with great success reported for such therapeutics in the treatment of cancer with kinase fusion proteins. However, the involvement of actionable alterations in solid tumors, especially regarding kinase fusions, remains unclear. Therefore, in this study, we aimed to compare the number of actionable alterations in patients with tyrosine or serine/threonine kinase domain fusions, mutations, and copy number alterations (CNAs). We analyzed 613 patients with 40 solid cancer types who visited our division between June 2020 and April 2024. Furthermore, to detect alterations involving multiple-fusion calling, we performed comprehensive genomic sequencing using FoundationOne® companion diagnostic (F1CDx) and FoundationOne® Liquid companion diagnostic (F1LCDx). Patient characteristics and genomic profiles were analyzed to assess the frequency and distribution of actionable alterations across different cancer types. Notably, 44 of the 613 patients had fusions involving kinases, transcriptional regulators, or tumor suppressors. F1CDx and F1LCDx detected 13 cases with kinase-domain fusions. We identified 117 patients with kinase-domain mutations and 58 with kinase-domain CNAs. The number of actionable alterations in patients with kinase-domain fusion, mutation, or CNA (median [interquartile range; IQR]) was 2 (1–3), 5 (3–7), and 6 (4–8), respectively. Patients with kinase fusion had significantly fewer actionable alterations than those with kinase-domain mutations and CNAs. However, those with fusion involving tumor suppressors tended to have more actionable alterations (median [IQR]; 4 [2–9]). Cancers with kinase fusions exhibited fewer actionable alterations than those with kinase mutations and CNAs. These findings underscore the importance of detecting kinase alterations and indicate the pivotal role of kinase fusions as strong drivers of cancer development, highlighting their potential as prime targets for molecular therapeutics. [ABSTRACT FROM AUTHOR]

Published
2025
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7. Comparison of actionable alterations in cancers with kinase fusion, mutation, and amplification

Author

Suzuki, Shinsuke, primary, Akahane, Toshiaki, additional, Tanimoto, Akihide, additional, Higashi, Michiyo, additional, Kitazono, Ikumi, additional, Kirishima, Mari, additional, Nishigaki, Masakazu, additional, Ikeda, Toshiro, additional, Kanemitsu, Shuichi, additional, Nakazawa, Junichi, additional, Akahane, Erina, additional, Nishihara, Hiroshi, additional, Uozumi, Kimiharu, additional, Yoshimitsu, Makoto, additional, Ishitsuka, Kenji, additional, and Ueno, Shin-ichi, additional

Published
2024
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9. Efficacy and Safety of Elobixibat in Parkinson's Disease with Chronic Constipation: CONST‐PD Study

Author

Hatano, Taku, primary, Oyama, Genko, additional, Shimo, Yasushi, additional, Ogaki, Kotaro, additional, Nishikawa, Noriko, additional, Nakamura, Ryota, additional, Tsunemi, Taiji, additional, Ogawa, Takashi, additional, Eguchi, Hiroto, additional, Daida, Kensuke, additional, Kurita, Naohide, additional, Ueno, Shin‐ichi, additional, Fukae, Jiro, additional, Sako, Wataru, additional, Shiina, Kenta, additional, Nakajima, Sho, additional, Oji, Yutaka, additional, Wakamori, Ryo, additional, Saiki, Shinji, additional, Nishioka, Kenya, additional, Okuzumi, Ayami, additional, Taniguchi, Daisuke, additional, Takeshige‐Amano, Haruka, additional, Fuse, Atsuhito, additional, Nakajima, Asuka, additional, Kano, Masayoshi, additional, Kamo, Hikaru, additional, Yamashita, Yuri, additional, Shindo, Atsuhiko, additional, Yanagisawa, Naotake, additional, and Hattori, Nobutaka, additional

Published
2024
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14. Propagative α-synuclein seeds as serum biomarkers for synucleinopathies

Author

Okuzumi, Ayami, Hatano, Taku, Matsumoto, Gen, Nojiri, Shuko, Ueno, Shin-ichi, Imamichi-Tatano, Yoko, Kimura, Haruka, Kakuta, Soichiro, Kondo, Akihide, Fukuhara, Takeshi, Li, Yuanzhe, Funayama, Manabu, Saiki, Shinji, Taniguchi, Daisuke, Tsunemi, Taiji, McIntyre, Deborah, Gérardy, Jean-Jacques, Mittelbronn, Michel, Kruger, Rejko, Uchiyama, Yasuo, Nukina, Nobuyuki, and Hattori, Nobutaka

Abstract

Abnormal α-synuclein aggregation is a key pathological feature of a group of neurodegenerative diseases known as synucleinopathies, which include Parkinson’s disease (PD), dementia with Lewy bodies and multiple system atrophy (MSA). The pathogenic β-sheet seed conformation of α-synuclein is found in various tissues, suggesting potential as a biomarker, but few studies have been able to reliably detect these seeds in serum samples. In this study, we developed a modified assay system, called immunoprecipitation-based real-time quaking-induced conversion (IP/RT-QuIC), which enables the detection of pathogenic α-synuclein seeds in the serum of individuals with synucleinopathies. In our internal first and second cohorts, IP/RT-QuIC showed high diagnostic performance for differentiating PD versus controls (area under the curve (AUC): 0.96 (95% confidence interval (CI) 0.95–0.99)/AUC: 0.93 (95% CI 0.84–1.00)) and MSA versus controls (AUC: 0.64 (95% CI 0.49–0.79)/AUC: 0.73 (95% CI 0.49–0.98)). IP/RT-QuIC also showed high diagnostic performance in differentiating individuals with PD (AUC: 0.86 (95% CI 0.74–0.99)) and MSA (AUC: 0.80 (95% CI 0.65–0.97)) from controls in a blinded external cohort. Notably, amplified seeds maintained disease-specific properties, allowing the differentiation of samples from individuals with PD versus MSA. In summary, here we present a novel platform that may allow the detection of individuals with synucleinopathies using serum samples.

Published
2024
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16. Systemic Metabolic Alteration Dependent on the Thyroid‐Liver Axis in Early PD

Author

Miyamoto, Kengo, primary, Saiki, Shinji, additional, Matsumoto, Hirotaka, additional, Suzuki, Ayami, additional, Yamashita, Yuri, additional, Iseki, Tatou, additional, Ueno, Shin‐Ichi, additional, Shiina, Kenta, additional, Kataura, Tetsushi, additional, Kamagata, Koji, additional, Imamichi, Yoko, additional, Sasazawa, Yukiko, additional, Fujimaki, Motoki, additional, Akamatsu, Wado, additional, and Hattori, Nobutaka, additional

Published
2022
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27. Systemic Metabolic Alteration Dependent on the Thyroid‐Liver Axis in Early PD.

Author

Miyamoto, Kengo, Saiki, Shinji, Matsumoto, Hirotaka, Suzuki, Ayami, Yamashita, Yuri, Iseki, Tatou, Ueno, Shin‐Ichi, Shiina, Kenta, Kataura, Tetsushi, Kamagata, Koji, Imamichi, Yoko, Sasazawa, Yukiko, Fujimaki, Motoki, Akamatsu, Wado, and Hattori, Nobutaka

Subjects
THYROID hormone regulation, PEROXISOME proliferator-activated receptors, PARKINSON'S disease, OLFACTORY bulb, LIVER cells, BLOOD testing
Abstract

Objective: Parkinson's disease (PD) is a common neurodegenerative disease characterized by initial involvement of the olfactory bulb/amygdala or autonomic nerves followed by nigral degeneration. Although autonomic innervation strictly regulates multiorgan systems, including endocrine functions, circulation, and digestion, how dysautonomia in PD affects systemic metabolism has not been identified. In this study, we tried to estimate the pathogenic linkage of PD by nuclear medicine techniques, trans‐omic analysis of blood samples, and cultured cell experiments. Methods: Thyroid mediastinum ratio of 123I‐metaiodobenzylguanidine (MIBG) scintigraphy was measured in 1,158 patients with PD. Furthermore, serum exosome miRNA transcriptome analysis and plasma metabolome analysis followed by trans‐omic analysis were performed in patients with de novo PD and age‐matched healthy control persons. Additionally, thyroid hormone was administered to skeletal muscle and liver derived cells to evaluate the effect of hypothyroidism for these organs. Results: Sympathetic denervation of thyroid correlating with its cardiac denervation was confirmed in 1,158 patients with PD by MIBG scintigraphy. Among patients with drug‐naïve PD, comprehensive metabolome analysis revealed decreased levels of thyroxine and insufficient fatty acid β‐oxidation, which positively correlate with one another. Likewise, both plasma metabolome data and transcriptome data of circulating exosomal miRNAs, revealed specific enrichment of the peroxisome proliferator‐activated receptor (PPARα) axis. Finally, association of thyroid hormone with PPARα‐dependent β‐oxidation regulation was confirmed by in vitro experiments. Interpretation: Our findings suggest that interorgan communications between the thyroid and liver are disorganized in the early stage of PD, which would be a sensitive diagnostic biomarker for PD. ANN NEUROL 2023;93:303–316 [ABSTRACT FROM AUTHOR]

Published
2023
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29. Diffusion MRI Captures White Matter Microstructure Alterations in PRKN Disease

Author

Koinuma, Takahiro, primary, Hatano, Taku, additional, Kamagata, Koji, additional, Andica, Christina, additional, Mori, Akio, additional, Ogawa, Takashi, additional, Takeshige-Amano, Haruka, additional, Uchida, Wataru, additional, Saiki, Shinji, additional, Okuzumi, Ayami, additional, Ueno, Shin-Ichi, additional, Oji, Yutaka, additional, Saito, Yuya, additional, Hori, Masaaki, additional, Aoki, Shigeki, additional, and Hattori, Nobutaka, additional

Published
2021
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30. Causal Connection Between Serum Levodopa Metabolic Profile and Medication in Parkinson’s Disease

Author

Chukyo, Akiko, primary, Fujimaki, Motoki, additional, Kaga, Naoko, additional, Taka, Hikari, additional, Li, Yuanzhe, additional, Ueno, Shin-Ichi, additional, Takeshige-Amano, Haruka, additional, Funayama, Manabu, additional, Ishimaru, Tomohiro, additional, Miyamoto, Kengo, additional, Teranishi, Hirofumi, additional, Hatano, Taku, additional, Ishikawa, Kei-Ichi, additional, Oji, Yutaka, additional, Mori, Akio, additional, Tsunemi, Taiji, additional, Ishiguro, Yuta, additional, Daida, Kensuke, additional, Imamichi, Yoko, additional, Sasazawa, Yukiko, additional, Kataura, Tetsushi, additional, Kitagawa, Mitsuhiro, additional, Nishikawa, Noriko, additional, Imoto, Masaya, additional, Ueno, Takashi, additional, Komori, Osamu, additional, Miura, Yoshiki, additional, Akamatsu, Wado, additional, Hattori, Nobutaka, additional, and Saiki, Shinji, additional

Published
2021
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32. Shared Metabolic Profile of Caffeine in Parkinsonian Disorders

Author

Takeshige‐Amano, Haruka, primary, Saiki, Shinji, additional, Fujimaki, Motoki, additional, Ueno, Shin‐Ichi, additional, Li, Yuanzhe, additional, Hatano, Taku, additional, Ishikawa, Kei‐Ichi, additional, Oji, Yutaka, additional, Mori, Akio, additional, Okuzumi, Ayami, additional, Tsunemi, Taiji, additional, Daida, Kensuke, additional, Ishiguro, Yuta, additional, Imamichi, Yoko, additional, Nanmo, Hisayoshi, additional, Nojiri, Shuko, additional, Funayama, Manabu, additional, and Hattori, Nobutaka, additional

Published
2020
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33. Variants in saposin D domain of prosaposin gene linked to Parkinson’s disease

Author

Oji, Yutaka, primary, Hatano, Taku, primary, Ueno, Shin-Ichi, primary, Funayama, Manabu, primary, Ishikawa, Kei-ichi, primary, Okuzumi, Ayami, primary, Noda, Sachiko, primary, Sato, Shigeto, primary, Satake, Wataru, primary, Toda, Tatsushi, primary, Li, Yuanzhe, primary, Hino-Takai, Tomoko, primary, Kakuta, Soichiro, primary, Tsunemi, Taiji, primary, Yoshino, Hiroyo, primary, Nishioka, Kenya, primary, Hattori, Tatsuya, primary, Mizutani, Yasuaki, primary, Mutoh, Tatsuro, primary, Yokochi, Fusako, primary, Ichinose, Yuta, primary, Koh, Kishin, primary, Shindo, Kazumasa, primary, Takiyama, Yoshihisa, primary, Hamaguchi, Tsuyoshi, primary, Yamada, Masahito, primary, Farrer, Matthew J, primary, Uchiyama, Yasuo, primary, Akamatsu, Wado, primary, Wu, Yih-Ru, primary, Matsuda, Junko, primary, and Hattori, Nobutaka, primary

Published
2020
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34. Nonmercaptalbumin as an oxidative stress marker in Parkinson’s and PARK2 disease

Author

Ueno, Shin‐Ichi, primary, Hatano, Taku, additional, Okuzumi, Ayami, additional, Saiki, Shinji, additional, Oji, Yutaka, additional, Mori, Akio, additional, Koinuma, Takahiro, additional, Fujimaki, Motoki, additional, Takeshige‐Amano, Haruka, additional, Kondo, Akihide, additional, Yoshikawa, Naoyuki, additional, Nojiri, Takahiro, additional, Kurano, Makoto, additional, Yasukawa, Keiko, additional, Yatomi, Yutaka, additional, Ikeda, Hitoshi, additional, and Hattori, Nobutaka, additional

Published
2020
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36. A metabolic profile of polyamines in parkinson disease: A promising biomarker

Author

Saiki, Shinji, primary, Sasazawa, Yukiko, additional, Fujimaki, Motoki, additional, Kamagata, Koji, additional, Kaga, Naoko, additional, Taka, Hikari, additional, Li, Yuanzhe, additional, Souma, Sanae, additional, Hatano, Taku, additional, Imamichi, Yoko, additional, Furuya, Norihiko, additional, Mori, Akio, additional, Oji, Yutaka, additional, Ueno, Shin‐Ichi, additional, Nojiri, Shuko, additional, Miura, Yoshiki, additional, Ueno, Takashi, additional, Funayama, Manabu, additional, Aoki, Shigeki, additional, and Hattori, Nobutaka, additional

Published
2019
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37. Metabolomics‐based identification of metabolic alterations in PARK2

Author

Okuzumi, Ayami, primary, Hatano, Taku, additional, Ueno, Shin‐Ichi, additional, Ogawa, Takashi, additional, Saiki, Shinji, additional, Mori, Akio, additional, Koinuma, Takahiro, additional, Oji, Yutaka, additional, Ishikawa, Kei‐Ichi, additional, Fujimaki, Motoki, additional, Sato, Shigeto, additional, Ramamoorthy, Sivapriya, additional, Mohney, Robert P., additional, and Hattori, Nobutaka, additional

Published
2019
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39. Quantitative evaluation of liver function with T1 relaxation time index on Gd-EOB-DTPA-enhanced MRI: Comparison with signal intensity-based indices

Author

Kamimura, Kiyohisa, primary, Fukukura, Yoshihiko, additional, Yoneyama, Tomohide, additional, Takumi, Koji, additional, Tateyama, Akihiro, additional, Umanodan, Aya, additional, Shindo, Toshikazu, additional, Kumagae, Yuichi, additional, Ueno, Shin-ichi, additional, Koriyama, Chihaya, additional, and Nakajo, Masayuki, additional

Published
2013
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48. Superior Mesenteric Artery Syndrome Associated with Total Situs Inversus

Author

Ishigami, Sumiya, Natsugoe, Shoji, Kuwahara, Hiroshi, Matsumoto, Masataka, Kitazono, Masaki, Shinchi, Hiroyuki, Ueno, Shin-ichi, and Aikou, Takashi

Subjects
total situs inversus, digestive, oral, and skin physiology, superior mesenteric artery
Abstract

A 58-year-old man was admitted to Kagoshima University Hospital after developing acute-onset abdominal distension. He had experienced anorexia and had lost 2 kg over the previous 3 months. An upper GI series and abdominal CT suggested duodenal obstruction with superior mesenteric artery syndrome (SMAS) and total situs inversus (TSI). As obstructive symptoms were refractory to conservative treatment with naso-gastric decompression and positional change, surgical treatment was performed 14 days after his admission. At laparotomy, complete transposition of the abdominal organs was observed. Although malrotation of the jejunum was not identified, a fibrotic stricture of the Treitz ligament was found. The duodenum and jejunum were reconstructed with duodeno-jejunostomy and jejuno-jejunostomy. Symptoms improved after surgery and the patient was discharged after 30 days, with no postoperative complications. SMA syndrome is very rarely associated with TSI, and to our knowledge, this is the first report in the literature written by English.

49. Zonisamide Administration Improves Fatty Acid β-Oxidation in Parkinson's Disease.

Author

Ueno, Shin-Ichi, Saiki, Shinji, Fujimaki, Motoki, Takeshige-Amano, Haruka, Hatano, Taku, Oyama, Genko, Ishikawa, Kei-Ichi, Yamaguchi, Akihiro, Nojiri, Shuko, Akamatsu, Wado, and Hattori, Nobutaka

Subjects
*PARKINSON'S disease diagnosis, *PARKINSON'S disease treatment, *NEURODEGENERATION, *BRAIN diseases, *FATTY acid analysis
Abstract

Although many experimental studies have shown the favorable effects of zonisamide on mitochondria using models of Parkinson's disease (PD), the influence of zonisamide on metabolism in PD patients remains unclear. To assess metabolic status under zonisamide treatment in PD, we performed a pilot study using a comprehensive metabolome analysis. Plasma samples were collected for at least one year from 30 patients with PD: 10 without zonisamide medication and 20 with zonisamide medication. We performed comprehensive metabolome analyses of plasma with capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography time-of-flight mass spectrometry. We also measured disease severity using Hoehn and Yahr (H&Y) staging and the Unified Parkinson's Disease Rating Scale (UPDRS) motor section, and analyzed blood chemistry. In PD with zonisamide treatment, 15 long-chain acylcarnitines (LCACs) tended to be increased, of which four (AC(12:0), AC(12:1)-1, AC(16:1), and AC(16:2)) showed statistical significance. Of these, two LCACs (AC(16:1) and AC(16:2)) were also identified by partial least squares analysis. There was no association of any LCAC with age, disease severity, levodopa daily dose, or levodopa equivalent dose. Because an upregulation of LCACs implies improvement of mitochondrial β-oxidation, zonisamide might be beneficial for mitochondrial β-oxidation, which is suppressed in PD. [ABSTRACT FROM AUTHOR]

Published
2019
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50. [A case of advanced rectal cancer with liver and lung metastasis showing a complete response by neo-adjuvant FOLFOX4 chemotherapy].

Author

Matsushita D, Kitazono M, Baba K, Ishigami S, Shinchi H, Ueno S, Ogawa H, and Natsugoe S

Subjects
Antimetabolites, Antineoplastic administration & dosage, Antineoplastic Agents, Phytogenic administration & dosage, Camptothecin administration & dosage, Camptothecin analogs & derivatives, Fluorouracil administration & dosage, Humans, Irinotecan, Leucovorin administration & dosage, Male, Middle Aged, Neoadjuvant Therapy, Rectal Neoplasms pathology, Rectal Neoplasms surgery, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Liver Neoplasms secondary, Lung Neoplasms secondary, Rectal Neoplasms drug therapy
Abstract

A 56-year-old man with abnormal chest X-P and stool occult bleeding was admitted. Colonoscopy detected rectal cancer and sigmoid al polyps. The biopsy results suggested that the rectal lesion was well- to moderately-differentiated adenocarcinoma and the sigmoidal polyp contained well -differentiated adenocarcinoma. CT scan revealed multiple lung, liver and lymph node metastasis. We judged the case to be inoperable and decided to start systemic chemotherapy (FOLFOX4). After treatment with chemotherapy, the tumor shrank and metastatic lesions disappeared. Low anterior resection was done, and final pathological examination revealed a complete response of the main tumor by treating with FOLFOX4.

Published
2010

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