研究者業績

藤垣 英嗣

フジガキ ヒデツグ  (Hidetsugu Fujigaki)

基本情報

所属
藤田医科大学 大学院医療科学研究科 准教授
学位
博士(医学)(岐阜大学大学院医学系研究科)

J-GLOBAL ID
201401031120168097
researchmap会員ID
B000235779

委員歴

 1

論文

 75
  • Masaya Hasegawa, Kazuo Kunisawa, Bolati Wulaer, Hisayoshi Kubota, Hitomi Kurahashi, Takatoshi Sakata, Honomi Ando, Suwako Fujigaki, Hidetsugu Fujigaki, Yasuko Yamamoto, Taku Nagai, Kuniaki Saito, Toshitaka Nabeshima, Akihiro Mouri
    British Journal of Pharmacology 2024年12月10日  
    Background and Purpose Alterations in tryptophan‐kynurenine (TRP‐KYN) pathway are implicated in major depressive disorder (MDD). α7 nicotinic acetylcholine (α7nACh) receptor regulates the hypothalamic–pituitary–adrenal (HPA) axis. We have shown that deficiency of kynurenine 3‐monooxygenase (KMO) induces depression‐like behaviour via kynurenic acid (KYNA; α7nACh antagonist). In this study, we investigated the involvement of the TRP‐KYN pathway in stress‐induced behavioural changes and the regulation of the HPA axis. Experimental Approach Mice were exposed to chronic unpredictable mild stress (CUMS) and subjected to behavioural tests. We measured TRP‐KYN metabolites and the expression of their enzymes in the hippocampus. KMO heterozygous mice were used to investigate stress vulnerability. We also evaluated the effect of nicotine (s.c.) on CUMS‐induced behavioural changes and an increase in serum corticosterone (CORT) concentration. Key Results CUMS decreased social interaction time but increased immobility time under tail suspension associated with increased serum corticosterone concentration. CUMS increased KYNA levels via KMO suppression with microglial decline in the hippocampus. Kmo+/− mice were vulnerable to stress: they exhibited social impairment and increased serum corticosterone concentration even after short‐term CUMS. Nicotine attenuated CUMS‐induced behavioural changes and increased serum corticosterone concentration by inhibiting the increase in corticotropin‐releasing hormone. Methyllycaconitine (α7nACh antagonist) inhibited the attenuating effect of nicotine. Conclusions and Implications CUMS‐induced behavioural changes and the HPA axis dysregulation could be induced by the increased levels of KYNA via KMO suppression. KYNA plays an important role in the pathophysiology of MDD as an α7nACh antagonist. Therefore, α7nACh receptor is an attractive therapeutic target for MDD.
  • Masaya Hasegawa, Moe Niijima, Kazuo Kunisawa, Tomoaki Teshigawara, Hisayoshi Kubota, Suwako Fujigaki, Hidetsugu Fujigaki, Yasuko Yamamoto, Hyoung-Chun Kim, Kuniaki Saito, Toshitaka Nabeshima, Akihiro Mouri
    Biochemical and Biophysical Research Communications 737 150922-150922 2024年12月  
  • Miho Imaeda, Satoshi Tanaka, Tomoko Oya-Ito, Mariko Uematsu, Hidetsugu Fujigaki, Kuniaki Saito, Masahiko Ando, Norio Ozaki
    Journal of Eating Disorders 12(1) 2024年12月  
    Background: Secondary carnitine deficiency in patients with anorexia nervosa has been rarely reported. This study aimed to investigate the occurrence of carnitine deficiency in severely malnourished patients with eating disorders during refeeding and assess its potential adverse effects on treatment outcomes. Method: In a cohort study of 56 female inpatients with eating disorders at a single hospital from March 2010 to December 2020, we measured plasma free carnitine (FC) levels and compared to those of a healthy control group (n = 35). The patients were categorized into three groups based on FC levels: FC deficiency (FC< 20 µmol/L), FC pre-deficiency (20 µmol/L ≤ FC< 36 µmol/L), and FC normal (36 µmol/L ≤ FC). Results: Upon admission, the patients had a median age of 26 years (interquartile range [IQR]: 21–35) and a median body mass index (BMI) of 13.8 kg/m2 (IQR: 12.8–14.8). Carnitine deficiency or pre-deficiency was identified in 57% of the patients. Hypocarnitinemia was associated with a decline in hemoglobin levels during refeeding (odds ratio [OR]: 0.445; 95% confidence interval [CI]: 0.214–0.926, p = 0.03), BMI at admission (OR: 0.478; 95% CI: 0.217–0.874, p = 0.014), and moderate or greater hepatic impairment at admission (OR: 6.385; 95% CI: 1.170–40.833, p = 0.032). Conclusions: Hypocarnitinemia, particularly in cases of severe undernutrition (BMI< 13 kg/m2 at admission) was observed in severely malnourished patients with eating disorders during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment at admission was considered a potential indicator of hypocarnitinemia. Although hypocarnitinemia was not associated with any apparent adverse events other than anemia during refeeding, the possibility that carnitine deficiency may be a risk factor for more serious complications during sudden increases in energy requirements associated with changes in physical status cannot be denied. Further research on the clinical significance of hypocarnitinemia in severely malnourished patients with eating disorders is warranted.
  • Yuya Ishihara, Hiroyuki Naruse, Hidetsugu Fujigaki, Reiko Murakami, Tatsuya Ando, Kouhei Sakurai, Komei Uehara, Koki Shimomae, Eirin Sakaguchi, Hidekazu Hattori, Masayoshi Sarai, Junnichi Ishii, Ryosuke Fujii, Hiroyasu Ito, Kuniaki Saito, Hideo Izawa
    Vaccines 12(7) 786-786 2024年7月17日  
    Preexisting cardiovascular disease (CVD) is a pivotal risk factor for severe coronavirus disease 2019 (COVID-19). We investigated the longitudinal (over 1 year and 9 months) humoral and cellular responses to primary series and booster doses of mRNA COVID-19 vaccines in patients with CVD. Twenty-six patients with CVD who received monovalent mRNA COVID-19 vaccines were enrolled in this study. Peripheral blood samples were serially drawn nine times from each patient. IgG against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) was measured using an enzyme-linked immunosorbent assay. The numbers of interferon-γ-releasing cells in response to SARS-CoV-2 peptides were measured using an enzyme-linked immunospot assay. The RBD-IgG titers increased 2 weeks after the primary series and booster vaccination and waned 6 months after vaccination. The S1-specific T cell responses in patients aged &lt; 75 years were favorable before and after booster doses; however, the Omicron BA.1-specific T cell responses were poor. These results suggest that regular vaccination is useful to maintain long-term antibody levels and has implications for booster dose strategies in patients with CVD. Additional booster doses, including Omicron variant-adapted mRNA vaccines, may be recommended for patients with CVD, regardless of age.
  • 竹村 正男, 藤垣 英嗣, 山本 康子, 佐藤 正夫, 出田 貴康, 清水 雅仁, 齋藤 邦明
    臨床化学 53(Suppl.1) 204-204 2024年7月  

MISC

 99

講演・口頭発表等

 42
  • 石田 秀和, 竹村 正男, 藤垣 英嗣, 佐藤 正夫, 四戸 隆基, 出田 貴康, 齋藤 邦明
    医療検査と自動化 2022年8月 (一社)日本医療検査科学会
  • 安藤 穂乃実, 藤垣 英嗣, 竹村 正男, 石田 秀和, 山本 康子, 齋藤 邦明
    医療検査と自動化 2022年8月 (一社)日本医療検査科学会
  • 藤垣 英嗣, 竹村 正男, 安藤 穂乃実, 齋藤 邦明
    医療検査と自動化 2022年8月 (一社)日本医療検査科学会
  • 竹村 正男, 出田 貴康, 佐藤 正夫, 石田 秀和, 藤垣 英嗣, 山本 康子, 佐々木 智弘, 竹村 恵里奈, 斉藤 邦明
    臨床リウマチ 2022年6月 (一社)日本臨床リウマチ学会
    LPSは炎症の成立に重要な役割を果たしている。LPSはLPS結合蛋白(LBP)と結合し、さらにCD14が結合することで炎症シグナルを細胞内に誘導する。今回、我々は長期療養(5年以上)のRA患者を対象に、高感度法によるLBPの定量とACPA抗体の変動を調査した。また炎症の指標とされているCRPおよびIL-6の測定を同時に行いバイオマーカーとしてのLBPの臨床的意義について検討を行った。血中LBP値(Mean±SD)は健常者3.69±1.26μg/mL、OA群6.05±2.40μg/mL、RA群11.10±5.16μg/mLであり、RA群で最も有意に高値を示した(p<0.0001)。さらにstage、classの亢進に伴いLBPが増加した。また、ACPAとは相関(r=0.410)を認め、陽性群と陰性群での比較では陽性例が有意(p<0.002)に高値であった。このことから高感度法によるLBPの測定はRAの新たな病態解析の指標の一つになる可能性が有るものと考える。(著者抄録)
  • 北川 順一, 岡本 晃直, 藤垣 英嗣, 入山 智沙子, 後藤 尚絵, 山本 秀行, 徳田 倍将, 加藤 俊晴, 宮尾 康太郎, 笠原 千嗣, 美山 貴彦, 三原 圭一郎, 岡本 昌隆, 齋藤 邦明, 冨田 章裕
    日本リンパ網内系学会会誌 2022年6月 (一社)日本リンパ網内系学会

共同研究・競争的資金等の研究課題

 9

その他

 1
  • ①高感度トリプトファン代謝産物測定系 ②キヌレニンアミノトランスフェラーゼ活性を阻害する化合物 ②抗新型コロナウイルス抗体測定系 *本研究シーズに関する産学共同研究の問い合わせは藤田医科大学産学連携推進センター(fuji-san@fujita-hu.ac.jp)まで