徳島大学 / 教育研究者総覧 --- 永井隆

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徳島大学 ⟩ 病院 ⟩ 中央診療施設等 ⟩ 地域小児科診療部 ⟩
徳島大学 ⟩ 病院 ⟩ 診療科 ⟩ 小児·周産·女性科 ⟩ 小児科 ⟩

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著書・論文

学術論文(審査論文):

1.	Maki Urushihara, Shuji Kondo, Yukiko Kinoshita, Natsuko Ozaki, Ariunbold Jamba, Takashi Nagai, Keisuke Fujioka, Tomoki Hattori and Shoji Kagami : (Pro)renin receptor promotes crescent formation via the ERK1/2 and Wnt/β-catenin pathways in glomerulonephritis., American Journal of Physiology, Renal Physiology, Vol.319, No.4, F571-F578, 2020. (要約) (Pro)renin receptor [(P)RR] has multiple functions, but its regulation and role in the pathogenesis in glomerulonephritis (GN) are poorly defined. The aims of the present study were to determine the effects of direct renin inhibition (DRI) and demonstrate the role of (P)RR on the progression of crescentic GN. The anti-glomerular basement membrane nephritis rat model developed progressive proteinuria (83.64 ± 10.49 mg/day) and glomerular crescent formation (percent glomerular crescent: 62.1 ± 2.3%) accompanied by increased macrophage infiltration and glomerular expression of monocyte chemoattractant protein (MCP)-1, (P)RR, phospho-extracellular signal-regulated kinase (ERK)1/2, Wnt4, and active β-catenin. Treatment with DRI ameliorated proteinuria (20.33 ± 5.88 mg/day) and markedly reduced glomerular crescent formation (20.9 ± 2.6%), induction of macrophage infiltration, (P)RR, phospho-ERK1/2, Wnt4, and active β-catenin. Furthermore, primary cultured parietal epithelial cells stimulated by recombinant prorenin showed significant increases in cell proliferation. Notably, while the ERK1/2 inhibitor PD98059 or (P)RR-specific siRNA treatment abolished the elevation in cell proliferation, DRI treatment did not abrogate this elevation. Moreover, cultured mesangial cells showed an increase in prorenin-induced MCP-1 expression. Interestingly, (P)RR or Wnt4-specific siRNA treatment or the β-catenin antagonist XAV939 inhibited the elevation of MCP-1 expression, whereas DRI did not. These results suggest that (P)RR regulates glomerular crescent formation via the ERK1/2 signaling and Wnt/β-catenin pathways during the course of anti-glomerular basement membrane nephritis and that DRI mitigates the progression of crescentic GN through the reduction of (P)RR expression but not inhibition of prorenin binding to (P)RR. (キーワード) Amides / Animals / Cell Proliferation / Cells, Cultured / Disease Models, Animal / Fumarates / Glomerulonephritis / 男性 (male) / Mesangial Cells / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / リン酸化 (phosphorylation) / Rats, Inbred WKY / Receptors, Cell Surface / Wnt Signaling Pathway / Wnt4 Protein / beta Catenin (出版サイトへのリンク) ● Publication site (DOI): 10.1152/ajprenal.00250.2020 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32830537 ● Summary page in Scopus @ Elsevier: 2-s2.0-85091470044 (DOI: 10.1152/ajprenal.00250.2020, PubMed: 32830537, Elsevier: Scopus)
2.	Keisuke Fujioka, Takashi Nagai, Yukiko Kinoshita, Maki Urushihara, Yuko Hamasaki, Seiichiro Shishido and Shoji Kagami : Successful treatment with voriconazole combined with amphotericin B-liposome for fluconazole-resistant pulmonary cryptococcosis after renal transplantation., CEN Case Reports, Vol.8, No.4, 261-265, 2019. (要約) Cryptococcosis is an invasive fungal infection that is common among organ transplant recipients, and it is challenging to treat among these patients because of their immunocompromised status. Fluconazole (FLCZ) is recommended as a first-line treatment modality for pulmonary cryptococcosis in organ transplant recipients. However, cases of FLCZ resistance among Cryptococcus neoformans isolates have been reported from the Asia Pacific region. Previous studies have reported the efficacy of voriconazole (VRCZ) in patients with FLCZ-resistant fungal infections. Herein, we report a case of FLCZ-resistant pulmonary cryptococcosis after renal transplantation that was successfully treated with VRCZ combined with amphotericin B-liposome (L-AMB). The patient was a-23-year-old woman who underwent living-donor kidney transplantation at age 20 years. She has attended our hospital since before for mental retardation, epilepsy, and dilated cardiomyopathy. At age 23 years, she presented to our hospital with fever and cough. She was diagnosed with pulmonary cryptococcosis based on positive-serum cryptococcal antigen. Chest radiography showed bilateral consolidations. Fosfluconazole (F-FLCZ) was administered, and her condition improved. However, she developed cough and fever again on day 60 of hospitalization. Cryptococcosis recurrence was suspected due to the high degree of cryptococcal antigen titers showed (1:2048) taken on the same day. Therefore, L-AMB was added, and F-FLCZ was substituted with VRCZ. Her condition improved, but L-AMB was discontinued due to hyponatremia, hypokalemia, and elevated serum creatinine. This indicates that VRCZ caused the remission. She was discharged after 6 months of admission. In conclusion, this case shows the efficacy of VRCZ combined with L-AMB for refractory pulmonary cryptococcosis. (キーワード) Amphotericin B / Antifungal Agents / Antigens, Fungal / Combined Modality Therapy / Cryptococcosis / Cryptococcus neoformans / Drug Resistance, Fungal / 女性 (female) / Fluconazole / Humans / Kidney Transplantation / Lung Diseases, Fungal / Radiography, Thoracic / Treatment Outcome / Voriconazole / Young Adult (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s13730-019-00403-6 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31161376 ● Summary page in Scopus @ Elsevier: 2-s2.0-85085231082 (DOI: 10.1007/s13730-019-00403-6, PubMed: 31161376, Elsevier: Scopus)
3.	Shuji Kondo, Sato Matsuura, Jamba Ariunbold, Yukiko Kinoshita, Maki Urushihara, Kenichi Suga, Natsuko Ozaki, Takashi Nagai, Keisuke Fujioka and Shoji Kagami : Expression of NADPH oxidase and production of reactive oxygen species contribute to ureteric bud branching and nephrogenesis., The Journal of Medical Investigation : JMI, Vol.66, No.1.2, 93-98, 2019. (要約) Ureteric bud branching and nephrogenesis are performed through large-scale proliferation and apoptosis events during renal development. Reactive oxygen species (ROS), produced by NADPH oxidase, may contribute to cell behaviors, including proliferation and apoptosis. We investigated the role of NADPH oxidase expression and ROS production in developing kidneys. Immunohistochemistry revealed that NADPH oxidase componentswere expressed on epithelial cells in ureteric bud branches, as well as on immature glomerular cells and epithelial cells in nephrogenic zones. ROS production, detected by dihydroethidium assay, was strongly observed in ureteric bud branches and nephrogenic zones, corresponding with NADPH oxidase localization. Organ culture of E14 kidneys revealed that the inhibition of NADPH oxidase significantly reduced the number of ureteric bud branches and tips, consistent with reduced ROS production. This was associated with reduced expression of phosphorylated ERK1/2 and increased expression of cleaved caspase-3. Organ culture of E18 kidneys showed that the inhibition of NADPH oxidase reduced nephrogenic zone size, accompanied by reduced ROS production, fewer proliferating cell nuclear antigen-positive cells, lower p-ERK1/2 expression, and increased expression of cleaved caspase-3. These results demonstrate that ROS produced by NADPH oxidase might play an important role in ureteric bud branching and nephrogenesis by regulating proliferation and apoptosis. J.Med. Invest. 66 :93-98, February, 2019. (キーワード) Animals / Caspase 3 / 女性 (female) / Kidney / NADPH Oxidases / Pregnancy / Rats / Rats, Sprague-Dawley / 活性酸素 (reactive oxygen species) / Ureter (徳島大学機関リポジトリ) ● Metadata: 113341 (出版サイトへのリンク) ● Publication site (DOI): 10.2152/jmi.66.93 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31064963 ● Summary page in Scopus @ Elsevier: 2-s2.0-85065765015 (徳島大学機関リポジトリ: 113341, DOI: 10.2152/jmi.66.93, PubMed: 31064963, Elsevier: Scopus)
4.	永井隆, 漆原真樹, 藤岡啓介, 木下ゆき子, 香美祥二 : 徳島県における小児末期腎不全患者の現況, 日本小児PD・HD研究会雑誌, Vol.29, 6-8, 2017年.

総説・解説:

1.	永井隆, 香美祥二 : IgA腎症・紫斑病性腎炎の治療戦略, 小児科, Vol.59, No.10, 1433-1438, 2018年.

国内講演発表:

1.	藤岡啓介, 永井隆, 木下ゆき子, 漆原真樹, 近藤秀治, 香美祥二 : 肉眼的血尿を契機に急性尿細管壊死による腎障害を呈したIgA腎症の一例, 第41回日本小児腎不全学会学術集会, 2019年11月.
2.	漆原真樹, 藤岡啓介, 永井隆, 近藤秀治, 香美祥二 : 小児IgA腎症における腎内レニン・アンジオテンシン系活性化と炎症機序との関係, 第26回日本小児高血圧研究会, 2019年9月.
3.	永井隆, 藤岡啓介, 漆原真樹, 近藤秀治, 香美祥二 : 急速進行性腎炎症候群を呈した免疫複合体型腎炎の14歳女児例, 第52回日本小児腎臓病学会学術集会, 2019年6月.
4.	藤岡啓介, 永井隆, 木下ゆき子, 漆原真樹, 香美祥二 : 溶連菌感染後急性糸球体腎炎との鑑別を要したC3腎症の1例, 第52回日本小児腎臓病学会学術集会, 2019年6月.
5.	藤岡啓介, 永井隆, 木下ゆき子, 漆原真樹, 香美祥二 : 生体腎移植後に肺クリプトコッカス症を発症し治療に難渋した1例, 第122回日本小児科学会学術集会, 2019年4月.
6.	藤岡啓介, 永井隆, 漆原真樹, 香美祥二 : Silent lupus nephritisの所見を呈した混合性結合組織病の1例, 第70回中国四国小児科学会, 2018年11月.
7.	藤岡啓介, 永井隆, 漆原真樹, 香美祥二 : Silent lupus nephritisの所見を呈した混合性結合組織病の1例, 第35回中国四国小児腎臓病学会, 2018年11月.
8.	永井隆, 藤岡啓介, 漆原真樹, 木下ゆき子, 森一博, 香美祥二 : 腎瘻造設術および片腎摘除術を要したActinotignum schaalii膿腎症の4歳男児例, 第48回日本腎臓学会西部学術集会, 2018年9月.
9.	藤岡啓介, 永井隆, 木下ゆき子, 漆原真樹, 香美祥二 : 生体腎移植後に肺クリプトコッカス症を発症し治療に難渋した1例, 第48回日本腎臓学会西部学術大会, 2018年9月.
10.	永井隆, 漆原真樹, 藤岡啓介, 木下ゆき子, 香美祥二 : 単一県における透析および腎移植症例を通じて考察した小児末期腎不全の地域医療, 第39回日本小児腎不全学会学術集会, 2017年9月.
11.	木下ゆき子, 藤岡啓介, 永井隆, 尾崎夏子, 漆原真樹, 近藤秀治, 塚口裕康, 香美祥二 : ADCK4の遺伝子異常が同定されたステロイド抵抗性ネフローゼ症候群(SRNS)の一男児例, 第52回日本小児腎臓病学会学術集会, 2017年6月.
12.	漆原真樹, 木下ゆき子, 近藤秀治, 永井隆, 藤岡啓介, 香美祥二 : ラット半月体形成性腎炎モデルにおける(プロ)レニン受容体を介した病態機序と直接レニン阻害薬の治療効果, 第60回日本腎臓学会学術総会, 2017年5月.
13.	木下ゆき子, 藤岡啓介, 永井隆, 尾崎夏子, 漆原真樹, 近藤秀治, 塚口裕康, 香美祥二 : ADCK4の遺伝子異常が同定されたステロイド抵抗性ネフローゼ症候群(SRNS)の一例, 第120回日本小児科学会学術集会, 2017年4月.

その他・研究会:

1.	永井隆, 藤岡啓介, 漆原真樹, 香美祥二, 山崎博輝, 木下ゆき子, 森一博 : 嚥下障害を伴った若年性皮膚筋炎の1例, 第151会日本小児科学会徳島地方会, 2018年12月.
2.	藤岡啓介, 永井隆, 木下ゆき子, 漆原真樹, 香美祥二 : 生体腎移植後に肺クリプトコッカス症を発症し治療に難渋した1例, 第150回日本小児科学会徳島地方会, 2018年6月.

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

ERK経路阻害剤による半月体形成性腎炎抑制効果の検討 (研究課題/領域番号: 19K17302 )
研究者番号（20835582）による検索