内耳前庭細胞由来の培養上清を用いた胚性幹細胞から内耳前庭有毛細胞への分化誘導

Vestibular hair cells (V-HCs) in the inner ear have important roles and various functions. When V-HCs are damaged, crippling symptoms, such as vertigo, visual field oscillation, and imbalance, are often seen. Recently, several studies have reported differentiation of embryonic stem (ES) cells, as pluripotent stem cells, to HCs, though a method for producing V-HCs has yet to be established. In the present study, we used vestibular cell conditioned medium (V-CM) and effectively induced ES cells to differentiate into V-HCs. Expressions of V-HC-related markers (Math1, Myosin6, Brn3c, Dnah5) were significantly increased in ES cells cultured in V-CM for 2 weeks, while those were not observed in ES cells cultured without V-CM. On the other hand, the cochlear HC-related marker Lmod3 was either not detected or detected only faintly in those cells when cultured in V-CM. Our results demonstrate that V-CM has an ability to specifically induce differentiation of ES cells into V-HCs.博士（医学）・甲第743号・令和2年3月16日© 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/)

内耳前庭細胞由来因子とオルガノイド培養を組み合わせたES細胞から内耳前庭有毛細胞への分化誘導

Vestibular hair cells (V-HCs) residing in the inner ear have important roles related to balance. Although differentiation of pluripotent stem cells into HCs has been shown, an effective method has yet to be established. We previously reported that use of vestibular cell-derived conditioned medium (V-CM) was helpful to induce embryonic stem (ES) cells to differentiate into V-HC-like cells in two-dimensional (2D) cultures of ES-derived embryoid bodies (EBs). In the present report, V-CM was used with three-dimensional (3D) cultures of EBs, which resulted in augmented expression of V-HC-related markers (Math1, Myosin6, Brn3c, Dnah5), but not of the cochlear HC-related marker Lmod3. Gene expression analyses of both 2D and 3D EBs cultured for two weeks revealed a greater level of augmented induction of HC-related markers in the 3D-cultured EBs. These results indicate that a 3D culture in combination with use of V-CM is an effective method for producing V-HCs.博士（医学）・甲第877号・令和5年3月15

Active Enhancement of Rat Cardiac Allografts by Donor-Specific B Lymphocytes

In an attempt to induce the active enhancement of the cardiac allografts, recipient rats were injected intravenously with 1 x 107 donor-specific spleen cells or an equal number of their T or B cell subpopulations on each of 7 days before transplantation. Mean survival times (MST) in the group pretreated with donor-specific spleen cells (MST 27.5 ± 7.8 days) and the group pretreated with donor-specific B cells (MST 37.5 ± 15.5 days) were significantly prolonged (p<0.01) compared with the untreated control (MST 11.6 ± 2.0 days) and the group pretreated with donor-specific T cells. To investigate the mechanisms of the beneficial effect of donor-specific B cells on rat cardiac allografts, inhibition assay of mixed lymphocyte reaction (MLR) were carried out by the addition of recipient rat sera or spleen cells harvested 7 days following the intravenous administration of donor-specific spleen cells or their T and B cell subpopulations. Recipient rat sera harvested 7 days following the intravenous administration of donor-specific B cells showed significant inhibition of MLR; this inhibition was correlated to the prolonged survival of histoincompatible rat cardiac allografts. In contrast, MLR suppressor cells could not be detected in any experimental group. Thus, donor-specific B cell given 7 days before transplantation may possibly have beneficial effect on rat cardiac allografts and MLR inhibition induced by the intravenous administration of donor-specific B cells may be essential for prolonged allograft survival

サリチル酸誘発耳鳴に対する牛車腎気丸の抑制効果の行動学的および免疫組織化学的な根拠

Many people are affected by tinnitus, a sensation of ringing in the ear despite the absence of external sound. Goshajinkigan (GJG) is one of the formulations of Japanese traditional herbal medicine and is prescribed for the palliative treatment of patients with tinnitus. Although GJG is clinically effective in these patients, its behavioral effects and the underlying neuroanatomical substrate have not been modeled in animals. We modeled tinnitus using salicylate-treated rats, demonstrated the effectiveness of GJG on tinnitus, and examined the underlying neuronal substrate with c-Fos expression. Intraperitoneal injection of sodium salicylate (400 mg/kg) into rats for three consecutive days significantly increased false positive scores, which were used to assess tinnitus behavior. When GJG was orally administered one hour after each salicylate injection, the increase in tinnitus behavior was suppressed. The analysis of c-Fos expression in auditory-related brain areas revealed that GJG significantly reduced the salicylate-induced increase in the number of c-Fos-expressing cells in the auditory cortices, inferior colliculus, and dorsal cochlear nucleus. These results suggest a suppressive effect of GJG on salicylate-induced tinnitus in animal models.博士（医学）・甲第851号・令和4年9月28日Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)

Demonstration of a spherical plasma mirror for the counter-propagating kilojoule-class petawatt LFEX laser system

A counter-propagating laser-beam platform using a spherical plasma mirror was developed for the kilojoule-class petawatt LFEX laser. The temporal and spatial overlaps of the incoming and redirected beams were measured with an optical interferometer and an x-ray pinhole camera. The plasma mirror performance was evaluated by measuring fast electrons, ions, and neutrons generated in the counter-propagating laser interaction with a Cu-doped deuterated film on both sides. The reflectivity and peak intensity were estimated as ∼50% and ∼5 × 1018 W/cm2, respectively. The platform could enable studies of counter-streaming charged particles in high-energy-density plasmas for fundamental and inertial confinement fusion research.Kojima S., Abe Y., Miura E., et al. Demonstration of a spherical plasma mirror for the counter-propagating kilojoule-class petawatt LFEX laser system. Optics Express 30, 43491 (2022); https://doi.org/10.1364/oe.475945

Differentiation of embryonic stem cells into inner ear vestibular hair cells using vestibular cell derived-conditioned medium.

Vestibular hair cells (V-HCs) in the inner ear have important roles and various functions. When V-HCs are damaged, crippling symptoms, such as vertigo, visual field oscillation, and imbalance, are often seen. Recently, several studies have reported differentiation of embryonic stem (ES) cells, as pluripotent stem cells, to HCs, though a method for producing V-HCs has yet to be established. In the present study, we used vestibular cell conditioned medium (V-CM) and effectively induced ES cells to differentiate into V-HCs. Expressions of V-HC-related markers (Math1, Myosin6, Brn3c, Dnah5) were significantly increased in ES cells cultured in V-CM for 2 weeks, while those were not observed in ES cells cultured without V-CM. On the other hand, the cochlear HC-related marker Lmod3 was either not detected or detected only faintly in those cells when cultured in V-CM. Our results demonstrate that V-CM has an ability to specifically induce differentiation of ES cells into V-HCs.博士（医学）・甲第743号・令和2年3月16日© 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).identifier:Biochemistry and biophysics reports Vol.19 Article No.100649 (2019 May)identifier:24055808identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3737identifier:Biochemistry and biophysics reports, 19: Article No.10064