2013年度博士論文 http://hdl.handle.net/10564/2586 2026-04-09T03:49:08Z 2026-04-09T03:49:08Z Toritsuka, Michihiro Kimoto, Sohei Muraki, Kazue Landek-Salgado, Melissa A Yoshida, Atsuhiro Yamamoto, Norio Horiuchi, Yasue Hiyama, Hideki Tajinda, Katsunori Keni, Ni Illingworth, Elizabeth Iwamoto, Takashi Kishimoto, Toshifumi Sawa, Akira Tanigaki, Kenji http://hdl.handle.net/10564/2716 2017-05-29T06:07:26Z 2013-10-21T15:00:00Z

タイトル: Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model. 著者: Toritsuka, Michihiro; Kimoto, Sohei; Muraki, Kazue; Landek-Salgado, Melissa A; Yoshida, Atsuhiro; Yamamoto, Norio; Horiuchi, Yasue; Hiyama, Hideki; Tajinda, Katsunori; Keni, Ni; Illingworth, Elizabeth; Iwamoto, Takashi; Kishimoto, Toshifumi; Sawa, Akira; Tanigaki, Kenji 抄録: 22q11 deletion syndrome (22q11DS) frequently accompanies psychiatric conditions, some of which are classified as schizophrenia and bipolar disorder in the current diagnostic categorization. However, it remains elusive how the chromosomal microdeletion leads to the mental manifestation at the mechanistic level. Here we show that a 22q11DS mouse model with a deletion of 18 orthologous genes of human 22q11 (Df1/+ mice) has deficits in migration of cortical interneurons and hippocampal dentate precursor cells. Furthermore, Df1/+ mice show functional defects in Chemokine receptor 4/Chemokine ligand 12 (Cxcr4/Cxcl12; Sdf1) signaling, which reportedly underlie interneuron migration. Notably, the defects in interneuron progenitors are rescued by ectopic expression of Dgcr8, one of the genes in 22q11 microdeletion. Furthermore, heterozygous knockout mice for Dgcr8 show similar neurodevelopmental abnormalities as Df1/+ mice. Thus, Dgcr8-mediated regulation of microRNA is likely to underlie Cxcr4/Cxcl12 signaling and associated neurodevelopmental defects. Finally, we observe that expression of CXCL12 is decreased in olfactory neurons from sporadic cases with schizophrenia compared with normal controls. Given the increased risk of 22q11DS in schizophrenia that frequently shows interneuron abnormalities, the overall study suggests that CXCR4/CXCL12 signaling may represent a common downstream mediator in the pathophysiology of schizophrenia and related mental conditions. 内容記述: 博士（医学）・乙1331号・平成26年3月17日

2013-10-21T15:00:00Z Kodama, Makoto Matsuura, Toyoaki Hara, Yoshiaki http://hdl.handle.net/10564/2715 2017-05-29T06:07:26Z 2013-06-30T15:00:00Z

タイトル: Structure of vitreous body and its relationship with liquefaction. 著者: Kodama, Makoto; Matsuura, Toyoaki; Hara, Yoshiaki 抄録: The aim of the study is to clarify the vitreous body structure and liquefaction phenomena. It was found that when melting a frozen rabbit vitreous body, the gel-sol transition phenomenon occurs and the gel structure is broken. This is almost like the liquefaction of the vitreous body in vivo. We try to clarify the liquefaction phenomenon by using this animal model. The native vitreous body has three dimensional meshwork structures. After liquefaction, it is changed into two parts, namely fiber aggregates and soluble amorphous aggregates. The surface of native vitreous body meshwork is mucopolysacharide, but that of fiber aggregates after liquefaction is changed into connective tissue, which means the conformational change of vitreous body in liquefaction. The soluble proteins after liquefaction were analyzed and identified as crystallin family. It is suggested that the liquefaction is induced by detachment of non-collagenous protein beads containing crystallins, resulting in the collapse of the three dimensional structure to release watery liquid trapped within. And the new gel-sol transition model of vitreous bod is proposed. 内容記述: 博士（医学）・乙1330号・平成26年3月17日

2013-06-30T15:00:00Z Aoki, Kumiko Obata, Koji Kurihara, Miyako Kuniyasu, Hiroki Kirita, Tadaaki Takaki, Miyako http://hdl.handle.net/10564/2714 2022-08-02T06:48:49Z 2013-06-03T15:00:00Z

タイトル: Possible peripheral mechanism for taste disorder in rats administered S-1. 著者: Aoki, Kumiko; Obata, Koji; Kurihara, Miyako; Kuniyasu, Hiroki; Kirita, Tadaaki; Takaki, Miyako 抄録: BACKGROUND: Taste disorders are frequently observed in cancer patients undergoing chemotherapy and are serious adverse events which impair the quality of life (QoL) of the cancer patient. Nevertheless, taste disorder mechanisms in cancer patients undergoing chemotherapy have not yet been fully elucidated. The aim of this study was to reveal taste disorder-related peripheral mechanisms using the two-bottle preference test (TBPT) and histological examination of tongues by hematoxylin-eosin staining and immunohistochemistry with protein-gene product 9.5. METHODS: In the TBPT, one bottle was filled with the 0.01 mM quinine hydrochloride (quinine), as a bitter compound, and the other was filled with water. Doses of 50 and 100 mg kg-1 day-1 S-1 (tegafur/gimeracil/oteracil potassium) are lethal to Wistar rats. Therefore, doses ranging from 2-20 mg kg-1 day-1 were administered to the rats for 3 weeks. The S-1 dose of 2 mg kg-1 day-1 corresponds to the clinical dose administered to cancer patients. The part of the tongue containing the circumvallate papillae was excised the following TBPT. RESULTS: The rate of increase in terms of the average preference rate for the quinine vs. all intake (quinine plus water) was significant from the initial S-1 period to the final one, compared with that in control rats, suggesting the possibility of a worsening sensation for the bitter taste. In S-1 rats, the area of taste nerve fibers were significantly decreased and the rate of degeneration of intra-tongue ganglionic nerve cells was significantly increased. These changes were significantly correlated with the rate of increase in average preference rate of the quinine. CONCLUSION: Neuropathy of the gustatory nerve at the periphery may be involved in taste disorders induced by an anticancer drug. 内容記述: 博士（医学）・乙1329号・平成26年3月17日; © Japan Society of Clinical Oncology 2013; This is a post-peer-review, pre-copyedit version of an article published in International journal of clinical oncology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10147-013-0572-3.

2013-06-03T15:00:00Z Katayama, Takeshi Ono, Hiroshi Suzuki, Daisuke Akahane, Manabu Omokawa, Shohei Tanaka, Yasuhito http://hdl.handle.net/10564/2713 2017-05-29T06:07:02Z 2013-08-31T15:00:00Z

タイトル: Distribution of primary osteoarthritis in the ulnar aspect of the wrist and the factors that are correlated with ulnar wrist osteoarthritis: a cross-sectional study. 著者: Katayama, Takeshi; Ono, Hiroshi; Suzuki, Daisuke; Akahane, Manabu; Omokawa, Shohei; Tanaka, Yasuhito 抄録: OBJECTIVE: The purpose of this cross-sectional study was to identify the distribution of primary osteoarthritis (OA) in the ulnar aspect of the wrist, and analyze the factors correlated with OA at this site. MATERIALS AND METHODS: A total of 1,128 cases of skeletally mature Japanese patients were collected over a 3-year period. We analyzed the posteroanterior and lateral wrist radiographs of these patients for the presence of primary OA in the ulnar aspect of the wrist, including the distal radioulnar (DRUJ), radiolunate, ulnolunate, lunotriquetral, triquetrohamate, lunohamate, and lunocapitate joints. All joints were examined for the frequency of primary OA. Multivariate logistic regression was used to investigate the factors correlated with the presence of degenerative arthritis in the ulnar aspect of the wrist joint. RESULTS: Primary OA of the ulnar wrist was identified in 145 out of 1,128 cases (12.8 %). Degenerative changes were most frequently identified in the DRUJ (12.3 %), followed by the ulnolunate joint (8.1 %). Variations in radial inclination (RI), carpal height ratio (CHR), and ulnar variance (UV) correlated with OA of the ulnar aspect of the wrist, with variations in UV showing the highest correlation. CONCLUSION: Primary OA of the ulnar wrist was most frequent in the DRUJ and second most frequent in the ulnolunate joint. UV correlated most with OA in the ulnar aspect of the wrist. 内容記述: 博士（医学）・乙1328号・平成26年3月17日; The definitive version is available at " http://dx.doi.org/10.1007/s00256-013-1665-9 "

2013-08-31T15:00:00Z