チアノーゼ性先天性心疾患に伴う褐色細胞腫及びパラガングリオーマの遺伝学的解析

京都大学新制・課程博士博士(医学)甲第24314号医博第4908号新制||医||1062(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 小林 恭, 教授 松田 文彦, 教授 柳田 素子学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

ミンジ シンタク ト イリュウブン トウキョウ チサイ ヘイセイ 30ネン 9ガツ 12ニチ ハンケツ ノ ケントウ

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Impact of extracellular matrix on engraftment and maturation of pluripotent stem cell-derived cardiomyocytes in a rat myocardial infarct model

Pluripotent stem cell-derived cardiomyocytes show great promise in regenerating the heart after myocardial infarction; however, several uncertainties exist that must be addressed before clinical trials. One practical issue is graft survival following transplantation. Although a pro-survival cocktail with Matrigel has been shown to enhance graft survival, the use of Matrigel may not be clinically feasible. The purpose of this study was to test whether a hyaluronan-based hydrogel, HyStem, could be a substitute for Matrigel. Human induced pluripotent stem cell-derived cardiomyocytes diluted with HyStem alone, HyStem plus pro-survival factors, or a pro-survival cocktail with Matrigel (PSC/MG), were transplanted into a rat model of acute myocardial infarction. Histological analysis at 4 weeks post transplantation revealed that, among the three groups, recipients of PSC/MG showed the largest graft size. Additionally, the grafted cardiomyocytes in the recipients of PSC/MG had a more matured phenotype compared to those in the other two groups. These findings suggest that further studies will be required to enhance not only graft size, but also the maturation of grafted cardiomyocytes.ArticleScientific reports 7(1) : 8630-(2017)journal articl

Long-run effects of early childhood exposure to cholera on final height: Evidence from industrializing Japan

Pandemic cholera is one of the most topical and urgent issues in many developing countries. However, although a growing body of research has shown the negative long-run effects of infectious disease exposure on human health, the long-run influences of early childhood exposure to cholera have thus far been understudied. To bridge this gap in the body of knowledge, we draw both on new data describing adult height from 1899 to 1910 from comprehensive official Japanese army records and on data recording the regional variation in the intensity of cholera pandemics. By using a difference-in-differences estimation strategy, we find that exposure to pandemic cholera had stunting effects on the final height of men at that time. Our estimates also suggest that early-infancy exposure to cholera seems to have a stronger long-run effect on adult height than late-infancy exposure. JEL: I19, Keywords: Early-life health, Fetal origins, Pandemic cholera, Height, Long-run effec

A Novel Hemocyte-Derived Peptide and Its Possible Roles in Immune Response of <i>Ciona intestinalis</i> Type A

A wide variety of bioactive peptides have been identified in the central nervous system and several peripheral tissues in the ascidian Ciona intestinalis type A (Ciona robusta). However, hemocyte endocrine peptides have yet to be explored. Here, we report a novel 14-amino-acid peptide, CiEMa, that is predominant in the granular hemocytes and unilocular refractile granulocytes of Ciona. RNA-seq and qRT-PCR revealed the high CiEma expression in the adult pharynx and stomach. Immunohistochemistry further revealed the highly concentrated CiEMa in the hemolymph of the pharynx and epithelial cells of the stomach, suggesting biological roles in the immune response. Notably, bacterial lipopolysaccharide stimulation of isolated hemocytes for 1–4 h resulted in 1.9- to 2.4-fold increased CiEMa secretion. Furthermore, CiEMa-stimulated pharynx exhibited mRNA upregulation of the growth factor (Fgf3/7/10/22), vanadium binding proteins (CiVanabin1 and CiVanabin3), and forkhead and homeobox transcription factors (Foxl2, Hox3, and Dbx) but not antimicrobial peptides (CrPap-a and CrMam-a) or immune-related genes (Tgfbtun3, Tnfa, and Il17-2). Collectively, these results suggest that CiEMa plays roles in signal transduction involving tissue development or repair in the immune response, rather than in the direct regulation of immune response genes. The present study identified a novel Ciona hemocyte peptide, CiEMa, which paves the way for research on the biological roles of hemocyte peptides in chordates