原爆の被爆継承に関する考察―青少年ピースボランティアを事例に―

本稿では、原爆の被爆継承においてこれからどのような方法が必要なのかを考察するために、青少年ピースボランティアを事例に取り上げ、アンケート調査を実施した。このアンケート調査で、青少年ピースボランティアのメンバーは様々な目的を持って参加し、様々な目的から活動を継続していることが明らかとなった。活動に原爆や平和に関することだけを含むのではなく、様々な要素を含め、入口を広くし、原爆や平和に関心がない人も取り入れる方法が必要である。また二次解析を行い、t検定で加入前と現在とで意識の有意差が見られ、相関係数を算出し「活動の満足度」と「被爆継承における貢献度」との関連性が高いことが明らかとなった

The development of the adult intestinal stem cells: Insights from studies on thyroid hormone-dependent amphibian metamorphosis

Adult organ-specific stem cells are essential for organ homeostasis and repair in adult vertebrates. The intestine is one of the best-studied organs in this regard. The intestinal epithelium undergoes constant self-renewal throughout adult life across vertebrates through the proliferation and subsequent differentiation of the adult stem cells. This self-renewal system is established late during development, around birth, in mammals when endogenous thyroid hormone (T3) levels are high. Amphibian metamorphosis resembles mammalian postembryonic development around birth and is totally dependent upon the presence of high levels of T3. During this process, the tadpole intestine, predominantly a monolayer of larval epithelial cells, undergoes drastic transformation. The larval epithelial cells undergo apoptosis and concurrently, adult epithelial stem/progenitor cells develop de novo, rapidly proliferate, and then differentiate to establish a trough-crest axis of the epithelial fold, resembling the crypt-villus axis in the adult mammalian intestine. We and others have studied the T3-dependent remodeling of the intestine in Xenopus laevis. Here we will highlight some of the recent findings on the origin of the adult intestinal stem cells. We will discuss observations suggesting that liganded T3 receptor (TR) regulates cell autonomous formation of adult intestinal progenitor cells and that T3 action in the connective tissue is important for the establishment of the stem cell niche. We will further review evidence suggesting similar T3-dependent formation of adult intestinal stem cells in other vertebrates

Magnetic characterization change by solvents of magnetic nanoparticles in liquid-phase magnetic immunoassay

Liquid-phase magnetic immunoassay (MIA) using magnetic nano-particles (MNPs) has been studied as a more rapid method compared to optical methods for inspecting proteins and viruses. MIA can estimate the number of conjugated antibodies without being washed differently from conventional optical immunoassay. However, in the case of the liquid phase, it is considered that the magnetic properties of MNPs are affected by physical properties such as viscosity and impurity substances such as biological substances contained in the blood. In this study, the effect of sodium chloride (NaCl) in buffer and serum solution was evaluated to reveal the effect of serum because the sodium (Na+) and chloride (Cl-) ions in the serum dominate ion balance of blood. The measurement results of AC magnetic susceptibility and a dynamic light scattering (DLS) showed that the aggregation of MNPs was largely affected by the concentration of NaCl. This effect of the NaCl could be explained by shielding of the surface charge of MNPs by ions in the solution. Although the concentrations of NaCl in the buffer and serum solution were almost same, we found that MNPs were aggregated more in their size for those in the serum solution because of other impurities, such as proteins. These results suggest evaluation of effects of the contaminants in serum and optimization of polymer coatings of MNPs could be important factors to realize measurements of magnetic immunoassay with high accuracy. (C) 2019 Author(s)

Laser monitoring of dynamic behavior of magnetic nanoparticles in magnetic field gradient

Manipulation of magnetic nanoparticles (MNP) by an external magnetic field has been widely studied in the fields of biotechnology and medicine for collecting and/or reacting biomaterials in the solutions. Here, dynamic behaviors of MNP in solution under changing gradient magnetic field were investigated using our newly developed laser transmission system (LTS) with a variable magnetic field manipulator. The manipulator consists of a moving permanent magnet placed beside the optical cell filled with MNP solution. A laser beam was focused on the cell and the transmitted laser beam was detected by a silicon photodiode, so that the localized concentration of the MNP at the focused area could be evaluated by the intensity of transmitted laser beam. In this study, the LTS was applied to evaluate dynamic behaviors of MNP in serum solution. Dispersion and aggregation of MNP in the solution were evaluated. While time evolution of dispersion depends on the serum concentration, the behavior during aggregation by the magnetic field was independent of the serum concentration. A series of measurements for zeta-potentials, distributions of particle size, and magnetization distributions was carried out to understand this difference in the behavior. The results indicated that a Brownian motion was main force to distribute the MNP in the solution; on the other hand, the magnetic force to the MNP mainly affected the behavior during aggregation of the MNP in the solution

去勢抵抗性前立腺癌におけるKlothoγのドセタキセル抵抗性との関連と新規治療としての可能性

The Klotho (KL) gene was first identified as a potent aging suppressor. The KL family currently comprises of three proteins: α-Klotho (KLA), β-Klotho (KLB), and γ-Klotho (KLG). Many studies have shown that KLA and KLB participate in tumor progression or suppression, depending on the type of cancer; however, the relationship between KLG and prostate cancer has not yet been studied. Some studies have claimed that KL is correlated to sensitivity to chemotherapy. Here, we investigated the oncogenic potential of KLG in castration-resistant prostate cancer (CRPC). Immunohistochemical analysis using prostate biopsy specimens revealed that patients with high KLG expression in primary prostate cancer tissue had a significantly poor prognosis for overall survival. In addition, the prostate-specific antigen response rate after docetaxel (DTX) therapy in patients with high KLG expression was lower than that in patients with low KLG expression. To evaluate the potential of KLG as a therapeutic target in human prostate cancer, we generated a xenograft model of human CRPC cell line (PC-3) in male athymic mice. The animals were randomly divided into four groups as follows: i) control group (vehicle only); ii) DTX group (intraperitoneal administration); iii) small interfering RNA targeting KLG (KLG siRNA) group (intratumoral administration); and iv) a combination group (DTX plus KLG siRNA). After 3 weeks of treatment, the tumor weight and tumor Ki-67 labeling index were significantly lower in the KLG siRNA group and the combination group than in the control group. Sensitivity to DTX was increased upon treatment with KLG siRNA. These findings suggest that KLG expression in primary prostate cancer lesions is associated with resistance to DTX in CRPC and has potential as a diagnostic and therapeutic target for patients with CRPC.博士（医学）・甲第740号・令和2年3月16日Copyright: © Onishiet al. This is an open access article distributed under theterms of CreativeCommons Attribution License(https://creativecommons.org/licenses/by-nc-nd/4.0/)

Spatio-Temporal Expression Profile of Stem Cell-Associated Gene LGR5 in the Intestine during Thyroid Hormone-Dependent Metamorphosis in Xenopus laevis

The intestinal epithelium undergoes constant self-renewal throughout adult life across vertebrates. This is accomplished through the proliferation and subsequent differentiation of the adult stem cells. This self-renewal system is established in the so-called postembryonic developmental period in mammals when endogenous thyroid hormone (T3) levels are high.The T3-dependent metamorphosis in anurans like Xenopus laevis resembles the mammalian postembryonic development and offers a unique opportunity to study how the adult stem cells are developed. The tadpole intestine is predominantly a monolayer of larval epithelial cells. During metamorphosis, the larval epithelial cells undergo apoptosis and, concurrently, adult epithelial stem/progenitor cells develop de novo, rapidly proliferate, and then differentiate to establish a trough-crest axis of the epithelial fold, resembling the crypt-villus axis in the adult mammalian intestine. The leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a well-established stem cell marker in the adult mouse intestinal crypt. Here we have cloned and analyzed the spatiotemporal expression profile of LGR5 gene during frog metamorphosis. We show that the two duplicated LGR5 genes in Xenopus laevis and the LGR5 gene in Xenopus tropicalis are highly homologous to the LGR5 in other vertebrates. The expression of LGR5 is induced in the limb, tail, and intestine by T3 during metamorphosis. More importantly, LGR5 mRNA is localized to the developing adult epithelial stem cells of the intestine.These results suggest that LGR5-expressing cells are the stem/progenitor cells of the adult intestine and that LGR5 plays a role in the development and/or maintenance of the adult intestinal stem cells during postembryonic development in vertebrates

頸動脈狭窄に対する自己拡張型ステント留置後フォローアップ時のステント径と内腔の検討

Purpose: We examined postoperative stent and lumen expansions after carotid artery stenting (CAS) in patients with carotid artery stenosis. Furthermore, we investigated factors influencing the stent and lumen expansions in a follow-up period. Subjects: 134 cases (128 patients) who underwent CAS and performed follow-up cerebral angiography 12 months after CAS were enrolled into this study. The stenosis rate based on the stent and lumen diameters on follow-up angiography as a percentage of that immediately after CAS was evaluated. Results: Both the stent and lumen diameters were significantly dilated 12 months after CAS (p <0.001). There were no significant stent-type-related differences in the stent expansion rate. In the symptomatic stenosis group, this expansion rate was significantly higher than in the asymptomatic stenosis group (p = 0.02). With respect to the presence or absence of a high signal intensity on time of flight (TOF) magnetic resonance (MR) images, the stent expansion rate was significantly higher in the high signal intensity group (p = 0.006). In patients with a plaque/sternocleidomastoid muscle signal intensity ratio of ≥1.50 on plaque images, it was significantly higher than in those with a value of <1.50 (p = 0.006). However, there were no significant differences in the lumen expansion rate among the groups. Conclusion: Both the stent and vascular lumen were dilated 12 months after CAS. Plaque fragility influenced the stent expansion rate; however, there were no significant factor-related differences in the vascular lumen expansion rate.博士（医学）・乙第1414号・平成30年3月15日©2017 The Editorial Committee of Journal of Neuroendovascular Therapy. All rights reserved. This is an open access article distributed under the terms of Creative Commons Attribution License(CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/

限局性腎細胞癌における腫瘍浸潤性リンパ球と関連サイトカインの予後因子としての意義

Renal cell carcinoma (RCC) is an immunogenic tumor and pathological specimen generally contain large quantities of tumor-infiltrating lymphocytes (TILs). Numerous cell types and cytokines could affect the immune escape mechanism of tumor cells. The aim of the present study was to investigate the prognostic impact of TILs and the associated circulating cytokines on localized clear cell RCC following radical nephrectomy. A total of 87 patients who had undergone radical nephrectomy and were pathologically diagnosed with localized clear cell RCC were included. The present study evaluated the profile of TILs with immunohistochemical analysis of tumor specimens using a panel of antibodies [cluster of differentiation (CD)-4, CD8, CD80, CD86, CD276, and Forkhead box p3 (Foxp3)]. Counts of each TIL were compared with clinicopathological variables. Based on the results of immunohistochemical analyses, putative cytokines, including interleukin (IL)-6, IL-10, IL-17, interferon-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β, were selected, and their levels in preoperative serum were measured by ELISA. The levels were compared with TIL counts in tumor specimens. High counts of the CD276+ and Foxp3+ TILs were identified as independent factors for poor prognosis for metastasis and local recurrence following radical nephrectomy (P=0.033 and 0.006, respectively). A high CD276+ TIL count was associated with preoperative serum levels of TNF-α and IFN-γ (P=0.027 and P=0.035, respectively), whereas a high count of Foxp3+ TILs was associated with preoperative serum levels of TGF-β (P=0.021). High levels of TNF-α and TGF-β were associated with recurrence-free survival (P=0.035 and P=0.031, respectively). Topical intra-tumoral immunoreaction and systemic immune status may be associated with patients with localized RCC. The topical induction of the CD276+ and Foxp3+ TILs was suggested to be associated with high levels of serum TNF-α and IFN-γ. Preoperative serum levels of TNF-α and TGF-β could be simple and non-invasive biomarkers for risk stratification before radical surgery.博士（医学）・甲第741号・令和2年3月16日Copyright © Spandidos Publications 2019. All rights reserved.Articles from Oncology Letters are provided here courtesy of Spandidos Publications

尿路上皮癌微小環境内におけるDisabled Homolog 2 (DAB2) は腫瘍細胞上皮間葉転換を介して遊走能・浸潤能を高める

Disabled homolog-2 (DAB2) has been reported to be a tumor suppressor gene. However, a number of contrary studies suggested that DAB2 promotes tumor invasion in urothelial carcinoma of the bladder (UCB). Here, we investigated the clinical role and biological function of DAB2 in human UCB. Immunohistochemical staining analysis for DAB2 was carried out on UCB tissue specimens. DAB2 expression levels were compared with clinicopathological factors. DAB2 was knocked-down by small interfering RNA (siRNA) transfection, and then its effects on cell proliferation, invasion, and migration, and changes to epithelial-mesenchymal transition (EMT)-related proteins were evaluated. In our in vivo assays, tumor-bearing athymic nude mice subcutaneously inoculated with human UCB cells (MGH-U-3 or UM-UC-3) were treated by DAB2-targeting siRNA. Higher expression of DAB2 was associated with higher clinical T category, high tumor grade, and poor oncological outcome. The knock-down of DAB2 decreased both invasion and migration ability and expression of EMT-related proteins. Significant inhibitory effects on tumor growth and invasion were observed in xenograft tumors of UM-UC-3 treated by DAB2-targeting siRNA. Our findings suggested that DAB2 expression was associated with poor prognosis through increased oncogenic properties including tumor proliferation, migration, invasion, and enhancement of EMT in human UCB.博士（医学）・甲第768号・令和3年3月15日© 2020 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 (http://creativecommons.org/licenses/by/4.0/)