細胞適合性ポリマーハイドロゲルマトリックスに内包した幹細胞の機能制御

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 石原 一彦, 東京大学教授 吉田 亮, 東京医科歯科大学教授 岸田 晶夫, 東京大学准教授 坂田 利弥, 東京大学准教授 金野 智浩University of Tokyo(東京大学

Structural variations in parotid glands induced by radiation therapy in patients with oral carcinoma observed on contrast-enhanced computed tomography

Background: Xerostomia is one of the commonest radiation-induced complications in patients with head and neck carcinoma. The aim of this study was to assess structural variations in parotid glands induced by radiation therapy in patients with oral carcinoma with contras-enhanced computed tomography (CECT). Material/Methods: A retrospective study was performed in 41 patients with oral carcinoma who underwent CECT for head and neck malignancies before and after radiotherapy. We analyzed the relationship between parotid density variations, parotid volume change, as seen on CECT, and the mean radiation dose applied to the parotid glands in patients with oral carcinoma immediately after radiotherapy, and 2 and 3 years later. Results: Immediately after radiotherapy, high-density changes on contrast-enhanced CT were observed in 70.5% of the irradiated parotids. Low-density changes due to fat degeneration were seen in 46.2% and 72.2% of the irradiated parotids 2 and 3 years after radiotherapy, respectively. The mean dose applied to the parotids with the low-density changes and without such changes 3 years after radiotherapy was 46.0 Gy and 27.7 Gy, respectively (p=0.049). Furthermore, parotid shrinkage was observed in 63.6% of the irradiated parotids. Conclusions: This study suggests that the structural variations in parotid glands induced by radiotherapy included high-density changes that were observed immediately after radiotherapy and low-density changes that were seen at late follow-up. This study should be useful for clinicians in the assessment of radiation-induced injuries in the parotids with respect to early prediction of xerostomia

Histone H3K27 acetylation precedes active transcription during zebrafish zygotic genome activation as revealed by live-cell analysis

Histone post-translational modifications are key gene expression regulators, but their rapid dynamics during development remain difficult to capture. We applied a Fab-based live endogenous modification labeling technique to monitor the changes in histone modification levels during zygotic genome activation (ZGA) in living zebrafish embryos. Among various histone modifications, H3 Lys27 acetylation (H3K27ac) exhibited most drastic changes, accumulating in two nuclear foci in the 64- to 1k-cell-stage embryos. The elongating form of RNA polymerase II, which is phosphorylated at Ser2 in heptad repeats within the C-terminal domain (RNAP2 Ser2ph), and miR-430 transcripts were also concentrated in foci closely associated with H3K27ac. When treated with α-amanitin to inhibit transcription or JQ-1 to inhibit binding of acetyl-reader proteins, H3K27ac foci still appeared but RNAP2 Ser2ph and miR-430 morpholino were not concentrated in foci, suggesting that H3K27ac precedes active transcription during ZGA. We anticipate that the method presented here could be applied to a variety of developmental processes in any model and non-model organisms

Long-term survival of a patient with diffuse midline glioma in the pineal region: A case report and literature review

Background: Diffuse midline glioma (DMG) is an invasive astrocytic tumor arisen from midline structures, such as the pons and thalamus. Five cases of DMG in the pineal region have been reported, but the clinical course was poor; there was no case of survival for more than 2 years.Case Description: We report the case of a 12-year-old boy with DMG in the pineal region who is living a normal daily life for more than 6 years following multimodal treatment. He complained of a headache accompanied by vomiting that had gradually worsened 1 month previously, and initial magnetic resonance imaging revealed a pineal tumor. Germinoma was initially suspected; however, a combination of chemotherapy using carboplatin and etoposide was ineffective. The first surgery was performed through the left occipital transtentorial approach (OTA); the diagnosis was DMG. After 60 Gy radiotherapy concomitant with temozolomide (TMZ), the tumor enlarged. Second surgery was performed through bilateral OTAs, and 90% of the tumor was removed. In addition, stereotactic radiotherapy (30 Gy, six fractions) was administered, and the local equivalent dose in 2 Gy/fraction reached 97.5 Gy. Maintenance chemotherapy using TMZ and bevacizumab was continued for 2 years. After finishing chemotherapy, the enhancing lesion enlarged again, and bevacizumab monotherapy was effective. Now, at 6 years after diagnosis, the patient leads an ordinary life as a student.Conclusion: Maximum resection and high-dose radiotherapy followed by bevacizumab may have been effective in the present case

Assessment of Lower-limb Vascular Endothelial Function Based on Enclosed Zone Flow-mediated Dilation

This paper proposes a novel non-invasive method for assessing the vascular endothelial function of lower-limb arteries based on the dilation rate of air-cuff plethysmograms measured using the oscillometric approach. The principle of evaluating vascular endothelial function involves flow-mediated dilation. In the study conducted, blood flow in the dorsal pedis artery was first monitored while lower-limb cuff pressure was applied using the proposed system. The results showed blood flow was interrupted when the level of pressure was at least 50 mmHg higher than the subject’s lower-limb systolic arterial pressure and that blood flow velocity increased after cuff release. Next, values of the proposed index, %ezFMDL, for assessing the vascular endothelial function of lower-limb arteries were determined from 327 adult subjects: 87 healthy subjects, 150 subjects at high risk of arteriosclerosis and 90 patients with cardiovascular disease (CAD). The mean values and standard deviations calculated using %ezFMDL were 30.5 ± 12.0% for the healthy subjects, 23.6 ± 12.7% for subjects at high risk of arteriosclerosis and 14.5 ± 15.4% for patients with CAD. The %ezFMDL values for the subjects at high risk of arteriosclerosis and the patients with CAD were significantly lower than those for the healthy subjects (p < 0.01). The proposed method may have potential for clinical application.This work was supported by JSPS KAKENHI Grant Number 16K21076

Wound healing in wild male baboons: Estimating healing time from wound size.

Wound healing in animals is important to minimize the fitness costs of infection. Logically, a longer healing time is associated with higher risk of infection and higher energy loss. In wild mammals, wounds caused by aggressive intraspecific interactions can potentially have lethal repercussions. Clarifying wounding rate and healing time is therefore important for measuring the severity of the attacks. In addition, impact of secondary damage of wounds (e.g., accidental peeling off of scabs) on heeling time is unknown despite the risk of infection in wild mammals. In baboons, most male injuries have been reported to result from male to male fights. Here, we investigated the relationship between wound size and healing time in wild anubis baboons to clarify the healing cost of physical attacks including secondary damage of wounds. Observations were conducted daily between August 2016 and July 2017 in Kenya for seven adult male anubis baboons. The individual wound rate was one per month on average. In 16 cases, we were able to assess the number of days required for wound healing, and the median healing time was 13 d. Wound healing time was longer for larger wounds. When the scab was peeled off accidentally because of external factors, healing time became longer. One of the causes of scabs' peeling off was baboons' scab-picking behavior, and the behaviour was considered self-injurious behavior. However, its predicted healing cost might not be high. We concluded that wounds less than 800 mm2 (the largest observed in this study) in baboon males have little effect on survival. Our results suggest that lethal wounds by physical attacks rarely occur in male baboons, and that healing time and delay caused by secondary damages can be estimated by measuring wound area

Effects of a message on the attitudes toward women's working among undergraduate students

大学生に我が国の経済状況の厳しさを呈示することによって, 女性の就労に対する態度を肯定的な方向に変容させることを試みた。メッセージ(有り, 無し)と実験参加者の性(男性, 女性)を独立変数とする2要因実験参加者間計画であり, 従属変数として女性の就労に対する2種類の態度を事前一事後測定法により測定した。本研究で用いたメッセージは, 女性の就労に対する希望を変容させるという直接的な効果はもたなかったものの, 男女の性役割態度を平等志向的方向へと変容させる効果をもつことが示された