環境化学物質の周産期曝露によるニューロン形態変化の解析

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 渡辺 知保, 東京大学教授 吉田 謙一, 東京大学教授 松島 綱治, 東京大学教授 尾藤 晴彦, 東京大学准教授 山末 英典University of Tokyo(東京大学

The collaborative role of oral surgery with plastic as well as head & neck surgery in head and neck cancers : Preoperative plate-bending method in cases with mandibular reconstruction using plaster 3D models

The collaboration of various medical teams is crucial for the appropriate treatment of cancer patients. However, in Japan, it is very difficult for oral surgeons to cooperate with head and neck surgeons due to conflicts in the treatment of those patients. There have been few studies on this subject. In the current work, we report on the collaboration of head and neck surgeons, plastic surgeons and oral surgeons in operations on two patients with gingival carcinomas in the mandible. We first prepared plaster 3D models of the patients'mouths by means of ink-jet from CT data. We pre-bent the reconstruction plates using the preoperative 3D models. Therefore, we could save the time required to bend the plate. Plaster models are cheaper than resin models. It is also easy to model the surgery using the plate. During the operation, head and neck surgeons resected the tumors, plastic surgeons performed reconstruction with vascularized bone or skin graft, and oral surgeons (dentists) did plate fixation and took charge of the patients'occlusion. This method resulted in patients having good occlusion after the operation

Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages

Autophagy is a cytoplasmic degradative pathway that can participate in biosynthetic processes, as in the yeast Cvt pathway, but is more commonly known for its functions in removing damaged or surplus organelles and macromolecular complexes. Here, we find that autophagy intersects with human immunodeficiency virus (HIV) biogenesis, mirroring the above dichotomy. Early, nondegradative stages of autophagy promoted HIV yields. HIV Gag-derived proteins colocalized and interacted with the autophagy factor LC3, and autophagy promoted productive Gag processing. Nevertheless, when autophagy progressed through maturation stages, HIV was degraded. This, however, does not occur, as the HIV protein Nef acts as an antiautophagic maturation factor through interactions with the autophagy regulatory factor Beclin 1, thus protecting HIV from degradation. The dual interaction of HIV with the autophagy pathway enhances viral yields by using the early stages while inhibiting the late stages of autophagy. The role of Nef in the latter process enhances yields of infectious HIV and may be of significance for progression to clinical AIDS

Genetic Control of MAP3K1 in Eye Development and Sex Differentiation

The MAP3K1 is responsible for transmitting signals to activate specific MAP2K-MAPK cascades. Following the initial biochemical characterization, genetic mouse models have taken center stage to elucidate how MAP3K1 regulates biological functions. To that end, mice were generated with the ablation of the entire Map3k1 gene, the kinase domain coding sequences, or ubiquitin ligase domain mutations. Analyses of the mutants identify diverse roles that MAP3K1 plays in embryonic survival, maturation of T/B cells, and development of sensory organs, including eye and ear. Specifically in eye development, Map3k1 loss-of-function was found to be autosomal recessive for congenital eye abnormalities, but became autosomal dominant in combination with Jnk and RhoA mutations. Additionally, Map3k1 mutation increased eye defects with an exposure to environmental agents such as dioxin. Data from eye developmental models reveal the nexus role of MAP3K1 in integrating genetic and environmental signals to control developmental activities. Here, we focus the discussions on recent advances in understanding the signaling mechanisms of MAP3K1 in eye development in mice and in sex differentiation from human genomics findings. The research works featured here lead to a deeper understanding of the in vivo signaling network, the mechanisms of gene–environment interactions, and the relevance of this multifaceted protein kinase in disease etiology and pathogenesis

Accuracy of magnetic resonance imaging for the evaluation of myometrial invasion in endometrial carcinoma

Endometrial carcinoma is the most common gynecologic malignancy and accounts for 6% of all cancers in women. In patients with endometrial cancer, preoperative knowledge of myometrial tumor extension has important prognostic and therapeutic implications. The aim of this retrospective study is to assess whether magnetic resonance (MR) imaging is useful to assess the depth of myometrial invasion by endometrial carcinoma. Sixty patients between 2003 and 2005 were included in the study. All patients were proven histopathologically endometrial carcinoma and underwent preoperative MR imaging and all data was compared in all cases. The histological results showed no myometrial invasion in 8 cases, myometrial invasion of less than 50% in 35 cases, and myometrial invasion of more than 50% in 17 cases. In the cases of no myometrial invasion, MR T2 weighted imaging had a sensitivity of 87.5%, a specificity of 86.5%, a positive predictive Value (PPV) of 50.0% and a negative predictive value (NPV) of 97.8%. In the cases of myometrial invasion of less than 50%, MR T2 weighted imaging had a sensitivity of 82.9%, a specificity of 72.0%, PPV of 80.6% and NPV of 75.0%. By contrast, in the cases of myometrial invasion of more than 50%, the sensitivity, specificity, PPV and NPV of MR T2 weighted imaging were 58.8%, 100%, 100% and 86.0% respectively. Errors in MR findings when determining myometrial tumor spread were more frequently underestimations rather than overestimations.Our results indicate that MR imaging is useful for the preoperative assessment of the depth of myometrial invasion in patients with endometrial carcinoma