論文1ページ目の下部に著作権を表示すること。（© 2016, American Society for Microbiology. ） / 京都大学 / 0048 / 新制・課程博士 / 博士(医科学) / 甲第19634号 / 医科博第72号 / 新制||医科||5(附属図書館) / 32670 / 京都大学大学院医学研究科医科学専攻 / (主査)教授 近藤 玄, 教授 篠原 隆司, 教授 秋山 芳展 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

This project focuses on the stabilisation, modification, delivery and treatment of phospholipid based vesicles for applications in advanced wound care, with a focus on paediatric burns. Vesicles, commonly referred to as liposomes or nanocapsules, are attractive drug delivery composites, due to their biocompatible properties. They have the ability to entrap active compounds within their core, which can be released at the point of use, (in vivo or ex vivo) either through passive diffusion, or in response to local environmental stimulus.

Cytokinesis, the final step of cell division, is characterized by formation of a cleavage furrow that ingresses to separate the cell into two daughter cells. This process requires rearrangement of the cytoskeleton and addition of membrane to the growing furrow. The phospholipid phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] has been implicated in regulating both actin dynamics and membrane trafficking and, thus, is uniquely poised to coordinate these different processes during cytokinesis. In this study, I show that PtdIns(4,5)P2 is involved in another aspect of cytokinesis: regulation of actomyosin contractility. Perturbing PtdIns(4,5)P2 levels in Drosophila spermatocytes caused constriction to fail and cleavage furrows to regress. Moreover, PtdIns(4,5)P2 hydrolysis is implicated in this process: inhibiting PLC or IP3R or chelating Ca2+ also caused defects in furrow ingression. In addition, I show that PLC and MLCK activities are required for myosin light chain phosphorylation and for proper myosin and actin localization to the cleavage furrow. Thus, I propose a model in which PtdIns(4,5)P2 hydrolysis-dependent Ca2+ release activates MLCK via Ca2+/calmodulin to maintain myosin filaments in the contractile ring and regulate cleavage furrow ingression. Furthermore, I show that PtdIns(4,5)P2 has a role in maintaining contractile ring components in the cleavage furrow that does not depend on PtdIns(4,5)P2 hydrolysis. I conclude that PtdIns(4,5)P2 regulates myosin contractility through a PLC-dependent pathway leading to myosin phosphorylation and is also involved in localizing contractile ring components to the furrow. Thus, PtdIns(4,5)P2 may coordinate signals leading to cytoskeleton rearrangement and actomyosin contractility during cytokinesis.

Cytokinesis, the final step of cell division, is characterized by formation of a cleavage furrow that ingresses to separate the cell into two daughter cells. This process requires rearrangement of the cytoskeleton and addition of membrane to the growing furrow. The phospholipid phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] has been implicated in regulating both actin dynamics and membrane trafficking and, thus, is uniquely poised to coordinate these different processes during cytokinesis. In this study, I show that PtdIns(4,5)P2 is involved in another aspect of cytokinesis: regulation of actomyosin contractility. Perturbing PtdIns(4,5)P2 levels in Drosophila spermatocytes caused constriction to fail and cleavage furrows to regress. Moreover, PtdIns(4,5)P2 hydrolysis is implicated in this process: inhibiting PLC or IP3R or chelating Ca2+ also caused defects in furrow ingression. In addition, I show that PLC and MLCK activities are required for myosin light chain phosphorylation and for proper myosin and actin localization to the cleavage furrow. Thus, I propose a model in which PtdIns(4,5)P2 hydrolysis-dependent Ca2+ release activates MLCK via Ca2+/calmodulin to maintain myosin filaments in the contractile ring and regulate cleavage furrow ingression. Furthermore, I show that PtdIns(4,5)P2 has a role in maintaining contractile ring components in the cleavage furrow that does not depend on PtdIns(4,5)P2 hydrolysis. I conclude that PtdIns(4,5)P2 regulates myosin contractility through a PLC-dependent pathway leading to myosin phosphorylation and is also involved in localizing contractile ring components to the furrow. Thus, PtdIns(4,5)P2 may coordinate signals leading to cytoskeleton rearrangement and actomyosin contractility during cytokinesis.

No description available.

Antiphospholipid syndrome (APS) is an autoimmune disorder defined as the persistent presence of antiphospholipid antibodies (aPL) associated with recurrent thrombotic events and/or fetal loss. The mechanisms for fetal loss in this syndrome have not yet been clearly explained, although several hypotheses based on experimental data have been put forward. It has been shown that proliferation of human umbilical vein endothelial cells (HUVECs) decreased significantly in cultures that contained sera positive for anticardiolipin antibody activity collected from patients with recurrent fetal loss. We explored the effect of ACAs on Vascular Endothelial Growth factor- A (VEGF-A) secretion of cultured HUVECs. VEGF appears to be the most endothelial cell-specific and unequivocal angiogenic factor. In vitro, VEGF causes endothelial cell proliferation and migration; in vivo, it is potently angiogenic and causes vascular permeability. We determined the effect of ACA IgG 40μg/ml and 80μg/ml on VEGF secretion using ELISA. The results were measured in mean ± SD and expressed in pg of VEGF/5 x 10⁴ cells. P ≤ 0.05 considered significant as compared to control. The results showed that ACA increases VEGF-A secretion and/or may bind at VEGF-A binding sites. This finding may be useful for finding therapies for patients with recurrent miscarriages. / Access to thesis permanently restricted to Ball State community only. / Department of Physiology and Health Science

Techn. Universiẗat, Diss., 2003--Berlin.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19966号 / 医博第4156号 / 新制||医||1017(附属図書館) / 33062 / 京都大学大学院医学研究科医学専攻 / (主査)教授 原田 浩, 教授 岩田 想, 教授 岩井 一宏 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Mechanical injuries to the cell often lead to disruptions of the cell’s phospholipid bilayer membrane and potential detrimental effects including cell death. Understanding the mechanical states required to disrupt the phospholipid bilayer would result in better multiscale constitutive models and further knowledge of cell injury. The objectives of this research were to perform biaxial deformations of the phospholipid bilayer to quantify phospholipid bilayer disruption and to identify potential parameters that can be used in multiscale constitutive equations. We show that the von Mises stress, 26.6-61.1, increases linearly with the von Mises strain rate, 1.7e8-6.7e8, and that the strain at failure is dependent on the stress state with non- and equibiaxial being the most detrimental when failing at <.73 von Mises strain. Understanding the effects of nanoscale mechanical trauma to the cell provides a better understanding of cell injury and may provide insight regarding initiation and progression of cell damage.