コラーゲンゲルマトリクスを用いた泌尿器悪性腫瘍に対する抗癌剤感受性試験法に関する研究

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1068号, 学位授与年月日：平成5年3月25日,学位授与年：199

Uncovering the Mysteries of Langerhans Cells, Inflammatory Dendritic Epidermal Cells, and Monocyte-Derived Langerhans Cell-Like Cells in the Epidermis

The identity of Langerhans cells (LCs) has been called into question of late due to the increasing evidence that LCs originate from macrophage lineage instead of dendritic cell (DC) lineage as previously thought. For many years, LCs have been assumed to be DCs due to its migratory capabilities. However, recent studies have demonstrated that LCs are from macrophage lineage of the adult fetal liver (FL) progenitor. Bona fide LCs are now considered tissue-resident macrophages as they originate from the FL as shown by fate mapping models. In recent years, studies have shown that there are three types of antigen-presenting cells present in the epidermis, such as LCs, monocyte-derived LC-like cells, and inflammatory dendritic epidermal cells (IDECs). Of these, LC-like cells have been characterized in both human and mouse studies, while IDECs have only been described in human studies. This has shed a new light on the area of epidermal macrophages, suggesting that there might be a misidentification and misclassification of LCs. IDECs and LC-like cells have been shown to be present in both steady state and inflammatory state, but they are present in more significant amounts under inflammatory conditions such as atopic dermatitis, ultra violet injury, and psoriasis. In this review, we discuss what is already known and discuss the possible roles of LCs, LC-like cells, and IDECs during inflammation. Most intriguingly, we discuss the possibility of LCs having a dual identity as both a macrophage and a DC. This is shown as LCs are the only tissue-resident macrophage to have shown migratory property-like DCs

Fusion of SPECT and multidetector CT images for accurate localization of pelvic sentinel lymph nodes in prostate cancer patients

金沢大学大学院医学系研究科OBJECTIVE: The present study was performed to investigate the feasibility of fusion of images obtained by SPECT and multidetector CT (MDCT) for the accurate localization of sentinel lymph nodes in prostate cancer patients. METHODS: To facilitate the fusion of both SPECT and CT images, a pelvic MDCT scan was performed with 3 markers of small plastic bullets attached to the skin over the bilateral iliac crests and the ventral midline at the same height. SPECT was performed after the same locations were marked with needle caps containing (99m)Tc-pertechnetate. The images were superimposed by use of free software (MRIcro). The results of hot lymph node detection with fusion images were compared with those of surgery. RESULTS: The images could be successfully superimposed for all 11 patients examined. Surgeons accurately confirmed 27 (87.1%) of 31 regional lymph nodes on fusion images. CONCLUSION: Fusion of SPECT and MDCT images is useful for the precise localization of sentinel lymph nodes in prostate cancer patients

Quantification of Cell Migration and Invasion, and Their Association with Periostin in Anaplastic Thyroid Cancer, Using a Real-time Cell Analyzer

Anaplastic thyroid cancer (ATC) is known to be a highly malignant cancer of the thyroid with a high mortality rate. In a previous study, we used real-time cell analysis (RTCA) to analyze cell migration and invasion of oral squamous cell carcinomas (OSCCs) of the tongue and floor of the mouth. In the present study, we investigated cell migration and invasion of ATC using RTCA, as well as their association with periostin, matrix metalloproteinases (MMPs), and integrins. Experiments were performed on TCO-1 and HTC/C3 cells, which are human ATC cell lines. OSCC cell lines were used for comparison. Using the cell analysis system, cell migration was assessed on fibronectin-coated CIM-Plates, whereas invasion was assessed on fibronectin- and matrigel-coated CIM-Plates. SCC-4 cells exhibited high cell migration and invasion activity compared with other OSCC cell lines. TCO-1 cells exhibited equivalent cell invasion but stronger migration than SCC-4 cells. Although TCO-1 cells had strong invasive activity, they did not express MMP-9, unlike SCC-4 cells. Conversely, periostin expression was high in TCO-1 cells. Therefore, periostin expression appears to be associated with the cell migration and invasion activity of ATC. The RTCA system will be useful for the analysis of the metastatic characteristics of ATC in head and neck cancer

Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model

Ablファミリーチロシンキナーゼが抗体の血管外輸送を制御することを解明 --生体内での抗体輸送メカニズム--. 京都大学プレスリリース. 2019-10-21.The pathway of homeostatic IgG extravasation is not fully understood, in spite of its importance for the maintenance of host immunity, the management of autoantibody-mediated disorders, and the use of antibody-based biologics. Here we show in a murine model of pemphigus, a prototypic cutaneous autoantibody-mediated disorder, that blood-circulating IgG extravasates into the skin in a time- and dose-dependent manner under homeostatic conditions. This IgG extravasation is unaffected by depletion of Fcγ receptors, but is largely attenuated by specific ablation of dynamin-dependent endocytic vesicle formation in blood endothelial cells (BECs). Among dynamin-dependent endocytic vesicles, IgG co-localizes well with caveolae in cultured BECs. An Abl family tyrosine kinase inhibitor imatinib, which reduces caveolae-mediated endocytosis, impairs IgG extravasation in the skin and attenuates the murine pemphigus manifestations. Our study highlights the kinetics of IgG extravasation in vivo, which might be a clue to understand the pathological mechanism of autoantibody-mediated autoimmune disorders

Virulence, pathology, and pathogenesis of Pteropine orthoreovirus (PRV) in BALB/c mice: Development of an animal infection model for PRV

<div><p>Background</p><p>Cases of acute respiratory tract infection caused by Pteropine orthoreovirus (PRV) of the genus <i>Orthoreovirus</i> (family: <i>Reoviridae</i>) have been reported in Southeast Asia, where it was isolated from humans and bats. It is possible that PRV-associated respiratory infections might be prevalent in Southeast Asia. The clinical course of PRV is not fully elucidated.</p><p>Methods</p><p>The virulence, pathology, and pathogenesis of two PRV strains, a human-borne PRV strain (isolated from a patient, who returned to Japan from Bali, Indonesia in 2007) and a bat-borne PRV (isolated from a bat [<i>Eonycteris spelaea</i>] in the Philippines in 2013) were investigated in BALB/c mice using virological, pathological, and immunological study methods.</p><p>Results</p><p>The intranasal inoculation of BALB/c mice with human-borne PRV caused respiratory infection. In addition, all mice with immunity induced by pre-inoculation with a non-lethal dose of PRV were completely protected against lethal PRV infection. Mice treated with antiserum with neutralizing antibody activity after inoculation with a lethal dose of PRV showed a reduced fatality rate. In this mouse model, bat-borne PRV caused respiratory infection similar to human-borne PRV. PRV caused lethal respiratory disease in an animal model of PRV infection, in which BALB/c mice were used.</p><p>Conclusions</p><p>The BALB/c mouse model might help to accelerate research on the virulence of PRV and be useful for evaluating the efficacy of therapeutic agents and vaccines for the treatment and prevention of PRV infection. PRV was shown for the first time to be a causative virus of respiratory disease on the basis of Koch’s postulations by the additional demonstration that PRV caused respiratory disease in mice through their intranasal inoculation with PRV.</p></div