包括的な運動療法が関節軟骨代謝に関する全身性バイオマーカーに与える効果について

京都大学0048新制・課程博士博士(医学)甲第21672号医博第4478号新制||医||1035(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 川上 浩司, 教授 古川 壽亮, 教授 上杉 志成学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

A Basic Study on Path Teaching Method for a Mobile Robot Using a Digital Camera

This paper proposes a novel path teaching method for a mobile robot. In this method an operator takes pictures at significant points such as turning points, half way points and a destination on robot´s path by a digital camera. Then, the operator teaches the robot landmarks to recognize the images and actions for the robot to take at the significant points. The robot travels autonomously searching the landmarks and obeys the instructions when it recognizes reaching the significant points. By using this method, it is possible to teach paths for the mobile robot more easily. In this paper, outline of the proposed method and results of fundamental experiments in both indoor and outdoor environment to confirm possibility of the method are described

The Role of Musculoskeletal Ultrasound in the Rheumatoid Arthritis Continuum

Purpose of Review: Rheumatoid arthritis (RA) is no longer considered a fixed phenotype but rather a disease continuum. This review outlines the current and potential value of applying ultrasound (US) along this continuum: from the prediction of progression to RA in at-risk individuals, to confirmation of the early diagnosis of RA, as well as the consideration of differential diagnoses, and the use in disease monitoring and defining remission. Recent Findings: In individuals at-risk of RA (i.e., positive autoantibodies with symptoms but without synovitis), US has shown a promising predictive value for the development of clinical arthritis, providing the opportunity to improve risk stratification (and disease prevention) of these individuals. The detection of inflammation on US in patients with early undifferentiated arthritis, in which a definite diagnosis cannot be reached, could predict evolution to persistent arthritis, mostly RA. This, in addition to the US potential ability to identify disease specific patterns for different rheumatic conditions, might facilitate early diagnosis and, therefore, improve the management of patients with RA, or other types of inflammatory arthritides. US has also demonstrated the capability to predict radiographic progression, and relapse risk after treatment discontinuation, in RA patients in remission according to the clinical instruments, raising implications in the management, including therapy discontinuation, of these patients. Summary: US has an undeniable value in the management of patients at different stages along the RA continuum. Further research is needed to identify which groups of patients benefit the most from US imaging

DIHS/DRESS患者における血清中HHV6B microRNAの変化

博士（医学）・甲第699号・平成31年3月15日Copyright © 2018. Acta Dermato-Venereologica. All rights reserved.This is an open access article under the CC BY-NC license(http://creativecommons.org/licenses/by-nc/4.0/)

抗糖尿病作用を有するテトラヒドロイソキノリン誘導体(PPARγおよびPPARγ+αアゴニスト)の合成研究

取得学位：博士(薬学），学位授与番号：博甲第1020号，学位授与年月日：平成20年3月22

Peculiar Distribution of Tumorous Xanthomas in an Adult Case of Erdheim-Chester Disease Complicated by Atopic Dermatitis

Erdheim-Chester disease is a rare non-Langerhans form of histiocytosis with multiple organ involvement. Approximately 20% of patients have xanthoma-like lesions, usually on the eyelids. We report a case of Erdheim-Chester disease in a 32-year-old male who showed peculiar xanthomatous skin lesions and also had atopic dermatitis. His skin manifestations included ring-like yellowish tumors on his periorbital regions, rope necklace-like tumors on his neck, and spindle-shaped tumors on his right preauricular region and cubital fossas. He also had exophthalmos and diabetes insipidus. Chronic eczematous lesions were present on the flexor aspect of his extremities, and his serum eosinophil numbers and immunoglobulin E levels were elevated. A histological examination of his right neck tumor showed foamy macrophages and touton-type giant cells, which were positive for CD68 and CD163 and negative for S-100 and CD1a. We suggest that the complication of atopic dermatitis may have contributed to the uncommon clinical features in this case

CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells

Recent studies have challenged the view that Langerhans cells (LCs) constitute the exclusive antigen-presenting cells of the skin and suggest that the dermal dendritic cell (DDC) network is exceedingly complex. Using knockin mice to track and ablate DCs expressing langerin (CD207), we discovered that the dermis contains five distinct DC subsets and identified their migratory counterparts in draining lymph nodes. Based on this refined classification, we demonstrated that the quantitatively minor CD207+ CD103+ DDC subset is endowed with the unique capability of cross-presenting antigens expressed by keratinocytes irrespective of the presence of LCs. We further showed that Y-Ae, an antibody that is widely used to monitor the formation of complexes involving I-Ab molecules and a peptide derived from the I-E α chain, recognizes mature skin DCs that express I-Ab molecules in the absence of I-E α. Knowledge of this extra reactivity is important because it could be, and already has been, mistakenly interpreted to support the view that antigen transfer can occur between LCs and DDCs. Collectively, these data revisit the transfer of antigen that occurs between keratinocytes and the five distinguishable skin DC subsets and stress the high degree of functional specialization that exists among them

Antigen-specific CD8 T cells can eliminate antigen-bearing keratinocytes with clonogenic potential via an IFN-γ-dependent mechanism

The immune system surveys the skin for keratinocytes (KCs) infected by viruses or with acquired genetic damage. The mechanism by which T cells mediate KC elimination is however undefined. In this study we show that antigen-specific CD8 T cells can eliminate antigen-bearing KCs in vivo and inhibit their clonogenic potential in vitro, independently of the effector molecules perforin and Fas-ligand (Fas-L). In contrast, IFN-gamma receptor expression on KCs and T cells producing IFN-gamma are each necessary and sufficient for in vitro inhibition of KC clonogenic potential. Thus, antigen-specific cytotoxic T lymphocytes (CTLs) may mediate destruction of epithelium expressing non-self antigen by eliminating KCs with potential for self-renewal through an IFN-gamma-dependent mechanism

Antigen-specific CD4 cells assist CD8 T-effector cells in eliminating keratinocytes

Keratinocytes expressing tumor or viral antigens can be eliminated by antigen-primed CD8 cytotoxic T cells. CD4 T-helper cells help induction of CD8 cytotoxic T cells from naive precursors and generation of CD8 T-cell memory. In this study, we show, unexpectedly, that CD4 cells are also required to assist primed CD8 effector T cells in rejection of skin expressing human growth hormone, a neo-self-antigen, in keratinocytes. The requirement for CD4 cells can be substituted by CD40 costimulation. Rejection of skin expressing ovalbumin (OVA), a non-self-antigen, by primed CD8 cytotoxic T cells can in contrast occur without help from antigen-specific CD4 T cells. However, rejection of OVA expressing keratinocytes is helped by antigen-specific CD4 T cells if only low numbers of primed or naive OVA-specific CD8 T cells are available. Effective immunotherapy directed at antigens expressed in squamous cancer may therefore be facilitated by induction of tumor antigen-specific CD4 helper T cells, as well as cytotoxic CD8 T cells