A 6 year old boy developed a fatal, rapidly progressive encephalopathy 5 months after a matched unrelated cord blood transplant. Autopsy findings revealed spongiform changes in his brain. The clinical course of this child's illness had many findings consistent with that of a transmissible spongiform encephalopathy (TSE). Pre-mortem and post-mortem studies failed to definitively determine an etiology. Spongiform encephalopathies include the TSEs and mitochondrial encephalopathies. Both should be considered in a post-hematopoietic stem cell transplant patient who develops a progressive encephalopathy when more common etiologies are not found.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13462号 / 論医博第2249号 / 新制||医||1055(附属図書館) / (主査)教授 萩原 正敏, 教授 松田 秀一, 教授 齊藤 博英 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23604号 / 医博第4791号 / 新制||医||1055(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 戸口田 淳也, 教授 河本 宏, 教授 江藤 浩之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

While technological advances in immunology and surgery have permitted rapid increases in the number of homotransplantations now performed, little is known about layman’s attitudes toward donation of organs. Implicit in such progress has been the medical field's assumption that enough donor organs will be forthcoming to meet the increasing demand. In order to research this area a dual emphasis on practical and theoretical issues was employed. The purpose of the present study then, was to investigate this medical assumption by sampling the attitudes and behavior of college students toward donation of organs for transplant purposes, and at the same time, to clarify some of the methodological issues resident in attitude research. The following experimental hypothesis was tested: individuals who express positive or negative attitudes toward organ donation, as measured on an attitude scale, behave in a manner consistent with their attitudes, behavior being measured by statements of intention and by behavioral commitment responses. A Likert-type summated rating scale was developed and utilized as the attitude measuring instrument in the study. A split-half reliability coefficient of .95 and a test-retest reliability of .94 were obtained. A test battery containing the attitude scale, a demographic questionnaire, a social desirability scale and an information test was administered to 389 college students in their classrooms. The validity study utilized two behavioral indices: 1) behavioral intent statements which were gathered following completion of the test battery, and 2) behavioral commitment responses as obtained in individual interviews. The second criterion involved 100 telephone interviews which took place from six to ten weeks after classroom testing. An additional 20 Ss followed up with personal interviews. Both criteria measures constituted Guttman scales. Several secondary issues were investigated. 1. As attitude scales have routinely been validated by use of signed behavioral intent statements the effect of anonymity was examined. Of the total number of Ss participating in the test battery 86 were requested to sign the intent statements; all others were anonymously filled out. 2. In order to evaluate any sensitizing effect on behavioral commitment responses, one-half of those Ss ticipating in the individual interviews had not received any testing in the classroom situation. 3. The Marlowe-Crowne Social Desirability Scale was used to control or the effect of social norms on attitude and behavioral scale scores in approval dependent individuals. 4. An information test was incorporated into the test battery to ascertain the relationship between cognition, affect and behavior. The major results lent strong support to the experimental hypothesis; Ss did tend to behave in a manner consistent with their measured attitudes. Validity coefficients of .38 (attitude and behavioral intent statements), .58 (attitude and behavioral commitment responses) and .64 (composite prediction) suggested that under certain conditions predictive salience can be obtained from attitude scale scores. With regard to the secondary measures, no significant effects were found for anonymity, pretest sensitization, or social desirability. There was some evidence which suggested a relationship between level of information and attitude; however, the results were not conclusive. Empirical findings did support the medical supposition that some people at least (i.e., college students) will be favorably disposed toward posthumous organ donation. Twenty percent of those Ss contacted made a substantial commitment. Further research is planned in order to gain normative data on more representative samples of the total population.

Solution de la « dernière chance » pour les patients atteints d'une grave maladie cardiaque, la transplantation n'est pas qu'une modification corporelle : elle apparaît également comme un choc émotionnel, représentationnel, social. Les questions relatives à l'inclusion d'une part d'autrui en soi, la vision d'un corps ouvert, fragmenté, en partie remplacé, les perturbations potentiellement engendrées dans l'ensemble des sphères sociales (telles la famille et le travail) font de la greffe un événement d'importance dans la biographie de l'individu. Toutefois, la lecture de cet événement par les personnes greffées apparaît encadrée par des normes et des discours qui tracent les « bonnes » et les « mauvaises » façons de penser et de se comporter. Ainsi, la représentation mécaniste du corps et un respect envers le donneur qui doit se faire distant constituent des règles que les patients doivent apprendre et gérer. Considérant que l'expérience de la transplantation est de ce fait éminemment sociale et s'inscrit dans un processus de socialisation secondaire, nous analysons les accords ou les résistances vis-à-vis de ces normes et représentations. En mobilisant les données issues d'enquêtes qualitatives (entretiens, observations) et quantitatives (questionnaires), nous démontrons que la définition de la greffe est variable, oscillant entre « maladie » ou support positif de sens pouvant déboucher sur la figure du « greffé professionnel ». / "Last chance" solution for patients with severe heart disease, transplantation is not only a body modification: it also appears as an emotional, representational, social shock. Including part of an Other into oneself, imagining one's body open, fragmented and partially replaced, and being potentially disturbed in all social spheres (such as family and work) make of transplantation a major event in the biography of the individual. However, the reading of this event by transplant recipients appears framed by norms and discourses that draw the lines bewteen the "right" and "wrong" ways of thinking and behaving. Thus, the mechanistic representation of the body and the respect for the donor are rules that patients must learn and manage. Considering that the experience of transplantation is consequently highly social and constitutes a secondary socialization process, we analyze the the individual's agreeing with or resisting to these norms and representations. Mobilizing data from qualitative research (interviews, observations ) and quantitative ones (surveys), we demonstrate that the definition of transplantation is variable, ranging from "illness" to positive support for meaning that can lead to the figure of the "professional transplant recipient".

Indiana University-Purdue University Indianapolis (IUPUI) / The entire hematopoietic system rests upon a group of very rare cells called hematopoietic stem cells (HSCs). Due to this extraordinarily crucial role, after birth HSCs are localized to the deep bone marrow niche, a hypoxic environment inside the bone where HSCs are under well-orchestrated regulation by both cellular and humoral factors. Among the cellular components regulating hematopoiesis are Leptin Receptor (LEPR)-expressing mesenchymal/stromal cells and adipocytes; both have been demonstrated to have significant influence on the maintenance of HSCs under homeostasis and in stress-related conditions. It has been reported in early work by others that HSCs and hematopoietic progenitor cells (HPCs) express LEPR. However, whether LEPR+ HSCs/HPCs are functionally different from other HSCs/HPCs was unknown. In this study, I demonstrated for the first time that murine LEPR+ Lineage-Sca-1+cKit+ (LSK, a heterogenous population consisting of HSCs/HPCs) cells even though constituting a small portion of total LSK cells are significantly enriched for both phenotypic and functional self-renewing long-term (LT) HSCs as shown in primary and secondary transplants in lethally irradiated recipients. LEPR+LSK cells are also more enriched for colony-forming progenitor cells assessed by colony-forming unit (CFU) assays. In addition, LEPR+ HSCs (defined as LSKCD150+CD48-) exhibited robust repopulating potential as compared to LEPR-HSCs in long-term competitive transplantation assays. To elucidate the molecular pathways that may govern functional properties of LEPR+HSCs, bulk RNA-seq on freshly sorted cells was done. Gene set enrichment analyses (GSEA) revealed Interferon Type I and Interferon γ (IFNγ) Pathways were significantly enriched in LEPR+HSCs while mitochondrial membrane protein gene set was significantly enriched in LEPR-HSCs. Interestingly, proinflammatory signaling including IFNγ pathway has been suggested to be critical for the emergence of embryonic HSCs from the hemogenic endothelium. Altogether, our work demonstrated that LEPR+HSCs represent a small subset of highly engrafting adult BM HSCs. These results may have potential therapeutic implications in the field of hematopoietic transplantation as LEPR is highly conserved between mice and humans.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第18289号 / 工博第3881号 / 新制||工||1595(附属図書館) / 31147 / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 岩田 博夫, 教授 木村 俊作, 教授 秋吉 一成 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18871号 / 医博第3982号 / 新制||医||1008(附属図書館) / 31822 / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 三森 経世, 教授 髙折 晃史 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18896号 / 医博第4007号 / 新制||医||1009(附属図書館) / 31847 / 京都大学大学院医学研究科医学専攻 / (主査)教授 坂井 義治, 教授 伊達 洋至, 教授 前川 平 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医科学) / 甲第18902号 / 医科博第58号 / 新制||医科||4(附属図書館) / 31853 / 京都大学大学院医学研究科医科学専攻 / (主査)教授 山下 潤, 教授 楠見 明弘, 教授 江藤 浩之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM