Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Trata-se de um estudo de natureza histórico-social cujo objeto é a atualização do habitus da enfermeira obstétrica durante o processo de implantação da assistência humanizada na maternidade Alexander Fleming, no período de 1998-2004. Os objetivos deste estudo são: descrever as circunstâncias da inserção das enfermeiras obstétricas na assistência ao parto humanizado na maternidade Alexander Fleming; analisar as estratégias de luta no processo de implantação das práticas humanizadas na maternidade Alexander Fleming e discutir as repercussões da implantação do modelo humanizado de assistência ao parto na maternidade Alexander Fleming sobre o campo obstétrico. O estudo apóia-se nas noções teóricas de campo, habitus, poder simbólico, luta simbólica e capital do sociólogo Pierre Bourdieu. O método utilizado foi a história oral temática. Na análise foi realizada a triangulação de dados, através da articulação dos depoimentos orais com os documentos escritos à luz das noções teóricas. Os resultados apontaram que no período estudado havia um contexto favorável ao Projeto de Implantação da Assistência de Enfermagem à Gestante e a Parturiente (PIAEGP). As estratégias utilizadas para o PIAEGP foram: a lotação e o remanejamento interno de enfermeiras da Secretaria Municipal de Saúde do Rio de Janeiro (SMS-RJ) interessadas em atuar na área obstétrica; a capacitação dessas profissionais foi realizada em parceria com a Faculdade de Enfermagem da Universidade do Estado do Rio de Janeiro (FENF/UERJ), com as feministas que atuavam na SMS-RJ e com as lideranças políticas da enfermagem obstétrica. A partir da inserção das enfermeiras no centro obstétrico da maternidade Alexander Fleming, as lutas pela defesa de sua identidade legítima e de suas práticas obstétricas se intensificaram, o que permitiu a ocupação de espaços e a imposição de sua visão de mundo segundo os princípios da humanização do parto e nascimento. Como efeitos da implantação do modelo humanizado na maternidade Alexander Fleming, através do PIAEGP, evidenciamos: a reconfiguração do ensino do Curso de Especialização em Enfermagem Obstétrica da FENF/UERJ e que a maternidade Alexander Fleming foi um dos pilares de sustentação para a criação da Casa de Parto Davi Capistrano Filho da SMS-RJ. A enfermeira obstétrica, por meio de suas estratégias de luta, conquistou espaços e posições que as distinguiram pelo desenvolvimento de práticas humanizadas que estavam de acordo com seu habitus atualizado. / The object of this historical-social study is the update of obstetrical nurses habitus during the process of implementing humanized care at the Alexander Fleming maternity, in the period from 1998 to 2004. The objectives are: to describe the circumstances of including obstetrical nurses in the process of care to humanized delivery at the Alexander Fleming maternity; to analyze the battle strategies in the process of implementing humanized practice at the Alexander Fleming maternity and discuss the repercussions of implementing the humanized delivery care model at the Alexander Fleming maternity in the obstetrical area. The foundations of the study are the theoretical notions of field, habitus, symbolic power, symbolic battle and capital of the sociologist Pierre Bourdieu. The method used was oral thematic history and the analysis was performed using data triangulation, by articulating the oral statements with the written documents under the light of the theoretical ideas. Results showed that the studied period there was a context that favored the Project for the Implementation of Nursing Care to Pregnant and Parturient Women (original name in Portuguese: Projeto de Implantação da Assistência de Enfermagem à Gestante e a Parturiente) (PIAEGP). The strategies used for the PIAEGP were: internal organization of the work stations assigned to nurses at the Rio de Janeiro Municipal Health Department (SMS-RJ) who were interested in working in obstetrics; the referred nurses were trained in a partnership with the Rio de Janeiro State University (FENF/UERJ) College of Nursing, with the feminists working with SMS-RJ and the political leaders in obstetrical nursing. With the inclusion of nurses at the obstetrics ward at the Alexander Fleming maternity, the battle for defending the nurses legitimate identity and obstetrical practices were intensified, which allowed them to take over positions and apply their view of the world according to the principles of humanizing delivery and child birth. We evinced the following effects from the implementation of the humanized care model at Alexander Fleming maternity, through the PIAEGP: a change in the teaching process used in the Obstetrical Nursing Specialization Course at FENF/UERJ and the fact that the Alexander Fleming maternity became one of the supporting pillars for establishing the SMS-RJ Davi Capistrano Filho Birth Center. Obstetrical nurses, by means of battle their strategies, have taken over areas and positions that distinguished them for the development of humanized practices that agree with their updated habitus.

A temática deste estudo está centrada na participação da enfermeira obstétrica no modelo humanizado de atenção ao parto e teve como objetivos: identificar as práticas de enfermeiras obstétricas atuantes no trabalho de parto e parto em uma maternidade municipal do Rio de Janeiro; avaliar a consonância das práticas desenvolvidas por enfermeiras obstétricas durante o trabalho de parto e parto com as recomendações do MS/OMS; analisar a implementação das práticas das enfermeiras obstétricas na assistência ao trabalho de parto e parto entre 2004 e 2008. Trata-se de um estudo descritivo, quantitativo, transversal. O período pesquisado foi de setembro de 2004 a setembro de 2008. A coleta dos dados foi através do livro de registro de partos onde foram registrados 4.510 partos assistidos por enfermeiras. Para a análise foram calculadas a média, mediana e proporção de cada variável estudada, conforme a indicação. As análises foram realizadas utilizando os programas Epi info versão 3.5.1 e Microsoft Word Excel 2007. Verificou-se que a maioria das parturientes assistidas foram jovens, sendo a mediana de idade de 23 anos, que já tinham engravidado duas vezes ou mais e que já tinham parido anteriormente pelo menos uma vez. Com relação à assistência pré-natal 92,8% realizaram o mesmo, contudo apenas 68,2% destas mulheres realizaram seis consultas ou mais. Identificou-se que o acompanhante esteve presente em 60,6% dos partos, porém esta presença foi maior nos partos das adolescentes (77,4%). A posição do parto predominante durante todo o período do estudo foi a vertical (77,6%). As lacerações perineais ocorreram em 52,3% dos partos e a mais incidente foi a laceração de primeiro grau (34,2%). As parturientes que não sofreram qualquer injúria perineal, seja esta espontânea ou cirúrgica, representaram 30,2% dos casos. As práticas obstétricas que não interferem na fisiologia do parto foram realizadas por 85,3% das parturientes, sendo que as mais utilizadas foram os exercícios respiratórios (73,6%), os movimentos pélvicos (42,1%) e a deambulação (29,8%). 67,9% das mulheres assistidas pelas enfermeiras receberam as práticas intervencionistas à fisiologia do parto, destas as mais registradas foram: a realização da amniotomia (25,1%), a administração endovenosa de ocitocina (54%), a realização da episiotomia (22,9%). A episiotomia foi mais utilizada entre as adolescentes (34,8%), nulíparas (44%) e naquelas que pariram na posição horizontal (28,8%). 40,2% das mulheres que não realizaram episiotomia não tiveram laceração perineal e a posição de parto com a menor incidência de laceração perineal foi a quatro apoios (25%), sendo esta classificada como primeiro grau. As adolescentes (55,1%) e as multíparas (71,8%) foram as que menos apresentaram lacerações de períneo. Conclui-se que tanto a prática apoiada no modelo tecnocrático, quanto àquela baseada no modelo humanizado de atenção ao parto, foram registradas na unidade pesquisada. Considera-se que tal fato pode ser investigado em outros estudos, com o objetivo de identificar os fatores que levam à realização de práticas que interferem na fisiologia do parto durante a assistência das enfermeiras obstétricas. / The theme of this study is centered on the participation of nurse midwives in humanized delivery, and was performed with the following objectives: identify the procedures carried out by nurse midwives while assisting labors and deliveries at a maternity hospital in Rio de Janeiro; evaluate the agreement of the assistance provided by nurse midwives during labor and delivery with the recommendations of the Brazilian Health Ministry and the World Health Organization; analyze the implementation of nurse midwife practice in labor and delivery care between 2004 and 2008. This descriptive, quantitative, cross-sectional study was performed from September 2004 to September 2008. Data was collected from the labor record book which listed 4.510 nurse-assisted deliveries. For the analysis, the mean, median and proportion of each studied variable was calculated, as per indication. The analyses were performed using Epi info 3.5.1 and Microsoft Word Excel 2007. It was found that most assisted parturients were young, with a median age of 23 years, had had two or more pregnancies and at least one previous delivery. As for the prenatal care, 92.8% followed the program, but only 68.2% of the women attended six appointments or more. It was observed that in 60.6% of the deliveries the womans partner was present, and this presence was greater among the adolescent womens deliveries (77.4%). Most women assumed a vertical delivery position (77.6%). Perineal lacerations occurred in 52.3% of the deliveries and the most frequent was first degree laceration (34.2%). Parturients who did not suffer any perineal injuries, either spontaneous or surgical, accounted for 30.2% of cases. Obstetrical practices that do not interfere in the physiology of delivery were performed by 85.3% of the parturients, with the most common being breathing exercises (73.6%), pelvic movements (42.1%) and walking (29.8%). Of the women assisted by nurse midwives, 67.9% received interventionist procedures, with the most frequent being: amniotomy (25.1%), venous administration of oxcytokin (54%), episiotomy (22.9%). Episiotomies were mostly used among adolescents (34.8%), nuliparae (44%) and those who delivered in the horizontal position horizontal (28.8%). Of the women who were not submitted to episiotomy 40.2% did not have perineal laceration and the delivery position with the smallest incidence of perineal laceration was on hands and knees (25%), classified as first stage. Adolescent (55.1%) and multipara women (71.8%) were those who least presented perineal lacerations. In conclusion practice based on both the technocratic model and humanized delivery models were observed in the studied unit. This fact could be investigated in other studies, with the purpose of identifying the factors that lead to nurse midwives to assisting with practices that interfere in the physiology of delivery.

Este estudo de perspectiva histórico-social estuda as transformações das práticas das enfermeiras obstétricas consequente ao movimento de humanização do campo obstétrico hospitalar. Tem por objetivos: identificar o capital global das enfermeiras obstétricas; analisar as concepções das enfermeiras sobre a prática profissional no campo obstétrico hospitalar no contexto do movimento de humanização; discutir as transformações percebidas pelas enfermeiras obstétricas sobre sua prática. Utilizei como método a história oral. Os sujeitos foram 25 enfermeiras que vivenciaram no campo obstétrico hospitalar, antes e após a implementação do movimento de humanização. Os cenários foram seis maternidades municipais do Rio de Janeiro. A técnica de coleta de dados foi a entrevista semiestruturada. À luz da perspectiva histórica realizarei a análise dos dados, tendo como base os pressupostos de Pierre Bourdieu. A conjuntura obstétrica do nascimento das entrevistadas era a de transição do parto domiciliar para o ambiente hospitalar. O cenário do parto e nascimento de muitas delas foi uma instituição pública de saúde ou conveniada. As agentes são oriundas de famílias humildes, com pouco capital econômico e cultural. Ressalta-se que as condições de acumulação de capital destas enfermeiras, à época, foram proporcionais às oportunidades que tiveram no campo social em que se encontravam e do processo de socialização. Algumas, após o curso de graduação em enfermagem, buscaram a especialização para adquirir um certificado, que lhes aumentasse o volume de capital e as legitimasse para a realização da assistência ao parto normal. O contexto político onde muitas adquiriram o título de especialista era o de implementação do modelo humanizado no campo obstétrico do município do Rio de Janeiro, favorável para a redução de práticas intervencionistas à parturiente com o incentivo ao parto normal focado na autonomia e no empoderamento feminino. Desse modo, as enfermeiras perceberam que as lutas dos agentes no campo obstétrico para a implantação de um novo modo de agir na obstetrícia foram importantes no processo de mudança de suas práticas. Especificamente sobre as transformações de sua práticas elas evidenciaram que, com esse movimento social e político elas passaram a ver e a assistir a mulher, de forma mais próxima, mais humanizada através da aquisição de capital cultural eficiente, outra evidência destacada foi quanto à questão das lutas, houve o reconhecimento de que as lutas foram importantes no processo de mudança, pois com estas foi possível adquirir lucros simbólicos significativos que permitiram gerar mudanças de posição e de práticas obstétricas no campo hospitalar. / This historical prospective study of social studies the changing practices of Obstetric Nurses (midwives) to the consequent movement of the humanization of obstetric field hospital. Its goals: to identify the global capital of midwives, to analyze the opinions of nurses on the practice field obstetric hospital in the context of humanization movement, to discuss the changes seen by the midwives on the practice. I used as a method of oral history. The subjects were twenty-five nurses who experienced obstetric hospital in the field before and after the implementation of humanization movement. The scenarios were six maternity hospitals in Rio de Janeiro. The technique of data collection was a semi-structured interview. In the light of historical perspective will perform data analysis, based on the assumptions of Pierre Bourdieu. The situation obstetric birth of the interviewees was the transition from home birth to hospital. The scene of childbirth for many of them was a public health institution or outsourced. The agents are from poor families, with little economic and cultural capital. It is emphasized that the conditions of capital accumulation of these nurses at the time were proportional to the opportunities they had in the social field they were in and the process of socialization. Some, after the undergraduate course in nursing have sought to acquire a specialization certificate, they increase the amount of capital and to legitimize the performance of normal delivery assistance. The political context where many have acquired the specialist title was the implementation of a humanized model in the field of obstetric Rio de Janeiro, favorable for the reduction of interventionist practices for women during childbirth to the promotion of normal birth focus on autonomy and female empowerment. Thus, the nurses realized that the struggles of workers in the field ward for the deployment of a new way of acting in obstetrics were in the process of changing their practices. Specifically on the transformation of their practice they showed that with this social and political movement they began to see and watch women as a closer, more human through the acquisition of cultural capital efficient, other evidence has highlighted the question of fighting, there was the recognition that the fights were in the process of change, because these could be acquired symbolic profits that have produced significant changes in position and obstetrical practices in hospitals.

Trata-se de um estudo de Avaliação Econômica Parcial cujo objeto é os custos diretos do protocolo assistencial da Casa de Parto David Capistrano Filho/RJ. O objetivo geral é realizar analise dos custos diretos assistenciais destinados ao ciclo gravídico puerperal na Casa de Parto David Capistrano Filho (CPDCF), situada no município do Rio de Janeiro. Os objetivos específicos deste estudo são: estimar o tipo e a quantidade dos recursos consumidos na execução do cuidado ao ciclo gravídico puerperal de acordo com o protocolo assistencial da CPDCF; analisar os custos diretos relacionados ao protocolo assistencial da CPDCF; comparar os custos avaliados no período da pesquisa ao orçamento municipal destinado a assistência das gestantes de baixo risco no mesmo período. O método utilizado foi a Avaliação de Economia em Saúde, a perspectiva adotada foi o Sistema Único de Saúde (SUS) como órgão gestor, foram avaliados os prontuário das gestantes que realizaram o pré-natal na CPDCF no ano de 2010, excluindo destes as que não pariram na unidade, computando um total de 161 prontuários. Na análise foi realizada a descrição dos custos diretos envolvidos na assistência ao ciclo gravídico puerperal, para isso, foram relacionados e contados os recursos utilizados, definidos como unidades de custo, para a assistência na CPDCF durante o pré-natal, trabalho de parto/parto e pós-parto, e posteriormente esses recursos foram valorados de acordo com as tabelas do Sistema de Gerência da Tabela de Procedimentos (SIGTAP), Medicamentos, Próteses e Materiais Especiais do Sistema Único de Saúde/Ministério da Saúde do Banco de Preços em Saúde (BPS) e da Secretaria Municipal de Saúde Defesa Civil/Rio de Janeiro (SMSDC/RJ). Os resultados apontaram que o custo do pré-natal por gestante foi de R$ 271,91, com prevalência de custos para os exames realizados no pré-natal. Em relação ao trabalho de parto e parto, os custos foram de R$ 352,50 por gestante, neste item os maiores custos foram com os recursos humanos. A pesquisa demonstrou que a CPDCF apresentou menor valor que o orçamento municipal destinado para o parto de acordo com a tabela do SIGTAP (R$ 443,40 a R$ 475,16). Apesar desses dados, e de acordo com o relato das diretoras, a CPDCF é ociosa, e esta influência pode ser negativa para os custos do parto. Em relação ao pós-parto foi avaliado o custo por binômio com uma média de custo de R$ 269,94, os maiores custos de pós-parto foram com os recursos humanos. O custo geral da assistência na CPDCF foi de R$ 894,36 por gestante, desse valor, 39,42% correspondeu aos custos com o parto, 30,40% correspondeu ao custo com o pré-natal e 30,18% com a assistência pós-natal. Para afirmar a eficiência e eficácia das ações na CPDCF, é preciso a realização de uma avaliação de economia em saúde completa; o trabalho de parto/parto foram os que mais representaram os custos; o custo do parto é menor que o valor orçado para o parto de baixo risco, mas medidas de ação sobre a ociosidade são necessárias, pois esta pode influenciar nos custos do parto. / This is a partial Economic Evaluation which object is the direct costs of care protocol of the Casa de Parto David Capistrano Filho / RJ. The overall goal is to perform analysis of the direct care costs of care for the pregnancy and childbirth in the Casa de Parto David Capistrano Filho (CPDCF), located in the municipality of Rio de Janeiro. The specific objectives of this study are: to estimate the type and amount of resources consumed in the implementation of care in pregnancy, childbirth and postpartum in accordance with the CPDCF protocol; analyze the direct costs related to the CPDCF protocol; compare costs assessed during the search the municipal budget for the assistance of low risk pregnant women in the same period. The method used was the Assessment of Health Economics, the adopted perspective was the Brazilian Public Health System as a managing agency, the medical records of pregnant women who underwent prenatal CPDCF in the year 2010 were evaleuted, excluding those who did not deliver at the unit, reaching a total of 161 records. The analysis was performed to describe the direct costs involved in pregnancy, childbirth and postpartum care, to that, the resources used were counted and assessed, defined as cost units for assistance in CPDCF during the prenatal, labor / delivery and postpartum, and then these resources were valued in accordance to the tables in the Table Management System Procedures, Drugs, Materials Prosthetics and Special Health System / Department of Health, Bank of Prices in Health and the Municipal Civil Defense Health / Rio de Janeiro. The results pointed that the cost of prenatal care for pregnant women was R$ 271.91, with a prevalence of costs for exams done along prenatal. In relation to labor and delivery costs were R$ 352.50 per pregnant woman, the highest costs associated with childbirth were human resources. The research demonstrated that CPDCF showed a lower value than the municipal budget allocated for delivery according to the Table Management System Procedures, Drugs, Materials Prosthetics and Special Health System / Department of Health (R$ 443.40 to R $ 475.16). Despite these data, and in accordance with the report of the directors, the CPDCF is idle, and this influence can be negative for the cost of delivery. Regarding postpartum the binomial cost was assessed at an average cost of R$ 269.94, the highest costs with postpartum were human resources. The overall cost of care in CPDCF was R$ 894.36 per pregnant woman, from that amount, 39.42% corresponded to the cost of labor, 30.40% corresponded to the cost prenatal and 30.18% with the postpartum care. To assert the efficiency and effectiveness of actions in CPDCF is necessary to carry out an economic assessment of the overall health. Labor / delivery were the most extensive costs. The cost of labor is less than the amount budgeted for low risk delivery, but action measures are necessary on idleness, as this can influence the cost of delivery.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Com a implantaÃÃo do Programa SaÃde da FamÃlia, a visita domiciliÃria vem ganhando forÃa nesta Ãltima dÃcada, apesar de ser uma atividade desenvolvida na Ãrea de SaÃde PÃblica desde o inÃcio do sÃculo. O presente estudo tem como objetivo compreender percepÃÃes do usuÃrio sobre a visita domiciliÃria como componente do Programa SaÃde da FamÃlia, referente Ãs dimensÃes: cuidado, humanizaÃÃo e integralidade. Trata-se de um estudo exploratÃrio, de natureza qualitativa. Fundamentado na fenomenologia hermenÃutica, inserindo-se na vertente crÃtico interpretativa dado investigar o fenÃmeno em estudo contrastando-o com a materialidade a que se relaciona, buscando apontar elementos para sua transformaÃÃo. Para tanto, foram realizadas 21 entrevistas em profundidade com usuÃrios que recebiam visita domiciliÃria e residiam nas Ãreas pertencentes Ãs seis Secretarias Executivas Regionais de SaÃde no MunicÃpio de Fortaleza. As entrevistas gravadas e transcritas constituÃram a base empÃrica do estudo. A anÃlise dos depoimentos de cada informante evidenciou trÃs eixos temÃticos centrais: 1) Aspectos Relacionais da Visita DomiciliÃria: percepÃÃes dos usuÃrios quanto aos aspectos relacionados à humanizaÃÃo do cuidado e integralidade da assistÃncia durante a visita das equipes. Esse eixo foi dividido em trÃs dimensÃes: percepÃÃo da relaÃÃo profissional usuÃrio, humanizaÃÃo do cuidado, o sentido da integralidade. O segundo eixo 2) CaracterÃsticas da Visita, enfoca caracterÃsticas da visita em relaÃÃo à prioridade e operacionalizaÃÃo da mesma. Emergiram nesse eixo duas dimensÃes: freqÃÃncia/duraÃÃo e seleÃÃo dos atendimentos. O terceiro e Ãltimo eixo temÃtico-VinculaÃÃo com o ServiÃo, levanta questÃes relacionadas com o serviÃo, enfocando aspectos funcionais e de integraÃÃo da atenÃÃo com outros serviÃos, e desdobrando-se em trÃs dimensÃes: funcionamento da unidade, equidade e integraÃÃo da atenÃÃo. As consideraÃÃes finais deste trabalho apontam como caminho para mudanÃas no paradigma da assistÃncia domiciliÃria, a prÃtica em saÃde baseada na aproximaÃÃo, conversaÃÃo e negociaÃÃo constante, entre profissionais, usuÃrios e comunidade / Although a public health practice since the early 20th century, home visits by health care teams from the newly implanted family health program have become increasingly popular over the past decade. The present study looks into usersâ perceptions of home visits within the context of the family health program with respect to completeness and humanization of care. The study was explorative and qualitative. Based on hermeneutic phenomenology and within a critical-interpretive perspective, the study contrasts the phenomenon under investigation with its own materiality in search of transforming elements. To this end 21 interviews were carried out in depth with users receiving home visits by family health teams within the six administrative health districts of Fortaleza. The empirical evidence of the study consisted of taped and transcribed interviews. An analysis of the interviews revealed the existence of three core themes: 1) Health professional/user relationships, i.e. usersâ perceptions of completeness and humanization of care during visits. This theme was divided into three items: perception of health professional/user relationships, humanization of care and the meaning of completeness; 2) Characterization of visits, with emphasis on priorities and operationalization. The theme was divided into two items: frequency/duration of visits and patient selection; and 3) User/health facility association, with focus on health facility management and integration with other services, divided into three items: health facility management, equity and integration of care. In conclusion, the study suggests that home visiting practices may be improved by enhancing the aspects of closeness, conversation and constant negotiation between professionals, users and the community

The kinetics of tumor growth and progression are governed by the interaction between tumor cells, the non-malignant stroma and both innate and adaptive immune cell lineages. Innate immunity has a critical role in the control of tumor cell growth and metastasis. The microenvironment of many tumors is populated with innate immune cells, including regulatory natural killer (NK) cells and dendritic cells (DCs), tumor associated macrophages, and myeloid derived suppressor cells, that suppress normal immune function. Much of our understanding of interactions between tumors and the innate immune system is based on experimental studies performed in mouse “syngenic” models. However, there is clear need for a mechanistic understanding of the human innate immune system within the tumor microenvironment. The goal of my thesis is to characterize the interactions between human innate immune cells and tumors and to define specific pathways and cell lineages that are targets for immune modulation. A central focus of my thesis is the use of cutting-edge humanized mouse models based on the immunodeficient NOD-scid IL2Rgnull (NSG) mouse strain to study human immuno-oncology. In the first section of my thesis I describe studies that evaluate the influence of inflammatory stimuli on innate immune control of tumors. Agents that induce inflammation have been used since the 18th century for the treatment of cancer. The inflammation induced by agents such as toll-like receptor (TLR) agonists is thought to stimulate tumor-specific immunity in patients and augment control of tumor burden. While NSG mice lack murine adaptive immunity (T and B cells), these mice maintain a residual murine innate immune system that responds to TLR agonists. Here I describe a novel NSG mouse strain lacking TLR4 that fails to respond to lipopolysaccharide (LPS). NSG-Tlr4null mice support human immune system engraftment and enables the study of human specific responses to TLR4 agonists. My data demonstrate that specific stimulation of TLR4 activates human innate immune system and promotes regression of human patient derived xenograft (PDX) tumors. In the second section of my thesis I describe the development of an NSG mouse strain that constitutively expresses human Interleukin 15 (IL15) and supports the development of functional human NK cells. Using humanized NSG-IL15 transgenic mice (NSG-Tg(Hu-IL15), my data clearly demonstrate a critical role for human NK cells in limiting growth of a PDX melanoma. In the third section of my thesis I describe, the use of the bone marrow/liver/thymus (BLT) humanized mouse model to study the interactions between the human immune system and PDX melanoma and to evaluate the response of the melanoma to immunotherapy modalities. My results collectively suggest that mice engrafted with human immune systems and bearing human tumors can be harnessed as translational models, which are critically needed as tools to study tumor immunotherapy. These humanized mouse models are an ideal translational tool to advance our understanding of human immuno-oncology and for development and testing of novel immune therapies for the treatment of malignancies.

Viral protein r (Vpr) of Human immunodeficiency virus type 1 (HIV-1) plays an important role in the ability of the virus to infect cells and cause disease. Two polymorphisms to Vpr have been shown to result in differences in disease progression in infected individuals. R36W tends to result in rapid disease progression while R77Q results in long-term non-progression. In order to better understand how these polymorphisms result in these different disease phenotypes, our lab has recently shown that in cell culture, the R36W polymorphism results in increased viral replication and greater induction of cell death. On the other hand, infection with R77Q results in increased G2 cell cycle arrest and increased induction of apoptosis. In this thesis, we have attempted to study how these two polymorphisms affect the ability of HIV-1 to cause cell death in primary CD4+ cells. We show that infection by a Vpr knockout virus results in increased apoptosis while infection with R77Q and R36W result in decreased apoptosis. Additionally, R77Q infection results in increased p24 production. Further, we attempted create a Rag2-/- γc-/- humanized mouse model in order to better study roles of these polymorphisms in vivo. An additional goal of this thesis was to characterize twelve novel Bacillus anthracis bacteriophage. B. anthracis is gram positive, anaerobic, rod best known for being the causative agent of anthrax. Bacteriophage, viruses that infect bacteria, have been used to identify bacterial contamination and to treat infection. Herein, we report the isolation, sequencing, and characterization of twelve novel phages that infect B. anthracis. The genomes were annotated using DNA Master and BLASTp. Hypothetical proteins were analyzed with Phyre2 to predict possible functions based on protein structure, revealing over 100 new predicted functions. Dotplot generation showed that these phages group into four distinct clusters. By running the major portal protein of one representative of each cluster through BLASTp, we have identified the closest relatives to our novel phages and placed them into their respective genera and groups.

京都大学 / 新制・課程博士 / 博士(医科学) / 甲第24885号 / 医科博第152号 / 新制||医科||10(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 河本 宏, 教授 濵﨑 洋子, 教授 上野 英樹 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Au Québec, le statut de paysage humanisé a été adopté en 2002 et, en 2021, l’ouest de l’île Bizard a été le premier territoire à recevoir le statut de paysage humanisé projeté. Ce statut vise à protéger la biodiversité qui découle de l’agriculture et des bocages datant du régime français sur le territoire de l’île. Avant l’adoption du statut de paysage humanisé, la protection des milieux agricoles a fait l’objet de plusieurs lois, politiques ou de projets d’aménagement. Malgré la multiplication des plans, les terres agricoles continuent d’être reprises à des fins de développement et continuent de perdre leur usage agricole. Selon nous, le statut de paysage humanisé propose un changement de paradigme où la perception du territoire comme ressource doit faire place au territoire comme paysage. En nous penchant sur le cas du paysage humanisé projeté de l’île Bizard, nous souhaitons explorer comment le statut de paysage humanisé s’articule à la loi sur la protection des terres et des activités agricoles (LPTAA) pour la protection des paysages agricoles. Comment le statut permet-il de protéger les usages agricoles en considérant le changement de paradigme ? Est-ce que le rôle des agriculteurs doit changer pour atteindre les objectifs du statut et, si oui, comment le plan de conservation propose-t-il d’accompagner ce changement de rôle ? L’analyse de la documentation issue de consultations publiques, les documents du paysage humanisé projeté ainsi que les règlements municipaux en parallèle avec la LPTAA a permis de constater que le statut de paysage humanisé ne rend pas explicite ce changement de rapport au territoire. L’articulation entre ce type d’aire protégée et la LPTAA est complexe, car les deux outils ont des visions divergentes de la conservation. Au niveau du ministère de l’Environnement (MELCC), responsable du statut de paysage humanisé, les pratiques de conservation préservationnistes et la mentalité de la gestion du territoire comme une ressource sont encore fortement ancrées. Ainsi, le statut de paysage humanisé n’agit pas directement pour la conservation des usages agricoles et pourrait même devenir un frein. Cependant, le statut permet à la communauté locale et à la Ville de Montréal de réfléchir et de se donner des objectifs en matière de conservation du paysage à long terme qui peuvent porter fruit si la sensibilisation des propriétaires et du public conduit à la création d’initiatives de conservation volontaires. La gouvernance du projet et les ressources disponibles pour la mise en œuvre du projet seront cruciales pour le développement du projet. L’une des lacunes du projet selon nous est le manque de connaissances détaillées à propos des activités humaines, de la biodiversité et des interactions entre ces deux dimensions cruciales du projet. Le rôle des agriculteurs est peu défini, mais une connaissance plus fine et spatialisée des pratiques agricoles bénéfiques et compatibles avec la biodiversité viendrait grandement préciser ce rôle et permettrait une meilleure conservation du paysage agricole. Dans le contexte de l’île Bizard, ces derniers ne semblent pas conscients de leur rôle de gardiens du paysage et de la biodiversité qui y est associée. / In Quebec, the “humanized landscape” (paysage humanisé) status was introduced in 2002 and in 2021. The western part of l’île Bizard was recognized as the first protected area of that type. This project is aimed at protecting the bocage landscape created by the agricultural practices dating back to the first French settlement on the island and the biodiversity that is associated with those practices. Before the adoption of this status, the protection of agricultural and rural areas was the subject of multiple laws, policies or planning projects. In spite of all these measures, agricultural land keeps losing ground to urban sprawl. According to our research, the humanized landscape status proposes a new paradigm in urban planning where the territory isn’t viewed as a resource, but as a landscape. Through a case study of the Île-Bizard humanized landscape project, we want to explore how the new protected area proposes to preserve the agricultural activities within this new framework of landscape protection. How is the status linked to the existing Loi pour la protection des terres et des activités agricoles (LPTAA)? What role do farmers have to play in this transition, and if their role has to change, how will this change be managed within the project’s framework? The review of documents pertaining to the humanized landscape project, the results of the public consultation and the municipal bylaws in relation to the LPTAA has led us to conclude that the project doesn’t render the paradigm shift explicitly. The links in between the LPTAA and the humanized landscape status are complex because each has a different vision for the preservation of agricultural land. Furthermore, the ministère de l’Environnement et de la Lutte aux changements climatiques de la Faune et des Parcs (MELCCFP), which is responsible for the application of the status, is entrenched in preservationist conservation practises and a framework that views the territory as a resource. Thus, the humanized landscape doesn’t directly act to protect the agricultural activities and could even become an impediment. However, the status may allow the local community and the city of Montreal to reflect and to devise plans and objectives through which long-term landscape conservation may be achieved. In order to do so, raising awareness with landowners and the public and fostering a culture of stewardship towards the protection of the environment and the landscape will be necessary. Also, ensuring that the project properly managed and funded are crucial to the achievement of conservation objectives. As of now, the role of farmers is poorly defined and more knowledge needs to be acquired about agricultural practices and their interactions with the biodiversity of the island. This may allow more precise interventions and offer a clearer picture of the responsibilities of farmers regarding the protection of biodiversity. Within the Île-Bizard humanized landscape project, farmers and landowners don’t seem conscious of their role as stewards of the land.

No description available.