Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Hepatobiliary disease can sometimes be difficult to diagnosis due to non-specific clinical signs, and diagnostic imaging is a vital tool in diagnosing these diseases. Multi-slice computed tomographic cholangiography (MSCTC) is a non-invasive way to obtain high quality images of the hepatobiliary system. Our objectives were to determine the best technique for performing MSCTC in normal dogs with regards to contrast agent, dose, and optimal time to imaging. Our test subjects included eight normal adult hounds. Four dogs were administered Cholografin and the other four Biliscopin. Two dose groups were established with four dogs receiving 0.5mL/kg and four receiving 1 mL/kg. Our results demonstrated that MSCTC is feasible in normal dogs and produces high quality images of the hepatobiliary system. The contrast agent Biliscopin at the higher dose subjectively produced the best quality images. The optimal time to image patients following contrast administration varied between contrast agents (15-60 minutes).

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24198号 / 医博第4892号 / 新制||医||1060(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 川口 義弥, 教授 松田 秀一, 教授 小濱 和貴 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成7年3月27日 金子健一朗氏の博士論文として提出された

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [92]-106).

Licentiatavhandling (sammanfattning) Linköping : Linköpings universitet, 2009. / Härtill 2 uppsatser.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-09-12T13:42:31Z No. of bitstreams: 1 Manuela dos Santos Caldas Alterações Iniciais...2016.pdf: 7635538 bytes, checksum: 6a93fba431df86f82cdcef4c267b57b0 (MD5) / Approved for entry into archive by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-09-12T13:54:54Z (GMT) No. of bitstreams: 1 Manuela dos Santos Caldas Alterações Iniciais...2016.pdf: 7635538 bytes, checksum: 6a93fba431df86f82cdcef4c267b57b0 (MD5) / Made available in DSpace on 2016-09-12T13:54:54Z (GMT). No. of bitstreams: 1 Manuela dos Santos Caldas Alterações Iniciais...2016.pdf: 7635538 bytes, checksum: 6a93fba431df86f82cdcef4c267b57b0 (MD5) Previous issue date: 2014-02-07 / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / O espaço-porta é o local de origem da fibrose em muitas doenças crônicas hepáticas. Essa área do fígado participa da drenagem linfática hepática e abriga diversos elementos celulares potencialmente fibrogênicos. Estudos sobre a fibrose hepática relacionados à infecção experimental de ratos pelo helminto Capillaria hepatica têm demonstrado que a fibrose começa em áreas portais com a distribuição de septos que sulcam o parênquima hepático se desenvolvendo em áreas próximas ao espaço de Disse. Entretanto, apesar de esta fibrose ocorrer de forma paralela aos sinusóides, estudos têm revelado que não apenas as células estreladas hepáticas participam da fibrose septal, mas também outros tipos celulares residentes nos espaços-porta. Diante destes aspectos, o presente estudo desenvolveu-se com o intuito de investigar a contribuição das células potencialmente fibrogênicas dos espaços-porta, nas fases iniciais da infecção, onde a fibrose se concentra. Para isso, foram utilizados fragmentos de fígado, em blocos parafinados, disponíveis nos arquivos do Laboratório de Patologia Experimental (CPqGM/Fiocruz) provenientes de ratos infectados com 800 ovos de Capillaria hepatica e foi possível observar que ocorreu a proliferação de colangiócitos e a concentração de miofibroblastos em áreas portais, além da ativação de células estreladas hepáticas, sendo todos os resultados vistos por meio da coloração de rotina HE, Picro-sírius vermelho e imunohistoquímica para α-actina de músculo liso, CD31 e GFAP. / Portal space is the local of origin for fibrosis in many chronic liver diseases. This area is involved with lymph drainage and contains several cell types, potentially fibrogenic. Experimental studies related to hepatic fibrosis during Capillaria hepatica infection in rats have suggested that the septal fibrosis indeed takes origin from portal spaces, with the distribution of the septs in the parenchymal region in proximity areas of Disse space. However, despite this fibrosis occurs in parallel to sinusoids, studies have revealed that not only the hepatic stellate cells participate in septal fibrosis, but also other resident cell types in the portal spaces. In face these aspects, the goal of present study was investigate the contribution of the cells potentially fibrogenic in the portal space, in the early phases of the infection. For this, blocks in paraffin available of the liver of rats infected with 800 eggs of Capillaria hepatica archived in the Laboratory of Experimental Pathology (Research Center Gonçalo Moniz, Fiocruz - BA), were utilized and it was observed that proliferation of colangiocytes and concentration of myofibroblasts occurred portal areas, in addition to the activation of hepatic stellate cells. All results were analised by routine staining HE, Sirius red and immunohistochemistry for α-SMA, GFAP and CD31

Orientador: Elinton Adami Chaim / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T00:49:38Z (GMT). No. of bitstreams: 1 Machado_RicardoRossetto_M.pdf: 1957576 bytes, checksum: 8139974c79a4445e5f71c069dd543c8a (MD5) Previous issue date: 2014 / Resumo: Contexto: As lesões iatrogênicas da via biliar são de difícil manejo e requerem equipes com experiência para a reconstrução da via biliar. O objetivo desse estudo foi avaliar tardiamente os 21 anos de experiência em um centro de referência terciário das reconstruções bileodigestivas após a lesão iatrogênica da via biliar pós-colecistectomia e os fatores envolvidos na estenose da anastomose bileodigestiva. Métodos: Análise retrospectiva de 91 pacientes submetidos a hepaticojejunostomia em Y de Roux entre 1993 e 2013. Dados pré-operatórios, sintomas clínicos após a lesão, reoperações, classificação da lesão e evolução ambulatorial foram avaliados. O teste de qui-quadrado e a regressão logística foram usados para determinar os fatores envolvidos na estenose da anastomose bileodigestiva. Resultados: Mulheres eram 84,5% dos pacientes, média de idade de 43 anos. Foi observada associação entre fístula biliar e derivação bileodigestiva no serviço de origem (p=0,009). Colangite e sintomas clínicos no seguimento ambulatorial foram associadas com a classificação de Bismuth (p=0,008 e p<0,001). O aumento em uma unidade na aspartato aminotransferase em 12 meses de pós-operatório, aumentou a chance de apresentar sintomas clínicos no ambulatório em 4,8% (IC 95%=1,003-1,096). A derivação bileodigestiva no serviço de origem aumentou a chance de associação com fístula biliar em 5,9 vezes (IC 95%=1,132-31,142). Conclusão: A reconstrução da via biliar após a lesão iatrogênica no tratamento cirúrgico da colecistectomia deve ser realizado por cirurgiões experientes e, de preferência, em centros de referência terciário / Abstract: Background: Iatrogenic bile duct injuries are difficult to manage and require surgical teams with experience in bile duct repair. The aim of the study was to describe and correlate factors associated with biliary-enteric anastomosis stricture in a tertiary referral center. Methods: A retrospective analysis of 91 patients undergoing Roux-en-Y hepaticojejunostomy from 1993 to 2013 was carried out. Preoperative data, symptoms following injury, reoperations, classification of lesions and outpatient outcome were evaluated. The chi-square test and logistic regression were used to determine factors involved in biliary-enteric anastomosis stricture. Results: Women comprised 84.5% of patients (mean age: 43 years). An association between bile leakage and biliary-enteric anastomosis at the original health care facility (p=0.009) was observed. Cholangitis and symptoms in the outpatient facility were associated with Bismuth classification (p=0.008 and p<0.001). For each additional unit increase in aspartate aminotransferase values in the 12-month postoperative period, the likelihood of outpatient symptoms increased by 4.8% (95% CI=1.003-1.096). A biliary-enteric anastomosis performed at the original health care facility increased 5.9-fold the chance that a bile leakage was associated (95% CI=1.132-31.142). Conclusion: Bile duct reconstruction due to iatrogenic injury is challenging. To achieve success, repair must be performed by experienced surgeons in tertiary referral centers / Mestrado / Fisiopatologia Cirúrgica / Mestre em Ciências

The development of checkpoint immunotherapy has been a paradigm shift in the treatment of cancer, leading to dramatic improvement in treatment outcomes across a broad range of tumor types. Nevertheless, our current understanding of the tumor immune microenvironment and mediators of resistance to therapy are limited. The recent development of high-throughput single-cell RNA-Sequencing (scRNA-Seq) technology has opened up an unprecedented window into the transcriptional states of distinct tumor-infiltrating immune and stromal cells. However, even this technology has its biological limitations, with very high levels of data dropout induced by low total mRNA molecules and capture efficiency. This thesis explores the application of a transcriptional regulatory protein activity inference approach to single-cell data in order to resolve gene dropout and more deeply characterize upstream drivers of cell state within the micro-environment of several distinct tumor types. To this end, algorithms for inference of protein activity, drug sensitivity, and cell-cell interaction have been adapted to scRNA-Seq data, along with an approach for querying enrichment of single-cell-derived population marker gene sets patient-by-patient in larger bulk-RNA-Seq cohorts. By applying these tools systematically, we have identified distinct cellular sub-populations associated with clinical outcome in different tumor types, including a novel population of C1Q+/TREM2+/APOE+ macrophages associated with post-surgical tumor recurrence in clear cell renal carcinoma, a sub-population of fibroblasts associated with improved response to immunotherapy in head and neck squamous cell carcinoma, tumor cell subpopulations with distinct inferred drug sensitivities in cholangiocarcinoma and prostate cancer, as well as tumor-specific regulatory T-cells (Tregs), active as a mechanism of immunotherapy resistance across a range of tumor types. In ongoing clinical trials from both primary and metastatic prostate cancer as well as clear cell renal carcinoma, we are able to assess which of these populations are enriched in non-responders to checkpoint immunotherapy. The proteomic master regulators of each of these single-cell types have direct utility as potential biomarkers for treatment response, but they may also be therapeutically modulated as novel targets for combination immunotherapy, potentially improving treatment response rates and treatment outcomes in future clinical trials. Finally, this thesis also presents a discovery-to-validation platform to accelerate micro-environment-directed drug repurposing in the context of immunotherapy resistance and rapid CRISPRko validation of novel therapeutic targets. This platform has been developed specifically to validate newly identified master regulators of tumor-specific immunosuppressive regulatory T-cells (Tregs), resulting in discovery of low-dose gemcitabine as a tumor-specific Treg-modulating drug synergistic with anti-PD1 checkpoint immunotherapy and TRPS1 as a proteomic master regulator with clinically significant effect on tumor Treg-infiltrating and tumor growth rate. However, the platform itself may be readily extended in future work to prioritize agents against immunosuppressive macrophage and fibroblast populations for clinical development and trials. As we have discovered, different cancers have different populations of cells driving therapy response and resistance. Taken together, the analytical and validation tools presented in this thesis represent an opportunity to tailor future immuno-therapies at the single-cell level to particular tumor types and to individual patients.