published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / abstract / toc / Botany / Master / Master of Philosophy

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Introduction: Hirschsprung’s Disease (HD) is the congenital absence of ganglion cells (GCs) within the distal intestine. Our objectives are to determine if apoptosis of myenteric GCs occurs during human development and to determine if myenteric GC apoptosis or injury contributes to HD. Materials and Methods: Apoptosis of myenteric GCs was assessed in archived fetal intestinal tissue (n = 4; 15-41 weeks gestational age) and in HD at the transition zone (TZ) (n = 6) using anti-cleaved caspase-3. Immunohistochemistry for GFAP, CD68, HLA-DR and APP was used to assess the presence of enteric reactive changes. Results: No activated caspase-3 expression was present in the myenteric GCs of the developing human intestine or the TZ of HD. No significant increase in GFAP, CD68, HLA-DR or APP expression was present. Conclusions: Apoptosis does not appear to occur during the development of the human myenteric plexus or, in conjunction with GC injury, in HD.

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No description available.

Introduction: Hirschsprung’s Disease (HD) is the congenital absence of ganglion cells (GCs) within the distal intestine. Our objectives are to determine if apoptosis of myenteric GCs occurs during human development and to determine if myenteric GC apoptosis or injury contributes to HD. Materials and Methods: Apoptosis of myenteric GCs was assessed in archived fetal intestinal tissue (n = 4; 15-41 weeks gestational age) and in HD at the transition zone (TZ) (n = 6) using anti-cleaved caspase-3. Immunohistochemistry for GFAP, CD68, HLA-DR and APP was used to assess the presence of enteric reactive changes. Results: No activated caspase-3 expression was present in the myenteric GCs of the developing human intestine or the TZ of HD. No significant increase in GFAP, CD68, HLA-DR or APP expression was present. Conclusions: Apoptosis does not appear to occur during the development of the human myenteric plexus or, in conjunction with GC injury, in HD.

ANTECEDENTES DEL TEMA: El estado ganglionar axilar es el factor pronóstico más importante para determinar la supervivencia y la recurrencia en el carcinoma de mama, puesto que es conocido que la afectación axilar en estas pacientes, disminuye la supervivencia a los 5 años del 85-95 % al 55-70 % y conlleva a que presenten metástasis a distancia con más frecuencia . De todos modos, la introducción y amplia utilización del cribado mamográfico está aumentando la detección de tumores incipientes en pacientes con tumores ocultos, localmente invasivos o in situ, situación que ha llevado a una disminución del tamaño medio de las lesiones detectadas, a un aumento en la frecuencia de detección de carcinomas in situ y, finalmente, a una menor afectación ganglionar de la axila. Estas pacientes, que presentan tumores pequeños precozmente detectados, son aquellas que se van a beneficiar de la técnica de la biopsia selectiva del ganglio centinela (BSGC). Si la biopsia es negativa, la linfadenectomía axilar (LDNA) se puede evitar con la consecuente disminución de la morbilidad. HIPÓTESIS: En los casos de BSGC negativa se evita la LDNA sin aumentar las recidivas axilares; en los casos de BSGC positiva existen factores que predicen la afectación del resto de ganglios axilares; la linfogammagrafía indica los territorios linfáticos que hay que abordar en cada paciente. OBJETIVOS: Valorar la consolidación de la técnica; analizar los factores predictores de la extensión ganglionar metastásica de la axila; conocer el drenaje linfático de cada paciente y valorar la necesidad de abordar los GC de la cadena mamaria interna (GC-MI). METODOLOGÍA: Estudio retrospectivo de la base de datos prospectiva, del servicio de Medicina Nuclear del Hospital Universitari de Bellvitge, de GC en pacientes con carcinoma de mama. RESULTADOS: La BSGC es una técnica precisa en la estadificación de los carcinoma de mama T1T2N0 sin aumentar la recidiva axilar; el tamaño de la metástasis en el GC y el número de GC positivos están relacionados con la presencia de metástasis en otros ganglios de la linfadenectomía axilar; el abordaje de los GC-MI mejora la estadificación y el manejo terapéutico. CONCLUSIONES: La BSGC se consolida como técnica segura en la estadificación axilar de las pacientes con carcinoma de mama, ofreciendo en los casos de negatividad del GC un control axilar del 100% a los 5 años de seguimiento. Dos factores estadísticamente relacionados con la presencia de metástasis en otros ganglios de la LDNA cuando el ganglio centinela axilar es positivo son el tamaño de la metástasis en el GC y el número de GC positivos. La BSGC-MI debería realizarse para obtener resultados que en un futuro permitan determinar si los cambios que conlleva en el tratamiento adyuvante incrementan las tasas de supervivencia o no. No obstante, podría evitarse en situaciones especiales en las que el riesgo es superior al beneficio. / Patients with beast cancer (BC) in early stages benefit from the sentinel lymph node biopsy (SLNB). If SLNB is negative, axillar lymph node dissection (ALND) can be avoided, resulting in a decrease of morbidity. Hypothesis: In cases of negative SLNB, ALND can be avoided without an increase in axillary recurrences; in cases of positive SLNB there are factors that predict the extent of metastatic involvement of the axilla; preoperative lymphoscintigraphy allows visualization of extraaxillary drainage. Aims: To determine: the accuracy of the technique; which preoperative factors could predict the presence of metastases in non-sentinel lymph nodes (non-SLNs), when positive-SLN; the evolution of patients with internal mammary chain (IMC) drainage whether the IMC-SLN was biopsied or not, as well as the clinical implications of the IMC-SLNB in early BC patients in whom the pre-surgical lymphoscintigraphy showed IMC lymphatic drainage. Methods: This is a retrospective analysis of patients with invasive BC included in a prospective SLNB database of the Department of Nuclear Medicine of the University Hospital of Bellvitge, who had conservative surgery and SLNB performed on them. Results: The SLNB is an accurate technique in the axillary stratification of T1T2N0 breast tumours; the probability of finding metastatic involvement of the axilla is statistically related to the size of the SLN metastases and the number of positive SLN; IMC-SLNB improves nodal staging in BC but has little impact on adjuvant treatment. Conclusions: SLNB is an accurate technique in the axillary stratification of patients with BC, offering in the cases of negative SLNB a safe axillary control after a 5-year follow-up. Two factors statistically related to metastatic involvement of the axilla are the size of the SLN metastases and the number of positive SLN. IMC-SLNB should be performed in order to determine in the future whether the changes in the chemotherapeutic regimes will improve the survival rates in this high-risk subgroup of breast cancer patients or not.

Title page, table of contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / The ophthalmic, maxillary and mandibular axon branches of the trigeminal ganglion (TG) provide cutaneous sensory innervation to the vertebrate face, and multiple families of guidance cues amalgamate to direct the navigation of these branches. However, target tissue specific guidance cues that discriminately guide the three TG axon branches are unknown. Prior work demonstrated that EphAs and ephrin-As could discriminately direct dorsal versus ventral motor axon projections into the hindlimb. Similarly, do EphA tyrosine kinases and ephrin-A ligands discriminately guide trigeminal ganglion ophthalmic (TGop) lobe versus maxillomandibular (TGmm) axon projections into the chick embryo face? The aims of this work were two-fold: (1) to identify candidate EphA and ephrin-A molecules during TG axon guidance, and (2) to detennine the functional significance of TG axon EphA and ephrin-A signalling in vitro. This study identified EphA3, EphA4, ephrin-A2 and ephrin-A5 at stages 13, IS and 20, as putative guidance cues to TG axons. TG-EphA3 and -ephrin-A5 were identified as putative receptors to guidance cues expressed in the target fields. EphA3 receptor was differentially expressed, with the TGop lobe expressing higher levels compared to the TGmm lobe. However, ephrin-A5 transcript was not differentially expressed between the two ganglion lobes. In a substratum choice in vitro assay, ephrin-AS-Fc was found to repel approximately 50% of axons growing from stage 20 whole TG explants. This population of axons was identified to be from the TGop lobe. The in vitro data supports the contention that during facial development there may be trigeminal ganglion lobe specific guidance of TGop in comparison to TGmm peripheral sensory axonal projections to target fields coordinated through EphA3 and ephrin-A2/A5 repulsive interactions. In vitro, EphA4-Fc caused morphological changes to TG growth cones, which is likely mediated through TG ephrin-A5 reverse signaling. Furthermore, this study provided in vitro evidence that trigeminal ganglion axons were not responsive to EphA4-Fc, possibly implying that EphAs expressed in the target fields were not repulsive to ganglionic axons during pathfinding. The data suggests that EphN ephrin-A interactions may specifically guide TGop projections into the ophthalmic process similar to lateral motor axon guidance into the hindlimb. For the first time, a model of how EphN ephrin-A interactions and other families of guidance cues may act in concert to guide trigeminal ganglion axons is suggested. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1179603 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2005