Thesis (Ph. D.)--University of Wisconsin--Madison, 1952. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

La maladie de Parkinson (MP) est une maladie du mouvement caractérisée par une neurodégénérescence de la substance noire et la présence d’inclusions d’α- synucléine (α-syn), les corps de Lewy, dans les neurones survivants. Elle se manifeste aussi par des symptômes non moteurs, dont certains, comme la constipation, surviennent précocement. La découverte que le système nerveux entérique (SNE) est fréquemment touché par la pathologie de Lewy a conduit à envisager que le tissu digestif puisse être source d'un biomarqueur précoce de la MP et que le processus pathologique de la maladie puisse s’initier dans le tube digestif pour gagner ensuite le système nerveux central par un mécanisme de type prion. L’objectif de mon travail de thèse a donc été d’optimiser la détection de l’α-syn dans le tube digestif et de comparer les propriétés de l’α-syn entérique et cérébrale. Nous avons montré que les méthodes immunohistochimiques (IHC) visant à détecter l’α-syn dans le tissu gastro-intestinal inclus en paraffine étaient limitées par des aspects techniques, mais qu’elles permettaient sur des coupes coliques avec paroi entière de détecter l’α-syn pathologique de façon performante. Puis, en utilisant une approche biochimique, nous avons montré que l’α-syn entérique native n’avait probablement pas la même tendance à s’assembler que dans le cerveau et que son niveau d’expression n’était pas modifié dans la MP. Nos travaux sont prometteurs pour la mise au point de marqueurs histologiques entériques de la MP et suggèrent une propension différente entre l’α-syn entérique et celle du cerveau à devenir pathogène. / Parkinson's disease (PD) is a movement disorder characterized by neurodegeneration in the substantia nigra and the presence of inclusions of α-synuclein (α- syn) aggregates, termed Lewy bodies, in surviving neurons. Patients may also exhibit various non-motor symptoms, such as constipation, which occur several years before the onset of motor symptoms. The discovery that the enteric nervous system (ENS) is frequently affected by Lewy pathology has led to consider the digestive tissue as a potential source for a specific PD biomarker and even to suggest that the pathological process (pathogenic α-syn) could be initiated in the gut and be propagated to central nervous system by a prion-like mechanism. The aim of my thesis was therefore (i) to optimize the detection of α-syn in the digestive tract in both physiological and pathological conditions and (ii) to compare the properties of α-syn enteric and nervous system central. In the first part, we showed that immunohistochemical methods (IHC) to detect α-syn in paraffin embedded gastrointestinal tissue were limited by some technical challenges, but when using full thickness colonic sample they allow to detect with high accuracy pathological α-syn. In the second part, using biochemical approach, we have shown that α-syn native enteric may not have the same tendency to assemble itself as in brain and its expression level was not changed in Parkinson's disease. Our results are promising for the development of enteric histological biomarkers of PD and suggest a different propensity between the enteric and brain α-syn to become pathological. Key

Thesis (B.A.(Hons.))--University of Adelaide, Dept. of Psychology, 1976.

Thesis (M.S.)--University of Michigan, 1978.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1983. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis--Wisconsin. / Vita. Includes bibliographical references (leaves 157-161).

[no abstract submitted] / Science, Faculty of / Physics and Astronomy, Department of / Graduate

The crystal and molecular structures of fifteen α-cycloalkylacetophenones and propiophenones have been determined with the use of X-ray crystallography. All of the compounds are known to undergo the Norrish type II reaction in the solid state, which involves abstraction of a favourably oriented Ƴ-hydrogen atom to yield a biradical which can undergo either cleavage or cyclization. The compounds were studied to examine the effect of variation in aromatic ring substituents and cycloalkyl ring size on the nature and surroundings of the reaction site, and, if possible, to develop structure-reactivity relationships for reactions in the solid state. Almost all of the acetophenone derivatives with simple cycloalkyl rings studied assume a common conformation in the solid state, with the acetophenone moiety occupying an equatorial position on the cycloalkyl ring, and with the Ƴ-hydrogen atom most likely to be abstracted utilizing a boatlike abstraction geometry. The effect of α-methyl substitution of the α-cycloalkylacetophenones (to produce the corresponding propiophenones) is to rotate the cycloalkyl moiety by approximately 100° about the acyl-carbon α-carbon bond. The conformations of the cycloalkyl rings are in accord with those expected. The cycloheptyl rings assume twist-chairs (though somewhat disordered), while the cyclooctyl ring all display boat-chair conformations. Four α-adamantylacetophenones assume similar conformations in the solid state (with chair like abstraction geometries), but small differences in conformation were found to account for large differences in photochemical behaviour. Structural studies of a 3-methyladamantyl derivative yielded information as to the preferred pathways for cyclobutanol formation in the solid state, and provided an opportunity for producing an optically active product mixture from an achiral starting. / Science, Faculty of / Chemistry, Department of / Graduate

In this work, spectroscopic observations of α Virginis have been reduced. The line profile variations observed in the He I (6678 A) line show that in spite of concern expressed by Lomb (1978) that the β Cephei variation was no longer active, the star is still pulsating - possibly in a non-radial mode. The binary orbit has been recalculated at the epoch of the observations and an analysis of this and earlier radial velocity data confirms the existence of apsidal motion and also suggests possible variation in the apsidal period. / Science, Faculty of / Physics and Astronomy, Department of / Graduate