Thesis (B.A. (Hons.)) - University of Queensland, 2005. / Includes bibliography.

In this thesis, immunological parameters in multiple sclerosis patients (MS) have been examined and techniques contributing to the study of these aspects have been developed. The epidemiology of MS suggests that both environmental and genetic factors contribute to the disease process. According to a widespread theory, an autoimmune reaction leading to demyelination could be induced, in genetically determined individuals, by an infectious agent (s) e.g a paramyxovirus or a retrovirus. In the first part of the thesis, the oligoclonal immunoglobulin (Igs) in the CSF of MS patients in relation to the paramyxovirus SV5 were studied. This was to complement an initial observation made in the department that a significant proportion of cerebrospinal fluids (CSF) could have oligoclonal bands directly acting against antigens (Ags) of this virus. In the second part of the thesis, techniques were developed for the analysis of proliferative capacity of peripheral lymphocytes of MS and control patients using possible MS autoantigens viz myelin and brain vessels. The humoral response against these Ags was also assessed by immunoblotting using MS, neurological and normal control patients. In parallel and in the view to obtaining antigens for the immunological studies, techniques for the purification and characterisation of human brain vessels from post mortem brains were assessed and attempts to culture human brain endothelial cell lines were made.

Thesis (M.S.)--Boston University

No description available.

No description available.

La sclérose en plaques est une maladie chronique, auto-immune et neurodégénérative qui se traduit par l’apparition de plaques inflammatoires démyélinisantes dans le système nerveux central. Pour caractériser la réponse immunitaire innée, j’ai développé des outils d’imagerie optique non linéaire multispectrale intravitale, et des solutions semi automatisées d’analyse d’images. J’ai participé à la mise au point d’un protocole d’identification des phénotypes immunitaires en cytométrie. Ces outils appliqués à l’étude de l’encéphalomyélite auto-immune expérimentale, un modèle murin de SEP, ont permis d’analyser la cascade immunitaire par immunomarquages et marquages fluorescents transgéniques, de décrire les distributions des populations cellulaires dans le SNC, et de les associer à la dégradation axonale sur des échelles de temps de la seconde à la semaine. Sur une lignée de souris transgénique, Thy1-CFP/Cd11c-EYFP/LysM-EGFP, j’ai suivi en microscopie biphotonique l’évolution des densités de cellules fluorescentes dans la moelle épinière pendant plusieurs semaines. J’ai conclu que la dégénération axonale et les déficits moteurs sont corrélés avec l’infiltration par les méninges de neutrophiles et monocytes. Les monocytes se différencient in situ en cellules dendritiques d’origine monocytaire (moDCs) parallèlement à l'activation de la microglie. Ces événements cellulaires, dont la maturation des moDCs sont corrélés avec la résorption de l’inflammation. La méthodologie est en place pour poursuivre ces investigations sur d’autres modèles. L’optimisation du microscope m’a aussi permis d’accéder simultanément au contraste endogène CARS pour visualiser la gaine de myéline. / Multiple sclerosis is a chronic auto-immune neurodegenerative disease characterized by the appearance of inflammatory plaques in the central nervous system. To characterize the innate immune response I have developed nonlinear optical tools for intravital multispectral imaging as well as semi-automated image processing solutions. I also contributed to the development of a flow cytometry protocol allowing the identification of immune cell phenotypes. Applied to study of Experimental Autoimmune Encephalomyelitis, a mouse model of MS, these tools have allowed to analyze the immune cascade thanks to immunolabelings and transgenic expression of fluorescence, describe the distributions of cell populations in the CNS with regard to neuron degeneration on time scales ranging from seconds to weeks. On a transgenic mouse line Thy1-CFP/Cd11c-EYFP/LysM-EGFP, I have followed by two-photon microscopy the evolution of fluorescent cells densities in the same area of the spinal cord for several weeks. I conclude that axonal degeneration and motor deficits are correlated with neutrophils and monocytes infiltration from the meninges. The monocytes differentiate in situ in monocyte-derived dendritic cells (moDCs) along with the recruitment of activated microglia. These cellular events correlated with a stabilization/remission phase of the disease. MoDCS maturation thus seems involved in the dampening of inflammation. Methodology and tools are now set for further investigations with other models. The microscope optimization for multicolor excitation allowed me to access simultaneously to the endogenous CARS contrast to visualize the myelin sheath.

Cette thèse propose d'explorer les capacités en mémoire épisodique de patients atteints de sclérose en plaques (sep). A notre connaissance, l'analyse des processus touchés et préservés a fait l'objet de peu de travaux. L'une des raisons historiques semble être la création, dès les années 1980, de batteries d'évaluation rapide destinées aux neurologues. Ainsi, le golden standard de l'évaluation mnésique dans cette affection est le srt (dujardin et al., 2004) qui permet difficilement de contrôler les troubles d'encodage et de récupération. L'objectif de cette thèse sera dans un premier temps de documenter à l'aide d'épreuves permettant une analyse des processus mnésiques, les capacités de mémoire épisodique verbale dans la sep. Les performances de trois groupes de patients (sep, maladies d'Alzheimer et de Parkinson) seront comparées dans l'épreuve rl/ri-16 items. Cette étude sera destinée à vérifier si une majorité de patients sep présente une amélioration du rappel libre après délai contrairement aux deux autres affections testées. Si tel est le cas, l'hypothèse d'un temps de traitement, insuffisamment long pour les patients sep entre les rappels immédiats, mériterait d'être testée. Pour cela, une version parallèle du cvlt sera créée. Ainsi, les performances des patients seront comparées intra-individuellement lors de l'administration de l'épreuve dans sa version originale et lors d'une version où les temps entre les présentations de la liste de courses seront allongés. Un troisième volet sera destiné à tester les capacités de consolidation à long terme (une étude dans ce domaine pour la sep). Une analyse anatomo-fonctionnelle sera conduite en éprouvant l'hypothèse d'un lien entre les performances de rappel à une semaine et la volumétrie hippocampique des patients sep. / This thesis suggests exploring capacities in memory episodic of patients reached by multiple sclerosis. To our knowledge, the analysis of the affected and protected processes was the object of few works. One of the historic reasons seems to be the creation, from the 1980s, of batteries of fast evaluation intended for the neurologists. So, standard Golden of the mnesic evaluation in this affection is the srt (dujardin and al ., on 2004) which allows with difficulty to check) the disorders of encoding and recovery. The objective of this thesis will at first be to document by means of tests allowing an analysis of the mnesic processes, capacities of verbal episodic memory in frog. The performances of three groups of patients (frog, Alzheimer's diseases and of Parkinson) will be compared in the test rl / ri-16 items. This study will be intended to verify if a majority of patients frog presents an improvement of the free reminder after deadline contrary to two other tested affections. If that was the case, the hypothesis of a processing time, insufficiently long for the patients frog between the immediate reminders), would deserve to be tested. For that purpose, a parallel version of the cvlt will be created. So, the performances of the patients will be compared intra - individually during the administration of the test in its original version and during the version where the times between the presentations of the shopping list will be lengthened. The third shutter will be intended to test the capacities of long-term consolidation (a study in this domain for frog). An anatomo-functional analysis will be led by feeling the hypothesis of a link between the performances of reminder in a week and the hippocampal volumetry of the patients frog.

The purpose of the present study was to examine whether or not luminance thresholds through static, chromatic perimetry could be used to distinguish visual threshold losses in multiple sclerosis from that of normal functioning. It was proposed that threshold losses would be greater at both the fovea and near foveal eccentricities due to the assumption that the cone system, unlike the rods, would be the most effected by MS. Twenty-two MS patients and thirty age matched normals were tested on an extensively modified version of the Fieldmaster F225 Automatic Perimeter. Thresholds were established for an achromatic, red, and blue stimulus along a 195 - 15 degree meridian. Testing was done using a 45 apostilb background, to which the subjects were preadapted prior to testing. Results indicated that there was extensive cone involvement (loss in chromatic thresholds) for the MS subjects. Significant differences existed at the fovea between normal and clinically definite subjects but not between normal and probable. Correlational analyses indicated great functional changes in retinal sensitivity for the MS patients. Similar results were obtained between MS patients with and without optic neuritis. Discriminant analyses indicated that the red filter could correctly classify 86.27% of the normals and MS patients with few false positives or negatives. Log threshold difference values between the fovea and 30 degree nasal eccentricity were used to determine a threshold value which could separate normal profiles from MS profiles. The typical "swiss cheese" defects reported in the clinical literature were found only for the achromatic and blue filters. No irregular profiles were found for the red filter. A possible theoretical model based on the results was discussed. Limitations of the study as well as possible future research were also discussed. / Arts, Faculty of / Psychology, Department of / Graduate

Thesis (M.D.)--Boston University

As current treatments for multiple sclerosis (MS) do not prevent the accumulation of long-term disability, researchers and persons with MS are interested in wellness behaviours and how they may be used to manage MS. This thesis includes a review of the literature on wellness-based interventions in persons with progressive MS. Following this review, a cross-sectional study was conducted to characterize dietary intake by disability status in this population, and to examine the functional and symptomatic correlates of dietary behaviours. Participants with MS and matched controls completed questionnaires and a three-day food intake record. There were significant differences in dietary intake with and without supplements between the MS and control groups. Correlates of dietary behaviours were also examined. Further research examining dietary intake in MS is necessary to understand how disability and other factors impact dietary intake behaviours, and which other correlates may be useful targets for future nutrition interventions.