Published also as Thesis (Ph. D.)--University of Chicago, 1916. / Includes bibliographical references.

Facsimile of Commentatio de examine physiologico organi visus et systematis cutanei, which was presented as the author's thesis, Breslau, 1823. / Text in Latin with German translation. Includes bibliographical references (p. 153-155) and index.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 92-98).

Thesis (Ph. D.)--York University, 2001. Graduate Programme in Psychology. / Typescript. Includes bibliographical references (leaves 178-190). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pNQ66349.

Thesis (M.A.)--York University, 2002. / Typescript. Includes bibliographical references (leaves 87-98). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pMQ71595.

published_or_final_version / Dental Surgery / Master / Master of Dental Surgery

Recently, there has been considerable interest in developing specific cell-based immunotherapies using dendritic cells (DCs). Here the mechanisms underlying the tolerogenic properties of DCs in the suppression of experimental autoimmune uveoretinitis (EAU), the mouse model of human sight threatening autoimmune uveitis, were examined. Immature DCs have the ability to promote immune tolerance to self antigens and to prevent the development of autoimmune disorders including EAU. However there is a risk that immature DCs placed in the inflammatory environment would undergo maturation and instead of tolerance promote immunity. Therefore much effort has been directed to develop protocols that stabilize the tolerogenic DC properties which would ultimately ensure safety and effectiveness of DC-based vaccines. Previous work demonstrated that activation of DCs with lipopolysaccharide (LPS) increases the ability of these cells to prevent EAU. Here, it was demonstrated that LPS promotes the activation of both TRIF and MyD88 signalling pathways in DCs which after 24 h LPS treatment secreted a significant amount of IL-10, IFN-β, IL-1β, IL-6 and TNF-α while the level of secreted IL-12 is low. It was further shown that LPSinduced enhancement of the tolerogenic properties of DCs correlates with the state of endotoxin tolerance in the DCs, rendering them refractory to further stimulation. It was hypothesised that the LPS-induced enhancement of DC tolerogenicity is due to the reduced expression of the TLR4, which subsequently disables several signalling pathways and prevent DCs from initiating adaptive T cell immunity. In summary, the presented data provides valuable insights into the mechanisms involved in the suppression of autoimmune uveitis using a DC-based therapy.

S100B is a member of the S100 calcium binding protein family and is highly expressed within astrocytes in the brain. Elevated levels of S100B are associated with brain and central nervous system disorders, due to the breakdown of the blood brain barrier. Therefore S100B is routinely used as a marker of disease. Traditionally S100B was thought only as a cell breakdown product but increasing evidence suggests that it may play a role in exacerbating inflammation, however this role is not clear. S100B is known to be present within the eye but its role in retinal inflammation has not been investigated. The aim of this project was therefore to examine the role of S100B using the animal model experimental autoimmune uveoretinitis (EAU). This is a well-established model for the sight-threatening human condition posterior endogenous uveoretinitis. In this disease model an autoimmune response is induced leading to retinal inflammation. Using S100B knockout mice, I have shown a significantly reduced level of disease, as determined by clinical and histological grading. Real-time PCR array analysis of diseased matched retinas indicated down regulation of cytokines and chemokines in S100B knockout mice. In vitro experiments on a macrophage cell line confirmed S100B to have a pro-inflammatory effect on macrophages, the main effector cell in EAU, with up-regulation of cytokine and chemokine expression. In particular IL-1β, CCR1 and CCL22 showed a marked increase in gene expression in response to S100B which was confirmed by real-time PCR. Increased protein production of IL-1β (pro-form), CCR1 and CCL22 was also confirmed. S100B inhibited activation of T cells separated from spleens, as shown by reduced CD25+ expression and IL-2 production. IFN-γ and IL-17 production however was not affected. CCL2 and IL-6 are main inflammatory mediators produced by retinal pigment epithelial cells which are known to be elevated during retinal inflammation. S100B promoted CCL2 and IL-6 production in retinal pigment epithelial cells at different concentrations. The work carried out in this thesis provides additional understanding of the actions of extracellular S100B on immune system cells and its potential role in posterior uveitis.

No description available.

Twelve spatial-cueing experiments examined stimulus-driven and goal-driven control of visual attention orienting under multiple-cue conditions. Spatial cueing involves presenting a cue at a potential target location before a target appears in a display, and measuring the cue's effect on responses to the target stimulus. Under certain conditions, a cue that appears abruptly in a display (direct cue) can speed responses to a target appearing at the previously cued location relative to other uncued locations (called the cue effect). The experiments in this dissertation used a new multiple-cue procedure to decouple the effects of stimulus-driven and goal-driven processes on the control of attention. This technique involved simultaneously presenting a red direct cue (Unique Cue) that was highly predictive of the target location along with multiple grey direct cues (Standard Cues) that were not predictive of the target location. The basic finding was that while cue effects occurred at all cued locations, they were significantly larger at the Unique-Cue location. This finding was interpreted as evidence for stimulus-driven cue effects at all cued locations with additional goal-driven cue effects at the Unique-Cue location. Further experiments showed that Standard-Cue effects could occur independently at multiple locations, that they seemed to involve a sensory-based interaction between the cues and the target, and that they were mediated by a limitedcapacity tracking mechanism. In addition, Unique-Cue effects were found to be the product of goal-driven operations, to interact with Standard-Cue effects, and to involve inhibited processing at unattended locations. These results were explained in terms of a filter-based model of attention control that assigns priority to potential attention-shift destinations. According to this model, stimulus-driven and goal-driven factors generate signals (activity distributions) that drive a filter to open an attention channel at the highest priority location by suppressing the signals at other locations. The final experiments confirmed the central assumptions of this model by providing evidence that the prioritydestination process was sufficient to produce cue effects independent of attention, and that attending to a location involved a suppression of processing at unattended locations. The implications of this model for the larger visual attention literature were also discussed.