The pathophysiology of eosinophilic esophagitis: Altered mechanisms of antigen detection in the esophagus

Recently, a chronic idiopathic disease of the esophagus has emerged, which is now known as eosinophilic esophagitis (EoE). Incomplete knowledge regarding the pathogenesis of EoE has limited treatment options. EoE is known to be a Th2-type immune-mediated disorder. Based on previous studies in both patients and experimental models, it is possible that an abnormal reaction to antigen mediates the pathophysiology of EoE. In this thesis, symptoms and signs unique to EoE were identified by an age-matched, case-controlled study of 326 patients with EoE and gastroesophageal reflux disease. The molecular mechanisms involved in antigen detection in the esophagus, in relation to EoE were then investigated. Esophageal epithelial cells were found, for the first time, to be capable of acting as non-professional antigen presenting cells, with the ability to engulf, process and present antigen on MHC class II to T helper lymphocytes. Antigen presentation by esophageal epithelial cells was induced by interferon-γ, which is increased in biopsies from patients with EoE. Next, it was discovered that esophageal epithelial cell lines expressed functional toll-like receptor (TLR) 2 and TLR3, but in esophageal mucosal biopsies only infiltrating immune cells (including eosinophils) expressed TLR2 and TLR3. Finally, the potential involvement of IgE in the pathogenesis of esophageal inflammation was investigated. IgE in the esophagus was found to be present on mast cells, which are increased in density in the esophageal mucosae of patients with EoE and especially those with a history of atopy. Mechanisms of antigen detection may mediate the pathophysiology of EoE in the esophagus through antigen presentation by epithelial cells, detection by TLRs on immune cells and detection through IgE on mucosal mast cells. Together, these findings demonstrate that mechanisms of antigen detection may actually contribute to the pathophysiology of EoE. Through increased understanding of the mechanisms of EoE, the results of this thesis may contribute to future therapy.

Amorous Ex/Incursions: Love in Writings of Badiou, Weil, Fromm, and Barthes

My dissertation explores the enabling contributions of love to the practice of ethico-political and cultural critique. Engaging with the work of Alain Badiou, Simone Weil, Erich Fromm, and Roland Barthes, I examine love in terms of the following modalities: waiting, giving, and looking. I place the aforementioned thinkers in dialogue with selected literary and cinematic texts to explicate and interrogate the meaningful possibilities of their discourse on love. In my chapter on Alain Badiou, I discuss his ontology, which I draw upon heavily to set the theoretical parameters of my study. I also discuss the logic of love that he develops in his philosophy. Speaking to the problem of pre-Evental agency that critics of his work identify, I suggest that waiting as attention, as theorized by Simone Weil, might be the closest form of agency that a pre-Evental (amorous) being can experience. In my discussion of Erich Fromm, I reevaluate his “art of loving” within the constellation of late capitalism. Reading his work through a Lacanian lens, I explore the utility of his prescriptions by examining Chuck Palahniuk’s controversial novel Fight Club. In my chapter on Roland Barthes, I theorize the possibility of cinematic looking that does not depend on the antagonism inherent in the binaries masculine/ feminine and (Gazing) spectator/ (to-be-looked-at) image. Towards this objective, I propose the “amorous look,” a mode of viewing occasioned by cinematic punctual encounters, that I contend is beyond the domain of desire and perversion. I deploy the “amorous look” as I reflect on Aureus Solito’s film Ang Pagdadalaga ni Maximo Olivares (The Blossoming of Maximo Olivares) and its representations of love and waiting.