Thesis (doctoral)--Universität Kiel, 1998. / Vita. Includes bibliographical references (p. 134-155).

Thesis (Ph. D.)--University of Washington, 1985. / Vita. Bibliography: leaves [113]-116.

The gastrointestinal tract forms the body’s largest interface with the external environment and is exposed to a vast amount of foreign material, including pathogenic and commensal bacteria, as well as food antigens. The gastrointestinal tract has multiple functions that are performed through complex interactions by its different components. It must be able to degrade food, absorb nutrients and eliminate waste, while at the same time maintain a balance between immune tolerance and protection against pathogenic and antigenic material. This concept of mucosally-induced tolerance is a key feature of the gut immune system, whereby a state of local and systemic unresponsiveness to food protein or systemic ignorance of commensal bacteria is maintained under homeostatic conditions through interactions between the host, dietary factors, and the intestinal microbiota. Dysfunctional interactions can lead to a breakdown in tolerance to otherwise innocuous antigens. One of the best characterized food sensitivities is celiac disease (CD). CD is a chronic immune-mediated disease triggered by the ingestion of gluten, the water insoluble protein fraction in wheat, rye and barley, in patients who are HLA/DQ2 or DQ8 positive. Celiac patients can experience a loss of oral tolerance to gluten any time throughout life. The clinical presentation of CD is variable and is often associated with extra-intestinal autoimmune diseases, such as type 1 diabetes (T1D). The increasing incidence of CD and the observation that only a small proportion of genetically susceptible individuals go on to develop active inflammation suggest a role for additional environmental factors in disease pathogenesis. The current treatment for CD is a strict, life-long adherence to a gluten-free diet (GFD), which is very demanding. Frequent gluten contamination can lead to persistent mucosal damage and symptoms, which have a negative effect on quality of life. Understanding the environmental and host factors that contribute to gluten tolerance is critical for the development of adjuvant therapies to the GFD. Therefore, the overall aim of my thesis is to characterize a humanized mouse model of gluten sensitivity in order to study factors that influence host-responses to gluten and to investigate potential therapeutic strategies. In chapter 3 of this thesis I characterized host responses to gluten using transgenic non-obese diabetic (NOD)/DQ8 mice. I found that gluten sensitization in NOD/DQ8 mice induced barrier dysfunction with a moderate degree of enteropathy and the development of anti-gliadin and anti-tissue-transglutaminase antibodies. I also explored the potential role of gluten in the development of T1D and found that gluten-induced barrier dysfunction was not sufficient to induce insulitis; a partial depletion of regulatory T cells (Tregs) plus gluten sensitization was required. In chapter 4, I utilized this model to demonstrate that the microbiota can modulate host responses to gluten. I found that both the presence and absence of a microbiota, as well as the composition of the microbiota influenced host responses to gluten in NOD/DQ8 mice. Finally, Chapters 5 and 6 of this thesis utilized transgenic DQ8 mice to explore two different adjuvant therapies for CD. In chapter 5, I showed that administration of a gluten binding polymer, P(HEMA-co-SS, to gluten-sensitive HLA/DQ8 mice reduced short-term and long-term gluten-induced barrier dysfunction and inflammation. In chapter 6, I discovered that elafin, a human anti-protease, was decreased in patients with active CD and in vitro, it inhibited the deamidation of gliadin peptides, a key step in the pathogenesis of CD. I showed that administration of elafin prevented gluten-induced barrier dysfunction and intraepithelial lymphocytosis. Together these results, (a) provide an in depth characterization of a humanized animal model for studying gluten-induced intestinal and extra-intestinal immune responses, (b) demonstrate the role of the microbiota as an environmental modulator of gluten-induced immune responses, (c) support the preclinical potential of two novel adjuvant therapies to the GFD. These findings emphasize the translational value of using relevant animal models to study the complex interactions between environmental and host factors that contribute to intestinal health and disease. / Thesis / Doctor of Philosophy (Medical Science)

No description available.

Celiac disease is a small intestinal immune-mediated enteropathy precipitated by exposure to gluten, a protein complex in the cereals wheat, barley and rye, in genetically susceptible people. Once considered an uncommon disorder restricted to children of European descent, it is now known to be one of the most common chronic diseases encountered in the Western world, with a serological prevalence of 1% that can be diagnosed at any age. Since it is so common much co-morbidity comprising malignant and non-malignant conditions will occur in association. Malignant complications particularly lymphoma were first described over 50 years ago but the natural history and how commonly these occurred were unknown until relatively recently. Similarly, many non-malignant conditions were known to occur but initially the risks were unclear. It was not until the frequency of coeliac disease could be determined accurately in the community and population-based studies of morbidity and mortality in coeliac disease patients carried out in defined cohorts that these questions could be answered. My research into these aspects of coeliac disease began in 1971 and a body of 35 of my publications spanning the years 1974 to 2018 on the morbidity and mortality of the disorder are presented in this thesis. I have introduced my research findings at many international and national meetings and these data have been influential in shaping the research agenda of other workers. One of my papers (Publication 9) published in Gut in 1989, was the most cited of all papers which appeared in the journal for that year. To date it has been cited 1122 times. Information exists for 24 papers presented here and for these the total number of citations stands at 3,887. This excludes references to book chapters. Anecdotal evidence indicates frequent mentions in lectures and clinical practice.

Thesis (MSD) --Boston University, Henry M. Goldman School of Dental Medicine, 2015 (Department of Molecular and Cell Biology). / Includes bibliography: leaves 46-50. / Celiac disease (CD) is an autoimmune disorder characterized by enteropathy caused by ingested gluten. Human transglutaminase 2 (TG 2) localized in the lamina propria of the small intestine modifies gluten by deamidating glutamine residues, which enhances gluten binding to T-cell receptors and downstream inflammatory immune responses. Many other human TGs and microbial transglutaminases (MTGs) share a similar catalytic activity with TG2. This study aimed to investigate the presence and activities of oral TGs from both human and microbial origins in whole saliva (WS) and dental plaque of healthy individuals. It also aimed to establish a method and positive control to detect MTG activity from oral bacteria. [TRUNCATED]

Thesis (M.S.)--California Polytechnic State University, 2009. / Mode of access: Internet. Title from PDF title page; viewed on September 23, 2009. Major professor: Michael Black, Ph.D. "Presented to the faculty of California Polytechnic State University, San Luis Obispo." "In partial fulfillment of the requirements for the degree [of] Master of Science in Biological Sciences." "May 2009." Includes bibliographical references (p. 82-85).

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2009. / Title from title screen (site viewed September 08, 2009). PDF text: vii, 85 p. ; 645 K. UMI publication number: AAT 3352597. Includes bibliographical references. Also available in microfilm and microfiche formats.

Class of 2008 Abstract / Objectives: To assess pharmacists’ and celiac patients’ knowledge and awareness about gluten in medications. Methods: People diagnosed with celiac disease were eligible to participate in the study. Patient questionnaires were administered at two of the quarterly Southern Arizona Celiac Support group meetings. Patients were surveyed regarding how to check the gluten-free status of prescription medications. Pharmacists from Tucson and Phoenix were included in the study. They were contacted by e-mail and invited to participate in the website questionnaire. Pharmacists were surveyed regarding their knowledge and comfort level of gluten content in medications. Both the patient questionnaires and pharmacist questionnaires utilized a rating scale of 0 to 5 (0=not at all, 5=very much). All other questions were multiple-choice. Results: Patient questionnaires were completed by 20 patients diagnosed for <5 years and 19 patients diagnosed ≥5 years. Seventy percent of patients reported that one of the ways they determine a medications’ gluten content is by asking a pharmacist which was significantly higher than any other method reported (p ≤ .010). Pharmacist questionnaires were completed by 40 clinical/hospital pharmacists and 25 community pharmacists. There were no significant differences in the two pharmacist groups’ reported level of knowledge (2.0±1.4 and 2.2±1.3, p=0.50), confidence in counseling (1.6±1.3 and 1.9 ±1.5 p= 0.41), or willingness to determine gluten content in medications (3.4±1.4 and 3.5±1.5). Conclusions: Celiac patients rely on pharmacists to determine the gluten content in medications. Pharmacists are willing to help patients determine gluten content, but are unconfident in their ability to do this.

Background: Celiac disease affects 1% of the population and the only treatment for CD is life-long adherence to a gluten-free diet, this affects every aspect of life including emotional, social, physical and psychological which in turn has an effect on patient quality of life. Objective: This pilot study is an effort in understanding the quality of life in the pediatric CD population and is a guide for a future, large sample research study. Design & Methods: Thirteen children diagnosed with CD by intestinal biopsy (mean 6 months) and their parent pair were asked to complete a generic QoL questionnaire (EQ-5D-CY) and a disease-specific questionnaire (TACQoL-CD). Results: The overall QoL was higher on the generic questionnaire, while the effects of CD and the GFD resulted in a lower quality of life as determined by the TACQoL-CD. Future research with a large sample at multiple timepoints is imperative.