Thesis (MScMedSc (Pharmacology))--University of Stellenbosch, 2005. / In this thesis, research results are reported on the role of natural and synthetic surfactants on the in vitro permeability characteristics of various chemical compounds across porcine (buccal, bronchial, arterial, venous and rectal) and human (vaginal) tissues. The permeability flux values of the different compounds (arecoline, 17β-estradiol, hydrocortisone, dexamethasone, vasopressin, oxytocin, zidovudine and isoniazid) were determined using a continuous flow-through diffusion system. Mean steady state flux values were compared statistically by means of a t-test at a significance level of 5% as well as an F-test using whole curve comparisons. The results indicated that the synthetic pulmonary surfactant Biopolsurf is an effective enhancer for the permeation of chemical compounds through most of the tissues tested and that molecular weight, electrostatic charge, partitioning of the molecules in surfactant and surfactant concentration play an important role in trans membrane diffusion. In addition the epithelial permeability of the different types of tissues for various chemical compounds (arecoline, 17β-estradiol, hydrocortisone, dexamethasone, vasopressin and oxytocin) across the above tissues were compared. The results obtained showed that the permeability flux values of the compounds across porcine bronchial and human vaginal tissues were consistently similar and that porcine buccal tissue had the lowest permeability of all tissues tested. This was in agreement with previous in vitro studies. It was concluded that a wide variation in the permeability characteristics of different epithelia exists and that the pulmonary epithelium, due to its high permeability, is probably the most effective epithelium for drug delivery purposes, especially for drugs that undergo extensive gastrointestinal or hepatic first-pass metabolism.

Knowledge of human T cell responses and the pathways for their differentiation and maintenance from development into adulthood remains largely sparse. Much of what is known concerning the adaptive immune response in humans derives from analysis of peripheral blood, even though the majority of T cells within the body reside in tissue sites. We have established a protocol with LiveOnNY, the organ procurement organization of the New York metropolitan area allowing us access to healthy tissues from individual organ donors of a diverse background. Through novel analysis of lymphoid and mucosal tissues from infant and adult organ donors, we reveal how naïve, regulatory, and memory T cells dynamically populate and are maintained in tissues and circulation over the human lifespan. An initial multidimensional, quantitative analysis of human T cell compartmentalization involving 56 organ donors of a broad age range revealed that distribution of naïve, effector, and memory T cell subsets is largely dependent on tissue localization and differentiation state. Furthermore, T cell homeostasis driven by cytokine or TCR-mediated signals is dependent on CD4+or CD8+ T cell subset. Examining whether T cell subset distribution was set at birth, we compared T cell populations from a cohort of pediatric organ donors in the first two years of life to tissues from young adult donors aged 15-25 years. Results show a dynamic compartmentalization of naïve and regulatory T cells in all tissues early in life that is rapidly replaced with effector memory T cells (TEM) especially in mucosal sites further revealing the importance of a local adaptive immune response. Interestingly, the proportion and distribution of these T cell populations in tissue sites show varying levels of reliance on thymic output. Further evidence for the compartmentalization of the adaptive immune response and mechanisms for T cell maintenance throughout life can be shown through the analysis of T cell receptor sequences. We examined naïve and TEM populations in lymph nodes and spleen as a function of thymic output revealing low sharing of the naïve T cell repertoire between tissue sites with higher amounts of overlapping clones seen in TEM populations, especially with CD8+ T cells. These differences highlight potentially different roles for CD4+ and CD8+ T cells in the response to pathogen and their maintenance with age.

Copy of one of the author's previously published articles inserted. / Bibliography: leaves 357-404. / 405 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Describes a methodology for the detailed evaluation of the processes involved in the assessment of recombinant orally administrable vaccines against mucosal pathogens (a bivalent vaccine against diarrhoeal disease in this case) / Thesis (M.D.)--University of Adelaide, Dept. of Medicine 1991

Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on December 12, 2007) Vita. Includes bibliographical references.

Most pathogens gain access to their host through mucosal surfaces. It is therefore desirable to develop mucosal vaccines that elicit an immune response to prevent this crucial first step in infection. Current mucosal vaccines are live attenuated strains of pathogens. More recent efforts have focused on the use of recombinant non-pathogenic gram-positive bacteria as live vaccine delivery vectors. Here I have tested the potential of Lactococcus lactis to be used as a vaccine vector. A recombinant strain of L. lactis has been constructed which expresses and displays on its surface the C repeat region (CRR) of the M6 protein of Streptococcus pyogenes. I show that nasal vaccination of mice with this strain elicited strong salivary IgA and serum lgG response. These responses protected mice against a nasal challenge with S. pyogenes. Subcutaneous vaccination with the same strain of L. lactis produced a strong serum lgG response, but no salivary lgA response. Subcutaneous vaccination did not protect the mice against nasal infections when the mice were challenged with S. pyogenes. The immune response and protection afforded by concomitant vaccination by both nasal and subcutaneous routes were better that that seen in nasal vaccination alone. This study shows that an effective vaccine against S. pyogenes is possible using L. lactis as a vaccine vector. It also opens up the potential of L. lactis to be used in the development of vaccines to other mucosal infections. / Graduation date: 2004

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Thesis (M.Sc.) (Honours) -- University of Western Sydney, Hawkesbury, 2001. / A thesis submitted for the degree of Master of Science (Honours), Centre for Farming Systems Research, University of Western Sydney, Hawkesbury, 2001. Bibliography : leaves 142-162.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Thesis (M.S.)--University of Michigan, 1974.

Thesis (Ph. D.)--West Virginia University, 2005 / Title from document title page. Document formatted into pages; contains ix, 155 p. : ill. Vita. Includes abstract. Includes bibliographical references.