Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2008. / Härtill 4 uppsatser.

Thesis (doctoral)--Malmö University, Sweden, 2002. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (Ph. D.)--Columbia University, 1924. / Vita. Bibliography: p. 17.

Thesis (doctoral)--Malmö University, Sweden, 2002. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Trichuriasis, caused by the intestinal nematode Trichuris, is a disease that affects up to a billion people worldwide. To date, most of our knowledge of this disease comes from the mouse model, Trichuris muris, which has been successfully used to dissect the immune-mediated effector mechanisms that elicit the expulsion of the nematode. Numerous studies have shown a temporal association between intestinal nematode expulsion and goblet cell hyperplasia; however their precise role in response to nematode infection remains elusive. Goblet cells found at mucosal surfaces secrete many constituent components of the mucus barrier, including the gel-forming mucins (Muc2 in the intestine); mucins are large multifunctional glycoproteins that provide the structural framework of the barrier. The studies presented in this thesis demonstrate that the mucosal barrier and in particular its mucin components, changes in response to acute and chronic T.muris infection. In animals resistant to chronic T. muris infection, IL-13-mediated increase in Muc2 production and secretion was observed at the site of infection. Critically, expulsion of the nematode was significantly delayed in the absence of Muc2. Further investigation subsequently showed that Muc5ac, a mucin normally expressed in non-intestinal mucosa was, in fact, expressed in the intestine following nematode infection and was associated with nematode expulsion in the resistant mice. Moreover, mice deficient in Muc5ac were susceptible to chronic infection, despite a strong underlying TH2-type immune response which is essential to eliminate the nematodes, suggesting that Muc5ac acts as a critical effector molecule. Several qualitative changes in the mucins were also noted during resistance: mucins were more highly charged and more sulphated during nematode expulsion. Overall, the changes within the mucus barrier during resistance result in altering the rheological properties of the mucus layer making it less porous and mucins were shown to directly 'damage' the nematodes during nematode expulsion as reflected by a significant reduction in ATP levels. Chronic infection was accompanied by decreased levels of low charged and highly sialylated Muc2. Additionally, we demonstrated that the excretory secretory products released by the nematode consist of serine proteases capable of depolymerising the Muc2 mucin network, which may be part of the nematodes regime to improve its niche and/or aid movement through the mucus layer. Overall, this resulted in a porous mucus layer and a favourable environment for the parasite.Data is presented to show that the intestinal mucus barrier and its constituent mucins are an integral part of the co-ordinated expulsion mechanisms that occur in animals resistant to T.muris infection and we identify a mechanism whereby the nematode exerts its effects on the mucin environment to promote its survival within the host.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaf 259).

Thesis (M.Sc.)--University of Alberta, 2009. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Experimental Surgery, Department of Surgery, University of Alberta. Title from pdf file main screen (viewed on July 28, 2009). Includes bibliographical references.

No description available.

The enteric protozoan parasite Entamoeba histolytica is the etiologic agent of the disease amebiasis which is characterized by colitis or hepatic lesions. Amebae colonize the colon by binding to mucous glycoproteins (mucins). Secretory mucins provide the gel nature to mucus and are a vital component of epithelial barrier function. Mucins prevent contact-dependent cytolysis of colonic cells by E. histolytica. To possibly circumvent this barrier, the parasite secretes a potent yet unidentified mucin secretagogue, which could deplete the stored mucin pool and render the mucous layer less protective. The objective of this study was to investigate the molecular mechanisms by which E. histolytica modulates colonic mucin exocytosis. We showed that E. histolytica converts exogenous arachidonic acid to prostaglandin E2 (PGE2), a known mucin secretagogue and potential mechanism by which the parasite evokes mucin secretion. Conversion was via a novel cyclooxygenase-like activity and was inhibitable with the known cyclooxygenase inhibitor aspirin. To study E. histolytica-mucin interactions, we developed an in vitro model of LS174T human colonic epithelial cells that secrete mucin constitutively and in response to mucin agonists. Highly purified mucins isolated from LS174T cells markedly inhibited amebic adherence to target cells and the mucous barrier protected the LS174T monolayers from amebic cytolysis. We have identified that Gal and GalNAc residues (O-linked sugars) of mucins are the protective moiety as O- but not N-linked glycosylation inhibitors decreased their protective effect. To understand how mucins are regulated during intestinal amebiasis and in the inflamed gut, we determined that PGE2 binds the EP4 receptor on LS174T cells and in rat colon to stimulate cyclic adenosine monophosphate-dependent mucin exocytosis. Taken together, these studies delineate how E. histolytica modulates host responses during infection to allow the parasite to survive and persist in th

Thesis (Ph. D.)--University of Wisconsin--Madison, 1987. / Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 159-183).