BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the interaction between CD46 and Helicobacter pylori (a bacterium that colonizes the human gastric mucosa and causes gastritis), peptic ulcers, and cancer. METHODS: Using gastric epithelial cells, we analyzed a set of H pylori strains and mutants for their ability to interact with CD46 and/or influence CD46 expression. Bacterial interaction with full-length CD46 and small CD46 peptides was evaluated by flow cytometry, fluorescence microscopy, enzyme-linked immunosorbent assay, and bacterial survival analyses. RESULTS: H pylori infection caused shedding of CD46 into the extracellular environment. A soluble form of CD46 bound to H pylori and inhibited growth, in a dose- and time-dependent manner, by interacting with urease and alkyl hydroperoxide reductase, which are essential bacterial pathogenicity-associated factors. Binding of CD46 or CD46-derived synthetic peptides blocked the urease activity and ability of bacteria to survive in acidic environments. Oral administration of one CD46 peptide eradicated H pylori from infected mice. CONCLUSIONS: CD46 is an antimicrobial agent that can eradicate H pylori. CD46 peptides might be developed to treat H pylori infection.

There are a lot of inflammatory agents, such as substance P, histamine, capsaicin, and lipopolysaccharide¡]LPS¡^. LPS is the component of all gram-negative bacterial cell wall that can stimulate the immune cells to release pro-inflammatory cytokines that can induce systemic acute inflammation and sepsis. The present study sought to investigate the location of leaky microvessels and magnitude of plasma leakage in the rat stomach secretory and non-secretory portions after an intravenous injection of high dose of LPS¡]15 mg/kg¡^. India ink¡]1 ml/kg¡^ and Evans blue¡]30 mg/ml¡^were used as tracer dyes to measure the magnitude of plasma leakage after LPS application. In the whole mounts of the stomach secretory and non-secretory portions with silver staining, the boundaries of endothelial cells and gaps between endothelial cells for plasma leakage in the blood vessels of microcirculation were made visible. Tissue sections were stained with Alcian blue and periodic acid-Schiff reagent to reveal the mucosubstance present in the mucous cells of the stomach secretory tissue. The result of study demonstrated that the magnitude of LPS-induced plasma leakage in the rat stomach secretory and non-secretory portions was larger than that of the vehicle control. Extensive plasma extravasation was found from 5 min to 30 min after LPS injection. Numerous endothelial gaps formed in both postcapillary venules and collecting venules in the rat stomach secretory portion at 5 min and 30 min after LPS, but the number of gaps declined strikingly 60 min after LPS. Endothelial gaps were rare in the stomach of vehicle control. Histological sections of the stomach secretory portion showed that the leaky vessels were present in the serosa and muscularis externa. Administration of LPS also resulted in release of mucus in gastric gland cells. It is concluded that endotoxin-induced increase in plasma leakage correlated with the formation of endothelial gaps, and associated with depletion of mucosubstance from the mucous cells.

Thesis (M. Phil.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 113-129).

Gastric cancer is one of the worldwide leading cancers which is highly prevalent in Eastern Asia. In Hong Kong, there were 1101 new cases and 687 cancer death in year 2011. So far gastric cancer is known to have poor prognosis and high relapse rate, for which a more effective therapy is sorely needed. With increasing knowledge in the role of HER2 in gastric cancer, a novel targeting agent, Trastuzumab, in combination with chemotherapy has become a promising personalized therapy for advanced gastric cancer and gastro-oesophageal junction cancer patients, particularly effective in HER2 positive patient subgroup. The clinical efficacy and safety of Trastuzumab therapy were ascertained by a recent worldwide phrase III randomized controlled trial called ToGA study in 2010. The assessment of the HER2 status has become crucial in selecting the right patient that will benefit most for the trastuzumab therapy. The aim of our study is to evaluate the local HER2 amplification rate in a group of gastric cancer patients and the associated tumour characteristics as well as sharing our technical experience in optimizing/standardizing the Silver ISH protocol including problem shooting in some difficult cases. From Oct 2012 to Apr 2014, we have accessed 68 requests of gastric cancer for HER2 status determination using Ventana Silver ISH assay, 61 were from stomach or gastro-oesophageal junction, 40 of them were endoscopic biopsy and 21 were resection specimens. Among them the majority were poorly differentiated (65.8%) and of intestinal sub-type (59.1%) according to Lauren classification. Thirteen out of 61 (21.3%) samples were found to be HER2 amplified. Majority of the HER2 positive cases were found in intestinal type and moderately differentiated adenocarcinoma. Eighty percent of the IHC 3+ cases and 29.6% of the IHC 2+ equivocal cases that required reflex tested with SISH were found to be HER2 amplified. There exists a great variation in the reported HER2 amplification rates in previous studies, which are apparently due to the difference in methodology and scoring algorithm apart from the different population groups. Recently, the introduction of the Hofmann’s modification on the scoring algorithm of HER2 assay dedicated for gastric cancer, and the increasing popularity in using DISH/SISH as a reliable alternative to FISH in detecting the HER2 status, have standardized the test and hence narrowed the variation. In order to achieve a more reliable staining result and accurate interpretation, optimization/ standardization of the analytical procedures, as well as the pre-analytical procedures become necessary. The standardization of the formalin fixation time seems to be a crucial factor in this regard. Therefore, the establishment of gastric cancer specimen handling guideline hospital-wide, and specific guideline recommendations for gastric cancer from ASCO/CAP are warranted. / published_or_final_version / Pathology / Master / Master of Medical Sciences

Transpyloric flow is the final step in gastric emptying prior to intestinal absorption of nutrients and medications. The details of this process are still incompletely understood. Transpyloric flow is bi-directional, contrasting with the general perception of solely forward flow implied by studies of gross gastric emptying. The degree to which the patterns of bi-directional transpyloric flow reflect emptying of meals of varied physicochemical composition, its mechanical determinants and effect on delivery of oral medications have been evaluated by the studies presented in this thesis. / Thesis (PhD)--University of South Australia, 2006.

Thesis (Ph. D.)--Cornell University, 1902. / Cover title. "Reprinted from the Biological Bulletin, vol. IV, no. 2, December 1902."

Thesis (Ph.D.)--University of California, San Francisco, 2004. / Bibliography: leaves 138-166. Also available online.

Thesis (M.Phil.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 113-129) Also available in print.

Proefschrift--Utrecht. / Bibliography: p. 101-104.

Thesis (Ph. D.)--University of Minnesota, 1923. / Cover title. Vita.