Throughout history a diversity of animal species have been used and studied extensively in the development of vaccines for the benefit of humans and animals alike. As mice are a relatively easy species to maintain, handle and manipulate, and have the advantage of being cost effective, they are commonly employed as animal models in the investigation of immunisation strategies against mucosal associated pathogens. Vaccine research against the human gastric pathogen Helicobacter pylori is extensively conducted in a mouse model and typically uses intra-gastric administration for the testing of potential vaccine candidates. An inherent complication with this route, however, is that the vaccine constituents may be inadequately delivered to sites of specific immunity and consequently may not be the optimal method for vaccine delivery. In the present study a mouse model of H. pylori infection was used to determine the efficacy of alternate mucosal routes of immunisation from examination of protective immunity, immune responses and the practical aspects of vaccine administration. Commencing with the optimisation of intra-intestinal immunisation, the direct injection of a H. pylori vaccine to initiator sites of the mucosal immune system established baseline data of dose rates for the comparative analysis of intra-gastric, intra-nasal and intra-rectal immunisation. Following the development of simple administration techniques whilst maintaining the welfare of the animals, intra-nasal immunisation was shown to elicit the highest level of prophylaxis against H. pylori challenge. Effective prophylaxis was also shown to be dependent upon a specific ratio of the vaccine constituents. When using whole cell lysate of H. pylori and the mucosal adjuvant cholera toxin, the ratio of antigen:adjuvant for optimal protective immunity was 10:1. The outcomes of this study have proved conclusively the necessity for optimisation of all aspects of immunisation in an animal model of infection. / Master of Science (Hons)

Background: Despite a declining trend in the incidence of gastric cancer (GC), it is still a major global public health concern of the 21st century. It afflicts one million people and kills 750,000 annually. It is believed that both genetic and environmental factors contribute to the gastric carcinogenesis. However geographic variation and immigrant studies highlight the role of environmental factors. Objective: To evaluate the association of GC with the environmental factors of diet, helicobacter pylori (H. pylori) infection, lifestyle and occupation as well as family history in Iran. Methodology: A population based case-control study was conducted in the Northwest of Iran where one of the highest incidence rates of the world has been reported. Two hundred and seventeen cases of GC and 394 age and gender matched controls were recruited. Participants were interviewed using a structured questionnaire which elicited information on demographic characteristics, socioeconomic status, family and medical history, lifestyle (smoking, alcohol drinking and substance abuse) and occupation. Ten milliliters of each subject???s blood was collected for blood grouping and to investigate presence of IgG antibodies against H. pylori using an ELISA kit which had been locally validated for this study. Results: Diet and H. pylori infection were found to be the most important determinants of GC in this study. High intake of allium vegetables and fruit, especially citrus fruit, appears to play a protective role. In addition to the consumption of fruit and vegetables, consumption of fresh fish was also inversely associated with GC. On the other, hand consumption of red meat and dairy products were positively associated with the risk of GC. Other dietary practices were also found to be important factors in the etiology of GC. People who had a preference for higher salt intake and drinking strong and hot tea were at higher risk. Finally, H. pylori infection was found to increase the risk of GC. Conclusion: This study has provided important and original information about the etiology of gastric cancer particularly in the Iranian context. These findings could be used in planning preventive strategies for this malignancy, which is a major health problem in Iran.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

共著者あり。共著者名:Asaka Masahiro, Kudo Mineo, Sukegawa Makoto, Katagiri Masaki, Koshiyama Tatsumi, Kagaya Hidetoshi, Nishikawa Keiko, Hokari Kaku, Takeda Hiroshi, Sugiyama Toshiro. / Hokkaido University (北海道大学) / 博士 / 医学

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

In paleopathology, the assessment of disease occurs through macroscopic observation, which is dependent on the preservation of the sample and the experience of the observer. Many disease events do not leave any visible signatures and therefore go undetected. The relatively new field of paleomicrobiology incorporates molecular techniques where microbial DNA, if present, is amplified from an archaeological sample. The identification of genetic material from micro-organisms, including bacteria and viruses, can confirm a diagnosis that was originally based on visible osteological or mummified tissue changes. Even more promising is the capability of molecular technology to detect microbial DNA evidence of disease processes that were not visibly evident.<p> Based on phylogenetic analyses of modern isolates, scientists have concluded that micro-organisms such as <i>Mycobacterium tuberculosis</i> and <i>Helicobacter pylori</i> have been associated with humans for thousands of years. <i>M. tuberculosis</i> is the causative agent of the disease tuberculosis, and <i>H. pylori</i> is known for its role in gastritis and peptic ulcers. Both are pathogenic bacteria that still impact the health of modern populations. Through the analysis of microbial DNA from these two bacteria in skeletal and mummified tissue, data can be accumulated regarding the spatial and temporal impact of these infections. Interestingly, due to the lengthy association between these bacteria and humans, phylogenetic studies on modern strains have shown that strain characterizations of both <i>M. tuberculosis</i> and <i>H. pylori</i> bacteria reveal connections with past human migrations.<p> In 1999, human remains were discovered eroding out of a glacier in northern British Columbia, Canada on the traditional territory of the Champagne and Aishihik First Nations. The Aboriginal elders named the site Kwäday Dän Tsìnchi, which means long ago person found. Radiocarbon testing of bone collagen and artifacts from the site suggested a time-frame of approximately AD 1670 to 1850, which is either pre-European contact or early post-contact for that area. I analyzed the tissues of the ancient individual specifically for genetic evidence of <i>M. tuberculosis</i> and <i>H. pylori</i> to identify partial health status and determine if a connection could be made to strains associated with European populations to clarify whether the site was pre or post-European contact.<p> Through polymerase chain reaction (PCR) testing of the individuals tissues with primers specific for the IS<i>6100</i> insertion sequence, <i>TbD1</i>, and <i>Rv3479</i>, <i>katG</i> and <i>gyrB</i> genes, I identified evidence of a possible latent tuberculosis infection. Genetic characterization of the <i>katG</i> gene associated with the ancient <i>M. tuberculosis</i> strain revealed a potential connection with European strains. Amplification and sequencing of the <i>gyrB</i> gene fragment indicated the presence of two alleles that may have been the result of a selective pressure.<p> PCR testing of the individuals stomach tissue with specific primers for regions with the <i>vacA</i> gene resulted in a positive identification of <i>H. pylori</i> DNA. Genetic characterization of this virulence-associated gene indicated that the strain contained a <i>vacA</i> signal (s) region s2 allele. This allele is more commonly identified in Western strains that do not cause disease, which suggests that the individual had no gastric symptoms and that European strains were present in northwestern Canada at that time. The vacA middle (m) region contained a hybrid m2a/m1d sequence. Modern hybrids are rare but they have been identified in Asian strains. Studies have shown that the m2a allele is more common in Western strains. A phylogenetic analysis identified that the m1d region clusters with previously published novel strains associated with Aboriginal individuals that are closely related to Asian strains. This indicates a past connection between the ancient individual and his ancestors who arrived in the New World from Asia thousands of years ago.

In paleopathology, the assessment of disease occurs through macroscopic observation, which is dependent on the preservation of the sample and the experience of the observer. Many disease events do not leave any visible signatures and therefore go undetected. The relatively new field of paleomicrobiology incorporates molecular techniques where microbial DNA, if present, is amplified from an archaeological sample. The identification of genetic material from micro-organisms, including bacteria and viruses, can confirm a diagnosis that was originally based on visible osteological or mummified tissue changes. Even more promising is the capability of molecular technology to detect microbial DNA evidence of disease processes that were not visibly evident.<p> Based on phylogenetic analyses of modern isolates, scientists have concluded that micro-organisms such as <i>Mycobacterium tuberculosis</i> and <i>Helicobacter pylori</i> have been associated with humans for thousands of years. <i>M. tuberculosis</i> is the causative agent of the disease tuberculosis, and <i>H. pylori</i> is known for its role in gastritis and peptic ulcers. Both are pathogenic bacteria that still impact the health of modern populations. Through the analysis of microbial DNA from these two bacteria in skeletal and mummified tissue, data can be accumulated regarding the spatial and temporal impact of these infections. Interestingly, due to the lengthy association between these bacteria and humans, phylogenetic studies on modern strains have shown that strain characterizations of both <i>M. tuberculosis</i> and <i>H. pylori</i> bacteria reveal connections with past human migrations.<p> In 1999, human remains were discovered eroding out of a glacier in northern British Columbia, Canada on the traditional territory of the Champagne and Aishihik First Nations. The Aboriginal elders named the site Kwäday Dän Tsìnchi, which means long ago person found. Radiocarbon testing of bone collagen and artifacts from the site suggested a time-frame of approximately AD 1670 to 1850, which is either pre-European contact or early post-contact for that area. I analyzed the tissues of the ancient individual specifically for genetic evidence of <i>M. tuberculosis</i> and <i>H. pylori</i> to identify partial health status and determine if a connection could be made to strains associated with European populations to clarify whether the site was pre or post-European contact.<p> Through polymerase chain reaction (PCR) testing of the individuals tissues with primers specific for the IS<i>6100</i> insertion sequence, <i>TbD1</i>, and <i>Rv3479</i>, <i>katG</i> and <i>gyrB</i> genes, I identified evidence of a possible latent tuberculosis infection. Genetic characterization of the <i>katG</i> gene associated with the ancient <i>M. tuberculosis</i> strain revealed a potential connection with European strains. Amplification and sequencing of the <i>gyrB</i> gene fragment indicated the presence of two alleles that may have been the result of a selective pressure.<p> PCR testing of the individuals stomach tissue with specific primers for regions with the <i>vacA</i> gene resulted in a positive identification of <i>H. pylori</i> DNA. Genetic characterization of this virulence-associated gene indicated that the strain contained a <i>vacA</i> signal (s) region s2 allele. This allele is more commonly identified in Western strains that do not cause disease, which suggests that the individual had no gastric symptoms and that European strains were present in northwestern Canada at that time. The vacA middle (m) region contained a hybrid m2a/m1d sequence. Modern hybrids are rare but they have been identified in Asian strains. Studies have shown that the m2a allele is more common in Western strains. A phylogenetic analysis identified that the m1d region clusters with previously published novel strains associated with Aboriginal individuals that are closely related to Asian strains. This indicates a past connection between the ancient individual and his ancestors who arrived in the New World from Asia thousands of years ago.

No description available.

No description available.