"March, 2003" / Ammendments to chapter 9 and a journal article co-authored by the author in back pocket. / Includes bibliographical references (leaves 162-205) / xviii, 211 leaves : ill. (some col.), plates (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 2003

"October 2004" / Includes bibliographical references (leaves 201-256) / xiv, 256 leaves, [9] p. : ill., plates (col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 2005

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

BACKGROUND: Endothelial dysfunction is a principal player in the development of allograft vasculopathy and allograft failure. The hallmark of endothelial dysfunction is impaired nitric oxide bioavailability. Recent evidence implicates endothelin-1 as an integral component of endothelial dysfunction. Immunosuppressive drugs have also been associated with the development of graft vasculopathy. We speculated that endothelin-1 results in endothelial dysfunction by impairing nitric oxide homeostasis and is a player in hypoxia and reperfusion induced vasomotor injury. In addition, we hypothesized that endothelin-1 antagonism with bosentan will limit hypoxia and reperfusion injury and prevent immunosuppressive drug injury. METHODS: We utilized human saphenous vein endothelial cells to evaluate the effects of endothelin-1, hypoxia and reperfusion on endothelial function, protein kinase modulation and cell survival. We also employed a rodent model of chronic drug therapy to assess the effect of cyclosporine and rapamycin treatment on vasomotor function. We investigated the role of nitric oxide augmentation and bosentan in preventing hypoxia and reperfusion injury and in limiting immunosuppressive drug induced vasomotor dysfunction. RESULTS: Elevated endothelin-1 levels resulted in impaired nitric oxide release and endothelial function. The effects of endothelin-1 as well as hypoxia and reperfusion were mediated by altered protein kinase B and protein kinase C activity resulting in endothelial dysfunction. We revealed that endothelin-1 is a key player in hypoxia and reperfusion induced endothelial injury. The immunosuppressive drug cyclosporine induced vasomotor dysfunction while rapamycin preserved vessel homeostasis. Vasomotor dysfunction was characterized by impaired nitric oxide and endothelin-1 homeostasis. Bosentan limited the deleterious effects of endothelin-1, hypoxic injury, reperfusion injury and cyclosporine induced vasomotor impairment. CONCLUSIONS: Our study revealed that endothelin-1 exposure as well as hypoxia and reperfusion results in endothelial dysfunction by altering specific protein kinase C isoform activities and inhibiting protein kinase B. Cyclosporine induced vasomotor dysfunction was mediated by altered nitric oxide and endothelin-1 homeostasis while rapamycin was endothelial protective. Bosentan proved to be an effective therapy at preventing endothelin-1, hypoxia and reperfusion and cyclosporine induced endothelial dysfunction. Protein kinase C modulation as well as bosentan may prove to be NOVEL therapies to prevent endothelial injury during cardiac transplantation.

No description available.

BACKGROUND: Endothelial dysfunction is a principal player in the development of allograft vasculopathy and allograft failure. The hallmark of endothelial dysfunction is impaired nitric oxide bioavailability. Recent evidence implicates endothelin-1 as an integral component of endothelial dysfunction. Immunosuppressive drugs have also been associated with the development of graft vasculopathy. We speculated that endothelin-1 results in endothelial dysfunction by impairing nitric oxide homeostasis and is a player in hypoxia and reperfusion induced vasomotor injury. In addition, we hypothesized that endothelin-1 antagonism with bosentan will limit hypoxia and reperfusion injury and prevent immunosuppressive drug injury. METHODS: We utilized human saphenous vein endothelial cells to evaluate the effects of endothelin-1, hypoxia and reperfusion on endothelial function, protein kinase modulation and cell survival. We also employed a rodent model of chronic drug therapy to assess the effect of cyclosporine and rapamycin treatment on vasomotor function. We investigated the role of nitric oxide augmentation and bosentan in preventing hypoxia and reperfusion injury and in limiting immunosuppressive drug induced vasomotor dysfunction. RESULTS: Elevated endothelin-1 levels resulted in impaired nitric oxide release and endothelial function. The effects of endothelin-1 as well as hypoxia and reperfusion were mediated by altered protein kinase B and protein kinase C activity resulting in endothelial dysfunction. We revealed that endothelin-1 is a key player in hypoxia and reperfusion induced endothelial injury. The immunosuppressive drug cyclosporine induced vasomotor dysfunction while rapamycin preserved vessel homeostasis. Vasomotor dysfunction was characterized by impaired nitric oxide and endothelin-1 homeostasis. Bosentan limited the deleterious effects of endothelin-1, hypoxic injury, reperfusion injury and cyclosporine induced vasomotor impairment. CONCLUSIONS: Our study revealed that endothelin-1 exposure as well as hypoxia and reperfusion results in endothelial dysfunction by altering specific protein kinase C isoform activities and inhibiting protein kinase B. Cyclosporine induced vasomotor dysfunction was mediated by altered nitric oxide and endothelin-1 homeostasis while rapamycin was endothelial protective. Bosentan proved to be an effective therapy at preventing endothelin-1, hypoxia and reperfusion and cyclosporine induced endothelial dysfunction. Protein kinase C modulation as well as bosentan may prove to be NOVEL therapies to prevent endothelial injury during cardiac transplantation.

Previous studies in the population genetics of the oyster drill Thais clavigera show that snails from the west coast of Taiwan belong to the same population. However, the genotype frequency of arginine kinase (Ark) in large snails is different among sites in the west coast. In general, changes of temperature and desiccation caused by tidal cycle are the most important twp environmental factors affect genetic variation of intertidal organisms. In the present study, the relationship between the frequency of Ark genotype and tide was evaluated through the following experiments. It has been found that the frequencies of Ark genotype of snails, collected in August with the size range of 25-35mm, were correlated to tides. A higher grequency of Ark63/100 (0.47~0.56) was in the upper intertidal and a higher frequency of Ark63/63 (0.49~0.66) was at the lower end. Moreover, the genotype frequency also varied with size, i.e. more Ark63/63 in small snails (<25mm) and more Ark63/100 in large snails (>35mm). Laboratory desiccative experiments indicated that snails with genotype of Ark63/100 preferred in the areas of high water level and Ark63/63 in areas of low water level. The laboratory results were consistent with the field data. To compare the enzyme activity, there was no difference among the genotypes of Ark63/63, Ark63/100 and Ark100/100at temperatures of 18, 24 and 30¢J. In summary, the frequencies of Ark genotype varied with tide and size and factors such as temperature, desiccation and reproduction may play important roles in the relationship.

MAP kinases and transcription factors homologous to Saccharomyces cerevisiae Fus3p/Kss1p and Ste12p have been identified in several plant pathogenic fungi and found to be required for pathogenicity and sexual reproduction. A gene encoding the homolog of Fus3p/Kss1p in Neurospora crassa was isolated previously and named mak- 2 (mitogen activated kinase -2). This dissertation describes the isolation of the Ste12p homolog, pp-1 (protoperithecia-1) and the comparison of the phenotypes of the mak-2 and pp-1 mutants. The similar phenotypes of the mak-2 and pp-1 null mutants suggest that these proteins are part of the same MAP kinase signaling cascade in N. crassa. In addition to reduced growth rate, the phenotypes of the mutants demonstrate that this pathway is required for female fertility, contributes to aerial hyphal development and repression of conidiophore development. The mak-2 MAP kinase pathway also regulates several genes putatively involved in secondary metabolism during the mating process. Among these is a gene cluster that is likely to be involved in the production of a polyketide secondary metabolite. An orthologous gene cluster was also identified in M. grisea, and the structural and functional homology of these two related gene clusters was characterized. Microarray analysis was used to extend the analysis of gene expression in mak-2 and pp-1 mutants, and a number of downstream target genes of the MAP kinase pathway were identified and called mak-2 kinase-regulated genes (mkr). A model of this MAP kinase pathway in N. crassa was developed. Since N. crassa is a saprophytic fungus but closely related to several plant pathogens, this research may provide an important perspective on the evolution of a major regulatory pathway governing fungal pathogenesis.

Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / "December 2001." Typescript. Vita. Includes bibliographical references (leaves 181-193). Also available on the Internet.

Background: Rotavirus (RV) is the leading agent of acute gastroenteritis in children under five years old, especially in children of 6~24 months. RV can lead to serious complications or even death. RV can cause a heavy burden of disease particularly in developing countries such as China. To prevent or reduce rotavirus diarrhea (RVD) and RV infection related diseases, damages or complications in children is an important task of public health. RV can also cause extraintestinal damage and complications. The finding of elevated CK-MB has been reported in a couple of Chinese literatures, but the epidemiology and the potential implication of this phenomenon remain poorly understood. Objective: 1. To study the prevalence of elevated serum CK-MB level among children hospitalized with rotavirus gastroenteritis in Guangzhou. 2. To examine factors associated with an elevated CK-MB level 3. To examine the clinical implication of elevated serum CK-MB level with different clinical symptomatology, severity, and disease outcome of rotavirus gastroenteritis in children. Methods: Aretrospective analysis of hospital records had carried out in Guangzhou Women and Children’s Medical Centre (GZWCMC), China. Hospital records during the period from 1 January 2011 to 31 December 2011 of inpatients from GZWCMC were screened and all inpatients with a diagnosis of rotavirus gastroenteritis in GZWCMC were recruited. Result and conclusion: Our study included418 cases of rotavirus infection hospitalized in GZWCMC in Guangdong in 2011, we found elevation of CK-MB a common phenomenon among patients of RV gastroenteritis, and identified a number of risk factors for elevated CK-MB level. These included patients of aged between 6-24 months, cases occurring in autumn or winter, patients coming from low income families, had never been breast-fed, or having dehydration, vomiting, malnutrition, fever, or having an abnormal blood gas and electrolyte. The elevated CK-MB level was positively associated with a higher occurrence of complications, a longer duration of hospitalization, and higher hospital cost per day. / published_or_final_version / Public Health / Master / Master of Public Health