Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 122-141) Also available in print.

Dissertation (Ph.D.)--University of Toledo, 2009. / "In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Sciences." Title from title page of PDF document. Bibliography: p. 70-80, p. 28-158.

Thesis (doctoral)--Lund University, 1992. / Added t.p. with thesis statement inserted.

Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, Discipline of Paediatrics, 2007. / "June 2007" Includes Addenda attached to back page. Bibliography: leaves 215-274. Also available in print form.

Thesis (doctoral)--Lund University, 1992. / Added t.p. with thesis statement inserted.

Thesis (M. Med. Sc.)--University of Hong Kong, 2005.

No description available.

Human adenoviruses (HAdV) are non-enveloped viruses with an icosahedral capsid and a linear double-stranded DNA genome. These viruses belong to the family Adenoviridae and genus Mastadenovirus. An important property of the HAdV is that it is non-enveloped making it highly resistant to detergents and harsh environmental conditions. This virus is grouped in seven species (A-G) with more than 88 genotypes. These seven species are associated with several diseases, such as, respiratory infections, keratoconjunctivitis, urinary infections, hepatitis and gastrointestinal infections. The HAdV is one of the etiological causes of acute gastroenteritis, mainly caused by HAdV-F40 and HAdV-F41. The virus can be transmitted via the faecal-oral route, inhalation of respiratory droplets and direct contact with contaminated environments. The virus is known to be ubiquitous in environments where human contamination is likely to occur such as wastewater treatment plants. These human contaminations could occur through contaminated secretion and excretions within aqueous environments. There is currently a limited amount of information on the HAdV in water Molecular characterisation of human adenoviruses from environmental environments, particularly in Tshwane, Gauteng. Therefore, the aim of the study was to investigate the presence and genotypes of human adenovirus in environmental samples namely raw sewage and treated effluent, using molecular methods. For genotypic characterisation, Sanger sequencing was used on amplicons from 12 HAdV positive samples and next generation sequencing were used on all the amplicons from HAdV positive samples. A total of 150 environmental samples (75 raw sewage and 75 effluent) were collected from two wastewater treatment plants in Tshwane over the study period of 18 months. These environmental samples comprised of 1 L raw sewage and 10 L treated effluent samples. The primary viral recovery for the 1 L raw sewage and 10 L treated effluent samples were performed using skimmed milk flocculation procedure and glass wool adsorption elution technique, respectively. For secondary viral recovery, both environmental samples were subjected to polyethylene glycol/sodium chloride precipitation. Manual extraction was used to extract the nucleic acids from the virus concentrate with mengovirus (MV) used as an extraction control. For the quantification of HAdV, standard curves prepared from known dilutions of HAdV and MV were used. Human adenovirus was detected in 140/150 (93%) of the environmental samples comprising of 69/75 (92%) being raw sewage and 71/75 (95%) being effluent samples. The HAdV concentrations detected in wastewater treatment plant 1 (WWTP 1) ranged from 1.38x105 gc/L to 4.50 x 109 gc/L for raw sewage and 5.08x103 gc/l to 4.30x108 gc/L for effluent. The HAdV concentrations detected in WWTP 2 ranged from 6.84x104 gc/L to 1.69x1012 gc/L for raw sewage and 5.27x103 gc/L to 1.16x108 gc/L for effluent. The HAdV hexon amplification success rate from the nucleic acids was 43/140 (31%). Eighteen HAdV genotypes were successfully characterised using Sanger sequencing. The HAdV-D was the most predominant species in both WWTPs, follow by HAdV-B and HAdV-F. The HAdV-A and HAdV-E species were the least identified. Next generation sequencing identified four times as many genotypes as Sanger sequencing (77 different genotypes). The HAdV-D (types 8, 9, 13, 17, 19, 20, 23, 24, 28, 29, 32, 33, 36, 42, 44, 47, 49, 51, 56, 60, 62, 64, 67 and 81) and HAdV-B (types 2, 3, 7, 11 and 66) were the most predominant species followed by HAdV-F (types 40 and 41), HAdV-A (types 12 and 76), HAdV-E ( type 4) and HAdV-C (type 1). Testing wastewater treatment plants is advantageous as it allows for the detection and identification of HAdV types circulating in the surrounding communities. Due to the large number of species identified using NGS, it is the superior typing method and should be used for future studies. These include strains causing symptomatic and asymptomatic infections. Human adenovirus was detected at comparable frequencies in raw sewage and treated effluent wastewater, with slightly higher detection in effluent samples. However, the viability of these viruses is unknown and should be investigated in further studies. The detection of viruses in wastewater treatment plants are a public health concern as the treated effluent is discharged into rivers, which may be used by communities for domestic and recreational purposes. / Dissertation (MSc (Medical Virology))--University of Pretoria, 2020. / NRF, PRF / Medical Virology / MSc (Medical Virology) / Restricted

No description available.

Malignant mesothelioma (MM) is an aggressive malignancy of the pleural and peritoneal surfaces. Australia has the highest reported national incidence of mesothelioma in the world, and rates are increasing (Leigh et al., 2002). The clinical outcome for patients with this disease is extremely poor, with median survival of 9 to 12 months (Rizzo et al., 2001; Carbone et al., 2002). The latest developments in chemotherapy, radiotherapy and radical surgery have done little to improve the overall survival rate (Kindler 2000; Zellos et al., 2002). New approaches to therapy are thus required (Nowak et al., 2002). Cancer therapy using conditionally replicative adenoviruses (CRAds) and attenuated measles virus (vaccine strain MV-Edm) are novel and promising approaches to cancer treatment. CRAds strategy relies on selective viral replication in tumour cells but not normal cells. Major efforts have been directed toward achieving selective replication by the deletion of viral functions dispensable in tumour cells or by the regulation of viral genes with tumour-specific promoters (Alemany et al., 2000). However, the major clinical limitation of viral therapy has been lack of efficacy rather than safety concerns. In this study, I constructed CRAds in which tumour-specific promoter for Flt-1 (vascular endothelial growth factor receptor) control the essential E1 gene expression, and evaluated the cell-killing efficacy and specificity of CRAds driven by VEGF and Flt-1 promoters in the number of established mesothelioma cell lines and actual primary tumour cells from patients. CRAds with either VEGF or flt-1 promoters showed a strong killeg effect on mesothelioma cells. Co-delivery of CRAds with MMP-9 (matrix metalloproteinase-9) was assessed to determine whether therapeutic efficacy could be improved by reducing tumourassociated fibrosis thereby enhancing viral spread through a tumour mass. Combined therapy did result in greater suppression of tumour growth in vivo. I also identified an immuno-competent murine model of mesothelioma that was permissive for adenoviral replication. Combined viral therapy with immunotherapy (FGK45, an anti-CD40 antibody) in this model resulted in greater effect than Adwt or FGK45 alone and in greatest survival. I evaluated the capacity of MV-Edm to infect human mesothelioma cells to form syncytia, and lead to apoptosis and cell death. I also assessed the mode of death by analysis of markers of apoptosis including caspase-3. In vivo study showed that MVEdm- GFP transduction could be detected in human xenografts in immune deficient mice. Further studies to evaluate the mechanisms and efficacy of anti-tumour immune stimulation induced by tumour cell killing with CRAds and MV-Edm will be discussed in this study. MV-Edm has good killing effect on mesothelioma cells in vitro. In summary the work presented herein provide new insights into stratgies to improve viral therapies for mesothelioma. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342596 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2008