Browsing by Author "Sutherland, Jason Robert"

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    The db mouse as a model for steatohepatitis
    (2006) Sutherland, Jason Robert; Hall, Pauline de la Motte; Marais, David
    Fatty liver disease is a collective phrase for a spectrum of diseases characterised by increased liver fat content. It ranges from fatty infiltration of the liver to an inflammatory condition, steatohepatitis, which may lead onto cirrhosis. Although not associated with alcohol consumption, non-alcoholic steatohepatitis (NASH) has strong associations with obesity, diabetes and dyslipidaemia. Overlapping pathological mechanisms may be involved. The course of the disease will remain unpredictable, and specific treatment will only be able to be instituted once the pathogenesis is fully understood. This thesis reviews current understanding of the pathogenesis and explores the suitability of a recently defined obese diabetic mouse model for its value as a model in the heterozygous and homozygous states. Observations revealed that the db/wt phenotype has a larger mass than the wt/wt and responds with hyperglycaemia. Lipid accumulation occurs in this model when alcohol is administered and lipid peroxidation occurs but histological changes of steatosis and steatohepatitis do not occur. The db/db model is phenotypically distinguished by a large amount of fat storage, diabetes and macrovesicular steatosis that has more lipid peroxidation but no steatohepatitis even when alcohol further increases lipid peroxidation. The model, as explored, did not reveal steatohepatitis either alone, or with alcohol as a single additional stressor, but both the db/wt and db/db mouse model could be further investigated to explore whether additional stressors could induce steaotohepatitis in this model.
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    The role of seminal plasma in cervical carcinoma
    (2010) Sutherland, Jason Robert; Katz, Arieh; Jabbour, Henry
    Cervical cancer is a worldwide public health problem with in excess of 370,000 cases being reported each year. It is the leading cause of death from cancer among women in the developing world where 80% of cases occur. Human papilloma virus (HPV) has been identified as the main causative factor linked with the development and progression of cancer of the cervix, although other factors are known to exist and include genital warts, consenting to sex at an early age, smoking, long term use of contraceptive pills and multiple sexual partners.
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    Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo
    (Public Library of Science, 2012) Sutherland, Jason Robert; Sales, Kurt J; Jabbour, Henry N; Katz, Arieh A
    Cervical cancer is one of the leading causes of cancer-related death in women in sub-Saharan Africa. Extensive evidence has shown that cervical cancer and its precursor lesions are caused by Human papillomavirus (HPV) infection. Although the vast majority of HPV infections are naturally resolved, failure to eradicate infected cells has been shown to promote viral persistence and tumorigenesis. Furthermore, following neoplastic transformation, exposure of cervical epithelial cells to inflammatory mediators either directly or via the systemic circulation may enhance progression of the disease. It is well recognised that seminal plasma contains an abundance of inflammatory mediators, which are identified as regulators of tumour growth. Here we investigated the role of seminal plasma in regulating neoplastic cervical epithelial cell growth and tumorigenesis. Using HeLa cervical adenocarcinoma cells, we found that seminal plasma (SP) induced the expression of the inflammatory enzymes, prostaglandin endoperoxide synthase (PTGS1 and PTGS2), cytokines interleukin (IL) -6, and -11 and vascular endothelial growth factor-A(VEGF-A). To investigate the role of SP on tumour cell growth in vivo, we xenografted HeLa cells subcutaneously into the dorsal flank of nude mice. Intra-peritoneal administration of SP rapidly and significantly enhanced the tumour growth rate and size of HeLa cell xenografts in nude mice. As observed in vitro, we found that SP induced expression of inflammatory PTGS enzymes, cytokines and VEGF-A in vivo. Furthermore we found that SP enhances blood vessel size in HeLa cell xenografts. Finally we show that SP-induced cytokine production, VEGF-A expression and cell proliferation are mediated via the induction of the inflammatory PTGS pathway.