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You searched for +publisher:"University of Otago" +contributor:("Wheatley, Antony M"). Showing records 1 – 2 of 2 total matches.

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University of Otago

1. Mallard, Beth. The role of Toll-like receptor 4 in Concanavalin A-induced immune-mediated hepatitis .

Degree: 2011, University of Otago

Background: Con A administration leads to T cell-mediated hepatitis in mice, the mechanism of which involves the cytokines interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Other nonparenchymal liver cells (NPLC) are also believed to be involved in Con A-induced hepatitis. Both T cells and the NPLC express TLR4. Although lipopolysaccharide (LPS)/TLR4 signalling pathway is involved in several forms of liver injury, its role in T cell-mediated hepatitis has not been elucidated. In the current study the impact of removing the LPS/TLR4 signalling pathway in Con A-induced liver injury was investigated. Methods: The ability of Con A to elicit liver injury was examined in three groups of mice. Group 1: C3H/HeN mice (functional TLR4) and C3H/HeJ mice (defective TLR4); group 2: mice with no TLR4 (TLR4-/- mice) and their wild-type counterparts (C57BL/6); and group 3: C57BL/6 mice with TLR4 blocked with antibody. All groups of mice were injected with Con A. Plasma ALT was measured to assess liver injury. Proinflammatory cytokine levels were measured using Bioplex suspension array. TLR4 expression on T cells and Kupffer cells from C57BL/6 mice was examined using FACS analysis. The requirement for gut-derived LPS was investigated by pre-treatment of C57BL/6 mice with antibiotics prior to Con A administration and assessing liver injury. The effect of Con A on gut permeability was assessed by oral administration of FITC and measurement of FITC in the systemic circulation. The effect of Con A on the microcirculation of C57BL/6 mice was measured by Laser Doppler Flowmetry (LDF) and by intravital fluorescence microscopy (IVFM). Results: Wild-type mice developed severe injury following Con A administration, indicated by elevated plasma ALT and confirmed by histology. However, no ALT increase was seen in mice lacking a functional LPS/TLR4 pathway. Wild-type mice pre-treated with antibiotics to eliminate gut-derived LPS did not display increased ALT or histological signs of liver injury in response to Con A administration. Plasma proinflammatory cytokines, TNF-α and IFN-γ, were significantly elevated rapidly following Con A administration in wild-type mice (C3H/HeN and C57BL/6) but not in mice without a functional TLR4 pathway. FACS analysis showed an increase in Kupffer cells expressing TLR4 (F4/80+, TLR4+ cells) and an increase in T cells expressing TLR4 (CD3+, TLR4+ cells) following Con A administration. Con A administration was followed by an increase in gut permeability. Con A administration also induced a fall in lobular perfusion and red blood cell velocity, which was partially attenuated by antibody blockade of TLR4. Furthermore, Con A administration induced an increase in leukocyte recruitment, which was partially attenuated by antibody blockade of TLR4. Discussion: Our results show that Con A causes liver injury and cytokine production in mice with functional TLR4. In the absence of a functional TLR4 pathway, cytokine production is attenuated and injury prevented. This thesis has demonstrated that Con A-induced… Advisors/Committee Members: Wheatley, Antony M (advisor).

Subjects/Keywords: TLR4; hepatitis; Con A

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Mallard, B. (2011). The role of Toll-like receptor 4 in Concanavalin A-induced immune-mediated hepatitis . (Doctoral Dissertation). University of Otago. Retrieved from http://hdl.handle.net/10523/606

Chicago Manual of Style (16th Edition):

Mallard, Beth. “The role of Toll-like receptor 4 in Concanavalin A-induced immune-mediated hepatitis .” 2011. Doctoral Dissertation, University of Otago. Accessed July 10, 2020. http://hdl.handle.net/10523/606.

MLA Handbook (7th Edition):

Mallard, Beth. “The role of Toll-like receptor 4 in Concanavalin A-induced immune-mediated hepatitis .” 2011. Web. 10 Jul 2020.

Vancouver:

Mallard B. The role of Toll-like receptor 4 in Concanavalin A-induced immune-mediated hepatitis . [Internet] [Doctoral dissertation]. University of Otago; 2011. [cited 2020 Jul 10]. Available from: http://hdl.handle.net/10523/606.

Council of Science Editors:

Mallard B. The role of Toll-like receptor 4 in Concanavalin A-induced immune-mediated hepatitis . [Doctoral Dissertation]. University of Otago; 2011. Available from: http://hdl.handle.net/10523/606


University of Otago

2. Sun, Cheuk Kwan. The impact of hepatic steatosis on liver circulation, transplantation, ischaemia-reperfusion injury and its relation with nitrous oxide .

Degree: University of Otago

Obesity is now a major health threat in the developed world. To investigate the impact of obesity-induced steatosis on hepatic blood flow, portal venous and hepatic arterial blood flow were measured in the anaesthetized lean and obese Zucker rats. Hepatic tissue oxygenation status was assessed by analyzing the NAD(P)H fluorescence. The results show that although the steatotic liver has a remarkably reduced total and portal venous blood flow, the hepatic arterial blood flow is well maintained. However, the tissue in the steatotic liver is still in a relatively hypoxic state as compared with the lean Zucker rats. The impact of systemic metabolic conditions on the development of liver steatosis was studied by transplanting normal non-steatotic liver grafts from lean Zucker rats to their obese littermates and following the changes in plasma lipid profile, body weight, graft perfusion, microvascular structure, and liver histology for 3 months. The results demonstrate that transplantation of a non-steatotic liver into an obese Zucker rat initially has a positive effect on lipid metabolism. However, 3 months after transplantation, the donor liver became steatotic with reduced perfusion. Hence, the recipient's metabolic status is pivotal in the maintenance of normal liver graft perfusion after transplantation. To investigate the vulnerability of the steatotic liver to ischaemia-reperfusion (IR) injury, partial hepatic IR (45' /60') was induced in anaesthetized lean and obese Zucker rats. Mitochondrial membrane potential, hepatocyte nucleus density, and leukocyte adherence were quantitated using intravital fluorescent microscopy (IVFM) during the process. Plasma transaminases and liver histology were also studied. The results indicate that IR leads to significantly depressed mitochondrial membrane potential and greater injury in the steatotic than in the normal liver. In conclusion, the increased sensitivity of the steatotic liver to IR injury would appear to involve both alterations in the microcirculation and to cellular changes. To elucidate the role of nitric oxide (NO) in the maintenance of hepatic haemodynamics under steatotic condition and during IR injury, hepatic haemodynamic parameters, hepatic microvascular features, and changes in mitochondrial membrane potential were measured during IR (60' /120') in the anaesthetized obese and lean Zucker rats with and without pretreatment with L-NAME (10mg·kg-1 i.a.). Plasma transaminase activities were also compared. The findings suggest that not only is NO vital in the control of hepatic haemodynamics and hepatic microcirculatory perfusion, it is also important in the maintenance of hepatic architecture and the alleviation of hepatic IR injury in both lean and obese Zucker rats. The results also suggest a protective role of NO in the maintenance of metabolic functions and cellular integrity during short-term IR in the steatotic liver. In an attempt to address in vivo the function of specific nitric oxide synthase (NOS) isoform in hepatic haemodynamics and during… Advisors/Committee Members: Wheatley, Antony M (advisor).

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Sun, C. K. (n.d.). The impact of hepatic steatosis on liver circulation, transplantation, ischaemia-reperfusion injury and its relation with nitrous oxide . (Doctoral Dissertation). University of Otago. Retrieved from http://hdl.handle.net/10523/8778

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Chicago Manual of Style (16th Edition):

Sun, Cheuk Kwan. “The impact of hepatic steatosis on liver circulation, transplantation, ischaemia-reperfusion injury and its relation with nitrous oxide .” Doctoral Dissertation, University of Otago. Accessed July 10, 2020. http://hdl.handle.net/10523/8778.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

MLA Handbook (7th Edition):

Sun, Cheuk Kwan. “The impact of hepatic steatosis on liver circulation, transplantation, ischaemia-reperfusion injury and its relation with nitrous oxide .” Web. 10 Jul 2020.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Sun CK. The impact of hepatic steatosis on liver circulation, transplantation, ischaemia-reperfusion injury and its relation with nitrous oxide . [Internet] [Doctoral dissertation]. University of Otago; [cited 2020 Jul 10]. Available from: http://hdl.handle.net/10523/8778.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Council of Science Editors:

Sun CK. The impact of hepatic steatosis on liver circulation, transplantation, ischaemia-reperfusion injury and its relation with nitrous oxide . [Doctoral Dissertation]. University of Otago; Available from: http://hdl.handle.net/10523/8778

Note: this citation may be lacking information needed for this citation format:
No year of publication.

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