Biomedical Physiology and Kinesiology - Theses, Dissertations, and other Required Graduate Degree Essays

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Abnormal Protein Phosphorylation in Human Amyotrophic Lateral Sclerosis

Author: 
Date created: 
2003
Abstract: 

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of neurons in cortex, brain stem and spinal cord. Currently, ALS is believed to be triggered by a number of distinct factors including glutamate excitotoxicity and mutations in the sod1 gene (mSOD). To explore the role of protein kinase C (PKC) in N-methyl-D-aspartate (NMDA)- mediated cytotoxicity, cell death assays were performed in NR 1 AINR2A-transfected human embryonic kidney (HEK) cells. NMDA-mediated cell death was potentiated by the activation of ca2+- and lipid-dependent isoforms of PKC, specifically PKCP 1. A discrete segment of the C-terminus of NR2A subunit contributed to this potentiation by PKC. These data demonstrate that the elevation of PKC activity increases cell death induced by NMDA receptor activation. To examine the involvement of abnormal protein phosphorylation in ALS, the expression of over 130 proteins were evaluated in postmortem spinal cord tissues from patients having sporadic ALS and controls. There was increased expression of protein kinases and phosphoproteins in ALS tissue such as PKCaIP, protein kinase B a (PKBa) and phospho-PKCalP. This suggests that both pro- and anti-apoptotic signaling pathways are up-regulated in ALS. It is possible that the final outcome for each individual cell is determined by which pathway dominates over the other. Transgenic mice over-expressing mSOD have been used extensively as a model of familial ALS. Comparative studies have revealed a striking similarity in pathology between mSOD mouse and human ALS. The morphological analogy between these two was investigated and we found that in G93A mSOD mice, the spinal nucleus of bulbocavernosus (SNB) is spared from degeneration, paralleling the survival of its functional and anatomical homologue, Onuf s nucleus. This provides evidence that mSOD mice may suitably models ALS. However, a distinct profile of changes in protein expression were observed in the CNS tissues of G93A mSOD mice compared with their control littermates, which was dissimilar to that between ALS patients and controls. This observation indicates that the activation of protein kinases is different with neuron loss in mSOD mouse compared with that seen in patients with sporadic ALS. These findings suggest an important role for abnormal protein phosphorylation in ALS.

Document type: 
Thesis
File(s): 
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
Thesis (Ph.D.)

Pulmonary ventilation following acclimation to a hot environment

Date created: 
2007
Abstract: 

Human pulmonary ventilation and the hyperoxic-centrally mediated ventilatory response to CO2 were studied before and after a 10-day passive heat acclimation (HA). It was hypothesized pulmonary ventilation during a passively- or actively-induced hyperthermia would adapt similarily to thermolytic heat loss responses and that chemosensitivity would be increased following HA. Following HA, onset of increased cutaneous vasodilatation, eccrine sweating and ventilation in both passively- and actively-induced hyperthermia were at significantly lower esophageal temperature thresholds (p<0.05). Addtitionally, following HA the breathing pattern during passively-induced hyperthermia adapted to promote respiratory heat loss and actively-induced hyperthermia gave a significantly (p<0.05) greater ventilation. Irrespective of acclimation state, hyperthermia significantly increased chemosensitivity (p=0.027) across all levels of end-tidal partial pressure of CO2. HA did not modify the normo- or hyperthermic ventilatory recruitment thresholds (VRT) or the supra-VRT chemosensitivity. In conclusion, pulmonary ventilation adapted similarly to thermolytic heat loss responses and chemosensitivity was unmodified following HA.

Document type: 
Thesis
File(s): 
Senior supervisor: 
M
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

Numerical and structural abnormalities of centrosomes in oral cancer and premalignancy

Author: 
Date created: 
2007
Abstract: 

Centrosomes play a critical role in cell division. Recent findings that both numerical and structural alterations to centrosomes occur in cancers support the possibility that such change may be a driving force for cancer development. However, little is known about centrosome alteration in oral cancers and premalignancies. The objective of this study was to assess the frequency of centrosome abnormalities in oral cancers and precancers utilizing immunofluorescence with antibodies to £^-tubulin, a well-characterized centrosomal component, and ƒÑ/ƒÒ-tubulin, the main component of centrioles. Fifty paraffin samples (13 oral cancers; 21 oral premalignancies; 16 nondysplastic controls) were used. The results showed a strong association of centrosome abnormalities and histology (cancer or presence/degree of dysplasia): size abnormalities: P<0.001; cluster formation: P=0.001, and more than 2 centrosomes in each cell: P<0.001. More than 90% of amplified centrosomes lacked centrioles. The results support a role for structural and numerical abnormalities of centrosomes in early carcinogenesis.

Document type: 
Thesis
File(s): 
Senior supervisor: 
M
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

Extracellular release of high mobility group box1 protein from necrotic beta-cells in the pathogenesis of type 1 diabetes mellitus

Author: 
Date created: 
2007
Abstract: 

Nonobese diabetic (NOD) mice, an animal model of human type 1 diabetes mellitus (T1DM), exhibit impaired phagocytosis of apoptotic cells. In addition to phagocytosis, degradation of apoptotic cells determines the level of dead cells in tissues. Therefore, the work examined the kinetics of apoptotic cell degradation in vitro. The work revealed that macrophages from NOD mice digested internalised apoptotic thymocytes at a reduced rate compared to macrophages from control mice. How defective clearance leads to the development of T1DM is unclear. Necrosis is associated with inflammation, and high mobility group box 1 protein (HMGB1) released from necrotic cells induce inflammation. The relationship between beta-cell death and HMGB1 release was investigated. The results showed that HMGB1 was released from necrotic beta-cells in a dose-dependent manner. If impaired, clearance of apoptotic beta-cells results in an increased population of necrotic beta-cells. HMGB1 release could initiate or exacerbate an inflammatory response in NOD mice.

Document type: 
Thesis
File(s): 
Senior supervisor: 
D
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

A comprehensive event-analysis of the extensive lifestyle management intervention trial

Date created: 
2007
Abstract: 

Cardiac rehabilitation programs (CRP) improve ischemic heart disease risk factors but these deteriorate after completion of the program. The purpose of this study was to determine whether the better management of risk factors achieved by the Extensive Lifestyle Management Intervention had an effect in survival after a four-year follow-up, as well as to determine predictors of survival. Methods: Data was analyzed with Kaplan-Meier curves to compare survival between the intervention and the usual care groups and the Cox regression model to determine predictors of survival. Results: Both groups had similar survival times for all end-points. Exercise capacity and lipid-lowering medications were predictors of increased survival, whereas age, illness intrusiveness and taking certain medications were predictors of decreased survival. Conclusion: Although group assignment was not a predictor of survival, risk factors that improved by the intervention were important predictors of mortality, and their management after graduation of the CRP is important.

Document type: 
Thesis
File(s): 
Senior supervisor: 
S
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

The size-weight illusion in a natural and augmented environment with congruent and incongruent size information

Date created: 
2007
Abstract: 

The size-weight illusion (SWI) occurs when the smaller of equally weighted objects is judged to feel heavier than the larger object. Experiment 1 compared the SWI generated in a natural versus augmented-reality environment while grasping and lifting three differently sized cubes of equal weight. Both environments induced the SWI for all twenty participants. Lift kinematics covariedwith cube size in both environments. Experiment 2 investigated the influence of incongruent visual size information on the SWI in an augmented environment. Physical cubes were paired with three graphical representations: a smaller, an equal-sized, and a larger cube. The SWI was influenced by both haptic and visual size information. Kinematics covariedwith physical size throughout the experiment. Results suggest that vision significantly impacts the bimodal SWI when haptic and visual size information is not redundant. Results have implications for theories of heaviness perception, multimodal interaction, and perception and action in augmented environments.

Document type: 
Thesis
File(s): 
Senior supervisor: 
C
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

Redox reactivity of vanadium toward cytochrome c_and oxygen

Author: 
Date created: 
1987
Document type: 
Thesis
File(s): 
Department: 
Theses (Dept. of Kinesiology) / Simon Fraser University
Thesis type: 
Thesis (M.Sc.)

Hypoxic responses in resting hyperthermic humans

Author: 
Date created: 
2005
Abstract: 

This thesis investigated the interaction between steady state hypoxia and passive hyperthermia on human ventilation and the influence of the PETCO2 on this interaction. On one of two days males twice breathed 12% oxygen for 20 min while either normothermic or hyperthermic with PETCO2 clamped -1 mm Hg above resting (iHVR). On the other day the same tests were performed except P&02 was uncontrolled (pHVR). Hyperthermia increased euoxic ventilation compared to normothermia (plO.OO1). During iHVR ventilation increased more during hyperthermia than normothermia (p=0.002), but not during pHVR (p=0.98). Heart rates at conclusion of pHVR compared to iHVR were greater for normothermia (p=0.05) and hyperthermia (p=0.004). Therefore during pHVR the decreasing P&02 levels blunt the ventilatory response to hypoxia more than hyperthermia augments it as seen during iHVR. Also pHVR increases cardiovascular responses to hypoxia more than iHVR. An end tidal forcing system was developed to control PETC02.

Document type: 
Thesis
File(s): 
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)