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(2007)Journal ArticleRecent advances in basic and clinical science have driven epigenetics to the forefront of cancer research. Together with genetic changes, the disruption of epigenetic mechanisms is now established as a hallmark of cancer in humans. Colorectal cancer, long a classic model for the genetic basis of cancer, is now providing researchers with the opportunity to view epigenetic events in the context of neoplasia in humans. Knowledge of the heritable changes in gene expression that result from epigenetic events is of increasing relevance to clinical practice, particularly in terms of diagnostic and prognostic molecular markers, as well as novel therapeutic targets.
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(2009)Journal ArticleStudy Design : Prospective experimental Objectives : To investigate inter-rater and intra-rater reliability of electrical perceptual threshold (EPT) testing in assessing somatosensory function in healthy volunteers. Setting: Spinal Injuries Unit, Royal North Shore Hospital, Sydney, NSW, Australia Methods: Cutaneous electrical stimulation of 4 dermatomes at American Spinal Injuries Association (ASIA) sensory key points (C3, T1, L3, S2) was performed on 40 control subjects. The lowest ascending stimulus intensity at which sensation was perceived was recorded as the EPT. Mean EPT values for each dermatome, as determined by 2 testers at two time points, were examined and plotted against a normative template. Differences and associations between intra- and inter-rater measurements, and left-right measurements were investigated. EPT results for 2 people with spinal cord injuries were also examined. Results : EPT measurements from left and right sides, obtained from the two time points and two testers, were found to be strongly associated, with the exception of left and right side measurements at the S2 dermatome. No significant differences in the mean EPT for tester or time period were found. The intra- and inter-rater reliability was good for all dermatomes tested. Mean EPT measurements fell within the range of a normative template at each of the 4 dermatomes tested. Conclusion : EPT is an objective, reproducible and quantifiable method of assessing sensation in a control group. However, caution should be applied in certain dermatomes such as S2 where there was large variation between left and right side measurements. Sponsorship : New South Wales Office of Science and Medical Research
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(2013)Journal ArticleA pathological hallmark of Alzheimer’s disease (AD) is the presence of amyloid-beta peptide (Aβ) plaques in the brain. Aβ is derived from a sequential proteolysis of the transmenbrane amyloid precursor protein (APP), a process which is dependent on the distribution of lipids present in the plasma membrane. Sphingomyelin is a major membrane lipid, however its role in APP processing is unclear. Here, we assessed the expression of sphingomyelin synthase (SGMS1; the gene responsible for sphingomyelin synthesis) in human brain and found that it was significantly elevated in the hippocampus of AD brains, but not in the cerebellum. Secondly, we assessed the impact of altering SGMS activity on Aβ generation. Inhibition of SGMS activity significantly reduced the level of Aβ in a dose and time dependent manner. The decrease in Aβ level occurred without changes in APP expression or cell viability. These results when put together indicate that SGMS activity impacts on APP processing to produce Aβ and it could be a contributing factor in Aβ pathology associated with AD.
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(2008)Journal ArticleAbstract OBJECTIVE: to determine the effects of a 15-week high intensity intermittent exercise (HIIE) program on subcutaneous and trunk fat and insulin resistance of young women. DESIGN AND PROCEDURES: subjects were randomly assigned to one of three groups: HIIE (n = 15), steady state exercise (SSE; n=15), or control (CONT; n=15). HIIE and SSE groups underwent a 15-week exercise intervention. SUBJECTS: forty-five women with a mean BMI of 23.2 + 2.0 kg/m2 and age of 20.2 + 2.0 years. RESULTS: both exercise groups demonstrated a significant improvement, P < 0.05, in cardiovascular fitness. However, only the HIIE group had a significant reduction in total body mass (TBM), fat mass (FM), trunk fat, and fasting plasma insulin levels. There was significant fat loss, P < 0.05, in legs compared to arms in the HIIE group only. Lean compared to overweight women lost less fat after HIIE. Decreases in leptin concentrations were negatively correlated with increases in (r = -.57, P < 0.05) and positively correlated with decreases in TBM (r = .47; P < 0.0001). There was no significant change in adiponectin levels after training. CONCLUSIONS: HIIE three times per week for 15 weeks compared to the same frequency of SSE exercise was associated with significant reductions in total body fat, subcutaneous leg and trunk fat, and insulin resistance in young women. Keywords: intermittent sprinting, body fat, insulin
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(2007)Journal ArticleThe prevalence of obesity is increasing worldwide, and the rising number of obese children and adolescents is of particular concern. In humans, smoking is a predisposing factor for abdominal obesity, glucose intolerance and insulin resistance. Maternal smoking is associated with preterm birth and low birth weight. On the other hand, the incidence of obesity is higher in children and adults born of smoking mothers. Disorders in eating behaviour, reduced physical activity, and increased risk of hypertension and nicotine addiction have been observed in the offspring of smoking mothers. Evidence from animal and human studies suggests that intrauterine smoke exposure may alter peripheral and central mediators involved in the regulation of appetite and energy metabolism. Smoking cessation during pregnancy is desirable to improve health outcomes in offspring.
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