Centre for behavioural research in cancer

The Centre for Behavioural Research in Cancer (CBRC) is one of two research centres housed at the Anti-Cancer Council of Victoria, the other being an epidemiological research centre. The CBRC's main focus for research is in smoking behaviour. A feature of the Centre is its close organisational and professional links with Victoria's large publicly funded smoking prevention programme. This provides opportunities to conduct programme-related research, to influence the nature of tobacco reduction interventions and to evaluate outcomes.     

Smokers of the future

Teenagers continue to be initiated into smoking, especially young women. A predictor of smoking is the existence ofstressors in their life. The major components of smoking motivation have been found to be similar in young smokers to those found in older smokers, except for the appearance of a group who are resisting the pressures against smoking. There is no evidence that the smokers of the future will be more extreme personality types than the smokers of 10 or more years ago. Changes in demographic characteristics of smokers in the United Kingdom and the United States in favour of relatively more women and more smokers from the poorer socio-economic groups requires investigation into whether this is attributable to different coping requirements in these groups.     

An Epidemic Model with a Density-Dependent Death Rate

This paper deals with a mathematical model for a disease wherethe death rate depends on the number of people in the population.This sort of model would be suitable for diseases in developingcountries or for diseases amongst animal and insect populations.We also assume that the population under consideration is regulatedby the disease so that there is a mortality induced by the disease.We use a compartmental model and perform an equilibrium andstability analysis to find that there is a threshold condition.If the threshold is exceeded, then there is a unique equilibriumwith disease present which is locally stable to small perturbations.We conclude by looking at several specific models and seeinghow the results relate to previous work.     

The design,synthesis and activity of pentapeptide pp60c-src inhibitors containing L-phosphotyrosine mimics

Efficient syntheses of 4-(R,S-hydroxyphosphonomethyl)-l -phenylalanine and 4-carboxy-l -phenylalanine within the context of the pentapeptide Ac-Ile-X-Gly-Glu-Phe-NH₂ (wherein X = the unnatural amino acid) illustrate the use of a divergent synthetic strategy from an advanced common peptide intermediate to more readily access peptide-based tyrosine kinase inhibitors. The key intermediate, Ac-Ile-Phe(4-formyl)-Gly-Glu(O-tBu)-Phe-NH₂, was synthesized by a facile palladium-catalyzed carbonylation of Ac-Ile-Phe(4-iodo)-Gly-Glu(O-tBu)-Phe-NH₂. Oxidation of Ac-Ile-Phe(4-formyl)-Gly-Glu(O-tBu)-Phe-NH₂ with tetrabutylammonium permanganate or addition of di-t-butylphosphite, both followed by trifluoroacetic acid deprotection, gave the target pentapeptide inhibitors wherein X = 4-carboxy-l -phenylalanine or 4-(R,S-hydroxyphosphonomethyl)-l -phenylalanine, respectively. These two peptides gave somewhat more potent inhibition of the tyrosine kinase pp60^c-src than the corresponding pentapeptide wherein X =l -phenylalanine, demonstrating that appended functionalities at the 4-position are accepted and can enhance binding through added interactions within the catalytic region of the active site.     

CASE REPORT: An inherited APC mutation in the first reported Australian case of Turcot's syndrome

The objective of this study was to determine the inherited gene mutation responsible for the first reported Australian case of Turcot's syndrome. DNA was extracted from the archival tissue blocks obtained at the time of the patient's original surgery and from fresh blood samples obtained from selected family members. These were analysed for mutations of the familial adenomatous polyposis gene ( APC ). Analysis of DNA from the archival blocks and from each of the affected family members revealed an inherited 5 base pair deletion at codon 1061 of APC . In this case, the central nervous system tumour represents an extracolonic manifestation of familial adenomatous polyposis. The underlying inherited mutation of APC has been identified. In some cases of Turcot's syndrome, other genes appear to be involved. Recent literature examining the molecular basis of Turcot's syndrome is reviewed.     

Percutaneous Removal of Infected Permanent Pacemaker Leads Using a Simple Coaxial Dilating System

A simple traction-countertraction technique using common and readily available materials was successfully used to remove infected pacemaker leads from two patients. The specific methodology is presented. Although somewhat technically demanding, this approach appears safe and cost-effective. This method provides another way to remove pacemaker leads without resorting to thoracotomy.     

ETHANOL AND DIET-INDUCED ALTERATIONS IN KUPFFER CELL FUNCTION

The effects of 6 weeks of alcohol feeding on phagocytic, metabolicand secretory functions as well as gene expression of hepaticKupffer cells were evaluated in vitro using cultured Kupffercells isolated from male Sprague-Dawley rats. The rats werefed either Teklad pelleted rat chow or the 1982 Lieber-DeCarliliquid diet containing 6% ethanol (36% calories) or the sameliquid diet with maltose-dextrin isocalorically substitutedfor the alcohol. Weight gain was greatest in the chow-fed animalsand least in those receiving ethanol. The alcohol-containingdiet stimulated Kupffer cell phagocytosis, mitochondrial reductionof Mil, secretion of tumor necrosis factor (TNF) and expressionof TNF mRNA. However, each of these cell functions was alsoenhanced by the control Lieber-DeCarli liquid diet alone andthe stimulating effect of the control diet often exceeded thatinduced by ethanol. The results suggest that early in chronicalcohol consumption, the immune system may be stimulated byethanol, and that during studies of ethanol-induced changesin immune system function, close attention must be given topotentially confounding effects of the diet.     

Transepicardial Defibrillation Dose Response: Current Versus Energy

In pentobarbital-anesthetized dogs, we compared the relative efficacy of current versus energy in applying the dose response method in transcardiac defibrillation. Damped sinusoidal shocks via epicardial patches were administered by a custom defibrillator permitting precise current delivery. Following the establishment of an initial estimated defibrillation threshold for energy and current, the dose response method was performed with regard to either energy defibrillation threshold (group E, n = 8) or current defibrillation threshold (group C, n = 8). Two sequential sets (I, II) of shocks (21 shocks each) were delivered in random order at each of seven doses: 0.55, 0.70, 0.85, 1.00, 1.15, 1.30, and 1.45 × defibrillation threshold. Data were subjected to nonlinear logistic regression analysis. There were no significant differences between sets I and II in either groups E or C for resistance or for raw and normalized values associated with 50% and 80% success expressed as energy, current, or voltage. Correlation coefficients (r) associated with nonlinear logistic regression analysis were significantly different for normalized current and energy for group E (0.70 ± 11 and 0.71 ± 12) compared to group C (0.86 ± 0.60 and 0.88 ± O.0.6). The difference. however, could be explained by a significantly narrower range of normalized current values tested in group E (0.79 to 1.31) versus group C (0.54 to 1.46). Thus, when resistance does not change, transcardiac current offers limited advantage over energy when applying a dose response method. The efficacy of nonlinear logistic regression analysis depends upon an adequate dose range.