The PCNA-associated factor KIAA0101/p15(PAF) binds the potential tumor suppressor product p33ING1b

The KIAA0101/p15(PAF)/OEATC-1 protein was initially isolated in a yeast two-hybrid screen for proliferating cell nuclear antigen (PCNA) binding partners, and was shown to bind PCNA competitively with the cell cycle regulator p21(WAF). PCNA is involved in DNA replication and damage repair. Using polyclonal antisera raised against a p15(PAF) fusion protein, we have shown that in a range of mammalian tumor and non-tumor cell lines the endogenous p15(PAF) protein localises to the nucleus and the mitochondria. Under normal conditions no co-localisation with PCNA could be detected, however following exposure to UV it was possible to co-immunoprecipitate p15(PAF) and PCNA from a number of cell lines, suggesting a UV-enhanced association of the two proteins. Overexpression of p15(PAF) in mammalian cells was also found to protect cells from UV-induced cell death. Based on similarities between the behaviour of p15(PAF) and the potential tumor suppressor product p33ING1b, we have further shown that these two proteins interact in the same complex in cell cultures. This suggests that p15(PAF) forms part of a larger protein complex potentially involved in the regulation of DNA repair, apoptosis and cell cycle progression. (c) 2005 Elsevier Inc. All rights reserved.

Socio-economic, migrant and geographic differentials in coronary heart disease occurrence in New South Wales

Objective: This study examines the variation in coronary heart disease (CHD) mortality and acute myocardial infarction (AMI) by socio-economic status (SES), country of birth (COB) and geography (urban/rural) in the total population of New South Wales (Australia) in 1991-95. Method: CHD deaths and AMI are from complete enumerations of deaths and hospital admissions, respectively; and population denominators are from census information. Data are examined separately by sex, and comparisons of SES groups (based on municipalities), COB and region are analysed using Poisson regression, after adjustment for age. Results: The study identified higher risk for AMI admissions and CHD mortality in lower SES populations with significant linear trends, for both sexes, adjusted for age, region and COB. According to the population attributable fractions (PAF), 23-41% of the risk of CHD occurrence is due to SES lower than the highest quartile. The higher age-adjusted risk for CHD occurrence in rural and remote populations for both sexes, compared with urban communities, was lessened by adjustment for COB, and all but abolished when also adjusted for SES. COB analysis indicated significantly lower age-adjusted AMI admissions and CHD mortality compared with the Australian-born, Conclusions: Higher risks for CHD in rural populations compared with the capital city (Sydney) are due, in part, to lower SES, lesser migrant composition. Implications: Strategies for reducing CHD differentials should consider demographic factors and the fundamental need to reduce socio-economic inequalities, as well as targeting appropriate prevention measures.

The fraction of ischaemic heart disease and stroke attributable to smoking in the WHO Pacific and South-East Asian regions

Background: Tobacco will soon be the biggest cause of death worldwide, with the greatest burden being borne by low and middle-income countries where 8/10 smokers now live. Objective: This study aimed to quantify the direct burden of smoking for cardiovascular diseases (CVD) by calculating the population attributable fractions (PAF) for fatal ischaemic heart disease (IHD) and stroke (haemorrhagic and ischaemic) for all 38 countries in the World Health Organization Western Pacific and South East Asian regions. Design and subjects: Sex-specific prevalence of smoking was obtained from existing data. Estimates of the hazard ratio (HR) for IHD and stroke with smoking as an independent risk factor were obtained from the,600 000 adult subjects in the Asia Pacific Cohort Studies Collaboration (APCSC). HR estimates and prevalence were then used to calculate sex-specific PAF for IHD and stroke by country. Results: The prevalence of smoking in the 33 countries, for which relevant data could be obtained, ranged from 28-82% in males and from 1-65% in females. The fraction of IHD attributable to smoking ranged from 13-33% in males and from < 1-28% in females. The percentage of haemorrhagic stroke attributable to smoking ranged from 4-12% in males and from < 1-9% in females. Corresponding figures for ischaemic stroke were 11-27% in males and < 1-22% in females. Conclusions: Up to 30% of some cardiovascular fatalities can be attributed to smoking. This is likely an underestimate of the current burden of smoking on CVD, given that the smoking epidemic has developed further since many of the studies were conducted.