Herpesvirus-specific CD8 T cell immunity in old age: Cytomegalovirus impairs the response to a coresident EBV infection

Aging in humans is associated with increased infections and the reduced proliferative capacity of T cells, part of the more global phenomenon termed immune senescence. The etiology of immune senescence is unknown but the accumulation of virus-specific memory T cells may be a contributory factor. We have examined CD8 T cell responses to two persistent herpesvirus infections, CMV and EBV, and to a recurrent virus infection, influenza, in different age cohorts of healthy donors using HLA-peptide tetramers and intracellular cytokine detection. Of these, CMV appears to be the most immunogenic, with the CD8 T cell response representing over 10% of the CD8 pool in many elderly donors. Interestingly, the effect of age upon EBV-specific responses depends upon donor CMV sero-status. In CMV seropositive donors, the magnitude of the EBV-specific immune response is stable with age, but in CMV seronegative donors, the response to EBV increases significantly with age. By contrast, the influenza-specific CD8 T cell immune response decreases with age, independent of CMV status. The functional activity of the herpesvirus-specific immune response decreases in elderly donors, although the characteristic phenotypes of CMV- and EBV-specific memory populations are retained. This demonstrates that aging is associated with a marked accumulation of CMV-specific CD8 T cells together with a decrease in immediate effector function. Moreover, infection with CMV can reduce prevailing levels of immunity to EBV, another persistent virus. These results suggest that carriage of CMV may be detrimental to the immunocompetent host by suppressing heterologous virus-specific immunity during aging.

Mutation in mitochondrial DNA as a cause of presbyacusis

Much of the hearing loss that occurs in old age is likely to be due to the long-term deterioration of the mitochondria in the different structures of the cochlea. The current review surveys some of the basic information on mitochondria and mitochondrial DNA, as a background to their possible involvement in presbyacusis. It is likely that oxygen radicals damage mitochondrial DNA and other components of the mitochondria, such as their proteins and lipids. This further compromises both oxidative phosphorylation and the repair processes in mitochondria, setting up a vicious cycle of degradation. Evidence is presented from inherited point mutations on the possibly most critical sites for mutations in mitochondrial DNA associated with hearing loss. It is suggested that random sorting and clonal expansion of mutations both maintain the integrity of the pool of mitochondrial DNA molecules and give rise to the apoptosis that leads to loss of vulnerable cells, and hence to deafness. It is moreover suggested that apoptosis of the vulnerable cells of the inner ear may to some extent be preventable, or at least delayed. Copyright (C) 2004 S. Karger AG, Basel.

Graphic satire and public life in the age of terror

This paper investigates media representations of international insecurity through a selection of newspaper cartoons from some of the major daily Australian broadsheets. Since 2001, cartoonists such as Bruce Petty, John Spooner and Bill Leak (in The Age and The Australian) have provided an ongoing and vehement critique of the Australian government’s policies of ‘border protection’, the ‘war on terror’ and the words of mass distraction associated with Australia joining the war in Iraq. Cartoonists are often said to represent the ‘citizen’s perspective’ of public life through their graphic satire on the editorial pages of our daily newspapers. Increasingly, they can also be seen to be fulfilling the role of public intellectuals, defined by Richard A. Posner as ‘someone whose place it is publicly to raise embarrassing questions, to confront orthodoxy and dogma, to be someone who cannot easily be co-opted by governments and corporations’. Cartoonists enjoy an independence and freedom from censorship that is rarely extended to their journalistic colleagues in the print media and it is this independence that is the vital component in their being categorised as public intellectuals. Their role is to ‘question over and over again what is postulated as self-evident, to disturb people’s mental habits, to dissipate what is familiar and accepted, to re-examine rules and institutions’ (Posner, 2003: 31). With this useful — if generalised — definition in mind, the paper considers how cartoonists have contributed to debates concerning international insecurity in public life since 2001.

Renal and hepatic accumulation of cadmium and lead in the expression of CYP4F2 and CYP2E1

The present study examined accumulation of the metal toxins cadmium (Cd) and lead (Pb) in relation to the abundance of cytochrome P450 4F2 (CYP4F2), CYP2E1 and concentrations of zinc and copper in liver and kidney samples using immunoblotting coupled with metal analysis. The post mortem liver and kidney cortex samples were from 23 males and 8 females aged 3-89 years. All were Caucasians who had not been exposed to metals in the workplace. Average kidney cortex Cd load of 17.4 mu g/g w.w. was 17 times greater than average liver Cd load (1.1 mu g/g w.w.). In contrast, average kidney cortex Ph load of 0.09 mu g/g w.w. was two times lower than liver Pb load of 0.19 mu g/g w.w. Average Zn and Cu concentrations in the kidney cortex samples were 67% and 33% lower than those in the liver. Liver and kidney Cd loads, but not liver or kidney Ph loads, correlated positively with donors' age. After controlling for liver Cd load, an inverse correlation was seen between Zn and age (partial r = -0.39, P = 0.02), suggesting reduction in liver Zn levels in old age. Liver CYP2E1 protein abundance correlated with age-adjusted Cd load (partial r = 0.37, P = 0.02) whereas kidney CYP4172 protein abundance showed a positive correlation with age-adjusted Cd loads (partial r = 0.40, P = 0.02). These findings suggest that Cd may be an inducer of renal CYP4172 and hepatic CYP2E1 and that increased renal CYP4172 expression may implicate in Cd-linked renal tubular dysfunction and high blood pressure, involving CYP4F2-dependent arachidonic acid metabolism. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

A comparison of the association between socioeconomic position and cardiovascular disease risk factors in three age cohorts of Australian women: findings from the Australian Longitudinal Study on Women's Health

Objectives To assess the associations between three measurements of socioeconomic position (SEP) - education, occupation and ability to cope on available income - and cardiovascular risk factors in three age cohorts of Australian women. Methods Cross-sectional analysis of three cohorts of Australian women aged 18-23, 45-50 and 70-75 years. Results In general, for all exposures and in all three cohorts, the odds of each adverse risk factor (smoking, obesity and physical inactivity) were lower in the most advantaged compared with the least advantaged. Within each of the three cohorts, the effects of each measurement of SEP on the outcomes were similar. There were, however, some notable between-cohort differences. The most marked differences were those with smoking. For women aged 70-75 (older), those with the highest educational attainment were more likely to have ever smoked than those with the lowest level of attainment. However, for the other two cohorts, this association was reversed, with a stronger association between low levels of education and ever smoking among those aged 18-23 (younger) than those aged 45-50 (mid-age). Similarly, for older women, those in the most skilled occupational classes were most likely to have ever smoked, with opposite findings for mid-age women. Education was also differently associated with physical inactivity across the three cohorts. Older women who were most educated were least likely to be physically inactive, whereas among the younger and mid-age cohorts there was little or no effect of education on physical inactivity. Conclusion These findings demonstrate the dynamic nature of the association between SEP and some health outcomes. Our findings do not appear to confirm previous suggestions that prestige-based measurements of SEP are more strongly associated with health-related behaviours than measurements that reflect material and psychosocial resources.

A simple lifestyle score predicts survival in healthy elderly men

Background. Although improvements in life expectancy have been attributed in part to the adoption or a more prudent lifestyle, few studies have examined the association of lifestyle with survival, using several lifestyle factors simultaneously, in a healthy elderly population. Methods. We investigated the association of health related behaviors with mortality in 7989 men aged 65 to 83 years participating in a population-based trial in Perth, Western Australia, by calculating a lifestyle score as a simple tally of flow many or eight prudent behaviors each individual followed. Results. Invitations to screening produced a corrected response of 70.5%. Out of a possible score of 8.46% of men had a score of less than 5. Within 5 years, a total of 703 men (9%) had died from any cause. The hazard ratio in men with a low lifestyle score was 1.3 [95% confidence interval (CI): 1.1-1.5] compared with men with a score of 5 or more. Conclusions. Lifestyle remains an important predictor of mortality even in old age. Survival in older men without a history of cardiovascular disease can potentially be enhanced by promoting a healthy lifestyle. © 2004 Elsevier Inc, All rights reserved.

Never-married childless women in Australia: Health and social circumstances in older age

A growing proportion of women reach older age without having married or having children. Assumptions that these older women are lonely, impoverished, and high users of social and health services are based on little evidence. This paper uses data from the Older cohort of the Australian Longitudinal Study on Women's Health to describe self-reported demographics, physical and emotional health, and use of services among 10,108 women aged 73-78, of whom 2.7% are never-married and childless. The most striking characteristic of this group is their high levels of education, which are associated with fewer reported financial difficulties and higher rates of private health insurance. There are few differences in self-reported physical or emotional health or use of health services between these and other groups of older women. Compared with older married women with children, they make higher use of formal services such as home maintenance and meal services, and are also more likely to provide volunteer services and belong to social groups. Overall, there is no evidence to suggest that these women are a problem group. Rather, it seems that their life experiences and opportunities prepare them for a successful and productive older age. (c) 2005 Elsevier Ltd. All rights reserved.

Treatment of falciparum malaria in the age of drug-resistance

The growing problem of drug resistance has greatly complicated the treatment for falciparum malaria. Whereaschloroquine and sulfadoxine/ pyrimethamine could once cure most infections, this is no longer true and requiresexamination of alternative regimens. Not all treatment failures are drug resistant and other issues such asexpired antimalarials and patient compliance need to be considered. Continuation of a failing treatment policyafter drug resistance is established suppresses infections rather than curing them, leading to increasedtransmission of malaria, promotion of epidemics and loss of public confidence in malaria control programs.Antifolate drug resistance (i.e. pyrimethamine) means that new combinations are urgently needed particularlybecause addition of a single drug to an already failing regimen is rarely effective for very long. Atovaquone/proguanil and mefloquine have been used against multiple drug resistant falciparum malaria with resistance toeach having been documented soon after drug introduction. Drug combinations delay further transmission ofresistant parasites by increasing cure rates and inhibiting formation of gametocytes. Most currentlyrecommended drug combinations for falciparum malaria are variants of artemisinin combination therapy wherea rapidly acting artemisinin compound is combined with a longer half-life drug of a different class. Artemisininsused include dihydroartemisinin, artesunate, artemether and companion drugs include mefloquine, amodiaquine,sulfadoxine/ pyrimethamine, lumefantrine, piperaquine, pyronaridine, chlorproguanil/dapsone. The standard ofcare must be to cure malaria by killing the last parasite. Combination antimalarial treatment is vital not only tothe successful treatment of individual patients but also for public health control of malaria.

Social communication in older age: Lessons from people with aphasia

Lessons on social communication in older age are drawn from the stories and qualitative case reports of three older people who have aphasia following stroke. Descriptive accounts of participant responses to qualitative interviews and stimulated recall of natural conversations, together with information from a social network diary, provide evidence of aspects of social communication relevant to the older person with aphasia. The perspectives of individuals and common themes relating to social communication with family and friends, the experience of aphasia, and living with aphasia in older age are presented. The prominence of conversations and the role of storytelling and of humor within the daily social communication of older people are illuminated. Key words: aphasia, older people, social communication

Employment services in an age of e-government

The increasing use of information and communications technologies among government departments and non-government agencies has fundamentally changed the implementation of employment services policy in Australia. The administrative arrangements for governing unemployment and unemployed people are now constituted by a complex contractual interplay between government departments as ‘purchasers’ and a range of small and large private organizations as ‘providers’. Assessing, tracking and monitoring the activities of unemployed people through the various parts of the employment services system has been made possible by developments in information technology and tailored computer programs. Consequently, the discretionary capacity that is traditionally associated with ‘street-level bureaucracy’ has been partly transformed into more prescriptive forms of ‘screen-level bureaucracy’. The knowledge embedded in these new computer-based technologies is considered superior because it is based on ‘objective calculations’, rather than subjective assessments of individual employees. The relationship between the sociopolitical context of unemployment policy and emerging forms of e-government is explored using illustrative findings from a qualitative pilot study undertaken in two Australian sites. The findings suggest that some of the new technologies in the employment services system are welcomed, while other applications are experienced as contradictory to the aims of delivering a personalized and respectful service.