The complexity of p53 stabilization and activation

A number of proteins are activated by stress stimuli but none so spectacularly or with the degree of complexity as the tumour suppressor p53 (human p53 gene or protein). Once stabilized, p53 is responsible for the transcriptional activation of a series of proteins involved in cell cycle control, apoptosis and senescence. This protein is present at low levels in resting cells but after exposure to DNA-damaging agents and other stress stimuli it is stabilized and activated by a series of post-translational modifications that free it from MDM2 (mouse double minute 2 but used interchangeably to denote human also), a ubiquination ligase that ubiquitinates it prior to proteasome degradation. The stability of p53 is also influenced by a series of other interacting proteins. In this review, we discuss the post-translational modifications to p53 in response to different stresses and the consequences of these changes.

Dramatic extension of tumor latency and correction of neurobehavioral phenotype in Atm-mutant mice with a nitroxide antioxidant

Mutations in the ATM gene (mutated in ataxia telangiectasia) in both humans and mice predispose to lymphoid tumors. A defect in this gene also causes neurodegeneration in humans and a less severe neurological phenotype in mice. There is some evidence that oxidative stress contributes to these defects, suggesting that antioxidants could alleviate the phenotype. We demonstrate here that the antioxidant 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) dramatically delays the onset of thymic lymphomas in Atm(-/-) mice which is not due to an enhancement of apoptosis by CTMIO. We also show that this compound corrects neurobehavioral deficits in these mice and reduces oxidative damage to Purkinje cells. The likely mechanism of action of CTMIO is due to a reduction in oxidative stress, which is protective against both the tumor progression and the development of neurological abnormalities. These data suggest that antioxidant therapy has considerable potential in the management of ataxia telangiectasia and possibly other neurodegenerative disorders where oxidative stress is implicated. (c) 2006 Elsevier Inc. All rights reserved.

Reflections on the centrality of power in medical sociology: an empirical test and theoretical elaboration

This paper explores the contemporary relevance of sociological theorisations centred on medical power, including the medical dominance and deprofessionalisation theses. To achieve this it examines two issues that have been tentatively linked to the relative decline of the power and autonomy of biomedicine - complementary and alternative medicine (CAM) and the Internet-informed patient. Drawing on these two different but interconnected social phenomena, this paper reflects on the potential limitations of power-based theorisations of the medical profession and its relationship to patients and other non-biomedically situated professional groups. It is argued that power-based conceptual schemas may not adequately reflect the non-linear and complex strategic adaptations that are occurring among professional groups.

An exploration of the needs and goals of the health professional and patient in a medical consultation

This Study is the first phase of a three-phase study continuing over three years. Twent)' health professionals from different disciplinary backgrounds (medical doctors, nurses, allied health professionals) and 20 patients across a range of medical condidons, education, gender, and socio-economic backgrounds, pardcipated in one-on-one semi-structured interviews. Participants described their experiences and percepdons of both effecdve and sadsfying medical consultations and dissadsf)'ing and ineffecdve ones. They also discussed their individual goals and needs in the consultation process. Results indicated that while there were some similarides in consultation goals and needs between health professionals, there were also clear differences across the different discipUnes. In addition, there were clear differences in goals and needs across the twenty padents. These findings are discussed within the framework of communicadon accommodadon theor}' (CAT) and the linguisdc model of padent pardcipadon (LMOPP) and focus on understanding the different dynamics that underpin varying health professional and padent interacdons.