Gene Dosage–limiting Role of Aire in Thymic Expression, Clonal Deletion, and Organ-specific Autoimmunity

Inactivation of the autoimmune regulator (Aire) gene causes a rare recessive disorder, autoimmune polyendocrine syndrome 1 (APS1), but it is not known if Aire-dependent tolerance mechanisms are susceptible to the quantitative genetic changes thought to underlie more common autoimmune diseases. In mice with a targeted mutation, complete loss of Aire abolished expression of an insulin promoter transgene in thymic epithelium, but had no effect in pancreatic islets or the testes. Loss of one copy of Aire diminished thymic expression of the endogenous insulin gene and the transgene, resulting in a 300% increase in islet-reactive CD4 T cells escaping thymic deletion in T cell receptor transgenic mice, and dramatically increased progression to diabetes. Thymic deletion induced by antigen under control of the thyroglobulin promoter was abolished in Aire homozygotes and less efficient in heterozygotes, providing an explanation for thyroid autoimmunity in APS1. In contrast, Aire deficiency had no effect on thymic deletion to antigen controlled by a systemic H-2K promoter. The sensitivity of Aire-dependent thymic deletion to small reductions in function makes this pathway a prime candidate for more subtle autoimmune quantitative trait loci, and suggests that methods to increase Aire activity would be a potent strategy to lower the incidence of organ-specific autoimmunity

Effect Of Microtubule Disassembly On P0071 Protein Distribution In Caco-2 Cell Lines

In cancer cells, malfunctions of various signaling pathways of protein interactions lead to uncontrolled cell growth. p0071 is a protein that is a member of the p120-subfamily of armadillo proteins. It has a dual localization in both adherens junctions and in the cytoplasm of epithelial cells. While the function of p0071 in adherens junctions is known, the function of p0071 in the signaling pathways in the cytoplasm is unknown. Microtubules, proteins of the cytoskeleton, are suspected to interact with p0071 in a signaling pathway. The aim of this research is to determine the interaction between p0071 and microtubules. This was achieved by destroying the microtubule network by placing the CaCo-2 cells on ice for two hours. Immunofluorescence microscopy techniques were then performed on the treated cells for the proteins CK8-18, desmoplakin, and Cingulin as controls, and alpha tubulin and p0071 as the respective independent and dependent variables. The preliminary data indicates an accumulation of p0071 around the cell borders of some, but not all, of the treated cells, whereas the untreated cells show an even distribution of p0071 throughout. This might indicate an interaction between p0071 and microtubules, but more research is needed to confirm the results. If confirmed, the relationship will allow a better understanding of the protein interactions involved in the cancer signaling pathway

Evaluation of an Australian primary care telephone cognitive behavioural therapy pilot

A telephone-based cognitive behavioural therapy pilot project was trialled from July 2008 to June 2010, via an Australian Government-funded primary mental health care program. A web-based minimum dataset was used to examine level of uptake, sociodemographic and clinical profile of consumers, precise nature of services delivered, and consumer outcomes. Key informant interviews with 22 project officers and 10 mental health professionals elicited lessons learnt from the implementation of the pilot. Overall, 548 general practitioners referred 908 consumers, who received 6607 sessions (33% via telephone). The sessions were delivered by 180 mental health professionals. Consumers were mainly females with an average age of 37 years and had a diagnosis of depressive and/or anxiety disorders. A combination of telephone and face-to-face sessions of 1 h in duration were conducted, delivering behavioural and cognitive interventions, usually with no cost to consumers. Several implementation issues were identified by project officers and mental health professionals. Although face-to-face treatment is preferred by providers and consumers, the option of the telephone modality is valued, particularly for consumers who would not otherwise access psychological services. Evidence in the form of positive consumer outcomes supports the practice of multimodal service delivery

Assessing patient satisfaction in an Australian primary mental health care context

This paper presents the first attempt to provide a national snapshot of patient satisfaction with the Access to Allied Psychological Services (ATAPS) programme in Australia. ATAPS is funded by the Department of Health and Ageing and provides focussed psychological strategies to patients with common mental health disorders. At the time this work was done, ATAPS was managed locally by Divisions of General Practice; it is now managed by Medicare Locals. We emailed the 105 Divisions operating ATAPS inviting them to provide any survey instruments they had used to gauge patient satisfaction data, as well as any available data. Nine Divisions provided surveys and data. The content of the surveys varied considerably. Eight of the nine surveys included a question regarding overall satisfaction with the service and/or the service provider. However, there were few other commonalities between the surveys. In total, 1,142 of the 1,211 respondents who answered the question about overall satisfaction (94.3%) rated it as positive or very positive. Since this study took place, measurement of patient satisfaction has become a national requirement for all Medicare Locals providing ATAPS services. Assessment of patient satisfaction is especially relevant as ATAPS continues to strive to reach vulnerable and hard-to-reach populations. Recommendations are made to assist Medicare Locals, and other systems of primary mental health care provision, in the further collection of patient satisfaction data