Association of stress proteins with autoantigens: a possible mechanism for triggering autoimmunity?

Patterns of autoantibody production are diagnostic of many autoimmune disorders; the recent observation of additional autospecificities towards stress-induced proteins may also provide insight into the mechanisms by which such responses arise. Grp78 (also known as BiP) is a target of autoaggressive B and T cell responses in our murine model of anti-Ro (SS-A) autoimmunity and also in rheumatoid arthritis. In this report we demonstrate reciprocal intermolecular spreading occurs between Ro52 and Grp78 in immunized mice, reflecting physiological association of these molecules in vivo. Moreover, we provide direct biochemical evidence that Grp78 associates with the clinically relevant autoantigen, Ro52 (SS-A). Due to the discrete compartmentalization of Ro52 (nucleocytoplasmic) and Grp78 (endoplasmic reticulum; ER) we propose that association of these molecules occurs either in apoptotic cells, where they have been demonstrated indirectly to co-localize in discrete apoptotic bodies, or in B cells themselves where both Ro52 and Grp78 are known to bind to immunoglobulin heavy chains. Tagging of molecules by association with Grp78 may facilitate receptor mediated phagocytotsis of the complex; we show evidence that exogenous Grp78 can associate with cell surface receptors on a subpopulation of murine splenocytes. Given the likelihood that Grp78 will associate with viral glycoproteins in the ER it is possible that it may become a bystander target of the spreading antiviral immune response. Thus, we propose a model whereby immunity elicited towards Grp78 leads to the selection of responses towards the Ro polypeptides and the subsequent cascade of responses observed in human disease.     

Ageing with long-standing hearing impairment and deafness

Until recently, ageing with a long-standing disability had not been a major consideration for governments around the world. Policy and planning for this substantial subgroup had not kept abreast with developments in regard to the growing numbers of older people in general. Consultations held in Australia provided information and recommendations for use by governments and service agencies. The focus was on the viewpoints of consumers. This article reports results for people with long-standing deafness and hearing impairment. It is believed that disadvantages throughout life act to restrict freedom of choice and well-being in old age. Important factors perceived to underlie disadvantage include lifelong restricted access to the opportunities afforded by education and employment and their concomitant effects on the ability to develop the skills, attitudes and knowledge necessary for independence in old age; attitudes of others (including service providers); and the complexity and inflexibility of service systems. However, there are positive aspects. Comparison with published reports about people who acquired hearing loss as a result of the ageing process suggests that people with long-standing disability have learned to live with their situation. In contrast, people whose loss was associated with ageing often report emotional issues and isolation.     

Validation of the Reactions to Ageing Questionnaire: assessing similarities across several countries

With the increasing numbers of older adults, factors impacting the effectiveness of provision of health care must be addressed. The literature suggests attitudes, particularly those of nurses, impact health service provision. This article reports the outcome of a multicountry validation study of the Reactions to Ageing Questionnaire (RAQ). The RAQ measures attitudes toward personal aging and has been used in Australia for 5 years. This study was designed to determine whether the psychometric characteristics and norms of the RAQ identified for Australian nurses also apply to nursing samples in Sweden and the United Kingdom. Findings indicate the internal structure of the RAQ extends outside Australia, with similar factors appearing across the three countries. Ranges and standard deviations indicate the instrument is able to discriminate between respondents within each country. Cronbach's alpha coefficients were consistent across countries and fell in the moderately high range. The findings indicate the RAQ has many potential applications in attitude assessment and in providing direction for training designed to address attitudinal factors that may impact the effectiveness of nursing practice for older adults.     

Older parent caregivers' engagement with the service system

Older parents of adults with intellectual disability are reported to be frequently isolated from the services designed to support their caregiving. The interaction between older parent caregivers' biographies and their involvement with the service system was examined. Parental status was predicted to be an explanatory mechanism for understanding the differential nature of their engagement with services. Analysis of interviews with 64 such caregivers of adults with intellectual disability revealed that their perceptions of their parental status were derived from a complex interaction of their values and beliefs, actions in relation to their adult child, constraints as well as resources available to them, and their relationships with service agencies. Implications for service delivery and directions for research are discussed.     

Prognostic assessment of gastrointestinal stromal tumor

The term "gastrointestinal stromal tumor" (GIST) has been applied to a collection of distinctive mesenchymal tumors occurring within the human gastrointestinal tract. As new drug therapy becomes available, data regarding the natural history of these unusual tumors are necessary to provide selection factors for treatment. Ninety-eight patients had light microscopy compatible with GIST at a single institution from 1989 to 2000. After immunostaining with c-kit and histopathologic review, 69 were judged to be GIST. All prognostic indicators were determined for gastric GIST, intestinal GIST, and all locations combined. The location of the GIST did not have a significant impact on survival. Clinically, tumor size, peritoneal cancer index, and completeness of cytoreduction had a significant impact on prognosis for GIST at all locations. Pathologically, cytologic atypia, necrosis, invasion and number of mitoses were significant prognostic indicators for GIST. Criteria to separate three pathologic groups of GIST according to the tumor size and the mitotic count were useful to evaluate the tumor behavior; in the borderline pathologic group invasion and cytologic atypia were statistically significant prognostic criteria. The cell phenotypes, as determined by immunostains, correlated with the prognosis of gastric GIST but not intestinal GIST. A correlation between the immunostain Ki-67 but not CD-34 or desmin and the prognosis was observed. It is possible to select clinical and pathologic parameters of GIST that impact on prognosis. Invasion and necrosis help to determine the prognosis with borderline tumors. The immunostain Ki-67 correlated with the prognosis and may be helpful to assess prognosis when dealing with small biopsy specimens.     

Fostering nursing research among nurse clinicians in an Australian area health service

BACKGROUND: The Nursing Research Centre for Adaptation in Health and Illness (NRCAHI) is a collaborative effort of the University of Sydney and Central Sydney Area Health Service (CSAHS) in Sydney, Australia. This article reports findings of a research needs-analysis of clinical nursing staff in CSAHS that was conducted to provide research training. METHOD: A questionnaire was administered to a random sample of nurses working in CSAHS. The questionnaire gathered information about employment and demographic information, interest in research participation, current and future levels of research skills, and areas where skill and knowledge enhancement is desired. RESULTS: Overall, nurses expressed low levels of perceived confidence, knowledge, and research skills. Results were used as the basis for developing a range of strategies designed to enhance research confidence and participation. These strategies were sufficiently flexible to cater for the needs of nurses with varying levels of research experience. CONCLUSION: Strategies implemented by the NRCAHI in its first 4 years of operation have produced positive outcomes in terms of increased research participation.     

A spatial national health facility database for public health sector planning in Kenya in 2008

Background  

Efforts to tackle the enormous burden of ill-health in low-income countries are hampered by weak health information infrastructures that do not support appropriate planning and resource allocation. For health information systems to function well, a reliable inventory of health service providers is critical. The spatial referencing of service providers to allow their representation in a geographic information system is vital if the full planning potential of such data is to be realized.     

Empirical modelling of government health service use by children with fevers in Kenya

An understanding of spatial patterns of health facility use allows a more informed approach to the modelling of catchment populations. In the absence of patient use data, an intuitive and commonly used approach to the delineation of facility catchment areas is Thiessen polygons. This study presents a series of methods by which the validity of these assumptions can be tested directly and hence the suitability of a Thiessen polygon catchment model explicitly assessed. These methods are applied to paediatric out-patient origin data from a sample of 81 government health facilities in four districts of Kenya. A geographical information system was used to predict the location of the catchment boundary along a transect between each pair of neighbouring facilities based on patient choice patterns. The mean location of boundaries between facilities of different type was found to be significantly displaced from the Thiessen boundary towards the lower-order facility. The affect of distance on within-catchment utilization rate was assessed by using exclusion buffers to remove the effect of neighbouring facilities. Utilization rate was found to exhibit a slight but steady decrease with distance up to 6 km from a facility. The accuracy of the future modelling of unsampled facility catchments can be increased by the incorporation of these trends.