As a result of expression of the influenza hemagglutinin (HA) in the pancreatic islets, the repertoire of HA-specific CD8+ T lymphocytes in InsHA transgenic mice (D2 mice expressing the HA transgene under control of the rat insulin promoter) is comprised of cells that are less responsive to cognate Ag than are HA-specific CD8+ T lymphocytes from conventional mice. Previous studies of tolerance induction involving TCR transgenic T lymphocytes suggested that a variety of different mechanisms can reduce avidity for Ag, including altered cell surface expression of molecules involved in Ag recognition and a deficiency in signaling through the TCR complex. To determine which, if any, of these mechanisms pertain to CD8+ T lymphocytes within a conventional repertoire, HA-specific CD8+ T lymphocytes from B10.D2 mice and B10.D2 InsHA transgenic mice were compared with respect to expression of cell surface molecules, TCR gene utilization, binding of tetrameric KdHA complexes, lytic mechanisms, and diabetogenic potential. No evidence was found for reduced expression of TCR or CD8 by InsHA-derived CTL, nor was there evidence for a defect in triggering lytic activity. However, avidity differences between CD8+ clones correlated with their ability to bind KdHA tetramers. These results argue that most of the KdHA-specific T lymphocytes in InsHA mice are not intrinsically different from KdHA-specific T lymphocytes isolated from conventional animals. They simply express TCRs that are less avid in their binding to KdHA.

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p53 is an attractive target for cancer immunotherapy because it is overexpressed in a high proportion of many different types of tumors. However, it is also expressed in normal tissues and acts as a toleragen in vivo. Previously, detailed examination of the repertoire specific for the murine p53261–269 epitope in conventional and p53-deficient mice demonstrated that because of expression of p53, the CD8+ T cells that respond to this epitope express low-affinity TCRs. It has been reported that tolerance to tumor Ags can be broken by in vivo administration of anti-CTLA-4 mAb. With the goal of overriding tolerance and achieving optimal activation of p53-specific CTL, the current study has assessed the effect of anti-CTLA-4 mAb on the p53-specific repertoire. It was found that blockade of CTLA-4 engagement at the time of antigenic stimulation induced a vigorous amplification of the CTL responses to p53 as well as proportionate expansion of the memory T cell pool. This effect was dependent on the presence of CD4+ T cell help and correlated with an enhancement of helper function. However, anti-CTLA-4 treatment did not enhance the avidity of the resultant p53-specific CTL populations and, therefore, could not reverse this important consequence of tolerance.

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Objective We have limited knowledge on ways to improve oral health-related behaviors for caregivers of minority preschoolers. Our objective was to evaluate the effectiveness of a bilingual educational flipchart. Methods We piloted a bilingual flipchart with Korean American caregivers of preschoolers (N=219) and administered pre-/post-intervention surveys. The paired t-test evaluated changes in knowledge and self-efficacy (for all caregivers and stratified by acculturation). Results There were significant improvements in knowledge on the bacterial etiology of tooth decay (P=.02), mother-to-child transmission of tooth decay (P=.03), fluoride toothpaste safety (P<.0001), and dental visit frequency (P<.0001). Caregivers' self-efficacy to keep their child's teeth healthy also improved (P<.0001). There were differences in knowledge measures based on caregivers' acculturation. Conclusions Bilingual educational materials help improve the oral health-related knowledge and self-efficacy of Korean American caregivers of preschoolers. Larger confirmatory studies are needed and future work should evaluate clinical outcomes associated with improved knowledge and self-efficacy.

BackgroundSystematic reviews provide evidence for clinical questions, however the literature suggests they are not used regularly by physicians for decision-making. A shortened systematic review format is proposed as one possible solution to address barriers, such as lack of time, experienced by busy clinicians. The purpose of this paper is to describe the development process of two shortened formats for a systematic review intended for use by primary care physicians as an information tool for clinical decision-making.MethodsWe developed prototypes for two formats (case-based and evidence-expertise) that represent a summary of a full-length systematic review before seeking input from end-users. The process was composed of the following four phases: 1) selection of a systematic review and creation of initial prototypes that represent a shortened version of the systematic review; 2) a mapping exercise to identify obstacles described by clinicians in using clinical evidence in decision-making; 3) a heuristic evaluation (a usability inspection method); and 4) a review of the clinical content in the prototypes.ResultsAfter the initial prototypes were created (Phase 1), the mapping exercise (Phase 2) identified components that prompted modifications. Similarly, the heuristic evaluation and the clinical content review (Phase 3 and Phase 4) uncovered necessary changes. Revisions were made to the prototypes based on the results.ConclusionsDocumentation of the processes for developing products or tools provides essential information about how they are tailored for the intended user. One step has been described that we hope will increase usability and uptake of these documents to end-users.

T cell recognition of self-major histocompatibility complex-peptide complexes dictates the composition of the T cell receptor repertoire. Research projects in our laboratory deal with the mechanisms that regulate the composition of the repertoire specific for self-antigens and the defects that can result in autoimmunity. Two different types of disease models are under investigation: juvenile (type I) diabetes and cancer. Both of these diseases are impacted by the presence of anti-self CD8 cells, yet in opposite ways. By understanding the mechanisms of peripheral tolerance and the reasons they fail in autoimmunity, we may learn how to prevent undesirable autoimmunity and how to encourage an autoimmune response when it is needed to eliminate tumor cells.

Falls in hospital are common and up to 70% result in injury, leading to increased length of stay and accounting for 10% of patient safety-related deaths. Yet, high-quality evidence guiding best practice is lacking. Fall prevention strategies have worked in some trials but not in others. Differences in study setting (acute, subacute, rehabilitation) and sampling of patients (cognitively intact or impaired) may explain the difference in results. This article discusses these important issues and describes the strategies to prevent falls in the acute hospital setting we have studied, which engage the cognitively impaired who are more likely to fall. We have used video clips rather than verbal instruction to educate patients, and are optimistic that this approach may work. We have also explored the option of co-locating high fall risk patients in a close observation room for supervision, with promising results. Further studies, using larger sample sizes are required to confirm our findings.