domain of polypharmacy, including an overview of the evidence base and definitions of each indicator. � Client focus: Clients who are prescribed multiple psychotropic medications � Project goal: Simplification of medication regimen if clinically feasible following clinical evaluation, for each client

All individuals previously infected with Epstein-Barr virus (EBV) harbor life-long a population of virus-infected B cells whose number appears to be controlled by EBVspecific, HLA-restricted (class I and class II) CTLs (CD4 andCD8) that recognize a functionally defined lymphocyte-determined membrane antigen, LYDMA (1, 2). There are two recognized types of EBV (A and B) that show sequence divergence within the reading frames encoding EBV nuclear antigens (EBNAs) 2, 3, 4, and 6 (3, 4) and differences in the molecular weight of these proteins (4, 5). Our general approach to identifyingCTL epitopes has been to isolate EBVspecific T cell clones that recognize autologous A-type transformant but fail to lyse the corresponding B-type transformant (6). The present report defines the first target epitope recognized by EBVspecific CTLs. Our approach to identifying this epitope has been to screen selected peptide sequences from the EBNA proteins using specific CTLs and the autologous B-type transformant. Materials and Methods Cell Lines. EBVtransformed cell lines (LCLs) were established either spontaneously (i.e.,

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Localized bone loss can be associated with certain inflammatory, hypermetabolic, and neoplastic diseases. The pathogenesis of osteolytic lesions in most of the latter conditions has not been elucidated. Lymphocytes have been shown to release factor(s) with osteolytic activity (1-3). One lymphokine, osteoclast activating factor (OAF), a product of T or B lymphocytes, has in part been chemically characterized (4-7). Bioassays have not been able to distinguish osteoclast-mediated bone resorption initiated by parathyroid hormone (PTH) from that caused by OAF. Both agents cause the release of calcium from bone with similar dose-dependency curves (8), both cause osteoclast activation as measured by increased cell number and size (9), and both agents activate adenylate cyclase in bone cells (10, 11). We therefore decided to look more closely at the sequence of biochemical events that occurs during lymphokine-mediated bone resorption. In particular, we examined endogenous bone synthesis and release of prostaglandins after exposure to a lymphokine preparation that probably contained OAF activity. Materials and Methods Prostaglandin Synthesis by Explanted Fetal Rat Bone Culture. The radii and ulnae from 20-d-old fetal rats were placed into culture as previously described (8). The classes of prostaglandins synthesized by the explanted bones were followed by measuring the conversion of tritiated

The epidermis is a barrier tissue that is exposed to the environment and susceptible to injury. Cooperation between epithelial cells, growth factors, chemokines, and inflammatory cells leads to rapid repair of most injuries. However, in creasing numbers of patients suffer from chro nic, nonhealing wounds (1). Although much is known about processes leading to effective tissue repair, the role of human epithelial–resident T cells in wound healing has not been examined. + T cells are found in both the epidermis and dermis of human skin (2–4). In contrast to ro dents, there is also a major resident population of epidermal + T cells (5). Other than analy sis of their presence, little is known about these human skin–resident T cell populations. The T cell compartment in mouse epidermis is exclu sively composed of + T cells, with invariant TCRs designated as dendritic epidermal T cells (DETCs) (6). These cells are critical for tumor immunosurveillance (7), skin homeostasis (8), and wound repair (9). Identification of a hu man skin T cell equivalent with specialized wound healing properties would provide crucial insight into the mechanism of effective repair of acute wounds and elucidate new targets for therapeutic intervention in the treatment of chronic wounds. In this report, we show that human epidermal + and + T cells contrib ute to the effective healing of acute wounds and are functionally defective in patients with chronic wounds, demonstrating a previously unrecognized component of human epidermal wound healing. RESULTS AND DISCUSSION V1 and TCR–bearing cells reside in normal human epidermis Before examining a role for + and + T cells in wound repair and homeostasis, we first investigated the presence of T cell populations in healthy human epidermis. We used a classical

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bronchus-associated lymphoid tissue serves as a general priming site for T cells and is maintained by dendritic cells

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Runx family transcription factors are essential for embryonic development and have key roles in hematopoiesis. They bind DNA through the conserved Runt domain and can activate or re-press transcription by cooperating with other sequence-specific transcription factors, coactiva-tors, and corepressors (Durst and Hiebert, 2004; Taniuchi and Littman, 2004). Runx1 (AML1) and Runx3 (AML2) are intimately linked to T cell fate choice and function by regulating tar-get genes that specify CD4/CD8 development in the thymus and the postthymic differentiation of Th1, Th2, and Th17 cells. Runx1 and Runx3 sequentially interact with the Cd4 silencer to block CD4 expression in double-negative and CD8 single-positive thymocytes (Taniuchi et al., 2002). Runx3 facilitates CD8 T cell lineage choice by repressing Zbtb7b, the gene encoding the CD4 lineage signature transcription factor Th-POK (Egawa and Littman, 2008; Setoguchi et al., 2008) and also plays a role in mature cyto-toxic T cells (Cruz-Guilloty et al., 2009). Runx1 is predominant in naive CD4 T cells and tran-siently down-regulated in response to activa-tion. Runx1 is reexpressed under Th2 culture conditions (Naoe et al., 2007), whereas Th1 cells express Runx3 (Djuretic et al., 2007; Naoe et al., 2007), which cooperates with T-bet to silence Il4 and activates Ifng expression (Djuretic et al., 2007). Runx1 promotes Th17 cell differ-entiation by up-regulating Rorc, the gene en-coding the Th17 signature transcription factor Ror-t, and II17 (Zhang et al., 2008). In T reg cells, Runx1 and the T reg signature transcrip-tion factor Foxp3 cooperate at the protein level to regulate downstream target genes (Ono et al., 2007), but the transcriptional regulation of T reg cell determinants by Runx proteins remains to be investigated.