University of Pittsburgh

About: University of Pittsburgh is a education organization based out in Pittsburgh, Pennsylvania, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 87042 authors who have published 201012 publications receiving 9656783 citations. The organization is also known as: Pitt & Western University of Pennsylvania.

Tolerogenic dendritic cells and the quest for transplant tolerance.

Abstract: In recent years, there has been a shift from the perception of dendritic cells (DCs) solely as inducers of immune reactivity to the view that these cells are crucial regulators of immunity, which includes their ability to induce and maintain tolerance. Advances in our understanding of the phenotypical and functional plasticity of DCs, and in our ability to manipulate their development and maturation in vitro and in vivo, has provided a basis for the therapeutic harnessing of their inherent tolerogenicity. In this Review, we integrate the available information on the role of DCs in the induction of tolerance, with a focus on transplantation.

Genome-wide Association Studies Prospects and Challenges for Oral Health

Abstract: The genomic era of biomedical research has given rise to the genome-wide association study (GWAS) approach, which attempts to discover novel genes affecting an outcome by testing a large number (i.e., hundreds of thousands to millions) of genetic variants for association. This article discusses the issues surrounding the GWAS approach with emphasis on the prospects and challenges relevant to the oral health research community.

Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand

Abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to induce apoptosis in various tumor cells but not in nontransformed, normal cells. Preclinical studies in mice and nonhuman primates have shown that administration of TRAIL can induce apoptosis in human tumors, but that no cytotoxicity to normal organs or tissues is found. The susceptibility of tumor cells to TRAIL and an apparent lack of activity in normal cells has lead to a proposal to use TRAIL in cancer therapy. Here, we assessed the sensitivity of hepatocytes from rat, mouse, rhesus monkey and human livers to TRAIL-induced apoptosis. TRAIL induced apoptosis in normal human hepatocytes in culture but not in hepatocytes isolated from the other species. Human hepatocytes showed characteristic features of apoptosis, including cytoplasmic shrinkage, the activation of caspases and DNA fragmentation. Apoptosis and cell death in human hepatocytes was massive and rapid, occurring in more than 60% of the cells exposed to TRAIL within 10 hours. These results indicate that there are species differences in sensitivity to TRAIL, and that substantial liver toxicity might result if TRAIL were used in human cancer therapy.

Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence

Abstract: The yeast Sir2 protein mediates chromatin silencing through an intrinsic NAD-dependent histone deacetylase activity. Sir2 is a conserved protein and was recently shown to regulate lifespan extension both in budding yeast and worms. Here, we show that SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells upon overexpression of either PML or oncogenic Ras (Ha-rasV12). SIRT1 binds and deacetylates p53, a component of PML nuclear bodies, and it can repress p53-mediated transactivation. Moreover, we show that SIRT1 and p53 co-localize in nuclear bodies upon PML upregulation. When overexpressed in primary mouse embryo fibroblasts (MEFs), SIRT1 antagonizes PML-induced acetylation of p53 and rescues PML-mediated premature cellular senescence. Taken together, our data establish the SIRT1 deacetylase as a novel negative regulator of p53 function capable of modulating cellular senescence.

The KEAP1-NRF2 System: a Thiol-Based Sensor-Effector Apparatus for Maintaining Redox Homeostasis

Abstract: The Kelch-like ECH-associated protein 1-NF-E2-related factor 2 (KEAP1-NRF2) system forms the major node of cellular and organismal defense against oxidative and electrophilic stresses of both exoge...