Identification of human CD4+ T cell populations with distinct antitumor activity

How naturally arising human CD4+ T helper subsets affect cancer immunotherapy is unclear. We reported that human CD4+CD26high T cells elicit potent immunity against solid tumors. As CD26high T cells are often categorized as TH17 cells for their IL-17 production and high CD26 expression, we posited these populations would have similar molecular properties. Here, we reveal that CD26high T cells are epigenetically and transcriptionally distinct from TH17 cells. Of clinical importance, CD26high and TH17 cells engineered with a chimeric antigen receptor (CAR) regressed large human tumors to a greater extent than enriched TH1 or TH2 cells. Only human CD26high T cells mediated curative responses, even when redirected with a suboptimal CAR and without aid by CD8+ CAR T cells. CD26high T cells cosecreted effector cytokines, produced cytotoxic molecules, and persisted long term. Collectively, our work underscores the promise of CD4+ T cell populations to improve durability of solid tumor therapies

Anatomic Reinforced Medial Meniscal Root Reconstruction With Gracilis Autograft

Meniscal root tears, left untreated, result in accelerated progression of arthritis. Numerous techniques to repair medial meniscus posterior root tears have been presented in the literature. Direct repair of the meniscus to bone without reconstructive tissue may result in a nonanatomic and biologically weak construct with a significant number of structural repair failures. Re-creation of the ligament-like structures that fix the meniscal root to bone is critical to restoring normal knee biomechanics. We present an arthroscopic reconstructive technique using gracilis autograft with suture reinforcement for medial meniscus posterior root tears

Fitness Costs of Pesticide Resistance in Hyalella azteca under Future Climate Change Scenarios

Survival/sex ratio, reproduction, lipids, dry mass, and water quality parameters for non-resistant and pyrethroid-resistant Hyalella 42 day test and grow-out

Transnational state entrepreneurship? Assessing Singapore's Suzhou industrial park project (1994-2004)

10.1111/j.1467-8373.2007.00348.xAsia Pacific Viewpoint483287-29

Conjugation of haloalkanes by bacterial and mammalian glutathione transferases: Mono- and dihalomethanes

A primary route of metabolism of dihalomethanes occurs via glutathione (GSH) transferase-catalyzed conjugation. Mammalian theta class GSH transferases and a group of bacterial dichloromethane dehalogenases are able to catalyze the hydrolytic dehalogenation of dihalomethanes via GSH conjugation and subsequent formation of HCHO. Dihalomethanes have been shown to induce revertants in Salmonella typhimurium TA 1535 expressing theta class GSH transferases. Two mammalian theta class GSH transferases (rat GST 5-5 and human GST T1) and the bacterial dehalogenase DM11 were compared in the in vitro conjugation of CH3Cl and using in vitro assays (HCHO formation) and the S. typhimurium mutagenesis assay with the dihalomethanes CH2Cl2, CH2Br2, CH2BrCl, CH2ICl, CH2I2, and CH2ClF. GSTs 5-5 and TI had similar characteristics and exhibited first-order rather than Michaelis-Menten kinetics for HCHO formation over the range of dihalomethane concentrations tested. In contrast, the DM11 enzyme displayed typical hyperbolic Michaelis-Menten kinetics for all of the compounds tested. A similar pattern was observed for the conjugation of CH3Cl The reversion tests with S. typhimurium expressing DM11 or GST 5-5 showed a concentration-dependent increase in revertants for most of the dihalomethanes, and DM11 produced revertants at dihalomethane concentrations lower than GST 5-5. Collectively, the results indicate that rates of conversion of dihalomethanes to HCHO are not correlated with mutagenicity and that GSH conjugates are genotoxic. The results are compared with the conjugation and genotoxicity of haloethanes in the preceding paper in this issue [Wheeler, J. B., Stourman, N. V., Armstrong, R. N., and Guengerich, F. P. (2001) Chem. Res. Toxicol. 14, 1107-1117]. The halide order appears most important in the dihalomethane conjugation reactions catalyzed by GST 5-5 and less so in GST T1 and DM11, probably due to changes in the rate-limiting steps