Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested a surrogate selection approach utilizing mutation at a reporter gene [hypoxanthine-guanine phosphoribosyltransferase (hprt)] as a probe for in vivo cell division, for detection of clonal T cell expansion in human T lymphotropic (HTLV-1) carriers. Peripheral blood samples from HTLV-1-infected individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) were tested to determine the hprt mutant frequency (Mf). Wild-type and hprt mutant T cell clones were isolated, and clonal identity determined by multiplex PCR and DNA sequencing of T cell receptor (TCR) variable region beta-chain (TCR BV) and third complementarity determining regions (CDR3). Seven samples from HAM/TSP patients were tested, and Mfs were within the normal range for adults (mean 11.3 x 10(-6), max 22.4 x 10(-6), min 5.6 x 10(-6)). The frequency of HTLV-1 infection in wild-type and hprt mutant T cells from HAM/TSP patients was determined to identify enrichment in the mutant fraction of cells. This analysis was performed on 196 isolates from 6 individuals with HAM/TSP. In each case, there is enrichment for virally infected cells in the hprt mutant fraction of isolates. Ten mutant and eight wild-type isolates from sample LS42A (Mf 8.4 x 10(-6)) were tested for clonality by TCR BV PCR and sequencing. Of the 10 hprt mutants, there were two in vivo-expanded clones (four isolates with two identical TCRs, or 80% unique TCR sequences). These studies may provide new insights into the precise mechanism of HTLV-1 leukemogenesis, and aid in the study of mutator phenotypes generated by a combination of Tax-mediated in vivo expansion and mutagenesis.
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PMID:Hypoxanthine-guanine phosphoribosyltransferase reporter gene mutation for analysis of in vivo clonal amplification in patients with HTLV type 1-associated Myelopathy/Tropical spastic paraparesis. 1108 Aug 21

Preclinical studies represent an important step towards a deep understanding of the biological response to ionizing radiations. The effectiveness of proton therapy is higher than photons and, for clinical purposes, a fixed value of 1.1 is used for the relative biological effectiveness (RBE) of protons considered 1.1. Recent in vitro studies have reported that the RBE along the spread-out Bragg peak (SOBP) is not constant and, in particular, the RBE value increases on the distal part of SOBP. The present work has been carried-out in the perspective of a preclinical hadrontherapy facility at LNS-INFN and was focused on the experimental preparation of an in vivo study concerning the RBE variation along the SOBP. The main purpose of this work was to determine, using GEANT4-based Monte Carlo simulations, the best configuration for small animal treatments. The developed GEANT4 application simulates the proton-therapy beam line of LNS-INFN (CATANA facility) and allows to import the DICOM-CT images as targets. The RBE will be evaluated using a deterministic radiation damage like myelopathy as end-point. In fact, the dose at which the 50% of animals will show the myelopathy is supposed to be LET-dependent. In this work, we studied different treatment configurations in order to choose the best two that maximize the LET difference reducing as much as possible the dose released to healthy tissue. The results will be useful to plan hadrontherapy treatments for preclinical in vivo studies and, in particular, for the future in vivo RBE studies.
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PMID:Monte Carlo GEANT4-based application for in vivo RBE study using small animals at LNS-INFN preclinical hadrontherapy facility. 3003 52