16 research outputs found
Detection of Murine Leukemia Virus or Mouse DNA in Commercial RT-PCR Reagents and Human DNAs
The xenotropic murine leukemia virus (MLV)-related viruses (XMRV) have been reported in persons with prostate cancer, chronic fatigue syndrome, and less frequently in blood donors. Polytropic MLVs have also been described in persons with CFS and blood donors. However, many studies have failed to confirm these findings, raising the possibility of contamination as a source of the positive results. One PCR reagent, Platinum Taq polymerase (pol) has been reported to contain mouse DNA that produces false-positive MLV PCR results. We report here the finding of a large number of PCR reagents that have low levels of MLV sequences. We found that recombinant reverse-transcriptase (RT) enzymes from six companies derived from either MLV or avian myeloblastosis virus contained MLV pol DNA sequences but not gag or mouse DNA sequences. Sequence and phylogenetic analysis showed high relatedness to Moloney MLV, suggesting residual contamination with an RT-containing plasmid. In addition, we identified contamination with mouse DNA and a variety of MLV sequences in commercially available human DNAs from leukocytes, brain tissues, and cell lines. These results identify new sources of MLV contamination and highlight the importance of careful pre-screening of commercial specimens and diagnostic reagents to avoid false-positive MLV PCR results
Excessive Biologic Response to IFNβ Is Associated with Poor Treatment Response in Patients with Multiple Sclerosis
Interferon-beta (IFNβ) is used to inhibit disease activity in multiple sclerosis (MS), but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified.he relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70) or poor response (n = 15). Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs).The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual ‘IFN response fingerprint’. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections.MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients
Structural and magnetic properties of Al-doped yttrium iron garnet ceramics: Fe-57 internal field NMR and Mossbauer spectroscopy study
The structural and magnetic properties of Al substituted yttrium-iron garnet (Y3AlxFe5-xO12, x = 0, 0.1, 0.2, 0.3, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, 1.6 and 1.8) ceramic powders synthesized using solution combustion method were investigated. Post combustion, the samples were calcination at 1045 degrees C for 6 h and subsequently at 1200 degrees C for 6 h to obtain phase-pure garnets. X-ray diffraction (XRD) results confirm the formation of garnets with la (3) over bard structure. The occupancy of Y3+ ions in the dodecahedral site and the distribution of Al3+ and Fe3+ ions in the tetrahedral and octahedral sites in the bcc structure of the garnet were confirmed by Rietveld refinement of XRD patterns, Mossbauer spectroscopy and( 57)Fe internal field NMR spectroscopy. For low Al content, Al3+ ions have preference to occupy tetrahedral (T-d) sites than the octahedral (O-h) sites. At higher Al content the distribution of Al tends towards a ratio of 3:2 at the tetrahedral:octahedral site. Increase in Al doping results in the decrease in the lattice parameter due to smaller size of Al-3 + as compared to Fe3+ ion. All the studied samples show coral-network-like surface morphology. The saturation magnetization (M-s) values decrease from -26.94 emu/g to 0.17 emu/g with increase in Al content from 0.0 to 1.8. Further addition of Al makes the sample paramagnetic at RT. Substitution of non-magnetic Al3+ reduces the saturation magnetization rapidly due to the decrease in the superexchange interaction in the crystal. (C) 2018 Elsevier B.V. All rights reserved