Because the NR1 subunit of the NMDA receptor is critical to full receptor activity, a reduction of NR1 in hippocampus in schizophrenia suggests a functional impairment in glutamatergic transmission at the NMDA receptor, resulting in reduced glutamatergic transmission within and possibly efferent from the hippocampus in schizophrenia. This defect could underlie a hypoglutamatergic state in regions of limbic cortex, consistent with published results from other lines of research in schizophrenia.

Aims: Urinary 8-oxo-7,8-dihydro-2¢-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical-and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject-and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs Kronos Science, Phoenix, Arizona. ANTIOXIDANTS & REDOX SIGNALINGVolume 18, Number 18, 2013 ª Mary Ann Liebert, Inc. DOI: 10.1089/ars.2012.4714 2377showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r p 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine-or SG-adjusted first morning samples are recommended.

Following the Fukushima accident, the International Commission on Radiological Protection (ICRP) convened a task group to compile lessons learned from the nuclear reactor accident at the Fukushima Daiichi nuclear power plant in Japan, with respect to the ICRP system of radiological protection. In this memorandum the members of the task group express their personal views on issues arising during and after the accident, without explicit endorsement of or approval by the ICRP. While the affected people were largely protected against radiation exposure and no one incurred a lethal dose of radiation (or a dose sufficiently large to cause radiation sickness), many radiological protection questions were raised. The following issues were identified: inferring radiation risks (and the misunderstanding of nominal risk coefficients); attributing radiation effects from low dose exposures; quantifying radiation exposure; assessing the importance of internal exposures; managing emergency crises; protecting rescuers and volunteers; responding with medical aid; justifying necessary but disruptive protective actions; transiting from an emergency to an existing situation; rehabilitating evacuated areas; restricting individual doses of members of the public; caring for infants and children; categorising public exposures due to an accident; considering pregnant women and their foetuses and embryos; monitoring public protection; dealing with 'contamination' of territories, rubble and residues and consumer products; recognising the importance of psychological consequences; and fostering the sharing of information. Relevant ICRP Recommendations were scrutinised, lessons were collected and suggestions were compiled. It was concluded that the radiological protection community has an ethical duty to learn from the lessons of Fukushima and resolve any identified challenges. Before another large accident occurs, it should be ensured that inter alia: radiation risk coefficients of potential health effects are properly interpreted; the limitations of epidemiological studies for attributing radiation effects following low exposures are understood; any confusion on protection quantities and units is resolved; the potential hazard from the intake of radionuclides into the body is elucidated; rescuers and volunteers are protected with an ad hoc system; clear recommendations on crisis management and medical care and on recovery and rehabilitation are available; recommendations on public protection levels (including infant, children and pregnant women and their expected offspring) and associated issues are consistent and understandable; updated recommendations on public monitoring policy are available; acceptable (or tolerable) 'contamination' levels are clearly stated and defined; strategies for mitigating the serious psychological consequences arising from radiological accidents are sought; and, last but not least, failures in fostering information sharing on radiological protection policy after an accident need to be addressed with recommendatio...

The induction of thymic lymphomas by whole-body X irradiation with four doses of 1.8 Gy (total dose: 7.2 Gy) in C57BL/6 mice was suppressed from a high frequency (90%) to 63% by preirradiation with 0.075 Gy X rays given 6 h before each 1.8-Gy irradiation. This level was further suppressed to 43% by continuous whole-body irradiation with 137Cs gamma rays at a low dose rate of 1.2 mGy/h for 450 days, starting 35 days before the challenging irradiation. Continuous irradiation at 1.2 mGy/h resulting in a total dose of 7.2 Gy over 258 days yielded no thymic lymphomas, indicating that this low-dose-rate radiation does not induce these tumors. Further continuous irradiation up to 450 days (total dose: 12.6 Gy) produced no tumors. Continuously irradiated mice showed no loss of hair and a greater body weight than unirradiated controls. Immune activities of the mice, as measured by the numbers of CD4+ T cells, CD40+ B cells, and antibody-producing cells in the spleen after immunization with sheep red blood cells, were significantly increased by continuous 1.2-mGy/h irradiation alone. These results indicate the presence of an adaptive response in tumor induction, the involvement of radiation-induced immune activation in tumor suppression, and a large dose and dose-rate effectiveness factor (DDREF) for tumor induction with extremely low-dose-rate radiation.

DNA amplification, manifested by homogeneously staining regions in chromosomes and by extrachromosomal, double minute bodies, is characteristic of many neuroblastoma cell lines. Sequences recruited from a specific domain on the short arm of chromosome 2 (2p) are amplified in advanced-stage primary neuroblastomas, whereas sequences from distinctly different regions of 2p are amplified in the neuroblastoma cell line IMR-32. Five different DNA segments, which include the oncogene N-myc, three other fragments derived from the homogeneously staining region of the neuroblastoma cell line IMR-32, and a fifth fragment, derived from the neuroblastoma cell line NB-9, showed differential and variable amplification in 24 advanced-stage neuroblastoma tumors out of 112 tested specimens. AU five fragments were mapped within the chromosomal region 2p23-2p25 by three different approaches. However, eight other fragments cloned from the homogeneously staining region of IMR-32 cells, which were not amplified in the tumor tissues examined, were mapped to two more proximal domains of 2p, thousands of kilobases apart from each other and from the chromosomal domain that is amplified in the tumors. These results establish the amplification, to different degrees, of a variable-sized segment of one domain near the terminus of 2p in advanced neuroblastomas. These tumors might ultimately be distinguished according to the pattern of amplification of DNA segments within this domain. The data presented also indicate the existence of a new and complex amplification mechanism in at least one neuroblastoma cell line (IMR-32), which involves not only relocation of DNA from specific genomic domains but also the formation of novel units by splicing together very distant DNA segments.