Atomic Bomb Survivor Studies and their Current Significance: Comparison between the Practices of the ABCC-RERF and the RIRBM

Medical research spurred by radiation exposure is a critically important theme for modern society. Accordingly, studies of this contemporary problem should be based on a perspective that is focused on that origin, medical investigations into the effects of radiation exposure on survivors of the atomic bombs. Therefore, we organized and evaluated survey programs and research of atomic bomb survivors that have been conducted by ABCC (Atomic Bomb Casualty Commission) –RERF (Radiation Effects Research Foundation) and RIRBM (Research Institute for Radiation Biology and Medicine) between 1949 and 1975. ABCC established a set of carefully defined cohorts and launched an integrated research program based on three phases of pure research. That work has formed the foundation for the research that the RERF is engaged in today. And among surveys and studies worldwide that have generated fundamental data on radiation protection standards, the findings of ABCC-RERF surveys and studies have provided important information. It has thus provided various international research organizations (WHO (World Health Organization), ICRP (International Commission on Radiological Protection), UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation), etc.) with important information and indicators. RIRBM has pursued studies and surveys that are distinct from the undertakings led by ABCC-RERF. RIRBM was able to do something that ABCC-RERF would have found difficult to implement: namely, flexibly launching projects on themes that directly met the needs of the local society at the time. Atomic bomb survivors’ medical data continue to grow, from the bombing to the present, and to the future. Data sharing, joint research, and collaboration by research institutions in this field will be effective ways to foster rationally coordinated surveys and studies

A comparison of the signal pathways between the TNF alpha- and oridonin-induced murine L929 fibrosarcoma cell death.

Oridonin, an active component isolated from Rabdosia rubescences, has been reported to have antitumor effects. In this study, we compared the signal transduction pathways between TNFalpha-and oridonin-induced L929 cell death. Oridonin and TNFalpha initiated apoptotic morphologic changes, but DNA fragmentation was found in TNFalpha-treated L929 cells but not in oridonin-treated ones. The pan-caspase inhibitor (z-VAD-fmk), caspase-8 inhibitor (z-IETD-fmk) and caspase-3 inhibitor (z-DEVD-fmk) augmented oridonin-and TNFalpha-induced cell death. However, the caspase-9 inhibitor (z-LEHD-fmk) only increased oridonin-induced L929 cell death. Moreover, poly (ADPribose) polymerase (PARP) was cleaved in oridonin-treated L929 cells but not in the TNFalpha-treated groups, and the caspase-3 inhibitor (z-DEVD-fmk) failed to inhibit PARP cleavage. These results showed that only oridonin-induced L929 cell death required PARP degradation in a caspase-3 independent manner. In addition, oridonin increased the ratio of Bax/Bcl-2 protein expression, but TNFalpha did not. TNFalpha induced p38 and ERK activation, whereas oridonin triggered only ERK activation. We also investigated the effect of oridonin on intracellular TNFalpha expression, and found that oridonin augmented endogenous pro-TNFalpha expression and its upstream protein IkB phosphorylation. These results indicated that although oridonin promoted endogenous pro-TNFalpha expression, a great difference existed between the signal pathways through which TNFalpha-and oridonin-induced cell death.</p

The augmentation of TNFalpha-induced cell death in murine L929 fibrosarcoma by the pan-caspase inhibitor Z-VAD-fmk through pre-mitochondrial and MAPK-dependent pathways.

We investigated the mechanism of the pan-caspase inhibitor z-VAD-fmk's augmentation of TNFalpha-induced L929 cell death and found this mechanism differs from that of TNFalpha-induced L929 cell death. In the presence of 20 ng/ml TNFalpha, z-VAD-fmk initiated apoptosis and necrosis in the majority of L929 cells as measured by an agarose gel electrophoresis and lactate dehydrogenase(LDH)activity based assay. Mitochondrial permeability transition (MPT) inhibitor (cyclosporine A) effectively inhibited z-VAD-fmk-augmented cell death. In addition, z-VAD-fmk plus TNFalpha increased Bax expression without affecting Bcl-2 and cytochrome expression. Western-blot analysis showed that z-VAD-fmk plus TNFalpha caused persistent JNK activation and ERK inactivation. Poly(ADP-ribose) polymerase (PARP) inhibitor (DPQ) effectively reversed the cell death which was augmented by z-VAD-fmk, and z-VAD-fmk plus TNFalpha also caused PARP cleavage to an 85 KDa fragment. These results indicate that in the presence of TNFalpha, z-VAD-fmk further augments cell death which requires the mitochondrial permeability transition and the JNK activation. However, we did not detect the changes in cytochrome c expression and the participation of caspase-9 in this process, suggesting that there might exist an unknown signal pathway(s) from the mitochondria to the downstream protein PARP, which is cleaved in a caspase-independent manner.</p

Chromosome order in HeLa cells changes during mitosis and early G1, but is stably maintained during subsequent interphase stages

Whether chromosomes maintain their nuclear positions during interphase and from one cell cycle to the next has been controversially discussed. To address this question, we performed long-term live-cell studies using a HeLa cell line with GFP-tagged chromatin. Positional changes of the intensity gravity centers of fluorescently labeled chromosome territories (CTs) on the order of several μm were observed in early G1, suggesting a role of CT mobility in establishing interphase nuclear architecture. Thereafter, the positions were highly constrained within a range of ∼1 μm until the end of G2. To analyze possible changes of chromosome arrangements from one cell cycle to the next, nuclei were photobleached in G2 maintaining a contiguous zone of unbleached chromatin at one nuclear pole. This zone was stably preserved until the onset of prophase, whereas the contiguity of unbleached chromosome segments was lost to a variable extent, when the metaphase plate was formed. Accordingly, chromatin patterns observed in daughter nuclei differed significantly from the mother cell nucleus. We conclude that CT arrangements were stably maintained from mid G1 to late G2/early prophase, whereas major changes of CT neighborhoods occurred from one cell cycle to the next. The variability of CT neighborhoods during clonal growth was further confirmed by chromosome painting experiments

Spectral Evolutions in Gamma-Ray Burst Exponential Decays Observed with Suzaku WAM

This paper presents a study on the spectral evolution of gamma-ray burst (GRB) prompt emissions observed with the Suzaku Wide-band All-sky Monitor (WAM). By making use of the WAM data archive, 6 bright GRBs exhibiting 7 well-separated fast-rise-exponential-decay (FRED) shaped light curves are presented and the evaluated exponential decay time constants of the energy-resolved light curves from these FRED peak light curves are shown to indicate significant spectral evolution. The energy dependence of the time constants is well described with a power-law function tau(E) ~ E^gamma, where gamma ~ -(0.34 +/- 0.12) in average, although 5 FRED peaks show consistent value of gamma = -1/2 which is expected in synchrotron or inverse-Compton cooling models. In particular, 2 of the GRBs were located with accuracy sufficient to evaluate the time-resolved spectra with precise energy response matrices. Their behavior in spectral evolution suggests two different origins of emissions. In the case of GRB081224, the derived 1-s time-resolved spectra are well described by a blackbody radiation model with a power-law component. The derived behavior of cooling is consistent with that expected from radiative cooling or expansion of the emission region. On the other hand, the other 1-s time-resolved spectra from GRB100707A is well described by a Band GRB model as well as with the thermal model. Although relative poor statistics prevent us to conclude, the energy dependence in decaying light curve is consistent with that expected in the former emission mechanism model.Comment: 11 pages, 7 figures, 5 tables. PASJ accepte

Tubulointerstitial Nephritis and Uveitis Syndrome Associated with Renal Tryptaseand Chymase-positive Mast Cell Infiltration

We report the clinical course and immunohistochemical analysis of a patient who presented with tubulointerstitial nephritis and uveitis syndrome (TINU syndrome). The patient, a 40-year-old woman, was referred to our hospital with general fatigue and a slight fever from another hospital. Mast cells are closely related to the development of renal interstitial fibrosis in patients with glomerulonephritis. To determine the role of mast cells in renal interstitial injury in TINU patients, we performed immunohistochemical studies on renal biopsy specimens using anti-human tryptase and anti-human chymase antibodies specific for mast cells. Double immunostaining of tryptase and chymase was also performed in renal tissues. In double immunofluorescence, cells with both chymase and tryptase (MCtc) were marked in the regions of interstitial fibrosis in this patient. It appears that mast cells are one of the constitutive cells of interstitial fibrosis in patients with TINU syndrome

Spectral Properties of Prompt Emission of Four Short Gamma-Ray Bursts Observed by the Suzaku-WAM and the Konus-Wind

We have performed a joint analysis of prompt emission from four bright short gamma-ray bursts (GRBs) with the Suzaku-WAM and the Konus-Wind experiments. This joint analysis allows us to investigate the spectral properties of short-duration bursts over a wider energy band with a higher accuracy. We find that these bursts have a high E$_{\rm peak}$, around 1 MeV and have a harder power-law component than that of long GRBs. However, we can not determine whether these spectra follow the cut-off power-law model or the Band model. We also investigated the spectral lag, hardness ratio, inferred isotropic radiation energy and existence of a soft emission hump, in order to classify them into short or long GRBs using several criteria, in addition to the burst duration. We find that all criteria, except for the existence of the soft hump, support the fact that our four GRB samples are correctly classified as belonging to the short class. In addition, our broad-band analysis revealed that there is no evidence of GRBs with a very large hardness ratio, as seen in the BATSE short GRB sample, and that the spectral lag of our four short GRBs is consistent with zero, even in the MeV energy band, unlike long GRBs. Although our short GRB samples are still limited, these results suggest that the spectral hardness of short GRBs might not differ significantly from that of long GRBs, and also that the spectral lag at high energies could be a strong criterion for burst classification.Comment: 23 pages, 6 figures, accepted for Publications of the Astronomical Society of Japa

Reviewing E(sub peak) Relations with Swift and Suzaku Data

In recent years several authors have derived correlations between gamma-ray burst (GRB) spectral peak energy (E(sub peak)) and either isotropic-equivalent radiated energy (E(sub iso)) or peak luminosity (L(sub iso)). Since these relationships are controversial, but could provide redshift estimators, it is important to determine whether bursts detected by Swift exhibit the same correlations. Swift has greatly added to the number of GRBs for which redshifts are known and hence E(sub iso) and L(sub iso) could be calculated. However, for most bursts it is not possible to adequately constrain E(sub peak) with Swift data alone since most GRBs have E(sub peak) above the energy range (15-50 keV) of the Swift Burst Alert Telescope (BAT). Therefore we have analyzed the spectra of 78 bursts (31 with redshift) which were detected by both Swift/BAT and the Suzaku Wide-band All-sky Monitor (WAM), which covers the energy range 50-5000 keV. For most bursts in this sample we can precisely determine E(sub peak) and for bursts with known redshift we can compare how the E(sub peak) relations for the Swift/Suzaku sample compare to earlier published results. Keywords: gamma rays: burst