Electrophoretic variants of blood proteins in Japanese. IV. Prevalence and enzymologic characteristics of glucose-6-phosphate dehydrogenase variants in Hiroshima and Nagasaki

Summary Electrophoretic screening of glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6PD) was conducted one sample of 9,260 children born to the atomic bomb survivors in Hiroshima (Honshu) and Nagasaki (Kyushu). The prevalence of electrophoretic variants was 0.11% in males and 0.42% in females in Hiroshima, and 0.16% in males and 0.31% in females in Nagasaki. Enzymologic characteristics of 10 variants obtained from three males and seven hemizygous fathers of heterozygous females were examined. As a result, three new types of G6PD variants were identified among five variants detected in Hiroshima, and three new types among five variants in Nagasaki. All the variants except one belonged to Class 3, as defined by Yoshida et al. (1971).     

Radiation-related ophthalmological changes and aging among Hiroshima and Nagasaki A-bomb survivors: a reanalysis.

The relationship of ionizing radiation to the age-related ophthalmological findings of the 1978-1980 ophthalmological examination of A-bomb survivors of Hiroshima and Nagasaki has been reanalyzed using DS86 eye organ dose estimates. The main purpose of this reevaluation was to determine whether age and radiation exposure, as measured using the recently revised dosimetry information (DS86), have an additive, synergistic, or antagonistic effect. The data in this study are limited to axial opacities and posterior subcapsular changes, for which a definite radiation-induced effect has been observed in Hiroshima and Nagasaki A-bomb survivors. The best model fitting for axial opacities gives a significant positive effect for both linear dose and linear age-related regression coefficients and a significant negative effect for an interaction between radiation dose and age. Such a negative interaction implies an antagonistic effect in that the relative risks in relation to radiation exposure doses become smaller with an increase in age. On the other hand, the best-fitting relationship for posterior subcapsular changes suggested a linear-quadratic dose and linear age-related effect. The estimate of the quadratic dose coefficient shows a highly negative correlation with age, but the negative quadratic dose term is extremely small and is of little biological significance.     

Ancestors and variants: tales from the cryptic

SUMMARY Those who work at the interface of development and evolution are united by the conviction that developmental comparisons can shed light on both the evolution of specific morphologies and the macroevolutionary process itself. In practice, however, the field comprises a diversity of approaches. As the field grows and practitioners attempt to digest a growing mountain of comparative data, the various approaches of "Evo Devo" have themselves evolved. A meeting organized by the authors and held at the University of Chicago in the Spring of 1999 illustrated some of these changes. This review will draw on its content to discuss recent developments in two areas: the reconstruction of common ancestors and the developmental basis of evolutionary change.     

Reassessment of gamma doses from the atomic bombs in Hiroshima and Nagasaki

Reassessment of gamma doses from the atomic bombs in Hiroshima and Nagasaki has been carried out with thermoluminescent measurements of ceramic materials, such as bricks and decorative tiles, which were collected from buildings that remain as they were at the time of the explosions. The thermoluminescent measurements were performed using thermoluminescent dating techniques generally used in archaeology. Annual background dose rates from natural radionuclides in the ceramic materials and from environmental radiation including cosmic rays were determined with commercially available thermoluminescent detectors. A time-zero point at the original firing of the ceramic materials was estimated from the age of the buildings given in "the register book." Total background dose was evaluated by multiplying the period between the time-zero point and the time of measurement by the annual dose rate. The resultant gamma doses in Hiroshima and Nagasaki are given as a function of distance from ground zero and are compared with the DS86 (Dosimetry System 1986) and the T65D (Tentative 1965 Dose) gamma doses.     

Sixty years of follow-up of Hiroshima and Nagasaki survivors: current progress in molecular epidemiology studies

This article provides an overview of the on-going molecular epidemiology studies among atomic-bomb survivors conducted at the Radiation Effects Research Foundation in Japan. The focus is on: (a) inter-individual variations in sensitivity to radiation-induced somatic mutations (glycophorin A (GPA) mutations) and their potential relevance to differences in susceptibility to radiation-related cancers and (b) the role of specific mutations/rearrangements in radiation-induced thyroid and colorectal cancers. The glycophorin A mutant fractions showed large differences between the survivors at each of the estimated bone marrow doses. Of note is the finding at doses>or=1 Gy; that the slope of the mutant fraction was significantly higher in the 'cancer group' than in the 'non-cancer group'. This study provided the basis for validating the use of gammaH2AX and reticulocyte micronucleus assays for evaluating radiosensitivity differences and genetic instability, respectively, in our studies in the coming years. Preliminary results from our molecular oncology studies on adult-onset papillary thyroid cancer provide evidence for the induction of RET/PTC rearrangements and BRAF point mutation (both known to be early stage events in adult-onset papillary thyroid cancer) but with a difference: cases associated with the rearrangements were more frequent at high doses, and developed sooner than those with BRAF mutation. In the case of colorectal cancer, the results suggest that radiation exposure might influence microsatellite instability (MSI) status through MSI-related epigenetic and genetic alterations-processes that might occur in the early stage of colorectal carcinogenesis.     

Imbalance of blood group A subtypes and the existence of superactive B gene in Japanese in Hiroshima and Nagasaki.

Blood type A can be classified into subgroups A1, A2, and A1-A2 intermediate on the basis of serological criteria. An excess of A2B over A2, noted in some black populations and among the Japanese, though not in caucasoids, is inconsistent with the classical Mendelian mode of inheritance of the allelic A1 and A2 genes. Characterization of the enzymatic properties of the blood group A and B enzymes in the serum has shown that serological A2B blood of some blacks contains A1 enzyme and a superactive B* enzyme. An excess of A2B found in a study of over 15,000 residents of Hiroshima and Nagasaki prompted investigation of the characteristics of the A and B enzymes in 60 blood samples, 37 from individuals in 13 unrelated families and 23 from other unrelated individuals in the two cities. Among 27 unrelated individuals whose blood types were unequivocally classified serologically as A2B, 15 were confirmed as A2B enzymatically; eight contained A1 and B* enzymes, not A2 or B enzymes, thus being A1B*; two contained Aint and B* enzymes, thus being AintB; and results for the remaining two were ambiguous. Hiroshima differs from Nagasaki in the frequency of the A2B serological type and also in the occurrence of the B* enzyme, Nagasaki having a higher proportion of both. If one considers those cases in which family study was possible, the transmission of the B* enzyme appears to be compatible with the Mendelian mode of inheritance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gamma-ray exposure from neutron-induced radionuclides in soil in Hiroshima and Nagasaki based on DS02 calculations

As a result of joint efforts by Japanese, US and German scientists, the Dosimetry System 2002 (DS02) was developed as a new dosimetry system, to evaluate individual radiation dose to atomic bomb survivors in Hiroshima and Nagasaki. Although the atomic bomb radiation consisted of initial radiation and residual radiation, only initial radiation was reevaluated in DS02 because, for most survivors in the life span study group, the residual dose was negligible compared to the initial dose. It was reported, however, that there were individuals who entered the city at the early stage after the explosion and experienced hemorrhage, diarrhea, etc., which were symptoms of acute radiation syndrome. In this study, external exposure due to radionuclides induced in soil by atomic bomb neutrons was reevaluated based on DS02 calculations, as a function of both the distance from the hypocenters and the elapsed time after the explosions. As a result, exposure rates of 6 and 4 Gy h(-1) were estimated at the hypocenter at 1 min after the explosion in Hiroshima and Nagasaki, respectively. These exposure rates decreased rapidly by a factor of 1,000 1 day later, and by a factor of 1 million 1 week later. Maximum cumulative exposure from the time of explosion was 1.2 and 0.6 Gy at the hypocenters in Hiroshima and Nagasaki, respectively. Induced radiation decreased also with distance from the hypocenters, by a factor of about 10 at 500 m and a factor of three to four hundreds at 1,000 m. Consequently, a significant exposure due to induced radiation is considered feasible to those who entered the area closer to a distance of 1,000 m from the hypocenters, within one week after the bombing.     

Ophthalmologic changes related to radiation exposure and age in adult health study sample, Hiroshima and Nagasaki

A 2-year ophthalmologic study of age and radiation-related ophthalmologic lesions among the atomic bomb survivors in Hiroshima and Nagasaki was conducted in 1978-80. The study sample in both cities was composed of all persons exposed to 100+ rad, their controls, and all other persons with a previous record of axial opacities or posterior subcapsular changes. Most of the losses were due to persons who refused to participate or for whom it was not possible to arrange for an ophthalmologic examination at the time of the regularly scheduled medical examination. It should be emphasized, however, that the loss of persons in both the control and the 100+ rad groups did not change systematically with increasing age by city. Increased lenticular opacities, other lens changes, and loss of visual acuity and accommodation occurred with increasing age in both exposed and control subjects as manifestations of the normal aging process. A highly significant excess risk for all age categories in the 300+ rad group in comparison to those in the control group was observed for both axial opacities and posterior subcapsular changes in Hiroshima, but not in Nagasaki. A stronger radiosensitive aging effect for persons who were under 15 years old at the time of the bombing (ATB) was observed for both axial opacities and posterior subcapsular changes in Hiroshima.     

Experimental derivation of relative biological effectiveness of A-bomb neutrons in Hiroshima and Nagasaki and implications for risk assessment

Epidemiological data on the health effects of A-bomb radiation in Hiroshima and Nagasaki provide the framework for setting limits for radiation risk and radiological protection. However, uncertainty remains in the equivalent dose, because it is generally believed that direct derivation of the relative biological effectiveness (RBE) of neutrons from the epidemiological data on the survivors is difficult. To solve this problem, an alternative approach has been taken. The RBE of polyenergetic neutrons was determined for chromosome aberration formation in human lymphocytes irradiated in vitro, compared with published data for tumor induction in experimental animals, and validated using epidemiological data from A-bomb survivors. The RBE of fission neutrons was dependent on dose but was independent of the energy spectrum. The same RBE regimen was observed for lymphocyte chromosome aberrations and tumors in mice and rats. Used as a weighting factor for A-bomb survivors, this RBE system was superior in eliminating the city difference in chromosome aberration frequencies and cancer mortality. The revision of the equivalent dose of A-bomb radiation using DS02 weighted by this RBE system reduces the cancer risk by a factor of 0.7 compared with the current estimates using DS86, with neutrons weighted by a constant RBE of 10.     

Study of cognitive function among the Adult Health Study (AHS) population in Hiroshima and Nagasaki

Although neuropsychological dysfunction is found among A-bomb survivors exposed in utero as it is among patients who receive central nervous system radiotherapy, neuropsychological examinations have not been conducted on the survivors. Its prevalence may be increased as a result of the increased rate of strokes reported among those exposed to a high radiation dose. In this study, we examined the effects of radiation exposure on cognitive function among adult survivors in the Adult Health Study (AHS). The study subjects were men and women born prior to September 1932 who had undergone biennial examinations during the period 1992-1996 in Hiroshima or 1993-1998 in Nagasaki. We evaluated cognitive performance for 3,113 subjects with the Cognitive Abilities Screening Instrument (CASI), and we examined the relationship between cognitive performance and potentially related factors (sex, age, city where the subjects were exposed, years of education, and radiation dose). In contrast to exposure to radiotherapy, exposure to atomic bomb radiation had no apparent effect on cognitive function. Factors that did affect cognitive function were age, sex, city and years of education. Further investigation, including examination of other neurological functions, is required before a final conclusion regarding radiation-induced neurological dysfunction can be reached.