Pathological and epidemiologic study of gastric cancer in atomic bomb survivors, Hiroshima and Nagasaki, 1959-77.
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Biomedical subjects
Publications and source records attributed to M Otake.
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Analysis carried out here generalized on earlier studies of chromosomal aberrations in the populations of Hiroshima and Nagasaki, by allowing extrabinomial variation in aberrant cell counts corresponding to within-subject correlations in cell aberrations. Strong within-subject correlations were detected with corresponding standard errors for the average number of aberrant cells that were often substantially larger than was previously assumed. The extrabinomial variation is accommodated in the analysis in the present report, as described in the section on dose-response models, by using a beta-binomial (beta-B) variance structure. It is emphasized that we have generally satisfactory agreement between the observed and the beta-B fitted frequencies by city-dose category. The chromosomal aberration data considered here are not extensive enough to allow a precise discrimination between competing dose-response models.
The basic defect in glycogen storage disease (GSD) type 1b was investigated in two patients: one, (Y.S.), a severely affected infant and the other, (Y.M.), an adult with mild clinical symptoms. The enzymatic studies on liver needle biopsy specimens from the two patients indicated that glucose-6-phosphate (G-6-P) phosphohydrolase activity of the "intact microsomes" was partially deficient (20% of that in controls) in Y.M. and undetectable in Y.S. Activities of G-6-P phosphohydrolase in the disrupted microsomes of Y.S. and Y.M. are higher than those in the disrupted microsomes of controls (12.60 mumole/min/g liver in Y.S., 9.18 in Y.M. and 6.26 +/- 1.22, mean +/- S.D. in controls). Our study also shows that PPi phosphohydrolase activities of the "intact microsomes" from both patients (6.07 mumol/min/g liver in Y.S. and 5.36 in Y.M.) were greater than those of the controls (3.23 +/- 0.77 mumole/min/g wet weight liver). These results indicate that the G-6-P translocase was the locus of the defect in both patients with GSD type 1b. Clinical symptoms and enzymatic studies suggest that the clinical severity of this disorder depends on the level of residual activities of G-6-P translocase. Kinetic studies showed an abnormally high Km of the residual G-6-P translocase in Y.M., suggesting a structural gene mutation. The systematic assay method for glucose-6-phosphatase system, which requires only 15 mg of liver tissues, is also described.
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.
Patients with glycogen storage disease (GSD) type 1b have shown normal activity of glucose-6-phosphatase (EC 3.1.3.9) as assayed in frozen liver, though their clinical and biochemical findings were similar to those of patients with GSD 1a (McKusick 23220) (Senior and Loridan, 1968). In 1978, we suggested that a basic defect of GSD 1b exists in the glucose-6-phosphate (G6P) transport system (Narisawa et al., 1978; Igarashi et al., 1979). Since then, there have been reports confirming our observation (Beaudet et al., 1980; Lange et al., 1980; Corbeel et al., 1981; Schaub et al., 1981). Recently, it was postulated that the G6Pase system contains a phosphate translocase which mediates the efflux of phosphate, in addition to a G6P translocase and a non-specific phosphohydrolase (Arion et al., 1980). Therefore, it is possible that GSD 1b is caused by a defect of phosphate translocase. In this paper, the basic defect in GSD type 1b was investigated in two patients; one with severe, the other with mild, clinical symptoms.
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Data are presented on four indicators of genetic effects from studies of children born to survivors of the atomic bombings of Hiroshima and Nagasaki. The indicators are frequency of untoward pregnancy outcomes (stillbirth, major congenital defect, death during the first postnatal weak); occurrence of death in live-born children, through an average of life expectancy of 17 years; frequency of children with sex chromosome aneuploidy; and frequency of children with mutation resulting in an eletrophoretic variant. In no instance is there a statistically significant effect of parental exposure; but for all indicators the observed effect is in the direction suggested by the hypothesis that genetic damage resulted from the exposure. On the basis of assumptions concerning the contribution that spontaneous mutation in the preceding generation makes to the indicators in question, it is possible to estimate the genetic doubling dose for radiation for the first three indicators (the data base is still too small for the fourth). The average of these estimates is 156 rems. This is some four times higher than the results from experimental studies on the mouse with comparable radiation sources, which have been the principal guide to the presumed human sensitivities. The relevance of these data in setting permissible limits for human exposures is discussed briefly.
A case of immunoglobulin E (IgE) myeloma with clinical features of "classic" myeloma is presented. Skeletal roentgenograms showed osteoporosis and compression fractures of the vertebrae but no osteosclerosis. Protein analyses revealed an M component of the IgE kappa type with a concentration of 3.1 g/dl. Although morphologic examination revealed that the plasma cells were not so differentiated, well-developed Golgi apparatus and abundant rough-surfaced endoplasmic reticulum were observed. An indirect immunofluorescence technique showed characteristic apple green fluorescence. The E myeloma protein of our patient had no antibody activity. Treatment with melphalan or cyclophosphamide resulted in a decrease in the serum IgE level and in the level of Bence Jones protein in the urine. The clinical and laboratory features of IgE myeloma were summarized and compared with those of other classes of myeloma.
A total of 289,868 locus tests, based on 28 different protein phenotypes and using one-dimensional electrophoresis to detect variant proteins, has yielded one probable mutation in the offspring of "proximally exposed" parents, who received an estimated average gonadal exposure of 31 to 39 rem in the atomic bombings of Hiroshima and Nagasaki. There were no mutations in 208,196 locus tests involving children of "distally exposed" parents, who had essentially no radiation exposure.
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