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Research describing a measuring system for the investigation of cryo-packaging technology for superconducting digital electronics is presented. The system is designed around a magnetically shielded wide band test fixture.

Research was conducted to examine the results of a digital transmission test of a YBa2Cu3Ox/MgO/Au microstrip line to coplanar waveguide transmission line converter. A further objective was to evaluate a digital transmission measuring system that includes the transmission line converter by an error performance analyzer. Results show that the transmission properties of the transmission line converter was almost the same as YBa2Cu3O(sub x)/MgO/Au microstrip line at frequencies from 40 MHz to 10 GHz at 30 K.

MgO features lower dielectric constant and smaller dielectric loss tangent than LaAlO3 making it more suitable for the preparation of high-quality c-axis oriented Tl2Va2CaCuOdelta thin films for high frequency applications. The thin films were annealed in a gold gasket-sealed alumina capsule. Results reveal that the structural properties of the thin films may be improved through the preannealing of the pellets for Tl compensation.

Anisotropic Tl2Ba2CaCusOx thin films on MgO substrates were used to fabricate superconductor-normal conductor-superconductor-type step-edge Josephson junctions and superconductor-insulator-superconductor intrinsic stacked Josephson junctions. The normal resistance of the junctions were controlled to enhance their applicability to millimeter wave receivers. A fundamental mixing efficient intermediate frequency output of up to 95 K was demonstrated.

The properties of Nb/MgO/BSCCO junctions with crystalline- and amorphous-MgO barriers grown by molecular beam epitaxy were studied. The differential conductance for the junctions were calculated as a function of the measured voltage obtained from the the current-voltage curve. Variations in the superconductor-insulator and superconductor-normal metal interfaces were also analyzed in terms of the proximity effect. Results show that the clear gap structure and energy differences in the junctions are caused by the proximity effect and the variations in the BSCCO surface conductivity, respectively.

High-quality c-axis oriented Tl/sub 2/Ba/sub 2/CaCu/sub 2/O/sub /spl delta// thin films have been prepared on MgO, which is more suitable for high frequency applications than LaAlO/sub 3/ because of its lower dielectric constant (/spl epsi/) and smaller dielectric loss tangent (tan /spl delta/). Annealing of the thin films was carried out in an alumina capsule sealed with a gold gasket. It was revealed that preannealing of the pellets for Tl compensation is effective in improving the structural properties of the thin films. X-ray diffraction (XRD) rocking curve scans of Tl/sub 2/Ba/sub 2/CaCu/sub 2/O/sub /spl delta// (0 0 12) reflection revealed that a full width of half maximum (FWHM) of thin films annealed with an unpreannealed pellet is 0.89/spl deg/, while that of thin films annealed with a preannealed pellet is 0.22/spl deg/. The highest critical temperature (T/sub c/) is 108 K and the highest critical current density J/sub c/ is 2/spl times/10/sup 6/ A/cm/sup 2/ at 77 K. [ABSTRACT FROM PUBLISHER]

Age-associated intramuscular adipose tissue (IntraMAT) deposition induces the development of insulin resistance and metabolic syndrome. However, the relationship between IntraMAT and biochemical parameters in older adults remains unclear. The purpose of this study, therefore, was to elucidate the relationship between adiponectin and echo intensity-estimated IntraMAT using ultrasonography in normal-weight older adults (men 9, women 13) and examine biochemical parameters. Blood tests were performed to determine fasting levels of glucose, insulin, hemoglobin A1c, total cholesterol (Total-C), high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol (LDL-C), free fatty acid, triglycerides (TGs), adiponectin, leptin, high-sensitivity C-reactive protein, and high-sensitivity tumor necrosis factor, and homoeostasis model assessment index of insulin resistance (HOMA-IR). Mean gray-scale echo intensity was calculated as the IntraMAT index of the vastus lateralis. Waist circumference was measured at the level of the navel as the visceral adipose tissue (VAT) index. Echo intensity was significantly inversely correlated with adiponectin or LDL-C, and that was significantly positively correlated with TG. Adiponectin level was inversely correlated with waist circumference. Partial correlation analysis with waist circumference as the control variable revealed that adiponectin was inversely correlated with echo intensity, independent of waist circumference, whereas no such correlation was observed after controlling for LDL-C and TG levels. When biochemical parameters were grouped in the principal component analysis, among men, Total-C, insulin, and HOMA-IR or hemoglobin A1c, and high-sensitivity tumor necrosis factor-alpha were grouped with the same distribution for factors 1 and 2. Among women, glucose, insulin, HOMA-IR, and Total-C or TGs were grouped with the same distribution for factors 1 and 2. These data suggest that adiponectin level is related to IntraMAT content, independent of VAT in normal-weight older adults. The dynamics of adiponectin might not be similar to those of other circulating biochemical parameters in older men and women., Competing Interests: The authors have declared that no competing interests exist.

Neurodevelopmental disorders (NDDs), including autism spectrum disorders (ASD) and intellectual disability (ID), are a large group of neuropsychiatric illnesses that occur during early brain development, resulting in a broad spectrum of syndromes affecting cognition, sociability, and sensory and motor functions. Despite progress in the discovery of various genetic risk factors thanks to the development of novel genomics technologies, the precise pathological mechanisms underlying the onset of NDDs remain elusive owing to the profound genetic and phenotypic heterogeneity of these conditions. Autism susceptibility candidate 2 ( AUTS2 ) has emerged as a crucial gene associated with a wide range of neuropsychological disorders, such as ASD, ID, schizophrenia, and epilepsy. AUTS2 has been shown to be involved in multiple neurodevelopmental processes; in cell nuclei, it acts as a key transcriptional regulator in neurodevelopment, whereas in the cytoplasm, it participates in cerebral corticogenesis, including neuronal migration and neuritogenesis, through the control of cytoskeletal rearrangements. Postnatally, AUTS2 regulates the number of excitatory synapses to maintain the balance between excitation and inhibition in neural circuits. In this review, we summarize the knowledge regarding AUTS2, including its molecular and cellular functions in neurodevelopment, its genetics, and its role in behaviors.

Background: Excessive intramyocellular lipid (IMCL) accumulation is a primary cause of skeletal muscle insulin resistance, especially in older adults, and interventions that reduce IMCL contents are important to improve insulin sensitivity. Electromyostimulation (EMS)-induced changes in IMCL content in older adults remain unknown. The purpose of this study was to clarify the effects of a single bout of EMS on the IMCL content of the vastus lateralis muscle in older adults., Methods: Twenty-two physically active, non-obese older men and women were randomly assigned to an EMS intervention group (69.0 ± 5.2 years, n = 12) or a control group (68.4 ± 3.5 years, n = 10). EMS was applied to the vastus lateralis (7 s on and 7 s off) for 30 min; control participants sat quietly for 30 min. IMCL content within the vastus lateralis was quantified with 1 H-magnetic resonance spectroscopy (n = 7 per group). Fasting plasma glucose and insulin values were determined from blood samples collected before and after the EMS intervention., Results: EMS induced a significant reduction in plasma glucose (93.1 ± 9.6 to 89.5 ± 9.1 mg/dL, p < 0.01), but not IMCL content (15.7 ± 15.7 to 15.8 ± 13.1 mmol/kg wet weight, p = 0.49) or insulin (5.4 ± 2.4 to 4.7 ± 2.7 μIU/mL, p = 0.18). In the control group, no changes in IMCL content in the vastus lateralis was observed after prolonged quiet sitting., Conclusion: EMS intervention for 30 min induces changes in plasma glucose, but no changes in IMCL content in older adults., Trial Registration: University hospital Medical Information Network (UMIN) Center ID: UMIN000020126 . Retrospectively registered on December 222,015. https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000023242.

Fluorescent reporter mouse lines and Cre/Flp recombinase driver lines play essential roles in investigating various molecular functions in vivo . Now that applications of the CRISPR/Cas9 genome-editing system to mouse fertilized eggs have drastically accelerated these knock-in mouse generations, the next need is to establish easier, quicker, and cheaper methods for knock-in donor preparation. Here, we reverify and optimize the phospho-PCR method to obtain highly pure long single-stranded DNAs (ssDNAs) suitable for knock-in mouse generation via genome editing. The sophisticated sequential use of two exonucleases, in which double-stranded DNAs (dsDNAs) amplified by a pair of 5'-phosphorylated primer and normal primer are digested by Lambda exonuclease to yield ssDNA and the following Exonuclease III treatment degrades the remaining dsDNAs, enables much easier long ssDNA productions without laborious gel extraction steps. By microinjecting these donor DNAs along with CRISPR/Cas9 components into mouse zygotes, we have effectively generated fluorescent reporter lines and recombinase drivers. To further broaden the applicability, we have prepared long ssDNA donors in higher concentrations and electroporated them into mouse eggs to successfully obtain knock-in embryos. This classical yet improved method, which is regaining attention on the progress of CRISPR/Cas9 development, shall be the first choice for long donor DNA preparation, and the resulting knock-in lines could accelerate life science research.

Autism susceptibility candidate 2 ( AUTS2 ), a risk gene for autism spectrum disorders (ASDs), is implicated in telencephalon development. Because AUTS2 is also expressed in the cerebellum where defects have been linked to ASDs, we investigated AUTS2 functions in the cerebellum. AUTS2 is specifically localized in Purkinje cells (PCs) and Golgi cells during postnatal development. Auts2 conditional knockout (cKO) mice exhibited smaller and deformed cerebella containing immature-shaped PCs with reduced expression of Cacna1a . Auts2 cKO and knock-down experiments implicated AUTS2 participation in elimination and translocation of climbing fiber synapses and restriction of parallel fiber synapse numbers. Auts2 cKO mice exhibited behavioral impairments in motor learning and vocal communications. Because Cacna1a is known to regulate synapse development in PCs, it suggests that AUTS2 is required for PC maturation to elicit normal development of PC synapses and thus the impairment of AUTS2 may cause cerebellar dysfunction related to psychiatric illnesses such as ASDs., Competing Interests: The authors declare no competing interests., (© 2020 The Author(s).)

For normal neurogenesis and circuit formation, delamination of differentiating neurons from the proliferative zone must be precisely controlled; however, the regulatory mechanisms underlying cell attachment are poorly understood. Here, we show that Down syndrome cell adhesion molecule (DSCAM) controls neuronal delamination by local suppression of the RapGEF2-Rap1-N-cadherin cascade at the apical endfeet in the dorsal midbrain. Dscam transcripts were expressed in differentiating neurons, and DSCAM protein accumulated at the distal part of the apical endfeet. Cre- loxP -based neuronal labeling revealed that Dscam knockdown impaired endfeet detachment from ventricles. DSCAM associated with RapGEF2 to inactivate Rap1, whose activity is required for membrane localization of N-cadherin. Correspondingly, Dscam knockdown increased N-cadherin localization and ventricular attachment area at the endfeet. Furthermore, excessive endfeet attachment by Dscam knockdown was restored by co-knockdown of RapGEF2 or N-cadherin Our findings shed light on the molecular mechanism that regulates a critical step in early neuronal development., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Impairments in synapse development are thought to cause numerous psychiatric disorders. Autism susceptibility candidate 2 (AUTS2) gene has been associated with various psychiatric disorders, such as autism and intellectual disabilities. Although roles for AUTS2 in neuronal migration and neuritogenesis have been reported, its involvement in synapse regulation remains unclear. In this study, we found that excitatory synapses were specifically increased in the Auts2-deficient primary cultured neurons as well as Auts2 mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression in Auts2 mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability. Auts2 mutant mice exhibited autistic-like behaviors including impairments in social interaction and altered vocal communication. Together, these findings suggest that AUTS2 regulates excitatory synapse number to coordinate E/I balance in the brain, whose impairment may underlie the pathology of psychiatric disorders in individuals with AUTS2 mutations., Competing Interests: Declaration of Interests The authors have declared that no conflict of interest exists., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: To investigate the prolonged effects of a 12-month exercise-plus-diet intervention in Japanese adults at risk of impaired glucose or lipid metabolism., Methods and Study Design: A total of 180 participants were randomly divided into an intervention group (n=94), and a control group (n=86). An exercise-plus- diet intervention was conducted on the intervention group for 12 months. The effects were evaluated by questionnaire, physical examinations, and blood tests at baseline, 3 months, 12 months (the end of intervention), and 24 months (one year after the end of intervention). The control group took only the same examinations as the intervention group., Results: At the end of the 12-month intervention, body weight, waist circumference, fasting glucose, HbA1c, triglycerides, and LDL-cholesterol were improved in the intervention group compared to the control group (all p<0.05). One year after the end of the intervention, body weight, waist circumference, fasting glucose, triglycerides, and LDL-cholesterol were still decreased in the intervention group compared to the control group (all p<0.05), especially among non-overweight participants. Among overweight persons, only body weight in the intervention group was lower than the control group. The personal behaviours of physical activity and diet in the intervention group were also improved., Conclusions: The 12-month exercise-plus-diet programs were found to be effective in improving glucose and lipid metabolism, as well as personal behaviour one year after completion of the intervention.

Background: Fat infiltration within skeletal muscle is known as intramuscular fat (IMF), which increases with aging. Studies have assessed IMF content, using the mid-thigh as a representative location. However, three-dimensional IMF distribution is not well understood. The aim of this study was to compare the IMF content in young and old adults by assessing its distribution along the length of the thigh., Methods: Consecutive transaxial images of the right thighs in 15 young (age, 21.0 ± 0.4) and 15 old (age, 70.7 ± 3.8) were obtained by magnetic resonance imaging. We measured IMF cross-sectional area (CSA), skeletal muscle CSA and calculated volume- and CSA-based IMF content for the quadriceps femoris (QF), hamstring (HM) and adductor (AD). CSA-based calculations were performed at every 10% of femur length (Lf), with 0% Lf and 100% Lf indicating the proximal and distal ends of femur., Results: IMF CSAs along the length of the thigh were similar in both age groups. In contrast, skeletal muscle CSAs in all three muscle groups were significantly lower in old adults than in young adults (variation: -15.2 to -1.6 cm 2 , P < 0.05). Thus, in volume-based measurements, the older adults had higher IMF contents than the younger adults (9.5% to 14.3% vs. 4.8% to 8.6%, respectively; P < 0.05). However, such age-dependent differences were not observed at the mid-thigh in the QF and AD., Conclusion: The results demonstrated an age-related increase in IMF content-confirmed in areas of the thigh-primarily based on finding lower amounts of skeletal muscle mass in CSAs in the older adults.

Photocatalytic organic reactions were performed using automatic photocatalytic microreactor, where several open-end capillaries with photocatalytic materials coated inside were just soaked in a test tube including a reactant solution. Organic reactions of the alkyl radicals generated from carboxylic acids due to the photo-Kolbe reaction was studied, in analogy with the reactions using a photosensitizer. This methodology features the reusability of the reactor and an easy process for analysis due to easy separation of the reactant solution.

In Japan, there is a higher incidence of childhood obesity in the Tohoku district than in other areas. It is known that reduced physical activity is associated with increased body weight, but little is known about the physical activity patterns of children in this area. Accordingly, this study was designed to measure the physical activity of 145 children (73 boys and 72 girls) in Hashikami Town, Aomori Prefecture. Physical activity was assessed through a questionnaire as well as through two weeks of pedometer use. Boys spent more time engaging in physical activity than girls did, reporting 9.5 (0.6-22.0) versus 7.0 (1.2-21.5) hours per week [median (range)] (p=0.002). On school days, boys took an average of 13,586+/-4,386 (mean+/-SD) steps per day, while girls took 12,248+/-4,112; on holidays, boys took 9,531+/-4,557, while girls took 9,419+/-4,524. There was no significant sex-based difference in the number of steps per day (F=1.197, p=0.276), but both boys and girls significantly reduced the number of steps they took on holidays (F=116.537, p<0.001). In addition, 36 (24.8%) children reduced the number of steps they took by more than 50% on holidays compared to school days. In general, the participants engaged in the internationally recommended amounts of physical activity. Yet their reduced level of physical activity on holidays seems to be a matter for concern, as it is a possible cause of the higher incidence of childhood obesity in this area.

To investigate the level of walking activity among residents of the Tohoku district in northern Japan, where no widespread public transport system has been developed, winter is severe. The participants were 50 town hall employees with an average age of 43.6+/-10.8 (SD) years. The walking activity of each participant was assessed using a pedometer for one week in summer and one week in winter. The participants' lifestyles, including their commuting methods, were assessed using a questionnaire. Forty-six participants (92%) usually commute to work by private car. The average numbers of steps/day on workdays and holidays were, in summer, 6,560+/-2,600 and 7,016+/-4,679, respectively, and, in winter, 5,236+/-2,253 and 4,770+/-3,039; these numbers were somewhat lower than those recorded in previous reports. We observed a significant reduction in walking during winter (F=19.016, p=0.0001), but no significant differences between workdays and holidays (F=0.001, p=0.966). A significant correlation between BMI and steps/day (r=-0.420, p<0.01) was obtained on workdays in winter. The unexpectedly low level of these participants' physical activity, especially in winter, is probably due to the fact that most of them commute by private car, which is likely a cause of the high incidence of obesity in this district. In addition, a seasonal effect should also be considered when physical activity is assessed, especially in cold climates.

Obese people may succeed in reducing their weight temporarily, but most of them regain the lost weight within a few years. We, therefore, recommend moderate long-term changes in habit rather than a strict temporary program. The purpose of this study was to examine whether physical activity of 40 minutes, mainly walking, was effective in improving or preventing metabolic syndrome when combined with dieting. Participants, all of whom had a waist circumference >or= 85 cm (men) or >or= 90 cm (women), were assigned into one of two groups: the control group (10 men and 11 women, age: 64.2 +/- 3.4 [SD] years) and the intervention group (10 men and 12 women, age: 62.4 +/- 4.2 years). Participants (n = 22) enrolled in a 52-week program; their diets were assessed using a 3-day dietary record and daily steps were measured with a pedometer. No significant change was seen in their dietary records, but the mean number of daily steps increased from 5,806 to 8,000-9,000. In the intervention group, BMI, waist circumference, and systolic and diastolic blood pressures decreased significantly by week 12 (all p < 0.001) and remained low until week 52. In fact, no significant change was seen between weeks 12 and 52. The control group showed no significant changes in all variables. These results indicate that gentle exercise of about 40 minutes in combination with dieting is effective in preventing metabolic syndrome among a sedentary population, although its effect may be limited.

Recently, many cross-sectional studies observed that body mass index (BMI) and percentage of body fat (%BF) were inversely associated with pedometer-determined physical activities, but studies on Asian populations, including the Japanese, are sparse. Height, weight, body fat percentage (%BF, bioelectrical impedance analyzer), and waist circumference were measured on 117 women (62.8+/-4.5 years, 22.2+/-2.2 kg/m(2)) and 62 men (64.0+/-4.6 years, 23.6+/-2.5 kg/m(2)). Pearson correlations and partial correlation coefficients after controlling for age were calculated between steps/day and variables. Furthermore, participants were classified into four groups as follows: <5,000, 5,000-7,499, 7,500-9,999, and >or=10,000 steps/day, and analyzed using ANOVA across activity groups. In women, a significant correlation was found between steps/day and BMI (r=-0.217, p=0.018), %BF (r=-0.292, p=0.0014), and the relationship was still significant after controlling for age. The relationship between steps/day and waist circumference was not significant. In men, a significant relationship was not observed between steps/day and obesity indices. The correlations between steps/day and both BMI and %BF were significant in Japanese women, but weak compared with Caucasian and African-American women as reported previously. A possible cause is racial difference in degree of obesity and body shape. The effects of physical activity on body shape and composition may differ according to race.

Bioelectrical impedance analysis (BIA) is commonly used to measure the percentage of body fat (%BF), but its accuracy is controversial. In addition, the equations are specific to the group for which they were established. As far as we know, there is no study examining the accuracy of BIA in Japanese middle-aged and older people. We compared %BF assessed using BIA with that of dual-energy X-ray absorptiometry (DEXA) in 102 female and 51 male local residents aged 40 to 78 y. Simple correlation coefficients were 0.79 for females and 0.69 for males, which are statistically significant (p<0.001). However, BIA tended to overestimate %BF in the lower BF group and underestimate it in the BF higher group, and only 45.1% for female and 47.1% for male subjects were measured accurately, i.e., within 10% of the measurement by DEXA. This result suggests that this model of BIA is an alternative for estimating %BF in Japanese middle-aged and older people as well as when subjects are within a normal body fat range, but greater accuracy is needed for lean and overweight subjects.

The association of human T-lymphotropic virus type I (HTLV-I) with autoimmune disorders was investigated on the basis of prevalence of antinuclear antibody (ANA), rheumatoid factor and anti-thyroglobulin antibody as well as immunoglobulin (Ig) serum level (IgG, IgA, and IgM). The subjects, all atomic bomb survivors, were 59 HTLV-I-seropositive people without HTLV-I-associated myelopathy or adult T-cell leukemia and 149 HTLV-I-seronegative persons. The mean serum level of IgM was higher in HTLV-I-seropositive subjects than in HTLV-I-seronegative subjects, and a significant association with HTLV-I and sex was indicated in the IgM serum level. No association with HTLV-I was indicated in the prevalence of the autoantibodies except for ANA. These results suggest some clear humoral immunity differences between HTLV-I-infected and noninfected subjects, but whether HTLV-I infection can lead to autoimmune disorders remains uncertain.

Background: To elucidate the impact of menopause on coronary risk factors, we determined the trends of serum cholesterol (mg/dL), blood pressure (BP, mm Hg), and body mass index (BMI, kg/m2) and investigated whether menopause affects these trends in women in Nagasaki, Japan., Methods and Results: Trends of cholesterol, systolic BP (SBP), and BMI from 9 years before menopause through 9 years after menopause in 579 women with natural menopause (ranging in age from 40.2+/-3.1 to 57.9+/-3.1 years; age at menopause, 49.4+/-3.0 years) and 134 women with surgical menopause (hysterectomy with or without bilateral oophorectomy; ranging in age from 34.9+/-4.5 to 51.7+/-5.1 years; age at menopause, 42.9+/-5.0 years) and those in 579 and 134 age- and time-matched male subjects (ranging in age from 40.1+/-3.1 to 57.8+/-3.2 years and from 35.2+/-4.5 to 51.6+/-5.0 years, respectively) in Nagasaki were determined by rearrangement of the data from 1958 to 1989 with time of menopause as the datum line. Although cholesterol tended to increase with age in both sexes, it increased significantly in women from 3 years before natural menopause to 1 year after natural menopause and from 1 year before surgical menopause to 1 year after surgical menopause. SBP and BMI did not exhibit a significant increase in relation to natural or surgical menopause. In male subjects, no significant increase of cholesterol, SBP, or BMI was observed at the age corresponding to natural or surgical menopause., Conclusions: Natural menopause and surgical menopause exert an effect only on cholesterol, and an increase in cholesterol precedes natural menopause by 3 years and occurs at the time of surgical menopause.

Adult T-cell leukemia (ATL), induced by human T- lymphotropic virus type-I (HTLV-I), is endemic in Nagasaki, Japan. To investigate the effects of atomic-bomb radiation on development of this specific type of leukemia, 6182 individuals in the Radiation Effects Research Foundation (RERF) Adult Health Study sample in Hiroshima and Nagasaki were examined for positive rate of HTLV-I antibody. Several lymphocyte parameters were also studied for 70 antibody- positive subjects in Nagasaki. The HTLV-I antibody-positive rate was higher in Nagasaki (6.36%) than in Hiroshima (0.79%) and significantly increased with increasing age, but no association was observed with radiation dose. Whether relationship existed between antibody titer levels and radiation dose among antibody-positive subjects was not The frequency of abnormal lymphocytes tended to be higher in antibody-positive subjects than in antibody-negative subjects, and higher in females than in males regardless of radiation dose. The lymphocyte count was lower in antibody-positive subjects than in antibody-negative subjects and lower in female than in male subjects. No evidence was found to suggest that atomic-bomb radiation plays an important role in HTLV-I infection.

To examine the potential causes of increased levels of calcium in serum with increasing dose of atomic bomb radiation, which was obtained from the previous preliminary analysis, levels of parathyroid hormone (PTH) and calcitonin in serum were examined among 1459 subjects in Hiroshima and Nagasaki. A significant effect of radiation on levels of calcium, PTH and calcitonin in serum was found, even after patients with hyperparathyroidism were excluded. The level of calcium in serum increased with radiation dose; this can be explained partly by the increase in the level of PTH with radiation dose. However, the dose effect on calcium remained even after adjustment for PTH, calcitonin and confounding factors such as renal function, serum albumin level and medication. Parathyroid hormone increased initially by 6.8% per gray, but the dose response leveled off after about 1 Gy. The level of calcitonin increased with radiation dose, probably in part due to feedback mechanisms stimulated by the increase in calcium. However, after adjustment for the level of calcium, the increase in the level of calcitonin with dose was still found. Although the etiological mechanisms of the effect of radiation on serum levels of calcium, PTH and calcitonin are unclear, radiation exposure may affect secretion of PTH and calcitonin and regulation of calcium a long time after atomic bomb exposure.

The purpose of this study was to determine if exposure to atomic bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE.

Using the longitudinal data of the Adult Health Study (AHS) cohort collected during 1958-1986, we examined for the first time the relationship between exposure to ionizing radiation and the incidence of 19 nonmalignant disorders in the A-bomb survivors. Affected individuals were ascertained through the three-digit codes of the International Classification of Diseases which are encoded in the AHS database subsequent to diagnoses made on the basis of general laboratory tests, physical examinations, and history-taking conducted during biennial AHS examinations. The disease onset time was estimated using the mid-point between the AHS examination data when the disease was initially reported and the previously attended disease-free examination date. Dosimetry System 86 organ doses judged to be most appropriate were used. Tests of dose effects were performed assuming a linear relative risk model with stratified background incidence. For the entire study period, significant excess risk was detected for uterine myoma (P < 0.001), chronic liver disease and cirrhosis (P = 0.006), and thyroid disease (P < 0.0001), defined broadly as the presence of one or more of certain noncancerous thyroid conditions. The incidence of myocardial infarction was shown to be increased (P = 0.03) in later years (1968-1986) among the younger heavily exposed AHS subjects, confirming the results of the recent Life Span Study (LSS) noncancer mortality report on coronary heart disease. The findings for uterine myoma may serve as additional evidence indicating benign tumor growth as a possible consequence of radiation exposure. Our results indicating the involvement of radiation in the development of liver diseases are consistent with the report of increased mortality from liver cirrhosis with radiation dose in the LSS cohort. An effect of age at exposure was detected for nonmalignant thyroid disease (P = 0.02), with an increased risk for those exposed who were under 20 years of age, but not for older survivors. Thus the AHS data suggest that thyroid glands in the young are more radiosensitive not only to the development of malignancies, but also to the development of nonmalignant disorders as well. The findings hold independently of the dose effects observed for thyroid cancer. This study also shows that for the period 1958-1986 new occurrences of lens opacity are not increased with radiation dose (P = 0.39) in the AHS subjects.

To determine the effect of exposure to atomic bomb radiation on the occurrence of hyperparathyroidism, the prevalence was determined among a population of 3,948 atomic bomb survivors and their controls in Hiroshima. The diagnosis of hyperparathyroidism was based upon histopathological findings or the presence of consistent hypercalcemia and elevated levels of serum parathyroid hormone. Primary hyperparathyroidism was diagnosed in 19 persons (3 males, 16 females). Females had approximately a threefold higher overall prevalence of hyperparathyroidism than males (P less than 0.05). The prevalence rates of hyperparathyroidism increased with radiation dose (chi2(1) = 12, P less than 0.001) after adjusting for sex and age at the time of the bombing. The estimated relative risk was 4.1 at 1 Gy (95% confidence limits 1.7 to 14). There was some evidence that the effect of radiation was greater for individuals who were younger at the time of the bombing. In conclusion, exposure to atomic bomb radiation affected the occurrence of hyperparathyroidism, suggesting that doses of radiation lower than those used in radiotherapy may also induce this disorder.

An examination of registered cases of parathyroid tumor in Hiroshima Prefecture between 1974 and 1987 revealed 23 cases. An epidemiological study showed that the incidence of parathyroid tumors in Hiroshima Prefecture was significantly higher in the total exposed, especially among the proximally exposed (within 2,000 m from the hypocenter), than in the control nonexposed group (P less than 0.001). A similar trend was seen for parathyroid tumor associated with primary hyperparathyroidism.

Parathyroid tumors in A-bomb survivors in Hiroshima have been studied. Thirteen cases of parathyroid tumor were confirmed from 4,136 autopsy cases between 1961 to 1977, and an elevated incidence of tumor with increase of dose (T65D) was demonstrated (P less than 0.01). A high proportion of 42.9%, 6 out of 14 parathyroid tumors extirpated at Hiroshima University Hospital between 1956 and 1988, were atomic bomb survivors exposed within 4.1 km from the hypocenter. From an epidemiological study using 23 parathyroid tumor cases detected in Hiroshima Prefecture between 1974 and 1987, an elevated incidence of parathyroid tumors with increase of dose (proximally exposed, other exposed and control nonexposed) was demonstrated (P less than 0.001).

At the Radiation Effects Research Foundation, medical examinations have been conducted biennially since 1958 on a fixed population of approximately 20,000 individuals. Blood pressure measurements and electrocardiographic (ECG) recordings are available for 6,569 individuals who were monitored for at least 11 of the 13 2 year intervals between 1958 and 1984. Data from 601 individuals who had satisfied the Foundation's ECG diagnostic criteria of left ventricular hypertrophy ("Kagan-Yano code") on at least one occasion were reviewed. Both the development and the regression of ECG left ventricular hypertrophy were ascertained in 61 subjects (17 men and 44 women). During the course of development of ECG left ventricular hypertrophy, hypertension (including borderline cases) was noted in 83.3% of the subjects. The most common pattern of ECG left ventricular hypertrophy development was high voltage, followed by ST-T changes. In about half of these cases, the condition of hypertrophy regression was associated with lowering of blood pressure, marked by the disappearance of high voltage ECG readings.

Day-by-day changes in ventricular-ejection time/heart-rate ratio (VET/HR) and in ejection time index (ETI), determined by an impedance method in a decompression chamber, were more labile in the mountaineers who had experienced high altitude (above 6,000 m) within the past 1 year, and the ETI values in the first hypoxic exposure were significantly high in these subjects, though close to those of the non-experienced group in the later exposures, suggesting that the effect of hypoxic acclimation on cardiac function might remain at least 1 year after return to sea level.

A patient who received an oral dose of iodine-131 for the treatment of metastatic thyroid carcinoma unexpectedly died with a large total-body retention of the radioiodine. An autopsy was required and the family requested the body to be transported out of state to their home town. Since the radiation intensity near the surface of the cadaver was above 200 mR/hr, advanced planning and special precautions were necessary in order for the autopsy to proceed safely. This required the immediate cooperation of the pathologists, nuclear medicine physicians, health physicists, an endocrine oncologist, and other hospital staff. As a result of team efforts, personnel radiation exposures were kept as low as reasonably achievable, contamination of the autopsy room was minimal, and the radiation level of the cadaver was adequately reduced for safe transport and burial.