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•Helium gas was detected by GC-TCD.•This is the first report to demonstrate helium gas in a heat-affected case.•Investigation of helium in cases of fire-related deaths is informative. We report here detection of helium in specimens derived from a burn autopsy case. A male was found in a burnt bedroom. Part of a heat-denatured plastic bag, sealing tape, and flexible tubing remained on his head and neck. In addition, five helium tanks were found near him. His history in conjunction with the discovery conditions suggested a suicide attempt by inhalation of helium. The body had extensive first to fourth degree burns caused by heat. A small amount of soot was deposited in the respiratory tract. Except for the thermal burns, no other injuries were found. Toxicologically, the blood carboxyhemoglobin saturation levels were less than 6%, while combustion-derived volatile hydrocarbons such as benzene or toluene were detected in the blood. In addition, tracheal gas, gastric gas, headspace gas of lung tissue, brain, and heart blood were collected during autopsy for detection of helium. Analysis was performed using headspace gas chromatography with a thermal conductivity detector. Helium was detected in all of the samples tested. Etizolam at a low limit of therapeutic concentration or less was detected in the blood. Neither ethanol nor other drugs of abuse were detected in his blood or urine. Autopsy findings and experiments suggest that the victim inhaled helium and was still alive when a fire broke out. The cause of his death was diagnosed as death from fire and flames. The present result suggests that helium may remain in a burned body and that investigation of helium in cases of fire-related deaths is informative for determination of the cause of death or confirmation of the ante mortem involvement of helium.

This paper reports, for the first time, on the analysis of ethanol (EtOH) and acetaldehyde (AcH) concentrations in the blood and brains of Aldh2-knockout (Aldh2-KO) and C57B6/6J (WT) mice. Animals were administrated EtOH (1.0, 2.0 or 4.0 g/kg) or 4-methylpyrazole (4-MP, 82 mg/kg) plus AcH (50, 100 or 200 mg/kg) intraperitoneally. During the blood tests, samples from the orbital sinus of the eye were collected. During the brain tests, dialysates were collected every 5 min (equal to a 15 µl sample) from the striatum using in vivo brain microdialysis. Samples were collected at 5, 10, 15, 20, 25, 30 and 60 min intervals post-EtOH and -AcH injection, and then analyzed by head-space GC. In the EtOH groups, high AcH levels were found in the blood and brains of Aldh2-KO mice, while only small traces of AcH were seen in the blood and brains of WT mice. No significant differences in EtOH levels were observed between the WT and the Aldh2-KO mice for either the EtOH dose. EtOH concentrations in the brain were comparable to the EtOH concentrations in the blood, but the AcH concentrations in the brain were four to five times lower compared to the AcH concentrations in the blood. In the AcH groups, high AcH levels were found in both WT and Aldh2-KO mice. Levels reached a sharp peak at 5 min and then quickly declined for 60 min. Brain AcH concentrations were almost equal to the concentrations found in the blood, where the AcH concentrations were approximately two times higher in the Aldh2-KO mice than in the WT mice, both in the blood and the brain. Our results suggest that systemic EtOH and AcH administration can cause a greater increase in AcH accumulation in the blood and brains of Aldh2-KO mice, where EtOH concentrations in the Aldh2-KO mice were comparable to the EtOH concentrations in the WT mice. Furthermore, detection of EtOH and AcH in the blood and brain was found to be dose-dependent in both genotypes.

Japan needs an effective guide training system. The London Blue Badge guide training program is considered a successful model to learn from in order to improve guide education. Therefore, as Japan-based researchers, we investigated the London Blue Badge guide training program to discover what makes the program so successful. Using an online survey and focus group interviews with trainees, trainers and qualified guides (N = 130), we discovered that guiding practice and observing model guiding were the most valued elements in the program. In addition, immediate verbal feedback from tutors after guiding practice was valued more than written feedback. •Most popular elements in the London Blue Badge guide training program identified.•Experiential guide practice identified as the most important part of guide training.•Immediate verbal feedback from tutors valued more than written feedback.•Recommendations for guide education programs.

The amount of 8‐hydroxydeoxyguanosine (8‐OH‐dG) excreted in urine can be used not only as an indicator of DNA repair capacity, but also as a potential marker of oxidative DNA damage. To clarify the oxidation‐related factors, in consideration of cancer risk, this study investigated how urinary 8‐OH‐dG was associated with occupational and lifestyle factors in 372 healthy workers. The creatinine‐adjusted urinary 8‐OH‐dG level was significantly higher in male subjects, smokers and drinkers compared with their counterparts. There were significant positive correlations of the 8‐OH‐dG level with average number of working hours, involvement in work, average number of cigarettes smoked, average volume of alcohol consumed and serum cortisol level, and there were significant negative correlations of the 8‐OH‐dG level with body mass index (BMI) and consumption of soybean products, rice and light‐colored vegetables. Multiple regression analysis showed that average number of working hours and average number of cigarettes smoked were significant predictors of increased 8‐OH‐dG levels, whereas being female and BMI were significant predictors of decreased 8‐OH‐dG levels. Working hours, BMI and smoking were significant predictors of urinary 8‐OH‐dG in male subjects, whereas age and BMI were significant predictors in female subjects. We suggest that several occupational and lifestyle factors, particularly long working hours and cigarette smoking, are linked to the formation of 8‐OH‐dG in workers. (Cancer Sci 2005; 96: 600 – 606)

The internal thoracic artery is commonly used as a graft in coronary artery bypass grafting. In this study, we aimed to investigate whether papaverine prevents vasoconstriction caused by various vasospasm inducers, including 5-hydroxytriptamine or serotonin, in endothelium-denuded internal thoracic artery at concentrations as low as 1.25 mM used for radial arteries. Human internal thoracic artery tissue was obtained from patients (n=6) undergoing coronary artery bypass grafting. The organ bath technique was used to determine the inhibitory effects of papaverine on vasoconstriction induced by ergonovine, adenosine diphosphate, 5-hydroxytriptamine, noradrenaline, and angiotensin II in isolated endothelium-denuded internal thoracic artery. Moreover, the inhibitory effect of papaverine on collagen-stimulated human platelet aggregation was examined at the same concentration. Papaverine inhibited ergonovine-induced vasoconstriction in a concentration-dependent manner. Papaverine at concentrations > 30 μM not only blocked ergonovine-induced vasoconstriction but also induced vasodilation. Papaverine at 30 μM significantly suppressed the vasoconstriction induced by 5-hydroxytriptamine or noradrenaline and completely blocked that induced by adenosine diphosphate or angiotensin II. However, 100 μM papaverine completely blocked the vasoconstriction induced by adenosine diphosphate, 5-hydroxytriptamine, noradrenaline, and angiotensin II. Additionally, papaverine significantly inhibited collagen-stimulated human platelet aggregation in a concentration-dependent manner. Overall, 100 μM papaverine prevented vasoconstriction by various vasospasm inducers, such as 5-hydroxytriptamine, and significantly suppressed collagen-stimulated platelet aggregation. These results suggest that papaverine at 100 μM, which is 1/10th the concentration used for radial artery, is sufficient to prevent vasospasm in internal thoracic artery during coronary artery bypass grafting.

The urinary levels of 8‐hydroxydeoxyguanosine (8‐OH‐dG), a marker of oxidative DNA damage, of 318 healthy men aged 18‐58 were measured with high resolution by a newly developed automated high‐pressure liquid chromatography (HPLC) system coupled to an electrochemical detector (ECD). The mean 8‐OH‐dG level (μMg/g creatinine) was 4.12±1.73 (SD). An eleven‐fold inter‐individual variation was observed. The accuracy of the measurement estimated from the recovery of an added 8‐OH‐dG standard was 90‐98%. By univariate analysis, it was found that moderate physical exercise (P=0.0023) and high body mass index (BMI) (P=0.0032) reduced the 8‐OH‐dG level, while physical labor (P=0.0097), smoking (P=0.032), and low meat intake (less than once/ week) (P=0.041) increased its level. Based on a multi‐regression analysis of the log‐transformed values, moderate physical exercise (P=0.0039), high BMI (P=0.0099), and age (P=0.021) showed significant reducing effects on the 8‐OH‐dG level, while low meat intake (P=0.010), smoking (P=0.013), and day‐night shift work (P=0.044) increased its level. These results suggest that many types of life‐style factors that either generate or scavenge oxygen radicals may affect the level of oxidative DNA damage of each individual.

Disruption of apolipoprotein E (APOE) is responsible for age-dependent neurodegeneration and cognitive impairment. Elderly individuals are more sensitive than young individuals to the effects of ethanol (EtOH), particularly those affecting cognition. We investigated the role of APOE deficiency and EtOH exposure on age-dependent alterations in choline acetyltransferase (ChAT) and brain-derived neurotrophic factor (BDNF) mRNA and protein expression in the mouse hippocampus. Three-month-old (young) and 12-month-old (aged) ApoE-knockout (ApoE-KO) and wild-type (WT) mice were treated with saline or 2 g/kg EtOH, and the bilateral hippocampus was collected after 60 min for real-time PCR and western blotting analyses. ChAT (P < 0.01) and BDNF (P < 0.01) expression were significantly decreased in both young and aged saline- and EtOH-treated ApoE-KO mice versus young and aged saline- and EtOH-treated WT mice. Aged saline- and EtOH-treated ApoE-KO mice exhibited greater differences in ChAT and BDNF expression (P < 0.01) than young saline- and EtOH-treated ApoE-KO mice. Aged EtOH-treated WT mice also exhibited larger decreases in BDNF expression (P < 0.01)—but not in ChAT expression—than young EtOH-treated WT mice. EtOH decreased ChAT and BDNF expression in both young (P < 0.01) and aged (P < 0.01) ApoE-KO mice versus EtOH-free ApoE-KO mice of the same age. EtOH also decreased BDNF expression in aged (P < 0.01) WT mice versus EtOH-free aged WT mice. In summary, these results suggest that APOE deficiency and EtOH exposure cause age-dependent decreases in ChAT and BDNF in the hippocampus. Importantly, the decreases in ChAT and BDNF were greater in aged EtOH-treated mice, particularly those lacking APOE, raising the possibility that APOE-deficient individuals who consume alcohol may be at greater risk of memory deficit.

Perinatal transmission plays a critical role in the spread of bovine leukemia virus (BLV) infection in cattle herds. In the Holstein breed, we previously identified BLV resistant and susceptible bovine leukocyte antigen (BoLA)-DRB3 alleles, including BoLA-DRB3*009:02 and *014:01:01 with a low BLV proviral load (PVL), and *015:01 and *012:01 with a high PVL. Here, we evaluated the perinatal BLV transmission risk in dams with different BoLA-DRB3 alleles. BoLA-DRB3 alleles of 120 dam-calf pairs from five dairy farms in Japan were identified; their PVL was quantified using the BLV-Coordination of Common Motifs (CoCoMo)-qPCR-2 assay. Ninety-six dams were BLV-positive, and 29 gave birth to BLV-infected calves. Perinatal transmission frequency was 19% in dams with resistant alleles suppressed to a low PVL level, and 38% and 25% in dams with susceptible and neutral alleles that maintained high PVL levels, respectively. Notably, all calves with resistant alleles were BLV free, whereas 30% of calves with susceptible genes were infected. Thus, vertical transmission risk was extremely lower for dams and calves with resistant alleles compared to those with susceptible alleles. Our results can inform the development of effective BLV eradication programs under field conditions by providing necessary data to allow for optimal selection of dams for breeding.

Objective: The proportion of elderly individuals (≥65 years old) in Japan has markedly increased. However, the definition of senility in Japan is controversial. The aim of the present study was to investigate changes and variations in the number of deaths due to senility in Japan. Methods: Information on the number of deaths due to senility between 1995 and 2018 as well as other major causes of death was obtained from the Statistics Bureau of Japan official website. Changes and variations in the number of deaths due to senility were compared with other major causes of death in Japan. The relationships between the number of deaths due to senility and socioeconomic factors were also examined in an ecological study. Results: The number of deaths due to senility was 35.7 ± 23.2/one hundred thousand people/year during the observation period and has continued to increase. A change point was identified in 2004 by a Jointpoint regression analysis. Variations in the number of deaths due to senility, which were evaluated by a coefficient of variation, were significantly greater than those due to other major causes of death, i.e., malignant neoplasm, heart diseases, cerebrovascular diseases, and pneumonia. The number of elderly individuals (≥65 years old) (%) and medical bills per elderly subject (≥75 years old) correlated with the number of deaths due to senility. Conclusion: The number of deaths due to senility has been increasing, particularly since 2004. However, variations in the number of deaths due to senility were observed among all prefectures in Japan.

Despite the promising effectiveness of the coronavirus disease 2019 vaccination using an mRNA vaccine, the short efficacy duration and some poor responses to the vaccination remain major concerns. We aimed to clarify the monthly kinetics of the anti-SARS-CoV-2 spike receptor-binding domain antibody response after two doses of the BNT162b2 vaccine in a Japanese population. A chemiluminescent enzyme immunoassay (CLIA) and an enzyme-linked immunosorbent assay were used to measure the antibody levels in 81 Japanese adults (age, <65 years). The antibody levels increased 10-fold at 2–3 weeks following the second dose of BNT162b2 and declined thereafter to approximately 50%, 20%, and 10% of the peak levels at 2, 3, and 6 months, respectively. To compare the antibody titers among different groups, older adults (age, >65 years; n = 38) and patients with systemic lupus erythematosus (SLE, n = 14) were also investigated. A decline in the mean relative antibody titers was observed in older men compared with younger men and in patients with SLE compared with individuals aged <65 years. Although the antibody levels increased drastically following two BNT162b2 doses, they then declined rapidly. Furthermore, poor responders to the vaccination were observed. Repeated vaccinations are required to maintain high antibody levels.