Development of an application tool to support returnees in Fukushima.

To promote radiation protection and health promotion among returning residents (returnees) in coastal areas of Fukushima, eHealth principles were used to develop a new application tool (app) that can record radiation exposure and health status while providing comprehensive support to returnees. Intended users are returnees and health and welfare workers. After assessing their needs, a flowchart and prototype for operational logic were created using commercially available software tools. Professional developers will focus on improving the user interface and ensuring data security. The finished app will be compatible with mobile telephones and tablets. Utility and ease of use are paramount to serve returnees of all ages effectively.

Health issues today in affected areas near Fukushima Daiichi nuclear power plant.

Due to vigorous efforts to decontaminate the environment following the accident at Fukushima Daiichi nuclear power plant, the size of the difficult-to-return zone has reduced significantly and people have started returning to their homes. As the population has increased, medical needs have ensued. A marked increase in traffic as well as decontamination and reconstruction projects has led to an increase in the number of road traffic and occupational accidents. Acceleration of population aging has resulted in an increased number of elderly residents with multiple medical problems. Uncontrolled/untreated medical problems among middle-aged to older workers have made them susceptible to deterioration of health conditions. Insufficient social support for elderly people living alone has resulted in delayed access to medical care. Early intervention and the prevention of health deterioration are instrumental. When responding to medical needs, proactive approaches, including home visits for elderly patients and health promotion, have been implemented. Human resource development is crucial to ensure the sustainability of these activities.

Medical and health surveillance in postaccident recovery: experience after Fukushima.

The accident at Fukushima Daiichi nuclear power plant occurred following the huge tsunami and earthquake of 11 March 2011. After the accident, there was considerable uncertainty and concern about the health effects of radiation. In this difficult situation, emergency responses, including large-scale evacuation, were implemented. The Fukushima Health Management Survey (FHMS) was initiated 3 months after the accident. The primary purposes of FHMS were to monitor the long-term health of residents, promote their well-being, and monitor any health effects related to long-term, low-dose radiation exposure. Despite the severity of the Fukushima accident and the huge impact of the natural disaster, radiation exposure of the public was very low. However, there were other serious health problems, including deaths during evacuation, increased mortality among displaced elderly people, mental health and lifestyle-related health problems, and social issues after the accident. The Nuclear Emergency Situations - Improvement of Medical and Health Surveillance (SHAMISEN) project, funded by the Open Project For European Radiation Research Area, aimed to develop recommendations for medical and health surveillance of populations affected by previous and future radiation accidents. This paper briefly introduces the points that have been learned from the Fukushima accident from the perspective of SHAMISEN recommendations.

Emergency Responses and Health Consequences after the Fukushima Accident; Evacuation and Relocation.

The Fukushima accident was a compounding disaster following the strong earthquake and huge tsunami. The direct health effects of radiation were relatively well controlled considering the severity of the accident, not only among emergency workers but also residents. Other serious health issues include deaths during evacuation, collapse of the radiation emergency medical system, increased mortality among displaced elderly people and public healthcare issues in Fukushima residents. The Fukushima mental health and lifestyle survey disclosed that the Fukushima accident caused severe psychological distress in the residents from evacuation zones. In addition to psychiatric and mental health problems, there are lifestyle-related problems such as an increase proportion of those overweight, an increased prevalence of hypertension, diabetes mellitus and dyslipidaemia and changes in health-related behaviours among evacuees; all of which may lead to an increased cardiovascular disease risk in the future. The effects of a major nuclear accident on societies are diverse and enduring. The countermeasures should include disaster management, long-term general public health services, mental and psychological care, behavioural and societal support, in addition to efforts to mitigate the health effects attributable to radiation.

Identification and quantification of viable Bifidobacterium breve strain Yakult in human faeces by using strain-specific primers and propidium monoazide.

AIMS: To develop a quick and accurate PCR-based method to evaluate viable Bifidobacterium breve strain Yakult (BbrY) in human faeces. METHODS AND RESULTS: The number of BbrY in faeces was detected by using strain-specific quantitative real-time PCR (qPCR) derived from a randomly amplified polymorphic DNA analysis. And using propidium monoazide (PMA) treatment, which combined a DNA-intercalating dye for covalently linking DNA in dead cells and photoactivation, only viable BbrY in the faeces highly and significantly correlated with the number of viable BbrY added to faecal samples within the range of 10(5) -10(9) cells per g of faeces was enumerated. After 11 healthy subjects ingested 10·7 log CFU of BbrY daily for 10 days, 6·9 (± 1·5) log CFU g(-1) [mean (± SD)] of BbrY was detected in faeces by using strain-specific transgalactosylated oligosaccharide-carbenicillin (T-CBPC) selective agar medium. Viable BbrY detected by qPCR with PMA treatment was 7·5 (± 1·0) log cells per g and the total number (viable and dead) of BbrY detected by qPCR without PMA treatment was 8·1 (± 0·8) log cells per g. CONCLUSIONS: Strain-specific qPCR with PMA treatment evaluated viable BbrY in faeces quickly and accurately. SIGNIFICANCE AND IMPACT OF THE STUDY: Combination of strain-specific qPCR and PMA treatment is useful for evaluating viable probiotics and its availability in humans.

Tryptophan aspartate-containing coat protein (CORO1A) suppresses Toll-like receptor signalling in Mycobacterium leprae infection.

Mycobacterium leprae is an intracellular pathogen that survives within the phagosome of host macrophages. Several host factors are involved in producing tolerance, while others are responsible for killing the mycobacterium. Tryptophan aspartate-containing coat protein (TACO; also known as CORO1A or coronin-1) inhibits the phagosome maturation that allows intracellular parasitization. In addition, the Toll-like receptor (TLR) activates the innate immune response. Both CORO1A and TLR-2 co-localize on the phagosomal membrane in the dermal lesions of patients with lepromatous leprosy. Therefore, we hypothesized that CORO1A and TLR-2 might interact functionally. This hypothesis was tested by investigating the effect of CORO1A in TLR-2-mediated signalling and, inversely, the effect of TLR-2-mediated signalling on CORO1A expression. We found that CORO1A suppresses TLR-mediated signal activation in human macrophages, and that TLR2-mediated activation of the innate immune response resulted in suppression of CORO1A expression. However, M. leprae infection inhibited the TLR-2-mediated CORO1A suppression and nuclear factor-kappaB activation. These results suggest that the balance between TLR-2-mediated signalling and CORO1A expression will be key in determining the fate of M. leprae following infection.

Circulating KL-6/MUC1 as an independent predictor for disseminated intravascular coagulation in acute respiratory distress syndrome.

OBJECTIVES: Acute respiratory distress syndrome (ARDS) patients show high levels of circulating mucin including KL-6/MUC1 (soluble MUC1 mucin). Because cancer mucin can bind vascular endothelial cells and platelets via selectins, mucin-selectin interactions are reported to trigger platelet aggregation and intravascular coagulation. Therefore, we hypothesized that KL-6/MUC1 is involved in the pathogenesis of disseminated intravascular coagulation (DIC) in ARDS. The aim of the current study is to evaluate the association between circulating KL-6/MUC1 and DIC in ARDS patients. DESIGN: Observational study with structured follow-up. SETTING: Intensive care unit in Hiroshima University Hospital. SUBJECTS: Fifty-six newly diagnosed patients with ARDS. INTERVENTIONS: Circulating levels of KL-6/MUC1 were measured during diagnosis and serially measured during the clinical course along with indices of respiratory failure, inflammation, coagulation and fibrinolysis and multiple organ dysfunction. RESULTS: Acute respiratory distress syndrome patients complicated with DIC showed significantly higher levels of serum KL-6/MUC1 than patients without DIC during the clinical course. Amongst the parameters analysed at diagnosis of ARDS, KL-6/MUC1 was an independent predictor for DIC complication. The baseline level of circulating KL-6/MUC1 at diagnosis of ARDS was significantly correlated with an increased DIC score following ARDS diagnosis. Using an optimum cutoff level of KL-6/MUC1 obtained by a receiver operating characteristic curve, the sensitivity and specificity for predicting future DIC development in ARDS patients were 88.9% and 55.3%, respectively. CONCLUSIONS: These results suggest that KL-6/MUC1 is associated with DIC development in ARDS patients. Elevated levels of KL-6/MUC1 at diagnosis could be a predictor of DIC complication in ARDS.

[Mitral valve disease in elderly patients].

It seems that mitral valve surgery in patients older than 80 years increase against the background of the aging society. Basically, there are not particular differences between elderly patients and younger patients in procedures for diagnosis and operative indication in mitral valve diseases. However, cardiac surgery for patients older than 80 years has been reported to have high mortality rate. Therefore, it is necessary that we should evaluate and treat complications of important organs such as brain/coronary artery/lungs/liver/kidney, adequately. Our mortality rate of the whole mitral valve operations was 2.4% and that of patients older than 75 years was 7.9%. This result compares favorably with those reported from other institutions. However, when we perform mitral valve operations for patients older than 80 years, it is necessary to investigate activities of daily living and quality of life before and after the operation.

Impairment of insulin-stimulated GLUT4 translocation in skeletal muscle and adipose tissue in the Tsumura Suzuki obese diabetic mouse: a new genetic animal model of type 2 diabetes.

BACKGROUND: In skeletal muscle and adipocytes, insulin-stimulated glucose transport has been known to occur through the translocation of glucose transporter (GLUT) 4 from the intracellular pool to the plasma membrane. The Tsumura Suzuki obese diabetic (TSOD) mouse, a new genetic animal model of type 2 diabetes, develops moderate degrees of obesity and diabetes that are especially apparent in animals more than 11 weeks old. A defect in insulin stimulation of GLUT4 translocation also contributes to the characteristics of type 2 diabetes. OBJECTIVE: To characterize this mouse further, we examined the alteration in insulin-stimulated GLUT4 translocation in the skeletal muscle and adipose tissue. METHODS: For glucose and insulin tolerance tests, the mice were given glucose or insulin and blood samples were collected. After isolation of low-density microsomal membrane and plasma membrane from skeletal muscle and adipose tissue, insulin-stimulated translocation of GLUT4 in these TSOD mice was examined by Western blot. RESULTS AND CONCLUSIONS: TSOD mice showed a significant increase in blood glucose after the glucose load, and exhibited a significantly attenuated decrease in blood glucose concentrations after administration of insulin, compared with that in control Tsumura Suzuki non-obese (TSNO) mice. The insulin-stimulated translocation of GLUT4 from low-density microsomal membranes to plasma membrane was significantly reduced in both skeletal muscle and adipose tissue of TSOD mice. These results indicate that the reduced insulin sensitivity in diabetic TSOD mice is presumably due, at least in part, to the impaired GLUT4 translocation by insulin in both skeletal muscle and adipocytes.

Tumor-specific responses in lymph nodes draining murine sarcomas are concentrated in cells expressing P-selectin binding sites.

Tumor-draining lymph node (TDLN) cells develop substantial antitumor activity after activation on immobilized alphaCD3 and culture in low-dose IL-2. This study found that the minor subset of TDLN T cells expressing binding sites for the adhesion receptor P-selectin (Plig(high) T cells) produced T lymphoblasts with the most tumor-specific IFN-gamma synthesis in vitro and antitumor activity following adoptive transfer in vivo. The Plig(high) T cells constituted <25% of the cells with the phenotype of recently activated cells including high levels of CD69, CD44, or CD25, and low levels of CD62L. The cultured Plig(high) TDLN were 10- to 20-fold more active against established pulmonary micrometastases than cultured unfractionated TDLN, and >30-fold more active than cultured TDLN cells depleted of the Plig(high) fraction before expansion (Plig(low) cells). Tumor-specific IFN-gamma synthesis in vitro paralleled the antitumor activities of the cultured fractions in vivo, implying that increased Tc1 and Th1 effector functions contributed to the tumor suppression. Neither nonspecific interaction with the P-selectin chimera used for sorting nor endogenous costimulatory activity in the Plig(high) fraction accounted for the marked increase in antitumor activities after culture. The cultured Plig(high) fraction contained a variety of potential effector cells; however, the CD8 and CD4 subsets of alphabeta T cells accounted for 95-97% of its antitumor activity. The authors propose that P-selectin sorting increased antitumor activities by concentrating Tc1 and Th1 pre-effector/effector cells before culture.

Antidiabetic activity of the rhizoma of Anemarrhena asphodeloides and active components, mangiferin and its glucoside.

The antidiabetic activity of the rhizoma of Anemarrhena asphodeloides was investigated in KK-Ay mice, an animal model of genetic type 2 diabetes. The water extract of the rhizoma (AA) (90 mg/kg) reduced blood glucose levels from 570 +/- 29 to 401 +/- 59 mg/dl 7 h after oral administration (p<0.05) and also tended to reduce serum insulin levels in KK-Ay mice. AA-treated KK-Ay mice had significantly reduced blood glucose levels in an insulin tolerance test. Based on these results, the antidiabetic mechanism of AA may be due to decreased insulin resistance. In addition, the active components of AA were confirmed to be mangiferin and its glucoside.

The suppressive effect of mangiferin with exercise on blood lipids in type 2 diabetes.

The effect of mangiferin (MF) with exercise on bood lipids was studied in KK-Ay mice, an animal model of type 2 diabetes. MF (30 mg/kg) reduced the blood cholesterol (p<0.05) and triglyceride level (p<0.01) of KK-Ay mice with exercise 2 weeks after oral administration when compared with the control group. Diabetes also often has elevated lipid levels. Therefore, it may be that MF has beneficial effects on hyperlipidemia in type 2 diabetes.

[Education of basic/advanced life support and emergency medicine for anesthesiologists: a survey of chairpersons at university department and newly board certified anesthesiologists].

To determine how the education of basic life support (BLS)/advanced cardiac life support (ACLS) and emergency medicine for anesthesiologists is conducted, we performed a survey of chairpersons at university departments and newly board certified anesthesiologists in 1999. Basic and advanced life support courses for residents were provided in more than half of the anesthesiology departments that responded to this survey. However, approximately only 10% of the respondents had regular BLS/ACLS courses for residents. On the other hand, more than 80% of respondents considered a rotation in emergency medicine desirable as a part of anesthesia training. To improve the resuscitation skills of anesthesiologists, an urgent need to establish regular BLS/ALS courses and educational programs in emergency medicine in anesthesia training does exist.

Characterization of bovine angiogenin-1 and lactogenin-like protein as glycyrrhizin-binding proteins and their in vitro phosphorylation by C-kinase.

Angiogenin-1 (p15, an angiogenesis inducer with RNase activity) and lactogenin-like protein (p17) isolated from partially purified bovine lactoferrin (bLF) preparations were characterized as glycyrrhizin (GL)-binding proteins (gbPs). As expected, bLF-affinity column chromatography confirmed these two gbPs to be bLF-binding proteins. These two purified gbPs exhibited RNase activities when incubated with poly(C) as a substrate. Both GL and glycyrrhetinic acid (GA) at 100 microM significantly inhibited RNase activities of these two gbPs, both of which functioned as phosphate acceptors of C-kinase in vitro. Phosphorylation of p15 and p17 by C-kinase was inhibited by GA in a dose-dependent manner with the 50% inhibition dose (ID50) of approx. 10 microM, whereas GL required a relatively high dose (300 microM) to inhibit significantly it. A GA derivative (oGA, ID50=approx. 0.3 microM) was found to be a potent inhibitor of the C-kinase-mediated phosphorylation of these two gbPs in vitro. In addition, a possible physiological significance of C-kinase on the physiological interaction between bLF and two bLF-binding proteins (p15 and p17) is noted.

Antidiabetic activity of a xanthone compound, mangiferin.

Mangiferin (MF) isolated from Anemarrhena asphodeloides Bunge rhizome, was tested for antidiabetic activity in KK-Ay mice, an animal model of type-2 diabetes. MF lowered the blood glucose level of KK-Ay mice 3 weeks after oral administration (p < 0.01). However, no effect on the blood glucose level in normal mice was seen, indicating that MF could be useful in treating type-2 diabetes. In addition, MF improved hyperinsulinemia and, on insulin tolerance test, reduced blood glucose levels of KK-Ay mice. From these findings, it seems likely that MF exerts its antidiabetic activity by decreasing insulin resistance.

The efficacy of esophageal detector devices in verifying tracheal tube placement: a randomized cross-over study of out-of-hospital cardiac arrest patients.

We performed this prospective study to evaluate the efficacy of esophageal detector devices (EDDs), both the bulb and the syringe-type, to indicate positioning of endotracheal tubes (ETTs) in out-of-hospital cardiac arrest patients. Forty-eight adult patients with out-of-hospital cardiac arrest were enrolled. Immediately after tracheal intubation and ETT cuff inflation in the emergency department, the patients were allocated randomly to two cross-over groups. In Group 1 (n = 24), patients underwent a bulb test and a syringe test in sequence. In Group 2 (n = 24), patients underwent a syringe test and a bulb test in sequence. End-tidal carbon dioxide (ETCO(2)) was also monitored. In 56 attempts at tracheal intubation, the bulb, the syringe, and ETCO(2) indicated all eight esophageal intubations. In 48 tracheal intubations, the bulb test correctly indicated 34 tracheal intubations (sensitivity, 70.8%). The syringe test identified 35 tracheal intubations (sensitivity, 72.9%). The results of both tests agreed in 33 tracheal intubations. ETCO(2) was detected in 31 tracheal intubations (sensitivity, 64.6%). No statistical difference was found among the tests. EDDs were less sensitive in detecting tracheal intubation for out-of-hospital cardiac arrest patients. Therefore, proper clinical judgment in conjunction with these devices should be used to confirm ETT placement in these difficult situations.

Antitumor reactivity of lymph node cells primed in vivo with dendritic cell-based vaccines.

Tumor lysate-pulsed dendritic cells were used to generate nodal effector T cells in the murine MCA 205 tumor model. Dendritic cells were derived from bone marrow and cultured in granulocyte-macrophage colony-stimulating factor/interleukin 4 before pulsation with tumor lysate. Multiple subcutaneous administrations of tumor lysate-pulsed dendritic cells (TP-DCs) resulted in an approximately eightfold hypertrophy of the vaccine draining nodes, with an increased influx of dendritic (CD11c+/CD80+) cells and B (B220+) cells. The vaccine-primed lymph node (VPLN) cells were secondarily activated with anti-CD3/interleukin 2 and exhibited specific interferon-gamma release to tumor antigen. The adoptive transfer of TP-DC VPLN cells resulted in regression of established 3-day pulmonary metastases. The antitumor reactivity of TP-DC VPLN cells was comparable to anti-CD3/interleukin 2 activated tumor-draining lymph node cells. However, the admixture of keyhole limpet hemocyanin (KLH) with tumor lysate during pulsation of dendritic cells significantly enhanced the induction of tumor-reactive VPLN cells. Tumor lysate-pulsed dendritic cells can be used as a strategy to generate effector T cells for adoptive immunotherapy.

Removal and decomposition of malodorants by using titanium dioxide photocatalyst supported on fiber activated carbon.

Effective and compact deodorization systems have been required for the measure of small-scale emission sources of offensive odors usually found in urban areas. We have developed a sheet material with titanium dioxide (TiO2) photocatalyst supported on fiber activated carbon (FAC) for a compact deodorization system. In the deodorization system using the TiO2/FAC sheet and a ultraviolet lamp, malodorants can be collected on the TiO2/FAC sheet by adsorption and then decomposed by photocatalysis with UV-irradiation. In this study, we obtained basic information about the removal and the decomposition of malodorants in the photocatalytic deodorization system using the TiO2/FAC sheet. The malodorants used in this study were methyl mercaptan, ammonia, and hydrogen sulfide. In addition, two kinds of light sources, a black light bulb (BLB; dominant wavelength: 365 nm) and an ultraviolet germicidal lamp (UV2; dominant wavelength: 254 nm) were used to analyze the effect on removal and decomposition characteristics by different dominant wavelengths. The removal rates of malodorants from the gas phase were determined in the deodorization system in the presence or absence of the TiO2/FAC sheet and UV-irradiation in order to study each removal effect due to adsorption onto the TiO2/FAC sheet, direct photolysis by UV-irradiation, and photocatalytic decomposition. The effect of adsorption onto the TiO2 /FAC sheet was pronounced in this batch-type experiment. The effect of photocatalysis was observed from the removal rates of methyl mercaptan. The percent oxidation of ammonia to nitrate and that of methyl mercaptan to sulfate were examined by determining products, i.e. nitrate and sulfate ions, with purified water after the reaction. The formation of nitrate or sulfate was not observed without UV-irradiation using the BLB, while the reactions progressed in the presence of the TiO2/FAC sheet. When the UV2 lamp was used, the oxidation of methyl mercaptan to sulfate occurred without the TiO2/FAC sheet. This suggests that the decomposition characteristics of malodorants were dependent on the wavelength of the light source.

Use of gene gun for genetic immunotherapy : in vitro and in vivo methods.

A major thrust in the application of gene transfer technology for cancer therapy has been the modulation of the immune response. There has been a veritable explosion of information regarding the components of the immune response that are required to generate a meaningful cellular response to tumorassociated antigens (TAAs) capable of eliciting rejection of established tumor. Many of the preclinical and clinical immunogenetic studies have focused on melanoma. Historically, melanoma has been an immunoresponsive tumor for which several melanoma TAAs have been identified.

Effect of epinephrine on GLUT2 protein content in mouse liver.

The intraperitoneal administration of epinephrine (EP) to mice caused a significant increase in the blood glucose level and a significant decrease in the liver glycogen content 1 h after its administration at 0.6 mg/kg (blood glucose; p < 0.01, liver glycogen; p < 0.01). The liver type glucose transporter (GLUT2) mRNA expression and protein content from mouse liver significantly increased in the intraperitoneally EP-treated mice when compared to that in normal mice (mRNA; p < 0.01, protein; p < 0.01). These results suggest that the hyperglycemic effect of EP is due, at least in part, to the increase of GLUT2 protein synthesis.