Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years

Development of HVJ-Liposome Mediated Gene Therapy Using HSV-Thymidine Kinase Gene for Hepatocellular Carcinoma

The suicide gene therapy for hepatocellular carcinoma (HCC) has given some promise, but the toxicity of adenovirusmediated gene delivery using the cytomegalovirus promoter (CMV) region linked to herpes simplex virus thymidine kinase gene (HSV-TK) in combination with ganciclovir (GCV) therapy was reported. In this study, to improve the technical issue of conventional gene therapy, we examined the usefulness of hemagglutinating virus of Japan (HVJ)-anionic-liposomemediated CMV-TK/GCV as an introductory target gene and development the selective application of alpha-fetoprotein (AFP) enhancer/promoter or heat shock protein (HSP) promoter for gene therapy. By the luciferase reporter gene assay, both HVJ-liposome transfection and the transcriptional activation of AFP enhancer/promoter or that of the HSP promoter by heat treatment were found to be quite effective in vivo and in vivo/in vitro models respectively. The toxicity of HVJ-anionic liposome-mediated gene therapy was smaller than that of adenovirus-driven approach as judged by histopathological examination of experimental animals\u27 liver and GPT blood test. Thus, the HVJ-liposome-mediated AFP-TK/GCV or HSPTK/ GCV technique may be a potent and useful strategy of the gene therapy of HCC

Genetic Analysis of Cardiacβ Myosin Heavy Chain(MHC)Gene in Seven Families with Hypertrophic Cardiomyopathy in Japan

The purpose of this study was to identify the presence of either mutation or polymorphism in the cardiac β myosin heavy chain (MHC) gene of the Japanese who had familial hypertrophic cardiomyopathy (FHCM). We analyzed exons 3-25 of the cardiac MHC gene in seven unrelated Japanese families (17 affected and 10 unaffected individual with HCM), using the polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. Our study showed that affected members of one family (proband; I.I.) had an identical pattern of aberrantly migrating band of exon 21.Similarly we found polymorphism and probable point mutation located on exon 3 of one patient with sporadic HCM (Pt;T.M.). Both proband;I. I. and Pt; T.M., developed lethal congestive heart failure with left ventricular (LV) dilatation as confirmed by autopsy. This suggest that PCR-SSCP analysis is an useful tool for clinical screening of HCM

Cellular Mechanism Underlying Highly-Active or Antiretroviral Therapy-Induced Lipodystrophy: Atazanavir, a Protease Inhibitor, Compromises Adipogenic Conversion of Adipose-Derived Stem/Progenitor Cells through Accelerating ER Stress-Mediated Cell Death in Differentiating Adipocytes

Lipodystrophy is a common complication in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) or antiretroviral therapy (ART). Previous studies demonstrated that endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR) is involved in lipodystrophy; however, the detailed mechanism has not been fully described in human adipogenic cell lineage. We utilized adipose tissue-derived stem cells (ADSCs) obtained from human subcutaneous adipose tissue, and atazanavir (ATV), a protease inhibitor (PI), was administered to ADSCs and ADSCs undergoing adipogenic conversion. Marked repression of adipogenic differentiation was observed when ATV was administered during 10 days of ADSC culture in adipogenic differentiation medium. Although ATV had no effect on ADSCs, it significantly induced apoptosis in differentiating adipocytes. ATV treatment also caused the punctate appearance of CCAAT-enhancer-binding (C/EBP) protein homologous protein (CHOP), and altered expression of CHOP and GRP78/Bip, which are the representation of ER stress, only in differentiating adipocytes. Administration of UPR inhibitors restored adipogenic differentiation, indicating that ER stress-mediated UPR was induced in differentiating adipocytes in the presence of ATV. We also observed autophagy, which was potentiated in differentiating adipocytes by ATV treatment. Thus, adipogenic cell atrophy leads to ATV-induced lipodystrophy, which is mediated by ER stress-mediated UPR and accelerated autophagy, both of which would cause adipogenic apoptosis. As our study demonstrated for the first time that ADSCs are unsusceptible to ATV and its deleterious effects are limited to the differentiating adipocytes, responsible target(s) for ATV-induced lipodystrophy may be protease(s) processing adipogenesis-specific protein(s)

The latest update on individual external doses in an early stage after the Fukushima nuclear accident

Following the Fukushima Daiichi Nuclear Power Plant accident, a survey for estimating individual external doses for the first 4 months after the accident was started, and it remains ongoing. Since the authors' previous paper, 44 605 new dose estimates have been made. The new dose estimates increase the number of dose estimates to 465 999 and are reported in this note. Since the previous paper, most of the recently collected responses have been gotten through public relations activities to encourage responses across the prefecture. Thus, recent respondents might be biased ('selection bias'). Also, the dose estimates were based on self-administered responses about personal behaviour, which relied on memories of residents. In this respect, incorrect behaviour records possibly resulted as memories have faded over time ('recall bias'). However, the effects of these biases on dose distribution on a whole-prefecture basis seemed to be small

Age dependence of individual external doses in an early stage after the Fukushima nuclear accident

Individual external doses for the first 4 months after the Fukushima accident have been estimated by the 'Basic Survey' of the Fukushima Health Management Survey. On the other hand, the UNSCEAR 2013 report presented the first-year effective dose due to external radiation for each municipality in nonevacuated areas of Fukushima Prefecture. In this study, the doses estimated by the Basic Survey were averaged for each of three age groups (infants, 0-5 y; children, 6-15 y; and adults, >16 y), in accordance with the categories adopted by the UNSCEAR report. The average dose ratios (infants/adults and children/adults) obtained from the Basic Survey were 1.08 and 1.06 for nonevacuated areas, respectively. These were smaller than the estimation by the UNSCEAR report (1.7 and 1.4, respectively). Three factors (body size factor, location factor and occupancy factor) were discussed and the location and occupancy factors were likely to be reasons for the difference

Influence of post-disaster evacuation on incidence of hyperuricemia in residents of Fukushima Prefecture: the Fukushima Health Management Survey

Aim: After the Great East Japan Earthquake, over 160, 000 residents in Fukushima Prefecture were forced to evacuate the area around the Fukushima Daiichi power plant following nuclear accident there. Health problems in these evacuees have since become a major issue. We have examined the association between evacuation and incidence of hyperuricemia among residents in Fukushima. Methods: We conducted a cohort study of residents aged 40–90 years without hyperuricemia at the time of the Fukushima disaster. Among 8173 residents who met the inclusion criteria before the disaster, 4789 residents (men: 1971, women: 2818; follow-up duration: 1.38 years; and follow-up rate: 58.6%) remained available for follow-up examinations at the end of March 2013. The main endpoint was incidence of hyperuricemia, defined by the Japanese committee guidelines, using local health data from before and after the disaster. We divided participants by evacuation status and compared outcomes between groups. Using a logistic regression model, we estimated the odds ratio for incidence of hyperuricemia, adjusting for potential confounders, age, gender, waist circumference, physical activity, and alcohol consumption. Results: Incidence of hyperuricemia was higher in evacuees (men 10.1%; women 1.1%) than in non-evacuees (men 7.4%, women 1.0%). Evacuees had higher body mass index, waist circumference, triglycerides, LDL-cholesterol, fasting plasma glucose, HbA1c, and lower HDL-cholesterol after the disaster than non-evacuees. We found that evacuation was associated with incidence of hyperuricemia (adjusted odds ratio: 1.38; 95% confidence interval: 1.03-1.86). Conclusion: This is the first study to demonstrate an association between evacuation after a disaster and increased incidence of hyperuricemia

Mental health conditions in Korean atomic bomb survivors: a survey in Seoul

More than 60 years have elapsed since the atomic bombings to Hiroshima and Nagasaki, and since all of the atomic bomb survivors have become old, the importance of caring their mental health has become increasing in Japan. Although approximately 70% of overseas atomic bomb are living in Korea, there have been quite few studies on their mental health. The objectives of the present study were to elucidate whether the mental health conditions of atomic bomb survivor in Korea are similar to those in Japan. The subjects were 181 Korean atomic bomb survivors living in Korea (cases) and 209 outpatients of a hospital in Seoul who were not exposed to atomic bombs (controls). Interviewers administered them at the hospital a questionnaire with Impact of Event Scale-Revised, General Health Questionnaire 12 (GHQ-12), Korean version of short form Geriatric Depression Scale and the K scale of the Minnesota Multiphasic Personality Inventory. Excluding subjects with incomplete responses we analyzed 162 cases and 189 controls. The proportion of subjects with high score of GHQ-12 ( 4) was significantly higher in cases (78/162 or 48.1%) than in controls (42/189 or 22.2%) (p < 0.0001, Fisher\u27s exact test). The present results, though preliminary, indicate that atomic bomb survivors in Korea have also mental health problems similar to those observed in Japanese atomic bomb survivors, indicating the necessity of a larger study

Evacuation after the Fukushima Daiichi Nuclear Power Plant Accident Is a Cause of Diabetes: Results from the Fukushima Health Management Survey

The Great East Japan Earthquake and Fukushima Daiichi nuclear disaster in 2011 forced the evacuation of a large number of residents and created changes in the lifestyle of the evacuees. These changes may have affected the evacuees\u27 glucose metabolism, thereby leading to an increase in the incidence of diabetes. This study included Japanese men and women who were living near the Fukushima Daiichi Nuclear Power Plant in Fukushima prefecture before the disaster. Subjects subsequently underwent annual health checkups with a focus on metabolic syndromes, which were conducted under the Health Care Insurers. Using the Comprehensive Health Check survey, we analyzed changes in the glucose metabolism before and after the disaster. A total of 27,486 subjects underwent follow-up examinations after the disaster, with a mean follow-up period of 1.6 years. After the disaster, the prevalence of diabetes increased significantly, and we observed that the incidence of diabetes was significantly greater among evacuees than among nonevacuees. Furthermore, multivariate logistic regression analysis revealed that evacuation was significantly associated with the incidence of diabetes. In conclusion, this is the first study to demonstrate that evacuation is associated with the incidence of diabetes. This information may be used to guide follow-up recommendations for evacuees