Association between evacuation and becoming overweight after the Great East Japan Earthquake: a 7-year follow-up of the Fukushima Health Management Survey.

OBJECTIVES: Disaster evacuation increases the risk of becoming overweight or obese owing to lifestyle changes and psychosocial factors. This study evaluated the effect of evacuation on becoming overweight during a 7-year follow-up among residents of Fukushima Prefecture during the Great East Japan Earthquake. STUDY DESIGN: This was a prospective cohort study. METHODS: We analysed data collected from 18,977 non-overweight Japanese participants who completed the 'Comprehensive Health Checkup Program' and 'Mental Health and Lifestyle Survey', as part of the Fukushima Health Management Survey, between July 2011 and November 2012. An evacuation was defined as the moving out of residents of municipalities designated as an evacuation zone by the government or having a self-reported experience of moving into shelters or temporary housing. Follow-up examinations were conducted in March 2018 to identify patients who became overweight. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using a Cox proportional hazards regression model. RESULTS: Among 15,875 participants (6091 men and 9784 women; mean age 63.0 ± 11.1 years) who received follow-up examination (mean follow-up, 4.29 years), 2042 (856 men and 1186 women) became overweight. Age-, baseline body mass index-, lifestyle-, and psychosocial status-adjusted HRs (95% CIs) for becoming overweight after evacuation were 1.44 (1.24-1.66) for men and 1.66 (1.47-1.89) for women. CONCLUSION: Evacuation was associated with the risk of becoming overweight 7 years after the disaster. Thus, maintaining physical activity, healthy diet, and sleep quality and removing barriers to healthy behaviour caused by disasters, including anxiety concerning radiation, may prevent this health risk among evacuees.

The KANNO blood group system.

The KANNO blood group system (International Society of Blood Transfusion [ISBT] 037) includes one high-prevalence antigen, KANNO1, across ethnic groups. Sporadic KANNO1- cases among East and South Asians are theoretically estimated by the DNA database library. Anti-KANNO1 has been found most often among Japanese women with current or prior pregnancy. Thus far, there are no reported cases of hemolytic transfusion reaction or hemolytic disease of the fetus and newborn due to anti-KANNO1.

Impact of prestorage leucoreduction of autologous whole blood on length of hospital stay with a subgroup analysis in bilateral hip arthroplasty.

BACKGROUND: Although prestorage leucoreduction (LR) of blood components for transfusion has gained favour around the world, evidence of its beneficial clinical effects is ambiguous. STUDY DESIGN AND METHODS: To reveal whether leucocytes and/or platelets in transfused blood are related to transfusion-related adverse effects, a prospective randomized crossover study was performed on patients who donated autologous blood prior to elective surgery. Among 1487 primary enrolees, a total of 192 patients undergoing two-stage, bilateral total hip arthroplasty were randomized to receive autologous blood that was either prestorage leucoreduced, or not, for the first procedure. For the second procedure, each patient was crossed over to receive alternatively processed autologous blood. Length of hospital stay served as a primary end-point, with perioperative infectious/thrombotic complications, pre- and postoperative laboratory values, and body temperature serving as secondary endpoints. RESULTS: No significant differences emerged between prestorage LR and non-LR cohorts in length of hospital stay, as well as perioperative infectious/thrombotic complications, postoperative body temperature and duration of fever. Postoperative laboratory values including white blood cell counts and C-reactive protein levels had no significant differences. CONCLUSION: This study could not prove any superiority of prestorage LR over non-LR for autologous whole blood among patients who underwent total hip arthroplasty.

T-cell-replete haploidentical stem cell transplantation is highly efficacious for relapsed and refractory childhood acute leukaemia.

BACKGROUND: Despite improvements in first-line therapies, the outcomes of relapsed or refractory childhood acute leukaemia that has not achieved complete remission after relapse, has relapsed after stem cell transplantation (SCT), has primary induction failure and has relapsed with a very unfavourable cytogenetic risk profile, are dismal. OBJECTIVES AND METHODS: We evaluated the feasibility and efficacy of T-cell-replete haploidentical peripheral blood stem cell transplantation (haplo-SCT) with low-dose anti-human thymocyte immunoglobulin (ATG), tacrolimus, methotrexate and prednisolone (PSL) in 14 paediatric patients with high-risk childhood acute leukaemia. RESULTS: All patients achieved complete engraftment. The median time to reaching an absolute neutrophil count of more than 0.5 × 10(9) L(-1) was 14 days. Acute graft-vs-host disease (aGVHD) of grades II-IV and III-IV developed in 10 (71%) and 2 (14%) patients, respectively. Treatment-related mortality and relapse occurred in one (7%) patient and six (43%) patients, respectively. Eleven patients were alive and seven of them were disease-free with a median follow-up of 36 months (range: 30-159 months). The probability of event-free survival after 2 years was 50%. CONCLUSION: These findings indicate that T-cell-replete haplo-SCT, with low-dose ATG and PSL, provides sustained remission with an acceptable risk of GVHD in paediatric patients with advanced haematologic malignancies.

Barriers and motivators to blood donation among university students in Japan: development of a measurement tool.

BACKGROUND AND OBJECTIVES: Despite growing demand for transfusion, the number of voluntary young blood donors has steadily decreased over recent years in Japan. This study aimed to develop an easy-to-use survey tool to assess barriers and motivators to blood donation among Japanese university students. MATERIALS AND METHODS: We conducted cross-sectional studies at two universities in Fukushima Prefecture, Japan, in December 2011 (Stage 1) and February 2012 (Stage 2) using self-administered questionnaires. A short list of motivators and barriers to blood donation was developed from the open-ended questions asked of 50 students in Stage 1. In the Stage 2, we asked 105 students how important these items were when they decided whether or not to donate blood. Items showing a significant difference between donors and non-donors were kept in the final list. RESULTS: Overall, 56% of the 100 participants analysed in Stage 2 were men, and ages ranged from 19 to 24 with a median of 20 years. Comparison of motivators and barriers between donors and non-donors revealed that only barrier item 8 ('Frightened by blood donation') showed a significant difference (P = 0·0006) in an expected direction and with a consistency between two universities. CONCLUSIONS: This study identified fear as being the most significant barrier to blood donation among Japanese university students, which could be used as a single convenient indicator to assess their readiness to donate. More academic and clinical efforts are needed to understand and address students' fear towards blood donation in order to increase the donor pool in Japan.

Maintenance of surface antigens and the absence of an apoptotic marker are observed during storage of granulocyte concentrates collected by bag separation method.

Granulocytes were collected by the bag separation method and stored in whole blood for up to 72h. We evaluated the expressions of various surface antigens: CD62L, CD11b, CD18, CD64, CD16b, and CD95. Apoptosis was assessed both by flow cytometry and by light microscopy. Expression levels of all the surface antigens were shown to be maintained during storage for up to 72h. Approximately 80% of granulocytes were annexin V negative until 72h after collection. The storage of granulocyte concentrates collected by the bag separation method may maintain granulocyte surface antigens and lack an apoptotic marker.

Non-D Rh antibodies appearing after apheresis platelet transfusion: stimulation by red cells or microparticles?

BACKGROUND: Apheresis platelets (APs) have gained favour over whole blood-derived platelets on the presumption that they are less likely to provoke alloimmunization to red-blood-cell antigens. CASE REPORTS: Non-D Rh antibodies appeared in three patients after apheresis platelet transfusion. Anti-C and anti-E arose in two female patients with previous antigen exposure. Both anti-c and anti-E arose in a male recipient with no prior transfusion history. MATERIALS AND METHODS: Fifty APs were analysed for residual RBCs and RBC-derived microparticles, using samples obtained from a local blood centre. Cells and microparticles were quantified with a flow cytometry gating scheme, using PE-labelled anti-CD235a (glycophorin A) and FITC-labelled anti-CD41a (platelet gp IIb/IIIa) to distinguish lineage. RESULTS: Apheresis platelets were found to contain a mean of 7·5×10(6) (95% C.I. [6·3-8·5×10(6) ]) RBCs on one manufacturer's device and 5·2×10(6) (95% C.I. [4·0-6·3×10(6) ]) RBCs on another's. RBC-derived microparticles averaged 210·7×10(6) (95% C.I. [166·2-254·2×10(6) ]) on one manufacturer's device and 232·3×10(6) (95% C.I. [194·3-272·9×10(6) ]) on another's. These counts all correspond to volumes of <1 µl. CONCLUSION: Despite RBC contamination of APs below commonly accepted thresholds for Rh immunogenicity, AP transfusion can provoke non-D Rh antibody formation. RBC-derived microparticles, smaller but more numerous than RBCs, are volumetrically comparable and may be a hitherto underappreciated antibody stimulus. Further microparticle research will guide considerations of extended phenotypic matching of platelet components.

Significance of pre-storage leucoreduction for autologous blood.

BACKGROUND AND OBJECTIVES: To reveal the associations between cytokines in blood and transfusion-related adverse events, we studied whether pre-storage leucoreduction of autologous blood could reduce the degree of inflammatory responses, infection rates, or the duration of hospitalizations. MATERIALS AND METHODS: Patients scheduled to donate autologous blood for elective orthopaedic surgery were assigned to receive either leucoreduced (LR) or non-leucoreduced (N-LR) autologous blood based on their date of birth. Levels of cytokines in the autologous blood, values for C-reactive protein, complete blood count and body temperature of the patients, as well as adverse clinical events, were evaluated periodically. RESULTS: Four hundred patients entered this study (LR group: 196, N-LR group: 204). The production of cytokines, excluding interleukin 1beta (IL-1beta), was suppressed for the LR group. However, for unknown reasons, IL-1beta actually increased during storage for the LR group. There were no differences between the two groups in the length of hospital stay, postoperative C-reactive protein changes, leucocyte count, or body temperature, and no clinical problems associated with blood transfusion were observed in either group. CONCLUSION: Pre-storage leucoreduction for autologous blood may be effective to suppress cytokine accumulation. However, clinical benefits such as prevention of febrile non-haemolytic reactions could not be demonstrated.

Consecutive national surveys of ABO-incompatible blood transfusion in Japan.

BACKGROUND AND OBJECTIVES: Morbidity and mortality from ABO-incompatible transfusion persist as consequences of human error. Even so, insufficient attention has been given to improving transfusion safety within the hospital. MATERIALS AND METHODS: National surveys of ABO-incompatible blood transfusions were conducted by the Japanese Society of Blood Transfusion, with support from the Ministry of Health, Labor and Welfare. Surveys concluded in 2000 and 2005 analysed ABO-incompatible transfusion data from the previous 5 years (January 1995 to December 1999 and January 2000 to December 2004, respectively). The first survey targeted 777 hospitals and the second, 1355 hospitals. Data were collected through anonymous questionnaires. RESULTS: The first survey achieved a 77.4% response rate (578 of 777 hospitals). The second survey collected data from 251 more hospitals, but with a lower response rate (61.2%, or 829 of 1355 hospitals). The first survey analysed 166 incidents from 578 hospitals, vs. 60 incidents from 829 hospitals in the second survey. The main cause of ABO-incompatible transfusion was identification error between patient and blood product: 55% (91 of 166) in the first survey and 45% (27 of 60) in the second. Patient outcomes included nine preventable deaths from 1995 to 1999, and eight preventable deaths from 2000 to 2004. CONCLUSION: Misidentification at the bedside persists as the main cause of ABO-incompatible transfusion.

Survival and recovery of apheresis platelets stored in a polyolefin container with high oxygen permeability.

BACKGROUND AND OBJECTIVES: Oxygen permeability is important in platelet storage media. We compared a new polyolefin container with enhanced oxygen permeability (PO-80; Kawasumi, Tokyo, Japan) to a widely used alternative (PL2410; Baxter Healthcare, Deerfield, IL, USA). MATERIALS AND METHODS: In vitro characteristics of paired platelet concentrates (PCs; mean 4.2 x 10(11)/250 ml plasma/bag) stored in PO-80 or PL2410 were assessed through 9 days of storage. In vivo recovery and survival of 7-day-old autologous PCs were assessed according to the Murphy method. RESULTS: Laboratory assessment of platelet quality favoured PO-80 during 9 days of storage with statistically significant differences in glucose consumption (2.75 vs. 4.93 mmol/10(12)/24 h in the interval 120-168 h), lactate generation (4.37 vs. 8.11 mmol/10(12)/24 h in the interval 120-168 h), pressure of oxygen (pO(2)) (59.3 vs. 38.1 mmHg at day 1), and HCO(3)(-) (14.7 vs. 13.4 mmol/l at day 1). Statistically significant differences were not seen in aggregation, hypotonic shock response or pH. In vivo assessment of autologous platelets stored 7 days in the PO-80 container revealed that recovery was 82.1% and survival was 81.0% of fresh control. Seven-day stored PCs in PO-80 were shown in vivo to be non-inferior to fresh platelets, with upper confidence limits (UCL(95)) in recovery and survival of stored PCs below the maximum acceptable difference (MAD); 15.3% UCL(95) < 20.4% MAD and 2.1 days UCL(95) < 2.1 days MAD. CONCLUSIONS: The in vitro characteristics of PCs stored in a highly oxygen-permeable container were stable at least 7 days. The in vivo study supports the suitability of PO-80 for 7-day platelet storage.

Cooperation of six and eya in activation of their target genes through nuclear translocation of Eya.

Drosophila sine oculis and eyes absent genes synergize in compound-eye formation. The murine homologues of these genes, Six and Eya, respectively, show overlapping expression patterns during development. We hypothesized that Six and Eya proteins cooperate to regulate their target genes. Cotransfection assays were performed with various combinations of Six and Eya to assess their effects on a potential natural target, myogenin promoter, and on a synthetic promoter, the thymidine kinase gene promoter fused to multimerized Six4 binding sites. A clear synergistic activation of these promoters was observed in certain combinations of Six and Eya. To investigate the molecular basis for the cooperation, we first examined the intracellular distribution of Six and Eya proteins in transfected COS7 cells. Coexpression of Six2, Six4, or Six5 induced nuclear translocation of Eya1, Eya2, and Eya3, which were otherwise distributed in the cytoplasm. In contrast, coexpression of Six3 did not result in nuclear localization of any Eya proteins. Six and Eya proteins were coimmunoprecipitated from nuclear extracts prepared from cotransfected COS7 cells and from rat liver. Six domain and homeodomain, two evolutionarily conserved domains among various Six proteins, were necessary and sufficient for the nuclear translocation of Eya. In contrast, the Eya domain, a conserved domain among Eya proteins, was not sufficient for the translocation. A specific interaction between the Six domain and homeodomain of Six4 and Eya2 was observed by yeast two-hybrid analysis. Our results suggest that transcription regulation of certain target genes by Six proteins requires cooperative interaction with Eya proteins: complex formation through direct interaction and nuclear translocation of Eya proteins. This implies that the synergistic action of Six and Eya is conserved in the mouse and is mediated through cooperative activation of their target genes.

Nonmyeloablative stem cell transplantation for nonmalignant diseases in children with severe organ dysfunction.

Allogeneic stem cell transplantation (SCT) can cure several nonmalignant diseases in children. However, patients frequently have significant morbidity before transplantation and there is a high transplant-related mortality. Nonmyeloablative SCT might achieve the same goals but with less toxicity. Six pediatric patients with nonmalignant diseases underwent nonmyeloablative SCT from different stem cell sources. All patients were conditioned with fludarabine/melphalan with additional anti-thymocyte globulin for haploidentical grafts and prophylaxis for graft-versus-host disease (GVHD) consisting of tacrolimus and methotrexate with additional prednisolone for haploidentical grafts. Hematopoietic stem cells were neither T-cell depleted nor purged. All patients had severe organ dysfunction that precluded transplantation with conventional conditioning. Five of the six are alive and in complete disease resolution at a median of 19 months (range, 7-53 months) after SCT. One patient died of bacteremia before engraftment. Three patients achieved complete donor chimerism. Two patients remained stable mixed chimerism. Short-term toxicities were minimal. Acute and chronic GVHD were not seen. In summary, the fludarabine-based nonmyeloablative regimen followed by SCT provides a good approach for children with nonmalignant diseases. Even patients with severe organ dysfunctions had adequate engraftment with acceptable toxicities.

EXTERNAL AND INTERNAL EXPOSURE TO FUKUSHIMA RESIDENTS.

The Great East Japan Earthquake of 11 March 2011, caused the Fukushima Daiichi Nuclear Power Plant Accident, which resulted in the release of a large amount of radioactive materials into the environment, and there is a serious concern about the radiation effects on the health of residents living in the affected areas. The evaluation of exposure dose is fundamental for the estimation of health effects, and whenever possible, the exposure dose should be evaluated by actual measurements as opposed to estimations. Here, the outline of the exposure doses of residents estimated from surveys or obtained by measurements is described. Fukushima Health Management Survey reported the results for 460 408 residents during the first 4 months after the accident; 66.3% received doses <1 mSv, 94.9% received <2 mSv, 99.7% received <5 mSv and the maximum dose was 25 mSv. Thus, it was demonstrated that the results from personal dosemeter measurements were comparable to the estimations. The dose assessment of internal exposure of 184 205 residents conducted by Fukushima Prefecture by using whole body counter showed that 99.986% received <1 mSv, with the maximum dose being 3 mSv. Regarding exposure of the thyroid, there is not enough data for the Fukushima accident, but it is presumed that thyroid doses are much lower than those from Chernobyl. The outline of exposure doses of residents in result of the accident is still being clarified, questions and uncertainties in dose assessment remain and further efforts for more accurate dosimetry are required continuously.

Tissue and developmental distribution of Six family gene products.

To examine the presence and distribution of Six family gene products in a variety of tissues at various developmental stages and in various cell types, we prepared specific antibodies against recombinant Six gene products. The distribution of Six2 and Six4 was examined by immunostaining in the developing mouse embryo. Production of Six2 was detected at E8.5 mainly in the mesenchyme, while Six4 was present in nuclei of neuronal cells in the peripheral region of the mantle layer of developing brain and spinal cord and in various ganglia at E10.5 and E11.5. Specific DNA binding activities of the Six proteins were analyzed by gel retardation super-shift assays using nuclear extracts from different rat tissues and cell lines. Six5 was the dominant isoform observed in the adult kidney, liver and lung but not in the brain. Six4 was not detected in all tested adult tissues, however, it was present in embryonic (FD21) lung nuclear extracts. In contrast, Six4 was detected in a variety of cultured cell lines, including HeLa, 3T3, MDCK and C2C12. Our results suggest that Six4 plays a specific role in the differentiation or maturation of neuronal cells, while Six5 is an adult type Six gene isoform product and is distributed in the kidney, liver and lung.

Identification and expression of six family genes in mouse retina.

We identified five cDNA clones of the Six gene family which are expressed in retina. They are Six2, Six3 alpha and Six3 beta (which are derived from alternative splicing forms), Six5, and AREC3/Six4. All of these Six family genes possess extensive sequence similarity among each other in the so-homologous region (Six domain and homeodomain) but differ greatly in structure in some other regions. The amino acid sequence similarity of the so-homologous region to the previously identified AREC3/Six4 is 70.1% for Six2, 57.3% for Six3 alpha and Six3 beta, and 70.3% for Six5. The expression of these genes was observed in inner and outer nuclear layer, ganglion cell layer, and pigment epithelium of mouse retina by in situ hybridization. The so-homologous region of each Six family protein has specific DNA binding activity. Six5 and Six2 bind to the same sequence as does AREC3/Six4, while Six3 does not. These observations suggest that some of the Six family genes can regulate the same target genes.

Age-dependent remodeling of peripheral blood CD4+ CD8+ T lymphocytes in cynomolgus monkeys.

Recently, we have found in adult cynomolgus monkeys that substantial peripheral blood CD4+ CD8+ double-positive (DP) T lymphocytes exhibit a resting memory phenotype and increase in proportion with age. In this study, we investigated whether phenotypic changes occur in the course of the increase in proportion of the DP T cells. The results obtained from 195 clinically healthy monkeys aged from 1 month to 31 years showed that the CD29hi and CD28 subpopulation in the DP T subset increased in proportion with age and that the increase reached a plateau at six years old for the CD29hi subpopulation and at eleven years old for the CD28 one, respectively. The phenotypic alteration preceded the abrupt increase in proportion of the DP T cells and was able to be classified into four phases on the basis of the qualitative and quantitative alteration.

Antepartum diagnosis of fetal intracranial hemorrhage due to maternal Bernard-Soulier syndrome.

BACKGROUND: Bernard-Soulier syndrome, a lack of glycoprotein IB/IX, is a rare autosomal recessive bleeding disorder characterized by platelet dysfunction. Women with Bernard-Soulier syndrome are at risk of being immunized against glycoprotein IB/IX, leading to severe isoimmune neonatal thrombocytopenia. CASE: A 26-year-old Japanese woman, gravida 1, para 0, with Bernard-Soulier syndrome presented at 35 weeks' gestation with changes in fetal heart rate patterns and ultrasonographic findings that strongly suggested fetal intracranial hemorrhage. Management was by cesarean hysterectomy and bilateral salpingo-oophorectomy at 36 weeks, but the neonate died 6 hours after birth. CONCLUSION: Maternal immunization to glycoprotein IB/IX during pregnancy can cause severe fetal thrombocytopenia and massive intracranial bleeding.

Pharmacological approaches to reduce perioperative transfusion requirements in the aged.

Although iron deficiency is undoubtedly the commonest cause of anaemia even in elderly people, the aetiology is not always clear owing to various underlying diseases. Correction of anaemia is sometimes needed before surgery. The use of drugs that may influence blood coagulation, such as aspirin (acetylsalicylic acid), should be checked. Perioperative allogenic blood transfusion can often be avoided by the use of autologous blood and improved surgical techniques. Autologous blood donations are preferable in cases of planned surgery. Epoetin (recombinant human erythropoietin) in combination with iron supplementation facilitates the donation of autologous blood, even in elderly patients. Another method of avoiding allogenic blood transfusion is the collection and reuse of the blood a patient sheds in operations. During and/or after surgery, many haemostatic agents are available. Moreover, recent developments in gene engineering have enabled the utilisation of recombinant cytokines and coagulation factors. Further work remains to be done to define the proper use of these agents.