Lifestyle behaviour patterns in the prevention of type 2 diabetes mellitus: the Fukushima Health Database 2015-2020.

OBJECTIVES: Lifestyle behaviours associated with the incidence of type 2 diabetes mellitus (T2DM) need further clarification using health insurance data. STUDY DESIGN: This is a cohort study. METHODS: In 2015, 193,246 participants aged 40-74 years attended the specific health checkups and were observed up to 2020 in Fukushima, Japan. Using the principal component analysis, we identified two patterns from ten lifestyle behaviour questions, namely, the "diet-smoking" pattern (including smoking, alcohol drinking, skipping breakfast, eating fast, late dinner, and snacking) and the "physical activity-sleep" pattern (including physical exercise, walking equivalent activity, walking fast, and sufficient sleep). Then, individual pattern scores were calculated; the higher the scores, the healthier the behaviours. RESULTS: The accumulative incidence rate of T2DM was 630.5 in men and 391.9 in women per 100,000 person-years in an average of 4 years of follow-up. Adjusted for the demographic and cardiometabolic factors at the baseline, the hazard ratio (95% confidence interval) of the highest versus lowest quartile scores of the "diet-smoking" pattern for T2DM risk was 0.82 (0.72, 0.92; P for trend = 0.002) in men and 0.87 (0.76, 1·00; P for trend = 0.034) in women; that of the "physical activity-sleep" pattern was 0.92 (0.82, 1·04; P for trend = 0.0996) in men and 0.92 (0.80, 1·06; P for trend = 0.372) in women. The "physical activity-sleep" pattern showed a significant inverse association in non-overweight men. CONCLUSIONS: Lifestyle behaviour associated with a healthy diet and lack of smoking may significantly lower the risk of T2DM in middle-aged Japanese adults.

Prevalence trends of metabolic syndrome in residents of postdisaster Fukushima: a longitudinal analysis of Fukushima Health Database 2012-2019.

OBJECTIVES: The study aimed to evaluate the long-term metabolic risk profiles of Fukushima residents after the Great East Japan Earthquake of March 2011. STUDY DESIGN: This was a cross-sectional and a longitudinal design. METHODS: The Fukushima Health Database (FDB) contains 2,331,319 annual health checkup records of participants aged 40-74 years between 2012 and 2019. We checked the validity of the FDB by comparing the prevalence of metabolic factors with the National Database of Health Insurance Claims and Specific Health Checkups (NDB). We applied a regression analysis to determine the changes and project the trends of metabolic factors over the years. RESULTS: Compared to the NDB, the prevalence of metabolic factors in Fukushima was higher than the country average from 2013 to 2018, and they showed the same trends as those from the FDB. The prevalence of metabolic syndrome (MetS) increased from 18.9% in 2012 to 21.4% in 2019 (an annual increase of 2.74%) in men and from 6.8 to 7.4% (an annual increase of 1.80%) in women in Fukushima. The standardized prevalence of MetS, being overweight, and diabetes is projected to continue increasing, with disparities among subareas being higher in evacuees than in non-evacuees. An annual decrease of 0.38-1.97% in hypertension was mainly observed in women. CONCLUSIONS: The prevalence of metabolic risk is higher in Fukushima as compared to the country average. The increasing metabolic risk in subareas, including the evacuation zone, highlights the need to control MetS in Fukushima residents.

Differential expression of immune-modulatory molecule HLA-E in non-neoplastic and neoplastic lesions of the thyroid.

Human leukocyte antigen (HLA)–E is a non-classical molecule of the histocompatibility complex that functions as one of the main ligands of the Natural Killer (NK) cell inhibitory receptor CD94/NKG2A and inhibits its potent cytotoxic activity. Due to the important role of NK cells in combating neoplasm, we hypothesized that the differential expression of HLA-E could favor the progression of heterogeneous thyroid tumors.Using an immunohistochemistry technique in 143 biopsies of thyroid tumors, including benign and malignant neoplasms and goiters, we evaluated the expression of HLA-E among various tumor types and its association with the clinicopathological factors of diseases. We verified high HLA-E expression in all types of neoplastic tumors, although no significant differences between the groups were found. Low expression was observed in 95 percent of the goiter samples, showing significant differences between neoplastic and non-neoplastic lesions. Furthermore, a significant result was found with regard to the tumor size, with high HLA-E expression being related to smaller tumors. Therefore, our data suggest that an increase in HLA-E may be associated with the establishment of thyroid neoplasms, with either benign or malignant features.

[Surgical treatment of postinfarction ventricular septal rupture].

BACKGROUND: Postinfarction ventricular septal rupture (VSR) is a lethal complication with high mortality. The aim of this study was to evaluate our surgical strategy and results of VSR. PATIENTS AND METHODS: Between 1996 and 2008, 13 consecutive patients underwent operation for VSR at our hospital. All patients required emergent operation because of severe cardiogenic shock. Surgical procedure consisted of endocardial patch repair with infarct exclusion, so called "Komeda-David operation". In patients with multiple coronary artery disease, myocardial revascularization was done simultaneously. RESULTS: These patients were divided into 2 groups according to the location of VSR. There were 9 patients of anterior VSR. Two of them could not be weaned from cardiopulmonary bypass and died of severe low output syndrome (LOS) at early postoperative period. The site of infarction in both patients was broad anteroseptal region including right ventricle. On the other hand, there were 4 patients of inferior VSP. Two of these patients were lost due to LOS. One patient was complicated with left ventricular free wall rupture. In another patient, infarction was extended proximally toward the mitral annulus and papillary muscles. Both cardiopulmonary bypass time and aortic crossclamp time were significantly longer in inferior VSR than in anterior region. There was no late death in 2 groups. CONCLUSIONS: Despite improvements of surgical procedures, such as infarct exclusion technique, the operative mortality remains high in cases with broad infarction and/or right ventricular infarction. In these particular circumstances, in should be mandatory to consider the optimal timing of operation and the modification of surgical technique itself.

[Sarcomatoid carcinoma of the thymus which caused acute epicarditis].

Thymic carcinoma is rare. Particularly sarcomatoid carcinoma of the thymus is a very rare disease it has been reported in only 15 patients to date. The prognosis is very poor and diagnosis and treatment have not yet been established. We report a case of 63-year-old man who was initially diagnosed with acute pericarditis and was finally found to be sarcomatoid carcinoma of the thymus. He underwent surgery and the tumor was completely resected. However, 6 months after surgery, local recurrence was noted. The patient was treated by radiotherapy followed by paclitaxel monotherapy. Partial remission was achieved transiently with paclitaxel, but the tumor again recurred. He died 33 months after surgery. The possibility of diseases like this tumor must be kept in mind for a patient with chest symptoms. Paclitaxel monotherapy is likely to be effective in treating sarcomatoid carcinoma of the thymus.

Genetic evidence for ATP-dependent endoplasmic reticulum-to-Golgi apparatus trafficking of ceramide for sphingomyelin synthesis in Chinese hamster ovary cells.

LY-A strain is a Chinese hamster ovary cell mutant resistant to sphingomyelin (SM)-directed cytolysin and has a defect in de novo SM synthesis. Metabolic labeling experiments with radioactive serine, sphingosine, and choline showed that LY-A cells were defective in synthesis of SM from these precursors, but not syntheses of ceramide (Cer), glycosphingolipids, or phosphatidylcholine, indicating a specific defect in the conversion of Cer to SM in LY-A cells. In vitro experiments showed that the specific defect of SM formation in LY-A cells was not due to alterations in enzymatic activities responsible for SM synthesis or degradation. When cells were treated with brefeldin A, which causes fusion of the Golgi apparatus with the endoplasmic reticulum (ER), de novo SM synthesis in LY-A cells was restored to the wild-type level. Pulse-chase experiments with a fluorescent Cer analogue, N-(4,4-difluoro-5,7-dimethyl-4-bora-3a, 4a-diaza-s-indacene-3-pentanoyl)-D-erythro-sphingosine (C5-DMB-Cer), revealed that in wild-type cells C5-DMB-Cer was redistributed from intracellular membranes to the Golgi apparatus in an intracellular ATP-dependent manner, and that LY-A cells were defective in the energy-dependent redistribution of C5-DMB-Cer. Under ATP-depleted conditions, conversion of C5-DMB-Cer to C5-DMB-SM and of [3H]sphingosine to [3H]SM in wild-type cells decreased to the levels in LY-A cells, which were not affected by ATP depletion. ER-to-Golgi apparatus trafficking of glycosylphosphatidylinositol-anchored or membrane-spanning proteins in LY-A cells appeared to be normal. These results indicate that the predominant pathway of ER-to-Golgi apparatus trafficking of Cer for de novo SM synthesis is ATP dependent and that this pathway is almost completely impaired in LY-A cells. In addition, the specific defect of SM synthesis in LY-A cells suggests different pathways of Cer transport for glycosphingolipids versus SM synthesis.

[Konno procedure for congenital aortic stenosis associated with complex left ventricular outflow tract obstruction].

Two successful cases of Konno procedure for congenital aortic stenosis and left ventricular outflow tract obstruction (LVOTO) were reported herein. A 3-year-old child previously underwent definitive repair of complete atrioventricular septal defect. Follow-up echocardiography revealed progression of valvular aortic stenosis and subaortic tunnel stenosis. Second patient was a 30-year-old male with congenital aortic stenosis, severe LVOTO and funnel chest. Both patients underwent Konno procedure, and their postoperative courses were uneventful. The Konno procedure is effective and stenotic lesion could be enlarged sufficiently even in complex LVOTO. Especially in the patient of advanced age, care should be taken to fragility of the left ventricular muscle and coronary malperfusion caused by the procedure itself.

[Surgical strategy for aortic root reconstruction in patients with Stanford type A acute aortic dissection].

BACKGROUND: Although the aortic root dissection is a common finding in patients with type A acute aortic dissection, it is potentially fatal. Several procedures are available for reconstruction of the aortic root, and the choice depends on the mode of dissection; rupture, coronary ostial disruption or pre-existing cardiovascular diseases (annulo-aortic ectasia, aortic regurgitation: AR). The purpose of this study was to evaluate our surgical strategy of type A acute aortic dissection with proximal involvement. METHODS: Between 1996 and 2008, 100 patients with type A acute aortic dissection underwent emergency operation at our hospital. Fifteen of them received aortic root intervention simultaneously. RESULTS: In the initial 3 patients, the dissected aortic root was reinforced by fibrin glue and concomitant coronary bypass grafting was performed. During the follow-up term, residual aortic insufficiency was noted in 2 patients. Aortic root reconstruction was performed in 12 patients. Of these, the most recent 2 young patients underwent a new type of aortic valve sparing procedure, so called "partial remodeling". The postoperative echocardiography demonstrated no AR. There was no operative death in this series, and the long-term results were good. CONCLUSION: The excellent outcome was demonstrated with the change of surgical strategy. Special care should be taken for precise recognition of the proximal extension of the aortic dissection at operation. Although we recommend consideration of the partial remodeling procedure as an alternative, close observation is mandatory in this particular circumstance.

[Postoperative management using ultra-short-acting beta-blocker (landiolol) in patients with aortic stenosis after aortic valve replacement].

Paroxysmal atrial fibrillation and other types of tachyarrhythmia are common, but might be potentially fatal complications in patients undergoing aortic valve replacement due to aortic stenosis. We report the effects of ultra-short-acting beta-blocker (landiolol) in treating 2 patients with postoperative tachycardia. The heart rate was controlled adequately without subsequent hypotension and postoperative course was uneventful. This strategy seems to be safe and beneficial in this particular circumstance.

Genome-wide profiling of promoter methylation in human.

DNA methylation in the promoter region of a gene is associated with a loss of that gene's expression and plays an important role in gene silencing. The inactivation of tumor-suppressor genes by aberrant methylation in the promoter region is well recognized in carcinogenesis. However, there has been little study in this area when it comes to genome-wide profiling of the promoter methylation. Here, we developed a genome-wide profiling method called Microarray-based Integrated Analysis of Methylation by Isoschizomers to analyse the DNA methylation of promoter regions of 8091 human genes. With this method, resistance to both the methylation-sensitive restriction enzyme HpaII and the methylation-insensitive isoschizomer MspI was compared between samples by using a microarray with promoter regions of the 8091 genes. The reliability of the difference in HpaII resistance was judged using the difference in MspI resistance. We demonstrated the utility of this method by finding epigenetic mutations in cancer. Aberrant hypermethylation is known to inactivate tumour suppressor genes. Using this method, we found that frequency of the aberrant promoter hypermethylation in cancer is higher than previously hypothesized. Aberrant hypomethylation is known to induce activation of oncogenes in cancer. Genome-wide analysis of hypomethylated promoter sequences in cancer demonstrated low CG/GC ratio of these sequences, suggesting that CpG-poor genes are sensitive to demethylation activity in cancer.

Plutonium and 137Cs in surface water of the South Pacific Ocean.

The present plutonium and 137Cs concentrations in South Pacific Ocean surface waters were determined. The water samples were collected in the South Pacific mid-latitude region (32.5 degrees S) during the BEAGLE expedition conducted in 2003-04 by JAMSTEC. 239,240Pu concentrations in surface seawater of the South Pacific were in the range of 0.5 to 4.1 mBq m(-3), whereas 137Cs concentrations ranged from 0.07 to 1.7 Bq m(-3). The observed 239,240Pu and 137Cs concentrations in the South Pacific were almost of the same level as those in the North Pacific subtropical gyre. The surface 239,240Pu in the South Pacific subtropical gyre showed larger spatial variations than 137Cs, as it may be affected by physical and biogeochemical processes. The 239,240Pu/137Cs activity ratios, which reflect biogeochemical processes in seawater, were generally smaller than that observed in global fallout, except for the most eastern station. The 239,240Pu/137Cs ratios in the South Pacific tend to be higher than that in the North Pacific. The relationships between anthropogenic radionuclides and oceanographic parameters such as salinity and nutrients were examined. The 137Cs concentrations in the western South Pacific (the Tasman Sea) and the eastern South Pacific were negatively correlated with the phosphate concentration, whereas there is no correlation between the 137Cs and nutrients concentrations in the South Pacific subtropical gyre. The mutual relationships between anthropogenic radionuclides and oceanographic parameters are important for better understanding of transport processes of anthropogenic radionuclides and their fate in the South Pacific.

Genomic imprinting in Dicer1-hypomorphic mice.

To address the function of RNA interference (RNAi) in transcriptional silencing in mammals, we analyzed genomic imprinting in Dicer1-hypomorphic mice, in which Dicer1 expression was significantly reduced. We did not observe any abnormality in the allelic expression of imprinted genes in these mice or their offspring, suggesting that reduced expression of Dicer1 did not significantly affect the maintenance and reprogramming of imprinting.

Development of adult T-cell leukemia-like disease in African green monkey associated with clonal integration of simian T-cell leukemia virus type I.

Proviral integration of a simian retrovirus highly homologous to human T-cell leukemia virus type I was examined in cellular DNAs extracted from primary peripheral blood lymphocytes of 31 adult African green monkeys (Cercopithecus aethiops) that were seropositive for simian T-cell leukemia virus type I (STLV-I). Among these monkeys, one case with overt leukemia, showing pleomorphic leukemia cells similar to those in human adult T-cell leukemia (ATL), and five cases in a preleukemic state of ATL-like disease were found. Judging from the integration site of the provirus genome, primary lymphocytes of these leukemic or preleukemic cases contained monoclonally proliferated STLV-I-infected cells, whereas lymphocytes of other seropositive monkeys without hematological abnormalities were polyclonal, and those of seronegative monkeys did not contain the provirus. The restriction patterns with PstI ans SstI of most STLV-I proviruses were identical to those of the previous isolate from this species, but in three monkeys there was a deletion of one PstI site. From the correlation of the development of simian ATL-like disease with the monoclonal integration of the STLV-I provirus genome, it should be indicated that STLV-I has similar leukemogenicity to human T-cell leukemia virus type I, and so STLV-I infection in African green monkeys will be useful as an animal model of human ATL.

Establishment of a phylogenetic survey system for AIDS-related lentiviruses and demonstration of a new HIV-2 subgroup.

We designed a universal primer (UNIPOL) for DNA amplification of AIDS-related viruses. The phylogenetic tree constructed from the presumed sequences amplified with UNIPOL was representative of the tree calculated from whole pol gene sequences so far reported. UNIPOL was able to amplify the sequences of all four major groups of primate lentiviruses and also that of a distinct virus from a Ghanaian patient with an AIDS-related complex, designated GH-2. This strain scarcely hybridizes with known HIV/simian immunodeficiency virus (SIV) DNA probes. Sequence analysis of the only amplified fragment revealed rapidly that GH-2 was quite similar to the recently reported HIV-2ALT(D205) and that these two viruses form a new subgroup distint from known HIV-2 and SIVmac/SIVsm in the large HIV-2 group. This system will be useful for further phylogenetic study of various primate lentiviruses.

Isolation and characterization of HIV-2 from an AIDS patient in Ghana.

This report describes the isolation and characterization of a retrovirus of the HIV-2 group from a Ghanaian AIDS patient which has different restriction patterns from previously reported HIV-2 viruses. The virus was morphologically very similar to HIV-1 and HIV-2, and had Mg2+-dependent reverse transcriptase. Like previous HIV isolates, it induced severe cytopathic effects in CD4-positive human lymphoid cell lines. Its major proteins were shown to be gp110, p66, p55, p41, gp32, p30 and p26 by Western blot analysis. In dot-blot hybridization experiments, the virus hybridized with a HIV-2 DNA probe, but not with HIV-1 and SIVagm probes in stringent conditions. These data indicate that this Ghanaian virus is a HIV-2 group virus. However, in a Southern blot hybridization experiment, the restriction patterns of this virus, designated HIV-2 [GH-1], were quite different from those of previously reported HIV-2 viruses from West Africa isolated at the Pasteur Institute.

Liposome oligomannose-coated with neoglycolipid, a new candidate for a safe adjuvant for induction of CD8+ cytotoxic T lymphocytes.

The cytotoxic T lymphocyte (CTL) response has recently been shown to play a role in protection against human immunodeficiency virus (HIV) and it is therefore thought that a vaccine against HIV must be able to elicit a CTL response. The development of a safe, effective adjuvant is very important because alum, the only adjuvant available for use in humans at present, can barely induce a response of this type. We demonstrate here that liposomes that contain an immunodominant peptide (15 amino acids) of the envelope glycoprotein gp120 of HIV-1 and that are coated with mannopentaose-dipalmitoylphosphatidylethanolamine conjugate induce a major histocompatibility complex class I-restricted CD8+ CTL response in mice with a single subcutaneous immunization, whereas non-coated liposomes do not. Since no damage to the skin at the injection site was caused by the liposomes, and since the oligomannose-coated liposomes consist of innocuous materials ubiquitously distributed throughout the human body, they may be highly suitable for use as a safe adjuvant in vaccines inducing a CTL response against HIV.

Oligomannose-coated liposomes as an adjuvant for the induction of cell-mediated immunity.

The effect of the coating of ovalbumin-reconstituted liposomes with various oligosaccharides on their immunogenicity was investigated in mice. The coating of liposomes with oligomannose or yeast mannan drastically enhanced their ability to induce an ovalbumin-specific delayed-type footpad swelling response with a peak at 24 to 48 h post-challenge. Among various oligosaccharides tested, only those with mannose residue at the nonreducing termini manifested the activity when applied to liposomes. Since such oligosaccharides are ubiquitously found in the body, these results suggested the usefulness of oligomannose-coated liposomes as a safe adjuvant for the induction of cell-mediated immunity.

Expression of cholesteryl ester transfer protein in human atherosclerotic lesions and its implication in reverse cholesterol transport.

Reverse cholesterol transport (RCT) is the major protective system against atherosclerosis. In this system, cholesteryl ester transfer protein (CETP) is known to facilitate the transfer of neutral lipids between lipoproteins in plasma. We reported the pathophysiological significance of CETP by clinical studies with genetic CETP deficiency, showing that this protein plays a crucial role in the RCT system. However, information about the expression of this protein in the initial step of RCT, macrophages (Mphi) in the blood vessels, is still very limited. In the present study, we have performed immunohistochemical analyses on the expression of CETP in human atherosclerotic lesions. The immunoreactive mass of CETP was abundantly detected in foam cells in human aortic and coronary atherosclerotic lesions, but not in the normal arterial wall. A double immunostaining showed that the majority of CETP-positive foam cells were derived from Mphi and a minor population appeared to derive from smooth muscle cells. Transient transfection of CETP cDNA into COS-7 cells showed that high density lipoprotein (HDL)-mediated efflux of free cholesterol from the cells expressing CETP was much higher than that from mock-transfected cells, while uptake of HDL-lipids was not affected in cells transfected with CETP cDNA. Efflux of free cholesterol from the Mphi obtained from CETP deficiency was significantly decreased compared with that from normal subjects. These data indicate that CETP is expressed in Mphi in the atherosclerotic lesions and may possess an anti-atherogenic function to remove cholesterol from the cells, suggesting another role of CETP at the initial step of RCT.

Different mechanisms between premitotic apoptosis and postmitotic apoptosis in X-irradiated U937 cells.

PURPOSE: Apoptosis is currently being evaluated for its importance as a pathway of radiation-induced cell death. However, the difference in the mechanisms between premitotic and postmitotic apoptosis following X-irradiation remains not well understood. We show here that the human monoblastoid cell line U937 can be induced to undergo these two different types of apoptosis. METHODS AND MATERIALS: U937 cells were irradiated at a dose of 5 or 20 Gy, and the DNA fragmentation rate was measured by both flow cytometric analysis and gel electrophoresis. Activation of caspase-3 was detected by Western blot analysis and fluorogenic assay using acetyl-Asp-Glu-Val-Asp-7-amino-4-methyl-coumarin (Ac-DEVD-AMC). Detection of mitochondrial transmembrane potential (DeltaPsi) was performed by using Rho123. Chasing of S-phase fraction following X-irradiation was performed after labeling with 5-bromo-2'-deoxyuridine (BrdU). Thymidine was used for synchronization of the cells. Inhibition of caspase-3 activity was achieved by Acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO). RESULTS: Time courses of the apoptotic rates, caspase activation, and DeltaPsi indicated that two different types of cell death were induced by the different X-ray doses. High-dose X-ray (20 Gy) induced a rapid and strong apoptosis, whereas low-dose X-ray (5 Gy) induced a slow and mild apoptosis. Cell-cycle analyses revealed that there was cell death before cell division in the former apoptosis but the cells must be dying after cell division in the latter apoptosis. By means of cell-cycle synchronization, the S-phase cells proved to be the most sensitive fraction to premitotic apoptosis, but an obvious difference in the susceptibility to cell death among the cell-cycle phases was not observed in postmitotic apoptosis. Ac-DEVD-CHO treatment effectively blocked caspase activity and premitotic apoptosis, but it failed to block postmitotic apoptosis. CONCLUSIONS: Irradiation of U937 cells at different X-ray doses induced two different types of apoptotic cell death, premitotic apoptosis and postmitotic apoptosis, which are characterized by the time course and cell-cycle specificity. Decision concerning these two types of apoptotic cell death may be made by the difference in the magnitude of cell damage following X-irradiation.

Genomic divergence of HIV-2 from Ghana.

Genetic variability in human immunodeficiency virus type 1 (HIV-1) has been studied extensively, but the total nucleotide sequence of the HIV-2 genome has been reported only in two strains. For phylogenetic analyses of HIV, the genetic variability of HIV-2 should be investigated. This paper reports the complete nucleotide sequence of an HIV-2 isolate from Ghana, HIV-2[GH-1]. This virus showed approximately 85% homology in overall nucleotide sequence with HIV-2ROD. The amino acid sequence of the gag and pol proteins of HIV-2[GH-1] showed 90% homology with those of HIV-2ROD, but its env gene and central regions were highly variable (more than 20% divergence in amino acids), indicating the presence of extensive genetic heterogeneity in HIV-2. However, the sequences with specific functions were relatively well conserved in these HIV-2 isolates.