アルドステロン/食塩投与ラットにおいてミゾリビンは腎臓のカスパーゼ1発現を抑制し、腎障害と高血圧を軽減する

広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

Protective Effects of Japanese Soybean Paste (Miso) on Stroke in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP)

[BACKGROUND AND HYPOTHESIS] Soybean isoflavones have been shown to reduce the risk of cerebral infarction in humans according to epidemiological studies. However, whether intake of miso can reduce the incidence of stroke in animal models remains unknown. In this study, we investigated the effects of soybean paste (miso) in an animal model of stroke. [METHODS] Stroke-prone spontaneously hypertensive rats (SHRSP) were fed a miso diet (normal diet 90%, miso 10%; final NaCl content 2.8%), a high salt diet (normal diet and NaCl 2.5%; final NaCl content 2.8%), or a low salt diet (normal diet; final NaCl content 0.3%). [RESULTS] Kaplan–Meier survival curves revealed a significantly lower survival rate in the high salt group compared to the miso group (P = 0.002) and the low salt group (P ≤ 0.001). Large hemorrhagic macules were found in the cerebrum in the high salt group, whereas none were found in the other 2 groups. There were also fewer histological and immunohistochemical changes in the brain and kidneys in the miso group compared to the high salt group. [CONCLUSION] Our results suggest that miso may have protective effects against stroke despite its high salt content.This work was supported by a grant-in-aid from the Central Miso Institute, Tokyo, Japa

High Human T Cell Leukemia Virus Type-1(HTLV-1) Provirus Load in Patients with HTLV-1 Carriers Complicated with HTLV-1-unrelated disorders

<p>Abstract</p> <p>Background</p> <p>To address the clinical and virological significance of a high HTLV-1 proviral load (VL) in practical blood samples from asymptomatic and symptomatic carriers, we simultaneously examined VL and clonal expansion status using polymerase chain reaction (PCR) quantification (infected cell % of peripheral mononuclear cells) and Southern blotting hybridization (SBH) methods.</p> <p>Results</p> <p>The present study disclosed extremely high VL with highly dense smears with or without oligoclonal bands in SBH. A high VL of 10% or more was observed in 16 (43.2%) of a total of 33 samples (one of 13 asymptomatic carriers, 8 of 12 symptomatic carriers, and 7 of 8 patients with lymphoma-type ATL without circulating ATL cells). In particular, an extremely high VL of 50% or more was limited to symptomatic carriers whose band findings always contained at least dense smears derived from polyclonally expanded cells infected with HTLV-1. Sequential samples revealed that the VL value was synchronized with the presence or absence of dense smears, and declined at the same time as disappearing dense smears. Dense smears transiently emerged at the active stage of the underlying disease. After disappearance of the smears, several clonal bands became visible and were persistently retained, explaining the process by which the clonality of HTLV-1-infected cells is established. The cases with only oligoclonal bands tended to maintain a stable VL of around 20% for a long time. Two of such cases developed ATL 4 and 3.5 years later, suggesting that a high VL with oligoclonal bands may be a predisposing risk to ATL.</p> <p>Conclusion</p> <p>The main contributor to extremely high VL seems to be transient emergence of dense smears detected by the sensitivity level of SBH, corresponding to polyclonal expansion of HTLV-1-infected cells including abundant small clones. Major clones retained after disappearance of dense smears stably persist and acquire various malignant characteristics step by step.</p

Risk Score to Predict 1-Year Mortality after Haemodialysis Initiation in Patients with Stage 5 Chronic Kidney Disease under Predialysis Nephrology Care

Background Few risk scores are available for predicting mortality in chronic kidney disease (CKD) patients undergoing predialysis nephrology care. Here, we developed a risk score using predialysis nephrology practice data to predict 1-year mortality following the initiation of haemodialysis (HD) for CKD patients. Methods This was a multicenter cohort study involving CKD patients who started HD between April 2006 and March 2011 at 21 institutions with nephrology care services. Patients who had not received predialysis nephrology care at an estimated glomerular filtration rate (eGFR) of approximately 10 mL/min per 1.73 m2 were excluded. Twenty-nine candidate predictors were selected, and the final model for 1-year mortality was developed via multivariate logistic regression and was internally validated by a bootstrapping technique. Results A total of 688 patients were enrolled, and 62 (9.0%) patients died within one year of HD initiation. The following variables were retained in the final model: eGFR, serum albumin, calcium, Charlson Comorbidity Index excluding diabetes and renal disease (modified CCI), performance status (PS), and usage of erythropoiesis-stimulating agent (ESA). Their β-coefficients were transformed into integer scores: three points were assigned to modified CCI�3 and PS 3–4; two to calcium>8.5 mg/dL, modified CCI 1–2, and no use of ESA; and one to albumin7 mL/min per 1.73 m2, and PS 1–2. Predicted 1-year mortality risk was 2.5% (score 0–4), 5.5% (score 5–6), 15.2% (score 7–8), and 28.9% (score 9–12). The area under the receiver operating characteristic curve was 0.83 (95% confidence interval, 0.79–0.89). Conclusions We developed a simple 6-item risk score predicting 1-year mortality after the initiation of HD that might help nephrologists make a shared decision with patients and families regarding the initiation of HD.This work was supported by grants from the Institute for Health Outcomes & Process Evaluation research

Single Event Tolerance of X-ray SOI Pixel Sensors

We evaluate the single event tolerance of the X-ray silicon-on-insulator (SOI) pixel sensor named XRPIX, developed for the future X-ray astronomical satellite FORCE. In this work, we measure the cross-section of single event upset (SEU) of the shift register on XRPIX by irradiating heavy ion beams with linear energy transfer (LET) ranging from 0.022 MeV/(mg/cm2) to 68 MeV/(mg/cm2). From the SEU cross-section curve, the saturation cross-section and threshold LET are successfully obtained to be $3.4^{+2.9}_{-0.9}\times 10^{-10}~{\rm cm^2/bit}$ and $7.3^{+1.9}_{-3.5}~{\rm MeV/(mg/cm^2)}$, respectively. Using these values, the SEU rate in orbit is estimated to be $\lesssim$ 0.1 event/year primarily due to the secondary particles induced by cosmic-ray protons. This SEU rate of the shift register on XRPIX is negligible in the FORCE orbit.Comment: 9 pages, 5 figures, accepted for publication in JATI

X-ray Radiation Damage Effects on Double-SOI Pixel Detectors for the Future Astronomical Satellite "FORCE"

We have been developing the monolithic active pixel detector "XRPIX" onboard the future X-ray astronomical satellite "FORCE". XRPIX is composed of CMOS pixel circuits, SiO2 insulator, and Si sensor by utilizing the silicon-on-insulator (SOI) technology. When the semiconductor detector is operated in orbit, it suffers from radiation damage due to X-rays emitted from the celestial objects as well as cosmic rays. From previous studies, positive charges trapped in the SiO2 insulator are known to cause the degradation of the detector performance. To improve the radiation hardness, we developed XRPIX equipped with Double-SOI (D-SOI) structure, introducing an additional silicon layer in the SiO2 insulator. This structure is aimed at compensating for the effect of the trapped positive charges. Although the radiation hardness to cosmic rays of the D-SOI detectors has been evaluated, the radiation effect due to the X-ray irradiation has not been evaluated. Then, we conduct an X-ray irradiation experiment using an X-ray generator with a total dose of 10 krad at the SiO2 insulator, equivalent to 7 years in orbit. As a result of this experiment, the energy resolution in full-width half maximum for the 5.9 keV X-ray degrades by 17.8 $\pm$ 2.8% and the dark current increases by 89 $\pm$ 13%. We also investigate the physical mechanism of the increase in the dark current due to X-ray irradiation using TCAD simulation. It is found that the increase in the dark current can be explained by the increase in the interface state density at the Si/SiO2 interface.Comment: 15 pages, 12 figures, accepted for publication in Journal of Astronomical Telescopes, Instruments, and System

Impaired psychological recovery in the elderly after the Niigata-Chuetsu Earthquake in Japan:a population-based study

BACKGROUND: An earthquake measuring 6.8 on the Richter scale struck the Niigata-Chuetsu region of Japan at 5.56 P.M. on the 23rd of October, 2004. The earthquake was followed by sustained occurrence of numerous aftershocks, which delayed reconstruction of community lifelines. Even one year after the earthquake, 9,160 people were living in temporary housing. Such a devastating earthquake and life after the earthquake in an unfamiliar environment should cause psychological distress, especially among the elderly. METHODS: Psychological distress was measured using the 12-item General Health Questionnaire (GHQ-12) in 2,083 subjects (69% response rate) who were living in transient housing five months after the earthquake. GHQ-12 was scored using the original method, Likert scoring and corrected method. The subjects were asked to assess their psychological status before the earthquake, their psychological status at the most stressful time after the earthquake and their psychological status at five months after the earthquake. Exploratory and confirmatory factor analysis was used to reveal the factor structure of GHQ12. Multiple regression analysis was performed to analyze the relationship between various background factors and GHQ-12 score and its subscale. RESULTS: GHQ-12 scores were significantly elevated at the most stressful time and they were significantly high even at five months after the earthquake. Factor analysis revealed that a model consisting of two factors (social dysfunction and dysphoria) using corrected GHQ scoring showed a high level of goodness-of-fit. Multiple regression analysis revealed that age of subjects affected GHQ-12 scores. GHQ-12 score as well as its factor 'social dysfunction' scale were increased with increasing age of subjects at five months after the earthquake. CONCLUSION: Impaired psychological recovery was observed even at five months after the Niigata-Chuetsu Earthquake in the elderly. The elderly were more affected by matters relating to coping with daily problems

The ability of contemporary cardiologists to judge the ischemic impact of a coronary lesion visually

Background: Landmark trials showed that invasive pressure measurement (Fractional Flow Reserve, FFR) was a better guide to coronary stenting than visual assessment. However, present-day interventionists have benefited from extensive research and personal experience of mapping anatomy to hemodynamics. Aims: To determine if visual assessment of the angiogram performs as well as invasive measurement of coronary physiology. Methods: 25 interventional cardiologists independently visually assessed the single vessel coronary disease of 200 randomized participants in The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial (ORBITA). They gave a visual prediction of the FFR and Instantaneous Wave-free Ratio (iFR), denoted vFFR and viFR respectively. Each judged each lesion on 2 occasions, so that every lesion had 50 vFFR, and 50 viFR assessments. The group consensus visual estimates (vFFR-group and viFR-group) and individual cardiologists' visual estimates (vFFR-individual and viFR-individual) were tested alongside invasively measured FFR and iFR for their ability to predict the placebo-controlled reduction in stress echo ischemia with stenting. Results: Placebo-controlled ischemia improvement with stenting was predicted by vFFR-group (p < 0.0001) and viFR-group (p < 0.0001), vFFR-individual (p < 0.0001) and viFR-individual (p < 0.0001). There were no significant differences between the predictive performance of the group visual estimates and their invasive counterparts: p = 0.53 for vFFR vs FFR and p = 0.56 for viFR vs iFR. Conclusion: Visual assessment of the angiogram by contemporary experts, provides significant additional information on the amount of ischaemia which can be relieved by placebo-controlled stenting in single vessel coronary artery disease

Factor structure of the General Health Questionnaire (GHQ-12) in subjects who had suffered from the 2004 Niigata-Chuetsu Earthquake in Japan: a community-based study

<p>Abstract</p> <p>Background</p> <p>Factor structure of the 12-item General Health Questionnaire (GHQ-12) was studied by a survey of subjects who had experienced the 2004 Niigata-Chuetsu earthquake (6.8 on the Richter scale) in Japan.</p> <p>Methods</p> <p>Psychological distress was measured at two years after the earthquake by using GHQ-12 in 2,107 subjects (99.0% response rate) who suffered the earthquake. GHQ-12 was scored by binary, chronic and Likert scoring method. Confirmatory factor analysis was used to reveal the factor structure of GHQ-12. Categorical regression analysis was performed to evaluate the relationships between various background factors and GHQ-12 scores.</p> <p>Results</p> <p>Confirmatory factor analysis revealed that the model consisting of the two factors and using chronic method gave the best goodness-of-fit among the various models for factor structure. Recovery in the scale for the factor 'social dysfunction' was remarkably impaired compared with that of the factor 'dysphoria'. Categorical regression analysis revealed that various factors, including advanced age, were associated with psychological distress. Advanced age affected the impaired recovery of factor 'social dysfunction' score as well as total GHQ score.</p> <p>Conclusion</p> <p>The two-factor structure of GHQ-12 was conserved between the survey at five month and that at two years after the earthquake. Impaired recovery in the ability to cope with daily problems in the subjects who had experienced the earthquake was remarkable even at two years after the earthquake.</p