The V protein of Sendai virus (SeV) suppresses innate immunity, resulting in enhancement of viral growth in mouse lungs and viral pathogenicity. The innate immunity restricted by the V protein is induced through activation of interferon regulatory factor-3 (IRF3). The V protein has been shown to interact with melanoma differentiation-associated gene 5 (MDA5) and to inhibit interferon-β production. In the present study, we infected MDA5 knockout mice with V-deficient SeV and found that MDA5 was largely unrelated to the innate immunity that the V protein suppresses in vivo. We therefore investigated the target of the SeV V protein. We previously reported interaction of the V protein with IRF3. Here we extended the observation and showed that the V protein appeared to inhibit translocation of IRF3 into the nucleus. We also found that the V protein inhibited IRF3 activation when induced by a constitutive active form of IRF3. The V proteins of measles virus and Newcastle disease virus inhibited IRF3 transcriptional activation as did that of SeV, while the V proteins of mumps virus and Nipah virus did not, and these inhibitions correlated with interaction of each V protein with IRF3. These results indicate that IRF3 is important as an alternative target of paramyxovirus V proteins.

BACKGROUND: Impairment of diastolic function and late remodeling are concerns after left ventricular restoration (LVR) for ischemic cardiomyopathy. This study aims to evaluate the effects of combined surgery of myoblast sheets (MS) implantation and LVR. METHODS: Rat myocardial infarction model was established 2 weeks after left anterior descending artery ligation. They were divided into three groups: sham operation (n=15; group sham), LVR by plicating the infracted area (n=15; group LVR), and MS implantation with LVR (n=15; group LVR+MS). RESULTS: Serial echocardiographic study revealed significant LV redilatation and decrease of ejection fraction 4 weeks after LVR in group LVR. MS implantation combined with LVR prevented those later deteriorations of LV function in group LVR+MS. Four weeks after the operation, a hemodynamic assessment using a pressure-volume loop showed significantly preserved diastolic function in group LVR+MS; end-diastolic pressure (LVR vs. LVR+MS: 9.0±6.6 mm Hg vs. 2.0±1.0 mm Hg, P<0.05), end-diastolic pressure-volume relationship (LVR vs. LVR+MS 42±23 vs. 13±6, P<0.05). Histological examination revealed cellular hypertrophy and LV fibrosis were significantly less and vascular density was significantly higher in group LVR+MS than in the other two groups. Reverse transcription polymerase chain reaction demonstrated significantly suppressed expression of transforming growth factor-beta, Smad2, and reversion-inducing cysteine-rich protein with Kazal motifs in group LVR+MS. CONCLUSIONS: MS implantation decreased cardiac fibrosis by suppressing the profibrotic gene expression and attenuated the impairment of diastolic function and the late remodeling after LVR. It is suggesting that MS implantation may improve long-term outcome of LVR for ischemic heart disease.

Background: Restrictive mitral annuloplasty (RMA) is widely employed for patients with functional mitral regurgitation (MR). Its improvement of left ventricular (LV) function has been demonstrated by only a gradual increase in LV ejection fraction (EF) in the chronic phase. However, the detailed evaluation of changes in LV function has not been fully elucidated in functional MR patients before and after RMA. Therefore, we performed two-dimensional speckle tracking echocardiography (2D-STE), which enables accurate evaluation of myocardial deformation and rotation that are undetectable by conventional echocardiography. Methods: We studied 13 patients (mean age 61 ± 10 years) with functional MR associated with cardiomyopathy undergoing RMA. In addition to conventional echocardiographic measurements, 2D-STE was performed to measure peak systolic radial (RS), circumferential (CS), and longitudinal (LS) strains and twist before and 4 ± 2 weeks after surgery. LV twist was defined as the difference between the apical and basal rotations. Results: After RMA, EF and LS remained unchanged, but RS and CS were significantly improved at the mid-LV (RS, 20.6 ± 10.8 vs 24.5 ± 11.6%; CS,-9.6 ± 5.2 vs -12.8 ± 5.6%) and at the apex (RS, 15.0 ± 12.2 vs 18.7 ± 8.6%; CS,-4.4 ± 3.0 vs -7.8 ± 4.8%). RS and CS were unchanged at the base. The apical and basal rotations changed significantly, from 3.5°± 0.7° to 9.2°± 2.1°, and -2.1°± 0.7° to -3.8°± 1.0°, respectively. Consequently, the LV twist increased significantly, from 5.6°± 1.0° to 13.0°± 1.9°. Conclusions: Radial and circumferential strains and LV twist increased significantly in the early postoperative period in functional MR patients after RMA and concomitant procedures.(Echocardiography 2012;29:445-450).

Background: The preoperative risk factors for left ventricular assist device (LVAD) implantation and their impact on the clinical outcome was analyzed to evaluate the optimal timing of LVAD implantation for severe heart failure patients. Methods and Results: From January 2006 to August 2011, 82 patients underwent 84 LVAD implantations at the Osaka University Hospital. These patients were categorized into 2 groups: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level 1 (n=41) and INTERMACS level 2/3 (n=43). The preoperative characteristics, early mortality, and cumulative survival between the 2 groups was compared. Ten (24.4%) patients died within 90 days in the INTERMACS level 1 group (multiple organ failure: 6, cerebrovascular event: 3, sepsis: 1), whereas 1 (2.3%) patient died because of a cerebrovascular event in the INTERMACS level 2/3 group (P=0.003). The cumulative survival rate was 82.9% at 30 days, 75.6% at 90 days, and 63.7% after 1 year in the INTERMACS level 1 group, and 100%, 97.7%, and 85.3% in the level 2/3 group (P=0.015). Using multivariate analysis for the INTERMACS level 1 group data, the preoperative serum creatinine level was the independent predictor of 90-day mortality. Conclusions: LVAD implantation in a stable condition contributes to better clinical outcome for severe heart failure patients. If critical cardiogenic shock occurs, LVAD implantation must be considered immediately before other organs' functions, especially renal function, deteriorate.

Objective: It was the aim of this study to evaluate the diagnostic utility of Notch-1 immunocytochemistry in distinguishing endometrial glandular and stromal breakdown (EGBD) from endometrial adenocarcinoma in endometrial cytology. Study Design: Samples of normal endometrium, EGBD and endometrial adenocarcinoma were subjected to immunocytochemical staining for Notch-1, and we examined the labeling index (LI) of Notch-1 (the ratio of intranuclear Notch-1-positive cells to total cells). We compared (1) the Notch-1 LI in normal endometrium,(2) the Notch-1 LI between normal endometrium and endometrial adenocarcinoma, and (3) the Notch-1 LI in normal endometrium, EGBD and endometrial adenocarcinoma. Results: In analysis item 1, the LI of Notch-1 was 32.9 ± 8.4, 19.4 ± 8.2 and 12.5 ± 7.5% in proliferative endometrium, secretory endometrium and atrophic endometrium, respectively. In analysis item 2, the LI of Notch-1 in endometrial adenocarcinoma was 45.2 ± 7.4%, which was significantly higher than that in normal endometrium. In analysis item 3, the LI of Notch-1 in EGBD was 31.3 ± 8.3%, which was significantly lower than that in endometrial adenocarcinoma. Conclusion: In conclusion, Notch-1 immunocytochemistry is a useful method for distinguishing between EGBD and endometrial carcinoma in endometrial cytology.

The conformation of 2,2,2-trifluoroethanol (TFE) in the 2-fluoropyridine-(TFE)_<i>m</i>-(H₂O)_<i>n</i> clusters in a supersonic jet has been investigated with a fluorescence-detected infrared spectroscopy and molecular orbital calculations. It is common to the observed clusters that they form chain structures containing the weak interaction of the pyridyl CH with the fluorine or oxygen atom in the terminal TFE. The detectable conformation of TFE is gauche only even in the case of the existence of the strong base such as 2-fluoropyridine. This result is explained by the change in hyperconjugation among several dominant orbitals. The preference of the terminal TFE in the mixed clusters with TFE and water solvents is observed, which is ascribed to the stronger cooperative effect of TFE than water.

Atrial fibrillation (AF) is the most common arrhythmia in clinical settings (Fuster et al., 2001), and it is often associated with congestive heart diseases (Issac et al., 2007). Many studies in both laboratory and clinical settings have sought to analyze the mechanisms of AF, develop treatments based on these mechanisms, and examine atrial remodeling in chronic AF. The aim of this paper is to analyze recent findings regarding the atrial remodeling that occurs in AF. In particular, we will describe the electrical and structural changes that involve atrial myocytes and the extracellular matrix. We will also describe the general classification and basic pathophysiology of AF and its surgical treatments.

Background: Perioperative risk during coronary artery bypass grafting (CABG) is reportedly high in patients with chronic renal disease. We aimed to determine postoperative mortality and morbidity and identify the perioperative risk factors of mortality during CABG in hemodialysis (HD)-dependent patients. Methods and Results: From the Japan Adult Cardiovascular Surgery Database, we compared 1,300 HD-dependent chronic renal failure patients with 18,387 non-HD patients who all underwent isolated CABG between January 2005 and December 2008. The operative mortality and mortality, including major morbidity, was 4.8% vs. 1.4% and 23.1% vs. 13.7% in the HD and non-HD groups, respectively. Preoperative predictors of operative mortality included age, chronic obstructive pulmonary disease, peripheral arterial disease, congestive heart failure, arrhythmia, preoperative inotropic agent requirement, New York Heart Association class IV, urgent or emergency operation, poor left ventricular function, aortic valve regurgitation (>2), and mitral valve regurgitation (>3). Postoperative predictors of operative mortality included stroke, infection, prolonged ventilation, pneumonia, heart block, and gastrointestinal complications. Conclusions: Compared with non-HD patients, CABG in HD patients was associated with high mortality and morbidity rates. An appropriate surgical strategy and careful perioperative assessment and management for prevention of respiratory and gastrointestinal complications might contribute to improved clinical outcomes after CABG in these patients.(Circ J 2012; 76: 1115-1120).

BACKGROUND Since the revision of the Japanese Organ Transplantation Act, children younger than 15 years old can donate their organs after brain death. METHODS AND RESULTS A teenage boy with endstage restrictive cardiomyopathy underwent the first heart transplantation with a pediatric donor heart in Japan on April 12, 2011. He had a good postoperative clinical course and no histological rejection episodes. His waiting period was relatively short (237 days) compared with adult patients, because of the pediatric patient-first policy for a pediatric donor heart. CONCLUSIONS To increase pediatric heart transplantation in Japan, further enlightenment of the general population about pediatric organ donation is desirable.

Flow coefficients v_{n} for n=2, 3, 4, characterizing the anisotropic collective flow in Au+Au collisions at sqrt[s_{NN}]=200  GeV, are measured relative to event planes Ψ_{n}, determined at large rapidity. We report v_{n} as a function of transverse momentum and collision centrality, and study the correlations among the event planes of different order n. The v_{n} are well described by hydrodynamic models which employ a Glauber Monte Carlo initial state geometry with fluctuations, providing additional constraining power on the interplay between initial conditions and the effects of viscosity as the system evolves. This new constraint can serve to improve the precision of the extracted shear viscosity to entropy density ratio η/s.