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Background: The clinical significance of induced left atrial macro-reentrant tachycardia (LA-AT) after encircling pulmonary vein isolation (EPVI) is unclear. Our objective was to determine whether induced LA-ATs are associated with the clinical recurrence of ATs., Methods: We studied 185 consecutive patients with paroxysmal atrial fibrillation (PAF) who underwent their first EPVI with an 8-mm tip, nonirrigated catheter approach. AT was induced by atrial burst pacing after the completion of EPVI, and the atrial activation pattern was evaluated using EnSite NavX. Induced LA-ATs were ablated only in patients with clinical ATs of suspected LA origin. The factors associated with occurrence of AT after the procedure were examined., Results: LA-ATs were induced in 38 patients and ablated in 5 patients. During a follow-up of 23 ± 7 months, the occurrence of AT did not differ between patients with nonablated LA-ATs (4/33, 12 %) and those without any inducible ATs (16/113, 14 %, p > 0.99). In multivariate analysis, the number of ablation points for completing EPVI was the only independent predictor of AT occurrence (odds ratio 1.07, p < 0.01). A repeat procedure was performed in 22 of 26 patients who developed AT. Nineteen patients became free from AT and AF after ablation of the conduction gaps (EPVI, n = 17; another line, n = 4), extra PV firing (n = 4), focal AT (n = 4), and induced LA-ATs (n = 3)., Conclusions: In patients who had EPVI for PAF using an 8-mm tip, nonirrigated catheter, the occurrence of AT after EPVI was mainly due to conduction gaps in the ablation line or extra PV triggers. In patients with PAF, LA-ATs induced during the first procedure did not require ablation if they were not associated with clinical AT.

Background: The QRS duration does not always reflect the left ventricular (LV) activation delay in patients with ventricular conduction disturbances. The R-wave offset in left chest leads may more closely reflect the LV activation delay than the QRS offset., Methods: We evaluated 138 cases with left bundle branch block (LBBB, n=11), right BBB (RBBB, n=38), non-specific intraventricular conduction disturbance (n=11), narrow QRS (<120ms, n=56) and right ventricular pacing (n=22). Cases with right axis deviation (120 to 270 degrees) were excluded. The intervals from the QRS onset to the V-waves in coronary sinus bipolar electrograms (QCS) were measured, and the longest interval was defined as the QCSmax. In the 12-lead electrocardiogram, the interval from the QRS onset to the R-wave offset (QR) was measured and then averaged in leads I-aVL, II-III-aVF, V1-V2, V3-V4 and V5-V6., Results: Significant correlations (p<0.05) were found between QCSmax and QR in I-aVL (r=0.83), II-III-aVF (r=0.51) and V5-V6 (r=0.86) in cases with a normal axis (0 to 90 degrees, n=64); and I-aVL (r=0.90), II-III-aVF (r=0.31) and V5-V6 (r=0.69) in cases with left axis deviation (-45 to -89 degrees, n=52). Overall, the QRS duration was also correlated with QCSmax (r=0.72, p<0.001); however, this correlation was weaker than the correlation between QCSmax and QR in I-aVL (r=0.89, p<0.001) due to disparities in RBBB (p<0.001)., Conclusions: The interval from the QRS onset to R-wave offset in the left chest leads reflects the degree of LV activation delay regardless of differences in QRS duration and morphology., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We investigated the antioxidant activities and locations of stable paramagnetic species in dry (or drying) shiitake mushroom (Lentinus edodes) using continuous wave (CW) electron paramagnetic resonance (EPR) and 9 GHz EPR imaging. CW 9 GHz EPR detected paramagnetic species (peak-to-peak linewidth (ΔHpp) = 0.57 mT) in the mushroom. Two-dimensional imaging of the sharp line using a 9 GHz EPR imager showed that the species were located in the cap and shortened stem portions of the mushroom. No other location of the species was found in the mushroom. However, radical locations and concentrations varied along the cap of the mushroom. The 9 GHz EPR imaging determined the exact location of stable paramagnetic species in the shiitake mushroom. Distilled water extracts of the pigmented cap surface and the inner cap of the mushroom showed similar antioxidant activities that reduced an aqueous solution of 0.1 mM 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl. The present results suggest that the antioxidant activities of the edible mushroom extracts are much weaker than those of ascorbic acid. Thus, CW EPR and EPR imaging revealed the location and distribution of stable paramagnetic species and the antioxidant activities in the shiitake mushroom for the first time.

The peroxisome proliferator-activated receptor (PPAR)α is mainly expressed in the liver and plays an important role in the regulation of lipid metabolism. It has been reported that PPARα activation enhances fatty acid oxidation and reduces fat storage. Therefore, PPARα agonists are used to treat dyslipidemia. In the present study, we found that 9-oxo-10(E),12(Z),15(Z)-octadecatrienoic acid (9-oxo-OTA), which is a α-linolenic acid (ALA) derivative, is present in tomato (Solanum lycopersicum) extract. We showed that 9-oxo-OTA activated PPARα and induced the mRNA expression of PPARα target genes in murine primary hepatocytes. These effects promoted fatty acid uptake and the secretion of β-hydroxybutyrate, which is one of the endogenous ketone bodies. We also demonstrated that these effects of 9-oxo-OTA were not observed in PPARα-knockout (KO) primary hepatocytes. To our knowledge, this is the first study to report that 9-oxo-OTA promotes fatty acid metabolism via PPARα activation and discuss its potential as a valuable food-derived compound for use in the management of dyslipidemia.

Nonionic gels were prepared from hydroxypropyl guar gum (HPG) with different molar substitution degrees by crosslinking with ethylene glycol diglycidyl ether (EGDE). FTIR and solid-state NMR spectroscopy revealed that the crosslinking degree of HPG gels increased with the amount of EGDE used during the reaction; this result was also confirmed by the water mobility in the swollen gels. Rheological characterization revealed behaviors typical of true gels, and their viscoelastic behaviors strongly depended on the crosslinking degree. The HPG gels absorbed buffers, aqueous saline, and water, and the absorption was not affected by the ionic strength or pH of the solution. In addition, HPG gels with high crosslinking degrees and molar substitution degrees exhibited gelation ability toward protic organic solvents such as methanol, ethanol, and 1-propanol. These HPG gels may find application as gelation agents for many industrial uses., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Peroxisome proliferator-activated receptor (PPAR)γ is expressed in adipose tissue and plays a key role in the regulation of adipogenesis. PPARγ activators are known to have potent antihyperglycemic activity and are used to treat insulin resistance associated with diabetes. Therefore, many natural and synthetic agonists of PPARγ are used in the treatment of glucose disorders. In the present study, we found that 13-oxo-9(Z),11(E),15(Z)-octadecatrienoic acid (13-oxo-OTA), a linolenic acid derivative, is present in the extract of tomato (Solanum lycopersicum), Mandarin orange (Citrus reticulata), and bitter gourd (Momordica charantia). We also found that 13-oxo-OTA activated PPARγ and induced the mRNA expression of PPARγ target genes in adipocytes, thereby promoting differentiation. Furthermore, 13-oxo-OTA induced secretion of adiponectin and stimulated glucose uptake in adipocytes. To our knowledge, this is the first study to report that 13-oxo-OTA induces adipogenesis through PPARγ activation and to present 13-oxo-OTA as a valuable food-derived compound that may be applied in the management of glucose metabolism disorders.

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal infectious neurodegenerative disorders. Their causative agents are prions, which are composed of disease-associated forms of prion protein (PrP(Sc)). Naturally occurring cases of TSEs are found in several mammalian species including humans, sheep, goats, minks, cattle and deer. Prions are also experimentally transmissible to other mammals such as mice, hamsters and monkeys, but interspecies transmission is often inefficient due to the 'species-barrier'. Studies have suggested that the barrier is not only simply determined by differences in amino acid sequences of cellular PrP (PrP(C)) among animal species, but also by prion strains which are closely associated with conformational properties of PrP(Sc) aggregates. Although the conformational properties of PrP(Sc) remain largely unknown, recent investigation of local structures of PrP(C) and, in particular, structural modelling of PrP(Sc) aggregates have provided molecular insight into this field. In this review, we discuss the species-barrier phenomenon in terms of the protein science.

Aims: Because benefits of cardiac resynchronization therapy (CRT) appear to be less favourable in non-left bundle branch block (LBBB) patients, this prospective longitudinal study tested the hypothesis that QRS morphology and echocardiographic mechanical dyssynchrony were associated with long-term outcome after CRT., Methods and Results: Two-hundred and seventy-eight consecutive New York Heart Association class III and IV CRT patients with QRS ≥120 ms and ejection fraction ≤35% were studied. The pre-specified primary endpoint was death, heart transplant, or left ventricular assist device over 4 years. Dyssynchrony assessed before CRT included interventricular mechanical delay (IVMD) and speckle-tracking radial strain using pre-specified cut-offs for each. Of 254 with baseline quantitative echocardiographic data available, 128 had LBBB, 81 had intraventricular conduction delay (IVCD), and 45 had right bundle branch block (RBBB). Radial dyssynchrony was observed in 85% of the patients with LBBB, 59% with IVCD*, and 40% with RBBB* (*P < 0.01 vs. LBBB). Of 248 (98%) with follow-up, LBBB patients had a significantly more favourable long-term survival than non-LBBB patients. However, non-LBBB patients with dyssynchrony had a more favourable event-free survival than those without dyssynchrony: radial dyssynchrony hazard ratio 2.6, 95% confidence interval (CI) 1.47-4.53 (P = 0.0008) and IVMD hazard ratio 4.9, 95% CI 2.60-9.16 (P = 0.0007). Right bundle branch block patients who lacked dyssynchrony had the least favourable outcome., Conclusion: Non-LBBB patients with dyssynchrony had a more favourable long-term survival than non-LBBB patients who lacked dyssynchrony. Mechanical dyssynchrony and QRS morphology are associated with outcome following CRT.

Prion diseases are characterized by the replicative propagation of disease-associated forms of prion protein (PrP(Sc); PrP refers to prion protein). The propagation is believed to proceed via two steps; the initial binding of the normal form of PrP (PrP(C)) to PrP(Sc) and the subsequent conversion of PrP(C) to PrP(Sc). We have explored the two-step model in prion-infected mouse neuroblastoma (ScN2a) cells by focusing on the mouse PrP (MoPrP) segment 92-GGTHNQWNKPSKPKTN-107, which is within a region previously suggested to be part of the binding interface or shown to differ in its accessibility to anti-PrP antibodies between PrP(C) and PrP(Sc). Exchanging the MoPrP segment with the corresponding chicken PrP segment (106-GGSYHNQKPWKPPKTN-121) revealed the necessity of MoPrP residues 99 to 104 for the chimeras to achieve the PrP(Sc) state, while segment 95 to 98 was replaceable with the chicken sequence. An alanine substitution at position 100, 102, 103, or 104 of MoPrP gave rise to nonconvertible mutants that associated with MoPrP(Sc) and interfered with the conversion of endogenous MoPrP(C). The interference was not evoked by a chimera (designated MCM2) in which MoPrP segment 95 to 104 was changed to the chicken sequence, though MCM2 associated with MoPrP(Sc). Incubation of the cells with a synthetic peptide composed of MoPrP residues 93 to 107 or alanine-substituted cognates did not inhibit the conversion, whereas an anti-P8 antibody recognizing the above sequence in PrP(C) reduced the accumulation of PrP(Sc) after 10 days of incubation of the cells. These results suggest the segment 100 to 104 of MoPrP(C) plays a key role in conversion after binding to MoPrP(Sc).

The radiopharmaceutical strontium chloride ((89)Sr) has been released as a new means of pain relief for painful bone metastasis in cancer patients. Because (89)Sr is a pure beta-emitting nuclide, it was considered difficult to know its distribution in the body from outside. Imaging with a gamma camera using bremsstrahlung radiation has been reported as one method, but there has been little detailed basic examination. We examined the optimal energy window and collimator when imaging with a gamma camera using bremsstrahlung radiation produced from (89)Sr beta rays. The results showed that setting the energy window at 75 keV, which is the peak formed by the characteristic X-ray of lead that is produced by the interaction of bremsstrahlung radiation and lead, is optimal for imaging. Also important are the material of the collimator and the use of an MELP collimator.

Previous methods to quantify dyssynchrony could not determine regional 3-dimensional (3-D) strain. We hypothesized that a novel 3-D speckle tracking strain imaging system can quantify left ventricular (LV) dyssynchrony and site of latest mechanical activation. We studied 64 subjects; 54 patients with heart failure were referred for cardiac resynchronization therapy (CRT) with an ejection fraction 25 +/- 6% and QRS interval 165 +/- 29 ms and 10 healthy volunteer controls. The 3-D speckle tracking system determined radial strain using a 16-segment model from a pyramidal 3-D dataset. Dyssynchrony was quantified as maximal opposing wall delay and SD in time to peak strain. The 3-D analysis was compared to standard 2-dimensional (2-D) strain datasets and site of 3-D latest mechanical activation, not possible by 2D was quantified. As expected, dyssynchrony in patients on CRT was significantly greater than in controls (maximal opposing wall delay 316 +/- 112 vs 59 +/- 12 ms and SD 124 +/- 48 vs 28 +/- 11 ms, p <0.001 vs normal). The 3-D opposing wall delay was closely correlated with 3-D 16-segment SD (r = 0.95) and 2-D mid-LV strain (r = 0.83) and SD (r = 0.85, all p values <0.001). The 3-D site of the latest mechanical activation was most commonly midposterior (26%), basal posterior (22%), midlateral (20%), and basal lateral (17%). Eleven patients studied after CRT demonstrated improvements in 3-D synchrony (300 +/- 124 to 94 +/- 37 ms) and ejection fraction (24 +/- 6% to 31 +/- 7%, p <0.05). In conclusion, 3-D speckle tracking can successfully quantify 3-D dyssynchrony and site the latest mechanical activation. This approach may play a clinical role in management of patients on CRT., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Although several echocardiographic approaches exist to quantify mechanical dyssynchrony, the comparative ability of different manufacturers' speckle-tracking software programs to predict response to cardiac resynchronization therapy (CRT) is unknown., Methods: Eighty-four patients with heart failure referred for CRT were studied (mean age, 64 +/- 12 years; mean ejection fraction [EF], 26 +/- 7%; mean QRS duration, 157 +/- 26 ms). Dyssynchrony was assessed using the same midventricular short-axis digital cine loop for each patient with 3 different offline speckle-tracking strain analysis programs: software A, speckle-tracking two-dimensional strain; software B, velocity vector imaging strain; and software C, speckle-tracking strain. Significant dyssynchrony was defined as an anterior septum-to-posterior wall delay > or =130 ms. Follow-up was available for 57 patients (mean, 7 +/- 4 months). Response to CRT was defined as an EF increase > or =15%., Results: Variability between software results was observed when patients had large degrees of dyssynchrony (> or =200 ms), with limits of agreement from 123 to 214 ms. However, close agreement for identifying patients with significant dyssynchrony was observed: 91% for software A versus B, 96% for software A versus C, and 93% for software B versus C. Importantly, the 3 software approaches' ability to predict EF outcome had similar sensitivities, specificities, and areas under receiver operating characteristic curves: 0.87, 0.86, and 0.86, respectively., Conclusions: Radial strain dyssynchrony analyses by 3 different speckle-tracking software programs were similarly able to predict EF response to CRT. Although variability in absolute values of dyssynchrony was observed, there was close agreement for determining the presence or absence of significant dyssynchrony. Speckle-tracking echocardiography has potential as a means to quantify dyssynchrony in a multicenter clinical trial or clinical practice.

Objective: To evaluate the usefulness of a breath-holding (BH) (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET) technique for PET/computed tomography (CT) scanning of pulmonary lesions near the diaphragm, where image quality is influenced by respiratory motion., Methods: In a basic study, simulated breath-holding PET (sBH-PET) data were acquired by repeating image acquisition eight times with fixation of a phantom at 15 s/bed. Free-breathing PET (FB-PET) was simulated by acquiring data even as moving the phantom at 120 s/bed (sFB-PET). Images with total acquisition times of 15 s, 30 s, 45 s, 60 s, and 120 s were generated for sBHPET. Receiver-operating characteristic (ROC) analyses and determination of the statistical significance of differences between sFB-PET images and sBH-PET images were performed. A total of 22 pulmonary lesions in 21 patients (12 men and 9 women, mean age 61.3 +/- 10.6 years, 10 benign lesions in 9 patients and 12 malignant lesions in 12 patients) were examined by FB-PET and BH-PET). For evaluation of these two acquisition methods, displacement of the lesion between CT and PET was considered to be a translation, and the statistical significance of differences in maximum standardized uptake value (SUV(max)) of the lesion was assessed using the paired t test., Results: In the basic study, sBH-PET images with acquisition times of 45 s, 60 s, and 120 s had significantly higher diagnostic accuracy than 120-s sFB-PET images (P < 0.05). In clinical cases, translation of the BH-PET images was significantly lower than that of the FB-PET images (benign: 5.29 +/- 4.02 mm vs. 11.79 +/- 8.27 mm, P = 0.005; malignant: 4.29 +/- 3.36 mm vs. 18.26 +/- 12.31 mm, P = 0.003). The SUV(max) of the lesions in the BH-PET images was significantly higher than that in the FB-PET images (benign: 2.40 +/- 0.86 vs. 2.20 +/- 0.85, P = 0.005; malignant: 4.84 +/- 2.16 vs. 3.75 +/- 2.11, P = 0.001)., Conclusions: BH-PET provides images with better diagnostic accuracy, avoids image degradation owing to respiratory motion, and yields more accurate attenuation correction. This method is very useful for overcoming the problem of respiratory motion.

The neurotoxicity of the 42-mer and 40-mer amyloid beta peptides (Abeta42 and Abeta40) is closely related to the radicalization at both Tyr10 and Met35. Abeta42 is more neurotoxic than Abeta40. Our previous structural analyses of Abeta42 suggested that Tyr10 and Met35 are brought closer together by the turn at positions 22 and 23, and the S-oxidized radical cation at position 35, which is the ultimate toxic radical species, can be produced effectively through oxidation by the phenoxy radical at position 10. To verify this idea, their separation was measured by site-directed spin labeling (MTSSL) by using ESR spectroscopy. Among the three kinds of Abeta42 derivatives, which are doubly or singly spin-labeled at position 10 and 35, only 10,35-MTSSL-Abeta42 showed a clear dipole coupling in continuous-wave ESR; this suggests that the intramolecular spin labels at position 10 and 35 in Abeta42 are located within approximately 15 A. In contrast, 10,35-MTSSL-Abeta40 did not give such signals. The distance between Tyr10 and Met35 in 10,35-MTSSL-Abeta40, which was successfully measured by pulsed ESR spectroscopy was 30 A long. The difference in the distance between Abeta42 and Abeta40 could explain in part the stronger neurotoxicity of Abeta42 compared to Abeta40.

A photoinduced analogue of the thermal Orton rearrangement reaction by which an N-chlorine atom from a side amino group is transferred to a phenyl ring was studied in the solid state. Contrary to the mixture of products obtained in solution, in the N-chloro-N-acetylaminobenzene crystals the photoreaction proceeds with complete preservation of crystallinity, affording selectively and quantitatively the para isomer of chloroacetanilide. Study of the reaction mechanism by in situ steady-state photodiffraction, a combination of photoexcitation by UV light and single-crystal X-ray diffraction analysis, provided evidence for creation of N-acetyl-N-phenylaminyl (AcPhN*) radical as a metastable reaction intermediate. The structure of the aminyl radical produced in 9.2% yield from the major disordered component in the statically 85.6:14.4 disordered crystal was directly observed for the first time. The unprecedented stability of the radical is prescribed to the solid-state cage effect, the reactive center of the radical species being locked away from the reactive target molecules. The creation of the radical and its head-to-tail chain reaction within the undulated hydrogen-bonded ribbons involving the acetyl carbonyl group are employed to explain the high selectivity of the photoinduced single-crystal to single-crystal Orton rearrangement. On the basis of the change of the crystal structure and the physicochemical data, a three-center five-atom mechanism involving homolytic cleavage of the N-Cl bond followed by hydrogen abstraction by the carbonyl group is suggested for the solid-state photoinduced Orton rearrangement.

The yeast prion [PSI(+)] represents an aggregated state of the translational release factor Sup35 (eRF3) and deprives termination complexes of functional Sup35, resulting in nonsense codon suppression. Protein-remodeling factor Hsp104 is involved in thermotolerance and [PSI(+)] propagation, however the structure-and-function relationship of Hsp104 for [PSI(+)] remains unclear. In this study, we engineered 58 chromosomal hsp104 mutants that affect residues considered structurally or functionally relevant to Hsp104 remodeling activity, yet most remain to be examined for their significance to [PSI(+)] in the same genetic background. Many of these hsp104 mutants were affected both in thermotolerance and [PSI(+)] propagation. However, nine mutants were impaired exclusively for [PSI(+)], while two mutants were impaired exclusively for thermotolerance. Mutations exclusively affecting [PSI(+)] are clustered around the lateral channel of the Hsp104 hexamer. These findings suggest that Hsp104 possesses shared as well as distinct remodeling activities for stress-induced protein aggregates and [PSI(+)] prion aggregates and that the lateral channel plays a role specific to [PSI(+)] prion propagation.

Introduction: Ventricular repolarization abnormalities are thought to contribute to lethal ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy (DCM). The purpose of this study was to evaluate exercise-induced T wave changes in DCM patients before and after beta-blocker therapy to investigate repolarization abnormalities., Methods and Results: Treadmill exercise testing was performed in 20 DCM patients and 50 normal subjects. T wave amplitude (TA: baseline to T wave apex; mV) and recovery time (RT: QRS onset to the maximum dV/dt point of the T wave; msec) were measured before and 1 minute after peak exercise. TA was averaged in the right and left precordial leads (TA(V1-3), TA(V4-6)). RT was normalized to the maximum QT interval in the 12-lead ECG and expressed as the %RT (%RT). %RT was also averaged in the precordial leads (%RT(V1-3), %RT(V4-6)). After exercise, TA increased and %RT decreased in both groups. In DCM patients, TA(V1-3) was greater and TA(V4-6) was less than in normal subjects before and after exercise. There was no difference in %RT(V1-3) between the groups, but %RT(V4-6) was greater in DCM patients both before and after exercise. DCM patients repeated the same evaluation after 6 months of oral beta-blocker therapy. Compared with measurements before beta-blocker therapy, TA(V1-3) and %RT(V1-3) did not change. However, TA(V4-6) increased and %RT(V4-6) decreased significantly both before and after exercise., Conclusion: DCM patients showed small TA and large %RT in the left precordial leads at rest as well as after exercise. Chronic beta-blocker therapy in DCM patients normalized these ventricular repolarization abnormalities.

Background: The yeast [PSI+] factor is transmitted by a prion mechanism involving self-propagating Sup35 aggregates. As with mammalian prions, a species barrier prevents prion transmission between yeast species. The N-terminal of Sup35 of Saccharomyces cerevisiae, necessary for [PSI+], contains two species-signature elements-a Gln/Asn-rich region (residues 1-41; designated NQ) that is followed by oligopeptide repeats (designated NR)., Results: In this study, we show that S. cerevisiae[PSI+] is transmissible through plasmid shuffling and cytoplasmic transfer to heterotypic Sup35s whose NQ is replaced with the S. cerevisiae NQ. In addition to homology, the N-terminal location is essential for NQ mediated susceptibility to [PSI+] transmission amongst heterotypic Sup35s. In vitro, a swap of NQ of S. cerevisiae Sup35 led to cross seeding of amyloid formation., Conclusions: These findings suggest that NQ discriminates self from non-self, and is sufficient to initiate [PSI+] transmission irrespective of whether NR is heterotypic. NR as well as NQ alone coalesces into existing [PSI+] aggregates, showing their independent potentials to interact with the identical sequence in the [PSI+] conformer. The role of NQ and NR in [PSI+] prion formation is discussed.