Publications by authors named "Yohei Ueno"

12 Publications

  • Page 1 of 1

Identification of Anemia for Predicting Mid-Term Prognosis After Transcatheter Aortic Valve Implantation in Japanese Patients - Insights From the OCEAN-TAVI Registry.

Circ Rep 2021 Apr 7;3(5):286-293. Epub 2021 Apr 7.

Department of Cardiology, Keio University School of Medicine Tokyo Japan.

Patients with anemia have a poor prognosis following transcatheter aortic valve implantation (TAVI). Given the unique distribution of hemoglobin levels in the Japanese cohort, the optimal cut-off hemoglobin value may help stratify Japanese patients' mortality following TAVI. Data of patients who underwent TAVI were collected from the prospective multicenter Optimized transCathEter vAlvular iNtervention (OCEAN)-TAVI Registry. Receiver operating characteristic analysis was used to calculate a hemoglobin cut-off value to stratify 2-year mortality following TAVI. In all, 2,588 patients (mean [±SD] age 84.4±5.2 years, 795 men) were included in the study. Of these patients, 909 (35.1%) had anemia, which was defined as hemoglobin <10.9 g/dL for men and <10.4 g/dL for women. The presence of anemia, uniquely defined for the Japanese cohort, was independently associated with 2-year mortality following TAVI, with an odds ratio of 1.77 (95% confidence interval 1.39-2.25) adjusted for 14 other clinical variables. The existence of anemia, uniquely defined for the Japanese cohort, was associated with mid-term mortality following TAVI.
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http://dx.doi.org/10.1253/circrep.CR-21-0026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099672PMC
April 2021

Impact of optimal heart rate on left ventricular reverse remodeling and functional improvement in patients with systolic heart failure.

Heart Vessels 2021 May 6. Epub 2021 May 6.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani Toyama, Toyama, 930-0194, Japan.

Heart rate modulation therapy using ivabradine reduces mortality and morbidity in patients with systolic heart failure, whereas too reduced heart rate seems to worsen the clinical outcome. The optimal heart rate during heart rate modulation therapy remains unknown. Consecutive patients with left ventricular ejection fraction < 50% who received echocardiographic assessments and simultaneous heart rate measurements were retrospectively investigated. Theoretically ideal heart rate was calculated using a previously proposed formula: 93 - 0.13 × (deceleration time [msec]). Impacts of heart rate on the 1-year echocardiographic left ventricular reverse remodeling were compared among the three groups stratified by the heart rate status: optimal heart rate group (within 10 bpm of ideal heart rate), below-optimal heart rate group (< 10 bpm of ideal heart rate), and above-optimal heart rate group (> 10 bpm of ideal heart rate). A total of 75 patients (70 years old, 60 men) were included. There were no significant differences in the baseline characteristics among the three groups, except for the higher prevalence of tolvaptan use and higher plasma B-type natriuretic peptide level in the below-optimal heart rate group. Left ventricular end-diastolic diameter (from 55 to 54) and left ventricular ejection fraction (from 39 to 46) improved significantly only in the optimal heart rate group at 1-year follow-up (p < 0.05 for both). Optimal heart rate, which was calculated using a formula consisting of deceleration time, was associated with cardiac reverse remodeling in patients with systolic heart failure. Prospective study to investigate the implication of deceleration time-guided aggressive heart rate optimization is the next concern.
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http://dx.doi.org/10.1007/s00380-021-01864-5DOI Listing
May 2021

Percutaneous transseptal transcatheter mitral valve-in-valve replacement for degenerated mitral bioprosthesis: The first experience in Japan.

J Cardiol Cases 2021 Jan 25;23(1):49-52. Epub 2020 Sep 25.

Cardiovascular Center, Toyama University Hospital, Toyama, Japan.

A 76-year-old woman had received surgical mitral valve replacement with Magna Mitral Ease (Edwards Lifesciences, Irvine, CA, USA) 25 mm for functional severe mitral regurgitation 6 years previously. She presented recurrence of heart failure due to severe stenotic and moderate regurgitant degeneration of the implanted mitral bioprosthesis. Considering her comorbidities and left ventricular systolic dysfunction, our heart valve team eventually decided to perform percutaneous transseptal transcatheter mitral valve-in-valve replacement instead of surgical redo mitral valve replacement, using a 26 mm SAPIEN 3 valve (Edwards Lifesciences) via trans-femoral approach. Post-procedural course was uneventful and she was discharged on post-procedural day 2. This is, to the best of our knowledge, the first case of successful percutaneous transseptal transcatheter mitral valve-in-valve replacement in Japan. Further large-scale prospective studies are warranted to validate its long-term safety and efficacy, particularly by comparing with the redo surgery. < We experienced an off-label transseptal mitral valve-in-valve replacement using SAPIEN 3 to treat degenerative mitral bioprosthesis for the first time in Japan. Although further large-scale prospective studies are warranted, this procedure should be a promising therapeutic alternative to conventional redo-surgery, particularly for elderly patients with multiple comorbidities.>.
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http://dx.doi.org/10.1016/j.jccase.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783651PMC
January 2021

Impact of the angle between aortic and mitral annulus on the occurrence of hemolysis during Impella support.

J Artif Organs 2020 Sep 14;23(3):207-213. Epub 2020 May 14.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.

Despite optimal management, we sometimes experience refractory hemolysis requiring extensive device speed reduction or continuous hemodiafiltration following Impella implantation. However, pre-procedural predictors of such a refractory hemolysis remain unknown. In this study, we investigated the pre-procedural factors, including the echocardiographic narrow angle between aortic and mitral annulus, associating with the occurrence of refractory hemolysis following Impella insertion. We enrolled 26 patients (71 years, 65% male) who received Impella insertion between March 2018 and November 2019. Among baseline characteristics, the angle between aortic and mitral annulus, < 126.5°, was an independent risk factor of refractory hemolysis with an adjusted hazard ratio of 7.840 (95% confidence interval 0.925-66.44) and was associated with lower 30-day survival (64% vs. 100%, p = 0.0116). The narrow angle between aortic and mitral annulus might be a useful tool to risk-stratify the occurrence of refractory hemolysis following Impella insertion.
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http://dx.doi.org/10.1007/s10047-020-01172-1DOI Listing
September 2020

The impact of changes in B-type natriuretic peptide levels on prognosis after transcatheter aortic valve implantation.

Cardiovasc Interv Ther 2020 Jul 16;35(3):283-290. Epub 2019 Sep 16.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

Higher B-type natriuretic peptide (BNP) levels at discharge predict higher cardiovascular events in transcatheter aortic valve implantation (TAVI) patients. However, it is not known whether the reduction in BNP levels effectively predicts prognosis. The purpose was to examine the predictive power of percentage changes in BNP levels for all-cause death and hospitalization of heart failure (HF) after TAVI in severe aortic stenosis (AS) patients. We analyzed 70 severe AS patients treated with TAVI who had a record of BNP > 200 pg/mL. Receiver operating characteristics (ROC) curves analysis for all-cause death and hospitalization for HF after TAVI revealed the cut-off percentage change in BNP, and we divided the study population into the "responder group" and the "non-responder group". The cut-off level for the percentage change in BNP evaluated by ROC analysis was a 40% decrease in BNP (AUC = 0.733, p < 0.001). There were 48 patients (68.6%) in the responder group and 22 patients (31.4%) in the non-responder group. Kaplan-Meier estimates showed that the responder group had lower all-cause death and hospitalization for HF than the non-responder group by a log rank test (all-cause mortality; p = 0.006, hospitalization rate for HF; p < 0.001). The predictor of the non-responder group using multivariate logistic regression analysis was AF (OR 4.2, 95% CI 1.15-16.2, p = 0.03). A reduction of BNP was associated with improved prognosis after TAVI.
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http://dx.doi.org/10.1007/s12928-019-00621-wDOI Listing
July 2020

Frozen State of Sephadex Gels of Different Crosslink Density Analyzed by X-ray Computed Tomography and X-ray Diffraction.

Gels 2018 May 18;4(2). Epub 2018 May 18.

Graduate School of Science and Technology, Gunma University, 4-2 Aramaki, Maebashi, Gunma 371-8510, Japan.

Water in Sephadex (crosslinked dextran) gels is known to indicate different freezing behavior which is dependent on the density of the crosslinks, and water in a Sephadex G25 gel remains partially unfrozen during cooling and crystallizes during rewarming. The mechanism of anomalous ice crystallization during rewarming is still unclear. The objective of this study is to observe the ice grains that form in Sephadex beads and to comprehend their frozen state with a focus on the ice crystallization during rewarming. Sephadex beads containing 50 wt % water were prepared and used for the measurements. The observation of the ice grains was carried out by using synchrotron radiation-sourced X-ray CT (computed tomography). XRD (X-ray diffraction) analysis was also conducted to investigate the frozen state. As a result, ice grains that were larger than ~1 μm were hardly observed after the slow cooling of Sephadex beads, except in the G25 beads. However, at the occurrence of ice crystallization during rewarming, ice grains that were larger than 10 μm appeared in the G25 beads. Using XRD, it was found that small incomplete ice crystals were formed in G25 beads and the presence of glassy water was indicated in the gel. In conclusion, the size and distribution of ice grains that formed in Sephadex beads were different depending on the density of the crosslinks.
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http://dx.doi.org/10.3390/gels4020044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209288PMC
May 2018

Highly efficient production of VHH antibody fragments in Brevibacillus choshinensis expression system.

Protein Expr Purif 2015 Jan 5;105:23-32. Epub 2014 Oct 5.

Applied and Molecular Microbiology, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan. Electronic address:

Anti-IZUMO1PFF VHH (variable domain of camelid heavy chain antibody) clones, N6 and N15, from immunized alpaca (Lama pacos) phage library were efficiently expressed and their VHH products were secreted into the culture medium of Brevibacillus choshinensis HPD31-SP3, e.g., at a level of 26-95mg in 100ml conventional flask culture. With a 3-L scale fed-batch culture for 65h, the N15 VHH protein with C-terminal His-tag was produced at ∼3g/l culture medium. The N6 and N15 proteins were easily purified to apparent homogeneity by cation exchange and Ni-affinity chromatographies. Both proteins showed specific antigen-binding activity by ELISA and high antigen binding affinity, KD=6.0-8.6nM, by surface plasmon resonance analysis. Size exclusion chromatography-multi-angle laser light scattering analysis revealed that N6 and N15 proteins purified were exclusively monomeric form in phosphate buffered saline. CD spectrum showed beta-sheet rich structure, consistent with a typical antibody structure and also suggested aromatic-aromatic interactions, as indicated by a positive peak at 232nm. Thermal melting analysis of the N15 protein with C-terminal His-tag demonstrated a clear thermal transition with a Tm at 67°C. The heat-denatured sample recovered antigen binding activity upon cooling, indicating a reversible denaturation.
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http://dx.doi.org/10.1016/j.pep.2014.09.017DOI Listing
January 2015

Molecular evolution of the substrate specificity of ent-kaurene synthases to adapt to gibberellin biosynthesis in land plants.

Biochem J 2014 Sep;462(3):539-46

‡Department of Biochemistry, Okayama University of Science, Ridaicho, Okayama 700-0005, Japan.

ent-Kaurene is a key intermediate in the biosynthesis of the plant hormone gibberellin. In ent-kaurene biosynthesis in flowering plants, two diterpene cyclases (DTCs), ent-copalyl diphosphate (ent-CDP) synthase (ent-CPS) and ent-kaurene synthase (KS), catalyse the cyclization of geranylgeranyl diphosphate to ent-CDP and ent-CDP to ent-kaurene, respectively. In contrast, the moss Physcomitrella patens has a bifunctional ent-CPS/KS (PpCPS/KS) that catalyses both cyclization reactions. To gain more insight into the functional diversity of ent-kaurene biosynthetic enzymes in land plants, we focused on DTCs in the lycophyte Selaginella moellendorffii. The present paper describes the characterization of two S. moellendorffii DTCs (SmKS and SmDTC3) in vitro. SmDTC3 converted ent-CDP into ent-16α-hydroxykaurane and also used other CDP stereoisomers as substrate. Remarkably, SmKS, which produces ent-kaurene from ent-CDP, showed similar substrate selectivity: both SmKS and SmDTC3 synthesized sandaracopimaradiene from normal CDP. Therefore, the diversity of substrate recognition among KSs from other plants was investigated. PpCPS/KS could use normal CDP and syn-CDP as well as ent-CDP as substrate. In contrast, lettuce KS showed high specificity for ent-CDP, and rice KS recognized only ent-CDP. Our studies imply that ancient KS having low substrate specificity has evolved to be specific for ent-CDP to the biosynthesis of gibberellin.
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http://dx.doi.org/10.1042/BJ20140134DOI Listing
September 2014

Enzymatic (13)C labeling and multidimensional NMR analysis of miltiradiene synthesized by bifunctional diterpene cyclase in Selaginella moellendorffii.

J Biol Chem 2011 Dec 25;286(50):42840-7. Epub 2011 Oct 25.

Institute of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan.

Diterpenes show diverse chemical structures and various physiological roles. The diversity of diterpene is primarily established by diterpene cyclases that catalyze a cyclization reaction to form the carbon skeleton of cyclic diterpene. Diterpene cyclases are divided into two types, monofunctional and bifunctional cyclases. Bifunctional diterpene cyclases (BDTCs) are involved in hormone and defense compound biosyntheses in bryophytes and gymnosperms, respectively. The BDTCs catalyze the successive two-step type-B (protonation-initiated cyclization) and type-A (ionization-initiated cyclization) reactions of geranylgeranyl diphosphate (GGDP). We found that the genome of a lycophyte, Selaginella moellendorffii, contains six BDTC genes with the majority being uncharacterized. The cDNA from S. moellendorffii encoding a BDTC-like enzyme, miltiradiene synthase (SmMDS), was cloned. The recombinant SmMDS converted GGDP to a diterpene hydrocarbon product with a molecular mass of 272 Da. Mutation in the type-B active motif of SmMDS abolished the cyclase activity, whereas (+)-copalyl diphosphate, the reaction intermediate from the conversion of GGDP to the hydrocarbon product, rescued the cyclase activity of the mutant to form a diterpene hydrocarbon. Another mutant lacking type-A activity accumulated copalyl diphosphate as the reaction intermediate. When the diterpene hydrocarbon was enzymatically synthesized from [U-(13)C(6)]mevalonate, all carbons were labeled with (13)C stable isotope (>99%). The fully (13)C-labeled product was subjected to (13)C-(13)C COSY NMR spectroscopic analyses. The direct carbon-carbon connectivities observed in the multidimensional NMR spectra demonstrated that the hydrocarbon product by SmMDS is miltiradiene, a putative biosynthetic precursor of tanshinone identified from the Chinese medicinal herb Salvia miltiorrhiza. Hence, SmMDS functions as a bifunctional miltiradiene synthase in S. moellendorffii. In this study, we demonstrate that one-dimensional and multidimensional (13)C NMR analyses of completely (13)C-labeled compound are powerful methods for biosynthetic studies.
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http://dx.doi.org/10.1074/jbc.M111.302703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234827PMC
December 2011

Human bitter taste receptors hTAS2R8 and hTAS2R39 with differential functions to recognize bitter peptides.

Biosci Biotechnol Biochem 2011 13;75(6):1188-90. Epub 2011 Jun 13.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

The strong bitter peptide, Phe-Phe-Pro-Arg, activated cultured cells expressing either of the known human bitter taste receptors, hTAS2R8 and hTAS2R39. The partial structure of Pro-Arg activated hTAS2R39, but did not activate hTAS2R8. These receptors may not indiscriminately recognize bitter peptides, but have a differential function in their recognition.
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http://dx.doi.org/10.1271/bbb.100893DOI Listing
October 2011

Evaluation of the bitterness of green tea catechins by a cell-based assay with the human bitter taste receptor hTAS2R39.

Biochem Biophys Res Commun 2011 Feb 25;405(4):620-5. Epub 2011 Jan 25.

School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.

Catechins have a broad range of physiological functions and act as the main taste ingredient of green tea. Although catechins show a strong bitterness, the bitter taste receptor for catechins has not been fully understood. The objective of this study was to identify the receptor for the major green tea catechins such as (-)-epicatechin (EC), (-)-epicatechin gallate (ECg), (-)-epigallocatechin (EGC), and (-)-epigallocatechin gallate (EGCg). By the cell-based assay using cultured cells expressing human bitter taste receptor, a clear response of hTAS2R39-expressing cells was observed to 300μM of either ECg or EGCg, which elicit a strong bitterness in humans. The response of hTAS2R39-expressing cells to ECg was the strongest among the tested catechins, followed by EGCg. Because the cellular response to EC and EGC is much weaker than those of ECg and EGCg, galloyl groups was strongly supposed to be involved in the bitter intensity. This finding is similar to the observations of taste intensity obtained from a human sensory study. Our results suggest the participation of hTAS2R39 in the detection of catechins in humans, indicating the possibility that bitterness of tea catechins can be evaluated by using cells expressing hTAS2R39.
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http://dx.doi.org/10.1016/j.bbrc.2011.01.079DOI Listing
February 2011

The human bitter taste receptor, hTAS2R16, discriminates slight differences in the configuration of disaccharides.

Biochem Biophys Res Commun 2010 Nov 20;402(4):595-601. Epub 2010 Oct 20.

General Research Institute of Food Science and Technology, Nissin Foods Holdings Co. Ltd., Shiga, Japan.

Sweetness and bitterness are key determinants of food acceptance and rejection, respectively. Sugars, such as sucrose and fructose, are generally recognized as sweet. However, not all sugars are sweet, and even anomers may have quite different tastes. For example, gentiobiose is bitter, whereas its anomer, isomaltose, is sweet. Despite this unique sensory character, the molecular basis of the bitterness of gentiobiose remains to be clarified. In this study, we used calcium imaging analysis of human embryonic kidney 293T cells that heterologously expressed human taste receptors to demonstrate that gentiobiose activated hTAS2R16, a bitter taste receptor, but not hT1R2/hT1R3, a sweet taste receptor. In contrast, isomaltose activated hT1R2/hT1R3. As a result, these anomers elicit different taste sensations. Mutational analysis of hTAS2R16 also indicated that gentiobiose and β-D-glucopyranosides, such as salicin share a common binding site of hTAS2R16.
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http://dx.doi.org/10.1016/j.bbrc.2010.10.059DOI Listing
November 2010