Advanced materials (Deerfield Beach, Fla.), Jan 27, 2015
Crystalline protein assemblies of polyhedra crystal (PhC) can be utilized as solid enzyme contain... more Crystalline protein assemblies of polyhedra crystal (PhC) can be utilized as solid enzyme containers for long-term storage of enzymes with retention of their enzymatic activity. The enzymes can be released from the crystals at the optimum pH for the enzymatic activity by dissolution of the crystals using in vivo crystal engineering.
Cardiovascular intervention and therapeutics, Jan 26, 2015
Several studies have shown coronary endothelial dysfunction and delayed arterial healing associat... more Several studies have shown coronary endothelial dysfunction and delayed arterial healing associated with first-generation drug-eluting stents. However, it remains unclear whether those issues persist for a longer term. We thus evaluated serial changes in endothelial function and intra-stent condition after paclitaxel-eluting stents (PES) implantation. Eight patients with stable effort angina were assessed at 9 and over 24 months (1st and 2nd follow-up) after PES implantation. Endothelial function was evaluated with intracoronary infusion of acetylcholine (Ach). Vascular responses were quantitatively measured. Intra-stent condition was evaluated using angioscopy. We assessed (1) the degree of neointimal coverage over the stent (grade 0: no coverage to grade 3: full coverage); (2) presence of yellow intima inside the stent, and (3) existence of in-stent thrombus. Vasomotions proximal to the stent at 2nd follow-up significantly improved compared with 1st follow-up (p = 0.04), whereas v...
Cardiovascular intervention and therapeutics, 2015
The impact of the fractional flow reserve (FFR) on clinical decision-making remains unclear in da... more The impact of the fractional flow reserve (FFR) on clinical decision-making remains unclear in daily practice. The CVIT-DEFER registry is a prospective multicenter registry enrolling consecutive patients with angiographically intermediate coronary stenosis for whom FFR measurement is clinically indicated. The treatment strategy determined from angiographic findings alone and the strategy selected after FFR measurement were compared. Data on the treatment strategy were obtained for 3093 subjects. The average age of these subjects was 69.5 ± 10.2 years and 73.8 % were men. The majority had stable coronary artery disease, including 60.4 % with stable angina pectoris. The treatment strategy based on angiographic findings was medical management in 34.5 %, percutaneous coronary intervention (PCI) in 63.5 %, and coronary artery bypass grafting in 2.1 %. The FFR was ≤0.8 in 1566 lesions (42.2 %). After FFR measurement, medical treatment was changed to revascularization in 19.7 %, while PCI ...
Cardiovascular intervention and therapeutics, 2014
The fractional flow reserve (FFR) is considered to be a reliable index for the assessment of clin... more The fractional flow reserve (FFR) is considered to be a reliable index for the assessment of clinically relevant coronary artery stenosis. However, mismatch in assessing the severity of coronary stenosis between coronary angiography and the FFR has been pointed out. The cardiovascular intervention therapeutics (CVIT)-DEFER registry is a prospective multicenter registry study that has enrolled 3,228 consecutive patients among 3,804 patients with angiographically moderate coronary artery lesions in whom FFR analysis was clinically indicated. The demographic and angiographic parameters associated with an FFR ≤0.8 were analyzed, and the incidence of discrepancy between the angiographic severity of coronary stenosis and the FFR was assessed. Based on the visual assessment, 1,609 (42.9%) lesions were categorized as showing 50% stenosis, 1,882 lesions (50.2%) as 75% stenosis, and 257 lesions (6.9%) as 90% stenosis. Angiographic-FFR "mismatch," which was defined as visual stenosis...
The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells ... more The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less neovascularization. Forkhead transcription factor 4 (FOXO4) was reported to play a pivotal role in apoptosis signaling of EPCs in response to oxidative stress. Accordingly, we assessed whether FOXO4-knockdown EPCs (FOXO4KD-EPCs) could suppress the oxidative stress-induced apoptosis and augment the neovascularization capacity in ischemic limbs. We transfected small interfering RNA targeted against FOXO4 of human EPCs to generate FOXO4KD-EPCs and confirmed a successful knockdown. FOXO4KD-EPCs gained resistance to apoptosis in response to hydrogen peroxide in vitro. Oxidative stress stained by dihydroethidium was stronger for the immunodeficient rat ischemic limb tissue than for the rat non-ischemic one. Although the number of apoptotic EPCs injected...
Cardiovascular intervention and therapeutics, 2013
Antiplatelet therapy could prevent stent thrombosis, but may be associated with an increased risk... more Antiplatelet therapy could prevent stent thrombosis, but may be associated with an increased risk of bleeding. Recent studies have revealed that bleeding complications are relatively frequent in patients with acute coronary syndromes. Our aim was to describe the current status of antiplatelet therapy for Japanese patients with acute myocardial infarction (AMI). The Japan AMI (J-AMI) registry is a prospective observational study that has enrolled 2,030 consecutive patients with stent thrombosis elevation myocardial infarction (STEMI) admitted to 213 participating Japanese institutions. Current antiplatelet therapy for STEMI was assessed, and the occurrence of bleeding complications (based on GUSTO bleeding criteria) and stent thrombosis was also evaluated. Additionally, the clinical course after bleeding episodes was investigated. Percutaneous coronary intervention (PCI) was done in 97.2% of the patients, using a drug-eluting stent in 30% and a bare metal stent in 63% of PCI cases. A...
Cardiovascular intervention and therapeutics, 2013
The door-to-balloon time and total ischemic time are important predictors of the outcome in patie... more The door-to-balloon time and total ischemic time are important predictors of the outcome in patients with ST elevation myocardial infarction (STEMI) receiving primary angioplasty, but the current situation in Japan is unknown. The Japan Acute Myocardial Infarction registry is a prospective observational study of 2,030 consecutive STEMI patients admitted to 213 Japanese institutions. The time from symptom onset to hospital arrival, door-to-balloon time, and in-hospital outcome were assessed. Data were compared between patients treated during regular hours or after hours. Percutaneous coronary angioplasty was done in 97.2 % of the patients, using drug-eluting stents in 30 % and bare metal stents in 63 % of the treated cases. The median symptom onset-to-door time (25th and 75th percentiles) was 135 min (64-305 min), median door-to-balloon time was 42 min (28-66 min), and mean procedural time was 98 ± 51 min. The on-call catheterization team performed 48.5 % of the procedures. There was...
Proceedings of the National Academy of Sciences of the United States of America, Jan 20, 2006
Protein-to-protein electron transfer (ET) is a critical process in biological chemistry for which... more Protein-to-protein electron transfer (ET) is a critical process in biological chemistry for which fundamental understanding is expected to provide a wealth of applications in biotechnology. Investigations of protein-protein ET systems in reductive activation of artificial cofactors introduced into proteins remains particularly challenging because of the complexity of interactions between the cofactor and the system contributing to ET. In this work, we construct an artificial protein-protein ET system, using heme oxygenase (HO), which is known to catalyze the conversion of heme to biliverdin. HO uses electrons provided from NADPH/cytochrome P450 reductase (CPR) through protein-protein complex formation during the enzymatic reaction. We report that a Fe(III)(Schiff-base), in the place of the active-site heme prosthetic group of HO, can be reduced by NADPH/CPR. The crystal structure of the Fe(10-CH(2)CH(2)COOH-Schiff-base).HO composite indicates the presence of a hydrogen bond between ...
Pediatrics international : official journal of the Japan Pediatric Society, 2001
The Research Committee of Ministry of Health, Labour and Welfare 'Study of treatment and long... more The Research Committee of Ministry of Health, Labour and Welfare 'Study of treatment and long-term management in Kawasaki disease' reported the guidelines for catheter intervention in coronary artery lesion in Kawasaki disease in this paper. The contents include: (i) background and natural history of coronary artery lesion in Kawasaki disease; (ii) indication of catheter intervention; (iii) types of procedure, and their indication and care; (iv) institute and backup system; (v) the management after procedure, evaluation and follow up; and (vi) prospects, especially in relation to bypass surgery.
Systematic analysis of in vivo angioscopy and postmortem histopathology for paclitaxel-eluting st... more Systematic analysis of in vivo angioscopy and postmortem histopathology for paclitaxel-eluting stents (PES) has not been previously reported. We assessed 1-month angioscopic and histopathologic sequelae of overlapping PES in pig coronary arteries. Overlapping PES and bare-metal stents (BMS; n=9, one pair per pig) were implanted, and animals were euthanized at 1 month. Late lumen loss was reduced in PES compared with BMS (0.46+/-0.63 mm versus 1.30+/-0.50 mm; P=0.01). Angioscopically, PES stent struts were clearly visible and accompanied by substantial red material indicating mural thrombi. In contrast, stent struts and mural thrombi were barely visible in BMS (P<0.001 versus PES). Macroscopically, mural thrombi were abundant but distributed irregularly throughout the PES, with greater concentration in overlapping segments. Only occasional mural thrombi were noted for BMS. Microscopically, neointima of BMS was fibrocellular and mature, whereas only a thin layer of immature neointi...
Advanced materials (Deerfield Beach, Fla.), Jan 27, 2015
Crystalline protein assemblies of polyhedra crystal (PhC) can be utilized as solid enzyme contain... more Crystalline protein assemblies of polyhedra crystal (PhC) can be utilized as solid enzyme containers for long-term storage of enzymes with retention of their enzymatic activity. The enzymes can be released from the crystals at the optimum pH for the enzymatic activity by dissolution of the crystals using in vivo crystal engineering.
Cardiovascular intervention and therapeutics, Jan 26, 2015
Several studies have shown coronary endothelial dysfunction and delayed arterial healing associat... more Several studies have shown coronary endothelial dysfunction and delayed arterial healing associated with first-generation drug-eluting stents. However, it remains unclear whether those issues persist for a longer term. We thus evaluated serial changes in endothelial function and intra-stent condition after paclitaxel-eluting stents (PES) implantation. Eight patients with stable effort angina were assessed at 9 and over 24 months (1st and 2nd follow-up) after PES implantation. Endothelial function was evaluated with intracoronary infusion of acetylcholine (Ach). Vascular responses were quantitatively measured. Intra-stent condition was evaluated using angioscopy. We assessed (1) the degree of neointimal coverage over the stent (grade 0: no coverage to grade 3: full coverage); (2) presence of yellow intima inside the stent, and (3) existence of in-stent thrombus. Vasomotions proximal to the stent at 2nd follow-up significantly improved compared with 1st follow-up (p = 0.04), whereas v...
Cardiovascular intervention and therapeutics, 2015
The impact of the fractional flow reserve (FFR) on clinical decision-making remains unclear in da... more The impact of the fractional flow reserve (FFR) on clinical decision-making remains unclear in daily practice. The CVIT-DEFER registry is a prospective multicenter registry enrolling consecutive patients with angiographically intermediate coronary stenosis for whom FFR measurement is clinically indicated. The treatment strategy determined from angiographic findings alone and the strategy selected after FFR measurement were compared. Data on the treatment strategy were obtained for 3093 subjects. The average age of these subjects was 69.5 ± 10.2 years and 73.8 % were men. The majority had stable coronary artery disease, including 60.4 % with stable angina pectoris. The treatment strategy based on angiographic findings was medical management in 34.5 %, percutaneous coronary intervention (PCI) in 63.5 %, and coronary artery bypass grafting in 2.1 %. The FFR was ≤0.8 in 1566 lesions (42.2 %). After FFR measurement, medical treatment was changed to revascularization in 19.7 %, while PCI ...
Cardiovascular intervention and therapeutics, 2014
The fractional flow reserve (FFR) is considered to be a reliable index for the assessment of clin... more The fractional flow reserve (FFR) is considered to be a reliable index for the assessment of clinically relevant coronary artery stenosis. However, mismatch in assessing the severity of coronary stenosis between coronary angiography and the FFR has been pointed out. The cardiovascular intervention therapeutics (CVIT)-DEFER registry is a prospective multicenter registry study that has enrolled 3,228 consecutive patients among 3,804 patients with angiographically moderate coronary artery lesions in whom FFR analysis was clinically indicated. The demographic and angiographic parameters associated with an FFR ≤0.8 were analyzed, and the incidence of discrepancy between the angiographic severity of coronary stenosis and the FFR was assessed. Based on the visual assessment, 1,609 (42.9%) lesions were categorized as showing 50% stenosis, 1,882 lesions (50.2%) as 75% stenosis, and 257 lesions (6.9%) as 90% stenosis. Angiographic-FFR "mismatch," which was defined as visual stenosis...
The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells ... more The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less neovascularization. Forkhead transcription factor 4 (FOXO4) was reported to play a pivotal role in apoptosis signaling of EPCs in response to oxidative stress. Accordingly, we assessed whether FOXO4-knockdown EPCs (FOXO4KD-EPCs) could suppress the oxidative stress-induced apoptosis and augment the neovascularization capacity in ischemic limbs. We transfected small interfering RNA targeted against FOXO4 of human EPCs to generate FOXO4KD-EPCs and confirmed a successful knockdown. FOXO4KD-EPCs gained resistance to apoptosis in response to hydrogen peroxide in vitro. Oxidative stress stained by dihydroethidium was stronger for the immunodeficient rat ischemic limb tissue than for the rat non-ischemic one. Although the number of apoptotic EPCs injected...
Cardiovascular intervention and therapeutics, 2013
Antiplatelet therapy could prevent stent thrombosis, but may be associated with an increased risk... more Antiplatelet therapy could prevent stent thrombosis, but may be associated with an increased risk of bleeding. Recent studies have revealed that bleeding complications are relatively frequent in patients with acute coronary syndromes. Our aim was to describe the current status of antiplatelet therapy for Japanese patients with acute myocardial infarction (AMI). The Japan AMI (J-AMI) registry is a prospective observational study that has enrolled 2,030 consecutive patients with stent thrombosis elevation myocardial infarction (STEMI) admitted to 213 participating Japanese institutions. Current antiplatelet therapy for STEMI was assessed, and the occurrence of bleeding complications (based on GUSTO bleeding criteria) and stent thrombosis was also evaluated. Additionally, the clinical course after bleeding episodes was investigated. Percutaneous coronary intervention (PCI) was done in 97.2% of the patients, using a drug-eluting stent in 30% and a bare metal stent in 63% of PCI cases. A...
Cardiovascular intervention and therapeutics, 2013
The door-to-balloon time and total ischemic time are important predictors of the outcome in patie... more The door-to-balloon time and total ischemic time are important predictors of the outcome in patients with ST elevation myocardial infarction (STEMI) receiving primary angioplasty, but the current situation in Japan is unknown. The Japan Acute Myocardial Infarction registry is a prospective observational study of 2,030 consecutive STEMI patients admitted to 213 Japanese institutions. The time from symptom onset to hospital arrival, door-to-balloon time, and in-hospital outcome were assessed. Data were compared between patients treated during regular hours or after hours. Percutaneous coronary angioplasty was done in 97.2 % of the patients, using drug-eluting stents in 30 % and bare metal stents in 63 % of the treated cases. The median symptom onset-to-door time (25th and 75th percentiles) was 135 min (64-305 min), median door-to-balloon time was 42 min (28-66 min), and mean procedural time was 98 ± 51 min. The on-call catheterization team performed 48.5 % of the procedures. There was...
Proceedings of the National Academy of Sciences of the United States of America, Jan 20, 2006
Protein-to-protein electron transfer (ET) is a critical process in biological chemistry for which... more Protein-to-protein electron transfer (ET) is a critical process in biological chemistry for which fundamental understanding is expected to provide a wealth of applications in biotechnology. Investigations of protein-protein ET systems in reductive activation of artificial cofactors introduced into proteins remains particularly challenging because of the complexity of interactions between the cofactor and the system contributing to ET. In this work, we construct an artificial protein-protein ET system, using heme oxygenase (HO), which is known to catalyze the conversion of heme to biliverdin. HO uses electrons provided from NADPH/cytochrome P450 reductase (CPR) through protein-protein complex formation during the enzymatic reaction. We report that a Fe(III)(Schiff-base), in the place of the active-site heme prosthetic group of HO, can be reduced by NADPH/CPR. The crystal structure of the Fe(10-CH(2)CH(2)COOH-Schiff-base).HO composite indicates the presence of a hydrogen bond between ...
Pediatrics international : official journal of the Japan Pediatric Society, 2001
The Research Committee of Ministry of Health, Labour and Welfare 'Study of treatment and long... more The Research Committee of Ministry of Health, Labour and Welfare 'Study of treatment and long-term management in Kawasaki disease' reported the guidelines for catheter intervention in coronary artery lesion in Kawasaki disease in this paper. The contents include: (i) background and natural history of coronary artery lesion in Kawasaki disease; (ii) indication of catheter intervention; (iii) types of procedure, and their indication and care; (iv) institute and backup system; (v) the management after procedure, evaluation and follow up; and (vi) prospects, especially in relation to bypass surgery.
Systematic analysis of in vivo angioscopy and postmortem histopathology for paclitaxel-eluting st... more Systematic analysis of in vivo angioscopy and postmortem histopathology for paclitaxel-eluting stents (PES) has not been previously reported. We assessed 1-month angioscopic and histopathologic sequelae of overlapping PES in pig coronary arteries. Overlapping PES and bare-metal stents (BMS; n=9, one pair per pig) were implanted, and animals were euthanized at 1 month. Late lumen loss was reduced in PES compared with BMS (0.46+/-0.63 mm versus 1.30+/-0.50 mm; P=0.01). Angioscopically, PES stent struts were clearly visible and accompanied by substantial red material indicating mural thrombi. In contrast, stent struts and mural thrombi were barely visible in BMS (P<0.001 versus PES). Macroscopically, mural thrombi were abundant but distributed irregularly throughout the PES, with greater concentration in overlapping segments. Only occasional mural thrombi were noted for BMS. Microscopically, neointima of BMS was fibrocellular and mature, whereas only a thin layer of immature neointi...
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Papers by Takafumi Ueno