Language：English   Publisher：The Society of Photopolymer Science and Technology(SPST)  

Silicone tubing is used in small-diameter long-sized tubes for medical applications, such as urinary catheters. However, bacteria in urine adhere to the catheters, forming colonies and biofilms and resulting in blockages and urinary tract infections. Therefore, we have reported a method of AC high-voltage plasma chemical vapor deposition to prevent bacterial adhesion by depositing diamond-like carbon (DLC) on a lumen of a silicone catheter and smoothing the surface. However, the sp³/sp² structure of DLC on the lumen surface is unresolved, and biomimetic DLC with a functionalized surface has not been investigated. Therefore, we analyzed a flexible membrane structure that can deform as the resin tube deforms. In addition, we developed a lumen surface-modification method using an AC high-voltage burst oxygen plasma processing to bring the DLC surface closer to the in vivo environment. We succeeded in creating biomimetic DLC and introducing carboxyl groups. Using this technology, the surface functionalization of medical tube materials is biocompatible with various protein-adsorption properties.

DOI： 10.2494/photopolymer.35.289

researchmap

Language：English   Publisher：The Society of Photopolymer Science and Technology(SPST)  

Biocompatible polymer brushes were successfully synthesized on diamond-like carbon (DLC) films via surface-initiated atom transfer radical polymerization (SI-ATRP) of 2-mtharyloyloxyethyl phosphorylcholine (MPC). The DLC film with a water contact angle (WCA) of approximately 71.9° was modified into a highly hydrophilic surface with a WCA of approximately 15.0° after MPC polymer brush modification. Protein adsorption tests using a quartz crystal microbalance showed that the MPC polymer brush modification dramatically decreased the physical adsorption of bovine albumin and fibrinogen when compared with the DLC film. This indicated an improvement in the surface biocompatibility. Considering that DLC coatings can be applied to various materials such as metals, polymers, and ceramics, MPC polymer brush modification of DLC films would be a versatile technology for improving the surface biocompatibility of a variety of biomedical devices.

DOI： 10.2494/photopolymer.35.303

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cureus, Inc.  

DOI： 10.7759/cureus.32418

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI  

Intracerebral hemorrhage (ICH) is recognized as a severe clinical problem lacking effective treatment. High mobility group box-1 (HMGB1) exhibits inflammatory cytokine-like activity once released into the extracellular space from the nuclei. We previously demonstrated that intravenous injection of rat anti-HMGB1 monoclonal antibody (mAb) remarkably ameliorated brain injury in a rat ICH model. Therefore, we developed a humanized anti-HMGB1 mAb (OKY001) for clinical use. The present study examined whether and how the humanized anti-HMGB1 mAb ameliorates ICH injury in common marmosets. The results show that administration of humanized anti-HMGB1 mAb inhibited HMGB1 release from the brain into plasma, in association with a decrease of 4-hydroxynonenal (4-HNE) accumulation and a decrease in cerebral iron deposition. In addition, humanized anti-HMGB1 mAb treatment resulted in a reduction in brain injury volume at 12 d after ICH induction. Our in vitro experiment showed that recombinant HMGB1 inhibited hemoglobin uptake by macrophages through CD163 in the presence of haptoglobin, suggesting that the release of excess HMGB1 from the brain may induce a delay in hemoglobin scavenging, thereby allowing the toxic effects of hemoglobin, heme, and Fe2+ to persist. Finally, humanized anti-HMGB1 mAb reduced body weight loss and improved behavioral performance after ICH. Taken together, these results suggest that intravenous injection of humanized anti-HMGB1 mAb has potential as a novel therapeutic strategy for ICH.

DOI： 10.3390/cells11192970

Web of Science

researchmap

Language：English   Publisher：FRONTIERS MEDIA SA  

DOI： 10.3389/fimmu.2022.956671

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE SOC MEDICAL & BIOLOGICAL ENGINEERING  

Cardiac arrest has been reported during participation in several sports. Of these sports, marathon running is a particularly popular sport but imposes high cardiac load. Indeed, its popularity has been growing worldwide. Risk of cardiac arrest during marathon races is also expected to increase. Several studies have recorded electrocardiographic (ECG) information during marathon races to protect athletes from cardiac arrest. Although evaluable ECG data have been obtained and analyzed, cost-effectiveness of the system, data quality, and clinical significance remain inadequate. This report is the first to describe an economical electrocardiograph built into a T-shirt for use during marathon race. Twenty healthy runners aged 20 to 59 years (mean 36 years) wore the ECG device while running. The ECG data were monitored and analyzed to assess the observed frequencies of specified arrhythmias and the sections of the marathon in which the arrhythmias occurred. Of the ECG data obtained from 14 runners who completed the full marathon, six ECG datasets were evaluable. In some runners, there was inadequate contact between the electrode and body surface or poor Bluetooth connection between the ECG wireless transmitter and smartphone. Regarding arrhythmia analysis, all evaluable data that were analyzed showed some rhythm fluctuations. In conclusion, this economical T-shirt type ECG sensor provided evaluable ECG data during marathon races, although the evaluable rate was not high. The data were used to analyze specified arrhythmias, but some difficulties were encountered. The ECG sensor did not function properly because of a system error. The ECG sensor was not adequately moistened to record ECGs accurately. Moreover, some runners chose an unsuitable shirt size, which impaired the stability and strength of the electrode-skin contact. These shortcomings produced noise in the ECG data, which made it difficult to analyze arrhythmias. The next step will be to solve these problems and acquire data from a large number of runners.

DOI： 10.14326/abe.11.151

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

During ischemia reperfusion (IR) injury, high mobility group box 1 (HMGB1), a chromatin binding protein, is released from necrotic cells and triggers inflammatory responses. We assessed the therapeutic effect of a neutralizing anti-HMGB1 monoclonal antibody (mAb) on lung IR injury. A murine hilar clamp model of IR was used, where mice were divided into sham and IR groups with intravenous administration of anti-HMGB 1 mAb or control mAb. We analyzed the effect of anti-HMGB1 mAb against IR injury by assessing lung oxygenation, lung injury score, neutrophil infiltration, expression of proinflammatory cytokines and chemokines, levels of mitogen-activated protein kinase (MAPK) signaling, and measurement of apoptotic cells. Anti-HMGB1 mAb significantly decreased the plasma level of HMGB1 elevated by IR. The severity of IR injury represented by oxygenation capacity, lung injury score, and neutrophil infiltration was significantly improved by anti-HMGB1 mAb treatment. The expression of proinflammatory factors, including IL-1β, IL-6, IL-12, TNF-α, CXCL-1, and CXCL-2, and phosphorylation of p38 MAPK were both significantly reduced by anti-HMGB1 mAb treatment. Furthermore, anti-HMGB1 mAb treatment suppressed apoptosis, as determined through TUNEL assays. Overall, anti-HMGB1 mAb ameliorated lung IR injury by reducing inflammatory responses and apoptosis. Our findings indicate that anti-HMGB1 mAb has potential for use as a therapeutic to improve IR injury symptoms during lung transplantation.

DOI： 10.1016/j.bbrc.2021.08.015

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Sudden cardiac accident (SCA) during a marathon is a concern due to the popularity of the sport. Preventive strategies, such as cardiac screening and deployment of automated external defibrillators have controversial cost-effectiveness. We investigated the feasibility of use of a new electrocardiography (ECG) sensor-embedded fabric wear (SFW) during a marathon as a novel preventive strategy against SCA. Twenty healthy volunteers participated in a full marathon race. They were equipped with a SFW hitoe® with a transmitter connected via Bluetooth to a standard smartphone for continuous ECG recording. All data were stored in a smartphone and used to analyze the data acquisition rate. The adequate data acquisition rate was > 90% in 13, 30-90% in 3, and < 10% in 4 runners. All of 4 runners with poorly recorded data were female. Inadequate data acquisition was significantly associated with the early phase of the race compared with the mid phase (P = 0.007). Except for 3 runners with poor heart rate data, automated software calculation was significantly associated with manual analysis for both the mean (P < 0.001) and maximum (P = 0.014) heart rate. We tested the feasibility of continuously recording cardiac data during a marathon using a new ECG sensor-embedded wearable device. Although data from 65% of runners were adequately recorded, female runners and the early phase of the race tended to have poor data acquisition. Further improvements in device ergonomics and software are necessary to improve ability to detect abnormal ECGs that may precede SCA.

DOI： 10.1007/s00380-021-01939-3

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

OBJECTIVES: To examine anti-adhesion and anti-biofilm effects of a diamond-like carbon coating deposited via a novel technique on the inner surface of a thin silicon tube. METHODS: Diamond-like carbon coatings were deposited into the lumen of a silicon tube with inner diameters of 2 mm. The surface of the diamond-like carbon was evaluated using physicochemical methods. We used three clinical isolates including green fluorescent protein-expressing Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. We employed a continuous flow system for evaluation of both bacterial adhesion and biofilm formation. Bacterial adhesion assays consisted of counting the number of colony-forming units and visualization of adhered bacterial cells by scanning electron microscope to evaluate the diamond-like carbon-coated/uncoated samples. The biofilm structure was analyzed by confocal laser scanning microscopy on days 3, 5, 7 and 14 for green fluorescent protein-expressing Pseudomonas aeruginosa. RESULTS: The smooth and carbon-rich structure of the intraluminal diamond-like carbon film remained unchanged after the experiments. The numbers of colony-forming units suggested lower adherence of green fluorescent protein-expressing Pseudomonas aeruginosa and Escherichia coli in the diamond-like carbon-coated samples compared with the uncoated samples. The scanning electron microscope images showed adhered green fluorescent protein-expressing Pseudomonas aeruginosa cells without formation of microcolonies on the diamond-like carbon-coated samples. Finally, biofilm formation on the diamond-like carbon-coated samples was lower until at least day 14 compared with the uncoated samples. CONCLUSIONS: Intraluminal diamond-like carbon coating on a silicone tube has anti-adhesion and anti-biofilm effects. This technology can be applied to urinary catheters made from various materials.

DOI： 10.1111/iju.14675

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本遠隔医療学会  

researchmap

Language：Japanese   Publisher：(一社)日本遠隔医療学会  

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Bovine jugular vein (BJV) and expanded polytetrafluoroethylene (ePTFE) conduits have been described as alternatives to the homograft for right ventricular outflow tract (RVOT) reconstruction. This study compared RVOT reconstructions using BJV and ePTFE conduits performed in a single institution. The valve functions and outcomes of patients aged < 18 years who underwent primary RVOT reconstruction with a BJV or ePTFE conduit between 2013 and 2017 were retrospectively investigated. 44 patients (20 and 24 with BJV and ePTFE conduits, respectively) met the inclusion criteria. The mean follow-up time was 4.5 ± 1.5 years. No significant differences in peak RVOT velocity (1.8 ± 0.9 m/s vs 2.1 ± 0.9 m/s, P = 0.27), branch pulmonary stenosis (P = 0.50), or pulmonary regurgitation (P = 0.44) were found between the BJV and ePTFE conduit groups, respectively. Aneurysmal dilatation of the conduit was observed in 25.0% of the patients in the BJV conduit group but not in the ePTFE conduit group (P = 0.011). All the cases with aneurysmal dilatation of the BJV conduit were complicated with branch pulmonary stenosis up to 3.0 m/s (P = 0.004). No conduit infections occurred during the follow-up period, and no significant difference in conduit replacement (20.0% vs 8.3%, P = 0.43) was found between the BJV and ePTFE conduit groups, respectively. The outcomes of the RVOT reconstructions with BJV and ePTFE conduits were clinically satisfactory. Aneurysmal dilatation was found in the BJV conduit cases, with branch pulmonary stenosis as the risk factor.

DOI： 10.1007/s00246-020-02458-0

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI  

Increasing evidence suggests that inflammatory responses are involved in the progression of brain injuries induced by a diverse range of insults, including ischemia, hemorrhage, trauma, epilepsy, and degenerative diseases. During the processes of inflammation, disruption of the blood-brain barrier (BBB) may play a critical role in the enhancement of inflammatory responses and may initiate brain damage because the BBB constitutes an interface between the brain parenchyma and the bloodstream containing blood cells and plasma. The BBB has a distinct structure compared with those in peripheral tissues: it is composed of vascular endothelial cells with tight junctions, numerous pericytes surrounding endothelial cells, astrocytic endfeet, and a basement membrane structure. Under physiological conditions, the BBB should function as an important element in the neurovascular unit (NVU). High mobility group box-1 (HMGB1), a nonhistone nuclear protein, is ubiquitously expressed in almost all kinds of cells. HMGB1 plays important roles in the maintenance of chromatin structure, the regulation of transcription activity, and DNA repair in nuclei. On the other hand, HMGB1 is considered to be a representative damage-associated molecular pattern (DAMP) because it is translocated and released extracellularly from different types of brain cells, including neurons and glia, contributing to the pathophysiology of many diseases in the central nervous system (CNS). The regulation of HMGB1 release or the neutralization of extracellular HMGB1 produces beneficial effects on brain injuries induced by ischemia, hemorrhage, trauma, epilepsy, and Alzheimer's amyloidpathy in animal models and is associated with improvement of the neurological symptoms. In the present review, we focus on the dynamics of HMGB1 translocation in different disease conditions in the CNS and discuss the functional roles of extracellular HMGB1 in BBB disruption and brain inflammation. There might be common as well as distinct inflammatory processes for each CNS disease. This review will provide novel insights toward an improved understanding of a common pathophysiological process of CNS diseases, namely, BBB disruption mediated by HMGB1. It is proposed that HMGB1 might be an excellent target for the treatment of CNS diseases with BBB disruption.

DOI： 10.3390/cells9122650

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)-mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy.

DOI： 10.1126/scitranslmed.abb3336

PubMed

researchmap

Language：Japanese   Publisher：(NPO)日本小児循環器学会  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

DOI： 10.1007/s10396-019-00986-8

Web of Science

PubMed

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本脈管学会  

researchmap

Language：Japanese   Publisher：(NPO)日本小児循環器学会  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(NPO)日本小児循環器学会  

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The majority of marathon deaths are caused by sudden cardiac arrest (SCA), which occur in approximately 1 in 57,000 runners. Such deaths are more common among older males and usually occur in the last 4 miles of the racecourse. Although prompt resuscitation, including early use of an automated external defibrillator (AED), improves survival, the deployment of enough trained medical staff and AEDs is difficult due to increased cost. Moreover, most victims of exercise-related SCA have no premonitory symptoms. Therefore, we tried to use a novel approach to prevent sudden cardiac deaths (SCD) related to SCA using real-time electrocardiographic tele-monitoring system, as an initial trial to assess operative possibility in a full marathon. As a result, 3 out of 5 runners had reasonable measurement results and sufficient tele-monitoring without complications related to this trial was possible. However, many investigations and improvements, such as improving cost-effectiveness, reducing noise, and automating the monitoring system, are needed for practical application of these devices for athletes. As a next step, we would establish a novel strategy to reduce SCDs in athletes using next-generation devices, which include an alarm system associated with early application of AED. <Learning objectives: Sudden cardiac arrest (SCA) is a major problem in sports cardiology. Here we investigated a novel approach using a real-time tele-monitoring system of electrocardiogram (ECG) to prevent sudden cardiac deaths by making use of an advanced alarm system which responds to SCA risk. Three out of five cases we monitored showed reasonable measurement of ECG with centralized observation in full marathon. This is the first report of this method, which may lead to the effective application of automated external defibrillator in athletes.>.

DOI： 10.1016/j.jccase.2019.03.008

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本循環器学会  

J-GLOBAL

researchmap

Language：Japanese   Publisher：The Japanese Society for Cardiovascular Surgery  

Patients with Behçet disease often develop postoperative valve detachment and pseudoaneurysm as a potentially fatal complication following aortic valve surgery, necessitating re-operation in a few cases. A 37-year-old man underwent 5 aortic valve and aortic root surgeries for the management of valve detachment after initial aortic valve replacement. Evaluation during the course of his disease revealed incomplete Behçet disease. He presented with high fever and Staphylococcus epidermidis bacteremia during the introduction of immunosuppressive therapy with infliximab. Contrast computed tomography revealed a pseudoaneurysm around the aortic root, and an aortic root replacement was performed using an aortic homograft after administration of a 6-week course of vancomycin. The patient is being observed at our outpatient clinic and has demonstrated no complications after 5 years from his last surgery.

DOI： 10.4326/jjcvs.47.133

CiNii Article

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

Left ventricular (LV) rupture after myocardial infarction (MI) occasionally results in formation of LV pseudoaneurysm (LVPA) which is prone to rupture because of its thin wall. However, cases of LVPA without ST changes including segment elevation in electrocardiogram (ECG) are rare. In this case, we describe a patient who had relatively mild symptoms and giant LVPA with no specific ECG changes following MI with a confirmed diagnosis via transthoracic echocardiography. Although surgical treatment options are often recommended, conservative therapy was adopted, following which the patient had been well-medicated using antihypertensive drugs and anticoagulants. &lt
Leaning objectives: Left ventricular pseudoaneurysm (LVPA) is usually accompanied by ST segment changes on electrocardiogram (ECG) due to myocardial damage. However, we should take into account a LVPA without ECG specific changes, so echocardiography is better to be considered for an identification. Although many LVPA patients undergo surgery because of risk for rupture, some cases with stable hemodynamic status can have long-term survival with conservative therapy such as anti-hypertension and coagulation.&gt

DOI： 10.1016/j.jccase.2018.01.006

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

RATIONALE: Intracoronary administration of cardiosphere-derived cells (CDCs) in patients with single ventricles resulted in a short-term improvement in cardiac function. OBJECTIVE: To test the hypothesis that CDC infusion is associated with improved cardiac function and reduced mortality in patients with heart failure. METHODS AND RESULTS: We evaluated the effectiveness of CDCs using an integrated cohort study in 101 patients with single ventricles, including 41 patients who received CDC infusion and 60 controls treated with staged palliation alone. Heart failure with preserved ejection fraction (EF) or reduced EF was stratified by the cardiac function after surgical reconstruction. The main outcome measure was to evaluate the magnitude of improvement in cardiac function and all-cause mortality at 2 years. Animal studies were conducted to clarify the underlying mechanisms of heart failure with preserved EF and heart failure with reduced EF phenotypes. At 2 years, CDC infusion increased ventricular function (stage 2: +8.4±10.0% versus +1.6±6.4%, P=0.03; stage 3: +7.9±7.5% versus -1.1±5.5%, P<0.001) compared with controls. In all available follow-up data, survival did not differ between the 2 groups (log-rank P=0.225), whereas overall patients treated by CDCs had lower incidences of late failure (P=0.022), adverse events (P=0.013), and catheter intervention (P=0.005) compared with controls. CDC infusion was associated with a lower risk of adverse events (hazard ratio, 0.411; 95% CI, 0.179-0.942; P=0.036). Notably, CDC infusion reduced mortality (P=0.038) and late complications (P<0.05) in patients with heart failure with reduced EF but not with heart failure with preserved EF. CDC-treated rats significantly reversed myocardial fibrosis with differential collagen deposition and inflammatory responses between the heart failure phenotypes. CONCLUSIONS: CDC administration in patients with single ventricles showed favorable effects on ventricular function and was associated with reduced late complications except for all-cause mortality after staged procedures. Patients with heart failure with reduced EF but not heart failure with preserved EF treated by CDCs resulted in significant improvement in clinical outcome. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01273857 and NCT01829750.

DOI： 10.1161/CIRCRESAHA.117.312311.

Web of Science

PubMed

researchmap

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

0

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Background: High-mobility group box 1 (HMGB-1) is a key substance mediating inflammation and development of atherosclerotic lesions (ALs), including abdominal aortic aneurysms (AAA). Serum levels of HMGB-1 are increased in patients with AAA than those in normal controls because the ALs in AAAs secrete HMGB-1. We therefore postulate that the serum HMGB-1 level should decrease after endovascular aortic repair (EVAR) or open aortic repair (OAR). However, there is no evidence of this in the literature. The purpose of this study was to investigate the changes in HMGB-1 levels after surgical intervention for AAA. We also aimed to determine if the HMGB-1 levels varied between the two procedures.
Methods: Serum HMGB-1 levels were determined in 24 patients with AAA and 25 healthy controls. Twelve of the 24 AAA patients underwent EVAR, whereas the other half underwent OAR. The relationship between HMGB-1 levels and presence of AAA or influence of operative methods on the serum HMGB-1 level were prospectively investigated.
Results: Serum HMGB-1 levels in AAA patients were significantly higher than those in healthy controls (9.4 +/- 5.7 vs. 4.1 +/- 2.0 ng/mL, P &lt; 0.01). The serum HMGB-1 levels in both the EVAR group and the OAR group were significantly decreased from baseline at both 3 mo and 1 y after surgery.
Conclusions: Removal or isolation of AL via surgical intervention significantly decreases serum HMGB-1 levels. The significant postoperative reduction in HMGB-1 levels suggests that important endocrinological changes occur after surgical treatment of AAA.

DOI： 10.1016/j.avsg.2016.08.017

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Rationale: Patients with single ventricle physiology are at high risk of mortality resulting from ventricular dysfunction. The preliminary results of the phase 1 trial showed that cardiosphere-derived cells (CDCs) may be effective against congenital heart failure.
Objective: To determine whether intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology.
Methods and Results: We conducted a phase 2 randomized controlled study to assign in a 1: 1 ratio 41 patients who had single ventricle physiology undergoing stage 2 or 3 palliation to receive intracoronary infusion of CDCs 4 to 9 weeks after surgery or staged reconstruction alone (study A). The primary outcome measure was to assess improvement in cardiac function at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC infusion on request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in the controls (+ 6.4% [SD, 5.5] versus + 1.3% [SD, 3.7]; P= 0.003). In study B, a late CDC infusion in 17 controls increased the ventricular function at 3 months compared with that at baseline (38.8% [SD, 7.7] versus 34.8% [SD, 7.4]; P&lt; 0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD, 6.6] versus 35.0% [SD, 8.2]; P&lt; 0.0001) and volumes (P&lt; 0.001), somatic growth (P&lt; 0.0001) with increased trophic factors production, such as insulin-like growth factor-1 and hepatocyte growth factor, and quality of life, along with a reduced heart failure status (P&lt; 0.0001) and cardiac fibrosis (P= 0.014) relative to baseline.
Conclusions: Intracoronary infusion of CDCs after staged palliation favorably affected cardiac function by reverse remodeling in patients with single ventricle physiology. This impact may improve heart failure status, somatic growth, and quality of life in patients and reduce parenting stress for their families.

DOI： 10.1161/CIRCRESAHA.116.310253

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY-ELSEVIER  

Objectives: Our aim was to assess midterm safety and clinical outcomes of intracoronary infusion of cardiosphere-derived cells (CDCs) after staged palliation in patients with hypoplastic left heart syndrome (HLHS).
Methods: In this prospective, controlled study, 14 consecutive patients with HLHS who were undergoing 2- or 3-stage surgical palliations were assigned to receive intracoronary CDC infusion 1 month after cardiac surgery (n = 7), followed by 7 patients allocated to a control group with standard care alone. The primary end point was to assess procedural feasibility and safety; the secondary end point was to evaluate cardiac function and heart failure status through 36-month follow-up.
Results: No complications, including tumor formation, were reported within 36 months after CDC infusion. Echocardiography showed significantly greater improvement in right ventricular ejection fraction (RVEF) in infants receiving CDCs than in controls at 36 months (+8.0% +/- 4.7% vs +2.2% +/- 4.3%; P = .03). These cardiac function improvements resulted in reduced brain natriuretic peptide levels (P = .04), lower incidence of unplanned catheter interventions (P = .04), and higher weight-for-age z score (P = .02) at 36 months relative to controls. As independent predictors of treatment responsiveness, absolute changes in RVEF at 36 months were negatively correlated with age, weight-for-age z score, and RVEF at CDC infusion.
Conclusions: Intracoronary CDC infusion after staged procedure in patients with HLHS is safe and improves RVEF, which persists during 36-month follow-up. This therapeutic strategy may enhance somatic growth and reduce incidence of heart failure.

DOI： 10.1016/j.jtcvs.2015.06.076

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本脈管学会  

researchmap

Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

左心低形成症候群14例を対象とした心臓内幹細胞自家移植療法の第I相臨床試験の結果を報告した。移植群7例においては両方向グレン手術あるいはフォンタン手術時に、右心房から採取した心臓組織から幹細胞を分離培養し、術後1ヵ月で30万個/kgの心筋幹細胞の選択的冠動脈内注入を行った。移植群で幹細胞注入に伴う心筋逸脱酵素の上昇はなく、心筋虚血症などの合併症もなかった。心臓超音波で評価した移植群の右室駆出率は、移植後3ヵ月から有意な改善を認め、18ヵ月時点では移植前と比較して平均+7.1%と効果が持続した。一方非移植群7例では+2.1%の改善にとどまり、細胞治療による改善効果が示された。またカテーテル検査値に基づく評価では、移植群で心筋弾性能やポンプ機能の改善を認め、心不全症状も著明に改善し、成長障害に対する有意な成長促進がみられた。非移植群では心不全症状の軽減や身体成長の改善は観察されなかった。

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Rationale: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function.
Objective: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome.
Methods and Results: Between January 5, 2011, and January 16, 2012, 14 patients (1.8 +/- 1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4 +/- 8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9%+/- 4.6% to 52.1%+/- 2.4%; P=0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5%+/- 6.8% versus 40.4%+/- 7.6%; P=0.049), improved somatic growth (P=0.0005), reduced heart failure status (P=0.003), and lower incidence of coil occlusion for collaterals (P=0.007).
Conclusions: Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes.

DOI： 10.1161/CIRCRESAHA.116.304671

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI PUBLISHING CORP  

Background. Congenital heart diseases often involve chronic pressure overload of the right ventricle (RV) which is a major cause of RV dysfunction. Pulmonary artery (PA) banding has been used to produce animal models of RV dysfunction. We have devised a new and easier method of constricting the PA and compared it directly with the partial ligation method. Methods. Eight-week-old male Sprague-Dawley rats (240-260 g) were divided into three groups: sham operation, partial pulmonary artery ligation (PAL) procedure, and pulmonary artery half-closed clip (PAC) procedure. RV function and remodeling were determined by echocardiography and histomorphometry. Results. Surgical mortality was significantly lower in the PAC group while echocardiography revealed significantly more signs of RV dysfunction. At the 8th week after surgery RV fibrosis rate was significantly higher in the PAC group. Conclusions. This procedure of pulmonary artery banding in rats is easier and more efficient than partial ligation.

DOI： 10.1155/2015/753210

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：日本小児血液・がん学会  

近年，再生医療の研究はますます盛んになり，心不全に対する心筋再生医療の臨床治験が徐々に報告されるようになった．初期技術として，骨髄幹細胞や間葉系幹細胞，臍帯血幹細胞などを用いた研究ではその有用性を示す報告が相次いでいる．とりわけ2002年の心筋幹細胞の発見は，心筋再生医療に大きな希望をもたらした．心筋幹細胞は他の幹細胞に比べ，より高い治療効果が期待されており，成人虚血性心疾患に対する心筋幹細胞移植は，海外での臨床治験が報告されており，治療効果が示されている．一方，先天性心疾患の一部の重症疾患群では，救命不能な症例がいまだ存在する．今回我々は，世界初の小児心疾患に対する心筋幹細胞移植療法の第1相臨床研究（TICAP試験）を行い，心臓内幹細胞移植療法の安全性と治療効果を確認した．続いて，第2相臨床研究（PERSEUS試験）を現在施行中であり，心筋幹細胞治療の標準医療化を目指している．一方，これまでの多くの臨床試験の初期成績により，心臓幹細胞移植療法の治療効果は確認されつつあるが，その作用機序は，幹細胞の心筋細胞への分化に加え，幹細胞の分泌するある種のサイトカインの関与などが考えられている．また，心臓への幹細胞の生着性を上げることでより高い治療効果を得られる可能性があり，心臓への移植細胞の誘導や足場となる生体材料の併用など様々な試みがなされている．近いうちに，心臓再生医療が心疾患の新しい治療手段となる時代が到来するであろう．

DOI： 10.11412/jspho.52.210

CiNii Article

researchmap

Other Link： http://search.jamas.or.jp/link/ui/2016089029

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

researchmap

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

researchmap

Language：Japanese   Publisher：Japanese Pharmacological Society  

Introduction

Spinal cord ischemia and reperfusion (I/R) injury is one of the most devastating complications after thoracic and thoracoabdominal aortic aneurysm surgery. Several studies showed that levels of HMGB1 in serum were increased in patients who suffered from spinal cord I/R injury. These data strongly suggest that HMGB1 may play a crucial role in spinal cord I/R injury.

Materials and Methods

Male New Zealand white rabbits were used for the experiments. The abdominal aorta at the level of the left renal artery was exposed, and, after heparinization, occluded for 11 minutes. The rabbits were intravenously administered an anti-HMGB1 mAb (#10-22, 2mg/kg) or class-matched control IgG (anti-keyhole limpet hemocyanin mAb) twice immediately and 6h after reperfusion. The neurological findings were assessed at 6, 24 and 48 hours after reperfusion. At 48hr after reperfusion, the rabbits were sacrificed to obtain the specimen of spinal cord and blood samples.

Results

Administration of anti-HMGB1 mAb ameliorated the intensity of spinal cord infarction and preserved the number of motor neuron cells, in association with decreased activated microglia and astrocyte. Consequently, anti-HMGB1 mAb significantly improved the neurological outcomes after spinal I/R injury in rabbits.  These results strongly indicate that HMGB1 plays a critical role in the development of spinal cord I/R induced secondary injury through the amplification of inflammatory response.

Conclusion

Intravenous injection of neutralizing anti-HMGB1 mAb has potential as a novel therapeutic strategy for spinal cord I/R injury.

DOI： 10.1254/jpssuppl.94.0_3-y-f2-1

CiNii Article

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：Japanese Pharmacological Society  

Intracerebral hemorrhage (ICH) is recognized as a serious clinical problem lacking effective treatment. High mobility group box-1 (HMGB1) exhibits inflammatory cytokine-like activity once released into the extracellular space from the nuclei. We previously demonstrated that intravenous injection of rat anti-HMGB1 monoclonal antibody (mAb) remarkably ameliorated brain injury induced by hemorrhage in the striatum of rat. In the present study, we examined whether and how humanized anti-HMGB1 mAb (OKY001) effects on ICH injury in common marmoset. The results show that administration of OKY001 inhibited the release of HMGB1 from brain into plasma, which was associated with the decrease of 4-HNE adduct accumulation in the brain and plasma. Besides, brain injury volume was ameliorated by treatment of OKY001 at 12 d after ICH induction. In vitro experiment showed that haptoglobin increased the uptake of hemoglobin and HMGB1 by THP1 cell respectively. However, recombinant HMGB1 inhibited the uptake of hemoglobin by THP1 cell, which suggested that abundant HMGB1 released form the brain impeded the absorption of hematoma. Moreover, OKY001 reduced body weight loss and improved the behavioral performance. Taken together, these results suggest that intravenous injection of OKY001 has potential as a novel therapeutic strategy for ICH disease.

DOI： 10.1254/jpssuppl.95.0_2-yia-43

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

CiNii Article

researchmap

Language：Japanese   Publisher：Japanese Society for Medical and Biological Engineering  

The majority of marathon deaths are caused by sudden cardiac arrest (SCA), which occur in approximately 1 in 57,000 runners. Although prompt resuscitation, including early use of AED, improves survival, the deployment of enough trained medical staff and AEDs is difficult due to increased cost. Moreover, most victims of exercise-related SCA have no premonitory symptoms. Therefore, we tried to use a novel approach to prevent sudden cardiac deaths (SCD) using monitoring system. As a result, 19 out of 20 runners had reasonable measurement results and sufficient monitoring without complications related to this trial was possible. However, many investigations and improvements, such as improving cost-effectiveness, reducing noise, and automating the monitoring system, are needed for practical application of these devices for athletes. As a next step, we would establish a novel strategy to reduce SCDs in athletes using next generation devices, which includes an alarm system with early application of AED.

DOI： 10.11239/jsmbe.annual58.406

CiNii Article

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本遠隔医療学会  

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

researchmap

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

researchmap

Language：Japanese   Presentation type：Oral presentation (general)  

researchmap

Language：English   Presentation type：Poster presentation  

researchmap

Language：Japanese  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Oral presentation (general)  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：English   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Oral presentation (general)  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：English   Presentation type：Poster presentation  

researchmap

Language：English   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：English   Presentation type：Poster presentation  

researchmap

Language：English   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Oral presentation (general)  

researchmap

Language：Japanese   Presentation type：Poster presentation  

researchmap

Language：Japanese   Presentation type：Oral presentation (general)  

researchmap

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

researchmap

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

researchmap

Language：Japanese   Presentation type：Oral presentation (general)  

researchmap

Language：Japanese   Presentation type：Oral presentation (general)  

researchmap