真幸 小平 | McGill University (original) (raw)
Papers by 真幸 小平
JACC: Cardiovascular Interventions, 2014
Coronary Artery Disease, 2016
Besides its potent plasma cholesterol-lowering activity, statin treatment has several other impor... more Besides its potent plasma cholesterol-lowering activity, statin treatment has several other important effects, including lowering high-sensitive C-reactive protein (hs-CRP), levels, and stabilizing risk factors of atherosclerosis, thereby reducing the risk of cardiovascular events. Our aim in this study was to identify how intensive statin therapy can affect plasma levels of inflammatory markers over the long term. We used a prospective, randomized, open blinded-endpoint design. A total of 30 patients with stable coronary artery disease treated with everolimus-eluting stent implantation were randomized to receive rosuvastatin 2.5 (standard therapy group) or 10 mg (intensive therapy group) for 12 months. Plasma levels of hs-CRP, pentraxin-3, monocyte chemoattractant protein-1, and CXC chemokine ligand 4 were measured after a percutaneous coronary intervention, at 1, 3, 6, 9, and 12 months. Levels of LDL cholesterol (LDL-C) and HDL cholesterol were also measured. We investigated short-term and long-term clinical outcomes. After 12 months of therapy, the intensive therapy group had lower levels of LDL-C than the standard therapy group. Plasma levels of hs-CRP largely fluctuated in the standard therapy group, whereas they were stable in the intensive therapy group during the follow-up period. There were no significant differences in serum pentraxin-3, monocyte chemoattractant protein-1, and CXC chemokine ligand 4 levels, or in the incidence of any clinical adverse events, between the standard and the intensive therapy groups. Intensive rosuvastatin therapy stabilizes hs-CRP levels, but not chemokine levels, besides lowering LDL-C levels. Thus, this therapy may inhibit the progression of atherosclerosis by stably inhibiting the inflammatory cascade.
Child psychiatry and human development, Jan 16, 2016
On March 11, 2011, Japan was struck by a massive earthquake and tsunami. The tsunami caused treme... more On March 11, 2011, Japan was struck by a massive earthquake and tsunami. The tsunami caused tremendous damage and traumatized children. We aimed to evaluate and compare the changes in the traumatic symptoms of high school girls 8, 20, 30, and 42 months after the 2011 tsunami. The Post-Traumatic Stress Symptoms for Children 15 items (PTSSC-15), a self-rating questionnaire on traumatic symptoms, was administered to 811 high school girls at the above-mentioned intervals. We calculated the total score, post-traumatic stress disorder (PTSD) subscale, and depression subscale of PTSSC-15. The total score was correlated with house damage, evacuation experience, and bereavement experience. The PTSSC-15 total scores of high school girls with traumatic experience were significantly higher than the scores of children without these experiences (all p < 0.0001). The PTSSC-15 total score did not decrease significantly over time. Furthermore, the PTSD subscale of the PTSSC-15 did not significant...
Sleep and Biological Rhythms, 2014
ABSTRACT Changes in sleep patterns among children following traumatic experiences may be indicati... more ABSTRACT Changes in sleep patterns among children following traumatic experiences may be indicative of post-traumatic psychiatric disorders and contribute to disease persistence. We evaluated long-term changes in the sleep habits of 1919 junior high school students who experienced the 2011 Japan earthquake and tsunami, and examined the associations among sleep patterns, trauma symptoms, and specific traumatic events. The Post-Traumatic Stress Symptoms for Children-15 items self-completion questionnaire was distributed to the children, and a questionnaire regarding three specific traumatic events (home damage, bereavement, and evacuation) was distributed to their teachers. Compared to the same survey conducted 8 months after the disaster, a 20-month post-disaster survey revealed significantly shorter mean sleep duration and a delay in sleep phase (P &lt; 0.0001). On the 20-month survey, weekday sleep duration was shorter and sleep–wake pattern delayed in children who had experienced home damage compared to children with no such experience (P &lt; 0.01). Children who had experienced bereavement also reported a shorter mean sleep duration on the 20-month survey compared to children reporting no bereavement experience (P &lt; 0.05). Differences in sleep duration between weekdays and holidays at 20 months post-disaster suggested a sleep debt due to sleep disruption. There were no significant differences in Post-Traumatic Stress Symptoms for Children-15 items total scores between groups defined by the type of traumatic experience. Traumatic events (home damage, bereavement) associated with the 2011 Japan earthquake and tsunami have caused long-term sleep disruption in children from this region.
Circulation, Nov 23, 2010
PloS one, 2015
The Questionnaire: Children with Difficulties (QCD) is a parent-assessed questionnaire designed t... more The Questionnaire: Children with Difficulties (QCD) is a parent-assessed questionnaire designed to evaluate child's difficulties in functioning during specific periods of the day. This study aimed to evaluate difficulties in daily functioning of children and adolescents with pervasive developmental disorder (PDD) using the QCD. Results were compared with those for a community sample. A case-control design was used. The cases comprised elementary school students (182 males, 51 females) and junior high school students (100 males, 39 females) with PDD, whereas a community sample of elementary school students (568 males, 579 females) and junior high school students (180 males, 183 females) was enrolled as controls. Their behavior was assessed using the QCD, the Tokyo Autistic Behavior Scale (TABS), the ADHD-rating scale (ADHD-RS), and the Oppositional Defiant Behavior Inventory (ODBI) for elementary and junior high school students, respectively. Effects of gender and diagnosis on th...
Nature communications, Jan 13, 2015
Duchenne muscular dystrophy (DMD) is a chronic and life-threatening disease that is initially sup... more Duchenne muscular dystrophy (DMD) is a chronic and life-threatening disease that is initially supported by muscle regeneration but eventually shows satellite cell exhaustion and muscular dysfunction. The life-long maintenance of skeletal muscle homoeostasis requires the satellite stem cell pool to be preserved. Asymmetric cell division plays a pivotal role in the maintenance of the satellite cell pool. Here we show that granulocyte colony-stimulating factor receptor (G-CSFR) is asymmetrically expressed in activated satellite cells. G-CSF positively affects the satellite cell population during multiple stages of differentiation in ex vivo cultured fibres. G-CSF could be important in developing an effective therapy for DMD based on its potential to modulate the supply of multiple stages of regenerated myocytes. This study shows that the G-CSF-G-CSFR axis is fundamentally important for long-term muscle regeneration, functional maintenance and lifespan extension in mouse models of DMD w...
Journal of affective disorders, Jan 20, 2015
The parent-assessed children-with-difficulties questionnaire (Questionnaire-Children with Difficu... more The parent-assessed children-with-difficulties questionnaire (Questionnaire-Children with Difficulties; QCD) is designed to evaluate a child׳s difficulties in functioning during specific periods of the day. This study aimed to use the QCD to evaluate the difficulties in daily functioning experienced by children with depressive disorders. A case-control design was used. The cases comprised 90 junior high school students with depressive disorder, whereas a community sample of 363 junior high school students was enrolled as controls. Behaviors were assessed using the QCD, Depression Self-Rating Scale (DSRS), Tokyo Autistic Behavior Scale (TABS), attention deficit hyperactivity disorder-rating scale (ADHD-RS), and Oppositional Defiant Behavior Inventory (ODBI). We then analyzed the effects of sex and diagnosis on the QCD scores as well as the correlation coefficients between the QCD and the other questionnaires. We included 90 cases (33 boys, 57 girls) with depressive disorders and 363 ...
FEBS open bio, 2015
Mitochondrial diseases are heterogeneous disorders, caused by mitochondrial dysfunction. Mitochon... more Mitochondrial diseases are heterogeneous disorders, caused by mitochondrial dysfunction. Mitochondria are not regulated solely by nuclear genomic DNA but by mitochondrial DNA. It is difficult to develop effective therapies for mitochondrial disease because of the lack of mitochondrial disease models. Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the major mitochondrial diseases. The aim of this study was to generate MELAS-specific induced pluripotent stem cells (iPSCs) and to demonstrate that MELAS-iPSCs can be models for mitochondrial disease. We successfully established iPSCs from the primary MELAS-fibroblasts carrying 77.7% of m.3243A>G heteroplasmy. MELAS-iPSC lines ranged from 3.6% to 99.4% of m.3243A>G heteroplasmy levels. The enzymatic activities of mitochondrial respiratory complexes indicated that MELAS-iPSC-derived fibroblasts with high heteroplasmy levels showed a deficiency of complex I activity but MELAS-iPS...
Pediatrics international : official journal of the Japan Pediatric Society, Jan 6, 2015
Sleep disorders are frequently associated with childhood behavioral problems and mental illnesses... more Sleep disorders are frequently associated with childhood behavioral problems and mental illnesses such as anxiety disorders. To identify promising behavioral targets for therapy ofpediatric anxiety disorders, we investigated the associations between specific sleep and behavioral problems. We conducted retrospective reviews of 105 patientsaged 4-12 yearswho met the DSM-IV criteria for primary diagnosis of generalized anxiety disorder (GAD; n = 33), separation anxiety disorder (SAD;n = 23), social phobia (SP; n = 21), or obsessivecompulsive disorder (OCD;n = 28). Sleep problems were evaluated using the Children's Sleep Habits Questionnaire (CSHQ) and behavioral problems bythe Spence Children's Anxiety Scale (SCAS), Oppositional Defiant Behavior Inventory (ODBI), and Depression Self-Rating Scale for Children (DSRS-C). Depressive behavior was weakly correlated with CSHQ subscores for sleep onset delayand night waking but not with total sleep disturbance.Anxiety was correlated wi...
PloS one, 2014
The aim of this study was to evaluate the frontopolar hemodynamic response and depressive mood in... more The aim of this study was to evaluate the frontopolar hemodynamic response and depressive mood in children with mild or moderate major depressive disorder during six weeks treatment without medication. The subjects were 10 patients with mild or moderate depression. They were depressive drug-naive children and adolescents. The scores of Depression Self Rating Scale (DSRS), the results of the Verbal Fluency Test (VFT), and the concentrations of oxy-hemoglobin (Oxy-Hb) of frontal pole brain assessed by two-channel near infrared spectroscopy (NIRS) after six weeks of treatment was compared with those of initial treatment. The score of DSRS was significantly reduced after six weeks of initial treatment (p<0.001, t-test). The word number of VFT was not significantly changed after six weeks of treatment. The oxy-Hb concentration significantly increased after six weeks of treatment (p<0.001, t-test). This study demonstrated that the concentration of oxy-Hb of frontopolar cortex in chi...
Psychiatry and clinical neurosciences, 2012
The aim of this research was to clarify the development of depression among boys with attention d... more The aim of this research was to clarify the development of depression among boys with attention deficit hyperactivity disorder (ADHD) by examining the correlation between depressive mood, oppositional defiant behavior, and age for each ADHD subtype. The Birleson Depression Self-Rating Scale (DSRS) was used to evaluate depressive mood while the Oppositional Defiant Behavior Inventory (ODBI) was used to evaluate oppositional defiant behavior. The 90 subjects were divided into three groups: 22 boys (mean age, 12.4 ± 1.9 years) were placed in the ADHD predominantly inattentive type (ADHD-I) group; 45 boys (mean age, 10.4 ± 2.0 years) were placed in the ADHD combined type (ADHD-C) group; and 23 boys (mean age, 12.7 ± 2.4 years) were placed in the depressive disorder (DD) group. The DD group was included to highlight characteristics of depressive mood among boys with ADHD. The DSRS score was significantly higher in the DD group compared to the ADHD-I and ADHD-C groups. The ODBI score was ...
Journal of the American Heart Association, 2014
Background Despite the accumulating genetic and molecular investigations into hypertrophic cardio... more Background Despite the accumulating genetic and molecular investigations into hypertrophic cardiomyopathy (HCM), it remains unclear how this condition develops and worsens pathologically and clinically in terms of the genetic–environmental interactions. Establishing a human disease model for HCM would help to elucidate these disease mechanisms; however, cardiomyocytes from patients are not easily obtained for basic research. Patient‐specific induced pluripotent stem cells ( iPSCs ) potentially hold much promise for deciphering the pathogenesis of HCM. The purpose of this study is to elucidate the interactions between genetic backgrounds and environmental factors involved in the disease progression of HCM. Methods and Results We generated iPSC s from 3 patients with HCM and 3 healthy control subjects, and cardiomyocytes were differentiated. The HCM pathological phenotypes were characterized based on morphological properties and high‐speed video imaging. The differences between contro...
PLoS ONE, 2014
Background: On March 11, 2011, Japan was struck by a massive earthquake and tsunami. The tsunami ... more Background: On March 11, 2011, Japan was struck by a massive earthquake and tsunami. The tsunami caused tremendous damage and traumatized several people, including children. The aim of this study was to assess changes in traumatic symptoms 8, 20, and 30 months of the 2011 tsunami. Methods: The study comprised three groups. Copies of the Post-Traumatic Stress Symptoms for Children 15 items (PTSSC-15), a self-rating questionnaire on traumatic symptoms, were distributed to 12,524 children (8-month period), 12,193 children (20-month period), and 11,819 children (30-month period). An effective response of children 8 months, 20 months, and 30 month after the disaster was obtained in 11,639 (92.9%), 10,597 (86.9%), and 10,812 children (91.4%), respectively. We calculated the total score, PTSD subscale, and Depression subscale of PTSSC-15. We calculated the total score, PTSD subscale, and Depression subscale of PTSSC-15. Results: The PTSSC-15 total score and PTSD subscale of children belonging to 1st-9th grade groups who were tested 30 and 20 months after the tsunami significantly decreased compared with those of children tested 8 months after the tsunami. The PTSSC-15 total score and PTSD subscale of children in 1st-9th grade groups tested after 30 months did not decrease significantly compared with those of children tested after 20 months. The PTSSC-15 Depression subscale and PTSD subscale of children in 1st-9th grade groups tested after 30 months significantly decreased compared with those of children tested 8 months after the tsunami. The PTSSC-15 Depression subscale of children in 1st-9th grade groups evaluated after 30 months significantly decreased compared with those of children evaluated after 20 months. Conclusions: This study demonstrates that the traumatic symptoms of children who survived the massive tsunami improved with time. Nonetheless, the traumatic symptoms, which in some cases did not improve with time.
PLoS ONE, 2014
Background: The 2011 Japan massive tsunami traumatized many children. The aim of this study was t... more Background: The 2011 Japan massive tsunami traumatized many children. The aim of this study was to assess changes in strengths and difficulties experienced in home and school by among surviving children after the 2011 tsunami, in comparison with published normal Japanese data. Methods: In November 2012 (20 months after the disaster) and September 2013 (30 months after the disaster), the Strengths and Difficulties Questionnaire (SDQ), a questionnaire on children's strengths and difficulties in home and school activities, were distributed to 12,193 and 11,819 children, respectively. An effective response of children 20 months and 30 month after the disaster was obtained in 10,597 children (86.9%), and 10,812 children (91.4%), respectively. The SDQ scores evaluated by parents and teachers were compared with published normal Japanese SDQ scores. Results: The SDQ scores (emotional problems, conduct problems, hyperactivity/ inattention, peer relationship problems, and total difficulty score) evaluated by parents of children in the 4th to 9th grade who were evaluated after 30 and 20 months were significantly high compared with the published normal data of children without traumatic experiences (all P,0.001). The SDQ scores (prosocial behavior) evaluated by teachers of children in the 4th to 9th grade who were evaluated after 30 and 20 months were significantly low compared with the published normal data of children without traumatic experiences (all P,0.001).
Cardiovascular Intervention and Therapeutics, 2013
Transcatheter closure of secundum atrial septal defect (ASD) has been widely performed as a less ... more Transcatheter closure of secundum atrial septal defect (ASD) has been widely performed as a less invasive alternative to surgery with zero mortality so far in Japan. In the US and Europe, intracardiac echocardiography (ICE) has replaced transesophageal echocardiography (TEE) as a primary imaging tool during percutaneous ASD closure. However, the experience of ICE in ASD closure is limited in Japan. Consecutive 51 patients underwent percutaneous ASD closure with ICE guidance. Clinical results were compared to those of 41 patients who underwent ASD closure with TEE guidance. Pediatric patients and patients with multiple ASDs who were expected to need multiple devices were excluded. Success rate was similar in both groups (ICE 96.1 %, TEE 92.7 %). Catheterization laboratory time was significantly shortened with ICE than with TEE (131 vs. 155 min, p = 0.0003). There were no complications related to the use of ICE. ICE-guided ASD closure is feasible in most adult patients. ICE is superior to TEE in shortening catheterization laboratory time and eliminating general anesthesia, and can potentially replace TEE as the primary image guide during percutaneous ASD closure.
JACC: Cardiovascular Interventions, 2014
Annals of General Psychiatry, 2013
Background Several lines of evidence suggest that dysfunction of the dorsolateral prefrontal cort... more Background Several lines of evidence suggest that dysfunction of the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) contributes to the pathophysiology of pervasive developmental disorders (PDD). The purpose of this study was to investigate neuropsychological dysfunctions in both the DLPFC and OFC of children and adolescents with high-functioning PDD. Methods The Iowa gambling task (IGT), which reflects OFC function, and the Wisconsin Card Sorting Test (WCST), which reflects DLPFC function, were assigned to 19 children and early adolescents with high-functioning PDD and 19 healthy controls matched for gender, age, and intelligence. Results Compared to healthy controls, patients with high-functioning PDD displayed poorer performance on the IGT and the WCST. Conclusions These results indicate that both the DLPFC and OFC could be impaired in children and early adolescents with high-functioning PDD.
JACC: Cardiovascular Interventions, 2014
Coronary Artery Disease, 2016
Besides its potent plasma cholesterol-lowering activity, statin treatment has several other impor... more Besides its potent plasma cholesterol-lowering activity, statin treatment has several other important effects, including lowering high-sensitive C-reactive protein (hs-CRP), levels, and stabilizing risk factors of atherosclerosis, thereby reducing the risk of cardiovascular events. Our aim in this study was to identify how intensive statin therapy can affect plasma levels of inflammatory markers over the long term. We used a prospective, randomized, open blinded-endpoint design. A total of 30 patients with stable coronary artery disease treated with everolimus-eluting stent implantation were randomized to receive rosuvastatin 2.5 (standard therapy group) or 10 mg (intensive therapy group) for 12 months. Plasma levels of hs-CRP, pentraxin-3, monocyte chemoattractant protein-1, and CXC chemokine ligand 4 were measured after a percutaneous coronary intervention, at 1, 3, 6, 9, and 12 months. Levels of LDL cholesterol (LDL-C) and HDL cholesterol were also measured. We investigated short-term and long-term clinical outcomes. After 12 months of therapy, the intensive therapy group had lower levels of LDL-C than the standard therapy group. Plasma levels of hs-CRP largely fluctuated in the standard therapy group, whereas they were stable in the intensive therapy group during the follow-up period. There were no significant differences in serum pentraxin-3, monocyte chemoattractant protein-1, and CXC chemokine ligand 4 levels, or in the incidence of any clinical adverse events, between the standard and the intensive therapy groups. Intensive rosuvastatin therapy stabilizes hs-CRP levels, but not chemokine levels, besides lowering LDL-C levels. Thus, this therapy may inhibit the progression of atherosclerosis by stably inhibiting the inflammatory cascade.
Child psychiatry and human development, Jan 16, 2016
On March 11, 2011, Japan was struck by a massive earthquake and tsunami. The tsunami caused treme... more On March 11, 2011, Japan was struck by a massive earthquake and tsunami. The tsunami caused tremendous damage and traumatized children. We aimed to evaluate and compare the changes in the traumatic symptoms of high school girls 8, 20, 30, and 42 months after the 2011 tsunami. The Post-Traumatic Stress Symptoms for Children 15 items (PTSSC-15), a self-rating questionnaire on traumatic symptoms, was administered to 811 high school girls at the above-mentioned intervals. We calculated the total score, post-traumatic stress disorder (PTSD) subscale, and depression subscale of PTSSC-15. The total score was correlated with house damage, evacuation experience, and bereavement experience. The PTSSC-15 total scores of high school girls with traumatic experience were significantly higher than the scores of children without these experiences (all p < 0.0001). The PTSSC-15 total score did not decrease significantly over time. Furthermore, the PTSD subscale of the PTSSC-15 did not significant...
Sleep and Biological Rhythms, 2014
ABSTRACT Changes in sleep patterns among children following traumatic experiences may be indicati... more ABSTRACT Changes in sleep patterns among children following traumatic experiences may be indicative of post-traumatic psychiatric disorders and contribute to disease persistence. We evaluated long-term changes in the sleep habits of 1919 junior high school students who experienced the 2011 Japan earthquake and tsunami, and examined the associations among sleep patterns, trauma symptoms, and specific traumatic events. The Post-Traumatic Stress Symptoms for Children-15 items self-completion questionnaire was distributed to the children, and a questionnaire regarding three specific traumatic events (home damage, bereavement, and evacuation) was distributed to their teachers. Compared to the same survey conducted 8 months after the disaster, a 20-month post-disaster survey revealed significantly shorter mean sleep duration and a delay in sleep phase (P &lt; 0.0001). On the 20-month survey, weekday sleep duration was shorter and sleep–wake pattern delayed in children who had experienced home damage compared to children with no such experience (P &lt; 0.01). Children who had experienced bereavement also reported a shorter mean sleep duration on the 20-month survey compared to children reporting no bereavement experience (P &lt; 0.05). Differences in sleep duration between weekdays and holidays at 20 months post-disaster suggested a sleep debt due to sleep disruption. There were no significant differences in Post-Traumatic Stress Symptoms for Children-15 items total scores between groups defined by the type of traumatic experience. Traumatic events (home damage, bereavement) associated with the 2011 Japan earthquake and tsunami have caused long-term sleep disruption in children from this region.
Circulation, Nov 23, 2010
PloS one, 2015
The Questionnaire: Children with Difficulties (QCD) is a parent-assessed questionnaire designed t... more The Questionnaire: Children with Difficulties (QCD) is a parent-assessed questionnaire designed to evaluate child's difficulties in functioning during specific periods of the day. This study aimed to evaluate difficulties in daily functioning of children and adolescents with pervasive developmental disorder (PDD) using the QCD. Results were compared with those for a community sample. A case-control design was used. The cases comprised elementary school students (182 males, 51 females) and junior high school students (100 males, 39 females) with PDD, whereas a community sample of elementary school students (568 males, 579 females) and junior high school students (180 males, 183 females) was enrolled as controls. Their behavior was assessed using the QCD, the Tokyo Autistic Behavior Scale (TABS), the ADHD-rating scale (ADHD-RS), and the Oppositional Defiant Behavior Inventory (ODBI) for elementary and junior high school students, respectively. Effects of gender and diagnosis on th...
Nature communications, Jan 13, 2015
Duchenne muscular dystrophy (DMD) is a chronic and life-threatening disease that is initially sup... more Duchenne muscular dystrophy (DMD) is a chronic and life-threatening disease that is initially supported by muscle regeneration but eventually shows satellite cell exhaustion and muscular dysfunction. The life-long maintenance of skeletal muscle homoeostasis requires the satellite stem cell pool to be preserved. Asymmetric cell division plays a pivotal role in the maintenance of the satellite cell pool. Here we show that granulocyte colony-stimulating factor receptor (G-CSFR) is asymmetrically expressed in activated satellite cells. G-CSF positively affects the satellite cell population during multiple stages of differentiation in ex vivo cultured fibres. G-CSF could be important in developing an effective therapy for DMD based on its potential to modulate the supply of multiple stages of regenerated myocytes. This study shows that the G-CSF-G-CSFR axis is fundamentally important for long-term muscle regeneration, functional maintenance and lifespan extension in mouse models of DMD w...
Journal of affective disorders, Jan 20, 2015
The parent-assessed children-with-difficulties questionnaire (Questionnaire-Children with Difficu... more The parent-assessed children-with-difficulties questionnaire (Questionnaire-Children with Difficulties; QCD) is designed to evaluate a child׳s difficulties in functioning during specific periods of the day. This study aimed to use the QCD to evaluate the difficulties in daily functioning experienced by children with depressive disorders. A case-control design was used. The cases comprised 90 junior high school students with depressive disorder, whereas a community sample of 363 junior high school students was enrolled as controls. Behaviors were assessed using the QCD, Depression Self-Rating Scale (DSRS), Tokyo Autistic Behavior Scale (TABS), attention deficit hyperactivity disorder-rating scale (ADHD-RS), and Oppositional Defiant Behavior Inventory (ODBI). We then analyzed the effects of sex and diagnosis on the QCD scores as well as the correlation coefficients between the QCD and the other questionnaires. We included 90 cases (33 boys, 57 girls) with depressive disorders and 363 ...
FEBS open bio, 2015
Mitochondrial diseases are heterogeneous disorders, caused by mitochondrial dysfunction. Mitochon... more Mitochondrial diseases are heterogeneous disorders, caused by mitochondrial dysfunction. Mitochondria are not regulated solely by nuclear genomic DNA but by mitochondrial DNA. It is difficult to develop effective therapies for mitochondrial disease because of the lack of mitochondrial disease models. Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the major mitochondrial diseases. The aim of this study was to generate MELAS-specific induced pluripotent stem cells (iPSCs) and to demonstrate that MELAS-iPSCs can be models for mitochondrial disease. We successfully established iPSCs from the primary MELAS-fibroblasts carrying 77.7% of m.3243A>G heteroplasmy. MELAS-iPSC lines ranged from 3.6% to 99.4% of m.3243A>G heteroplasmy levels. The enzymatic activities of mitochondrial respiratory complexes indicated that MELAS-iPSC-derived fibroblasts with high heteroplasmy levels showed a deficiency of complex I activity but MELAS-iPS...
Pediatrics international : official journal of the Japan Pediatric Society, Jan 6, 2015
Sleep disorders are frequently associated with childhood behavioral problems and mental illnesses... more Sleep disorders are frequently associated with childhood behavioral problems and mental illnesses such as anxiety disorders. To identify promising behavioral targets for therapy ofpediatric anxiety disorders, we investigated the associations between specific sleep and behavioral problems. We conducted retrospective reviews of 105 patientsaged 4-12 yearswho met the DSM-IV criteria for primary diagnosis of generalized anxiety disorder (GAD; n = 33), separation anxiety disorder (SAD;n = 23), social phobia (SP; n = 21), or obsessivecompulsive disorder (OCD;n = 28). Sleep problems were evaluated using the Children's Sleep Habits Questionnaire (CSHQ) and behavioral problems bythe Spence Children's Anxiety Scale (SCAS), Oppositional Defiant Behavior Inventory (ODBI), and Depression Self-Rating Scale for Children (DSRS-C). Depressive behavior was weakly correlated with CSHQ subscores for sleep onset delayand night waking but not with total sleep disturbance.Anxiety was correlated wi...
PloS one, 2014
The aim of this study was to evaluate the frontopolar hemodynamic response and depressive mood in... more The aim of this study was to evaluate the frontopolar hemodynamic response and depressive mood in children with mild or moderate major depressive disorder during six weeks treatment without medication. The subjects were 10 patients with mild or moderate depression. They were depressive drug-naive children and adolescents. The scores of Depression Self Rating Scale (DSRS), the results of the Verbal Fluency Test (VFT), and the concentrations of oxy-hemoglobin (Oxy-Hb) of frontal pole brain assessed by two-channel near infrared spectroscopy (NIRS) after six weeks of treatment was compared with those of initial treatment. The score of DSRS was significantly reduced after six weeks of initial treatment (p<0.001, t-test). The word number of VFT was not significantly changed after six weeks of treatment. The oxy-Hb concentration significantly increased after six weeks of treatment (p<0.001, t-test). This study demonstrated that the concentration of oxy-Hb of frontopolar cortex in chi...
Psychiatry and clinical neurosciences, 2012
The aim of this research was to clarify the development of depression among boys with attention d... more The aim of this research was to clarify the development of depression among boys with attention deficit hyperactivity disorder (ADHD) by examining the correlation between depressive mood, oppositional defiant behavior, and age for each ADHD subtype. The Birleson Depression Self-Rating Scale (DSRS) was used to evaluate depressive mood while the Oppositional Defiant Behavior Inventory (ODBI) was used to evaluate oppositional defiant behavior. The 90 subjects were divided into three groups: 22 boys (mean age, 12.4 ± 1.9 years) were placed in the ADHD predominantly inattentive type (ADHD-I) group; 45 boys (mean age, 10.4 ± 2.0 years) were placed in the ADHD combined type (ADHD-C) group; and 23 boys (mean age, 12.7 ± 2.4 years) were placed in the depressive disorder (DD) group. The DD group was included to highlight characteristics of depressive mood among boys with ADHD. The DSRS score was significantly higher in the DD group compared to the ADHD-I and ADHD-C groups. The ODBI score was ...
Journal of the American Heart Association, 2014
Background Despite the accumulating genetic and molecular investigations into hypertrophic cardio... more Background Despite the accumulating genetic and molecular investigations into hypertrophic cardiomyopathy (HCM), it remains unclear how this condition develops and worsens pathologically and clinically in terms of the genetic–environmental interactions. Establishing a human disease model for HCM would help to elucidate these disease mechanisms; however, cardiomyocytes from patients are not easily obtained for basic research. Patient‐specific induced pluripotent stem cells ( iPSCs ) potentially hold much promise for deciphering the pathogenesis of HCM. The purpose of this study is to elucidate the interactions between genetic backgrounds and environmental factors involved in the disease progression of HCM. Methods and Results We generated iPSC s from 3 patients with HCM and 3 healthy control subjects, and cardiomyocytes were differentiated. The HCM pathological phenotypes were characterized based on morphological properties and high‐speed video imaging. The differences between contro...
PLoS ONE, 2014
Background: On March 11, 2011, Japan was struck by a massive earthquake and tsunami. The tsunami ... more Background: On March 11, 2011, Japan was struck by a massive earthquake and tsunami. The tsunami caused tremendous damage and traumatized several people, including children. The aim of this study was to assess changes in traumatic symptoms 8, 20, and 30 months of the 2011 tsunami. Methods: The study comprised three groups. Copies of the Post-Traumatic Stress Symptoms for Children 15 items (PTSSC-15), a self-rating questionnaire on traumatic symptoms, were distributed to 12,524 children (8-month period), 12,193 children (20-month period), and 11,819 children (30-month period). An effective response of children 8 months, 20 months, and 30 month after the disaster was obtained in 11,639 (92.9%), 10,597 (86.9%), and 10,812 children (91.4%), respectively. We calculated the total score, PTSD subscale, and Depression subscale of PTSSC-15. We calculated the total score, PTSD subscale, and Depression subscale of PTSSC-15. Results: The PTSSC-15 total score and PTSD subscale of children belonging to 1st-9th grade groups who were tested 30 and 20 months after the tsunami significantly decreased compared with those of children tested 8 months after the tsunami. The PTSSC-15 total score and PTSD subscale of children in 1st-9th grade groups tested after 30 months did not decrease significantly compared with those of children tested after 20 months. The PTSSC-15 Depression subscale and PTSD subscale of children in 1st-9th grade groups tested after 30 months significantly decreased compared with those of children tested 8 months after the tsunami. The PTSSC-15 Depression subscale of children in 1st-9th grade groups evaluated after 30 months significantly decreased compared with those of children evaluated after 20 months. Conclusions: This study demonstrates that the traumatic symptoms of children who survived the massive tsunami improved with time. Nonetheless, the traumatic symptoms, which in some cases did not improve with time.
PLoS ONE, 2014
Background: The 2011 Japan massive tsunami traumatized many children. The aim of this study was t... more Background: The 2011 Japan massive tsunami traumatized many children. The aim of this study was to assess changes in strengths and difficulties experienced in home and school by among surviving children after the 2011 tsunami, in comparison with published normal Japanese data. Methods: In November 2012 (20 months after the disaster) and September 2013 (30 months after the disaster), the Strengths and Difficulties Questionnaire (SDQ), a questionnaire on children's strengths and difficulties in home and school activities, were distributed to 12,193 and 11,819 children, respectively. An effective response of children 20 months and 30 month after the disaster was obtained in 10,597 children (86.9%), and 10,812 children (91.4%), respectively. The SDQ scores evaluated by parents and teachers were compared with published normal Japanese SDQ scores. Results: The SDQ scores (emotional problems, conduct problems, hyperactivity/ inattention, peer relationship problems, and total difficulty score) evaluated by parents of children in the 4th to 9th grade who were evaluated after 30 and 20 months were significantly high compared with the published normal data of children without traumatic experiences (all P,0.001). The SDQ scores (prosocial behavior) evaluated by teachers of children in the 4th to 9th grade who were evaluated after 30 and 20 months were significantly low compared with the published normal data of children without traumatic experiences (all P,0.001).
Cardiovascular Intervention and Therapeutics, 2013
Transcatheter closure of secundum atrial septal defect (ASD) has been widely performed as a less ... more Transcatheter closure of secundum atrial septal defect (ASD) has been widely performed as a less invasive alternative to surgery with zero mortality so far in Japan. In the US and Europe, intracardiac echocardiography (ICE) has replaced transesophageal echocardiography (TEE) as a primary imaging tool during percutaneous ASD closure. However, the experience of ICE in ASD closure is limited in Japan. Consecutive 51 patients underwent percutaneous ASD closure with ICE guidance. Clinical results were compared to those of 41 patients who underwent ASD closure with TEE guidance. Pediatric patients and patients with multiple ASDs who were expected to need multiple devices were excluded. Success rate was similar in both groups (ICE 96.1 %, TEE 92.7 %). Catheterization laboratory time was significantly shortened with ICE than with TEE (131 vs. 155 min, p = 0.0003). There were no complications related to the use of ICE. ICE-guided ASD closure is feasible in most adult patients. ICE is superior to TEE in shortening catheterization laboratory time and eliminating general anesthesia, and can potentially replace TEE as the primary image guide during percutaneous ASD closure.
JACC: Cardiovascular Interventions, 2014
Annals of General Psychiatry, 2013
Background Several lines of evidence suggest that dysfunction of the dorsolateral prefrontal cort... more Background Several lines of evidence suggest that dysfunction of the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) contributes to the pathophysiology of pervasive developmental disorders (PDD). The purpose of this study was to investigate neuropsychological dysfunctions in both the DLPFC and OFC of children and adolescents with high-functioning PDD. Methods The Iowa gambling task (IGT), which reflects OFC function, and the Wisconsin Card Sorting Test (WCST), which reflects DLPFC function, were assigned to 19 children and early adolescents with high-functioning PDD and 19 healthy controls matched for gender, age, and intelligence. Results Compared to healthy controls, patients with high-functioning PDD displayed poorer performance on the IGT and the WCST. Conclusions These results indicate that both the DLPFC and OFC could be impaired in children and early adolescents with high-functioning PDD.