担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Bioscientifica  

Summary

Rett syndrome (RS) is an X-linked neurodevelopmental disorder primarily affecting females. RS and diabetes mellitus (DM) type 1 are rare disorders with distinct etiologies. Although some cases of RS complicated by DM type 1 have been reported, the association between these distinct conditions is poorly understood and warrants further studies to elucidate the underlying mechanisms and inform clinical management. We report the case of a 10-year-old girl diagnosed with RS and DM type 1. The patient initially presented at 3 years of age with polydipsia, polyuria and decreased appetite over several weeks. Physical examination showed signs of dehydration, and laboratory evaluation revealed hyperglycemia, elevated HbA1c, glycosuria, ketonuria and low C-peptide levels. Anti-glutamic acid decarboxylase antibodies were positive, confirming autoimmune DM type 1. Fluid resuscitation and insulin therapy were initiated with good glycemic control on continuous subcutaneous insulin infusion. A review of her history revealed normal early developmental milestones, including the onset of stereotypical hand movements at 3 years, communication impairment and seizures at 4 years and a diagnosis of autism spectrum disorder. At 10 years of age, genetic testing revealed a pathogenic MECP2 mutation. Clinical features, including breathing abnormalities, bruxism, abnormal tone and inappropriate laughing, met the diagnostic criteria for RS. This is the reported first case of RS with a confirmed MECP2 mutation complicated by DM type 1. Our case report contributes to the increasing evidence supporting the potential association between RS and DM type 1.

Learning points

There is a possible link between RS and DM type 1.

This is the first case report of RS with a confirmed MECP2 mutation complicated by DM type 1.

In cases where patients with RS develop diabetic ketoacidosis, it may manifest as mild acidosis or normal pH despite the presence of high blood sugar levels and dehydration.

DOI： 10.1530/edm-24-0010

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その他リンク： https://edm.bioscientifica.com/downloadpdf/journals/edm/2025/1/EDM-24-0010.xml

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.cca.2025.120130

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Gallstone ileus is an uncommon complication of cholelithiasis and the delayed diagnosis may be associated with increased risk of mortality. When gallstones block the cystic duct, they can lead to cholecystitis. If a fistula forms between the inflamed gallbladder and the adjacent intestine, the gallstones may pass into the intestinal tract and cause obstruction in the intestine. We report a case of 25‐year‐old female with developmental and epileptic encephalopathy who was intraoperatively diagnosed with gallstone ileus during surgery for small bowel obstruction of unknown origin. The patient had potential risk factors enhancing the formation of cholesterol gallstones, including long‐term use of phenobarbital, vagus nerve injury in open gastrostomy and laparoscopic fundoplication, and tube feeding; however, the patient’s gallstone had been undiagnosed for a long time. Computed tomography of the abdomen showed small bowel obstruction and pneumobilia. The presence of pneumobilia in a patient without a surgical history of the biliary system should raise suspicion of a bilioenteric fistula. The awareness of this complication of cholelithiasis is important to make an early diagnosis and to initiate the appropriate treatment.

DOI： 10.1155/crgm/4901433

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.radcr.2025.04.083

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.scr.2024.103584

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41439-024-00296-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

3β-Hydroxysteroid dehydrogenases (3β-HSDs) catalyze the oxidative conversion of delta (5)-ene-3-beta-hydroxy steroids and ketosteroids. Human 3β-HSD type 2 (HSD3B2) is predominantly expressed in gonadal and adrenal steroidogenic cells for producing all classes of active steroid hormones. Mutations in HSD3B2 gene cause a rare form of congenital adrenal hyperplasia with varying degree of salt wasting and incomplete masculinization, resulting from reduced production of corticoids and androgens. Therefore, evaluation of the HSD3B2 enzymatic activity in both pathways for each steroid hormone production is important for accurately understanding and diagnosing this disorder. Using progesterone receptor (PR)- and androgen receptor (AR)-mediated transactivation, we adapted a method that easily evaluates enzymatic activity of HSD3B2 by quantifying the conversion from substrates [pregnenolone (P5) and dehydroepiandrosterone (DHEA)] to (progesterone and androstenedione). HEK293 cells were transduced to express human HSD3B2, and incubated medium containing P5 or DHEA. Depending on the incubation time with HSD3B2-expressing cells, the culture media progressively increased luciferase activities in CV-1 cells, transfected with the PR/AR expression vector and progesterone-/androgen-responsive reporter. Culture media from human and other mammalian HSD3B1-expressing cells also increased the luciferase activities. HEK293 cells expressing various missense mutations in the HSD3B2 gene revealed the potential of this system to evaluate the relationship between the enzymatic activities of mutant proteins and patient phenotype.

DOI： 10.3389/fendo.2024.1480722

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Backgroud: Rett syndrome is a neurodevelopmental disorder that affects 1 in 10,000 females. Various treatments have been explored; however, no effective treatments have been reported to date, except for trofinetide, a synthetic analog of glycine-proline-glutamic acid, which was approved by the FDA in 2023. Serological biomarkers that correlate with the disease status of RTT are needed to promote early diagnosis and to develop novel agents. Methods: In this study, we performed a high-depth proteomic analysis of extracellular vesicles containing preparations extracted from patient plasma samples to identify novel biomarkers. Results: We identified 33 upregulated and 17 downregulated candidate proteins among a total of 4273 proteins in RTT compared to the healthy controls. Among these, UBE3B was predominantly increased in patients with Rett syndrome and exhibited a strong correlation with the clinical severity score, indicating the severity of the disease. Conclusions: We demonstrated that the proteomics of high-depth extracellular vesicles containing preparations in rare diseases could be valuable in identifying new disease biomarkers and understanding their pathophysiology.

DOI： 10.3390/biomedicines12102172

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担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（研究会，シンポジウム資料等）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.ensci.2024.100520

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/cga.12582

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.7759/cureus.67797

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ  

Objectives

To investigate the association between multimorbidity during pregnancy and neurodevelopmental delay in offspring using data from a Japanese nationwide birth cohort study.

Design

This study was a prospective birth cohort study.

Setting

This study population included 104 059 fetal records who participated in The Japan Environment and Children’s Study from 2011 to 2014.

Participants

Pregnant women whose children had undergone developmental testing were included in this analysis.

Primary and secondary outcome measures

Neurodevelopment of offspring was assessed using the Japanese version of the Ages and Stages Questionnaire, third edition, comprising five developmental domains. The number of comorbidities among the pregnant women was categorised as zero, single disease or multimorbidity (two or more diseases). Maternal chronic conditions included in multimorbidity were defined as conditions with high prevalence among women of reproductive age. A multivariate logistic regression analysis was conducted to examine the association between multimorbidity in pregnant women and offspring development.

Results

Pregnant women with multimorbidity, single disease and no disease accounted for 3.6%, 30.6% and 65.8%, respectively. The ORs for neurodevelopmental impairment during the follow-up period were similar for infants of mothers with no disease comorbidity and those with a single disease comorbidity. However, the ORs for neurodevelopmental impairment were significantly higher for children born to mothers with multimorbidity compared with those born to healthy mothers.

Conclusion

An association was observed between the number of comorbidities in pregnant women and developmental delay in offspring. Multimorbidity in pregnant women may be associated with neurodevelopmental delay in their offspring. Further research is required in this regard in many other regions of the world.

DOI： 10.1136/bmjopen-2023-082585

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Public Library of Science (PLoS)  

Socioeconomic status and smoking are reportedly associated with underweight and obesity; however, their associations among pregnant women are unknown. This study aimed to investigate whether socioeconomic factors, namely educational attainment, household income, marital status, and employment status, were associated with pre-pregnancy body mass index (BMI) categories, including severe-moderate underweight (BMI ≤ 16.9 kg/m²), mild underweight (BMI, 17.0–18.4 kg/m²), overweight (BMI, 25.0–29.9 kg/m²), and obese (BMI ≥ 30.0 kg/m²) among Japanese pregnant women using data from the Japan Environment and Children’s Study (JECS). In total, pregnant women were included 96,751. Age- and parity-adjusted multivariable multinomial logistic regression analyses assessed socioeconomic factors and smoking associations with falling within abnormal BMI categories (normal BMI as the reference group). Lower education and lower household were associated with overweight and obesity, and, especially, lowest education and household income had relatively higher point estimate relative ratios (RRs) of 3.97 and 2.84, respectively. Regarding the risks for underweight, however, only junior high school education had a significantly higher RR for severely to moderately underweight. Regarding occupational status, homemakers or the unemployed had a higher RR for severe-moderate underweight, overweight, and obesity. Unmarried, divorced, or bereaved women had significantly higher RRs for mildly underweight status. Quitting smoking early in pregnancy/still smoking had higher RRs for all four not having normal BMI outcomes; however, quitting smoking before pregnancy had a higher RR only for obese individuals. Lower educational attainment and smoking are essential intervention targets for obesity and severe-moderate underweight prevention in younger women. Lower household income is also a necessary target for obesity.

DOI： 10.1371/journal.pone.0304844

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jns.2024.123063

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.scr.2024.103432

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Background

Four-dimensional flow magnetic resonance imaging (MRI) enables blood flow visualization. The absence of left atrial vortex flow (LAVF) has been implicated in the development of thrombus formation and arrhythmias. However, the clinical relevance of this phenomenon in patients with congenital heart disease (CHD) remains unclear. This study aimed to unravel the relationship of LAVF with left atrial functions in patients with CHD.

Results

Twenty-five participants who underwent cardiac MRI examinations were included (8 postoperative patients with CHD aged 17–41 years and 17 volunteers aged 21–31 years). All participants were in sinus rhythm. Four-dimensional flow MRI (velocity encoding 100 cm/s) assessed the presence of LAVF, and its relationship with left atrial function determined by transthoracic echocardiography was explored. LAVF was detected in 16 patients. Upon classification of the participants based on the presence or absence of LAVF, 94% of participants in the LAVF group were volunteers, while 78% of those in the without LAVF group were postoperative patients. Participants without LAVF had a significantly lower left atrial ejection fraction (61% vs. 70%, p = 0.019), reservoir (32% vs. 47%, p = 0.006), and conduit (22% vs. 36%, p = 0.002) function than those with LAVF.

Conclusions

LAVF occurred during the late phase of ventricular systole, and left atrial reservoir function may have contributed to its occurrence. Many postoperative patients with CHD experienced a loss of LAVF. LAVF may indicate early left atrial dysfunction resulting from left atrial remodeling.

DOI： 10.1186/s43044-024-00486-2

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その他リンク： https://link.springer.com/article/10.1186/s43044-024-00486-2/fulltext.html

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/ped.15825

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Background

Shiga toxin‐producing Escherichia coli‐associated hemolytic uremic syndrome (STEC‐HUS) is a life‐threatening condition complicated by acute kidney injury, acute respiratory distress syndrome, and central nervous system disorders. The early identification of high‐risk patients is required to facilitate timely and appropriate treatment.

Methods

The medical records of patients with STEC‐HUS treated at 11 hospitals in Hokkaido, Japan, were reviewed retrospectively. A multi‐institutional retrospective analysis was performed in which patients were divided into two groups according to the presence or absence of severe complications requiring blood purification therapy or encephalopathy. We compared the laboratory values at diagnosis between the severe and mild groups. To identify patients at high risk of developing severe complications, a scoring system, referred to as the “STEC‐HUS severity (STEC‐HUSS) score,” was constructed based on the parameters showing significant differences.

Results

Of the 41 patients with STEC‐HUS, 11 were classified into the severe group and 30 into the mild group. Significant differences were observed between the groups in terms of white blood cell count, activated partial thromboplastin time, fibrinogen, D‐dimer, total protein, aspartate transaminase, alanine transaminase, lactate dehydrogenase, creatinine, and C‐reactive protein levels. The STEC‐HUSS score was calculated on a scale of 0–10 by summing the number of test items that demonstrated abnormal values. The STEC‐HUSS score, when the cut‐off value was 4, showed a sensitivity of 100% and a specificity of 91% in the severe group.

Conclusion

We developed a novel scoring system to identify patients at high risk of severe STEC‐HUS.

DOI： 10.1111/ped.15833

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担当区分：最終著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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担当区分：最終著者   記述言語：日本語  

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担当区分：最終著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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担当区分：最終著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

Abstract

Background

Long term re-coarctation of the aorta can cause aortic dilatation, hypertension, and cardiac dysfunction due to increased left ventricular afterload. It is difficult to detect changes in left ventricular function due to increased afterload if the contractile force of the left ventricle is maintained. Herein, we have reported a case of re-coarctation of the aorta, for which 4D flow magnetic resonance imaging (MRI) scan was obtained both before and after balloon dilatation for aortic re-coarctation. Ultimately, improvement in aortic helical flow and left ventricular hemodynamics was observed.

Case Summary

A 29-year-old female was diagnosed with coarctation of the aorta and a bicuspid aortic valve after birth and underwent surgery at one month. At 8 years of age, she underwent balloon dilatation for re-coarctation. At the age of 28 years, she was diagnosed with re-coarctation triggered by hypertension. She underwent balloon dilatation as her cardiac catheterization revealed a systolic pressure gradient of 40 mmHg. Pretreatment 4D flow MRI demonstrated helical flow in the ascending aorta and descending thoracic aorta and left ventricular blood flow analysis revealed a decrease in left ventricular kinetic energy during systole; these improved after treatment.

Discussion

The use of helical flow evaluation by 4D flow MRI for aortic re-coarctation is well known in clinical practice. However, our report is the first to evaluate intraventricular blood flow before and after the re-coarctation treatment. The MRI evaluation demonstrated that the helical flow and left ventricular blood flow distribution improved after re-coarctation treatment due to the reduction of afterload.

DOI： 10.1093/ehjcr/ytad514

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.clinbiochem.2023.110650

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s00380-023-02313-1

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その他リンク： https://link.springer.com/article/10.1007/s00380-023-02313-1/fulltext.html

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Pathogenic variants of HECW2 have been reported in cases of neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL; OMIM #617268). A novel HECW2 variant (NM_001348768.2:c.4343 T > C,p.Leu1448Ser) was identified in an NDHSAL infant with severe cardiac comorbidities. The patient presented with fetal tachyarrhythmia and hydrops and was postnatally diagnosed with long QT syndrome. This study provides evidence that HECW2 pathogenic variants can cause long QT syndrome along with neurodevelopmental disorders.

DOI： 10.1038/s41439-023-00245-w

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その他リンク： https://www.nature.com/articles/s41439-023-00245-w

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.7759/cureus.39845

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ  

Objectives

Multimorbidity is defined as the coexistence of two or more chronic physical or psychological conditions within an individual. The association between maternal multimorbidity and adverse perinatal outcomes such as preterm delivery and low birth weight has not been well studied. Therefore, this study aimed to investigate this association.

Methods

We conducted a prospective cohort study using data from the Japan Environment and Children’s Study of pregnant women between 2011 and 2014. Those with data on chronic maternal conditions were included in the study and categorised as having no chronic condition, one chronic condition or multimorbidities. The primary outcomes were the incidence of preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA). Adjusted logistic regression was performed to estimate ORs (aORs) and 95% CIs.

Results

Of the 104 062 fetal records, 86 885 singleton pregnant women were analysed. The median maternal age and body mass index were 31 years and 20.5 kg/m², respectively. The prevalence of pregnant women with one or more chronic conditions was 40.2%. The prevalence of maternal multimorbidity was 6.3%, and that of PTB, LBW, and SGA were 4.6%, 8.1%, and 7.5%, respectively. Pre-pregnancy underweight women were the most common, observed in 15.6% of multimorbidity cases, followed by domestic violence from intimate partner in 13.0%. Maternal multimorbidity was significantly associated with PTB (aOR 1.50; 95% CI 1.33–1.69), LBW (aOR 1.49; 95% CI 1.35–1.63) and SGA (aOR 1.33; 95% CI 1.20–1.46).

Conclusion

Maternal multimorbidity was associated with adverse perinatal outcomes, including PTB, LBW and SGA. The risk of adverse perinatal outcomes tends to increase with a rise in the number of chronic maternal conditions. Multimorbidity becomes more prevalent among pregnant women, making our findings important for preconception counselling.

DOI： 10.1136/bmjopen-2022-069281

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.braindev.2023.02.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jns.2023.120597

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/ped.15506

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

Proper development and function of the central nervous system require precise regulation of gene expression. MicroRNAs (miRNAs), a group of small non-coding RNAs that can negatively regulate gene expression at the post-transcriptional level, are critical regulators of neuronal development, and dysregulation of microRNAs has been implicated in various neurological disorders. Changes in microRNA expression and repertoire are related to the emergence of social and behavioral variations in closely related primates, including humans, during evolution. MicroRNA-514a (miR-514a) is an X-linked miRNA that is conserved in species with higher social and cognitive functions, and frequent tandem duplications of miR-514a have been found in primate genomes. Here, we demonstrate that miR-514a plays a crucial role in neuronal development in neurons derived from human induced pluripotent stem cells (iPSCs). Overexpression of miR-514a increased dendritic length, soma size, and activity levels of mammalian target of rapamycin (mTOR) signaling in induced pluripotent stem cell-derived neurons, whereas blocking of endogenous miR-514a inhibited neuronal development. Furthermore, we performed a functional analysis of the miR-514a variation found during primate evolution, to investigate the impact of miR-514a sequence variation and associated changes in expression on brain development during evolution. We found that mutation in miR-514a significantly reduced the expression of the mature form and abolished the effects observed when native miR-514a was expressed. Our findings provide new insights into the functional role of miR-514a in the regulation of neuronal development and evolution of primate brain development.

DOI： 10.3389/fcell.2023.1096463

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

It was reported that nicotinic acetylcholine receptor (nAChR)-mediated signaling pathways affect the proliferation and differentiation of pluripotent stem cells. However, detail expression profiles of nAChR genes were unrevealed in these cells. In this study, we comprehensively investigated the gene expression of α subunit of nAChRs (Chrna) during differentiation and induction of pluripotent stem cells. Mouse embryonic stem (ES) cells expressed multiple Chrna genes (Chrna3-5, 7 and 9) in undifferentiated status. Among them, Chrna9 was markedly down-regulated upon the differentiation into mesenchymal cell lineage. In mouse tissues and cells, Chrna9 was mainly expressed in testes, ES cells and embryonal F9 teratocarcinoma stem cells. Expression of Chrna9 gene was acutely reduced during differentiation of ES and F9 cells within 24 h. In contrast, Chrna9 expression was increased in induced pluripotent stem cells established from mouse embryonic fibroblast. It was shown by the reporter assays that T element-like sequence in the promoter region of Chrna9 gene is important for its activities in ES cells. Chrna9 was markedly reduced by siRNA-mediated knockdown of Tbx3, a pluripotency-related transcription factor of the T-box gene family. These results indicate that Chrna9 is a nAChR gene that are transcriptionally regulated by Tbx3 in undifferentiated pluripotent cells.

DOI： 10.1038/s41598-023-28814-7

PubMed

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Diabetes Association  

DOI： 10.2337/dc22-1573

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jns.2022.120498

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Background

The extremes of maternal pre-pregnancy body mass index (BMI) are known to be risk factors associated with obstetric and adverse perinatal outcomes. Among Japanese women aged 20 years or older, the prevalence of underweight (BMI < 18.5 kg/m²) was 11.5% in 2019. Maternal thinness is a health problem caused by the desire to become slim. This study aimed to investigate the association between the severity of maternal low pre-pregnancy BMI and adverse perinatal outcomes, including preterm birth (PTB), low birth weight (LBW), and small-for-gestational age (SGA).

Methods

We conducted a prospective cohort study using data from the Japan Environment and Children’s Study, which recruited pregnant individuals between 2011 and 2014. Pre-pregnancy BMI was categorized as severe-moderate underweight (BMI < 16.9 kg/m²), mild underweight (BMI, 17.0–18.4 kg/m²), low-normal weight (BMI, 18.5–19.9 kg/m²), high-normal weight (BMI, 20.0–22.9 kg/m²), overweight (BMI, 23.0–24.9 kg/m²), and obese (BMI ≥ 25.0 kg/m²). The high-normal weight group was used as the reference for statistical analyses. Adjusted logistic regression was performed to evaluate the association between pre-pregnancy BMI and PTB, LBW, and SGA.

Results

Of 92,260 singleton pregnant individuals, the prevalence was 2.7% for severe-moderate underweight, 12.9% for mild underweight, and 24.5% for low-normal weight. The prevalence of adverse outcomes was 4.6% for PTB, 8.1% for LBW, and 7.6% for SGA. The adjusted odds ratios (aORs) for PTB were 1.72 (95% confidence interval [CI], 1.46–2.03) for severe-moderate underweight and 1.26 (95% CI, 1.14–1.39) for mild underweight. The aORs of LBW were 2.55 (95% CI, 2.27–2.86) for severe-moderate underweight, 1.64 (95% CI, 1.53–1.76) for mild underweight, and 1.23 (95% CI, 1.16–1.31) for low-normal weight. The aORs of SGA were 2.53 (95% CI, 2.25–2.84) for severe-moderate underweight, 1.66 (95% CI, 1.55–1.79) for mild underweight, and 1.29 (95% CI, 1.21–1.38) for low-normal weight.

Conclusions

A dose-response relationship was found between the severity of low pre-pregnancy BMI and PTB, LBW, and SGA. Even low-normal BMI (18.5–19.9 kg/m²) increased the risk of LBW and SGA. This study provides useful information for pre-conception counseling in lean individuals.

DOI： 10.1186/s12884-022-04418-3

PubMed

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その他リンク： https://link.springer.com/article/10.1186/s12884-022-04418-3/fulltext.html

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Leigh syndrome is the most genetically heterogenous phenotype of mitochondrial disease. We describe a patient with Leigh syndrome whose diagnosis had not been confirmed because of normal metabolic screening results at the initial presentation. Whole-exome sequencing identified pathogenic variants in NARS2, the gene encoding a mitochondrial asparaginyl-tRNA synthetase. One of the biallelic variants was novel. This highlights the essential role of genetic testing for a definite diagnosis of Leigh syndrome.

DOI： 10.1038/s41439-022-00191-z

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その他リンク： https://www.nature.com/articles/s41439-022-00191-z

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Cambridge University Press (CUP)  

Abstract

Background:

Assessing the hepatic status of children with CHD is very important in the post-operative period. This study aimed to assess the usefulness of paediatric liver T1/T2 values and to evaluate the impact of respiration on liver T1/T2 values.

Methods:

Liver T1/T2 values were evaluated in 69 individuals who underwent cardiac MRI. The mean age of the participants was 16.2 ± 9.8 years. Two types of imaging with different breathing methods were possible in 34 participants for liver T1 values and 10 participants for liver T2 values.

Results:

The normal range was set at 620–830 msec for liver T1 and 25–40 ms for liver T2 based on the data obtained from 17 healthy individuals. The liver T1/T2 values were not significantly different between breath-hold and free-breath imaging (T1: 769.4 ± 102.8 ms versus 763.2 ± 93.9 ms; p = 0.148, T2: 34.9 ± 4.0 ms versus 33.6 ± 2.4 ms; p = 0.169). Higher liver T1 values were observed in patients who had undergone Fontan operation, tetralogy of Fallot operation, or those with chronic viral hepatitis. There was a trend toward correlation between liver T1 values and liver stiffness (R = 0.65, p = 0.0004); and the liver T1 values showed a positive correlation with the shear wave velocity (R = 0.62, p = 0.0006).

Conclusions:

Liver T1/T2 values were not affected by breathing patterns. Because liver T1 values tend to increase with right heart overload, evaluation of liver T1 values during routine cardiac MRI may enable early detection of future complications.

DOI： 10.1017/s1047951122003274

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jns.2022.120381

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE Publications  

Although children with orofacial clefts have an increased risk for sleep-disordered breathing, no studies have examined the association of sleep duration. Thus, this study aimed to examine associations between orofacial clefts and sleep duration at 1 month, 6 months, 1 year, and 3 years of age in Japan.

A cohort study from the Japan Environment and Children's Study.

This study consisted of 91 497 children, including ones with isolated cleft lip and palate (n = 69), isolated cleft lip only (n = 48), and isolated cleft palate only (n = 37), for which recruitment was undertaken during 2011 to 2014.

Seep durations (hours per day) at 1 month, 6 months, 1 year, and 3 years of age, as reported by their mothers.

In the control group, mean sleep durations and standard deviations at 1 month, 6 months, 1 year, and 3 years of age were 15.2 (2.5), 13.6 (1.9), 12.9 (1.6), and 11.6 (1.2) h, respectively. Compared to the control group, linear regression models reported effect sizes and 95% confidence intervals shorter than 1 h for sleep duration of each type of isolated orofacial cleft at each time point.

This study suggested null associations between isolated orofacial clefts and sleep duration at 1 month, 6 months, 1 year, and 3 years of age. Children with isolated orofacial clefts had sufficient mean sleep duration.

DOI： 10.1177/10556656221128425

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その他リンク： http://journals.sagepub.com/doi/full-xml/10.1177/10556656221128425

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

This study aimed to document the complication status of infants with orofacial clefts born between 2011 and 2014 in Japan. This was a descriptive study using data from the Japan Environment and Children's Study. Among 103 060 pregnancies, 248 infants with orofacial clefts were included (livebirth, 239; stillbirth, 4; miscarriage, 5). The items of interest were complication status of orofacial clefts: isolated (typical orofacial clefts only); multi-malformed (orofacial clefts with unrelated major defects); syndromic (orofacial clefts with a syndrome or a chromosomal defect). Regarding the cleft subtypes, of 248 infants with orofacial clefts, 104 had cleft lip with cleft palate (CLP) (41.9%), 68 had cleft lip without cleft palate (CL) (27.4%), 58 had cleft palate without cleft lip (CP) (23.4%), and 18 were nonclassified (7.3%). In infants with CLP, the proportions of isolated, multi-malformed, and syndromic phenotypes were 73.1%, 15.4%, and 11.5%, respectively. In infants with CL, the proportions were 79.4%, 16.2%, and 4.4%, respectively. In infants with CP, the proportions were 69.0%, 13.8%, and 17.2%, respectively. The most frequently associated congenital anomaly was congenital heart disease. In infants with syndromic CLP, 41.7% had trisomy 13. In infants with syndromic CP, 80.0% had the Pierre Robin sequence. Congenital heart disease could be the most frequently associated congenital anomaly. The most frequently associated syndrome could be trisomy 13 in those with CLP and Pierre Robin sequence in those with CP.

DOI： 10.1111/cga.12496

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.envres.2022.114302

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

ABSTRACT: Myofibrillar myopathy is a clinically and genetically heterogeneous group of muscle disorders characterized by myofibrillar degeneration. Bcl-2-associated athanogene 3 (BAG3)-related myopathy is the rarest form of myofibrillar myopathy. Patients with BAG3-related myopathy present with early-onset and progressive muscle weakness, rigid spine, respiratory insufficiency, and cardiomyopathy. Notably, the heterozygous mutation (Pro209Leu) in BAG3 is commonly associated with rapidly progressive cardiomyopathy in childhood. We describe a male patient with the BAG3 (Pro209Leu) mutation. The patient presented at age 7 years with muscle weakness predominantly in the proximal lower limbs. Histologic findings revealed a mixture of severe neurogenic and myogenic changes. His motor symptoms progressed rapidly in the next decade, becoming wheelchair-dependent by age 17 years; however, at the age of 19 years, cardiomyopathy was not evident. This study reports a case of BAG3-related myopathy without cardiac involvement and further confirmed the wide phenotypic spectrum of BAG3-related myopathy.

DOI： 10.1097/cnd.0000000000000392

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Galenos Yayinevi  

DOI： 10.4274/jcrpe.galenos.2022.2022-4-11

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

Rett syndrome (RTT) is a severe progressive neurodevelopmental disorder characterized by various neurological symptoms. Almost all RTT cases are caused by mutations in the X-linked methyl-CpG-binding protein 2 (MeCP2) gene, and several mouse models have been established to understand the disease. However, the neuroanatomical abnormalities in each brain region of RTT mouse models have not been fully understood. Here, we investigated the global and local neuroanatomy of the Mecp2 gene-deleted RTT model (Mecp2-KO) mouse brain using T2-weighted 3D magnetic resonance imaging with different morphometry to clarify the brain structural abnormalities that are involved in the pathophysiology of RTT. We found a significant reduction in global and almost all local volumes in the brain of Mecp2-KO mice. In addition, a detailed comparative analysis identified specific volume reductions in several brain regions in the Mecp2-deficient brain. Our analysis also revealed that the Mecp2-deficient brain shows changes in hemispheric asymmetry in several brain regions. These findings suggest that MeCP2 affects not only the whole-brain volume but also the region-specific brain structure. Our study provides a framework for neuroanatomical studies of a mouse model of RTT.

DOI： 10.3389/fnins.2022.885335

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担当区分：最終著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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担当区分：最終著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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担当区分：最終著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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担当区分：最終著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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担当区分：最終著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：S. Karger AG  

Hereditary spastic paraplegias (HSPs) are rare neurological disorders caused by degeneration of the corticospinal tract. Among the 79 causative genes involved in HSPs, variants in <i>SPAST</i> on chromosome 2p22, which encodes the microtubule-severing protein spastin, are responsible for spastic paraplegia type 4 (SPG4), the most common form of HSPs. SPG4 is characterized by a clinically pure phenotype that is associated with restricted involvement of the corticospinal tract; however, it is often accompanied by additional neurological symptoms such as epilepsy and cognitive impairment. There are few reports regarding the clinical course and treatment of epilepsy associated with SPG4. We describe a 21-year-old male patient with progressive weakness and spasticity of the lower limbs since infancy, which was complicated by epilepsy and cognitive impairment. Magnetic resonance imaging of the brain showed right hippocampal atrophy before the onset of epilepsy. Genetic analysis revealed a novel missense variant (NM_014946.4:c.1330G>C, p.Asp444His) in the <i>SPAST</i> gene. At the age of 13, the patient developed focal epilepsy, characterized by focal onset seizures that were preceded by a sensation of chest tightness. Carbamazepine, levetiracetam, and zonisamide were ineffective in controlling the seizures; however, the use of lacosamide in combination with lamotrigine and valproate was highly effective in improving the seizure symptoms and led to the patient being seizure free for at least 2 years. In conclusion, the missense variant in <i>SPAST</i> may cause a complex SPG4 phenotype accompanied by epilepsy and cognitive impairment, suggesting that the clinical manifestations of this condition do not confine to the motor system.

DOI： 10.1159/000520433

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担当区分：最終著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) converts androstenedione (A4) into testosterone (T), which regulates sex steroid production. Because various mutations of the HSD17B3 gene cause disorder of sex differentiation (DSD) in multiple mammalian species, it is very important to reveal the molecular characteristics of this gene in various species. Here, we revealed the open reading frame of the ovine HSD17B3 gene. Enzymatic activities of ovine HSD17B3 and HSD17B1 for converting A4 to T were detected using ovine androgen receptor-mediated transactivation in reporter assays. Although HSD17B3 also converted estrone to estradiol, this activity was much weaker than those of HSD17B1. Although ovine HSD17B3 has an amino acid sequence that is conserved compared with other mammalian species, it possesses two amino acid substitutions that are consistent with the reported variants of human HSD17B3. Substitutions of these amino acids in ovine HSD17B3 for those in human did not affect the enzymatic activities. However, enzymatic activities declined upon missense mutations of the HSD17B3 gene associated with 46,XY DSD, affecting amino acids that are conserved between these two species. The present study provides basic information and tools to investigate the molecular mechanisms behind DSD not only in ovine, but also in various mammalian species.

DOI： 10.3390/ani11102876

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1212/wnl.0000000000012130

PubMed

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jsbmb.2021.105847

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

Although 11-ketotestosterone (11KT) and testosterone (T) are major androgens in both teleosts and humans, their 5α-reduced derivatives produced by steroid 5α-reductase (SRD5A/srd5a), i.e., 11-ketodihydrotestosterone (11KDHT) and 5α-dihydrotestosterone (DHT), remains poorly characterized, especially in teleosts. In this study, we compared the presence and production of DHT and 11KDHT in Japanese eels and humans. Plasma 11KT concentrations were similar in both male and female eels, whereas T levels were much higher in females. In accordance with the levels of their precursors, 11KDHT levels did not show sexual dimorphism, whereas DHT levels were much higher in females. It is noteworthy that plasma DHT levels in female eels were higher than those in men. In addition, plasma 11KDHT was undetectable in both sexes in humans, despite the presence of 11KT. Three srd5a genes (srd5a1, srd5a2a and srd5a2b) were cloned from eel gonads. All three srd5a genes were expressed in the ovary, whereas only both srd5a2 genes were expressed in the testis. Human SRD5A1 was expressed in testis, ovary and adrenal, whereas SRD5A2 was expressed only in testis. Human SRD5A1, SRD5A2 and both eel srd5a2 isoforms catalyzed the conversion of T and 11KT into DHT and 11KDHT, respectively, whereas only eel srd5a1 converted T into DHT. DHT and 11KDHT activated eel androgen receptor (ar)α-mediated transactivation as similar fashion to T and 11KT. In contrast, human AR and eel arβ were activated by DHT and11KDHT more strongly than T and 11KT. These results indicate that in teleosts, DHT and 11KDHT may be important 5α-reduced androgens produced in the gonads. In contrast, DHT is the only major 5α-reduced androgens in healthy humans.

DOI： 10.3389/fendo.2021.657360

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01232&link_issn=&doc_id=20210301280005&doc_link_id=%2Fcl1nohat%2F2021%2F005302%2F009%2F0129-0132%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcl1nohat%2F2021%2F005302%2F009%2F0129-0132%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

This study aimed to elucidate the clinical characteristics of MECP2 duplication syndrome (MDS), particularly at initial presentation, and to provide clinical clues for the early diagnosis of this condition. We conducted a nationwide survey for MDS by sending questionnaires to 575 hospitals where board-certified pediatric neurologists were working and 195 residential hospitals for persons with severe motor and intellectual disabilities in Japan. This survey found 65 cases of MDS, and clinical data of 24 cases in which the diagnosis was genetically confirmed were analyzed. More than half of the patients (52%) had visited a hospital at least once during infancy due to symptoms associated with MDS, with a median age at the initial visit of 7 months. The symptoms that were frequently prevalent at the first visit were facial dysmorphic features, hypotonia, motor developmental delay, and recurrent infections. Dysmorphic features included small mouth, tented upper lip, tapered fingers, and hypertelorism. Other symptoms, including epilepsy, intellectual disabilities, autistic features, stereotypic movements, and gastrointestinal problems, generally appeared later with age. Some symptoms of MDS were found to be age-dependent and may not be noticeable in infancy. Recognition of these clinical characteristics may facilitate the early diagnosis and proper treatment of patients with MDS, improve their long-term outcomes, and help adapt appropriate genetic counseling.

DOI： 10.1016/j.jns.2021.117321

PubMed

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/ccr3.3883

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.3883

掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

DNA variants affecting mRNA expression and processing in genetic diseases are often missed or poorly characterized. We previously reported a generic assay to identify variants that affect mRNA expression and splicing in Pompe disease, a monogenic disorder caused by deficiency of acid α-glucosidase (GAA). However, this assay could miss mRNA that is subjected to degradation. Here, we inhibited mRNA degradation using cycloheximide and performed unbiased splicing analysis of all GAA exons using exon flanking RT-PCR and exon internal RT-qPCR. In four patients that were suspected of harboring splicing variants but for which aberrant splicing could not be detected in normally growing cells, we detected a total of 10 novel splicing events in cells treated with cycloheximide. In addition, we found that sequences of GAA introns 6 and 12 were naturally included in a subset of transcripts from patients and healthy controls, indicating inefficient canonical splicing. Identification of aberrant splicing caused by the common Asian variant c.546G>T allowed the development of an antisense oligonucleotide that promoted canonical GAA pre-mRNA splicing and elevated GAA enzymatic activity. Our results indicate that this extended generic splicing assay allows the detection of aberrant splicing in cases of mRNA degradation to enable functional analysis of unknown splicing variants and the development of targeted treatment options.

DOI： 10.1038/s41431-020-00751-3

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その他リンク： http://www.nature.com/articles/s41431-020-00751-3

記述言語：日本語   出版者・発行元：(財)小児愛育協会  

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記述言語：日本語   出版者・発行元：日本てんかん学会-北海道地方会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.braindev.2020.06.012

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jns.2020.117041

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掲載種別：研究論文（学術雑誌）   出版者・発行元：John Libbey Eurotext  

DOI： 10.1684/epd.2020.1187

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/mgg3.1122

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mgg3.1122

掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/mgg3.1088

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mgg3.1088

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jsbmb.2019.105493

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.braindev.2019.09.001

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：日本てんかん学会-北海道地方会  

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記述言語：日本語   出版者・発行元：日本てんかん学会-北海道地方会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.seizure.2019.05.017

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/mrd.23163

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mrd.23163

掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ  

Background

Rett syndrome (RTT) is a characteristic neurological disease presenting with regressive loss of neurodevelopmental milestones. Typical RTT is generally caused by abnormality of methyl-CpG binding protein 2 (MECP2). Our objective to investigate the genetic landscape of MECP2-negative typical/atypical RTT and RTT-like phenotypes using whole exome sequencing (WES).

Methods

We performed WES on 77 MECP2-negative patients either with typical RTT (n=11), atypical RTT (n=22) or RTT-like phenotypes (n=44) incompatible with the RTT criteria.

Results

Pathogenic or likely pathogenic single-nucleotide variants in 28 known genes were found in 39 of 77 (50.6%) patients. WES-based CNV analysis revealed pathogenic deletions involving six known genes (including MECP2) in 8 of 77 (10.4%) patients. Overall, diagnostic yield was 47 of 77 (61.0 %). Furthermore, strong candidate variants were found in four novel genes: a de novo variant in each of ATPase H⁺ transporting V0 subunit A1 (ATP6V0A1), ubiquitin-specific peptidase 8 (USP8) and microtubule-associated serine/threonine kinase 3 (MAST3), as well as biallelic variants in nuclear receptor corepressor 2 (NCOR2).

Conclusions

Our study provides a new landscape including additional genetic variants contributing to RTT-like phenotypes, highlighting the importance of comprehensive genetic analysis.

DOI： 10.1136/jmedgenet-2018-105775

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掲載種別：研究論文（学術雑誌）   出版者・発行元：The Turkish Journal of Pediatrics  

DOI： 10.24953/turkjped.2019.06.018

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.braindev.2018.05.011

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.braindev.2018.03.008

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.braindev.2017.07.007

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1186/s13256-017-1497-7

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1038/s41598-017-08780-7

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その他リンク： http://www.nature.com/articles/s41598-017-08780-7.pdf

記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01232&link_issn=&doc_id=20170706230005&doc_link_id=%2Fcl1nohat%2F2017%2F004904%2F006%2F0255-0259%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcl1nohat%2F2017%2F004904%2F006%2F0255-0259%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/cge.12902

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).IntroductionMoyamoya disease (MMD) is characterized by progressive stenosis and occlusion in the terminal portion of both internal carotid arteries (ICAs) and the formation of an abnormal vascular network. Because of the fragile structure of the collateral vessels, MMD is frequently accompanied by intracranial aneurysms that are mainly located within the abnormal basal network or the circle of Willis. However, the association between MMD and aneurysms of the ICAs has never been reported previously.Case reportA 1-month-old infant presented with a decreased level of consciousness and arterial infarction in the right frontal and temporal lobes. Brain computed tomography angiography results showed aneurysms in both ICAs and occlusions of the distal part of the aneurysms without moyamoya collateral vessels. Aspirin therapy was initiated, and his clinical status stabilized. At 12 months of age, collateral networks of small vessels were found in the distal part of both ICAs, and MMD had evolved. At 24 months of age, he remains on aspirin therapy, and no further ischemic events have occurred.ConclusionsThis is the first report of MMD in which ICA aneurysms and occlusions developed bilaterally in early infancy without moyamoya collateral vessels. Our case indicates that angiogenesis at the base of the brain may occur following extracellular matrix remodeling at the terminal portion of the ICAs.

DOI： 10.1016/j.ensci.2017.01.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.braindev.2016.01.002

Web of Science

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

the Creative Commons Attribution 4.0BACKGROUND:Genetic aberrations in PAFAH1B1 result in isolated lissencephaly sequence (ILS), a neuronal migration disorder associated with severe mental retardation and intractable epilepsy. Approximately 60 % of patients with ILS show a 17p13.3 deletion or an intragenic variation of PAFAH1B1 that can be identified by fluorescence in situ hybridization (FISH) analysis or gene sequencing. Using multiplex ligation-dependent probe amplification (MLPA), 40-80 % of the remaining patients show small genomic deletions or duplications of PAFAH1B1. The intragenic duplications within PAFAH1B1 are predicted to abolish the PAFAH1B1 function, although a detailed characterization of the duplication regions have not been reported.RESULTS:Here we describe a female patient with ILS occurring predominantly in the posterior brain regions. MLPA was used to identify a small duplication within PAFAH1B1. This result was confirmed by array-based comparative genomic hybridization analysis, revealing a duplication of the 29-kb region encompassing putative regulatory elements and exon 2 of PAFAH1B1. The region was characterized as an intragenic tandem duplication by sequencing, revealing a 28-bp microhomology sequence at the breakpoint junctions. Parental genetic testing confirmed that the tandem duplication occurred de novo. Reverse transcription-PCR on RNA extracted from peripheral blood leukocytes revealed that the expression level of PAFAH1B1 decreased to that in a patient with Miller-Dieker syndrome, a contiguous gene-deletion disorder characterized by classical lissencephaly and a facial dysmorphism.CONCLUSIONS:This study expanded the spectrum of PAFAH1B1 variants and identified a unique genomic architecture including microhomology sequences in PAFAH1B1 underlying an intragenic tandem duplication leading to ILS.

DOI： 10.1186/s13039-015-0186-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.braindev.2014.11.006

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

BACKGROUND: Human herpesvirus-6 (HHV-6) is the etiological agent of exanthema subitum-associated encephalopathy, which usually occurs in children younger than 3 years. Brain imaging shows various abnormalities. PATIENT: A previously healthy 4-year-old girl developed acute encephalopathy with clinical features consisting of fever, repetitive seizures, and a disturbance of consciousness. The patient did not show skin rash suggestive of exanthema subitum during the course of her illness. The primary HHV-6 infection was diagnosed based on the absence of IgG against HHV-6 and identification of the virus DNA in the acute phase serum and a significant increase of the anti-HHV-6 IgG titers in the convalescent phase sera. Diffusion-weighted images showed transient high signal intensity in the bilateral periventricular white matter and splenium of the corpus callosum and in the gray matter structures such as the bilateral basal ganglia and thalami. Upon therapy with steroid and γ-globulin, the patient recovered without any neurological deficits. CONCLUSION: Primary HHV-6 infection can cause acute encephalopathy without exanthema subitum. The etiological diagnosis is possible only by examining the blood and cerebrospinal fluid, when the patient shows no skin rash. This condition should be included in the differential diagnosis of acute encephalopathy even in patients older than 3 years.

DOI： 10.1016/j.braindev.2014.12.005

PubMed

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/ped.12622

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

著者最終原稿版BACKGROUND/AIMS:Atomoxetine (ATX), a selective norepinephrine reuptake inhibitor, is the first approved non-stimulant drug for treatment of attention deficit/hyperactivity disorder (AD/HD). The present study examined the effects of long-term treatment with ATX on prefrontal hemodynamic activity in AD/HD children during a continuous performance task (CPT) using near-infrared spectroscopy (NIRS).METHODS:Prefrontal hemodynamic activity was measured in 12 children with AD/HD during experimental sessions conducted before and 6 months or more after starting ATX treatment. The average maintenance dose of ATX was 1.6 mg/kg/day. Fourteen age-matched typically developing children participated as a control group.RESULTS:In the control group, the CPT induced a significant increase in oxygenated hemoglobin (oxy-Hb) concentration in the bilateral dorsolateral prefrontal cortex (DLPFC). In the AD/HD group in the pre-ATX condition, the CPT did not induce a significant increase in oxy-Hb concentration in any of the NIRS channels, but induced a significant decrease in oxy-Hb concentration in the left ventrolateral prefrontal cortex (VLPFC). In the AD/HD group in the post-ATX condition, significant activation was observed in the right DLPFC and the decrease in oxy-Hb concentration in the left VLPFC disappeared.CONCLUSIONS:These results suggest that long-term treatment with ATX improved prefrontal hemodynamic activity in AD/HD children, and NIRS may be useful for assessment of the prefrontal hemodynamic response to ATX treatment.

DOI： 10.1016/j.braindev.2014.03.011

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その他リンク： http://search.jamas.or.jp/link/ui/2015294741

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

CC BY-NC-ND 4.0Eyelid myoclonia with absences is classified as a unique type of generalized seizure. Its pathogenesis is proposed to involve the functional abnormalities in cortical–subcortical networks. Here, we describe the case of a 7-year-old boy who had eyelid myoclonia with absences, along with focal motor seizures. Video-EEG monitoring demonstrated eyelid myoclonia associated with 4- to 5-Hz generalized polyspike–waves preceded by focal frontal discharges. Interictal EEG showed focal epileptiform discharges over the frontal regions. Our case suggests an important role of the frontal lobe in the generation of eyelid myoclonia with absences.

DOI： 10.1016/j.ebcr.2015.06.006

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1186/1752-1947-8-174

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その他リンク： http://link.springer.com/article/10.1186/1752-1947-8-174/fulltext.html

掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1186/1742-2094-11-28

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.braindev.2013.11.007

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.braindev.2013.09.006

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記述言語：日本語   出版者・発行元：(株)総合医学社  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00643&link_issn=&doc_id=20140804110017&doc_link_id=%2Fag1snrsd%2F2014%2F006708%2F017%2F1355-1358%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2014%2F006708%2F017%2F1355-1358%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/epi.12668

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記述言語：日本語   出版者・発行元：金原出版(株)  

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：日本てんかん学会-北海道地方会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J02553&link_issn=&doc_id=20140806150006&doc_link_id=%2Fen4tenka%2F2013%2F003200%2F007%2F0047-0052%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fen4tenka%2F2013%2F003200%2F007%2F0047-0052%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.pediatrneurol.2013.06.004

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記述言語：日本語   出版者・発行元：(株)総合医学社  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J00643&link_issn=&doc_id=20130925170009&doc_link_id=%2Fag1snrsd%2F2013%2F006610%2F011%2F2049-2053%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2013%2F006610%2F011%2F2049-2053%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/ana.23736

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/j.1399-0004.2011.01819.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.braindev.2011.08.005

CiNii Books

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1016/j.ijdevneu.2011.07.003

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1016/j.ijdevneu.2011.07.003

掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/j.1468-1331.2011.03354.x

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J01232&link_issn=&doc_id=20110907240006&doc_link_id=1390001205517980544&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001205517980544&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：5  

DOI： 10.11251/ojjscn.43.373

Scopus

PubMed

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s11064-010-0391-0

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その他リンク： http://link.springer.com/article/10.1007/s11064-010-0391-0/fulltext.html

担当区分：筆頭著者   記述言語：日本語   出版者・発行元：日本てんかん学会-北海道地方会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J02553&link_issn=&doc_id=20110913150003&doc_link_id=%2Fen4tenka%2F2010%2F002900%2F004%2F0030-0037%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fen4tenka%2F2010%2F002900%2F004%2F0030-0037%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society for Cell Biology (ASCB)  

Cyclin-dependent kinase 5 (Cdk5) plays a key role in the development of the mammalian nervous system; it phosphorylates a number of targeted proteins involved in neuronal migration during development to synaptic activity in the mature nervous system. Its role in the initial stages of neuronal commitment and differentiation of neural stem cells (NSCs), however, is poorly understood. In this study, we show that Cdk5 phosphorylation of p27^Kip1at Thr187 is crucial to neural differentiation because 1) neurogenesis is specifically suppressed by transfection of p27^Kip1siRNA into Cdk5^+/+NSCs; 2) reduced neuronal differentiation in Cdk5^−/−compared with Cdk5^+/+NSCs; 3) Cdk5^+/+NSCs, whose differentiation is inhibited by a nonphosphorylatable mutant, p27/Thr187A, are rescued by cotransfection of a phosphorylation-mimicking mutant, p27/Thr187D; and 4) transfection of mutant p27^Kip1(p27/187A) into Cdk5^+/+NSCs inhibits differentiation. These data suggest that Cdk5 regulates the neural differentiation of NSCs by phosphorylation of p27^Kip1at theThr187 site. Additional experiments exploring the role of Ser10 phosphorylation by Cdk5 suggest that together with Thr187 phosphorylation, Ser10 phosphorylation by Cdk5 promotes neurite outgrowth as neurons differentiate. Cdk5 phosphorylation of p27^Kip1, a modular molecule, may regulate the progress of neuronal differentiation from cell cycle arrest through differentiation, neurite outgrowth, and migration.

DOI： 10.1091/mbc.e10-01-0054

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.braindev.2009.10.004

CiNii Books

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.earlhumdev.2010.03.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

http://dx.doi.org/10.1016/j.braindev.2008.12.009Serotonin (5-hydroxytryptamine; 5-HT)-containing neurons trophically affect target neurons and modulate central nervous system neuronal activity. We studied effects of neonatal hypoxia on postnatal development of intraspinal 5-HT fibers in spinal motoneuron pools. Postnatal day (PND) 0 Sprague–Dawley rats received a hypoxic load and survivors were used for histological analyzes on PNDs 1, 7, and 14. Spinal motoneurons were labeled using choleratoxin B subunit as a retrograde neurotracer, and 5-HT fibers were detected immunohistochemically. On PND 1, 5-HT fibers were present in the lateral portion of the ventral horn at the cervical level, but were sparsely distributed at the lumbar level. On PND 14, cervical and lumbar level distributions were nearly identical. The 5-HT fibers and varicosities in close apposition to motoneurons increased from PNDs 1–14, however, the close apposition of cervical motoneurons was significantly different from lumbar motoneurons only on PND 1. Density of 5-HT fibers in control and hypoxic rats was not different on PND 1, while those in hypoxic rats were significantly reduced on PND 14. Close appositions of lumbar motoneurons were reduced more than cervical MNs after neonatal hypoxia. Neurodevelopmental deficit after neonatal hypoxia with a rostro-caudal gradient is associated with significant changes in the 5-HT system.

DOI： 10.1016/j.braindev.2008.12.009

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2010210555

担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.2353/ajpath.2010.081158

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.braindev.2008.08.010

CiNii Books

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Publishing Group  

DOI： 10.1038/jhg.2009.66

CiNii Books

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その他リンク： http://www.nature.com/articles/jhg200966

記述言語：日本語   出版者・発行元：(株)総合医学社  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J00643&link_issn=&doc_id=20090727200015&doc_link_id=%2Fag1snrsd%2F2009%2F006208%2F016%2F1875-1879%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2009%2F006208%2F016%2F1875-1879%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.bbrc.2009.04.038

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.eplepsyres.2008.03.010

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.braindev.2007.10.004

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.earlhumdev.2007.08.006

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/j.1399-0004.2007.00944.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1442-200x.2007.02483.x

CiNii Books

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記述言語：日本語   出版者・発行元：(財)小児愛育協会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2006&ichushi_jid=J01547&link_issn=&doc_id=20060831180011&doc_link_id=%2Fda3risyo%2F2006%2F005403%2F011%2F0087-0090%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fda3risyo%2F2006%2F005403%2F011%2F0087-0090%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：金原出版(株)  

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Proceedings of the National Academy of Sciences  

Cocaine, a drug of abuse, increases synaptic dopamine levels in the striatum by blocking dopamine reuptake at axon terminals. Cyclin-dependent kinase 5 (Cdk5) and its activator p35, proteins involved in phosphorylation of substrates in postmitotic neurons, have been found to be up-regulated after chronic exposure to cocaine. To further examine the effects of Cdk5 and p35 induction on striatal dopamine signaling, we generated two independent transgenic mouse lines in which Cdk5 or p35 was overexpressed specifically in neurons. We report here that increased Cdk5 activity, as a result of p35 but not of Cdk5 overexpression, leads to attenuation of cocaine-mediated dopamine signaling. Increased Cdk5-mediated phosphorylation of dopamine and cAMP-regulated phosphoprotein, molecular mass 32 kDa (DARPP-32) at Thr-75, was accompanied by decreased phosphorylation of DARPP-32 at Thr-34. Increased Cdk5-mediated phosphorylation of extracellular signal-regulated kinase kinase 1 at Thr-286 was accompanied by decreased activation of extracellular signal-regulated kinase 1/2. These effects contributed to attenuation of cocaine-induced phosphorylation of cAMP response element-binding protein as well as a lesser induction of c-fos in the striatum. These results support the idea that Cdk5 activity is involved in altered gene expression after chronic exposure to cocaine and hence impacts the long-lasting changes in neuronal function underlying cocaine addiction.

DOI： 10.1073/pnas.0409456102

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Podocytes are highly specialized and terminally differentiated glomerular cells that play a vital role in renal physiology, including the prevention of proteinuria. Cyclin-dependent kinase 5 (CDK5) has been shown to influence several cellular processes in other terminally differentiated cells, in particular neurons. In this study, we examined the role of CDK5 in podocyte differentiation, proliferation, and morphology. In conditionally immortalized mouse podocytes in culture, CDK5 increased in association with podocyte differentiation. During mouse glomerulogenesis in vivo, CDK5 expression was predominantly detected in podocytes from the capillary loop stage to maturation and persisted in the podocytes of adult glomeruli. In contrast, CDK5 was markedly decreased in the proliferating and dedifferentiated podocytes of mice with anti-glomerular basement membrane nephritis and in human immunodeficiency virus transgenic mice. p35, the activator of CDK5, was also detected in podocytes and the p35/CDK5 complex was active. Cell fractionation studies showed that active p35/CDK5 was mainly localized to the plasma membrane. Specific inhibition of CDK5 in differentiated cultured podocytes, either pharmacologically or with siRNA, induced shape changes, with cellular elongation and loss of process formation compared to the characteristic arborized phenotype. These data suggest a role for CDK5 as a regulator of podocyte differentiation, proliferation, and morphology.

PubMed

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Proceedings of the National Academy of Sciences  

Cyclin-dependent kinase 5 (Cdk5) is essential for the proper development of the CNS, as is evident from the perinatal lethality of conventional Cdk5 knockout (Cdk5-/-) mice. Cdk5 is also implicated in numerous complex functions of the adult CNS such as synaptic transmission, synaptic plasticity, and neuronal signaling. To elucidate the molecular roles of Cdk5 in the adult CNS, we have abrogated neuronal expression of Cdk5 in perinatal mice by using a cre-loxP system. The Cdk5-loxP flanked mice were crossed with the cre-transgenic mice in which the cre expression is driven by the murine neurofilament-heavy chain promoter, resulting in generation of viable Cdk5 conditional knockout mice with the restricted deletion of the Cdk5 gene in specific neurons beginning around embryonic day 16.5. Twenty-five percent of the Cdk5 conditional knockout mice carrying the heterozygous cre allele had neuronal migration defects confined to brain areas where neuronal migration continues through the perinatal period. These results indicate that abrogation of Cdk5 expression in mature neurons results in a viable mouse model that offers further opportunities to investigate the molecular roles of Cdk5 in the adult CNS.

DOI： 10.1073/pnas.0307322101

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1046/j.1471-4159.2003.02256.x

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掲載種別：研究論文（学術雑誌）  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1074/jbc.m302004200

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1074/jbc.m211964200

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Society for Neuroscience  

DOI： 10.1523/jneurosci.22-10-04036.2002

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1093/emboj/21.3.324

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Proceedings of the National Academy of Sciences  

Members of the N -methyl- d -aspartate (NMDA) class of glutamate receptors (NMDARs) are critical for development, synaptic transmission, learning and memory; they are targets of pathological disorders in the central nervous system. NMDARs are phosphorylated by both serine/threonine and tyrosine kinases. Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells. Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks both long-term potentiation induction and NMDA-evoked currents in rat CA1 hippocampal neurons. These results suggest that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs.

DOI： 10.1073/pnas.211428098

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1523/jneurosci.21-17-06758.2001

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Tohoku University Medical Press  

DOI： 10.1620/tjem.193.279

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/s0887-8994(99)00075-2

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/s0887-8994(99)00080-6

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/s0387-7604(98)00095-3

CiNii Books

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/s0387-7604(99)00017-0

CiNii Books

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s004310051033

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その他リンク： http://link.springer.com/article/10.1007/s004310051033/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/s0387-7604(98)00072-2

CiNii Books

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/s0887-8994(98)00102-7

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/s0887-8994(98)00054-x

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE Publications  

DOI： 10.1177/088307389801300810

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/s0387-7604(98)00017-5

CiNii Books

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1086/301751

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記述言語：日本語   出版者・発行元：日本てんかん学会-北海道地方会  

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/s0387-7604(97)00079-x

CiNii Books

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/s0387-7604(97)00052-1

CiNii Books

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

DOI： 10.1177/088307389701200812

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s002340050438

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その他リンク： http://link.springer.com/article/10.1007/s002340050438/fulltext.html

掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/j.1442-200x.1997.tb03588.x

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記述言語：日本語   出版者・発行元：日本てんかん学会-北海道地方会  

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記述言語：日本語   出版者・発行元：日本てんかん学会-北海道地方会  

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掲載種別：研究論文（学術雑誌）  

CiNii Books

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/bf01876336

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その他リンク： http://www.nature.com/articles/jhg199643

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/0387-7604(95)00119-0

CiNii Books

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記述言語：日本語   出版者・発行元：日本てんかん学会-北海道地方会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1996&ichushi_jid=J02553&link_issn=&doc_id=19960312510016&doc_link_id=http%3A%2F%2Famcor.asahikawa-med.ac.jp%2Fmodules%2Fxoonips%2Fdetail.php%3Fid%3D1996180788&url=http%3A%2F%2Famcor.asahikawa-med.ac.jp%2Fmodules%2Fxoonips%2Fdetail.php%3Fid%3D1996180788&type=%88%AE%90%EC%88%E3%89%C8%91%E5%8Aw%81F%88%AE%90%EC%88%E3%89%C8%91%E5%8Aw%8Aw%8Fp%90%AC%89%CA%83%8A%83%7C%83W%83g%83%8A_AMCoR&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80003_3.gif

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/0887-8994(95)00258-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Scopus

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1528-1157.1995.tb00478.x

CiNii Books

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/0887-8994(95)00146-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/0387-7604(95)00077-o

CiNii Books

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(株)永井書店  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/0387-7604(95)00043-b

CiNii Books

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1995&ichushi_jid=J01232&link_issn=&doc_id=19950630140006&doc_link_id=1390001204554690304&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001204554690304&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1995&ichushi_jid=J01232&link_issn=&doc_id=19950042040013&doc_link_id=1390282679531478272&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390282679531478272&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/bf02072107

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その他リンク： http://link.springer.com/article/10.1007/BF02072107/fulltext.html

担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(財)小児愛育協会  

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記述言語：日本語   出版者・発行元：日本てんかん学会-北海道地方会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1995&ichushi_jid=J02553&link_issn=&doc_id=19950079550023&doc_link_id=%2Fen4tenka%2F1994%2F001500%2F025%2F0155-0159%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fen4tenka%2F1994%2F001500%2F025%2F0155-0159%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：日本てんかん学会-北海道地方会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1995&ichushi_jid=J02553&link_issn=&doc_id=19950079550025&doc_link_id=%2Fen4tenka%2F1994%2F001500%2F027%2F0169-0175%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fen4tenka%2F1994%2F001500%2F027%2F0169-0175%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児放射線学会  

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/0887-8994(94)90011-6

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/j.1442-200x.1994.tb03203.x

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(株)診断と治療社  

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記述言語：日本語   出版者・発行元：日本てんかん学会-北海道地方会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1994&ichushi_jid=J02553&link_issn=&doc_id=19940080670038&doc_link_id=%2Fen4tenka%2F1993%2F001400%2F039%2F0252-0256%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fen4tenka%2F1993%2F001400%2F039%2F0252-0256%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(一社)日本周産期・新生児医学会  

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記述言語：日本語   出版者・発行元：(財)小児愛育協会  

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記述言語：日本語   出版者・発行元：(財)小児愛育協会  

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記述言語：日本語   出版者・発行元：(財)小児愛育協会  

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記述言語：日本語   出版者・発行元：旭川医科大学  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J03513&link_issn=&doc_id=20171127380011&doc_link_id=http%3A%2F%2Famcor.asahikawa-med.ac.jp%2Fmodules%2Fxoonips%2Fdetail.php%3Fid%3Df1701047&url=http%3A%2F%2Famcor.asahikawa-med.ac.jp%2Fmodules%2Fxoonips%2Fdetail.php%3Fid%3Df1701047&type=%88%AE%90%EC%88%E3%89%C8%91%E5%8Aw%81F%88%AE%90%EC%88%E3%89%C8%91%E5%8Aw%8Aw%8Fp%90%AC%89%CA%83%8A%83%7C%83W%83g%83%8A_AMCoR&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80003_3.gif

記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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担当区分：筆頭著者   掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）  

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：旭川医科大学  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J03513&link_issn=&doc_id=20100415440017&doc_link_id=http%3A%2F%2Famcor.asahikawa-med.ac.jp%2Fmodules%2Fxoonips%2Fdetail.php%3Fid%3Df1001093&url=http%3A%2F%2Famcor.asahikawa-med.ac.jp%2Fmodules%2Fxoonips%2Fdetail.php%3Fid%3Df1001093&type=%88%AE%90%EC%88%E3%89%C8%91%E5%8Aw%81F%88%AE%90%EC%88%E3%89%C8%91%E5%8Aw%8Aw%8Fp%90%AC%89%CA%83%8A%83%7C%83W%83g%83%8A_AMCoR&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80003_3.gif

担当区分：筆頭著者   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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担当区分：筆頭著者   掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）  

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記述言語：日本語   出版者・発行元：(公財)成長科学協会  

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記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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