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  

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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：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

PubMed

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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

PubMed

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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

PubMed

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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

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：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

PubMed

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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

PubMed

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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  

IQSEC2はXp11.22に位置し、シナプス後肥厚部に存在して興奮性シナプス伝達を調節するグアニンヌクレオチド交換因子(GEF)をコードしている。この遺伝子変異は、2010年にX連鎖性知的障害を有する家系で初めて同定されたが、その後に女性例や乳児期発症てんかんを合併する例も報告されており、多彩で広い臨床像に関連していることがわかってきた。我々は、IQSEC2エクソン1のフレームシフト変異NM_001111125.2:c.693del[p.(Thr232Profs*25)]によって、最長型IQSEC2アイソフォームの全ての機能性ドメインを失っていると考えられた男児例を経験した。患者は、乳児期から筋緊張低下と斜視に気づかれ、後に精神運動発達遅滞と自閉性障害が顕在化した。脳MRI検査で、軽度の脳萎縮と脳梁の菲薄化および側脳室周囲白質のT2高信号を指摘された。2歳時よりミオクロニー発作が出現し、強直間代発作、非定型欠神発作も認めた。発作間欠期脳波では全般性多棘徐波を認め、てんかん発作は薬剤抵抗性を示した。4歳時に全脳梁離断術を受け、転倒発作は消失し表情も豊かになった。しかし、運動機能の改善はなく、有意語の表出がない状態に変化はなかった。臨床経過は、発達性てんかん性脳症に合致しており、多彩な発作型を有する難治性てんかん、自閉性障害、斜視、特徴的な脳MRI所見を伴っていた。これらの所見は、IQSEC2変異に関連した最も重症な表現型と考えることができる。(著者抄録)

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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  

重症筋無力症は自己抗体によって、神経筋の刺激伝達が障害される自己免疫疾患である。今回われわれは、眼瞼下垂を主訴とした乳児例において、併存する全身症状と球麻痺症状の把握から早期に治療開始できた全身型重症筋無力症の一例を経験した。患者は、10ヵ月の女児。眼瞼下垂を主訴に当科を受診した。病歴聴取により、日内変動を伴う四つ這い移動の速度低下などの全身症状、および水分摂取時の咳込みなどの球麻痺症状の併存が判明した。塩酸エドロホニウムテストおよび正中神経の誘発筋電図検査では、いずれも神経筋接合部障害が確認された。全身型重症筋無力症と診断し、発症後13日目よりプレドニゾロン内服を開始し症状は改善した。眼瞼下垂の鑑別には全身型重症筋無力症も念頭に置き、乳児期特有の全身症状と球麻痺症状を含む詳細な病歴の聴取が重要である。(著者抄録)

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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  

症例は2歳6ヵ月男児で、生後4ヵ月時、未頸定であやしても反応に乏しいため、精査目的で入院となった。身体診察では頭部から腹部に皮下出血等を認めず、胸腹部所見に異常を認めなかったが、胸部CTにて右第4〜7肋骨および左第3〜8肋骨に多発骨折を認めた。また、頭部MRIでは右前頭葉から頭頂葉にかけて広範囲な脳実質損傷を認め、左大脳半球の皮質下白質にも複数の脳損傷がみられた。検査結果から身体的虐待が疑われたため児童相談所に通告し、父親による身体的虐待であったことが判明した。その後、生後8ヵ月時に焦点てんかんを発症し、当初脳波は右半球の限局性異常であったが、1歳8ヵ月時にヒプサリズミアに変化し、発作型はシリーズ形成するてんかん性スパズムに変容した。1歳10ヵ月時にACTH療法目的で入院となり、開始6日目からてんかん性スパズムが消失し、治療開始14日目の脳波でヒプサリズミアの消失を確認した。

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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  

5歳時に中心側頭部に棘波を示す良性癲癇(BECTS)を発症し発作頻度の高かった女児例を経験し、抗癲癇薬カルバマゼピン(CBZ)による治療を行った。CBZは発作のコントロールには有効であったが、睡眠期の癲癇性放電の出現頻度が増加した。抗癲癇薬をクロバザムに変更したところ癲癇性放電は消失したが、その効果は一時的であった。しかし、脳波所見の悪化に伴う認知行動異常は認めなかったため、抗癲癇薬による治療を中止して経過をみる方針とした。経過観察中も脳波検査で癲癇性放電を認めたが、癲癇発作の再燃はなく、10歳の現在まで認知行動異常の出現も認めていない。

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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  

8歳男児。2歳頃から精神運動発達の遅れが顕在化し、3歳時の新版K式発達検査では全領域発達指数70であった。4歳時に非誘発性の全身痙攣を認め、焦点癲癇と診断されVPAによる治療が開始された。その後、焦点意識減損発作重積で入院となるエピソードが数回あったが、LTG・CLB併用療法を開始されて以来、発作は消失していた。6歳5ヵ月時、活気がなくなり、問いかけに対する反応も鈍くなり、脳波検査で異常所見を認められ、精査加療目的で当科に紹介された。睡眠期持続性棘徐波を示す癲癇性脳症と診断し、ジアゼパム大量療法を行ったところ脳波所見は速やかに改善し臨床症状も改善した。ジアゼパムは約4ヵ月かけて漸減中止したが、終了後2ヵ月も経たずに認知機能が再び低下した。7歳5ヵ月時に脳波所見の悪化を認め、メチルプレドニゾロンパルス療法を2クール施行したところ脳波所見・臨床症状とも著明に改善し、1年以上経過している現在まで発作の再燃や脳波所見の悪化は認めていない。

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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  

【目的】不登校児の発達特性と転帰に影響する因子を検討した。【方法】2007年から2009年に当センターを受診した不登校児80名の発達障害や精神疾患の有無、在籍学級、転帰等を調査した。【結果】不登校児の57%が広汎性発達障害や注意欠陥/多動性障害などの発達障害を、また24%が不安障害などの精神疾患を有していた。87%が不登校になって初めて発達障害と診断された。91%に睡眠障害や頭痛などの身体愁訴を認めた。不登校となった誘因は複数混在し、対人関係の問題を契機とする例が最も多かった。1年後の転帰は完全登校48%、部分登校26%、不登校26%だった。小学生は60%が完全登校に至ったが、中学・高校生は41%に留まった。1年後不登校の割合は、発達障害をもたない児で42%であったのに対し発達障害を有する児では17%で、特別支援学級へ転籍した児では1例もなかった。【結論】不登校児は発達障害や精神疾患を背景に持つことが多く、登校転帰の改善には発達特性の把握と教育的・心理的な支援が有用である可能性が示唆された。(著者抄録)

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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）   出版者・発行元：Elsevier BV  

Objectives: To evaluate the outcome of ketogenic diets (KDs) in patients with glucose transport type 1 deficiency syndrome (GLUT1DS) in Japan.Methods: A nationwide survey for GLUT1DS was conducted by sending questionnaires to board-certified pediatric neurologists nationwide to obtain clinical and laboratory data.Results: Among 39 patients whose diagnosis was confirmed molecularly or by the 3-O-methylglucose uptake assay, 31 were treated with KDs for longer than 1 month. Seventeen patients (55%) were on the modified Atkins diet, 11 (35%) were on the classic KD, and 3 were on the medium-chain triglyceride (MCT) diet. The median values and ranges of serum P-hydroxybutyrate levels in patients on the modified Atkins diet, classic KD and MCT diet were 2.5 mM (0.75-4.1), 1.7 mM (0.23-3.5) and 2.6 mM (1.5-3.0), respectively. The KDs were effective on seizures (80%), aggravation after fasting (80%) and ataxia (79%). Thus, ataxia was as responsive as seizures. Two patients on the classic KD with a ketogenic ratio as low as 1:1 showed improvement in neurological symptoms. The development or intelligence quotient measured using the same psychological scales before and after the KDs in 9 patients did not show a significant improvement; the median quotients before and after the diets were 40 (12-91) and 46 (12-67).Conclusion: The KDs were most effective on seizures, transient aggravation after fasting and ataxia. The efficacy on intellectual development was equivocal. The modified Atkins diet was more commonly used for GLUT1DS in this study, and its ketogenicity was equivalent to the classic KD. (C) 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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）   出版者・発行元：Elsevier BV  

Objectives: We conducted a nationwide survey of glucose transporter type-1 deficiency syndrome (GLUT-1DS) in Japan in order to clarify its incidence as well as clinical and laboratory information.Subjects and methods: A questionnaire to survey the number of genetically and clinically confirmed cases of GLUT-1DS was sent to 1018 board-certified pediatric neurologists, which resulted in 57 patients being reported. We obtained the clinical and laboratory data of 33 patients through a secondary questionnaire.Results: The age of the 33 patients (male: 15, female: 18) at the time of the study ranged between 3 and 35 years (mean: 13.5 years). The age of these patients at the onset of initial neurological symptoms ranged between the neonatal period and 48 months (mean: 9.4 months). GLUT-1DS was diagnosed at a mean age of 8.4 years (range: 1 year to 33 years). The initial symptom was convulsive seizures, which occurred in 15 cases, and was followed by abnormal eye movements in 7 cases and apneic or cyanotic attacks in 4 cases. The latter two symptoms most frequently occurred early in infancy. Thirty-two patients (97%) exhibited some type of epileptic seizure. Neurological findings revealed that most patients had muscle hypotonia, cerebellar ataxia, dystonia, and spastic paralysis. Mild to severe mental retardation was detected in all 33 cases. Furthermore, paroxysmal episodes of ataxia, dystonia/dyskinesia, and motor paralysis were described in approximately 1/3 of all patients. The factors that frequently aggravated these events were hunger, exercise, fever, and fatigue, in that order. The mean CSF/blood glucose ratio was 0.36 (0.28-0.48). Pathological mutations in the SLC2A1 gene were identified in 28 out of 32 cases (87.5%).Conclusion: The results described herein provided an insight into the early diagnosis of GLUT1-DS, including unexplained paroxysmal abnormal eye movements, apneic/cyanotic attacks, and convulsive seizures in infancy, as well as uncommon paroxysmal events (ataxia, atonia, and motor paralysis) in childhood. (C) 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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  

患者は2歳4ヵ月の男児。1歳時より、発熱時のけいれん発作を繰り返し、複雑型熱性けいれんと診断されていた。アデノウイルス感染症の入院中に施行された脳波検査中に偶然にけいれん発作を起こし、発作時脳波が記録された。脳波所見から部分起始のけいれん発作であることがわかり、複雑型熱性けいれんの病態の一つとして、局在する脳機能異常の関与が考えられた。(著者抄録)

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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  

転倒発作を抑制することを目的として脳梁離断術を行った潜因性レノックス・ガストー症候群の2症例について報告した。症例1は特別支援学校中等部に通学中の15歳の女子であり、幼児期より知的に遅れがあり、6歳時よりてんかんを発症した。14歳時に全脳梁離断術を受けた。症例2は特別支援学校中等部に通学中の13歳の男子で、3歳時に強直発作を起こしてんかんを発症した。8歳時に全脳梁離断術を受けた。症例1は脱力発作に伴い転倒することが多く、このような転倒発作は脳梁離断術後に完全に消失した。しかし、症例2は強直発作に伴い転倒することが多く、脳梁離断術後も転倒発作の頻度は減少しなかった。脳梁離断術の効果はてんかん発作型により異なり、脱力発作に対して最も効果的であることが示唆された。また、この事実はレノックス・ガストー症候群で見られる全般発作における脳梁の果たす役割が、発作型により異なるということを示していると考えられた。

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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  

左片麻痺で発症したtumefactive demyelinating lesion(TDL)の女児例を経験した。MRI上、右頭頂部〜右後頭部の白質に6×3.5cmの腫瘤を認め、脳腫瘍を疑った。開頭生検による病理検査では、反応性の星細胞と泡沫細胞の増生および脱髄所見が認められTDLと診断した。ステロイドパルス療法により症状・画像所見は軽快した。多発性硬化症類縁疾患でみられるTDLの発生頻度は稀ではあるが、脳腫瘍との鑑別が困難なことがあり、十分に認識して診療にあたる必要があると考えられた。(著者抄録)

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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  

機能的右半球切除術を施行したRasmussen脳炎(Rasmussen encephalitis;RE)3小児例の発作、精神・神経学的および運動機能の回復過程について検討した。手術直前には抗てんかん薬、免疫療法に抵抗性の持続性部分てんかん発作(epilepsia partialis continua;EPC)と進行性片麻痺により坐位保持も困難であった。術後EPCは消失し、片麻痺は残存したが、理学療法により1.5から5ヵ月で補助具での歩行が可能になり、日常生活活動(activities of daily living;ADL)は回復した。健側半球の覚醒時脳波では後頭部α波を認め、知能検査では退行の阻止を確認した。REでは発作、片麻痺が進行し、ADLが低下してきた場合、早期に機能的半球切除術を考慮すべきと考えた。(著者抄録)

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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  

We investigated seizure, intelligence quotient (IQ), and neurological outcomes including the process of motor function recovery after functional right hemispherectomy in 3 children with Rasmussen's encephalitis (RE). Before the procedure, they were unable to walk, nor sit without support due to progressive worsening of left hemiplegia and relentless epilepsia partialis continua (EPC) of the left extremities, which were refractory to antiepileptic drug and immunological treatment. After functional right hemispherectomy, EPC completely disappeared, although complete left hemiplegia was sustained. However, they recovered up to being able to walk independently with assistance devices, and to have an ordinary life with family support within 1.5 to 5 months through rehabilitation. At the same time, the interictal EEG improved on the unaffected side of hemisphere, exhibiting a posterior alpha rhythm. Their IQ also improved, and they were able to attend school. Early functional hemispherectomy should be considered before patients with RE are left in a serious condition due to progressive worsening of hemiplegia and seizures refractory to the available treatment.

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  

14歳女子。成長、発達の経過に異常はなかった。学校で急に動きが止まり、意識消失する発作があり、救急搬送された。傾眠傾向を示す軽度の意識障害が持続し、脳波検査では右半球に高振幅徐波を認めた。初回発作から1年10ヵ月後、左上下肢に間代性けいれんが出現した。種々の抗けいれん薬を用いた治療は効果がなく、持続性部分てんかん(EPC)を生じた。右大脳半球の萎縮が出現し、EPC発症2ヵ月後には左片麻痺がみられた。Rasmussen脳炎と診断し、ガンマグロブリン療法、ステロイドパルス療法を試みたが、効果は一時的であった。EPC発症9ヵ月後に、右大脳半球の機能的半球離断術を施行した。けいれん発作は消失していたが発作性に嘔気・嘔吐が出現する自律神経発作が再燃した。右側頭葉の離断が不完全であったと考え、右側頭葉の焦点切除術を追加した。以後、けいれん発作の再燃はなく、全ての抗けいれん薬を中止することができた。

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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  

症例は1歳7ヵ月の女児。ロタウイルス腸炎を発症した3日目に全身性間代けいれんの群発とせん妄が出現した。頭部MRIの拡散強調画像で、脳梁膨大部に高信号域を認め、apparent diffusion coefficient(ADC)値は低下していた。けいれん発作の群発はこの第3病日のみであったが、せん妄状態は3日間持続した。臨床症状が改善した第9病日に行った頭部MRIでは、同部位の異常信号は消失していた。本症例は、可逆性の脳梁膨大部病変を有する軽症脳炎・脳症という疾患概念に合致する経過であった。病変部のADC値は低下していたことから、拡散強調画像で見られた高信号は、脳梁膨大部の髄鞘の浮腫を反映していたと考えられた。(著者抄録)

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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  

2002年2月から2005年2月に旭川厚生病院1ヵ月健診を受診した暦年齢1ヵ月の児に施行したヘパプラスチンテスト値(%)について検討した.対象は1,500名で,平均±SDは88.0±13.3%(-2SD値61.3%),最低は52%であった.60%未満は20名(1.33%)で,12例が母乳栄養,8例が混合栄養で人工乳栄養のみは0例だった.全例にビタミンK2をケイツーTMシロップとして2mg内服とし,1週間後に再検査できた13名では全例60%以上であった.今回ビタミンK欠乏性出血症はいなかったが,本検査法による1ヵ月健診時のスクリーニングは,生後5〜8週に頭蓋内出血としての発症が多い乳児ビタミンK欠乏性出血症を予防する上でのスクリーニング検査となりうる可能性があり,特に母乳栄養児に対しては考慮すべきである(著者抄録)

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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)  

12歳女児で,発熱と軽度咳嗽が出現した.血液検査では白血球減少,血小板減少を認めた.γ-グロブリンを投与されたが発熱は遷延し,播種性血管内凝固(DIC)も認められた.入院時,血球減少と,グルタミン酸オキザロ酢酸トランスアミナーゼ(AST)・乳酸脱水素酵素(LDH)・フェリチン・尿中β2-microglobulin高値を認めた.骨髄検査ではphagocyteによる貪食像を散見した.胸部CTでは少量の胸水,左肺下葉の浸潤像,すりガラス様陰影を認めた.Chlamydia pneumoniae(C.pneumoniae)IgM抗体価は1.88IDで,C.pneumoniaeを契機に発症した血球貪食症候群(HPS)と診断した.DICへのメシル酸ナファモスタット・ヘパリンナトリウム投与,HPSへのγ-グロブリン大量療法,プレドニゾロン(PSL)投与により,翌日には解熱傾向がみられた.C.pneumoniaeにはクラリスロマイシンを2週間投与した.PSLは第76病日に中止したが,再燃はない.経過中にAST・LDHの上昇,血球減少を認めた場合には,HPS合併を疑うことが重要だと思われた

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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  

乳幼児期に発症した複雑部分発作が11歳で再燃した2女児例でWISC-Rと123I-IMP SPECTを10年以上にわたって検討した.左頭頂葉のFocal cortical dysplasia(FCD)で計算障害や健忘性失語があった14歳女児では,再燃後に文章の意味が解らなくなり,言語性IQも94から63に低下.SPECTの集積低下部位も左頭頂葉から側頭葉に及んだが,発作消失後に改善.左前頭葉に病変のある12歳女児では,痙攣再燃後に言語性IQが91から76,下位検査の「知識」の評価点が8から4に低下.左前頭葉の集積(カウント比)も,0.86から0.64に低下.FCD患児では,癲癇発作が認知障害に影響を及ぼしており,123I-IMP SPECTは両者の関連を明らかにするのに有用であった

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2000&ichushi_jid=J01232&link_issn=&doc_id=20000830140005&doc_link_id=1390282679530697344&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390282679530697344&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_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/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  

Valproate sodium,clonazepamを含む10種類以上の抗てんかん薬に抵抗性で,強直発作,非定型欠神,ミオクロニー発作が群発したLennox-Gastaut症候群(LGS)の13歳男児例.発作群発時にはイライラが強く,攻撃的であった.発作群発に対しlidocaine持続静注と後療法としてmexiletine経口投与を行った.この結果,非定型欠神及びミオクロニー発作は消失し,強直発作は週1回程度に減少した.これらの効果は現在まで2年以上持続し,脳波所見,精神症状も改善し,明らかな副作用はなかった.LGSにおける発作群発時に,lidocaine持続静注と後療法としてmexiletine経口投与は試みる価値がある治療法と思われた

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1999&ichushi_jid=J01232&link_issn=&doc_id=19990831130010&doc_link_id=1390001204552744704&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001204552744704&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

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  

全例哺乳力低下を認め,皮疹に対する治療は行なっていなかった.初診時,全身の湿疹が著明で,滲出液が多量に認められた.短期間の電解質液の補液と,ステロイド軟膏の全身塗布を行なったところ,びらん・滲出液の消失に伴って電解質異常,低蛋白血症は正常化し,発育障害も改善した.精査を行なった1例では高アルドステロン・高レニン血症,尿中Na排泄量低下及び尿中K排泄量増加を認めた.また便中α1-アンチトリプシンクリアランスは正常であった.各種検査結果から,偽性低アルドステロン症や蛋白漏出性胃腸症は否定的であった.湿疹からの滲出液の喪失と哺乳量低下による低栄養状態がこれら合併症の原因と推定した

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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  

非定型欠神,ミオクロニー発作,強直発作などをもつLennox-Gastaut症候群の13歳男児患者について,諸々の抗てんかん薬は無効であった.lidocaine(4mg/kg/時)の持続静注により発作波(SWCと速リズム)の持続時間が30秒/10分から7秒/10分に減少した.それに加えて経口mexiletine(200mg/日)を用いることにより1年以上にわたり発作を抑制し,精神状態をも改善した.難治性てんかんの一例にlidocaineとmexiletineの併用が有効であった

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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  

第1子にのみ点頭てんかんが発症し,第2子にはけいれん発作のなかった早産双生児例において,両者の臨床経過・神経画像所見を比較・検討した.脳室周囲白質軟化は両者に合併し,経過を追って行った頭部エコー検査より,その発生時期は第1子は出生後で第2子は出生前と考えられた.MRIでみられた白質軟化の程度は,第1子より第2子で重度であった.しかし,SPECTでは第1子は第2子と比較して,大脳皮質全体,特に前頭頭頂葉での低集積が顕著であった.これは,点頭てんかん発症には大脳白質病変よりも皮質機能異常が深く関与していることを示している

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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  

本症例は,痙攀発作の再燃に伴い言語理解,表出といった高次脳機能の障害が進行した例であるが,てんかんの手術を行うと,現在は存在しない半盲,運動麻痺が出現する可能性が高い.このため,本症例では抗痙攣剤による治療を続けることにした

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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  

9歳,Zonisamide開始後,学習障害が改善し,とりわけ算数において顕著であった.又,生活面でも積極的になった.重積時の発作波は全般化し局在は不明であったが,発作間欠期脳波で左前頭部優位の棘徐波が出現し,SPECTで左前頭部の集積低下の所見と総合して,患児のてんかん焦点は左前頭部と考えられた

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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）  

L1CAM is a member of the immunoglobulin gene superfamily of neural adhesion molecule. Abnormality of the L1CAM gene is associated with X-linked recessive form of congenital hydrocephalus (HSAS
hydrocephalus due to congenital stenosis of aqueduct of Sylvius) and some allelic disorders. Four new patients with congenital hydrocephalus consistent with the X-linked type were described. One of them had a novel mutation in the L1CAM gene.

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  

甲状腺機能低下症の女児で,アキレス腱反射弛緩相の延長を他覚的に示し,それは治療効果も反映する指標となることを確かめた.その病態として,脛骨神経group 1 b線維の発射閾値が高くなるという神経原性の機序の関与を提唱した

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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  

2歳時に部分てんかんで発症した左頭頂葉を主とする局在性ニューロン遊走障害の女児例に対し,9歳で高次脳機能検査を施行した.臨床症状では左右・手指失認,健忘失語があり,WISC-RでIQは83だったが,下位項目の算数や構成・作業課題で評価点が低く,Benton視覚記銘検査では,正解数3,誤謬数15でゆがみや置き違いが多かった.頭頂葉障害を主とする高次脳機能障害があり,MRI, SPECT及び脳波で得られた異常部位と一致していた

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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  

8年間に部分発作をもつ患児178例にcarbamazepine(CBZ)を投与し,4例(2.2%)でてんかん発作が増悪した.年齢は11ヵ月から12歳,低酸素性虚血性脳症2例,頭部外傷と異所性灰白質各1例で脳の比較的広範な障害に伴う症候性部分てんかんであった.CBZ投与後,全例,部分発作が増悪し,1例は脱力発作も新たに出現した.脳波は,CBZ開始前は全例,焦点性棘波,棘徐波であったが,開始後2例で全般性棘徐波複合が出現した.CBZ血中濃度は7.0〜9.5μg/mlと治療域内であった.CBZを中止しphenytoinに変更した後,何れも発作は良好にコントロールされ,脳波では焦点性異常波のみが残存した

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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=19960117700004&doc_link_id=1390282679530221184&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390282679530221184&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  

1年間に罹患したムンプス448人のうち髄膜炎を合併した39例について,神経学的後遺症および脳波異常の有無を検討した。脳波異常は,発症1〜2週後では20.5%にみられ,背景波の異常が多かった。1〜2ヵ月後では35.9%に異常があり,突発波が多かった。これまでに痙攣発作を起こした児はいないが,無菌性髄膜炎では,髄膜にとどまらず脳の炎症もあることを示唆する結果であった

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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  

1)家族歴から,遺伝形式は伴性劣性遺伝と推定した。2)身体所見として,前額部の広い顔貌,両眼の白内障,著明な筋緊張低下,深部腱反射減弱が特徴的であった。3)検査所見として,尿細管性蛋白尿,汎アミノ酸尿,脳萎縮が特徴的であった

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記述言語：日本語   出版者・発行元：(財)小児愛育協会  

新生児期にイレウス症状を呈し,外科的治療を必要とした29例について検討した.1)症例は院内出生が5例,院外出生が24例であり,院外出生の児の中に脱水が著明で全身状態が不良な児が多くみられた.2)死亡例は4例で,3例が消化管の穿孔をおこしていた.3)近年,胎児エコーによる出生前診断が盛んとなっているが,異常なく出生した児であっても出生後に嘔吐・腹部膨満がみられた場合には,積極的に初期嘔吐などの機能的疾患と鑑別すべきである

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記述言語：日本語   出版者・発行元：(財)小児愛育協会  

1990年6月までの5年間に入院した823名の患児のうち吐血,下血を呈した新生児は43名で,適例39名のうち真性メレナと診断した例が31例,仮性メレナが8例であった.1)真性メレナのうち3分の2がvit. K欠乏性出血症であり,vit. K投与により速やかに症状は改善した.2)新生児のvit. Kシロップ剤の服用がルーチン化した時期に一致してvit. K欠乏性出血症の発生頻度が減少傾向を示した.3)真性メレナの中にはvit. K欠乏性出血症以外に胃潰瘍,胃穿孔,肝不全という重篤な疾患が存在した.4)出血性ショックに至る場合は消化性潰瘍を考慮し,H2ブロッカー投与や内視鏡検査などの迅速な対応が必要である

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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  

＜Key Points＞(1)Rasmussen症候群は、てんかん発作が難治に経過し、しだいに片麻痺と知的障害が出現し、適切な治療がないと不可逆的な神経障害を残す慢性進行性の疾患である。(2)一側大脳半球に限局する慢性炎症を病理学的特徴とし、細胞傷害性Tリンパ球を介した自己免疫反応が関与している。(3)内科的治療に対する反応が乏しい場合には、早期に半球離断術を考慮すべきである。(著者抄録)

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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  

Rett症候群は、主に女児に発症する神経発達障害である。その診断は、臨床症状に基づいて行われ、回復期や安定期が後続する神経症状の退行があることを必要要件とする。病因遺伝子は、メチル化DNAに結合して遺伝子の転写を制御するmethyl-CpG-binding protein 2(MECP2)をコードする。Rett症候群に類似するが異なった臨床経過を示すものを非典型的Rett症候群とよび、"早期発症てんかん型"や"先天型"が知られている。前者の病因遺伝子は、樹状突起棘に局在するリン酸化酵素cyclin-dependent kinase-like 5(CDKL5)をコードしている。後者の病因遺伝子は、終脳の発生に重要な転写因子forkhead box G1(FOXG1)をコードしている。このように非典型的Rett症候群の病態は、典型的Rett症候群とは異なることを理解する必要がある。(著者抄録)

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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=J01232&link_issn=&doc_id=20140303290009&doc_link_id=1390001205519316992&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001205519316992&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：(株)東京医学社  

＜Key Points＞(1)家族歴を有することがある。(2)発症前の発達は正常である。(3)好発年齢は3ヵ月〜2歳である。(4)発症時にけいれんが群発しやすい。(5)発作間欠期脳波に異常はない。(6)抗けいれん薬によく反応する。(7)長期予後は良好である。(著者抄録)

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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（商業誌、新聞、ウェブメディア）  

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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（学術雑誌）  

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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  

日齢0の新生ラットに低酸素を負荷し,日齢14, 28に運動細胞の形態的評価を行った.細胞体の大きさは,低酸素負荷群と対照群の間に差はなかった.しかし,樹状突起の発達は,頸髄の運動細胞では差はなかったが,腰髄の運動細胞では低酸素負荷群でその発達は不良であった

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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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