植物における２つのRAB5グループの活性化機構の研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 中野 明彦, 東京大学准教授 上田 貴志, 東京大学准教授 杉山 宗隆, 東京大学准教授 佐藤 健, 群馬大学教授 佐藤 健University of Tokyo(東京大学

Therapeutic drug monitoring of ganciclovir for postnatal cytomegalovirus infection in an extremely low birth weight infant: a case report

Background: Ganciclovir is a therapeutic choice for extremely premature infants with severe postnatal cytomegalovirus disease, but little is known about its optimal dose size and dosing interval for them. Case presentation: We treated an extremely premature female infant with postnatal cytomegalovirus infection with intravenous administration of ganciclovir since 49 days of life (postmenstrual age of 31 weeks). After ganciclovir treatment was initiated at a dose of 5 mg/kg every 12 h, cytomegalovirus loads in the peripheral blood were markedly decreased. However, since plasma ganciclovir trough level was too high, the interval was extended to every 24 h. Subsequently, the trough level and the estimated 12-h area under the concentration-time curve (AUC0-12) were decreased from 3.5 mg/L to 0.3 mg/L and 53.9 mg ・ h/L to 19.2 mg ・ h/L, respectively, resulting in an exacerbation of viremia and clinical condition. Adjustment of dosing interval from 24 h to 12 h led to a peak level of 4.2 mg/L, trough level of 1.1 mg/L, and AUC0-12 of 31.8 mg ・ h/L, resulting in a marked suppression of viral load. Conclusions: Monitoring the therapeutic drug levels and cytomegalovirus loads is useful in obtaining a proper treatment effect and preventing overdosage during ganciclovir therapy in premature infants with postnatal cytomegalovirus infection

Becker Muscular Dystrophy Accompanied by Anti-HMGCR Antibody-positive Immune-mediated Necrotizing Myopathy

International audienc

Additional file 1: of Therapeutic drug monitoring of ganciclovir for postnatal cytomegalovirus infection in an extremely low birth weight infant: a case report

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Fukuyama-type congenital muscular dystrophy (FCMD) and a-dystroglycanopathy

Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), and muscle-eye-brain (MEB) disease are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. We identified the gene for FCMD and MEB, which encodes the fukutin protein and the protein O-linked mannose β1, 2-N-acetylglucosaminyltransferase (POMGnT1), respectively. α-dystroglycan is a key component of the dystrophin-glycoprotein-complex, providing a tight linkage between the cell and basement membranes by binding laminin via its carbohydrate residues. Recent studies have revealed that posttranslational modification of α-dystroglycan is associated with these congenital muscular dystrophies with brain malformations. Key Words: Fukuyama congenital muscular dystrophy (FCMD), muscle-eye-brain (MEB) disease, fukutin, α-dystroglycan, glycosylation. Basic Appl Myol 13(6): 287-292, 2003 Fukuyama-type congenital muscular dystrophy (FCMD

TH1 cell-inducing Escherichia coli strain identified from the small intestinal mucosa of patients with Crohn’s disease

International audienceDysbiotic microbiota contributes to the pathogenesis of Crohn's disease (CD) by regulating the immune system. Although pro-inflammatory microbes are probably enriched in the small intestinal (SI) mucosa, most studies have focused on fecal microbiota. This study aimed to examine jejunal and ileal mucosal specimens from patients with CD via double-balloon enteroscopy. Comparative microbiome analysis revealed that the microbiota composition of CD SI mucosa differs from that of non-CD controls, with an increased population of several families, including Enterobacteriaceae, Ruminococcaceae, and Bacteroidaceae. Upon anaerobic culturing of the CD SI mucosa, 80 bacterial strains were isolated, from which 9 strains representing 9 distinct species (Escherichia coli, Ruminococcus gnavus, Klebsiella pneumoniae, Erysipelatoclostridium ramosum, Bacteroides dorei, B. fragilis, B. uniformis, Parabacteroides distasonis, andStreptococcus pasteurianus) were selected on the basis of their significant association with CD. The colonization of germ-free (GF) mice with the 9 strains enhanced the accumulation of T(H)1 cells and, to a lesser extent, T(H)17 cells in the intestine, among which anE. colistrain displayed high potential to induce T(H)1 cells and intestinal inflammation in a strain-specific manner. The present results indicate that the CD SI mucosa harbors unique pro-inflammatory microbiota, including T(H)1 cell-inducingE. coli, which could be a potential therapeutic target

Dementia and Car Driving - Looking back on the five years since the establishment of the driver’s license outpatient clinic, consider the future prospects -

　認知症の重症度とともに運転事故の危険性は高まることから，中等度以上の認知症では運転 すべきでないという点についての世界的コンセンサスは得られているが，専門学会ごとに認知症の 運転中止基準は異なる．当院では2017年４月よりものわすれ外来とは別に運転免許外来を新設し， 時間をかけた丁寧な診療と告知，指導，運転免許返納後の生活確保・支援ができるよう，多職種で 受診者に対応してきた．2021年７月までの当外来受診者は64人（のべ117人）で，ほとんどが免許更新時の第１分類該当や交通違反のための受診であった．当外来にて施行した神経心理検査の平均点は，MMSE-J 21.3/30，DASC-21 28.4，CDR 0.6と全般的認知機能低下が比較的軽度な者が多かったが，FAB 10.9/18，TMT-A 102.4s，TMT-B 261s と注意，前頭葉機能，視覚情報処理や遂行機能の低下は明らかであった．当外来を受診した患者には上記の検査結果を踏まえて全例に運転免許返納を推奨したが，全患者が運転継続を強く希望し，運転中止に至った例は20例のみで，残りのうち更に20例は半年毎に当院を再診し現在も運転継続している．この20例は，MMSE-J 22.3/30， DASC-21 26.2，CDR 0.5とやはり全般的認知機能は比較的保たれており，19例（95％）を軽度認知障害と診断している．全般的認知機能が比較的保たれている軽度認知障害の患者は現実的に運転 できていることから，都市部と異なりインフラ整備が十分には整っていない地域での運転の重要性 を鑑みると，社会インフラの整備，限定免許や安全運転技術などのサポート体制の強化など高齢者の運転継続の可能性についても模索すべきであると考えられる．　There is a global consensus that people with moderate or severe dementia should not drive because the risk of driving accidents increases with the severity of dementia. However, the proposed criteria for prohibiting dementia patients from driving a car differ by academic societies. In April 2017, we established a specialized clinic to evaluate eligibility to hold a driver’s license. Multidisciplinary staff collaborate to provide medical examinations, notification, guidance, and support for everyday activities for those who have returned their driver’s license. 　By July 2021, 64 people had visited this clinic (117 visits including re-examinations). Most were classified as having possible dementia (the first category) by the official driving aptitude test failure or more traffic violations. Their average score in the neuropsychological tests were as follows; Mini Mental State Examination-Japanese (MMSE-J) is 21.3/30, Dementia Assessment Sheet in Community-based Integrated Care System (DASC-21) is 28.4, Clinical Dementia Rating (CDR) is 0.6, Frontal Assessment Battery (FAB) is 10.9/18, Trail Making Test (TMT)-A is 102.4s, and TMT-B is 261s. Many of the group had relatively mild cognitive decline, especially in attention, frontal lobe function, visuospatial processing, and executive function domains. We recommended that all people to return their driver’s licenses. However, only 20 followed our recommendation. Rest 20 are still driving with regular visit every 6 months. In these 20 cases, MMSE-J is 22.3/30, DASC-21 is 26.2, CDR is 0.6 and overall cognitive function was relatively maintained, and 19 cases (95%) were diagnosed as Mild cognitive impairment. 　Our data showed that patients with mild cognitive impairment can drive practically. Considering that insufficient public transportation system in suburban areas, continue driving is essential for elderly people to maintain their everyday life. It is important to find the way to continue driving in cognitively declined elderly people with limited licenses or driving assistant system in super-aged society