2024/03/29 更新

写真a

サイトウ アキヒコ
齋藤 昭彦
SAITOH Akihiko
所属
教育研究院 医歯学系 医学系列 教授
医学部 医学科 教授
医歯学総合研究科 生体機能調節医学専攻 内部環境医学 教授
職名
教授
連絡先
メールアドレス
外部リンク

学位

  • 博士(医学) ( 2008年9月   新潟大学 )

研究キーワード

  • 予防接種

  • ヒト免疫不全ウイルス

  • 小児感染症

  • パレコウイルス

  • 微生物診断

経歴(researchmap)

  • 新潟大学医学部 副学部長

    2020年2月 - 現在

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  • University of California, San Diego   , Pediatrics   准教授

    2019年9月 - 現在

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  • 新潟大学   小児科   教授

    2011年8月 - 現在

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  • 国立研究開発法人国立成育医療研究センター   感染症科   館長

    2008年7月 - 2011年6月

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  • カルフォルニア大学サンディエゴ校   小児感染症   講師、助教授

    2003年4月 - 2008年6月

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    国名:アメリカ合衆国

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  • カルフォルニア大学サンディエゴ校   小児感染症   クリニカルフェロー

    2000年4月 - 2003年3月

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    国名:アメリカ合衆国

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  • ロサンゼルス郡・南カルフォルニア大学メディカルセンター   小児科   研修医

    1997年7月 - 2000年3月

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    国名:アメリカ合衆国

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  • ハーバーUCLAメディカルセンター   アレルギー・臨床免疫部門   研究員

    1995年6月 - 1997年6月

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    国名:アメリカ合衆国

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  • 聖路加国際病院   小児科   レジデント

    1991年4月 - 1995年3月

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経歴

  • 新潟大学   医学部 医学科   教授

    2011年8月 - 現在

  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻 内部環境医学   教授

    2011年8月 - 現在

学歴

  • 新潟大学

    2007年10月 - 2008年9月

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  • 新潟大学   医学部

    1985年4月 - 1991年3月

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所属学協会

  • 日本臨床ウイルス学会

    2015年4月 - 現在

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  • 日本ワクチン学会

    2010年4月

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  • 日本感染症学会

    2009年4月 - 現在

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  • 日本小児感染症学会

    2008年6月 - 現在

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  • 米国感染症学会

    2000年4月 - 現在

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  • 日本小児科学会

    1991年4月 - 現在

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留学歴

  • University of California, San Diego   Clinical Fellow and Assistant Professor

    2000年4月 - 2008年6月

  • University of Southern California   Resident

    1997年7月 - 2000年3月

  • Harbor-UCLA Medical Center   Research Fellow

    1995年7月 - 1997年6月

取得資格

  • 医師

 

論文

  • Innate Immune Responses in Serum and Cerebrospinal Fluid from Neonates and Infants Infected with Parechovirus-A3 or Enteroviruses. 査読 国際誌

    Rie Habuka, Yuta Aizawa, Ryohei Izumita, Hisanori Domon, Yutaka Terao, Hayato Takihara, Okuda Shujiro, Akihiko Saitoh

    The Journal of Infectious Diseases   222 ( 4 )   681 - 689   2020年3月

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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)  

    BACKGROUND: Parechovirus-A3 (PeV-A3) and enteroviruses (EV) are the most common viruses causing sepsis and meningoencephalitis in neonates and young infants. Clinical manifestations of PeV-A3 infection are more severe than those of EV infection, and no pleocytosis with a positive PCR result for PeV-A3 in cerebrospinal fluid (CSF) are characteristic findings. We hypothesized that innate immune responses to PeV-A3 and EV are distinct in serum and CSF. METHODS: We evaluated 22 cytokines/chemokines in serum and CSF from PeV-A3- or EV-infected patients younger than 4 months in Niigata, Japan, from 2015 through 2018. Infection was diagnosed with real-time PCR followed by sequencing. Febrile neonates and infants with sepsis-like syndrome who had negative bacterial culture and viral PCR for both PeV-A and EV were also included (non-PeV-A/EV patients). RESULTS: Among 192 febrile patients, we evaluated 16 PeV-A3-infected, 15 EV-infected, and 8 non-PeV-A/EV patients. Serum pro-/anti-inflammatory cytokine/chemokine levels were higher in PeV-A3-infected patients than in EV-infected patients (P<.02). While most cytokine/chemokine were elevated in CSF from EV-infected patients, levels were low or undetectable in PeV-A3-infected and non-PeV-A/EV patients (P<.001). CONCLUSIONS: Distinct cytokine/chemokine patterns in serum and CSF may explain the different clinical manifestations of PeV-A3-infected and EV-infected neonates and young infants.

    DOI: 10.1093/infdis/jiaa131

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  • Parechovirus-A3 encephalitis presenting with focal seizure mimicking herpes simplex virus infection. 査読 国際誌

    Sakiko Arai, Takayuki Yamanaka, Masashi Kasai, Tetsuhiro Fukuyama, Yuta Aizawa, Ko Matsui, Masanori Sato, Hiroko Matsui, Akihiko Saitoh

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   26 ( 7 )   736 - 740   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Febrile neonates and young infants presenting with seizure require immediate evaluation and treatment. Herein we experienced two young infants with parechovirus-A3 (PeV-A3) encephalitis, initially presented with focal seizure suspecting herpes simplex virus (HSV) encephalitis. CASES: We have experienced 2 infantile cases, initially presented with focal seizure. At presentation, HSV encephalitis was strongly suspected and empiric acyclovir therapy was started; however, serum and/or cerebrospinal fluid (CSF) PCR for HSV were negative. Instead, serum and/or CSF PCR for parechovirus-A was positive. PeV-A3 infection was confirmed by genetic sequence analyses. Both cases required multiple anticonvulsant therapy and intensive care for intractable seizure. Diffusion-weighted imaging of brain magnetic resonance imaging (MRI) showed distinct findings; high-intensity lesions in the gray matter of parietal and occipital lobes in Case 1, and bilateral decreased diffusion of the deep white matter and corpus callosum in Case 2. We have followed two cases more than four years; Case 1 developed epilepsy, has been on an anticonvulsant to control her seizure. Case 2 has significant neurodevelopmental delay, unable to stand or communicate with language. CONCLUSIONS: PeV-A3 encephalitis needs to be in differential diagnosis when neonates and young infants present with focal seizure, mimicking HSV encephalitis. Special attention may be necessary in patients with PeV-A3 encephalitis given it could present with intractable seizure with high morbidity in a long-term.

    DOI: 10.1016/j.jiac.2020.02.003

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  • Novel scoring system for differentiating parechovirus-A3 and enterovirus infection in neonates and young infants. 査読 国際誌

    Ryohei Izumita, Yuta Aizawa, Rie Habuka, Kanako Watanabe, Taketo Otsuka, Nobutaka Kitamura, Kohei Akazawa, Akihiko Saitoh

    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology   124   104256 - 104256   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Parechovirus-A3 (PeV-A3) and the enteroviruses (EVs) are the most common viral pathogens responsible for sepsis and meningoencephalitis in neonates and young infants; however, differences in the clinical presentations of two infections are not well described. OBJECTIVES: To describe the clinical presentations of PeV-A3- and EVs-related diseases and develop a novel scoring system to differentiate two diseases. STUDY DESIGN: This prospective study used real-time PCR and genetic sequencing to evaluate viral etiologies of febrile neonates and infants <4 months with suspected sepsis or meningoencephalitis in Niigata area, Japan, in 2014-2016. The clinical manifestations of PeV-A3- and EVs-infected patients were compared, and a novel scoring system was developed after identifying the most distinguishable clinical findings, followed by the external cohort validation. RESULTS: In 210 patients evaluated, we identified 56 PeV-A3-infected (27%) and 43 EVs-infected (20%) patients. The following clinical manifestations were significant in PeV-A3-infected patients, as compared with EVs-infected patients; a higher body temperature (38.9°C vs. 38.5°C, P < .01) and heart rate (181/min vs. 168/min, P = .01), cold extremities (72% vs. 34%, P < .01) and skin mottling (65% vs. 23%, P < .01), lower white blood cell count (5,200/μL vs. 8,900/μL, P < .01) and incidence of cerebrospinal fluid (CSF) pleocytosis (2% vs. 63%, P < .01). Using some of these significant findings, the scoring system successfully distinguished the diseases (accuracy: 86% and 83% for the derivative and external validation cohorts, respectively). CONCLUSIONS: We found significant clinical manifestations in PeV-A3-infected patients compared to EVs-infected patients. The scoring system may be helpful to distinguish two infections, especially at onset of outbreak.

    DOI: 10.1016/j.jcv.2019.104256

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  • Intrafamilial Transmission of Parechovirus A and Enteroviruses in Neonates and Young Infants. 査読 国際誌

    Ryohei Izumita, Kazuki Deuchi, Yuta Aizawa, Rie Habuka, Kanako Watanabe, Taketo Otsuka, Akihiko Saitoh

    Journal of the Pediatric Infectious Diseases Society   8 ( 6 )   501 - 506   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Parechovirus A (PeV-A) is an important cause of sepsis and meningoencephalitis in neonates and young infants. Thus, identifying the source of PeV-A is essential for prevention; however, little is known regarding the spread of PeV-A among family members of PeV-A-infected neonates and young infants. METHODS: In this prospective study, we evaluated stool samples from family members of PeV-A-infected neonates and infants younger than 4 months who presented with sepsis, meningoencephalitis, or both in Niigata, Japan, in 2016. Because of a simultaneous outbreak, enteroviruses (EVs) were also evaluated during this period. Real-time polymerase chain reaction followed by sequence analysis was used for viral diagnosis using serum and/or cerebrospinal fluid samples. RESULTS: Among 54 febrile patients, the stool samples of 14 (26%) and 12 (22%) patients tested positive for PeV-A and EV, respectively. Stool samples from 54 family members (38 adults and 16 children) of 12 PeV-A-infected patients were available. The rate of PeV-A positivity in these samples was higher among the children (88% [14 of 16]) than the adults (34% [13 of 38]). Among family members with a PeV-A-positive stool sample, 29% (4 of 14) of the children and 77% (10 of 13) of the adults were asymptomatic. Similarly, among 53 stool samples from family members (31 adults and 22 children) of 11 EV-infected patients, the rate of EV positivity in the stool samples was higher among the children (91% [20 of 22]) than among the adults (42% [13 of 31]). The asymptomatic-patient rates were 45% (9 of 20) among the children and 85% (11 of 13) among the adults in family members with EV-positive stool. CONCLUSIONS: Similar to EVs, PeV-A was detected frequently in stool samples from family members of PeV-A-infected patients. Among family members with PeV-A-positive stool, adults were more likely than children to be asymptomatic and therefore could be an important source of PeV-A infection.

    DOI: 10.1093/jpids/piy079

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  • Persistence of High Neutralizing Antibody Titers After Neonatal and Early Infantile Infection with Parechovirus-A3. 査読 国際誌

    Ryohei Izumita, Yuta Aizawa, Kanako Watanabe, Akihiko Saitoh

    The Pediatric infectious disease journal   38 ( 7 )   e159-e161   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This 3-year follow-up study evaluated neutralizing antibody titers (NATs) against parechovirus-A3 (PeV-A3) in neonates and young infants who developed PeV-A3 infection. All children had low NATs at disease onset and high NATs after infection during infancy. At age 3 years, all 16 patients tested had high NATs (≥1:512) against PeV-A3 indicating that specific PeV-A3 NATs persist into childhood.

    DOI: 10.1097/INF.0000000000002245

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  • Human parechovirus type 3 infection: An emerging infection in neonates and young infants. 査読 国際誌

    Yuta Aizawa, Ryohei Izumita, Akihiko Saitoh

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   23 ( 7 )   419 - 426   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Human parechoviruses (HPeVs) are RNA viruses that have characteristics similar to those of enteroviruses and usually cause mild respiratory or gastrointestinal symptoms. Human parechovirus type 3 (HPeV3), first reported in 2004, is exceptional because it can provoke sepsis and meningoencephalitis leading to neurological sequelae, and even death, in neonates and young infants. Pediatricians and researchers are increasingly aware that HPeV3 is responsible for serious disease in neonates and young infants. Retrospective studies and several reports of epidemics of HPeV3 infection have provided data on epidemiology, clinical symptoms and signs, laboratory findings, and outcomes. However, the pathogenesis of HPeV3 infection remains unclear, which explains the lack of specific antiviral therapy and effective prevention measures. Maternal antibodies are important in protection against severe HPeV3-related disease, and this may be a clue regarding its pathogenesis. HPeV3 epidemics are likely to continue, and because the clinical manifestations of HPeV3 are severe, determining the pathogenesis of HPeV3 infection and establishing specific antiviral therapies are important goals for future research.

    DOI: 10.1016/j.jiac.2017.04.009

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  • RE: "SEVERE HUMAN PARECHOVIRUS INFECTIONS IN INFANTS AND THE ROLE OF OLDER SIBLINGS". 査読 国際誌

    Akihiko Saitoh

    American journal of epidemiology   184 ( 8 )   603 - 604   2016年10月

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    記述言語:英語  

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  • Human parechovirus type 3 infection: Cause of apnea in infants born prematurely. 査読 国際誌

    Jun Nirei, Yuta Aizawa, Minoru Okazaki, Akira Kobayashi, Junya Onozuka, Osamu Numata, Tomohiro Oishi, Akihiko Saitoh

    Pediatrics international : official journal of the Japan Pediatric Society   58 ( 5 )   400 - 402   2016年5月

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    記述言語:英語  

    Four infants born prematurely presented with multiple apnea episodes caused by human parechovirus type 3 (HPeV3) infection. All patients required oxygen supplementation, and one patient required mechanical ventilation. HPeV3 infection might be included in the differential diagnosis of apnea in neonates and young infants, especially those born prematurely.

    DOI: 10.1111/ped.12869

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  • Role of Maternal Antibodies in Infants with Severe Diseases Related to Human Parechovirus Type 3. 査読 国際誌

    Yuta Aizawa, Kanako Watanabe, Tomohiro Oishi, Harunobu Hirano, Isao Hasegawa, Akihiko Saitoh

    Emerging infectious diseases   21 ( 11 )   1966 - 72   2015年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Human parechovirus type 3 (HPeV3) is an emerging pathogen that causes sepsis and meningoencephalitis in young infants. To test the hypothesis that maternal antibodies can protect this population, we measured neutralizing antibody titers (NATs) to HPeV3 and other genotypes (HPeV1 and HPeV6) in 175 cord blood samples in Japan. The seropositivity rate (≥1:32) for HPeV3 was 61%, similar to that for the other genotypes, but decreased significantly as maternal age increased (p<0.001). Furthermore, during the 2014 HPeV3 epidemic, prospective measurement of NATs to HPeV3 in 45 patients with severe diseases caused by HPeV3 infection showed low NATs (≤1:16) at onset and persistently high NATs (≥1:512) until age 6 months. All intravenous immunoglobulin samples tested elicited high NATs to HPeV3. Our findings indicate that maternal antibodies to HPeV3 may help protect young infants from severe diseases related to HPeV3 and that antibody supplementation may benefit these patients.

    DOI: 10.3201/eid2111.150267

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  • Asymptomatic children might transmit human parechovirus type 3 to neonates and young infants. 査読 国際誌

    Yuta Aizawa, Takayuki Yamanaka, Kanako Watanabe, Tomohiro Oishi, Akihiko Saitoh

    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology   70   105 - 108   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Human parechovirus type 3 (HPeV3) epidemics occur worldwide and can lead to severe disease in neonates and young infants. Little is known about the source of HPeV3 infection. OBJECTIVES: To investigate the source of HPeV3 infection and the role of asymptomatic children in the families of infected children. STUDY DESIGN: During a 2014 HPeV3 epidemic in Niigata, Japan, we analyzed (1) clinical information on sick contacts for 43 neonates and young infants with HPeV3-related disease diagnosed by PCR analysis of serum and/or cerebrospinal fluid and (2) stool samples from symptomatic and asymptomatic siblings/cousins of index patients. To confirm transmission, the P1 (VP0, VP3, and VP1) and 3D(pol) regions of HPeVs were sequenced and analyzed. RESULTS: Sick contact with family members was confirmed for 51% (n=22) of patients. Among the 30 symptomatic family members, 67% (n=20) were siblings, 20% (n=6) were mothers, and 13% (n=4) were other relatives. Stool samples from symptomatic and asymptomatic siblings/cousins of 4 HPeV3-infected patients yielded positive results for HPeVs on PCR analysis. Furthermore, the P1 and 3D(pol) nucleotide sequences of family members were 100% identical to those of the respective index cases. CONCLUSIONS: Identification of genetically identical virus from HPeV3-infected patients and asymptomatic children in their families suggests that the latter are a source of infection in neonates and young infants with HPeV3-related diseases.

    DOI: 10.1016/j.jcv.2015.07.300

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  • Human Parechoviruses. 査読

    Yuta Aizawa, Akihiko Saitoh

    Uirusu   65 ( 1 )   17 - 26   2015年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Human parechoviruses (HPeVs) are single-stranded, positive-sense RNA viruses and are classified in the genus Parechovirus of the family Picornaviridae. Echovirus 22 and 23 were reclassified as HPeV1 and 2 in 1999. Although HPeVs were considered to be one of the common viruses which cause mild gastroenteritis and respiratory infections, the concept of HPeVs has changed significantly after the discovery of HPeV3 in 2004. HPeV3 infection is an emerging infectious disease which attracts the attention of pediatricians, because it can cause sepsis and meningoencephalitis in neonates and infants younger than 3 months, which could lead to neurological sequelae and death. In Japan, the epidemics of HPeV3 infection have occurred every 2 or 3 years since 2006 and we had an epidemic in 2014 summer. Fever, severe tachycardia, poor activity and appetite are typical symptoms of HPeV3 infection.In addition, abdominal distention, umbilical protrusion, palmar-plantar erythema,and mottled skin are occasionally observed in patients with HPeV3 infection. Currently diagnosis is usually made by PCR using serum and/or cerebrospinal fluid. The reason why severe disease occur only in neonates and young infants remain unknown; however, negative or low maternally derived neutralizing antibody titers to HPeV3 are suggested to be a risk factor for developing severe HPeV3-related diseases in neonates and young infants. So far, no specific antiviral therapy is available, thus supportive care is the only option. It is likely that epidemics of HPeV3 continue to occur given there are children with absence or lack of neutralizing antibodies against HPeV3. The research related to HPeV3 pathogenesis, specific therapy, and prevention are definitely warranted.

    DOI: 10.2222/jsv.65.17

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  • Dermatologic manifestations of human parechovirus type 3 infection in neonates and infants. 査読 国際誌

    Kensuke Shoji, Hisako Komuro, Ippei Miyata, Isao Miyairi, Akihiko Saitoh

    The Pediatric infectious disease journal   32 ( 3 )   233 - 6   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Human parechovirus type 3 (HPeV3) infection can cause sepsis-like syndrome and meningoencephalitis in neonates and young infants. Although maculopapular rash is a reported clinical manifestation of HPeV3 infection, the frequency and detailed characteristics of rash in neonates and young infants with HPeV3 infection are unknown. METHODS: We retrospectively reviewed the clinical characteristics of neonates and young infants who received a diagnosis of HPeV3 infection on the basis of real-time polymerase chain reaction analysis of serum and/or cerebrospinal fluid specimens at the National Center for Child Health and Development in Tokyo between November 2010 and September 2011. RESULTS: Fifteen neonates and young infants were diagnosed as having HPeV3 infection; median age was 33 days (range: 10-81 days). The most common clinical presentation on admission was fever (80%), the median duration of which was 3 days (range: 1-4 days). Five (33%) children required admission to the intensive care unit for close observation, and 2 (13%) required mechanical ventilation for cardiovascular instability. After hospitalization, all children developed rash, mainly on the extremities, at a mean of 3 days (range: 1-5 days) after fever onset. The most striking finding was that 80% (12/15) of patients developed a distinctive palmar-plantar erythematous rash, which disappeared after a median of 3 days (range: 2-7 days). All patients were discharged from hospital without serious sequelae. CONCLUSIONS: Palmar-plantar erythema in febrile neonates and young infants may be a diagnostic clue of HPeV3 infection.

    DOI: 10.1097/INF.0b013e31827b1fd0

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  • Acute Flaccid Myelitis With Human Rhinovirus A19 Detection: Case Report and Literature Review 査読

    Yurie Murayama, Yuta Aizawa, Tatsuki Ikuse, Ryohei Izumita, Shunsuke Nukaga, Masahiro Kaneko, Takeshi Yamada, Takeshi Ono, Ko Matsui, Masashi Suda, Akihiko Saitoh

    Pediatric Infectious Disease Journal   2024年3月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1097/INF.0000000000004317

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  • Detection of enterovirus D68 among children with severe acute respiratory infection in Myanmar 査読

    Tatsuki Ikuse, Yuta Aizawa, Ryotaro Kachikawa, Kazuhiro Kamata, Hidekazu Osada, Su Mon Kyaw Win, Lasham Di Ja, Nay Chi Win, Khin Nyo Thein, Aye Thida, Aye Tun, Ai Ito, Yadanar Kyaw, Htay Htay Tin, Yugo Shobugawa, Hisami Watanabe, Reiko Saito, Akihiko Saitoh

    Journal of Microbiology, Immunology and Infection   2024年1月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jmii.2024.01.001

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  • Hypocarnitinemia in twins after maternal pivalate-conjugated antibiotic therapy. 国際誌

    Takuya Fuse, Yuta Aizawa, Hiromi Nyuzuki, Kentaro Sawano, Keisuke Nagasaki, Akihiko Saitoh

    Pediatrics international : official journal of the Japan Pediatric Society   66 ( 1 )   e15750   2024年

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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/ped.15750

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  • GPATCH4 contributes to nucleolus morphology and its dysfunction impairs cell viability. 国際誌

    Kazuki Kodera, Ryuichi Hishida, Akiko Sakai, Hiromi Nyuzuki, Noriko Matsui, Tomoyuki Yamanaka, Akihiko Saitoh, Hideaki Matsui

    Biochemical and biophysical research communications   693   149384 - 149384   2023年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The nucleolus serves a multifaceted role encompassing not only rRNA transcription and ribosome synthesis, but also the intricate orchestration of cell cycle regulation and the modulation of cellular senescence. G-patch domain containing 4 (GPATCH4) stands as one among the nucleolar proteins; however, its functional significances remain still unclear. In order to elucidate the functions of GPATCH4, we examined the effects of its dysfunction on cellular proliferation, alterations in nucleolar architecture, apoptotic events, and cellular senescence. Through experimentation conducted on cultured neuroblastoma SH-SY5Y cells, the reduction of GPATCH4 caused inhibition of cellular proliferation, concurrently fostering escalated apoptotic susceptibilities upon exposure to high-dose etoposide. In the realm of nucleolar morphology comparisons, a discernible decline was noted in the count of nucleoli per nucleus, concomitant with a significant expansion in the area occupied by individual nucleoli. Upon induction of senescence prompted by low-dose etoposide, GPATCH4 knockdown resulted in decreased cell viability and increased expression of senescence-associated markers, namely senescence-associated β-galactosidase (SA-β-GAL) and p16. Furthermore, GPATCH4 dysfunction elicited alterations in the gene expression profile of the ribosomal system. In sum, our findings showed that GPATCH4 is a pivotal nucleolar protein that regulates nucleolar morphology and is correlated with cell viability.

    DOI: 10.1016/j.bbrc.2023.149384

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  • Incidence of Omicron Variant Reinfection and Reduction of Reinfection Risk After Coronavirus Disease 2019 Vaccination in Children. 国際誌

    Tatsuki Ikuse, Yuta Aizawa, Satoshi Hasegawa, Masashi Takahashi, Takanori Hayashi, Miyako Kon, Tsutomu Tamura, Haruki Matsumoto, Akihiko Saitoh

    Journal of the Pediatric Infectious Diseases Society   2023年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Data are limited on the incidence of coronavirus disease 2019 (COVID-19) reinfection in children. This population-based cohort study in Niigata, Japan from January to November 2022 demonstrated the incidence of reinfection was 1337/48 099 (2.8%), and the hazard ratio for reinfection in vaccinated children was 0.29 (95% confidence interval, 0.20-0.40).

    DOI: 10.1093/jpids/piad093

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  • Cord blood granulocyte Colony-Stimulating factor level as an optimal predictor of umbilical cord arteritis associated with brain injury at term equivalent age in preterm neonates

    Jun Nirei, Akira Kobayashi, Rie Habuka, Hisanori Domon, Yutaka Terao, Akihiko Saitoh

    Cytokine   171   156369 - 156369   2023年11月

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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.cyto.2023.156369

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  • Human Rhinovirus as a Cause of Fever in Neonates and Young Infants During the COVID-19 Pandemic, 2020-2022. 国際誌

    Yuta Aizawa, Tatsuki Ikuse, Ryohei Izumita, Rie Habuka, Takayuki Yamanaka, Akihiko Saitoh

    The Pediatric infectious disease journal   2023年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Human rhinovirus (HRV) was predominant and persistent during the coronavirus disease 2019 (COVID-19) pandemic despite nonpharmaceutical interventions. The data whether HRV persistence also occurred in neonates and young infants were very limited. METHODS: This prospective observational study was conducted in Niigata, Japan, between January 2020 and September 2022. The participants were hospitalized neonates and infants aged less than 4 months with fever. We excluded patients with evidence of bacterial infection or obvious sick contact with influenza or respiratory syncytial virus infection, as confirmed by rapid antigen detection tests. COVID-19 diagnosed by polymerase chain reaction (PCR) or rapid antigen detection tests were also excluded. Parechovirus and enterovirus were examined by PCR using serum and/or cerebrospinal fluid. FilmArray Respiratory Panel v1.7 was conducted on nasopharyngeal swabs. If HRV was positive, the genotype was identified. RESULTS: We included 72 patients (median age, 54 days; interquartile range, 28.5-79 days), and sepsis was diagnosed in 31 (43.1%) patients. In total, 27 (37.5%) patients had had positive multiplex PCR tests. These patients were more likely to have rhinorrhea (P = 0.004), cough (P = 0.01), and sick contact (P < 0.001) than those who with negative multiplex PCR. HRV was the most frequently detected virus (n = 23, 85.2%), and species A (n = 15, 71.4%) and C (n = 6, 28.6%) were genotyped. No seasonality or monthly predominance of the specific HRV types was observed. CONCLUSIONS: HRV was an important cause of fever in neonates and young infants during the COVID-19 pandemic, 2020 to 2022.

    DOI: 10.1097/INF.0000000000004139

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  • Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan 2022. 国際誌

    Naruhiko Ishiwada, Masayoshi Shinjoh, Yoshiki Kusama, Hirokazu Arakawa, Tomohiro Ohishi, Akihiko Saitoh, Akira Suzuki, Hiroyuki Tsutsumi, Junichiro Nishi, Tadashi Hoshino, Toshihiro Mitsuda, Isao Miyairi, Noriko Iwamoto-Kinoshita, Hisato Kobayashi, Kouichiro Satoh, Akihiko Shimizu, Kenichi Takeshita, Takaaki Tanaka, Daisuke Tamura, Osamu Tokunaga, Kentaro Tomita, Koo Nagasawa, Takanori Funaki, Muhehiro Furuichi, Ippei Miyata, Mizuki Yaginuma, Yoshio Yamaguchi, Shota Yamamoto, Suzuko Uehara, Tomomichi Kurosaki, Kenji Okada, Kazunobu Ouchi

    The Pediatric infectious disease journal   2023年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The members of the Japanese Society for Pediatric Infectious Diseases and the Japanese Society of Pediatric Pulmonology have developed Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating appropriate diagnosis, treatment and prevention of respiratory infections in children. The first edition was published in 2004 and the fifth edition was published in 2022. The Guideline 2022 consists of 2 parts, clinical questions and commentary, and includes general respiratory infections and specific infections in children with underlying diseases and severe infections. This executive summary outlines the clinical questions in the Guidelines 2022, with reference to the Japanese Medical Information Distribution Service Manual. All recommendations are supported by a systematic search for relevant evidence and are followed by the strength of the recommendation and the quality of the evidence statements.

    DOI: 10.1097/INF.0000000000004041

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  • Purulent nasal discharge due to gonococcal nasopharyngitis in a neonate. 国際誌

    Satoshi Inaba, Yuta Aizawa, Satoshi Kataoka, Akihiko Saitoh

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   2023年8月

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    記述言語:英語  

    Neonatal gonorrhea, caused by Neisseria gonorrhoeae, is an uncommon but important disease to prevent because its complications, such as gonococcal ophthalmia neonatorum (GON) causes blindness if untreated. Neonatal gonococcal nasopharyngitis is a rare, but important clinical manifestation to suspect gonococcal infection in a neonate. Herein we report a case of neonatal gonococcal nasopharyngitis, presented with purulent nasal discharge. A full-term male neonate without perinatal complications developed purulent eye discharge on the 7th day of life. N. gonorrhoeae was isolated from the eye discharge culture; however, he did not receive the standard regimen. Subsequently, he presented to our hospital with fever and nasal discharge on the 20th day of life. N. gonorrhoeae was also isolated from nasal discharge and nasopharyngeal swabs without any evidence of chlamydia or syphilis. He received intravenous cefotaxime until disseminated gonococcal infection was ruled out and was discharged without any sequelae. Rhinorrhea in newborns requires consideration of mother-to-child transmission of various microorganisms, not only common respiratory viruses, but also rare, serious preventable infections such as gonorrhea or syphilis. Along with the recent syphilis patients on the rise in Japan, gonorrhea is an important disease to recognize, and the incidence could increase. Clinical manifestations of neonatal gonococcal infections, including nasopharyngitis, need to be recognized to suspect the diagnosis and initiate appropriate treatment to prevent serious complications.

    DOI: 10.1016/j.jiac.2023.08.005

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  • Outcomes of Hematopoietic Stem Cell Gene Therapy for Wiskott-Aldrich Syndrome. 国際誌

    Roxane Labrosse, Julia Chu, Myriam Armant, John K Everett, Danilo Pellin, Niharika Kareddy, Andrew L Frelinger, Lauren A Henderson, Amy E O'Connell, Amlan Biswas, Jet Coenen-van der Spek, Alexandra Marina Miggelbrink, Claudia Fiorini, Hriju Adhikari, Charles C Berry, Vito Adrian Cantu, Johnson Fong, Jason Roy Jaroslavsky, Derin F Karadeniz, Quan-Zhen Li, Shantan Reddy, Aoife M Roche, Chengsong Zhu, Jennifer S Whangbo, Colleen Dansereau, Brenda L Mackinnon, Emily Morris, Stephanie M Koo, Wendy B London, Safa Baris, Ahmet Ozen, Elif Karakoc-Aydiner, Jenny McDade Despotovic, Lisa R Forbes Satter, Akihiko Saitoh, Yuta Aizawa, Alejandra King, Mai Anh T Nguyen, Vy Do Uyen Vu, Scott B Snapper, Anne Galy, Luigi D Notarangelo, Frederic D Bushman, David A Williams, Sung-Yun Pai

    Blood   142 ( 15 )   1281 - 1296   2023年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by combined immunodeficiency, eczema, microthrombocytopenia, autoimmunity, and lymphoid malignancies. Gene therapy (GT) to modify autologous CD34+ cells is an emerging alternative treatment with advantages over standard allogeneic hematopoietic stem cell transplant for patients who lack well-matched donors, avoiding graft-versus-host-disease. We report the outcomes of a phase I/II clinical trial in which 5 patients with severe WAS underwent GT using a self-inactivating lentiviral (SIN-LV) vector expressing the human WAS cDNA under the control of a 1.6kB fragment of the autologous promoter after busulfan and fludarabine conditioning. All subjects were alive and well with sustained multi-lineage vector gene marking (median follow-up: 7.6 years). Clinical improvement of eczema, infections and bleeding diathesis was universal. Immune function was consistently improved despite sub-physiological levels of transgenic WAS protein expression. Improvements in platelet count and cytoskeletal function in myeloid cells were most prominent in patients with high vector copy number in the transduced product. Two patients with a history of autoimmunity had flares of autoimmunity post-GT, despite similar percentages of WASp-expressing cells and gene marking as those without autoimmunity. Patients with flares of autoimmunity demonstrated poor numerical recovery of T cells and regulatory T cells (Tregs), IL-10 producing regulatory B cells (Bregs), and transitional B cells. Recovery of the Breg compartment, along with Tregs, thus appears to be protective against development of autoimmunity post-GT. These results indicate that clinical and laboratory manifestations of WAS are improved with GT with an acceptable safety profile. This trial is registered with ClinicalTrials.gov (NCT01410825).

    DOI: 10.1182/blood.2022019117

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  • An outbreak investigation of parechovirus-A3 in a newborn nursery. 国際誌

    Yuta Aizawa, Keisuke Saeki, Kazuetsu Mori, Tatsuki Ikuse, Ryohei Izumita, Akihiko Saitoh

    Infection control and hospital epidemiology   1 - 5   2023年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: To investigate parechovirus-A3 (PeV-A3) transmission in a newborn nursery, after encountering 3 neonates with fever and rash. DESIGN: An observational study. SETTING: At a newborn nursery at the general hospital in Hyogo, Japan. PARTICIPANTS: Symptomatic neonates and their family members, and asymptomatic neonates born during the same period. METHODS: PCR assays for PeV-A and genotyping were used for the investigation of PeV-A3. Preserved umbilical cords were used to identify the route of transmission. RESULTS: PeV-A3 infection was confirmed in the three symptomatic neonates. The index case had fever and rash, and the 2 neonates treated later became symptomatic and had serum, cerebrospinal fluid, and stool specimens that were positive for PeV-A3 on PCR. The umbilical cord of the index case was positive for PeV-A3 on PCR. The family members of the index case, including the mother, were asymptomatic before delivery. The older sister and cousin of the PeV-A3-infected neonate had positive PCR results. The sequence analysis suggested 2 possible transmission routes: vertical and horizontal transmission in a newborn nursery and/or a family outside the hospital. The incubation period of PeV-A3 infection was estimated to be 1-3 days (maximum, 7 days). CONCLUSION: Horizontal transmission of PeV-A3 was confirmed in a newborn nursery. Vertical transmission was suggested by the detection of RNA in an umbilical cord sample from the index case. These observations indicate that PeV-A3 can be horizontally transmitted in a newborn nursery and that special caution is required to prevent healthcare-associated transmission of PeV-A3.

    DOI: 10.1017/ice.2023.142

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  • Detection of parechovirus-A in hospitalized children with acute lower respiratory infection in Myanmar, 2017-2018. 国際誌

    Jun Tachikawa, Yuta Aizawa, Tetsuya Kobayashi, Tatsuki Ikuse, Kazuhiro Kamata, Su Mon Kyaw Win, Lasham Di Ja, Khin Nyo Thein, Nay Chi Win, Aye Thida, Aye Tun, Yuko Suzuki, Ai Ito, Hidekazu Osada, Irina Chon, Wint Wint Phyu, Tomomi Ota, Yadanar Kyaw, Htay Htay Tin, Kanako Watanabe, Yugo Shobugawa, Hisami Watanabe, Reiko Saito, Akihiko Saitoh

    Journal of medical virology   95 ( 7 )   e28964   2023年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Parechovirus-A (PeV-A) causes emerging infection in children, and clinical presentation depends on genotype. The virus has been investigated mainly in developed countries; however, data from developing countries, especially in Asia, are sparse. This study investigated whether PeV-A circulated in children in Myanmar. This retrospective study evaluated PeV-A in nasopharyngeal samples from children aged 1 month to 12 years who were hospitalized with acute lower respiratory infection at Yankin Children Hospital, Yangon, Myanmar, during the period from May 2017 to April 2019. Real-time polymerase chain reaction (PCR) was used to detect PeV-A, and PCR-positive samples were used for genotyping and phylogenetic analysis. In total, 11/570 (1.9%) of samples were positive for PeV-A; 7 were successfully genotyped by sequencing the VP3/VP1 region, as follows: PeV-A1 (n = 4), PeV-A5 (n = 1), PeV-A6 (n = 1), and PeV-A14 (n = 1). Median age was 10.0 months (interquartile range 4.0-12.0 months), and other respiratory viruses were detected in all cases. Phylogenetic analysis showed that all detected PeV-A1 strains were in clade 1 A, which was a minor clade worldwide. Four PeV-A genotypes were detected in Myanmar. The clinical impact of PeV-A in children should be evaluated in future studies.

    DOI: 10.1002/jmv.28964

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  • Severe Disease in Children with Parechovirus-A Infection

    Jun Tachikawa, Yuta Aizawa, Akihiko Saitoh

    CURRENT CLINICAL MICROBIOLOGY REPORTS   2023年7月

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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  

    Purpose of ReviewParechovirus-A (PeV-A) is an important emerging virus. Clinical manifestations of pediatric PeV-A infection vary by genotype and range from mild acute illness to severe disease. This review discusses the global epidemiological profile of pediatric PeV-A infection and the relationship of PeV-A genotype to severe disease in neonates and young infants.Recent FindingsIn neonates and young infants the most important PeV-A3-associated conditions are sepsis and meningoencephalitis, which have been reported in many countries. The high morbidity of encephalitis due to PeV-A3 is a serious concern. Although rare, severe PeV-A-associated diseases due to other genotypes have also been reported in children. The pandemic of coronavirus disease 2019 significantly affected PeV-A3 detection.PeV-A, especially PeV-A3, is an important emerging virus that causes severe disease in children. PeV-A genotyping will improve our understanding of the epidemiology of PeV-A and the relationship of PeV-A genotype with severe disease. Specific antiviral therapies are needed to treat severe diseases caused by PeV-A.

    DOI: 10.1007/s40588-023-00197-3

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  • 小児科医に潜在するワクチン忌避(Vaccine Hesitancy)に対する教育プログラム

    勝田 友博, 天羽 清子, 荒木 かほる, 石和田 稔彦, 大宜見 力, 神谷 元, 越田 理恵, 高野 智子, 津川 毅, 富樫 篤生, 中野 貴司, 西村 直子, 野崎 昌俊, 菱木 はるか, 保科 隆之, 細矢 光亮, 前田 明彦, 水野 由美, 宮入 烈, 宮崎 雅仁, 吉川 哲史, 和田 泰三, 岩田 敏, 尾内 一信, 岡田 賢司, 岡部 信彦, 是松 聖悟, 清水 直樹, 菅 秀, 宮崎 千明, 森内 浩幸, 大城 誠, 藤岡 雅司, 森岡 一朗, 塚原 宏一, 齋藤 昭彦, 多屋 馨子, 日本小児科学会予防接種・感染症対策委員会

    日本小児科学会雑誌   127 ( 5 )   787 - 794   2023年5月

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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  

    予防接種後有害事象(AEFI)および予防接種ストレス関連反応(ISRR)に関連する動画講義視聴が小児科医の予防接種に対する知識、態度、自信、役割認識、自己効力感、行動に与える影響を調査した。介入前評価(pre study)に回答した日本小児科学会会員368名をA群とB群に分けてA群にのみオンラインでISRRに関する約20分間の動画講義を配布し、pre studyから約1ヵ月後にA群・B群に介入後評価(Post study)を行った。Post studyの回答者A群74名、B群95名を対象に動画講義視聴による介入効果について検討した。その結果、AEFIおよびISRRに関連する調査によってA群・B群の知識レベルが向上したが、予防接種に対する態度、自信、役割認識、自己効力感、実際の接種行動に与える影響は限定的であった。

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  • 小児科医に潜在するワクチン忌避(Vaccine Hesitancy)に対する教育プログラム

    勝田 友博, 天羽 清子, 荒木 かほる, 石和田 稔彦, 大宜見 力, 神谷 元, 越田 理恵, 高野 智子, 津川 毅, 富樫 篤生, 中野 貴司, 西村 直子, 野崎 昌俊, 菱木 はるか, 保科 隆之, 細矢 光亮, 前田 明彦, 水野 由美, 宮入 烈, 宮崎 雅仁, 吉川 哲史, 和田 泰三, 岩田 敏, 尾内 一信, 岡田 賢司, 岡部 信彦, 是松 聖悟, 清水 直樹, 菅 秀, 宮崎 千明, 森内 浩幸, 大城 誠, 藤岡 雅司, 森岡 一朗, 塚原 宏一, 齋藤 昭彦, 多屋 馨子, 日本小児科学会予防接種・感染症対策委員会

    日本小児科学会雑誌   127 ( 5 )   787 - 794   2023年5月

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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  

    予防接種後有害事象(AEFI)および予防接種ストレス関連反応(ISRR)に関連する動画講義視聴が小児科医の予防接種に対する知識、態度、自信、役割認識、自己効力感、行動に与える影響を調査した。介入前評価(pre study)に回答した日本小児科学会会員368名をA群とB群に分けてA群にのみオンラインでISRRに関する約20分間の動画講義を配布し、pre studyから約1ヵ月後にA群・B群に介入後評価(Post study)を行った。Post studyの回答者A群74名、B群95名を対象に動画講義視聴による介入効果について検討した。その結果、AEFIおよびISRRに関連する調査によってA群・B群の知識レベルが向上したが、予防接種に対する態度、自信、役割認識、自己効力感、実際の接種行動に与える影響は限定的であった。

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  • Myeloid-associated differentiation marker is an essential host factor for human parechovirus PeV-A3 entry

    Kanako Watanabe, Tomoichiro Oka, Hirotaka Takagi, Sergei Anisimov, Shun-ichi Yamashita, Yoshinori Katsuragi, Masahiko Takahashi, Masaya Higuchi, Tomotake Kanki, Akihiko Saitoh, Masahiro Fujii

    Nature Communications   14 ( 1 )   2023年3月

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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  

    Abstract

    Human parechovirus (PeV-A) is an RNA virus that belongs to the family Picornaviridae and it is currently classified into 19 genotypes. PeV-As usually cause mild illness in children and adults. Among the genotypes, PeV-A3 can cause severe diseases in neonates and young infants, resulting in neurological sequelae and death. In this study, we identify the human myeloid-associated differentiation marker (MYADM) as an essential host factor for the entry of six PeV-As (PeV-A1 to PeV-A6), including PeV-A3. The infection of six PeV-As (PeV-A1 to PeV-A6) to human cells is abolished by knocking out the expression of MYADM. Hamster BHK-21 cells are resistant to PeV-A infection, but the expression of human MYADM in BHK-21 confers PeV-A infection and viral production. Furthermore, VP0 capsid protein of PeV-A3 interacts with one extracellular domain of human MYADM on the cell membrane of BHK-21. The identification of MYADM as an essential entry factor for PeV-As infection is expected to advance our understanding of the pathogenesis of PeV-As.

    DOI: 10.1038/s41467-023-37399-8

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    その他リンク: https://www.nature.com/articles/s41467-023-37399-8

  • Comparison of Clinical Characteristics of Children Infected with Coronavirus Disease 2019 between Omicron Variant BA.5 and BA.1/BA.2 in Japan. 国際誌

    Tatsuki Ikuse, Yuta Aizawa, Takayuki Yamanaka, Satoshi Hasegawa, Takanori Hayashi, Miyako Kon, Tsutomu Tamura, Akihiko Saitoh

    The Pediatric infectious disease journal   2023年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has dramatically altered the clinical profile of pediatric coronavirus disease 2019 (COVID-19). In Japan, we experienced a pandemic of omicron subvariant BA.1/BA.2 from January through June 2022. However, after the emergence of BA.5 in early July 2022, the number of children hospitalized with COVID-19 increased dramatically in Japan. METHODS: We collected data on monthly numbers of cases and clinical characteristics of hospitalized children with COVID-19 in 13 hospitals, the total number of pediatric COVID-19 cases, and COVID-19 vaccination rates in Niigata, Japan, for the period from January 2020 through August 2022. We compared clinical presentation during the periods of BA.1/BA.2 predominance (January-June 2022) and BA.5 predominance (July-August 2022) and estimated vaccine effectiveness (VE) against hospitalization during the BA.5-predominant period. RESULTS: Between January 1, 2020, and August 31, 2022, 49,387 children (19,085 children/100,000 population) were newly diagnosed as having COVID-19, and 393 were hospitalized for COVID-19. Hospitalization for febrile seizure, especially complex seizure, was significantly higher during BA.5 predominance than during BA.1/BA.2 predominance (27.9% vs. 7.0%, P < 0.01). VE against hospitalization during BA.5 predominance was estimated to be 75% (95% confidence interval, 48%-88%, P < 0.01). CONCLUSIONS: The emergence of BA.5 significantly affected children in Japan; the number with complex febrile seizure who required hospitalization was higher than during BA.1/BA.2 predominance. The COVID-19 vaccination rate in children must be increased to prevent hospitalization for COVID-19 and to prepare for current and future variant outbreaks.

    DOI: 10.1097/INF.0000000000003894

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  • コロナウイルス感染症2019流行下における国内小児医療の現状に関する調査

    中村 幸嗣, 勝田 友博, 清水 直樹, 神谷 元, 天羽 清子, 大城 誠, 菅 秀, 津川 毅, 西村 直子, 菱木 はるか, 藤岡 雅司, 細矢 光亮, 水野 由美, 吉川 哲史, 和田 泰三, 石和田 稔彦, 是松 聖悟, 中野 貴司, 宮入 烈, 尾内 一信, 相澤 悠太, 庄司 健介, 齋藤 昭彦, 森内 浩幸, 多屋 馨子, 日本小児科学会予防接種・感染症対策委員会

    日本小児科学会雑誌   127 ( 1 )   84 - 89   2023年1月

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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  

    国内の地域偏在を調整後に無作為に抽出した小児科1次医療施設100施設、2次医療施設100施設と全ての3次医療施設119施設を候補として、2020年4月(I期)、2020年10月(II期)、2021年4月(III期)の各時点における診療体制についてインターネットを介してアンケート調査した。回答があったのは1次医療施設27施設(回答率27%)、2次医療施設19施設(回答率19%)、3次医療施設72施設(回答率61%)であった。発熱患者の診療応需についてはコロナウイルス感染症2019(COVID-19)接触歴を有する場合、1次医療施設で応需困難となったのはI期で29.6%であったが、II期22.2%、III期14.8%と経時的に減少した。COVID-19患者の診療体制はIII期においても3次医療施設の約半数で軽症・無症状患者の診療が応需されていた。面会制限は大多数の施設で導入され、面会禁止とした施設がIII期においても2次医療施設の63.2%、3次医療施設の38.9%で存在した。

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  • データベースを用いた国内小児新型コロナウイルス感染症の臨床症状に関する評価

    勝田 友博, 清水 直樹, 神谷 元, 天羽 清子, 大城 誠, 菅 秀, 津川 毅, 西村 直子, 菱木 はるか, 藤岡 雅司, 細矢 光亮, 水野 由美, 吉川 哲史, 和田 泰三, 石和田 稔彦, 是松 聖悟, 中野 貴司, 宮入 烈, 尾内 一信, 齋藤 昭彦, 森内 浩幸, 多屋 馨子, 日本小児科学会予防接種・感染症対策委員会

    日本小児科学会雑誌   127 ( 1 )   79 - 83   2023年1月

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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  

    2020年2月~2022年4月に専用データベースに報告された小児コロナウイルス感染症2019患者のうち、0~15歳の5411例(男児2889例、女児2522例)の急性期における臨床的特徴を解析した。オミクロン株流行により感染経路は家庭内感染から学校・幼稚園・保育所へ変化した。オミクロン株流行期に初発症状でけいれん発作を起こした割合は1~4歳で13.4%、5~11歳で7.4%、オミクロン株流行期に初発症状で悪心・嘔吐を認めた割合は1~4歳で12.2%、5~11歳で22.6%、12~15歳で14.6%であり、いずれもデルタ株流行前またはデルタ株流行期と比較して大幅に増加した。最終的に全体の約2%にけいれんを伴う合併症が報告された。肺炎の合併率は変異株の違いによる変化をほとんど認めなかった。発症後28日を超えた症例報告書が提出された1697例(男児899例、女児798例、年齢中央値6.3歳)のうち、55例(3.2%)に発症後28日を超えても何らかの症状が残存した。

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  • Multiple pneumatoceles and lung abscesses caused by early-onset E. coli sepsis in a preterm neonate. 国際誌

    Jun Tachikawa, Yuta Aizawa, Taiki Shimotsuma, Takayuki Kaneko, Akihiko Saitoh

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   2022年12月

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    記述言語:英語  

    Early-onset sepsis (EOS) is a serious and fatal illness in neonates, Group B Streptococcus and Escherichia coli are major causative pathogens. We report a case of EOS and pneumonia caused by E. coli in a preterm neonate with multiple pneumatoceles and lung abscesses. A male neonate weighing 1670g was delivered at 33 6/7 weeks' gestation by a mother with clinical chorioamnionitis. He showed respiratory distress soon after birth and developed septic shock. He was intubated and mechanical ventilation was started. E.coli was detected in blood culture obtained from both the patient and his mother. He developed multiple pneumatoceles and lung abscesses. Surgical drainage was complicated, cefotaxime was thus continued until day 74. Pneumatoceles and lung abscesses are complications of neonatal pneumonia, rarely reported by E. coli. Multiple lung abscesses in our patient are distinct from single abscesses in previous case studies of neonatal lung abscesses. We speculate that bacteremia along with pneumatoceles led to multiple lung abscesses in our patient. These complications require long-term antibiotic therapy, to minimize morbidity and mortality, and should thus be considered when managing EOS caused by E. coli.

    DOI: 10.1016/j.jiac.2022.12.015

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  • Acute and Postacute Clinical Characteristics of Coronavirus Disease 2019 in Children in Japan. 国際誌

    Tomohiro Katsuta, Yuta Aizawa, Kensuke Shoji, Naoki Shimizu, Kenji Okada, Takashi Nakano, Hajime Kamiya, Kiyoko Amo, Naruhiko Ishiwada, Satoshi Iwata, Makoto Oshiro, Nobuhiko Okabe, Seigo Korematsu, Shigeru Suga, Takeshi Tsugawa, Naoko Nishimura, Haruka Hishiki, Masashi Fujioka, Mitsuaki Hosoya, Yumi Mizuno, Isao Miyairi, Chiaki Miyazaki, Tsuneo Morishima, Tetsushi Yoshikawa, Taizo Wada, Kazunobu Ouchi, Hiroyuki Moriuchi, Keiko Tanaka-Taya, Akihiko Saitoh

    The Pediatric infectious disease journal   42 ( 3 )   240 - 246   2022年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The clinical features of coronavirus disease 2019 (COVID-19) in children have been changing because of the emergence and rapid spread of variants of concern (VOC). The increase in cases infected with VOC has brought concern with persistent symptoms after COVID-19 in children. This survey aimed to analyze the clinical manifestations and persistent symptoms of pediatric COVID-19 cases in Japan. METHODS: We analyzed the clinical manifestations of pediatric COVID-19 cases reported between February 2020 and April 2022 in Japan, using a dedicated database updated voluntarily by the members of the Japan Pediatric Society. Using the same database, we also analyzed persistent symptoms after COVID-19 in children who were diagnosed between February 2020 and November 2021. RESULTS: A total of 5411 and 1697 pediatric COVID-19 cases were included for analyzing clinical manifestations and persistent symptoms, respectively. During the Omicron variant predominant period, the percentage of patients with seizures increased to 13.4% and 7.4% in patient groups aged 1-4 and 5-11 years, respectively, compared with the pre-Delta (1.3%, 0.4%) or Delta period (3.1%, 0.0%). Persistent and present symptoms after 28 days of COVID-19 onset were reported in 55 (3.2%). CONCLUSIONS: Our survey showed that the rate of symptomatic pediatric COVID-19 cases increased gradually, especially during the Omicron variant predominant period, and a certain percentage of pediatric cases had persistent symptoms. Certain percentages of pediatric COVID-19 patients had severe complications or prolonged symptoms. Further studies are needed to follow such patients.

    DOI: 10.1097/INF.0000000000003792

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  • Increased CaV1.2 late current by a CACNA1C p.R412M variant causes an atypical Timothy syndrome without syndactyly. 国際誌

    Junichi Ozawa, Seiko Ohno, Dario Melgari, Qi Wang, Megumi Fukuyama, Futoshi Toyoda, Takeru Makiyama, Masao Yoshinaga, Hiroshi Suzuki, Akihiko Saitoh, Tomohiko Ai, Minoru Horie

    Scientific reports   12 ( 1 )   18984 - 18984   2022年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Timothy syndrome (TS) is a rare pleiotropic disorder associated with long QT syndrome, syndactyly, dysmorphic features, and neurological symptoms. Several variants in exon 8 or 8a of CACNA1C, a gene encoding the α-subunit of voltage-gated Ca2+ channels (Cav1.2), are known to cause classical TS. We identified a p.R412M (exon 9) variant in an atypical TS case. The aim of this study was to examine the functional effects of CACNA1C p.R412M on CaV1.2 in comparison with those of p.G406R. The index patient was a 2-month-old female infant who suffered from a cardio-pulmonary arrest in association with prolonged QT intervals. She showed dysmorphic facial features and developmental delay, but not syndactyly. Interestingly, she also presented recurrent seizures from 4 months. Genetic tests identified a novel heterozygous CACNA1C variant, p.R412M. Using heterologous expression system with HEK-293 cells, analyses with whole-cell patch-clamp technique revealed that p.R412M caused late Ca2+ currents by significantly delaying CaV1.2 channel inactivation, consistent with the underlying mechanisms of classical TS. A novel CACNA1C variant, p.R412M, was found to be associated with atypical TS through the same mechanism as p.G406R, the variant responsible for classical TS.

    DOI: 10.1038/s41598-022-23512-2

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  • 小児NAFLD患者の背景疾患と移行医療への課題

    上村 博輝, 佐藤 毅昂, 山崎 文紗子, 坂牧 僚, 土屋 淳紀, 寺井 崇二, 長崎 啓祐, 齋藤 昭彦

    肥満研究   28 ( Suppl. )   290 - 290   2022年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肥満学会  

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  • NKp44-based chimeric antigen receptor effectively redirects primary T cells against synovial sarcoma 国際誌

    Yudai Murayama, Yasushi Kasahara, Nobuhiro Kubo, Chansu Shin, Masaru Imamura, Naoki Oike, Takashi Ariizumi, Akihiko Saitoh, Minori Baba, Tomohiro Miyazaki, Yuko Suzuki, Yiwei Ling, Shujiro Okuda, Keichiro Mihara, Akira Ogose, Hiroyuki Kawashima, Chihaya Imai

    Translational Oncology   25   101521 - 101521   2022年11月

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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: T-cell receptor-engineered T-cell therapies have achieved promising response rates against synovial sarcoma in clinical trials, but their applicability is limited owing to the HLA matching requirement. Chimeric antigen receptor (CAR) can redirect primary T cells to tumor-associated antigens without requiring HLA matching. However, various obstacles, including the paucity of targetable antigens, must be addressed for synovial sarcoma. Ligands for natural killer (NK) cell-activating receptors are highly expressed by tumor cells. METHODS: The surface expression of ligands for NK cell-activating receptors in synovial sarcoma cell lines was analyzed. We analyzed RNA sequencing data deposited in a public database to evaluate NKp44-ligand expression. Primary T cells retrovirally transduced with CAR targeting NKp44 ligands were evaluated for their functions in synovial sarcoma cells. Alterations induced by various stimuli, including a histone deacetylase inhibitor, a hypomethylating agent, inflammatory cytokines, and ionizing radiation, in the expression levels of NKp44 ligands were investigated. RESULTS: Ligands for NKp44 and NKp30 were expressed in all cell lines. NKG2D ligands were barely expressed in a single cell line. None of the cell lines expressed NKp46 ligand. Primary synovial sarcoma cells expressed the mRNA of the truncated isoform of MLL5, a known cellular ligand for NKp44. NKp44-based CAR T cells specifically recognize synovial sarcoma cells, secrete interferon-γ, and exert suppressive effects on tumor cell growth. No stimulus altered the expression of NKp44 ligands. CONCLUSION: NKp44-based CAR T cells can redirect primary human T cells to synovial sarcoma cells. CAR-based cell therapies may be an option for treating synovial sarcomas.

    DOI: 10.1016/j.tranon.2022.101521

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  • 大腸菌による新生児早発型敗血症に合併した多発肺膿瘍の1例

    太刀川 潤, 相澤 悠太, 下妻 大毅, 金子 孝之, 齋藤 昭彦

    日本小児感染症学会総会・学術集会プログラム・抄録集   54回   252 - 252   2022年11月

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    記述言語:日本語   出版者・発行元:(一社)日本小児感染症学会  

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  • Genotyping and macrolide-resistant mutation of Bordetella pertussis in East and South-East Asia. 国際誌

    Kentaro Koide, ShuMan Yao, Chuen-Sheue Chiang, Phung Thi Bich Thuy, Do Thi Thuy Nga, Do Thu Huong, Tran Minh Dien, Ork Vichit, Yong Vutthikol, Siphan Sovannara, Chham Samnang, Ikuyo Takayama, Akira Ainai, Noriko Nakajima, Nao Otsuka, Kazunari Kamachi, Akihiko Saitoh

    Journal of global antimicrobial resistance   2022年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: Macrolide-resistant Bordetella pertussis (MRBP) has been emerging and prevailing in mainland China since 2011. In this study, we aimed to investigate the genotype and macrolide resistance of circulating B. pertussis in East and South-East Asia using genetic analyses. METHODS: A total of 302 DNA extracts from clinical specimens and isolates during 2010-2020 were analyzed: 145 from Vietnam, 76 from Cambodia, 48 from Taiwan, and 33 from Japan. Genotypes were determined by multilocus variable-number tandem-repeat analysis (MLVA). Macrolide-resistant A2047G mutation in B. pertussis 23S rRNA was investigated using the duplex Cycleave real-time PCR assay. Whole-genome sequencing was performed on two MRBP isolates, identified for the first time in Taiwan. RESULTS: In all, 286 DNA extracts (95%) generated a complete MLVA genotype and 283 DNA extracts (94%) yielded a complete result for the A2047G mutation analysis. The A2047G mutation was detected in 18 DNA extracts: fourteen from Vietnam, one from Cambodia, two from Taiwan, and one from Japan. Most of them (78%) showed the genotypes MT104 and MT195, which have previously been reported in Chinese MRBP isolates. Further, the Taiwanese MRBP isolates were classified into the MT104 clade of Chinese MRBP isolates. CONCLUSION: After MRBP emerged and spread in mainland China, it may have spread to East and South-East Asia in the 2010s. Continued surveillance targeting the A2047G mutation of MRBP is needed to prevent further spread of this emerging pathogen.

    DOI: 10.1016/j.jgar.2022.10.007

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  • Laryngeal herpes zoster with multiple symptoms in a child. 国際誌

    Shun Maki, Takayuki Yamanaka, Ryohei Izumita, Hiroshi Matsuyama, Shinya Tsukano, Akihiko Saitoh

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   2022年10月

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    記述言語:英語  

    Herpes zoster caused by reactivation of latent varicella-zoster virus (VZV) usually develop in later adulthood. In the pediatric population, herpes zoster is unusual, and involvement of pharyngolaryngeal lesion and cranial nerves is rare. Here, we report a 14-year-old boy who was diagnosed with laryngeal herpes zoster (LHZ), and developed subsequent cranial nerve symptoms suspected of vagus neuropathy. This case provides additional evidence that children can develop LHZ and subsequent cranial nerve symptoms. LHZ should be considered if a pediatric patient with a history of varicella, has unilateral throat pain, with or without cranial nerve symptoms.

    DOI: 10.1016/j.jiac.2022.10.001

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  • Performance of Nanopore and Illumina Metagenomic Sequencing for Pathogen Detection and Transcriptome Analysis in Infantile Central Nervous System Infections. 国際誌

    Kazuhiro Horiba, Yuka Torii, Yuta Aizawa, Makoto Yamaguchi, Kazunori Haruta, Toshihiko Okumura, Takako Suzuki, Yoshihiko Kawano, Jun-Ichi Kawada, Shinya Hara, Akihiko Saitoh, Christian G Giske, Tomoo Ogi, Yoshinori Ito

    Open forum infectious diseases   9 ( 10 )   ofac504   2022年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Infantile central nervous system infections (CNSIs) can be life-threatening and cause severe sequelae. However, the causative microorganism remains unknown in >40% of patients with aseptic infections. This study aimed to analyze the metagenome for detection of pathogens and the transcriptome for host immune responses during infection in a single cerebrospinal fluid (CSF) sample using 2 different next-generation sequencing (NGS) platforms, Nanopore and Illumina. Methods: Twenty-eight CNSIs patients (<12 months) were enrolled, and 49 clinical samples (28 CSF and 21 blood) were collected. The DNA extracted from all 49 samples was sequenced using the Illumina sequencer for the detection of pathogens. Extracted RNA was obtained in sufficient quantities from 23 CSF samples and subjected to sequencing on both Nanopore and Illumina platforms. Human-derived reads subtracted during pathogen detection were used for host transcriptomic analysis from both Nanopore and Illumina sequencing. Results: RNA metagenomic sequencing using both sequencing platforms revealed putative viral pathogens in 10 cases. DNA sequencing using the Illumina sequencer detected 2 pathogens. The results of Nanopore and Illumina RNA sequencing were consistent; however, the mapping coverage and depth to the detected pathogen genome of Nanopore RNA sequencing were greater than those of Illumina. Host transcriptomic analysis of Nanopore sequencing revealed highly expressed genes related to the antiviral roles of innate immunity from pathogen-identified cases. Conclusions: The use of Nanopore RNA sequencing for metagenomic diagnostics of CSF samples should help to elucidate both pathogens and host immune responses of CNSI and could shed light on the pathogenesis of these infections.

    DOI: 10.1093/ofid/ofac504

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  • Pilot Study of Evaluating Attitudes toward Childhood Immunization among Healthcare Workers in Japan. 国際誌

    Aya Saitoh, Yugo Shobugawa, Isamu Sato, Yuki Yonekura, Ai Kawabata, Akihiko Saitoh, Reiko Saito

    Vaccines   10 ( 7 )   2022年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Providing appropriate immunization information during the perinatal period is important for improving immunization rates among infants and children; however, the distribution of immunization information by healthcare workers (HCWs) is not standardized in Japan. We investigated HCWs' attitudes toward childhood immunization and factors related to vaccine hesitancy. We conducted a cross-sectional descriptive survey of HCWs involved in childhood immunization in Niigata City, Japan, from November 2017 to January 2018. We assessed contextual, individual and group, and vaccine/vaccination-specific influences. Of 290 HCWs, 139 (47.9%) returned completed questionnaires. Most HCWs (87/139, 64.9%) reported providing immunization information verbally to parents; 51/87 (58.6%) spent fewer than five minutes doing so. Pediatricians provided vaccines based on the parents' best interest, whereas public health nurses and midwives emphasized government policy. Nurses had greater hesitancy related to personal perceptions and social/peer factors than pediatricians (p &lt; 0.001). Nurses were significantly more likely than pediatricians to suggest that children receive more shots than necessary (p &lt; 0.01). Nurses tended to have more negative attitudes toward vaccination and little awareness of immunization promotion compared to pediatricians. Thus, all HCWs involved in childhood immunization should receive sufficient information to provide timely and appropriate immunization to infants and children.

    DOI: 10.3390/vaccines10071055

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  • Time Course of Conical Teeth in Anhidrotic Ectodermal Dysplasia with Immunodeficiency. 国際誌

    Yuta Aizawa, Chihaya Imai, Akihiko Saitoh

    Journal of clinical immunology   42 ( 6 )   1168 - 1170   2022年6月

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  • Household Secondary Transmission of the Severe Acute Respiratory Syndrome Coronavirus 2 Alpha Variant From a Community Cluster in a Nursery in Japan. 国際誌

    Tatsuki Ikuse, Yuta Aizawa, Yugo Shobukawa, Nobuko Tomiyama, Hitoshi Nakayama, Masako Takahashi, Kensuke Muto, Satoshi Hasegawa, Masashi Takahashi, Miyako Kon, Tsutomu Tamura, Haruki Matsumoto, Reiko Saito, Akihiko Saitoh

    The Pediatric infectious disease journal   41 ( 9 )   e358-e364   2022年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Spread of variants of concerns (VOCs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an increase in children with coronavirus disease 2019 (COVID-19). In February 2021, clusters of the Alpha variant of SARS-CoV-2 started to be reported in Niigata, Japan, including a large nursery cluster. We investigated the transmission routes and household secondary attack rates (SARs) in this cluster. METHODS: Epidemiologic data related to a nursery cluster in Niigata, Japan, particularly child-origin and adult-origin SARs, were analyzed. VOCs were confirmed by whole-genome sequencing of virus from patients. RESULTS: In total, 42 persons (22 children and 20 adults) in the cluster were infected with the Alpha variant. In the nursery, 13 of 81 children (16.0%) and 4 of 24 teachers (16.7%) were infected. SARS-CoV-2 later spread to 25 persons (10 children and 15 adults) outside the nursery. Child-origin and adult-origin household SARs were 27.7% (13/47) and 47.0% (8/17) (P = 0.11), respectively, which were higher than rates attributable to non-VOCs in previous studies. CONCLUSIONS: As compared with non-VOCs, the Alpha variant of SARS-CoV-2 exhibited high transmissibility among children and adults and may pose a high risk for household secondary transmission from SARS-CoV-2-infected children. Increased transmissibility of current or future VOCs could lead to greater transmission from children to adults or other children.

    DOI: 10.1097/INF.0000000000003607

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  • Molecular Evolution and Epidemiology of Parechovirus-A3 in Japan, 1997-2019. 国際誌

    Yuta Aizawa, Takuhiro Kasamatsu, Koo Nagasawa, Kanako Watanabe, Akihiko Saitoh

    The Journal of infectious diseases   227 ( 2 )   288 - 294   2022年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Parechovirus-A3 (PeV-A3), first reported in 2004 in Japan, is an emerging pathogen that causes sepsis and meningoencephalitis in neonates and young infants. Although PeV-A3 has been identified worldwide, its epidemiological characteristics differ by region. To investigate the molecular evolution and epidemiology of PeV-A3, we performed genetic analyses of 131 PeV-A3 strains from the years 1997-2019 in Niigata, Japan. During 2016-2019, annual numbers remained steady, in contrast to the PeV-A3 epidemic interval of every 2-3 years that was observed in Japan from 2006. Bayesian evolutionary analysis of the complete viral protein 1 region revealed alternate dominant clusters during years of PeV-A3 epidemics. The branch including the oldest and first isolated PeV-A3 strains in Japan has been disrupted since 2001. The year of PeV-A3 emergence was estimated to be 1991. Continuous surveillance with genetic analyses of different regions will improve understanding of PeV-A3 epidemiology worldwide.

    DOI: 10.1093/infdis/jiac213

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  • Short Stature as an Initial Presenting Presentation of Unicentric Castleman Disease in a Child: A Case Report With Long-Term Follow-Up and a Literature Review. 国際誌

    Kaori Sonoda, Utako Kaneko, Makoto Hiura, Yoshiaki Kinoshita, Hajime Umezu, Shuichi Ito, Akihiko Saitoh, Chihaya Imai

    Modern rheumatology case reports   7 ( 1 )   261 - 266   2022年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Short stature is a common clinical condition in pediatric outpatient clinics and is associated with various clinical conditions, ranging from normal variants to severe diseases. Short stature is known to be caused by chronic inflammatory conditions, in which over-produced inflammatory cytokines are reported to be involved in growth suppression. Castleman disease is a rare lymphoproliferative disorder known as a chronic inflammatory disease with overproduction of interleukin 6 (IL-6), which often causes systemic symptoms such as fever, fatigue, weight loss, and night sweats. Here, we report the case of a ten-year-old female diagnosed with unicentric Castleman disease, who presented with short stature as the sole clinical sign but lacked typical systemic symptoms of Castleman disease. An elevated serum C-reactive protein level led us to suspect a chronic inflammatory condition, and we found an intra-abdominal tumor that was histopathologically confirmed as Castleman disease. The tumor removal resulted in a steady catch-up in her height in the six years following the surgery. We also present a brief review of relevant literature on pediatric cases of Castleman disease associated with growth impairment. Clinicians should be aware that chronic inflammatory conditions can cause growth impairment, which may be a key clinical manifestation of such conditions.

    DOI: 10.1093/mrcr/rxac034

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  • Loss of GBA in zebrafish leads to dopaminergic neurodegeneration, but overexpression of α-synuclein does not further worsen degeneration. 国際誌

    Kazuki Kodera, Noriko Matsui, Akihiko Saitoh, Hideaki Matsui

    Neuroreport   33 ( 7 )   320 - 325   2022年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: Parkinson's disease is a neurodegenerative disorder that causes motor and nonmotor symptoms due to the loss of dopaminergic nerves and is characterized by the presence of Lewy bodies, which are mainly composed of α-synuclein. Glucosylceramidase beta (GBA), which is a causative gene of autosomal recessive Gaucher disease, is also known to be a risk gene for Parkinson's disease. In this study, we tried to detect synergistic effects of α-synuclein accumulation and gba depletion on dopaminergic neurodegeneration in zebrafish. METHODS: We generated a transgenic line of zebrafish overexpressing the A53T α-synuclein and gba mutant fish, and analyzed pathologies of α-synuclein aggregation and neurodegeneration. RESULTS: Zebrafish overexpressing the A53T α-synuclein did not exhibit α-synuclein aggregate formation. After the loss of gba function in this mutant α-synuclein transgenic line, we observed the marked presence of α-synuclein aggregates. Loss of gba function in zebrafish resulted in dopaminergic and noradrenergic neurodegeneration but this level of neurodegeneration was not exacerbated by overexpression of mutant α-synuclein. CONCLUSIONS: These results indicate that loss of gba function was sufficient to generate a neurodegenerative phenotype in zebrafish regardless of the expression of α-synuclein.

    DOI: 10.1097/WNR.0000000000001788

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  • High rates of vaccine hesitancy among pregnant women during the coronavirus disease 2019 (COVID-19) pandemic in Japan. 国際誌

    Aya Saitoh, Mayumi Takaku, Akihiko Saitoh

    Human vaccines & immunotherapeutics   18 ( 5 )   1 - 7   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This study aimed to 1) determine the prevalence and contents of vaccine hesitancy among pregnant women during the coronavirus disease 2019 (COVID-19) pandemic and 2) evaluate its association with maternal sociodemographic factors. A cross-sectional survey was conducted between August and December 2020 among pregnant women between 28 and 32 weeks of gestation who received antenatal care at four clinics and hospitals in Niigata City, Japan. Vaccine hesitancy was assessed using the Parent Attitudes about Childhood Vaccines survey, and associations between vaccine hesitancy and sociodemographic factors were analyzed. In total, 113/200 (56.5%) subjects responded to the survey. Overall, 46/113 (40.7%) pregnant women were resistant or hesitant to receive the vaccine. Women with vaccine hesitancy were more likely to fear adverse reactions (concern 79.6%, not concerned 15.9%, and not sure 4.4%), safety (concerned 69.0%, not concerned 23.9%, and not sure 7.1%), and efficacy (concerned 47.8%, not concerned 35.4%, and not sure 16.8%) compared to those without vaccine hesitancy (P < .01, < .01, and <.01, respectively). In the multivariate logistic regression analyses, primipara women had higher rates of vaccine hesitancy than multipara pregnant women (odds ratio: 2.38, P = .04). In conclusion, the prevalence of vaccine hesitancy among pregnant Japanese women, especially primipara women, was higher than that in other countries during the COVID-19 pandemic. Their major concerns were adverse reactions, safety, and the efficacy of childhood vaccines. Further strategies are needed to provide appropriate vaccine information to prevent vaccine-preventable diseases in both infants and children.

    DOI: 10.1080/21645515.2022.2064686

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  • Clinical manifestations and outcome of viral acute lower respiratory infection in hospitalised children in Myanmar. 国際誌

    Kazuhiro Kamata, Khin Nyo Thein, Lasham Di Ja, Nay Chi Win, Su Mon Kyaw Win, Yuko Suzuki, Ai Ito, Hidekazu Osada, Irina Chon, Wint Wint Phyu, Yuta Aizawa, Tatsuki Ikuse, Tomomi Ota, Yadanar Kyaw, Htay Htay Tin, Yugo Shobugawa, Hisami Watanabe, Reiko Saito, Akihiko Saitoh

    BMC infectious diseases   22 ( 1 )   350 - 350   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Acute lower respiratory infection (ALRI) remains the leading cause of death in children worldwide, and viruses have been the major cause of ALRI. In Myanmar, ALRI is associated with high morbidity and mortality in children, and detailed information on ALRI is currently lacking. METHODS: This prospective study investigated the viral aetiologies, clinical manifestations, and outcomes of ALRI in hospitalised children aged 1 month to 12 years at the Yankin Children Hospital, Yangon, Myanmar from May 2017 to April 2019. The sample size was set to 300 patients for each year. Two nasopharyngeal swabs were obtained for the patients with suspected viral ALRI; one for rapid tests for influenza and respiratory syncytial virus (RSV), and the other for real-time PCR for the 16 ALRI-causing viruses. Pneumococcal colonization rates were also investigated using real-time PCR. Clinical information was extracted from the medical records, and enrolled patients were categorised by age and severity for comparison. RESULTS: Among the 5463 patients admitted with a diagnosis of ALRI, 570 (10.4%) were enrolled in this study. The median age of the patients was 8 months (interquartile range, 4-15 months). The most common symptoms were cough (93%) and difficulty in breathing (73%), while the most common signs of ALRI were tachypnoea (78%) and chest indrawing (67%). A total of 16 viruses were detected in 502 of 570 patients' samples (88%), with RSV B (36%) and rhinovirus (28%) being the most commonly detected. Multiple viruses were detected in 221 of 570 samples (37%) collected from 570 patients. Severe ALRI was diagnosed in 107 of 570 patients (19%), and RSV B and human rhinovirus were commonly detected. The mortality rate was 5%; influenza virus A (29%) and RSV B (21%) were commonly detected, and stunting and lack of immunization were frequently observed in such cases. Additionally, 45% (259/570) of the patients had pneumococcal colonization. CONCLUSIONS: Viral ALRI in hospitalised children with a median of 8 months has significant morbidity and mortality rates in Myanmar. RSV and rhinovirus were the most commonly detected from nasopharyngeal swabs, while influenza virus and RSV were the most frequently associated with fatal cases.

    DOI: 10.1186/s12879-022-07342-1

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  • Introduction of the Japanese Society for Pediatric Infectious Diseases. 国際誌

    Akihiko Saitoh, Kazunobu Ouchi, Hiroyuki Moriuchi

    The Pediatric infectious disease journal   41 ( 4 )   e110-e112   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The Pediatric Infectious Disease Journal became an official English journal of the Japanese Society for Pediatric Infectious Diseases starting from 2022. Japanese Society for Pediatric Infectious Diseases, with a history of more than 50 years and more than 3200 members in Japan, would like to contribute to the enhancement of child health and well-being in the field of pediatric infectious diseases by collaborating academic societies and organizations worldwide through the Pediatric Infectious Disease Journal.

    DOI: 10.1097/INF.0000000000003456

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  • Changes in Exanthema Subitum Incidence and Patient Age Distribution During the COVID-19 Pandemic in Japan. 国際誌

    Jun Tachikawa, Yuta Aizawa, Tatsuki Ikuse, Miyako Kon, Akihiko Saitoh

    The Pediatric infectious disease journal   41 ( 3 )   e90-e92   2022年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Incidences of community-acquired infectious diseases other than COVID-19 decreased during the coronavirus disease 2019 pandemic; however, exanthema subitum incidence before (2016-2019) and during the pandemic (2020) in Niigata, Japan, did not substantially differ, although the proportion of age less than 1-year-old was lower in 2020. These findings suggest that exanthema subitum is transmitted mainly among family members, not in the community.

    DOI: 10.1097/INF.0000000000003430

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  • Diagnosis of Chromosome 15q-Terminal Deletion Syndrome through Elevated Fasting Serum Growth Hormone Levels

    Masato Ono, Masato Tanaka, Shota Hiroshima, Kentaro Sawano, Yohei Ogawa, Keisuke Nagasaki, Akihiko Saitoh

    Endocrines   2022年2月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/endocrines3010008

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  • Association Between Real-time Polymerase Chain Reaction Cycle Threshold Value and Clinical Severity in Neonates and Infants Infected With Bordetella pertussis. 国際誌

    Do Thi Thuy Nga, Phung Thi Bich Thuy, Akira Ainai, Ikuyo Takayama, Do Thu Huong, Aya Saitoh, Satoshi Nakagawa, Tran Minh Dien, Noriko Nakajima, Akihiko Saitoh

    The Pediatric infectious disease journal   41 ( 5 )   388 - 393   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Polymerase chain reaction (PCR) is highly sensitive and is thus the standard method for diagnosing pertussis. Real-time PCR is widely used because of its accuracy and the simplicity of the simultaneous cycle threshold (Ct) value, which represents the copy numbers of the target gene. Little is known of the association of Ct value with pertussis severity in neonates and infants. METHODS: This study determined Ct values in neonates and infants diagnosed with pertussis by real-time PCR using nasopharyngeal samples at Vietnam National Children's Hospital in Hanoi in 2017 and 2019. The association of disease severity and clinical parameters were analyzed using univariate and multivariate analyses. RESULTS: We evaluated 108 patients with pertussis [median age: 63 days, interquartile range (IQR): 41-92 days]. Only 6/108 (6%) received at least 1 dose of a pertussis-containing vaccine. Among them, 24 (22.2%) had severe disease requiring care in a pediatric intensive care unit, 16 (13.8%) required mechanical ventilation, and 3 (2.6%) died. The median Ct value was lower in patients with severe disease (19.0, IQR: 16.5-22.0, n = 24) than in those without severe disease (25.5, IQR: 20.0-30.0, n = 84) (P = 0.002). Logistic regression analyses demonstrated that PCR Ct value [odds ratio (OR): 1.783, 95% confidence interval (CI): 1.013-3.138, P = 0.045], age (OR: 3.118, 95% CI: 1.643-5.920, P = 0.001), and white blood cell counts (OR: 0.446, 95% CI: 0.261-0.763, P = 0.003) remained significantly associated with severe disease. CONCLUSIONS: Real-time PCR Ct values for pertussis might be useful as a predictor of severe disease in neonates and infants.

    DOI: 10.1097/INF.0000000000003471

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  • Decline in pediatric admission on an isolated island in the COVID-19 pandemic. 国際誌

    Takuya Fuse, Tatsuki Ikuse, Yuta Aizawa, Michiko Fuse, Fumihiro Goto, Minoru Okazaki, Atsushi Iwaya, Akihiko Saitoh

    Pediatrics international : official journal of the Japan Pediatric Society   64 ( 1 )   e15326   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: A decrease in pediatric hospitalizations during the COVID-19 pandemic has been reported worldwide; however, few studies have examined areas with a limited number of COVID-19 cases, where influenced by viral interference by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is minimum. METHODS: We conducted an epidemiological study of pediatric hospitalizations on Sado, an isolated island in Niigata, Japan, that was unique environment with few COVID-19 cases and reliable pediatric admissions monitoring. We compared numbers of monthly hospitalizations and associated diagnoses for the periods April 2016 to March 2020 (pre-pandemic period) and April 2020 to March 2021 (pandemic period). RESULTS: Data were analyzed for 1,144 and 128 patients in the pre-pandemic and pandemic periods, respectively. We observed only three adults and no pediatric COVID-19 cases during the pandemic period. The number of monthly admissions was significantly lower in the pandemic period (median [interquartile ranges (IQR)]: 11.0 [7.0-14.0]) than in the pre-pandemic period (23.0 [20.8-28.3]; P < 0.001). Similar decreases were observed for hospitalizations due to respiratory tract infection (P < 0.01), but not for asthma exacerbation (P = 0.15), and gastrointestinal tract infection (P = 0.33). CONCLUSIONS: Pediatric hospitalizations during the pandemic significantly decreased on an isolated Japanese island where COVID-19 was not endemic and all pediatric admissions were ascertainable. This observation highlights the impact of decreased travel and increased awareness of infection control measures on pediatric hospitalizations due to infectious diseases, not by the SARS-CoV-2 viral interference.

    DOI: 10.1111/ped.15326

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  • Resolution of Pediococcus acidilactici bacteremia without antibiotic therapy in a 16-year-old adolescent with leukemia receiving maintenance chemotherapy. 国際誌

    Jun Tachikawa, Yuta Aizawa, Ryohei Izumita, Chansu Shin, Chihaya Imai, Akihiko Saitoh

    IDCases   27   e01384   2022年

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    記述言語:英語  

    Pediococcus spp. have been reported to cause infections in patients with underlying conditions. However, the pathogenicity of this bacteria is unclear. Herein, we describe the first case of Pediococcus acidilactici bacteremia, which occurred in a 16-year-old male with dasatinib-induced hemorrhagic colitis during maintenance therapy for leukemia and resolved without antibiotic treatment. P. acidilactici bacteremia might be self-limiting, even in immunocompromised patients receiving chemotherapy.

    DOI: 10.1016/j.idcr.2022.e01384

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  • Drug-induced panniculitis in a child with acute lymphoblastic leukemia. 国際誌

    Haruko Iwabuchi, Takayuki Takachi, Nobuhiro Kubo, Masaru Imamura, Hajime Umezu, Akihiko Saitoh, Chihaya Imai

    Pediatric blood & cancer   69 ( 5 )   e29501   2021年12月

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    記述言語:英語  

    DOI: 10.1002/pbc.29501

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  • Effectiveness of 4-1BB-costimulated HER2-targeted chimeric antigen receptor T cell therapy for synovial sarcoma. 国際誌

    Yudai Murayama, Hiroyuki Kawashima, Nobuhiro Kubo, Chansu Shin, Yasushi Kasahara, Masaru Imamura, Naoki Oike, Takashi Ariizumi, Akihiko Saitoh, Keichiro Mihara, Hajime Umezu, Akira Ogose, Chihaya Imai

    Translational oncology   14 ( 12 )   101227 - 101227   2021年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Synovial sarcoma is a rare malignant soft-tissue tumor that is prevalent in adolescents and young adults, and poor prognosis has been reported in patients with metastatic lesions. Chimeric antigen receptor (CAR) T-cell therapy is an emerging novel therapy for solid tumors; however, its application in synovial sarcoma has not yet been explored. METHODS: A novel human epidermal growth factor receptor 2 (HER2)-targeted CAR containing scFv-FRP5, CD8α hinge and transmembrane domains as well as 4-1BB costimulatory and CD3ζ signaling domains was developed. Three synovial sarcoma cell lines that expressed the fusion transcript SS18-SSX1/2/4 were used in the study. Cytokine secretion assay, cytotoxicity assay, and real-time cell analysis experiments were conducted to confirm the function of T cells transduced with the CAR gene. RESULTS: High cell-surface expression of HER2 was observed in all the cell lines. HER2-targeted/4-1BB-costimulated CAR T cells specifically recognized the synovial sarcoma cells, secreted interferon gamma and tumor necrosis factor alpha, and exerted cytotoxic effects in these cells. CONCLUSION: To the best of our knowledge, this is the first study to indicate that HER2-targeted CAR T cells are directly effective against molecularly defined synovial sarcoma cells. Furthermore, our findings might set the basis for developing improved CAR T cell-based therapies for chemo-refractory or relapsed synovial sarcoma.

    DOI: 10.1016/j.tranon.2021.101227

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  • 抗菌薬を使用せずに消失した白血病維持療法中のPediococcus acidilactici菌血症の1例

    太刀川 潤, 相澤 悠太, 泉田 亮平, 申 将守, 今井 千速, 齋藤 昭彦

    日本小児感染症学会総会・学術集会プログラム・抄録集   53回   187 - 187   2021年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児感染症学会  

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  • Coronavirus Disease 2019 Cluster Originating in a Primary School Teachers' Room in Japan. 国際誌

    Yuta Aizawa, Yugo Shobugawa, Nobuko Tomiyama, Hitoshi Nakayama, Masako Takahashi, Junko Yanagiya, Noriko Kaji, Tatsuki Ikuse, Ryohei Izumita, Takayuki Yamanaka, Satoshi Hasegawa, Tsutomu Tamura, Reiko Saito, Akihiko Saitoh

    The Pediatric infectious disease journal   40 ( 11 )   e418-e423   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: School closures are a subject of debate during the present coronavirus disease 2019 (COVID-19) pandemic. Because children are not the main driver of COVID-19 transmission in the community, school education must be prioritized in conjunction with appropriate infection prevention and control measures, as determined by local COVID-19 incidence. METHODS: We investigated the causes and transmission routes of a primary school cluster of COVID-19 that occurred during November and December 2020 in Niigata, Japan. RESULTS: In the cluster, the virus spread among teachers, then from teachers to students, and then to their family members. This primary school cluster comprised 26 infected patients and included teachers (13/33, 39%), students (9/211, 4%), and family members (4/65, 6%). The secondary attack rate from the 3 index teachers to the remaining 30 teachers was 33%; however, the rate to students was only 4%. Factors contributing to cluster formation include the fact that 2 of the index teachers continued working while symptomatic and that the environment and infection prevention measures in the teachers' room were inadequate. CONCLUSIONS: To open schools safely and without interruption, adequate measures to prevent COVID-19 infection in schools should be emphasized not only for children but also for teachers and their environment.

    DOI: 10.1097/INF.0000000000003292

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  • Soluble LR11 as a Novel Biomarker in Acute Kawasaki Disease

    Kenichi Watanabe, Hiroshi Suzuki, Meizi Jiang, Shinya Tsukano, Satoshi Kataoka, Sueshi Ito, Takatsugu Sakai, Toru Hirokawa, Hisanori Haniu, Fujito Numano, Satoshi Hoshina, Satoshi Hasegawa, Masamichi Matsunaga, Kousei Chiba, Naka Saito, Hiroshi Yoshida, Satoru Takami, Soichiro Okubo, Harunobu Hirano, Akihiko Saitoh, Hideaki Bujo

    Circulation Journal   86 ( 6 )   977 - 983   2021年9月

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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:Japanese Circulation Society  

    BACKGROUND: Intimal smooth muscle cells (SMCs) play an important role in the vasculitis caused by Kawasaki disease (KD). Lipoprotein receptor 11 (LR11) is a member of the low-density lipoprotein receptor family, which is expressed markedly in intimal vascular SMCs and secreted in a soluble form (sLR11). sLR11 has been recently identified as a potential vascular lesion biomarker. sLR11 is reportedly elevated in patients with coronary artery lesions long after KD, but there is no description of sLR11 in acute KD. Our aim was to determine the sLR11 dynamics in acute KD and to assess its usefulness as a biomarker.Methods and Results: 106 acute KD patients and 18 age-matched afebrile controls were enrolled. KD patients were classified into the following subgroups: intravenous immunoglobulin (IVIG) responders (n=85) and non-responders (n=21). Serum sLR11 levels before IVIG therapy were higher in non-responders (median, 19.6 ng/mL; interquartile range [IQR], 13.0-24.9 ng/mL) than in controls (11.9 ng/mL, 10.4-14.9 ng/mL, P<0.01) or responders (14.3 ng/mL, 11.7-16.5 ng/mL, P<0.01). Using a cutoff of >17.5 ng/mL, non-responders to initial IVIG therapy were identified with 66.7% sensitivity and 78.8% specificity. CONCLUSIONS: sLR11 can reflect the state of acute KD and might be a biomarker for patient response to IVIG therapy.

    DOI: 10.1253/circj.cj-20-1271

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  • A case of adolescent trichorhinophalangeal syndrome undergoing pelvic osteotomy for bilateral acetabular dysplasia.

    Kentaro Sawano, Hiromi Nyuzuki, Keisuke Nagasaki, Hayato Suzuki, Ken Suda, Dai Miyasaka, Norio Imai, Akihiko Saitoh

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   2021年9月

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  • Development of Novel PCR Assays for Improved Detection of Enterovirus D68. 国際誌

    Tatsuki Ikuse, Yuta Aizawa, Hayato Takihara, Shujiro Okuda, Kanako Watanabe, Akihiko Saitoh

    Journal of clinical microbiology   59 ( 11 )   JCM0115121   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Enterovirus D68 (EV-D68) causes a range of clinical manifestations, including asthma-like illness, severe respiratory disease, and acute flaccid myelitis. EV-D68 has caused worldwide outbreaks since 2014 and is now recognized as a re-emerging infection in many countries. EV-D68-specific PCR assays are widely used for the diagnosis of EV-D68 infection; however, assay sensitivity is a concern because of genetic changes in recently circulated EV-D68. To address this, we summarized EV-D68 sequences from previously reported world outbreaks from 2014 through 2020 on GenBank, and found several mutations at the primer and probe binding sites of the existing EV-D68-specific PCR assays. Subsequently, we designed two novel assays corresponding to the recently reported EV-D68 sequences: an EV-D68-specific real-time and semi-nested PCR. In an analysis of 22 EV-D68-confirmed cases during a recent EV-D68 outbreak in Japan, the new real-time PCR had higher sensitivity than the existing assay (100% vs. 45%, P < 0.01) and a lower median Ct value (27.8 vs. 32.8, P = 0.005). Sensitivity was higher for the new non-nested PCR (91%) than for the existing semi-nested PCR assay (50%, P < 0.01). The specificity of the new real-time PCR was 100% using samples from non-EV-D68-infected cases (n = 135). In conclusion, our novel assays had higher sensitivity than the existing assay and might lead to more accurate diagnosis of recently circulating EV-D68. To prepare for future EV-D68 outbreaks, EV-D68-specific assays must be continuously monitored and updated.

    DOI: 10.1128/JCM.01151-21

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  • The clinical characteristics of pediatric coronavirus disease 2019 in 2020 in Japan 国際誌

    Tomohiro Katsuta, Naoki Shimizu, Kenji Okada, Keiko Tanaka‐Taya, Takashi Nakano, Hajime Kamiya, Kiyoko Amo, Naruhiko Ishiwada, Satoshi Iwata, Makoto Oshiro, Nobuhiko Okabe, Ryutaro Kira, Seigo Korematsu, Shigeru Suga, Takeshi Tsugawa, Naoko Nishimura, Haruka Hishiki, Masashi Fujioka, Mitsuaki Hosoya, Yumi Mizuno, Mahito Mine, Isao Miyairi, Chiaki Miyazaki, Ichiro Morioka, Tsuneo Morishima, Tetsushi Yoshikawa, Taizo Wada, Hiroshi Azuma, Koichi Kusuhara, Kazunobu Ouchi, Akihiko Saitoh, Hiroyuki Moriuchi

    Pediatrics International   64 ( 1 )   e14912   2021年7月

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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  

    BACKGROUND: The COVID-19 pandemic has affected the lives of people of all ages. Most reports on pediatric cases suggest that children experience fewer and milder symptoms than do adults. This is the first nationwide study in Japan focusing on pediatric cases reported by pediatricians, including cases with no or mild symptoms. METHODS: We analyzed the epidemiological and clinical characteristics and transmission patterns of 840 pediatric (<16 years old) COVID-19 cases reported between February and December 2020 in Japan, using a dedicated database which was maintained voluntarily by members of the Japan Pediatric Society. RESULTS: Almost half of the patients (47.7%) were asymptomatic, while most of the others presented mild symptoms. At the time of admission or first outpatient clinic visit, 84.0% of the cases were afebrile (<37.5°C). In total, 609 cases (72.5%) were exposed to COVID-19-positive household members. We analyzed the influence of nationwide school closures that were introduced in March 2020 on COVID-19 transmission routes among children in Japan. Transmission within households occurred most frequently, with no significant difference between the periods before and after declaring nationwide school closures (70.9% and 74.5%, respectively). CONCLUSIONS: COVID-19 symptoms in children are less severe than those in adults. School closure appeared to have a limited effect on transmission. Controlling household transmission from adult family members is the most important measure for prevention of COVID-19 among children.

    DOI: 10.1111/ped.14912

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  • Changes in childhood vaccination during the coronavirus disease 2019 pandemic in Japan. 国際誌

    Yuta Aizawa, Tomohiro Katsuta, Hiroshi Sakiyama, Keiko Tanaka-Taya, Hiroyuki Moriuchi, Akihiko Saitoh

    Vaccine   39 ( 29 )   4006 - 4012   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has greatly affected daily life. COVID-19 often causes asymptomatic or mild disease in children; however, delayed routine childhood immunization is a concern, as it could increase the risk of vaccine-preventable disease. No study has evaluated the status of childhood vaccinations in Japan during the COVID-19 pandemic. METHODS: This retrospective observational study evaluated the number of vaccine doses administered to children in 4 Japanese cities (2 cities in the Tokyo metropolitan area and 2 cities far from Tokyo) during the period from 2016 to 2020. Vaccine doses administered between January and September 2020 during the COVID-19 pandemic were compared, by month, with those given during 2016-2019. Age-stratified demographic data were collected to determine whether factors other than change in the child population over time affected vaccination trends. RESULTS: In all cities the decrease in vaccine doses administered was most apparent in March and April 2020, i.e., just before or coincident with the declaration of a nationwide COVID-19 emergency on April 7, 2020. The decrease started as early as February in the Tokyo metropolitan area. As child age increased, the decrease became more apparent. Before the lift of national emergency on May 25, catch-up of the vaccination was observed in all age groups in all cities. Vaccine doses persistently increased in older age groups but not in infants. The overall vaccination trends did not differ significantly among the 4 cities. CONCLUSIONS: The COVID-19 pandemic significantly affected routine childhood immunization in Japan. Thus, a nationwide electronic surveillance system and announcements for guardians to encourage timely routine immunization are warranted.

    DOI: 10.1016/j.vaccine.2021.05.050

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  • Changes and remaining challenges for the Japanese immunization program: Closing the vaccine gap. 国際誌

    Akihiko Saitoh, Nobuhiko Okabe

    Vaccine   39 ( 22 )   3018 - 3024   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The Japanese immunization program has made considerable progress since 2009: several new vaccines have been introduced and most are included in the National Immunization Program (NIP). In October 2020, the Japanese law on immunization was revised, which resulted in a few laudable achievements. First, rotavirus vaccines were added to the NIP, 10 years after their introduction, and noteworthy studies of vaccine effectiveness and the incidence of intussusception in Japanese children were published. Second, rules on vaccine intervals-which had been a longstanding concern-were withdrawn. In addition to this revision of the law, the Japanese version of the Vaccine Information Statement (VIS) was released by the Japan Pediatric Society in 2018. The VIS provides useful caregiver information on general immunization concepts and individual vaccines. Further challenges for the Japanese immunization program include (1) administering a booster dose of pertussis-containing vaccine to preschool children or teenagers, (2) reestablishing the active recommendation for human papilloma virus vaccines, (3) adding the mumps and influenza vaccines to the NIP, and (4) ensuring optimal dosing of seasonal influenza vaccines. During the current coronavirus disease 2019 (COVID-19) pandemic, vaccination rates among children have been decreasing in many countries. In Japan, vaccination rates have been stable in infants, but declining among toddlers and school-aged children, despite public awareness of the need for timely administration of vaccines during the pandemic. Clearly, further action is needed if we are to adequately protect children living in Japan from vaccine-preventable diseases.

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  • 新規のエンテロウイルスD68特異的PCR法の開発 今後の世界的流行に備えて

    幾瀬 樹, 相澤 悠太, 渡邉 香奈子, 齋藤 昭彦

    臨床とウイルス   49 ( 2 )   S85 - S85   2021年5月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • 新潟県における23年間のパレコウイルスA3の分子進化疫学

    相澤 悠太, 渡邉 香奈子, 齋藤 昭彦

    臨床とウイルス   49 ( 2 )   S84 - S84   2021年5月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • 肢端紅痛症で発症し、無症候性後天性フォンウィルブランド症候群を合併した本態性血小板血症の小児例

    村山 ゆり恵, 田屋 光将, 申 将守, 馬場 みのり, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    小児科臨床   74 ( 5 )   553 - 558   2021年5月

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    記述言語:日本語   出版者・発行元:(株)日本小児医事出版社  

    症例は12歳男児。両側の手指、足趾、手掌の肢端紅痛症で発症し、99.7万/μLの血小板増多を認め、骨髄所見やJAK2変異陽性から、本態性血小板血症(essential thrombocythemia;ET)と診断した。肢端紅痛症に対し少量アスピリン投与を開始したところ、症状は速やかに消失した。アスピリン投与開始後、血小板数は140万/μLへと増加傾向を示したため、後天性フォンウィルブランド症候群の検索を行い、合併が判明した。ガイドラインではアスピリンは原則禁忌となり細胞減少療法の適応となるが、本症例では出血症状は皆無であり、年齢や殺細胞薬使用に伴う白血病転化リスクを考慮した結果、アスピリン療法単独を継続し、6年経過した現在まで安全に管理できている。小児ETは非常に稀な疾患であり、治療アルゴリズムは確立していない。小児期特有の問題を加味した診療指針が作成されることが望まれる。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00643&link_issn=&doc_id=20210427420011&doc_link_id=%2Fag1snrsd%2F2021%2F007405%2F012%2F0553-0558%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2021%2F007405%2F012%2F0553-0558%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Clinically Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion Associated with Rhinovirus. 国際誌

    Noriko Soma, Yuta Aizawa, Masamichi Matsunaga, Akihiko Saitoh

    The Pediatric infectious disease journal   40 ( 3 )   e122-e125   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 2-year-old girl with fever and seizures was diagnosed as having clinically mild encephalitis/encephalopathy with a reversible splenial lesion, as indicated by magnetic resonance imaging. Virologic analysis identified human rhinovirus A49 in her serum. Although human rhinovirus rarely involves the central nervous system, such involvement could result in mild encephalitis/encephalopathy with a reversible splenial lesion.

    DOI: 10.1097/INF.0000000000002995

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  • Acute heart failure due to dilated cardiomyopathy exacerbated by systemic parechovirus A1 infection in an infant. 国際誌

    Shun Maki, Yuta Aizawa, Yuki Ito, Masashi Suda, Akihiko Saitoh

    International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases   104   273 - 275   2021年3月

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    記述言語:英語  

    Parechovirus A1 (PeV-A1) often causes mild respiratory or gastrointestinal disease. Herein we report a case of acute heart failure due to dilated cardiomyopathy exacerbated by acute PeV-A1 infection in a 10-month-old infant. He was brought to our hospital with acute respiratory distress and compensated shock. Echocardiogram showed a dilated left ventricle and severe mitral regurgitation, consistent with dilated cardiomyopathy. PeV-A1 infection was confirmed by (1) positive PCR test results for PeV-A in multiple anatomical sites, including blood, stool, and throat, (2) the genetic sequence of viral protein, and (3) an increase in paired serum PeV-A1-specific neutralizing antibody titers. A few, scattered case reports in infants and young children also indicate the association between myocarditis and/or dilated cardiomyopathy and PeV-A1 infection. In conclusion, PeV-A1 infection could be associated with exacerbation of myocardial diseases in infants and young children; thus PeV-A1 needs to be evaluated as a viral cause of such a condition.

    DOI: 10.1016/j.ijid.2021.01.021

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  • 早期乳児の発熱に対する網羅的ウイルス診断

    相澤 悠太, 山中 崇之, 塚野 真也, 鈴木 博, 齋藤 昭彦

    日本小児科学会雑誌   125 ( 2 )   286 - 286   2021年2月

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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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  • PCR detection rates for serum and cerebrospinal fluid from neonates and young infants infected with human parechovirus 3 and enteroviruses. 国際誌

    Yuko Suzuki, Yuta Aizawa, Ryohei Izumita, Rie Habuka, Kanako Watanabe, Akihiko Saitoh

    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology   135   104736 - 104736   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Human parechovirus 3 (HPeV-3) and enteroviruses (EV) are commonly detected viruses in febrile neonates and young infants and are usually diagnosed by PCR. However, in this population, data on detection rates for samples from different anatomical sites are limited. OBJECTIVES: To determine PCR detection rates for HPeV-3 and EVs in serum and cerebrospinal fluid (CSF) samples from febrile neonates and young infants. STUDY DESIGN: This prospective study identified viruses in serum and CSF samples collected from febrile neonates and young infants (age <4 months) in Niigata, Japan, during 2014-2018. HPeV-3 or EV infection was defined as a positive quantitative real-time PCR result for the virus in serum or CSF. Genotypes were identified by sequence analyses of the viral protein 1 region. RESULTS: Among 216 patients, we identified 56 HPeV-3-infected (26 %) and 48 EV-infected patients (22 %). All (56/56; 100 %) HPeV-3-infected patients had a positive PCR result for serum, and 49/56 (88 %) had a positive result for CSF. In EV-infected patients, 40/48 (83 %) were positive for serum, and 34/48 (71 %) were positive for CSF, and 22/48 (46 %) were positive for serum (n = 14) or CSF (n = 8). If only a CSF sample had been obtained, 7 (12 %) HPeV-3 infections and 14 (29 %) EV infections would have been undiagnosed. Detection rates in serum and CSF differed by genotype in EV-infected patients. CONCLUSIONS: Viral RNA detection rates differed between serum and CSF in HPeV-3- and EV-infected neonates/infants. Combined evaluation of serum and CSF samples is important for accurate viral diagnosis in this population.

    DOI: 10.1016/j.jcv.2021.104736

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  • Outbreak of Enterovirus D68 Among Children in Japan-Worldwide Circulation of Enterovirus D68 Clade B3 in 2018. 国際誌

    Tatsuki Ikuse, Yuta Aizawa, Takayuki Yamanaka, Rie Habuka, Kanako Watanabe, Taketo Otsuka, Akihiko Saitoh

    The Pediatric infectious disease journal   40 ( 1 )   6 - 10   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Enterovirus D68 (EV-D68) causes asthma-like respiratory infection in children. Several EV-D68 outbreaks have been reported worldwide since the largest outbreak occurred in the United States in 2014. We experienced an accumulation of pediatric cases with asthma-like respiratory illness in Niigata, Japan, in 2018. STUDY DESIGN: To determine whether EV-D68 was responsible for the case accumulation, this prospective observational study evaluated children hospitalized in 1 of 8 hospitals with asthma-like respiratory illness in Niigata, Japan, during October and November 2018. Diagnoses were made by EV-D68-specific RT-PCR using nasopharyngeal samples. The clade was identified by sequence analyses, and a phylogenetic tree was created. To evaluate seasonal variation, data from pediatric cases with asthma-like respiratory illness in 2018 were retrospectively analyzed. RESULTS: In 2018, 114 children were hospitalized with asthma-like respiratory illness in October and November, and 47 nasopharyngeal samples were collected. EV-D68 was detected in 22/47 (47%) patients during the study period. The phylogenetic tree revealed that all strains belonged to the clade B3 branch, which has been detected worldwide every 2 years since 2014. CONCLUSIONS: EV-D68 was the associated pathogen for asthma-like respiratory illness in children in Japan in 2018. Clade B3, the dominant clade in outbreaks worldwide, was responsible for the outbreak. Detection and detailed virologic analysis of EV-D68 is important as part of worldwide surveillance, as it will aid in understanding the epidemiologic characteristics of EV-D68 infection.

    DOI: 10.1097/INF.0000000000002889

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  • Case Report: Analysis of Preserved Umbilical Cord Clarified X-Linked Anhidrotic Ectodermal Dysplasia With Immunodeficiency in Deceased, Undiagnosed Uncles. 国際誌

    Satoshi Inaba, Yuta Aizawa, Yuki Miwa, Chihaya Imai, Hidenori Ohnishi, Hirokazu Kanegane, Akihiko Saitoh

    Frontiers in immunology   12   786164 - 786164   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Family history is one key in diagnosing inborn errors of immunity (IEI); however, disease status is difficult to determine in deceased relatives. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is one of the hyper IgM syndromes that is caused by a hypomorphic variant in the nuclear factor kappa beta essential modulator. We identified a novel IKBKG variant in a 7-month-old boy with pneumococcal rib osteomyelitis and later found that his mother has incontinentia pigmenti. Genetic analysis of preserved umbilical cords revealed the same variant in two of his deceased maternal uncles. Analysis of preserved umbilical cord tissue from deceased relatives can provide important information for diagnosing IEI in their descendants.

    DOI: 10.3389/fimmu.2021.786164

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  • 新生児・早期乳児におけるパレコウイルスA3感染症とエンテロウイルス感染症の臨床像の違いをどう説明するか? 自然免疫の観点から

    羽深 理恵, 相澤 悠太, 鈴木 優子, 渡邉 香奈子, 齋藤 昭彦

    臨床とウイルス   48 ( 5 )   308 - 316   2020年12月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

    パレコウイルスA3(parechovirus-A3、以下PeV-A3)とエンテロウイルス(enterovirus、以下EV)は、新生児・早期乳児に敗血症や髄膜炎をきたす代表的なウイルスである。PeV-A3感染症は、EV感染症とくらべ、重症感が強いが髄液細胞数の増多をみることは少ない。今回、これら臨床像の違いについて、血清と髄液のサイトカインを測定し、自然免疫の観点から検討した。PeV-A3患児16例、EV患児15例のサイトカインをMILLIPLEX MAP bead panelを用いて測定した。ウイルス量はリアルタイムPCR法で測定した。結果、血清サイトカインはPeV-A3患児で高値(P≦.011)、髄液ではEV患児で高値であった(P≦.036)。ウイルス量は、血清でPeV-A3患児で高値(P=.004)、髄液ではEV患児で高値であった(P=.02)。また、EV患児で髄液サイトカインと髄液細胞数に正の相関を認めた(r>.54、P<.05)。PeV-A3患児は、血清ウイルスゲノム量が多く、サイトカインが高いことが重症感に関与していると示唆された。PeV-A3患児とEV患児では、血清と髄液で異なる自然免疫反応が起こり、その異なる病態生理に寄与している可能性がある。(著者抄録)

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  • 小児の気管支喘息様発作とエンテロウイルスD68 2018年新潟県の流行から

    幾瀬 樹, 相澤 悠太, 山中 崇之, 渡邉 香奈子, 齋藤 昭彦

    臨床とウイルス   48 ( 5 )   301 - 307   2020年12月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

    エンテロウイルスD68(enterovirus(EV)-D68)は、気管支喘息様呼吸器疾患の原因ウイルスである。国外では2014年から周期的に流行し、国内では2015年に流行した。2018年9月に新潟県内で小児喘息様発作患者の報告が相つぎ、EV-D68の流行の有無について前方視的疫学調査を行った。同年10〜11月に新潟県内8施設に気管支喘息様呼吸器疾患で入院した小児患者(n=47)から鼻咽頭拭い液を採取した。EV-D68感染症の診断はviral protein 1(VP1)領域を標的とした特異的PCRを用い、陽性検体にはVP1領域のPCRで塩基配列を同定した。2014年以降に各国で流行した株とともに系統樹解析を行った。47検体のうち、22検体(47%)でEV-D68が陽性であった。系統樹解析では、すべての株がclade B3に分類され、2014年以降世界的に流行したものと同一であった。今回の小児喘息発作患者の急増において、EV-D68clade B3の流行を認めた。EV-D68 clade B3は国内外で周期的な流行を認めており、今後も継続的なサーベイランスが必要である。(著者抄録)

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  • Pott's puffy tumour: a rare and life-threatening disease. 国際誌

    Nahoko Ikoma, Yuta Aizawa, Takanobu Sasaki, Makoto Oishi, Naka Saito, Hiroshi Yoshida, Akihiko Saitoh

    The Lancet. Infectious diseases   20 ( 12 )   1482 - 1482   2020年12月

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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/S1473-3099(20)30684-8

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  • Effect of a vaccine information statement (VIS) on immunization status and parental knowledge, attitudes, and beliefs regarding infant immunization in Japan. 国際誌

    Aya Saitoh, Akihiko Saitoh, Tomohiro Katsuta, Mahito Mine, Hajime Kamiya, Isao Miyairi, Naruhiko Ishiwada, Makoto Oshiro, Ryutaro Kira, Naoki Shimizu, Shigeru Suga, Takeshi Tsugawa, Masashi Fujioka, Chiaki Miyazaki, Ichiro Morioka, Seigo Korematsu, Takashi Nakano, Keiko Tanaka-Taya, Tetsushi Yoshikawa, Satoshi Iwata, Koichi Kusuhara, Hiroshi Azuma, Hiroyuki Moriuchi, Nobuhiko Okabe, Mitsuaki Hosoya, Hiroyuki Tsutsumi, Kenji Okada

    Vaccine   38 ( 50 )   8049 - 8054   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Because of the overabundance of vaccination information on the internet, in the media, and on social media, providing clear and correct information on immunization is critical for parental decision-making. In 2018, the Japan Pediatric Society created and distributed a Vaccine Information Statement (VIS) to provide appropriate immunization information to caregivers. The objectives of the present study were to evaluate the effect of the VIS on immunization rates, adherence to schedule, and parental understanding of immunization in Japan. METHODS: This cross-sectional study was conducted at 18 centers in 2 prefectures in Japan. Caregivers were assigned to an intervention group, which received the VIS and a questionnaire when their child reached the age of 1 month, and a control group, which received only the questionnaire. Using the self-reported questionnaires, we evaluated vaccination rates and schedule adherence at age 2 months, and parental knowledge, attitudes, and beliefs regarding immunization. Three months later, the questionnaires were returned, and the findings were compared between the 2 groups. RESULTS: We contacted 422 and 428 persons in the intervention and control groups, respectively, and 111/422 (26.3%) and 119/428 (27.8%) returned the surveys. Vaccination rates and adherence rates for the first dose of 4 recommended vaccines did not differ significantly (P > 0.25); however, there were some positive effects on items related to vaccine knowledge (P = 0.03), perceived benefits (P = 0.02), perceived barriers (P < 0.001), and perceived behavioral control (P = 0.01). CONCLUSION: The VIS improved parent comprehension of infant immunization. Future studies should examine if the effects of such an intervention persist and affect vaccine uptake throughout childhood.

    DOI: 10.1016/j.vaccine.2020.10.049

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  • パレコウイルスA3に対する母乳の抗ウイルス効果の検討

    泉田 亮平, 相澤 悠太, 渡邉 香奈子, 齋藤 昭彦

    日本小児感染症学会総会・学術集会プログラム・抄録集   52回   222 - 222   2020年11月

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    記述言語:日本語   出版者・発行元:日本小児感染症学会  

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  • 大学病院と市中病院による小児感染症専門医教育研修プログラムと感染症コンサルテーションの経時的変化

    山中 崇之, 相澤 悠太, 塚野 真也, 齋藤 昭彦

    日本小児感染症学会総会・学術集会プログラム・抄録集   52回   177 - 177   2020年11月

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    記述言語:日本語   出版者・発行元:日本小児感染症学会  

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  • 新型コロナウイルス感染症-パンデミック下の小児科医 COVID-19流行期における大学病院小児感染症医の役割

    相澤 悠太, 齋藤 昭彦

    日本小児感染症学会総会・学術集会プログラム・抄録集   52回   91 - 91   2020年11月

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    記述言語:日本語   出版者・発行元:日本小児感染症学会  

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  • 4ヵ月未満の発熱児におけるパレコウイルス/エンテロウイルスPCR陰性児の臨床像

    槇 竣, 山中 崇之, 泉田 亮平, 相澤 悠太, 齋藤 昭彦, 塚野 真也

    日本小児感染症学会総会・学術集会プログラム・抄録集   52回   222 - 222   2020年11月

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    記述言語:日本語   出版者・発行元:日本小児感染症学会  

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  • ランゲルハンス細胞組織球症との鑑別を要した播種性BCG感染症を合併したIFN-γR1部分欠損症

    原田 瑞生, 久保 暢大, 高地 貴行, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 梅津 哉, 山中 崇之, 今井 耕輔, 岡田 賢, 今井 千速

    日本小児血液・がん学会雑誌   57 ( 3 )   309 - 313   2020年11月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

    症例は9ヵ月男児.繰り返す発熱,腋窩リンパ節腫大,全身の膿疱性皮疹を主訴に当院に紹介された.当初,前頭骨の骨融解像,臨床像,sIL-2R異常高値からランゲルハンス組織球症との鑑別を要し,皮膚生検を施行したが確定診断に至らず,腋窩リンパ節生検を施行した.生検組織からBCG菌が同定され,播種性BCG感染症と診断した.皮膚生検ではBCG菌は検出されず,BCG菌への過敏性反応による結核疹と考えられた.重症細菌感染,ウイルス感染の既往はなく,メンデル遺伝型マイコバクテリア易感染症を疑い精査した結果,IFNGR1遺伝子の既知のde-novoヘテロ変異が同定され,IFN-γR1部分欠損症と診断した.抗結核薬イソニアジド,リファンピシンの2剤による治療で症状は速やかに軽快した.18ヵ月間内服を継続し,終了後半年の現在も再燃なく経過している.ランゲルハンス組織球症として非典型的な皮疹や経過の場合にはBCG感染症を考える必要がある.(著者抄録)

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  • プロスタグランジンE1製剤長期使用による骨膜肥厚の検討

    塚田 正範, 馬場 恵史, 小澤 淳一, 阿部 忠朗, 沼野 藤人, 齋藤 昭彦

    日本小児循環器学会雑誌   36 ( Suppl.2 )   s2 - 255   2020年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本小児循環器学会  

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  • ADO1離脱時のデバイス移動を予測する

    阿部 忠朗, 塚田 正範, 馬場 恵史, 小澤 淳一, 沼野 藤人, 齋藤 昭彦, 星名 哲, 塚野 真也, 佐藤 誠一

    日本小児循環器学会雑誌   36 ( Suppl.2 )   s2 - 287   2020年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本小児循環器学会  

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  • Comparison of immunization systems in Japan and the United States - What can be learned? 国際誌

    Tomohiro Katsuta, Charlotte A Moser, Kristen A Feemster, Akihiko Saitoh, Paul A Offit

    Vaccine   38 ( 46 )   7401 - 7408   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Recently, efforts have been made to fill a so-called "vaccine gap" between Japan and other countries; however, more work remains. Concerns about adverse events following immunization (AEFI) resulted in an historically passive approach to policy making in the National Immunization Program (NIP). For example, reports of AEFI following human papillomavirus vaccine (HPVV) in 2013 led the Japanese government to withdraw its proactive recommendations, resulting in a sharp drop in HPVV coverage rate to less than 1.0%. In this report, we review key historical incidents that led to the current immunization system in Japan, compare it to that in the United States, and discuss strategies for improving the Japanese immunization system. By strengthening existing policies and programs, such as National Immunization Technical Advisory Groups and AEFI reporting, compensation laws, and immunization education, the remaining vaccine gap in Japan could be filled.

    DOI: 10.1016/j.vaccine.2020.09.028

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  • 高リスク神経芽腫の治療後に発症した治療関連KMT2A再構成陽性急性リンパ性白血病

    馬場 みのり, 今村 勝, 申 将守, 笠原 靖史, 岩渕 晴子, 斎藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   57 ( 4 )   333 - 333   2020年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • パレコウイルスA3に対するアンチセンス・ペプチド治療薬の効果の検討

    鈴木 優子, 相澤 悠太, 渡邉 香奈子, 齋藤 昭彦

    臨床とウイルス   48 ( 3 )   S108 - S108   2020年9月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • 焦点発作のために単純ヘルペスウイルス脳炎が疑われたパレコウイルスA3による急性脳炎

    山中 崇之, 相澤 悠太, 齋藤 昭彦

    臨床とウイルス   48 ( 3 )   S105 - S105   2020年9月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • 国内の小児入院施設における新生児、早期乳児のパレコウイルスA3感染症の前方視的疫学調査(第1報)

    相澤 悠太, 宇田 和宏, 伊藤 健太, 庄司 健介, 大竹 正悟, 笠井 正志, 鈴木 優子, 渡邉 香奈子, 齋藤 昭彦

    臨床とウイルス   48 ( 3 )   S102 - S102   2020年9月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • 佐渡島内で流行したロタウイルス胃腸炎の検討

    山田 慧, 後藤 文洋, 岡崎 実, 岩谷 淳, 新井 礼子, 田村 務, 相澤 悠太, 齋藤 昭彦

    臨床とウイルス   48 ( 3 )   S113 - S113   2020年9月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • ライノウイルス感染との関連が示唆された可逆性脳梁膨大部病変を有する軽症脳炎・脳症の1例

    相馬 規子, 相澤 悠太, 鈴木 優子, 齋藤 昭彦

    臨床とウイルス   48 ( 3 )   S97 - S97   2020年9月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • パレコウイルスA1が血清・咽頭・便から検出された拡張型心筋症による急性心不全の1例

    槇 竣, 相澤 悠太, 鈴木 優子, 渡邉 香奈子, 齋藤 昭彦

    臨床とウイルス   48 ( 3 )   S104 - S104   2020年9月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • Serostatus following polio-containing vaccination before and after liver transplantation. 国際誌

    Takanori Funaki, Akinari Fukuda, Seisuke Sakamoto, Mureo Kasahara, Akihiko Saitoh, Isao Miyairi

    Pediatric transplantation   24 ( 6 )   e13766   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The strategy to eradicate polio is based on preventing infection by immunizing all children until the world is polio-free. However, data regarding efficacy of polio-containing vaccination in immunocompromised patients such as LT recipients are limited. METHODS: We conducted an observational study at the largest pediatric transplant center in Japan from January 2011 to January 2015. LT recipients were enrolled after transplantation, and those who had completed the Japanese polio vaccination program were eligible for the study. Patients' demographics were collected from their medical records. Antibody titers against poliovirus serotypes 1-3 were measured using the neutralization test at the routine follow-up visits after enrollment. Factors associated with seropositivity against each type of poliovirus were evaluated. RESULTS: Sixty-four patients who had received the complete polio vaccination series were enrolled in the study. Of these, 37 patients had received all series of polio-containing vaccination before LT. Median age of the patients was 75 months. Their underlying diseases included the following: 40 (63%) with cholestatic liver diseases and 11 (17%) with metabolic disorders. After a median interval of 43 months after LT, seropositivity rates against poliovirus 1, 2, and 3 were 93.8% (60/64), 92.2% (59/64), and 54.7% (35/64), respectively. Among 32 patients who had received only oral polio vaccine (OPV), seropositivity against poliovirus 3 was particularly low (25.0%). No factors associated with seropositivity against each type of poliovirus were identified. CONCLUSIONS: In the LT recipients, seropositivity for poliovirus 3 was low, suggesting a need for additional inactivated polio-containing vaccination after LT, especially for patients who had received only OPV.

    DOI: 10.1111/petr.13766

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  • 国内の小児入院施設における新生児、早期乳児のパレコウイルスA3感染症の前方視的疫学調査(第1報)

    相澤 悠太, 宇田 和宏, 伊藤 健太, 庄司 健介, 大竹 正悟, 笠井 正志, 鈴木 優子, 渡邉 香奈子, 齋藤 昭彦

    臨床とウイルス   48 ( 3 )   S102 - S102   2020年9月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • Skin thickness in neonates: Implications for intradermal vaccination. 国際誌

    Akihiko Saitoh, Jun Nirei, Takeshi Tanaka, Hisanori Haniu, Takatsugu Sakai, Soichiro Okubo, Harunobu Hirano

    Vaccine   38 ( 35 )   5659 - 5664   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: Intradermal (ID) injection is an alternate route that enhances vaccine immunogenicity and decreases vaccine dose. Regular immunization usually starts at age 2 months, and the limited immune capacity of neonates and young infants makes them vulnerable to infection. Successful ID vaccine delivery in this population requires knowledge of skin thickness. Although skin thickness has been evaluated in infants aged 2 months or older, no comparable data are available for neonates, including preterm neonates. METHODS: This prospective observational study used ultrasonography to assess skin thickness in 70 neonates (35 full-term and 35 preterm neonates) at deltoid, suprascapular, and thigh sites. The measurements were compared in relation to anatomical site, between full-term and preterm infants, and with skin thickness values for children aged 2 months or older, which were collected in our previous study using the same measurement technique. RESULTS: In full-term neonates, skin was significantly thicker at the suprascapular site than at the deltoid and thigh sites (P < 0.05); in preterm neonates, skin was significantly thicker at the suprascapular site than at the thigh site (P < 0.05). Skin thickness values at all three sites were significantly lower in preterm neonates than in full-term neonates (P < 0.05). As compared with skin thickness values for infants aged 2 months, values for full-term neonates were significantly lower for the deltoid and suprascapular sites (P < 0.001). CONCLUSIONS: Skin thickness values for neonates were affected by prematurity and were significantly lower than those for infants aged 2 months. These findings are important in the design of ID injection devices for neonates and young infants.

    DOI: 10.1016/j.vaccine.2020.06.061

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  • Degeneration of dopaminergic neurons and impaired intracellular trafficking in Atp13a2 deficient zebrafish 査読

    Hiromi Nyuzuki, Shinji Ito, Keisuke Nagasaki, Yohei Nitta, Noriko Matsui, Akihiko Saitoh, Hideaki Matsui

    IBRO Reports   2020年6月

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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.ibror.2020.05.002

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  • Changes in laboratory findings in Parechovirus-A infection in nine neonates and infants. 国際誌

    Keiko Nimura, Yuta Maruyama, Yuta Aizawa, Akihiko Saitoh, Yozo Nakazawa

    Pediatrics international : official journal of the Japan Pediatric Society   62 ( 6 )   755 - 758   2020年6月

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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/ped.14197

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  • 心室中隔欠損を合併し急速に心不全が進行したMarfan症候群の乳児例

    伊藤 裕貴, 鈴木 博, 渡辺 健一, 羽二生 尚訓, 星名 哲, 白石 修一, 高橋 昌, 齋藤 昭彦

    日本小児循環器学会雑誌   36 ( 2 )   159 - 165   2020年6月

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    記述言語:日本語   出版者・発行元:(NPO)日本小児循環器学会  

    Marfan症候群(MFS)に心室中隔欠損(VSD)を合併し、急速に心不全が進行し、手術前後で心機能が低下した乳児例を経験した。症例は2ヵ月の女児で、VSDによる高肺血流性心不全と診断され、当院を紹介となった。家族歴、身体所見からMFSが疑われた。高肺血流に心機能低下も伴うため、段階的に修復術を施行された。肺動脈絞扼術直後と心内修復術直後にそれぞれ心機能は低下したが、徐々に回復した。3歳時に水晶体脱臼を認め、父がMFSであることから改訂Ghent基準を満たした。MFSは潜在的な心機能障害を有する可能性があり、治療介入が必要な先天性心疾患を合併する例では、術前の心不全の進行や術後管理に注意し、慎重な経過観察や治療戦略を考慮すべきである。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J02003&link_issn=&doc_id=20200817180011&doc_link_id=10.9794%2Fjspccs.36.159&url=https%3A%2F%2Fdoi.org%2F10.9794%2Fjspccs.36.159&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • Improving Hand Hygiene Adherence in Healthcare Workers Before Patient Contact: A Multimodal Intervention in Four Tertiary Care Hospitals in Japan. 査読 国際誌

    Akihiko Saitoh, Kiyomi Sato, Yoko Magara, Kakuei Osaki, Kiyoko Narita, Kumiko Shioiri, Karen E Fowler, David Ratz, Sanjay Saint

    Journal of hospital medicine   15 ( 5 )   262 - 267   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Hand hygiene is key to preventing healthcare-associated infection and the spread of respiratory viruses like the novel coronavirus that causes COVID-19. Unfortunately, hand hygiene adherence of healthcare workers (HCWs) in Japan is suboptimal according to previous studies. OBJECTIVES: Our objectives were to evaluate hand hygiene adherence among physicians and nurses before touching hospitalized patients and to evaluate changes in hand hygiene adherence after a multimodal intervention was implemented. DESIGN, SETTING, AND PARTICIPANTS: We conducted a pre- and postintervention study with HCWs at four tertiary hospitals in Niigata, Japan. Hand hygiene observations were conducted from June to August 2018 (preintervention) and February to March 2019 (postintervention). INTERVENTION: The multimodal hand hygiene intervention recommended by the World Health Organization was tailored to each hospital and implemented from September 2018 to February 2019. MAIN OUTCOMES AND MEASURES: We observed hand hygiene adherence before touching patients in each hospital and compared rates before and after intervention. Intervention components were also evaluated. RESULTS: There were 2,018 patient observations preintervention and 1,630 postintervention. Overall, hand hygiene adherence improved from 453 of 2,018 preintervention observations (22.4%) to 548 of 1,630 postintervention observations (33.6%; P < .001). Rates improved more among nurses (13.9 percentage points) than among doctors (5.7 percentage points). Improvement varied among the hospitals: Hospital B (18.4 percentage points) was highest, followed by Hospitals D (11.4 percentage points), C (11.3 percentage points), and Hospital A (6.5 percentage points). CONCLUSIONS: A multimodal intervention improved hand hygiene adherence rates in physicians and nurses in Niigata, Japan; however, further improvement is necessary. Given the current suboptimal hand hygiene adherence rates in Japanese hospitals, the spread of COVID-19 within the hospital setting is a concern.

    DOI: 10.12788/jhm.3446

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  • Spontaneous remission of infant acute myeloid leukemia with a novel four-way translocation. 査読 国際誌

    Nobuhiro Kubo, Haruko Iwabuchi, Masaru Imamura, Akihiko Saitoh, Chihaya Imai

    Pediatric blood & cancer   67 ( 2 )   e28052   2020年2月

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    記述言語:英語  

    DOI: 10.1002/pbc.28052

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  • ヒトパレコウイルス3型関連血球貪食症候群を発症した1ヵ月男児例

    重田 英臣, 本田 裕子, 伊藤 琢磨, 浅井 完, 押田 康一, 保科 隆之, 相澤 悠太, 齋藤 昭彦, 楠原 浩一

    日本小児科学会雑誌   124 ( 2 )   433 - 433   2020年2月

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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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  • 2019年の国内における新生児・早期乳児のパレコウイルス感染症の広がり

    相澤 悠太, 川口 直樹, 宇田 和宏, 船木 孝則, 笠井 正志, 坂田 晋史, 古野 憲司, 齋藤 昭彦

    日本小児科学会雑誌   124 ( 2 )   255 - 255   2020年2月

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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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  • 夜尿症治療中に発症し内服中止により速やかに改善した薬剤性肺障害の一例

    松下 仁美, 今井 千速, 申 将守, 笠原 靖史, 岩渕 晴子, 今村 勝, 齋藤 昭彦

    日本小児科学会雑誌   124 ( 2 )   444 - 444   2020年2月

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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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  • 日本小児科学会・米国小児科学会合同予防接種教育プロジェクト「知っておきたいわくちん情報」の効果の検証

    岡田 賢司, 齋藤 昭彦, 齋藤 あや, 中野 貴司, 石和田 稔彦, 大城 誠, 勝田 友博, 神谷 元, 吉良 龍太郎, 清水 直樹, 菅 秀, 津川 毅, 藤岡 雅司, 細矢 光亮, 宮入 烈, 宮崎 千明, 森内 浩幸, 楠原 浩一, 東 寛, 日本小児科学会予防接種・感染症対策委員会

    日本小児科学会雑誌   124 ( 1 )   113 - 114   2020年1月

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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  

    生後1ヵ月健診の保護者を対象に、「知っておきたいわくちん情報」を配布する介入群111例と配布しない非介入群119例に分け、生後3ヵ月までの4ワクチン接種状況と保護者の予防接種に対する知識・態度・信念を比較検討した。その結果、4ワクチン接種率は2群間で有意差を認めなかった。保護者の態度と信念に関しては有益性の認知の1項目と自己効力感の1項目が、非介入群と比較して介入群で有意に高かった。障害の認知のスコアは非介入群と比べ、介入群で有意に低かった。今回の検討から、「知っておきたいわくちん情報」の配布により、保護者が乳児期の予防接種に関して肯定的に考え、その必要性を理解・納得し、接種の判断ができる可能性が示唆された。

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  • Epidemic of influenza A(H1N1)pdm09 analyzed by full genome sequences and the first case of oseltamivir-resistant strain in Myanmar 2017. 査読 国際誌

    Su Mon Kyaw Win, Reiko Saito, Nay Chi Win, Di Ja Lasham, Yadanar Kyaw, Nay Lin, Khin Nyo Thein, Irina Chon, Takashi Odagiri, Win Thein, Latt Latt Kyaw, Ommar Swe Tin, Akihiko Saitoh, Tsutomu Tamura, Chika Hirokawa, Yuko Uchida, Takehiko Saito, Shinji Watanabe, Takato Odagiri, Kazuhiro Kamata, Hidekazu Osada, Clyde Dapat, Hisami Watanabe, Htay Htay Tin

    PloS one   15 ( 3 )   e0229601   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A community outbreak of human influenza A(H1N1)pdm09 virus strains was observed in Myanmar in 2017. We investigated the circulation patterns, antigenicity, and drug resistance of 2017 influenza A(H1N1)pdm09 viruses from Myanmar and characterized the full genome of influenza virus strains in Myanmar from in-patients and out-patients to assess the pathogenicity of the viruses. Nasopharyngeal swabs were collected from out-patients and in-patients with acute respiratory tract infections in Yangon and Pyinmana City in Myanmar during January-December 2017. A total of 215 out-patients and 18 in-patients infected with A(H1N1)pdm09 were detected by virus isolation and real-time RT-PCR. Among the positive patients, 90.6% were less than 14 years old. Hemagglutination inhibition (HI) antibody titers against A(H1N1)pdm09 viruses in Myanmar were similar to the recommended Japanese influenza vaccine strain for 2017-2018 seasons (A/Singapore/GP1908/2015) and WHO recommended 2017 southern hemisphere vaccine component (A/Michigan/45/2015). Phylogenetic analysis of the hemagglutinin sequence showed that the Myanmar strains belonged to the genetic subclade 6B.1, possessing mutations of S162N and S164T at potential antigenic sites. However, the amino acid mutation at position 222, which may enhance the severity of disease and mortality, was not found. One case with no prior history of oseltamivir treatment possessed H275Y mutated virus in neuraminidase (NA), which confers resistance to oseltamivir and peramivir with elevated IC50 values. The full genome sequence of Myanmar strains showed no difference between samples from in-patients and out-patients, suggesting no additional viral mutations associated with patient severity. Several amino acid changes were observed in PB2, PB1, and M2 of Myanmar strains when compared to the vaccine strain and other Asian strains. However, no mutations associated with pathogenicity were found in the Myanmar strains, suggesting that viral factors cannot explain the underlying reasons of the massive outbreak in Myanmar. This study reported the first detection of an oseltamivir-resistant influenza virus in Myanmar, highlighting the importance of continuous antiviral monitoring and genetic characterization of the influenza virus in Myanmar.

    DOI: 10.1371/journal.pone.0229601

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  • Fatal Progressive Meningoencephalitis Diagnosed in Two Members of a Family With X-Linked Agammaglobulinemia. 国際誌

    Yasushi Kasahara, Masaru Imamura, Chansu Shin, Hiroshi Shimizu, Jirou Utsumi, Ryosuke Hosokai, Haruko Iwabuchi, Takayuki Takachi, Akiyoshi Kakita, Hirokazu Kanegane, Akihiko Saitoh, Chihaya Imai

    Frontiers in pediatrics   8   579 - 579   2020年

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    記述言語:英語  

    Chronic enteroviral meningoencephalitis is a well-known complication in patients with X-linked agammaglobulinemia (XLA). However, progressive neurodegenerative disorders or chronic neuroinflammatory diseases with no causative microorganisms have been recognized as rare central nervous system (CNS) complications in XLA. We herein report a family in which two of three members with XLA had developed progressive meningoencephalitis with an unknown etiology. A 15-month-old male infant presented with left-sided ptosis. Initially, the family denied any family history of inherited diseases, but later disclosed a family history of agammaglobulinemia previously diagnosed in two family members. In the early 1980s, one of the elder brothers of the index patient's mother who had been treated with intramuscular immunoglobulin [or later intravenous immunoglobulin (IVIG)] for agammaglobulinemia deceased at 10 years of age after showing progressive neurological deterioration during the last several years of his life. The index patient was diagnosed with XLA caused by Bruton tyrosine kinase deficiency (654delG; Val219Leufs*9), and chronic meningoencephalitis with an unknown infectious etiology. Magnetic resonance imaging of the brain demonstrated inflammatory changes in the basal ganglia, hypothalamus, midbrain, and pons, with multiple nodular lesions with ring enhancement, which showed impressive amelioration after the initiation of IVIG replacement therapy. Pleocytosis, which was characterized by an increase in CD4-positive and CD8-positive T cells expressing an activation marker and an elevation in inflammatory cytokines in the cerebrospinal fluid, was identified. No microorganism was identified as a cause of CNS complications. He thereafter developed brain infarction at 19 months of age and fatal status epilepticus at 5 years of age, despite regular IVIG with high trough levels and regular intraventricular immunoglobulin administration. The etiology of this rare CNS complication in XLA is currently unknown. Previous studies have suggested a possible association of IVIG, which was clearly denied in our index case because of the demonstration of his neurological disorder at presentation. In the future, extensive and unbiased molecular methods to detect causative microorganisms, as well as to investigate the possible role of autoimmunity are needed to clarify the etiology of CNS complications.

    DOI: 10.3389/fped.2020.00579

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  • Timing of hyponatremia development in patients with salt-wasting-type 21-hydroxylase deficiency.

    Rohi Shima, Kentaro Sawano, Nao Shibata, Hiromi Nyuzuki, Sunao Sasaki, Hidetoshi Sato, Yohei Ogawa, Yuki Abe, Keisuke Nagasaki, Akihiko Saitoh

    Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology   29 ( 3 )   105 - 110   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Newborn screening (NBS) can detect 21-hydroxylase deficiency (21-OHD), allowing for early treatment initiation. However, many patients present with adrenal crises or hyponatremia at their first visit. Age (in days) of hyponatremia development in infants with salt-wasting (SW)-type 21-OHD remains unclear. Therefore, we determined the earliest age of hyponatremia diagnosis in this retrospective observational study using medical records of 40 patients with classic 21-OHD in Niigata Prefecture, Japan, from April 1989 to March 2019. We determined the earliest diagnosis of hyponatremia (serum sodium levels < 130 mEq/L) and created a sodium decrease rate model to estimate hyponatremia development age. Of 23 patients with SW-type 21-OHD, 10 (43.5%) were identified during NBS; the earliest case to present with hyponatremia was at day 7. Serum sodium levels were significantly and negatively correlated with age in days, and hyponatremia was estimated to develop at 6.6 d after birth. Genotype or serum 17-hydroxyprogesterone levels were not associated with sodium decrease rate. Thus, hyponatremia development age is earlier (within 7 d) than the previously described time-point (10-14 d) in infants with SW-type 21-OHD. Efforts to reduce the time lag from obtaining results to consultation may be required in patients with high 17-hydroxyprogesterone levels on NBS.

    DOI: 10.1297/cpe.29.105

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  • Development and characterisation of NKp44-based chimeric antigen receptors that confer T cells with NK cell-like specificity. 国際誌

    Yasushi Kasahara, Chansu Shin, Nobuhiro Kubo, Keichiro Mihara, Haruko Iwabuchi, Takayuki Takachi, Masaru Imamura, Akihiko Saitoh, Chihaya Imai

    Clinical & translational immunology   9 ( 7 )   e1147   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objectives: One of the reasons as to why chimeric antigen receptors (CAR)-T cell therapy for malignancies other than CD19- or BCMA-positive tumors has yet to produce remarkable progress is the paucity of targetable antigens. NKp44 is only expressed by activated natural killer cells and detects a variety of transformed cells, while it reportedly does not react with normal tissues. The aim of this study is to develop CAR-T cell that can target multiple types of tumor cells. Methods: We created a series of novel CAR constructs in first-generation (1G) and second-generation (2G) CAR format with the extracellular immunoglobulin-like domain of NKp44 (NKp44-CAR). Results: Transduction of the best 1G construct into human primary T cells led to specific cytotoxic effects and cytokine secretion upon encountering multiple types of neoplastic cells including AML, T-ALL and childhood solid tumors. Replacement of the extracellular hinge domain of NKp44 with that of CD8α resulted in diminished CAR function. The 1G NKp44-CAR-T cells exhibited significantly better tumor control in long-term co-culture assays compared with activated NK cells, as well as with NK cells transduced with identical NKp44-CAR. T cells transduced with the best 2G-CAR construct with 4-1BB co-stimulatory domain proliferated at significantly higher levels upon single antigen exposure and showed significantly better tumor control compared with the 1G-CAR and 2G-CAR with CD28 co-stimulatory domain. Conclusions: NKp44-based CAR endows T cells with NK cell-like anti-tumor specificity. The CAR gene created in this study will be useful for the development of novel gene-modified T-cell immunotherapy.

    DOI: 10.1002/cti2.1147

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  • ヒトパレコウイルス3型による成人の流行性筋痛症の1例

    河野 真奈実, 稲田 賢人, 船積 雅登, 渡邊 稔之, 吉田 紗衣子, 織田 奈都子, 上田 研, 相澤 悠太, 齋藤 昭彦, 長田 薫

    日本内科学会関東地方会   656回   58 - 58   2019年12月

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    記述言語:日本語   出版者・発行元:日本内科学会-関東地方会  

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  • 【小児の救急・搬送医療】病態と疾患 感染症 パレコウイルス感染症

    相澤 悠太, 齋藤 昭彦

    小児内科   51 ( 増刊 )   727 - 730   2019年11月

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    記述言語:日本語   出版者・発行元:(株)東京医学社  

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  • 【話題のウイルス感染症】ヒトパレコウイルス感染症

    相澤 悠太, 齋藤 昭彦

    臨床と微生物   46 ( 6 )   697 - 702   2019年11月

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    記述言語:日本語   出版者・発行元:(株)近代出版  

    ヒトパレコウイルスのうち、特に3型は生後4ヵ月未満の早期乳児に敗血症、髄膜脳炎をきたす、小児科医の間で注目を集めている新興ウイルス感染症である。特異的な臨床症状や徴候が明らかになりつつある一方で、疫学や病態生理はまだ不明な点が多い。(著者抄録)

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  • 気管吸引痰および鼻咽頭拭い液のリアルタイムPCRにより診断確定に至ったB型インフルエンザウイルス性鋳型気管支炎の1例

    松岡 太朗, 長村 敏生, 小林 奈歩, 加藤 大吾, 東道 公人, 藤井 法子, 大前 禎毅, 相澤 悠太, 齋藤 昭彦

    日本小児救急医学会雑誌   18 ( 3 )   390 - 394   2019年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児救急医学会  

    症例は5歳男児。当科受診2日前から発熱、咳嗽を認め、第2病日に近医を受診したが、鼻咽頭拭い液のインフルエンザウイルス(Influenza virus:flu)迅速抗原キット検査は陰性で、自宅での経過観察を指示された。しかし、同日夜に喘鳴が出現し、第3病日昼からは呼吸困難も訴え、14時に当科へ救急搬送された。搬入2時間後、気管挿管した直後に鋳型の粘液栓が吸引されて、鋳型気管支炎と診断した。ベラミビル、ステロイド投与、肺理学療法により第17病日に退院となり、以後の再発はない。来院直後の当科での鼻咽頭拭い液のflu迅速抗原キット検査は陰性であったが、同日の検体を用いたリアルタイムPCRではfluBが気管吸引痰、鼻咽頭拭い液ともに陽性で、前者でウイルス量がより多かった。下気道感染症の診断は上気道検体の迅速抗原キット検査のみでは確定できない場合があり、下気道検体を用いた検査の重要性を再認識した。(著者抄録)

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  • Klebsiella oxytocaによる抗菌薬関連出血性大腸炎の2例

    山田 明日実, 渡邉 広樹, 稲葉 聡, 幾瀬 樹, 井口 英幸, 田嶋 直哉, 小嶋 絹子, 鈴木 博, 相澤 悠太, 齋藤 昭彦

    日本小児感染症学会総会・学術集会プログラム・抄録集   51回   233 - 233   2019年10月

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    記述言語:日本語   出版者・発行元:日本小児感染症学会  

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  • 大学病院と市中病院による小児感染症専門医教育研修プログラム

    相澤 悠太, 山中 崇之, 大塚 岳人, 齋藤 昭彦

    日本小児感染症学会総会・学術集会プログラム・抄録集   51回   211 - 211   2019年10月

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    記述言語:日本語   出版者・発行元:日本小児感染症学会  

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  • Clinical Characteristics of Saffold Virus Infection in Children. 査読 国際誌

    Satoko Ugai, Atsushi Iwaya, Hiromichi Taneichi, Chika Hirokawa, Yuta Aizawa, Shuji Hatakeyama, Akihiko Saitoh

    The Pediatric infectious disease journal   38 ( 8 )   781 - 785   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Saffold virus (SAFV) is a novel human cardiovirus that was identified in 2007. Recently, SAFV has been isolated from nasal and stool specimens of infants presenting with respiratory and gastrointestinal symptoms and from cerebrospinal fluid (CSF) specimens of children with central nervous system infection. However, little is known regarding clinical characteristics of SAFV in children. METHODS: We reviewed 5412 specimens from the database of the infectious agents surveillance system in Niigata prefecture, Japan, between January 2006 and December 2013, and identified SAFV-infected patients. Subsequently, we retrospectively reviewed their medical records and evaluated their clinical characteristics. RESULTS: We identified 9 SAFV-infected patients (median age: 5 years; range: 2-16 years). Seven patients were diagnosed with pharyngitis, one with meningitis and one with fever of unknown origin. Dominant symptoms were high fever, appetite loss and headache. The median duration of the fevers was 2 days in patients with pharyngitis; however, the patient with meningitis remained febrile for 5 days. All blood tests available in this case series revealed leukocytosis with a predominance of neutrophils. CSF profiles showed mild lymphocytic pleocytosis. All patients recovered fully without complications. CONCLUSIONS: A few clinical characteristics of SAFV infection were clarified, including high fever of short duration in patients with pharyngitis, and neutrophil-dominant leukocytosis. The clinical course and CSF profiles of a case of meningitis were similar to those of other aseptic meningitis. SAFV needs to be included in the differential diagnosis of pharyngitis or meningitis when commonly identified viruses are not identified in such patients.

    DOI: 10.1097/INF.0000000000002298

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  • Dynamic QT Changes in Long QT Syndrome Type 8. 査読

    Mizuki Harada, Hiroshi Suzuki, Seiko Ohno, Junichi Ozawa, Akihiko Saitoh, Minoru Horie

    Circulation journal : official journal of the Japanese Circulation Society   83 ( 7 )   1614 - 1614   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1253/circj.CJ-18-0984

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  • 新生児・早期乳児におけるパレコウイルスA3とエンテロウイルス感染症 血清と髄液のPCR陽性率の比較

    鈴木 優子, 相澤 悠太, 渡邉 香奈子, 齋藤 昭彦

    臨床とウイルス   47 ( 2 )   S99 - S99   2019年4月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • 小児脳腫瘍のトランスレーショナルリサーチと基礎研究 膠芽腫に対する新たなCAR-T療法の基礎的検討(NKp44-based CAR)

    笠原 靖史, 申 将守, 久保 暢大, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    小児の脳神経   44 ( 2 )   142 - 142   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本小児神経外科学会  

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  • The association of epileptic focus estimated by magnetoencephalography with cognitive function in non-lesional epilepsy with continuous spikes and waves during slow wave sleep (ECSWS) children. 査読 国際誌

    Shinichi Magara, Takao Komatsubara, Moemi Hojo, Yu Kobayashi, Mihoko Yoshino, Akihiko Saitoh, Jun Tohyama

    Brain & development   41 ( 2 )   163 - 172   2019年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Epilepsy with continuous spikes and waves during slow sleep (ECSWS) is associated with cognitive deficits. The underlying mechanism is thought to relate to disturbance of functions of the foci by the persistent epileptic activity. However, the relationship between epileptic foci and cognitive deficits remains largely unknown, except for in Landau-Kleffner syndrome. The aim of this study was to evaluate the relationship of epileptic foci estimated from magnetoencephalography (MEG) with cognitive functions at the period of diagnosis in non-lesional ECSWS children, excluding those with Landau-Kleffner syndrome. METHODS: MEG data and the Wechsler intelligence scale for children-III scores at ECSWS diagnosis, and medical records, were reviewed. Multiple regression analysis was performed to examine the relationship of parameters of MEG spike dipole clusters, including anatomical location or laterality, with the Wechsler intelligence scale for children-III scores at ECSWS diagnosis. RESULTS: Sixteen patients were included, all of whom were right-handed. Epilepsy onset (first unprovoked seizure) ranged from 31 to 110 months (mean, 68.5). The age at ECSWS diagnosis ranged from 72 to 156 months (mean, 108.9). The dipole clusters were estimated on the right Rolandic area (RA) in 4 patients (25%), right supramarginal gyrus (SMG) in 3 (19%), left RA in 2 (13%), left SMG in 2 (13%), bilateral RA in 3 (19%), multiple anatomical locations in 2 (13%). The age at epilepsy onset had the strongest prognostic effect, and full-scale intelligence quotient was relatively less-affected if the cluster was found on the SMG (β = 14.7, p = 0.031). Cases with only a right side cluster exhibited reduced impairment of perceptual organization compared with those with only a left side cluster or bilateral clusters (β = 17.48, p = 0.02). In 12 patients, long-term intellectual prognosis was evaluated, and was associated with intellectual level at the period of ECSWS diagnosis. CONCLUSION: In non-lesional ECSWS, the relationship between epileptic focus and cognitive deficits differs from that observed in adults. Rather, it is similar to epilepsies associated with congenital or early infantile brain insults, in that the left epileptic foci in right-handed patients were associated with lower non-verbal functions. Future studies are required to determine the role of plasticity of the immature brain in driving these differences.

    DOI: 10.1016/j.braindev.2018.09.005

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  • 繰り返す腸重積で発見されフローサイトメトリーでlight chain restrictionを認めた虫垂リンパ過形成の1例

    小貫 孝則, 高地 貴行, 久保 暢大, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    小児科臨床   72 ( 2 )   170 - 174   2019年2月

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    記述言語:日本語   出版者・発行元:(株)日本小児医事出版社  

    繰り返す腸重積を契機に発見され、フローサイトメトリーでλ鎖優位のlight chain restriction(LCR)を認めた虫垂リンパ過形成の6歳女児例を経験した。腹部造影CTでは最大径2.5cmの全周性虫垂腫大を認め、迅速病理診断およびスタンプ標本からも成熟B細胞リンパ腫で矛盾のない所見を得たが、免疫グロブリン遺伝子やc-myc遺伝子の再構成は認めず、最終的に永久病理標本により虫垂リンパ過形成の診断となった。追加の治療介入は行わず経過観察の方針としたが、約12ヵ月を経過し再発は認めていない。文献上、LCRを認める虫垂リンパ過形成は極めて稀で、4〜6歳の4例が報告されているのみである(すべてλ鎖優位のLCR)。本例の経験から、反復性腸重積の稀な原因として虫垂リンパ過形成があること、そして、反応性の病態ながらもLCRを示す場合があることを念頭に置く必要があることが示された。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00643&link_issn=&doc_id=20190124480010&doc_link_id=%2Fag1snrsd%2F2019%2F007202%2F010%2F0170-0174%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2019%2F007202%2F010%2F0170-0174%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • WHIM症候群の一家系

    石井 孝規, 久保 暢大, 笠原 靖史, 岩渕 晴子, 岡田 賢, 今村 勝, 斎藤 昭彦, 今井 千速

    日本小児科学会雑誌   123 ( 2 )   510 - 510   2019年2月

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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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  • Immunization with pneumococcal elongation factor Tu enhances serotype-independent protection against Streptococcus pneumoniae infection. 査読 国際誌

    Kosuke Nagai, Hisanori Domon, Tomoki Maekawa, Takumi Hiyoshi, Hikaru Tamura, Daisuke Yonezawa, Rie Habuka, Akihiko Saitoh, Yutaka Terao

    Vaccine   37 ( 1 )   160 - 168   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Vaccination is an effective strategy to prevent pneumococcal diseases. Currently, licensed vaccines include the pneumococcal polysaccharide vaccine (PPSV) and the pneumococcal conjugate vaccine (PCV), which target some of the most common of the 94 serotypes of S. pneumoniae based on their capsular composition. However, it has been reported that PPSV is not effective in children aged less than 2 years old and PCV induces serotype replacement, which means that the pneumococcal population has changed following widespread introduction of these vaccines, and the non-vaccine serotypes have increased in being the cause of invasive pneumococcal disease. Therefore, it is important that there is development of novel pneumococcal vaccines to either replace or complement current polysaccharide-based vaccines. Our previous study suggested that S. pneumoniae releases elongation factor Tu (EF-Tu) through autolysis followed by the induction of proinflammatory cytokines in macrophages via toll-like receptor 4, that may contribute to the development of pneumococcal diseases. In this study, we investigated the expression of EF-Tu in various S. pneumoniae strains and whether EF-Tu could be an antigen candidate for serotype-independent vaccine against pneumococcal infection. Western blotting and flow cytometry analysis revealed that EF-Tu is a common factor expressed on the surface of all pneumococcal strains tested, as well as intracellularly. In addition, we demonstrate that immunization with recombinant (r) EF-Tu induced the production of inflammatory cytokines and the IgG1 and IgG2a antibodies in mice, and increased the CD4+ T-cells proportion in splenocytes. We also reveal that anti-EF-Tu serum increased the phagocytic activity of mouse peritoneal macrophages against S. pneumoniae infection, independent of their serotypes. Finally, our results indicate that mice immunized with rEF-Tu were significantly and non-specifically protected against lethal challenges with S. pneumoniae serotypes (2 and 15A). Therefore, pneumococcal EF-Tu could be an antigen candidate for the serotype-independent vaccine against pneumococcal infection.

    DOI: 10.1016/j.vaccine.2018.11.015

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  • Aphthous lesions on the soft palate in a neonate. 査読 国際誌

    Ryo Suzuki, Minoru Watanabe, Touhei Usuda, Akihiko Saitoh

    Pediatrics international : official journal of the Japan Pediatric Society   61 ( 1 )   107 - 108   2019年1月

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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/ped.13723

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  • 結核疹を伴う播種性BCG感染症を契機に診断されたIFN-γR1部分欠損症

    原田 瑞生, 久保 暢大, 高地 貴行, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 岡田 賢, 今井 千速

    日本小児血液・がん学会雑誌   55 ( 4 )   310 - 310   2018年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • A nationwide population-based surveillance of invasive Haemophilus influenzae diseases in children after the introduction of the Haemophilus influenzae type b vaccine in Japan. 査読 国際誌

    Shigeru Suga, Naruhiko Ishiwada, Yuko Sasaki, Hideki Akeda, Junichiro Nishi, Kenji Okada, Mikiya Fujieda, Megumi Oda, Kazutoyo Asada, Takashi Nakano, Akihiko Saitoh, Mitsuaki Hosoya, Takehiro Togashi, Mayumi Matsuoka, Kouji Kimura, Keigo Shibayama

    Vaccine   36 ( 38 )   5678 - 5684   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Haemophilus influenzae type b (Hib) vaccine was introduced as a voluntary vaccine in December 2008 and was included in the national routine immunization program in April 2013 in Japan. Currently, no nationwide data are available to evaluate the effectiveness of Hib vaccine in Japan. METHODS: To evaluate the effectiveness of Hib vaccine in Japan, nationwide active population-based surveillance of culture-proven invasive infections caused by H. influenzae in children was performed in 2008-2017 in 10 prefectures in Japan (covering approximately 23% of the total Japanese population). Clinical data were recorded on a standardized case report form. Capsular type and antimicrobial susceptibility of the H. influenzae isolates were examined. The incidence rate ratio (IRR) and its confidence interval (CI) were calculated to compare data from 5 years before and that from after the introduction of the national routine Hib vaccine immunization program. RESULTS: During the 10-year study period, 566 invasive H. influenzae disease cases including 336 meningitis cases were identified. The average number of invasive H. influenzae disease cases among children <5 years of age during 2013-2017 decreased by 93% (IRR: 0.07, 95%CI 0.05-0.10, p < 0.001) compared with those occurring during 2008-2012. Hib strains have not been isolated from invasive H. influenzae disease cases since 2014; however, non-typeable H. influenzae and H. influenzae type f isolates have been noted as causes of invasive H. influenzae diseases among children <5 years in the post-Hib vaccine era. CONCLUSIONS: After the governmental subsidization of the Hib vaccine, invasive Hib disease cases decreased dramatically in the study population, as per our surveillance. Continuous surveillance is necessary to monitor the effectiveness of Hib vaccine and for detecting any emerging invasive capsular types.

    DOI: 10.1016/j.vaccine.2018.08.029

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  • PD-1リガンドを標的とした新規キメラ抗原受容体T細胞の作製(Development of novel chimeric antigen receptor targeting PD-1 ligands in cancer cells)

    申 将守, 久保 暢大, 笠原 靖史, 高地 貴行, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    臨床血液   59 ( 9 )   1587 - 1587   2018年9月

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    記述言語:英語   出版者・発行元:(一社)日本血液学会-東京事務局  

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  • Differential Diagnosis Between Catecholaminergic Polymorphic Ventricular Tachycardia and Long QT Syndrome Type 1 - Modified Schwartz Score. 査読

    Junichi Ozawa, Seiko Ohno, Yusuke Fujii, Takeru Makiyama, Hiroshi Suzuki, Akihiko Saitoh, Minoru Horie

    Circulation journal : official journal of the Japanese Circulation Society   82 ( 9 )   2269 - 2276   2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) has been often misdiagnosed as long QT syndrome (LQTS) type 1 (LQT1), which phenotypically mimics CPVT but has a relatively better prognosis. Methods and Results: The derivation and validation cohorts consisted of 146 and 21 patients, respectively, all of whom had exercise- or emotional stress-induced cardiac events. In the derivation cohort, 42 and 104 patients were first clinically diagnosed with CPVT and LQTS, respectively. Nine of 104 patient who had initial diagnosis of LQTS were found to carry RYR2 mutations. They were misdiagnosed due to 4 different reasons: (1) transient QT prolongation after cardiopulmonary arrest; (2) QT prolongation after epinephrine test; (3) absence of ventricular arrhythmia after the exercise stress test (EST); and (4) assumption of LQTS without evidence. Based on genetic results, we constructed a composite scoring system by modifying the Schwartz score: replacing the corrected QT interval (QTc) at 4 min recovery time after EST >480 ms with that at 2 min, or with ∆QTc (QTc at 2 min of recovery-QTc before exercise) >40 ms and assigning a score of -1 for ∆QTc <10 ms or documented polymorphic ventricular arrhythmias. This composite scoring yielded 100% sensitivity and specificity for the clinical differential diagnosis between LQT1 and CPVT when applied to the validation cohort. CONCLUSIONS: The modified Schwartz score facilitated the differential diagnosis between LQT1 and CPVT.

    DOI: 10.1253/circj.CJ-17-1032

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  • 多発結節性腎病変を呈した前駆B細胞性急性リンパ性白血病の症例

    中林 大器, 高地 貴行, 久保 暢大, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    小児科臨床   71 ( 8 )   1409 - 1414   2018年8月

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    記述言語:日本語   出版者・発行元:(株)日本小児医事出版社  

    急性リンパ性白血病(ALL)は腎腫大を含め様々な臓器浸潤を来すが、腎臓に結節性病変を呈することは少ない。症例は1歳4ヵ月の男児。発熱が持続し、血液検査でLDHの異常高値を指摘され、造影CTで両側腎腫大と多発結節性病変を認めた。末梢血中に芽球の出現があり、骨髄穿刺で前駆B細胞性急性リンパ性白血病と診断した。寛解導入療法後に両側腎腫大および腎多発結節性病変は消失し完全寛解に至った。腎の多発結節性病変の鑑別として造血器腫瘍も考慮すべきである。(著者抄録)

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  • Progress and challenges for the Japanese immunization program: Beyond the "vaccine gap". 査読 国際誌

    Akihiko Saitoh, Nobuhiko Okabe

    Vaccine   36 ( 30 )   4582 - 4588   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The Japanese immunization program has made considerable recent progress. The introduction of several new vaccines, especially foreign-produced vaccines, and the inclusion of important new vaccines in the National Immunization Program (NIP) are closing the "vaccine gap", i.e., the delay in the Japanese immunization program relative to programs in other developed countries. Major progress in the Japanese immunization program since 2014 includes (1) elimination of measles in March 2015, (2) introduction of a varicella vaccine as a routine immunization in the NIP in October 2015, and (3) introduction of hepatitis B virus vaccines as routine immunizations in the NIP in October 2016. Despite these promising developments, important issues remain. First, the government withdrew the active recommendation for human papilloma virus vaccines temporarily in 2013. The withdrawal has continued and unresolved despite new scientific evidence confirming the safety of these vaccines. Second, a few important voluntary vaccines, including vaccines for mumps and rotavirus, have not been included in the NIP since their introduction to Japan. Finally, there are concerns related to a shortage of mandatory domestic vaccines, which was caused by a natural disaster in the area where a vaccine-producing factory was located. Additionally, the manufacturer included unauthorized additives in some vaccine products with falsifying the production-process records. To avoid problems related to vaccine shortages, essential vaccines need to be stockpiled, and the future vaccine needs for children should to be discussed. New initiatives must continue to close the vaccine gap, as this will protect children living in Japan from vaccine-preventable diseases.

    DOI: 10.1016/j.vaccine.2018.01.092

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  • A novel CACNA1C mutation identified in a patient with Timothy syndrome without syndactyly exerts both marked loss- and gain-of-function effects. 査読 国際誌

    Junichi Ozawa, Seiko Ohno, Hideki Saito, Akihiko Saitoh, Hiroshi Matsuura, Minoru Horie

    HeartRhythm case reports   4 ( 7 )   273 - 277   2018年7月

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  • Parvovirus B19: A Cause of Sepsislike Syndrome in an Infant. 査読 国際誌

    Satoko Ugai, Yuta Aizawa, Tetsuya Kanayama, Akihiko Saitoh

    Pediatrics   141 ( 6 )   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Parvovirus B19 (PB19) is an important human pathogen that results in a wide spectrum of clinical outcomes, from mild, self-limiting erythema infectiosum in immunocompetent children and arthralgia in adults to lethal cytopenia in immunocompromised patients and intrauterine fetal death. However, there have been few reports of PB19 infection in neonates or young infants (aged 28-90 days), and no previous reports contained descriptions of PB19 infection as a cause of sepsislike syndrome in this age group. We report a case of sepsislike syndrome caused by PB19 infection in a 56-day-old infant whose mother had polyarthralgia at the time of his admission. PB19 infection was diagnosed on the basis of positive polymerase chain reaction results for PB19 DNA in the serum and cerebrospinal fluid. Positive immunoglobulin M and negative immunoglobulin G for PB19 suggested acute infection. He was admitted to the ICU because of poor peripheral circulation, but fully recovered without antibiotic administration. After excluding other possible pathogens, PB19 should be suspected as a cause of sepsislike syndrome in young infants, especially those who have close contact with PB19-infected individuals.

    DOI: 10.1542/peds.2017-1435

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  • Thyroid function in asphyxiated newborns who received hypothermia therapy. 査読 国際誌

    Akira Kobayashi, Touhei Usuda, Masaki Wada, Takayuki Kaneko, Kinuko Kojima, Akihiko Saitoh

    Pediatrics international : official journal of the Japan Pediatric Society   60 ( 5 )   433 - 437   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Thyroid function in asphyxiated newborns who received hypothermia therapy and its relation to neurological outcome are not well described. METHODS: We performed a prospective study to measure thyroid function in 12 asphyxiated newborns who received hypothermia therapy. We measured serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) on admission, at 24, 72, and 96 h after birth, and at discharge (range, 17-54 days). The 12 newborns were divided into two groups based on the presence of brain injury on head magnetic resonance imaging (six in the abnormal imaging group and six in the normal imaging group), and thyroid function was compared between the two groups. RESULTS: Serum TSH was within the normal range in the 12 newborns. Serum FT3 and FT4 remained low at 24, 72, and 96 h after birth, and returned to normal range at discharge in the 12 newborns. There was no significant difference in serum TSH between the two groups, but serum FT3 at 96 h after birth, and serum FT4 at 72 and 96 h after birth, were significantly lower in the abnormal imaging group than in the normal imaging group (P = 0.02; P = 0.03; and P = 0.01, respectively). CONCLUSIONS: Asphyxiated newborns have transient low thyroid hormone levels at 24-96 h after birth. Serum FT3 and FT4 between 72 and 96 h after birth may predict brain injury in asphyxiated newborns.

    DOI: 10.1111/ped.13534

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  • Pharyngolaryngeal edema in mumps virus infection: Rare complication. 査読 国際誌

    Ryo Suzuki, Naotaka Aizawa, Masaki Wada, Hiroshi Suzuki, Akihiko Saitoh

    Pediatrics international : official journal of the Japan Pediatric Society   60 ( 5 )   493 - 494   2018年5月

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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/ped.13552

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  • 細菌性髄膜炎を契機に診断された先天性皮膚洞の一例

    原田 瑞生, 鈴木 博, 白井 崇準, 小嶋 絹子, 板垣 成孝, 和田 雅樹, 井口 英幸, 大橋 伯, 大塚 岳人, 齋藤 昭彦

    新潟医学会雑誌   132 ( 5 )   203 - 207   2018年5月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    症例は10ヵ月の男児。発熱とけいれんを主訴に当院に入院した。Haemophilus influenzae type b(Hib)ワクチンおよび肺炎球菌ワクチンは接種済み。健診で異常を指摘されたことはなかった。入院時、多核球優位の髄液細胞数増多を認め、細菌性髄膜炎と診断された。セフトリアキソン、バンコマイシン、デキサメタゾンで治療を開始され、一旦は解熱したが、入院4日目から再度発熱した。腰仙部中央に痂皮形成を伴う発赤があり、痂皮下に軽微な陥凹を認めたため腰部MRIを施行した。皮膚洞、硬膜内に連続する嚢状構造物を認め、先天性皮膚洞と硬膜内膿瘍が疑われた。入院8日目の髄液検査では再度細胞数の増多を認めた。標準的な抗菌薬治療でも解熱せず、外科的介入が必要と判断された。入院11日目に高次医療機関に転院し、皮膚洞と嚢胞を摘出された。転院後の髄液培養でStaphylococcus lugdunensisが検出された。病理の結果、先天性皮膚洞、類皮嚢胞と診断された。術後経過は良好で転院26日目に退院した。術後の運動発達は良好で、1歳で独歩を獲得している。本症例は髄膜炎が先天性皮膚洞発見の契機となった。非感染時の皮膚症状が軽微で健診では確認が困難であったが、入院時の診察で皮膚異常を認めたことで診断に至った。先天性皮膚洞は早期発見と介入が重要である。皮膚所見が軽微でも、臀裂内にない陥凹等のリスクのある症例を見逃さないことが大切と考えられた。Hib、肺炎球菌ワクチン接種済みの症例や通常想定されない起因菌の細菌性髄膜炎では、解剖学的異常を含めた基礎疾患の可能性を特に考えるべきである。(著者抄録)

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  • Nonsense mutations in FZD2 cause autosomal-dominant omodysplasia: Robinow syndrome-like phenotypes. 査読 国際誌

    Keisuke Nagasaki, Gen Nishimura, Toru Kikuchi, Hiromi Nyuzuki, Sunao Sasaki, Yohei Ogawa, Akihiko Saitoh

    American journal of medical genetics. Part A   176 ( 3 )   739 - 742   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Omodysplasia-2 (OMOD2; OMIM%16475) is a rare autosomal dominant (AD) skeletal dysplasia characterized by shortened humeri, short first metacarpal, craniofacial dysmorphism (frontal bossing, depressed nasal bridge, bifid nasal tip, and long philtrum), and variable degrees of genitourinary anomalies. This clinical phenotype overlaps with that of AD type Robinow syndrome. Recently, a mutation in FZD2 encoding a Frizzled Class Receptor 2 has been identified in a family with AD omodysplasia (an affected girl and her affected mother). Here, we present the second report on a heterozygous novel nonsense FZD2 mutation in OMOD2 or Robinow syndrome-like phenotype. The proband was a 16-year-old boy, who has been followed from infancy to adolescence. He presented with rhizomelic short stature with elbow restriction, mild facial dysmorphism (depressed broad bridge, short nose, anteverted nostrils, long philtrum, and low-set ears), and genital hypoplasia. Radiological examination in infancy showed short, broad humeri with relatively narrow distal ends, mildly broad femora, thick proximal ulnae with hypoplastic, dislocated proximal radii, and short first metacarpals. The abnormal skeletal pattern was persistent in adolescence; however, the humeri and femora became less undermodeled, while the humeri and radii became mildly bowed. Molecular analysis identified a de novo, heterozygous, nonsense mutation (c.1640C>A, p.S547*) in FZD2. The affected codon was next to the previously reported mutation (p.Trp548*). The results indicate that OMOD2 or Robinow syndome-like phenotype can be caused by a heterozygous nonsense FZD2 mutation impairing Wnt signaling. Further molecular studies will permit better clarification of the phenotypic spectrum in patients with OMOD2.

    DOI: 10.1002/ajmg.a.38623

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  • Pneumococcal DNA-binding proteins released through autolysis induce the production of proinflammatory cytokines via toll-like receptor 4. 査読 国際誌

    Kosuke Nagai, Hisanori Domon, Tomoki Maekawa, Masataka Oda, Takumi Hiyoshi, Hikaru Tamura, Daisuke Yonezawa, Yoshiaki Arai, Mai Yokoji, Koichi Tabeta, Rie Habuka, Akihiko Saitoh, Masaya Yamaguchi, Shigetada Kawabata, Yutaka Terao

    Cellular immunology   325   14 - 22   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Streptococcus pneumoniae is a leading cause of bacterial pneumonia. Our previous study suggested that S. pneumoniae autolysis-dependently releases intracellular pneumolysin, which subsequently leads to lung injury. In this study, we hypothesized that pneumococcal autolysis induces the leakage of additional intracellular molecules that could increase the pathogenicity of S. pneumoniae. Liquid chromatography tandem-mass spectrometry analysis identified that chaperone protein DnaK, elongation factor Tu (EF-Tu), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were released with pneumococcal DNA by autolysis. We demonstrated that recombinant (r) DnaK, rEF-Tu, and rGAPDH induced significantly higher levels of interleukin-6 and tumor necrosis factor production in peritoneal macrophages and THP-1-derived macrophage-like cells via toll-like receptor 4. Furthermore, the DNA-binding activity of these proteins was confirmed by surface plasmon resonance assay. We demonstrated that pneumococcal DnaK, EF-Tu, and GAPDH induced the production of proinflammatory cytokines in macrophages, and might cause host tissue damage and affect the development of pneumococcal diseases.

    DOI: 10.1016/j.cellimm.2018.01.006

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  • Herpetic Whitlow. 査読 国際誌

    Kensuke Shoji, Akihiko Saitoh

    The New England journal of medicine   378 ( 6 )   563 - 563   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1056/NEJMicm1711479

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  • 小児血液・腫瘍疾患における菌血症の臨床的検討 患者受け入れ再開後12年の変遷

    久保 暢大, 申 将守, 笠原 靖史, 吉田 咲子, 細貝 亮介, 高地 貴行, 岩渕 晴子, 今村 勝, 今井 千速, 齋藤 昭彦

    日本小児科学会雑誌   122 ( 2 )   359 - 359   2018年2月

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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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  • Neuropsychiatric Disorder Associated with Group G Streptococcus Infection. 査読 国際誌

    Rie Okumura, Sawako Yamazaki, Tsukasa Ohashi, Shinichi Magara, Jun Tohyama, Hiroshi Sakuma, Masaharu Hayashi, Akihiko Saitoh

    Case reports in pediatrics   2018   6047318 - 6047318   2018年

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    記述言語:英語  

    Immune-mediated central nervous system manifestations of group A β-hemolytic Streptococcus (GABHS) infection include Sydenham's chorea, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS)-which includes tic and obsessive compulsive disorders-and a variety of neurobehavioral disorders. We report a case of Streptococcus dysgalactiae subspecies equisimilis (group G Streptococcus) (GGS) infection associated with involuntary movements, complex tics, and emotional lability in an 11-year-old Japanese girl. Serum IgM and IgG antibodies to lysoganglioside were positive, and she responded rapidly to intravenous immunoglobulin treatment. Neuropsychiatric disorder associated with GGS infection was ultimately diagnosed. The present findings suggest that neuropsychiatric disorders can result from GGS infection and that the pathogenic mechanism is similar to that of GABHS infection. Future large-scale studies should examine the relation between GGS infection and onset of neuropsychiatric disorder.

    DOI: 10.1155/2018/6047318

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  • Improved parental attitudes and beliefs through stepwise perinatal vaccination education. 査読 国際誌

    Aya Saitoh, Akihiko Saitoh, Isamu Sato, Tomohiro Shinozaki, Hajime Kamiya, Satoko Nagata

    Human vaccines & immunotherapeutics   13 ( 11 )   2639 - 2645   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This study examined the effects of providing vaccination education during the perinatal period on Japanese parents' knowledge, attitudes, and beliefs about childhood vaccination. A cluster-randomized controlled-trial method was used on a sample of 160 pregnant women recruited from 9 obstetrical sites in Niigata, Japan. The treatment group received a stepwise interactive education intervention, while the control group received a general vaccination leaflet. Changes in parental attitudes toward and beliefs about infant vaccination were assessed on the child's one-month and 6-month birthdays using paper questionnaires. Of the initial 188 participants, 160 (90.4%) completed the final post-survey questionnaire. Scores on injunctive social norms (a morally neutral perception of the behavior of the majority) and descriptive social norms (a moral perception of what individuals should do) significantly increased in the treatment group (p = .02 and p = .01, respectively). There was a significant difference between the 2 groups over time in terms of perceived benefit (efficacy of available preventive actions) (p = .03), but no significant differences in perceived severity (seriousness of a disease outcome), perceived susceptibility (likelihood of getting a disease), perceived benefits, perceived behavioral control, or descriptive social norms between the groups at any time point or in the patterns of change over time (p > .31). Thus, stepwise perinatal vaccination education was found to positively influence maternal attitudes and beliefs about infant vaccination. This study suggests the importance of vaccination education during the perinatal period.

    DOI: 10.1080/21645515.2017.1368601

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  • Subcutaneous chest wall abscess as a complication of BCG vaccination. 査読 国際誌

    Taketo Otsuka, Ryosuke Hosokai, Toru Watanabe, Naruhiko Ishiwada, Akihiko Saitoh

    Pediatrics international : official journal of the Japan Pediatric Society   59 ( 11 )   1206 - 1208   2017年11月

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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/ped.13382

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  • PTEN mutation in a Japanese boy with autonomously functioning thyroid nodule. 査読 国際誌

    Hiromi Nyuzuki, Takahiko Kogai, Akira Hishinuma, Yohei Ogawa, Akihiko Saitoh, Keisuke Nagasaki

    Pediatrics international : official journal of the Japan Pediatric Society   59 ( 11 )   1223 - 1224   2017年11月

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    記述言語:英語  

    DOI: 10.1111/ped.13427

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  • ヒトパレコウイルス4型による敗血症様症候群を呈した新生児の1例

    中山 有美, 相澤 悠太, 大塚 岳人, 齋藤 昭彦

    小児感染免疫   29 ( 3 )   259 - 262   2017年10月

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    記述言語:日本語   出版者・発行元:日本小児感染症学会  

    日齢22の男児が入院前日からの発熱を主訴に来院し、体幹と四肢に網状チアノーゼを認め、敗血症様症候群と診断された。血清のリアルタイムPCRと遺伝子解析により、ヒトパレコウイルス4型(human parechovirus type 4:HPeV4)が同定された。さらに、HPeV4に対するペア血清で中和抗体価の上昇を確認し、診断を確定した。同定された17の遺伝子型の内、ヒトパレコウイルス3型(human parechovirus type 3:HPeV3)は新生児に敗血症や髄膜脳炎など、重症感染症を引き起こすことが知られているが、HPeV4は軽症の胃腸炎や呼吸器感染症の患者の便からの報告がほとんどである。HPeV4が敗血症様症候群を呈した症例報告は世界でも数例であり、この症例は国内初の報告である。ヒトパレコウイルスの異なる遺伝子型の感染症の臨床像を明らかにするためには、遺伝子型の同定が必要であり、また、症例の集積が重要である。(著者抄録)

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  • 自家末梢血幹細胞移植後のHBV再活性化に対するエンテカビルの使用経験

    久保 暢大, 高地 貴行, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   54 ( 4 )   374 - 374   2017年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • EBウイルス関連血球貪食症候群に対する免疫化学療法に合併したClostridium difficile結腸炎の1例

    坂井 知倫, 岩渕 晴子, 久保 暢大, 高地 貴行, 今村 勝, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   54 ( 4 )   375 - 375   2017年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 各種治療が無効であったが、発症10年後に自然軽快したびまん性肺リンパ管腫症の1例

    申 将守, 久保 暢大, 笠原 靖史, 高地 貴行, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   54 ( 4 )   330 - 330   2017年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 繰り返す腸重積で発見されλ鎖陽性B細胞のモノクローナル増殖を呈した虫垂atypical lymphoid hyperplasiaの一例

    小貫 孝則, 高地 貴行, 久保 暢大, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   54 ( 4 )   322 - 322   2017年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • Successful treatment of histiocytic sarcoma with cladribine and high-dose cytosine arabinoside in a child. 査読

    Haruko Iwabuchi, Hiroyuki Kawashima, Hajime Umezu, Takayuki Takachi, Masaru Imamura, Akihiko Saitoh, Akira Ogose, Chihaya Imai

    International journal of hematology   106 ( 2 )   299 - 303   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Histiocytic sarcoma, a rare hematopoietic neoplasm with evidence of histiocytic differentiation, is often refractory to conventional chemotherapy and radiotherapy, and its prognosis is generally dismal. The optimal management of this malignancy has not been established. We report a case of 8-year-old girl with histiocytic sarcoma involving the left femur. The tumor rapidly responded to a combination of cladribine and high-dose cytosine arabinoside, an aggressive salvage regimen for refractory Langerhans cell histiocytosis, and became impalpable during the first cycle. The patient has remained in complete remission more than 7 years from diagnosis.

    DOI: 10.1007/s12185-017-2202-8

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  • 2008年以降に新潟県で発生した再生不良性貧血の臨床的検討

    久保 暢大, 高地 貴行, 岩渕 晴子, 今村 勝, 申 将守, 笠原 靖史, 細貝 亮介, 吉田 咲子, 渡辺 輝浩, 小川 淳, 今井 千速, 齋藤 昭彦

    日本小児科学会雑誌   121 ( 8 )   1419 - 1419   2017年8月

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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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  • 軟部組織病変を呈し特異な臨床経過を示したランゲルハンス細胞組織球症の1例

    古寺 一樹, 今村 勝, 高地 貴行, 申 将守, 笠原 靖史, 岩渕 晴子, 川島 寛之, 生越 章, 梅津 哉, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   54 ( 2 )   157 - 160   2017年6月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

    ランゲルハンス細胞組織球症(LCH)は、ランゲルハンス細胞様細胞(LCH細胞)のモノクローナルな腫瘍性増殖をきたす疾患である。骨病変の頻度が最も高く、軟部組織単独病変は稀である。今回我々は、胸椎の骨融解病変、胸膜病変、および骨病変に連続しない後頸部の軟部組織病変を伴う多臓器型LCHの5歳女児例を経験した。本例は当初、後頸部皮下膿瘍および化膿性脊椎炎の疑いで抗菌薬が投与され、解熱し病変部位の腫脹が軽減消失したことから、結果的に化学療法の同意が得られず経過観察の方針となった。約9ヵ月間で2回の再燃を観察し、いずれも抗菌薬投与のみで解熱し、局所症状も軽減消失した。最終的に多剤併用化学療法を導入したところ、速やかに寛解が得られ、4年間再発なく経過良好である。本例はLCHでは稀な軟部組織病変を伴うのみならず、抗菌薬による一時的効果が観察された点で、LCHの複雑な病態を考察する上で貴重と思われる。(著者抄録)

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  • Glomerular Density and Volume in Renal Biopsy Specimens of Children with Proteinuria Relative to Preterm Birth and Gestational Age. 査読 国際誌

    Kentaro Koike, Yohei Ikezumi, Nobuo Tsuboi, Go Kanzaki, Kotaro Haruhara, Yusuke Okabayashi, Takaya Sasaki, Makoto Ogura, Akihiko Saitoh, Takashi Yokoo

    Clinical journal of the American Society of Nephrology : CJASN   12 ( 4 )   585 - 590   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND OBJECTIVES: A low total nephron number, which is associated with low birth weight (LBW), may indicate increased susceptibility to early-onset renal diseases in children. However, few studies have assessed renal biopsy findings in LBW children. We examined the relationship between LBW and glomerular density (GD) and/or glomerular volume (GV) in renal biopsy samples as a surrogate for total nephron number. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Renal biopsy findings of children of LBW were compared with those of age-matched control subjects of normal birth weight (NBW) who were histopathologically diagnosed with FSGS or minimal change nephrotic syndrome (MCNS) from 1995 to 2011. The GD and GV were estimated on the basis of measurements obtained by computerized image analysis. RESULTS: A total of 31 subjects (mean age 11 years; eight with low birth weight-FSGS [LBW-FSGS], 10 with normal birth weight-FSGS [NBW-FSGS], and 13 with normal birth weight-minimal change nephrotic syndrome [NBW-MCNS]) were analyzed. The mean birth weight of each group was 777 g (629-1000), 3110 g (2888-3358), and 3120 g (2748-3398), respectively (median [25th-75th percentile]). Age, body mass index, BP, and degrees of globally sclerotic glomeruli at biopsy were comparable between the groups. The GD was lower (LBW-FSGS, 1.4±0.6/mm2; NBW-FSGS, 3.3±1.2/mm2; and NBW-MCNS, 3.6±1.1/mm2; P<0.05) and the GV was greater (LBW-FSGS, 4.1 [3.1-5.1]×106µm3; NBW-FSGS, 1.6 [1.5-2.1]×106µm3; and NBW-MCNS, 1.3 [1.1-1.8]×106µm3 [median, (25th-75th percentile)]; P<0.05) in patients with LBW-FSGS than in the other patient groups. The GD showed close positive correlations with birth weight (r=0.48) and gestational age (r=0.54), independent of renal function and degree of global glomerular sclerosis. CONCLUSIONS: A low GD together with marked glomerular enlargement characterizes renal biopsy samples of children born with a LBW at an early stage of gestation.

    DOI: 10.2215/CJN.05650516

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  • Long term survival of a patient with Perlman syndrome due to novel compound heterozygous missense mutations in RNB domain of DIS3L2. 査読 国際誌

    Noriko Soma, Ken Higashimoto, Masaru Imamura, Akihiko Saitoh, Hidenobu Soejima, Keisuke Nagasaki

    American journal of medical genetics. Part A   173 ( 4 )   1077 - 1081   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Perlman syndrome is a rare overgrowth syndrome characterized by polyhydramnios, macrosomia, distinctive facial appearance, renal dysplasia, and a predisposition to Wilms' tumor. The syndrome is often associated with a high neonatal mortality rate and there are few reports of long-term survivors. We studied a 6-year-old Japanese female patient, who was diagnosed with Perlman syndrome, with novel compound heterozygous mutations in DIS3L2 (c.[367-2A > G];[1328T > A]), who has survived long term. Most reported DIS3L2 mutations have been the homozygous deletion of exon 6 or exon 9, and these mutations would certainly have caused the loss of both RNA binding and degradation activity. We have identified new compound heterozygous mutations in the DIS3L2 of this long-term survivor of Perlman syndrome. The reason our patient has survived long-term would be a missense mutation (c.1328 T > A, p.Met443Lys) having retained RNA binding in both the cold-shock domains and the S1 domain, and through partial RNA degradation. If partial exonuclease functions remain in at least one allele, long-term survival may be possible. Further studies of Perlman syndrome patients with proven DIS3L2 mutations are needed to clarify genotype-phenotype correlation.

    DOI: 10.1002/ajmg.a.38111

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  • Donor Killer Immunoglobulin-Like Receptor Haplotype B/x Induces Severe Acute Graft-versus-Host Disease in the Presence of Human Leukocyte Antigen Mismatch in T Cell-Replete Hematopoietic Cell Transplantation. 査読 国際誌

    Ryosuke Hosokai, Masayoshi Masuko, Yasuhiko Shibasaki, Akihiko Saitoh, Tatsuo Furukawa, Chihaya Imai

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   23 ( 4 )   606 - 611   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Natural killer cells have been identified as a mediator of alloimmune reactions in allogeneic hematopoietic stem cell transplantation (HSCT). Killer immunoglobulin-like receptors (KIRs) are an important determinant of natural killer cell function. The relationship between KIR genotypes/haplotypes and clinical outcomes of allogeneic HSCT is complex and inconsistent among several reports. We assessed the clinical impact of KIR haplotype on T cell-replete allogeneic HSCTs performed in a single Japanese center for hematological malignancies (n = 106). A comparison of 2 groups, donor haplotypes A/A and B/x, revealed no significant differences in overall survival, relapse, and nonrelapse mortality. However, grade III to IV acute graft-versus-host disease (GVHD) occurred significantly more frequently in the KIR haplotype B/x group (A/A versus B/x: 4.9% versus 20.0%; P = .02). This was even more evident when HLA mismatch was present. The highest incidences of grade II to IV and grade III to IV acute GVHD were observed in patients who received allografts from HLA-mismatched donors with KIR haplotype B/x. These data highlight the importance of KIR genotyping in donor matching, especially when HLA mismatch allogeneic grafting is planned.

    DOI: 10.1016/j.bbmt.2016.12.638

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  • Effect of stepwise perinatal immunization education: A cluster-randomized controlled trial. 査読 国際誌

    Aya Saitoh, Akihiko Saitoh, Isamu Sato, Tomohiro Shinozaki, Hajime Kamiya, Satoko Nagata

    Vaccine   35 ( 12 )   1645 - 1651   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Perinatal immunization education is important for improving the immunization outcomes of infants; however, the content of educational materials used at each perinatal period has not been carefully evaluated. We hypothesized that stepwise education offered at different perinatal periods would improve infant immunization status and enhance maternal immunization knowledge. METHODS: In this cluster-randomized controlled trial, pregnant women were recruited from nine obstetric sites in Niigata, Japan. The intervention group received a stepwise, interactive education intervention (prenatally, postnatally, and 1month after birth). The control group received a leaflet containing general information on immunization. Infant immunization status was evaluated at 6months of age, and maternal immunization knowledge was evaluated by a written survey after each intervention. RESULTS: Among 188 study participants, 151 (80.3%) replied to the final post-intervention survey. At 6months of age, the percentage of children who completed three doses of inactivated polio, diphtheria, tetanus toxoid, and acellular pertussis (DTaP-IPV) vaccine was higher in the intervention group than in the control (p=0.04); however, no differences between groups were observed for the Haemophilus influenzae type b (Hib) (p=0.67) or 13-valent pneumococcal conjugate (PCV13) vaccines (p=0.20). The duration to the completion of the third dose of the DTaP-IPV, Hib, and PCV13 vaccines was shorter in the intervention group than in the control (p=0.03, p<0.01, and p<0.01, respectively). Furthermore, maternal knowledge scores exhibited significantly greater improvement in the intervention group over time compared with those of the control group (p=0.02). CONCLUSIONS: Stepwise perinatal immunization education improved immunization schedule adherence for required vaccines and improved maternal immunization knowledge.

    DOI: 10.1016/j.vaccine.2017.01.069

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  • 母子感染予防実施後に神経芽腫に対する化学療法を契機としたB型肝炎再活性化の一例

    古寺 一樹, 今村 勝, 久保 暢大, 高地 貴行, 岩渕 晴子, 今井 千速, 齋藤 昭彦

    日本小児科学会雑誌   121 ( 2 )   237 - 237   2017年2月

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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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  • 遺伝子解析法により診断したBCGワクチン株による皮下腫瘤の幼児例 査読

    大塚 岳人, 井口 英幸, 細貝 亮介, 渡辺 徹, 竹内 典子, 石和田 稔彦, 齋藤 昭彦, 大楠 美佐子

    日本小児科学会雑誌   121 ( 2 )   459 - 459   2017年2月

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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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  • B.cereus髄膜炎を合併した急性骨髄性白血病の救命例 TDMの重要性

    久保 暢大, 吉田 咲子, 申 将守, 笠原 靖史, 高地 貴行, 岩渕 晴子, 今村 勝, 今井 千速, 齋藤 昭彦

    日本小児科学会雑誌   121 ( 2 )   467 - 467   2017年2月

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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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  • 細菌性髄膜炎を契機に診断された先天性皮膚洞の一例

    榎本 瑞生, 白井 崇準, 小嶋 絹子, 板垣 成孝, 鈴木 博, 和田 雅樹, 井口 英幸, 大橋 伯, 大塚 岳人, 斎藤 昭彦

    日本小児科学会雑誌   121 ( 2 )   464 - 464   2017年2月

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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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  • Suppression of MUC5AC expression in human bronchial epithelial cells by interferon-γ. 査読 国際誌

    Takahito Oyanagi, Takumi Takizawa, Akira Aizawa, Orosoo Solongo, Hisako Yagi, Yutaka Nishida, Harumi Koyama, Akihiko Saitoh, Hirokazu Arakawa

    Allergology international : official journal of the Japanese Society of Allergology   66 ( 1 )   75 - 82   2017年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Excessive mucin secretion in the airway is an important feature of airway inflammatory diseases. MUC5AC expression is regulated by a variety of stimuli such as cytokines. Little is known about the role of interferon (IFN)-γ in MUC5AC expression in human bronchial epithelial cells. METHODS: Human pulmonary mucoepidermoid carcinoma cell line (NCI-H292) and normal human bronchial epithelial (NHBE) cells were used to assess the effects of IFN-γ on MUC5AC transcription. RESULTS: Transforming growth factor (TGF)-α and double-stranded RNA (polyI:C)-induced MUC5AC mRNA and protein expression was repressed by IFN-γ in a concentration-dependent manner. IFN-γ showed limited effects on TGF-α and polyI:C-induced activation of epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK). A chromatin immunoprecipitation assay indicated that Sp1 bound to its cognate sequence located on the MUC5AC promoter. The Sp1 inhibitor mithramycin A inhibited MUC5AC mRNA expression, implying a critical role for Sp1 in MUC5AC induction. Importantly, IFN-γ impeded Sp1 binding to the MUC5AC promoter. CONCLUSIONS: These results suggest that IFN-γ represses MUC5AC expression, disturbing binding of Sp1 to its target sequences.

    DOI: 10.1016/j.alit.2016.05.005

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  • Rituximab protects podocytes and exerts anti-proteinuric effects in rat adriamycin-induced nephropathy independent of B-lymphocytes. 査読 国際誌

    Yuichi Takahashi, Yohei Ikezumi, Akihiko Saitoh

    Nephrology (Carlton, Vic.)   22 ( 1 )   49 - 57   2017年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: This study was aimed at examining the effects of treatment with rituximab, a chimeric monoclonal antibody against the protein CD20, in a B-lymphocyte independent adriamycin-induced rat model of nephrotic syndrome. Rituximab is an emerging rescue therapy used in patients with complicated nephrotic syndrome and, therefore, we sought to elucidate the apparent B-lymphocyte independent mechanism underlying its anti-proteinuric effect. METHODS: Adriamycin-induced nephropathy was established in Wistar rats by intravenously injecting 10 mg/kg of adriamycin, which were then treated with rituximab or purified human IgG weekly and euthanized on day 28. Proteinuria, glomerular expression of sphingomyelin phosphodiesterase acid-like 3b protein, and podocyte-related proteins were examined using immunofluorescence staining and a reverse transcription-polymerase chain reaction. RESULTS: Rituximab treatment of rats with adriamycin-induced nephropathy significantly reduced urinary protein excretion 14 to 28 days after induction of disease, compared with those treated with purified normal human IgG. Furthermore, rituximab treatment also prevented the reduction of glomerular nephrin and podocin expression on day 28. Double-immunofluorescence staining revealed that after in vivo administration, rituximab was bound to the glomeruli, which also expressed synaptopodin or sphingomyelin phosphodiesterase, acid-like 3b. Moreover, sphingomyelin phosphodiesterase, acid-like 3b expression was significantly decreased on day 28 of adriamycin-induced nephropathy, which was also prevented by rituximab. CONCLUSIONS: This study demonstrated that rituximab directly affected glomerular podocytes and ameliorated proteinuria in adriamycin-induced nephropathy in rats. Furthermore, protection of podocyte function by rituximab may be mediated by direct modulation of a sphingomyelin phosphodiesterase, acid-like 3b-dependent mechanism.

    DOI: 10.1111/nep.12737

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  • Haemophilus influenzae peritonitis in a girl on automated peritoneal dialysis: Case report and review of the literature. 査読 国際誌

    Taketo Otsuka, Hiroya Hasegawa, Takeshi Yamada, Utako Kaneko, Akihiko Saitoh

    IDCases   9   47 - 49   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Haemophilus influenzae is a rare cause of peritonitis in patients on peritoneal dialysis (PD). We report a case of peritonitis due to non-typeable H. influenzae in a 5-year-old girl on automated PD. The patient was successfully treated with intraperitoneal cefepime and cefazolin. The isolate was multilocus sequence type 3 and contained the hmw and hia genes but was IS1016-negative. Seven of the eight reported cases were female, indicating that sex-associated factors may be important in H. influenzae peritonitis in patients on PD. Determination of the pathogenesis of PD-associated H. influenzae peritonitis requires gene analysis and a swab sample from the vaginal introitus.

    DOI: 10.1016/j.idcr.2017.06.003

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  • Performance of a real-time PCR-based approach and droplet digital PCR in detecting human parechovirus type 3 RNA. 査読 国際誌

    Yuta Aizawa, Akihide Koyama, Tomohiko Ishihara, Osamu Onodera, Akihiko Saitoh

    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology   84   27 - 31   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Human parechovirus type 3 (HPeV3) is an emerging virus that causes sepsis and meningoencephalitis in neonates and young infants. Correct diagnosis of HPeV3 infection is critical in determining appropriate management and predicting patients' clinical course. Real-time reverse transcription PCR (RT-PCR) analysis of serum and/or cerebrospinal fluid (CSF) has been used to diagnose HPeV3 infection; however, the assay detection limits have not been fully evaluated. OBJECTIVES: We tested the hypothesis that droplet digital RT-PCR (RT-ddPCR)-a novel technique that precisely quantitates low-copy target genes by diluting and partitioning samples into compartments-increases the detection rate of HPeV3 RNA as compared with real-time RT-PCR. STUDY DESIGN: Using samples with predetermined HPeV3 copy numbers, we evaluated one-step and two-step RT-ddPCR. Then, we tested two-step RT-ddPCR and real-time RT-PCR, using clinical samples with low copy numbers. Finally, we used two-step RT-ddPCR to evaluate clinical samples obtained from HPeV3-infected patients with positive serum but negative CSF, as determined by real-time RT-PCR. RESULTS: Two-step RT-ddPCR was less variable and more specific than one-step RT-ddPCR. Two-step RT-ddPCR detected HPeV3 RNA in all six CSF samples; four samples (67%) were reproducibly positive and the other two samples (33%) were positive at least once in four replicates. Finally, no nonspecific droplet was positive by two-step RT-ddPCR. CONCLUSIONS: Two-step RT-ddPCR may enhance the rate of HPeV3 RNA detection from samples with low viral loads, thereby improving diagnosis and management of HPeV3-infected patients.

    DOI: 10.1016/j.jcv.2016.09.009

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  • 初期治療18年後に眼窩外多発転移再発した両側性網膜芽細胞腫の治療経験(Extraocular multiple metastatic recurrence 18 years after the initial treatment of bilateral retinoblastoma: a case report and literature review)

    高地 貴行, 申 将守, 岩渕 晴子, 今村 勝, 梅津 哉, 川島 寛之, 生越 章, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   53 ( 4 )   364 - 364   2016年11月

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    記述言語:英語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 髄芽腫術後2週間以内の全脳脊髄照射及びSJM-96式自家末梢血幹細胞救援併用反復大量化学療法の実現可能性(Feasibility of SJMB-96 based repetitive high-dose chemotherapy with PBSC rescue and CSI within two weeks after surgery for medulloblastoma)

    今村 勝, 久保 暢大, 申 将守, 笠原 靖史, 細貝 亮介, 高地 貴行, 吉田 咲子, 岩渕 晴子, 齋藤 昭彦, 青山 英史, 吉村 淳一, 今井 千速

    日本小児血液・がん学会雑誌   53 ( 4 )   360 - 360   2016年11月

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    記述言語:英語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • ヒトprimary NK細胞へのインターロイキン21遺伝子の導入は抗白血病作用を増強する(Genetic engineering of primary natural killer cells with human Interleukin-21 enhances their anti-leukemic capacity)

    笠原 靖史, 申 将守, 高地 貴行, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   53 ( 4 )   279 - 279   2016年11月

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    記述言語:英語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • A novel mutation in the human mineralocorticoid receptor gene in a Japanese family with autosomal-dominant pseudohypoaldosteronism type 1. 査読

    Yoshimi Nishizaki, Makoto Hiura, Hidetoshi Sato, Yohei Ogawa, Akihiko Saitoh, Keisuke Nagasaki

    Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology   25 ( 4 )   135 - 138   2016年10月

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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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  • Intradermal vaccination for infants and children. 査読 国際誌

    Akihiko Saitoh, Yuta Aizawa

    Human vaccines & immunotherapeutics   12 ( 9 )   2447 - 55   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Intradermal (ID) vaccination induces a more potent immune response and requires lower vaccine doses as compared with standard vaccination routes. To deliver ID vaccines effectively and consistently, an ID delivery device has been developed and is commercially available for adults. The clinical application of ID vaccines for infants and children is much anticipated because children receive several vaccines, on multiple occasions, during infancy and childhood. However, experience with ID vaccines is limited and present evidence is sparse and inconsistent. ID delivery devices are not currently available for infants and children, but recent studies have examined skin thickness in this population and reported that it did not differ in proportion to body size in infants, children, and adults. These results are helpful in developing new ID devices and for preparing new vaccines in infants and children.

    DOI: 10.1080/21645515.2016.1176652

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  • 大脳白質障害を認めた新生児ヒトパレコウイルス感染症の2例

    萩原 秀俊, 松本 浩, 橋本 逸美, 藤田 基資, 野村 智章, 田村 義輝, 茂木 陽, 若松 太, 川口 裕之, 相澤 悠太, 齋藤 昭彦, 野々山 恵章

    日本小児科学会雑誌   120 ( 7 )   1087 - 1093   2016年7月

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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  

    症例1(在胎37週0日に出生した2590gの男児)。日齢7より哺乳時にチアノーゼが認め近医を受診、体重増加不良、無呼吸発作を指摘され、日齢10に著者らの施設へ紹介となった。症例2(在胎40週0日に出生した2935gの男児)。日齢29に発熱、意識レベル低下、四肢振戦を認めるようになり、日齢30に前医を受診、細菌性髄膜炎を疑われ、入院加療を受けるも無呼吸が出現したため、日齢31に著者らの施設へ転院となった。両症例とも新生児敗血症様症状で発症し、血清AST、LDH、フェリチン、sIL-2Rの上昇や凝固機能障害ほか、脳MRIでは大脳白質障害を呈していた。治療として、症例1は挿管・人工呼吸管理、症例2は経鼻持続気道陽圧呼吸が行われた。ステロイド治療は施行されなかったが、明らかな神経学的後遺症なく、症状の改善が得られた。尚、患者それぞれの血清、髄液から逆転写PCRでHPeVゲノムが検出され、本症例は新生児ヒトパレコウイルス感染症の診断に至った。

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  • 先天性心疾患児における胸郭の形態変化と肺静脈狭窄との関連

    星名 哲, 額賀 俊介, 馬場 恵史, 塚田 正範, 鳥越 司, 羽二生 尚訓, 沼野 藤人, 鈴木 博, 齋藤 昭彦

    日本小児循環器学会雑誌   32 ( Suppl.1 )   s1 - 274   2016年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本小児循環器学会  

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  • 自然軽快したEBウイルス関連血球貪食性リンパ組織球症の1例

    皆川 雄介, 申 将守, 高地 貴行, 岩渕 晴子, 今村 勝, 今井 千速, 齋藤 昭彦

    日本小児科学会雑誌   120 ( 5 )   917 - 918   2016年5月

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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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  • Immunization practices in solid organ transplant recipients. 査読 国際誌

    Isao Miyairi, Takanori Funaki, Akihiko Saitoh

    Vaccine   34 ( 16 )   1958 - 64   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Vaccine-preventable diseases are a significant cause of morbidity and mortality in solid organ transplant recipients who undergo immunosuppression after transplantation. The primary strategy for immunizing transplant recipients is to deliver all potential vaccines prior to transplantation. However, time constraints limit the number of vaccines that may be delivered. In such cases, the administration of live attenuated vaccines that are contraindicated after transplantation should be prioritized. Simultaneous vaccination is also encouraged to maximize the number of vaccines delivered. Immunity induced by both inactivated and live vaccines wane after transplantation. The limited but available evidence suggests that immunization using inactivated vaccines in transplant recipients is both effective and safe. An increasing number of studies also suggest that once patients are under minimal immunosuppression, live attenuated vaccines may be given effectively and safely. The need for serologic monitoring and booster immunizations remain issues for future research.

    DOI: 10.1016/j.vaccine.2016.03.001

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  • Symposium report of the 17th annual meeting of the Japanese Society for Vaccinology, 2013: Bacterial vaccines: Effectiveness and issues. 査読 国際誌

    Takashi Nakano, Masahiro Watanabe, Akihiko Saitoh, Shigeru Suga, Kazunori Oishi, Naoko Nishimura

    Vaccine   34 ( 16 )   1956 - 7   2016年4月

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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.vaccine.2015.09.084

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  • Criteria for radiologic diagnosis of hypochondroplasia in neonates. 査読 国際誌

    Tomoko Saito, Keisuke Nagasaki, Gen Nishimura, Masaki Wada, Hiromi Nyuzuki, Masaki Takagi, Tomonobu Hasegawa, Naoko Amano, Jun Murotsuki, Hideaki Sawai, Takahiro Yamada, Shuhei Sato, Akihiko Saitoh

    Pediatric radiology   46 ( 4 )   513 - 8   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: A radiologic diagnosis of hypochondroplasia is hampered by the absence of age-dependent radiologic criteria, particularly in the neonatal period. OBJECTIVE: To establish radiologic criteria and scoring system for identifying neonates with fibroblast growth factor receptor 3 (FGFR3)-associated hypochondroplasia. MATERIALS AND METHODS: This retrospective study included 7 hypochondroplastic neonates and 30 controls. All subjects underwent radiologic examination within 28 days after birth. We evaluated parameters reflecting the presence of (1) short ilia, (2) squared ilia, (3) short greater sciatic notch, (4) horizontal acetabula, (5) short femora, (6) broad femora, (7) metaphyseal flaring, (8) lumbosacral interpedicular distance narrowing and (9) ovoid radiolucency of the proximal femora. RESULTS: Only parameters 1, 3, 4, 5 and 6 were statistically different between the two groups. Parameters 3, 5 and 6 did not overlap between the groups, while parameters 1 and 4 did. Based on these results, we propose a scoring system for hypochondroplasia. Two major criteria (parameters 3 and 6) were assigned scores of 2, whereas 4 minor criteria (parameters 1, 4, 5 and 9) were assigned scores of 1. All neonates with hypochondroplasia in our material scored ≥6. CONCLUSION: Our set of diagnostic radiologic criteria might be useful for early identification of hypochondroplastic neonates.

    DOI: 10.1007/s00247-015-3518-2

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  • Soluble LR11 is a novel biomarker for vascular lesions late after Kawasaki disease. 査読 国際誌

    Kenichi Watanabe, Hiroshi Suzuki, Meizi Jiang, Hisanori Haniu, Fujito Numano, Satoshi Hoshina, Akihiko Saitoh, Makoto Uchiyama, Hideaki Bujo

    Atherosclerosis   246   94 - 7   2016年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Coronary artery lesions (CALs) and a risk for early onset of atherosclerosis are major concerns following Kawasaki disease (KD). Intimal smooth muscle cells (SMCs) have an important role in vascular lesions in KD. It is known that soluble LR11 (sLR11) is a novel biomarker for vascular lesions and LR11 is markedly expressed in intimal SMCs in atherosclerotic lesions. In this study, we hypothesized that sLR11 reflects the presence of vascular lesions late after KD. METHODS: Twenty-three age-matched controls (group 1) and 59 patients with a history of KD were enrolled; 36 with KD had normal coronary arteries or regressed aneurysms (group 2), and 23 had CALs (group 3). RESULTS: Serum sLR11 levels in group 3 (median, interquartile range (IQR): 11.1 ng/mL, 9.3-13.9 ng/mL) were significantly higher than those in groups 1 (8.4 ng/mL, 7.1-10.2 ng/mL, p < 0.001) and 2 (9.0 ng/mL, 7.7-10.1 ng/mL, p < 0.01). Levels of sLR11 were positively correlated with levels of high-sensitivity C-reactive protein (r = 0.480, p < 0.01) and lipoprotein (a) (r = 0.486, p < 0.01). CONCLUSION: These findings suggest that sLR11 reflects the development of vascular lesions in patients with serious CALs.

    DOI: 10.1016/j.atherosclerosis.2015.12.035

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  • High rate of vaccine failure after administration of acellular pertussis vaccine pre- and post-liver transplantation in children at a children's hospital in Japan 査読

    K. Ito, M. Kasahara, A. Saitoh, H. Honda, I. Miyairi

    Transplant Infectious Disease   18 ( 1 )   150 - 154   2016年2月

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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:Blackwell Publishing Inc.  

    We assessed the serological response to pertussis vaccines administered pre- and post-liver transplantation in 58 pediatric patients at a children's hospital in Japan. A high rate of pertussis vaccine failure was observed, 44.8% against the pertussis toxin and 69.0% against filamentous hemagglutinin, with no difference in the seropositivity rate with respect to the timing of the vaccination during the peritransplant period.

    DOI: 10.1111/tid.12484

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  • Clinical utility of serum samples for human parechovirus type 3 infection in neonates and young infants: The 2014 epidemic in Japan. 査読 国際誌

    Yuta Aizawa, Yuko Suzuki, Kanako Watanabe, Tomohiro Oishi, Akihiko Saitoh

    The Journal of infection   72 ( 2 )   223 - 32   2016年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    During the 2014 human parechovirus type 3 (HPeV3) epidemic in Niigata, Japan, this prospective observational study identified HPeV3 from 43/85 (51%) febrile young infants <4 months using PCR analysis of serum (n = 42) and/or cerebrospinal fluid (CSF) (n = 32) and genetic sequencing of the VP1 region of HPeV3. HPeV3-infected patients (median age, 32 days; range, 4-113 days) were diagnosed as having sepsis (79%), sepsis-like syndrome (19%), or encephalitis with septic shock (2%). Other than fever, mottled skin (67%) was significantly more frequent in HPeV3-infected patients than other virus-infected patients (P = 0.005). The rate of HPeV3 RNA detection in CSF without pleocytosis was high (88%; 28/32). Among the 32 patients whose serum and CSF samples were available, all patients were positive for serum PCR; however, 4 (12%) patients were negative for CSF PCR. Serum HPeV3 RNA level on admission was associated with younger age (P = 0.002), bad temper (P = 0.041), and grunting (P = 0.008). Among 6 patients with sequential data on serum HPeV3 RNA level, levels decreased rapidly without specific therapy. In conclusion, serum samples at disease onset are the most useful compared to CSF in detection of HPeV RNA and serum HPeV3 RNA level on admission was associated with important clinical manifestations in HPeV3-infected patients.

    DOI: 10.1016/j.jinf.2015.10.010

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  • Local leukocyte proliferation as a target for cyclophosphamide in the treatment of Henoch-Schönlein purpura nephritis grade VI. 査読 国際誌

    Masahiro Kaneko, Yohei Ikezumi, Takeshi Yamada, Hiroya Hasegawa, Utako Kaneko, Akihiko Saitoh

    Nephrology (Carlton, Vic.)   21 ( 1 )   68 - 71   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Henoch-Schönlein purpura nephritis (HSPN) is one of the most common types of chronic glomerulonephritis in children; however, there have been few reports on the pathogenesis and management of grade VI HSPN. We present the case of a 6-year-old boy with grade VI HSPN accompanied by severe nephrotic syndrome and hypocomplementaemia. Immunohistological studies revealed profound glomerular accumulation of CD45- and CD68-positive inflammatory cells. Moreover, some cells expressed the proliferating marker proliferating cell nuclear antigen. His proteinuria and general oedema persisted despite repeated high-dose steroid therapy; however, these clinical symptoms immediately improved after beginning treatment with cyclophosphamide (CyP). Grade VI HSPN was successfully treated with steroids and immunosuppressants. Among immunosuppressive drugs, CyP was considered the most effective.

    DOI: 10.1111/nep.12558

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  • Pediatric Cohort With Long QT Syndrome - KCNH2 Mutation Carriers Present Late Onset But Severe Symptoms. 査読

    Junichi Ozawa, Seiko Ohno, Takashi Hisamatsu, Hideki Itoh, Takeru Makiyama, Hiroshi Suzuki, Akihiko Saitoh, Minoru Horie

    Circulation journal : official journal of the Japanese Circulation Society   80 ( 3 )   696 - 702   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: In children with long QT syndrome (LQTS), risk factors for cardiac events have been reported, but age-, gender- and genotype-related differences in prognosis remain unknown in Asian countries. METHODS AND RESULTS: The study examined clinical prognosis at age between 1 and 20 years in 496 LQTS patients who were genotyped as either of LQT1-3 (male, n=206). Heterozygous mutations were observed in 3 major responsible genes:KCNQ1in271,KCNH2in 192, andSCN5Ain 33 patients. LQTS-associated events were classified into 3 categories: (1) syncope (n=133); (2) repetitive torsade de pointes (TdP, n=3); and (3) cardiopulmonary arrest (CPA, n=4). The risk of cardiac events was significantly lower in LQT1 girls than boys≤12 years (HR, 0.55), whereas LQT2 female patients ≥13 years had the higher risk of cardiac events than male patients (HR, 4.60). Patients in the repetitive TdP or CPA group included 1 LQT1 female patient, 1 LQT2 male patient, and 5 LQT2 female patients. All LQT2 patients in these groups had TdP repeatedly immediately after the antecedent event. In addition, all 5 female LQT2 patients in these groups had the event after or near puberty. CONCLUSIONS: Female LQT2 children might have repeated TdP shortly after prior events, especially after puberty. (Circ J 2016; 80: 696-702).

    DOI: 10.1253/circj.CJ-15-0933

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  • Current practices and needs regarding perinatal childhood immunization education for Japanese mothers. 査読 国際誌

    Aya Saitoh, Akihiko Saitoh, Isamu Sato, Tomohiro Shinozaki, Satoko Nagata

    Vaccine   33 ( 45 )   6128 - 33   2015年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Accurate, standardized information on childhood immunization is not available in Japan. We investigated current practices in perinatal childhood immunization education in the community and the needs and interest for such education among Japanese mothers. METHODS: This cross-sectional, descriptive study evaluated pregnant and postnatal women at four institutions in Niigata, Japan from May through July 2014. Data were collected using questionnaires inquiring about demographics, immunization education received, intent to receive childhood vaccines, and needs regarding information on childhood immunization. RESULTS: Questionnaires were distributed to 300 women, and 116 (38.6%) were returned; 70 (59.6%) of the respondents were pregnant women and 46 (40.3%) were postnatal women. Fourteen (20%) of the 70 pregnant women reported receiving some form of immunization education; in contrast, 34 (73.9%) of 46 postnatal women had received such education within 1 month of delivery. The rates of respondents who felt that the information was insufficient were high: 78.6% among pregnant women and 52.9% among postnatal women. Pregnant women reported that the most important information was general concepts of immunization; in contrast, postnatal women desired more-detailed information, e.g., on immunization scheduling. CONCLUSIONS: Japanese women do not receive sufficient perinatal immunization education. The information needed during the prenatal and postnatal periods differs. Thus, educational approaches may need to provide carefully targeted information.

    DOI: 10.1016/j.vaccine.2015.08.069

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  • Nationwide population-based surveillance of invasive pneumococcal disease in Japanese children: Effects of the seven-valent pneumococcal conjugate vaccine. 査読 国際誌

    Shigeru Suga, Bin Chang, Kazutoyo Asada, Hideki Akeda, Junichiro Nishi, Kenji Okada, Hiroshi Wakiguchi, Akihiko Maeda, Megumi Oda, Naruhiko Ishiwada, Akihiko Saitoh, Tomohiro Oishi, Mitsuaki Hosoya, Takehiro Togashi, Kazunori Oishi, Toshiaki Ihara

    Vaccine   33 ( 45 )   6054 - 60   2015年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: In Japan, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2010. PCV13 has replaced PCV7 since November 2013. METHODS: The effectiveness of PCV7 in protecting against invasive pneumococcal disease (IPD) in children aged <5 years was evaluated in a nationwide active population-based surveillance of IPD in 2008-2013 in 10 prefectures in Japan. RESULTS: 1181 cases were identified; 711 pneumococcal strains were analyzed for serotyping and antimicrobial resistance. Compared with the baseline IPD incidence (25.0 per 100,000), a 98% decline in IPD caused by PCV7 serotypes was found after the introduction of PCV7. This was partially offset by an increased incidence of IPD caused by PCV13 minus PCV7 and non-PCV13 serotypes, resulting in a 57% decline in overall IPD incidence. Absolute increases in the incidence rates of IPD caused by PCV13 minus PCV7 and non-PCV13 serotypes were 2.1 and 2.8 per 100,000 during the study period, respectively. The proportion of meropenem-nonsusceptible strains, especially with serotypes 19A and 15A, increased significantly after PCV7 introduction. CONCLUSIONS: Our data confirmed a 98% decline in IPD incidence caused by PCV7 serotypes in children aged <5 years and serotype replacement after PCV7 introduction. This shows the importance of continuing surveillance of serotypes responsible for IPD and their antimicrobial resistance in Japan.

    DOI: 10.1016/j.vaccine.2015.07.069

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  • Risk Factors for Bloodstream Infection After Living-donor Liver Transplantation in Children. 査読 国際誌

    Kensuke Shoji, Takanori Funaki, Mureo Kasahara, Seisuke Sakamoto, Akinari Fukuda, Florin Vaida, Kenta Ito, Isao Miyairi, Akihiko Saitoh

    The Pediatric infectious disease journal   34 ( 10 )   1063 - 8   2015年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Postoperative bloodstream infection (BSI) is the most important determinant of recipient morbidity and mortality after liver transplantation (LT). Children who underwent LT are at the highest risk of developing BSI because of the significant surgical intervention, use of multiple devices, and administration of immunosuppressive agents. However, information regarding the risk factors for BSI in children after LT is limited. METHODS: We retrospectively reviewed 210 children who underwent living-donor LT at the largest pediatric LT center in Japan. Patients' characteristics, blood culture results and clinical outcomes were extracted from electronic medical records. Univariate and multivariate analyses were performed to identify the risk factors for BSI. RESULTS: Among the 210 LT recipients, 53 (25%) recipients experienced 86 episodes of BSI during the observational period. The source of the BSI was identified only in 38%: catheter-related BSI (27%) peritonitis (7%), urinary tract infection (2%), pneumonia (1%) and infectious endocarditis (1%). A multivariate analysis demonstrated that body weight (P = 0.03), volume of blood loss during LT (P < 0.001) and cytomegalovirus (CMV) antigenemia positivity (P = 0.04) were independently associated with the development of BSI. The risk factors for BSI differed when we analyzed the subjects according to age (≤24 months and >24 months), blood loss and pediatric end-stage liver disease/model for end-stage liver disease versus positive CMV antigenemia. CONCLUSIONS: The volume of blood loss, postoperative CMV antigenemia positivity and body weight were associated with the development of BSI after LT in pediatric living-donor recipients. To identify the age-specific predictors of BSI in children who underwent LT, age-specific analyses are crucial.

    DOI: 10.1097/INF.0000000000000811

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  • 小児・思春期再生不良性貧血にウサギATGを使用した免疫抑制治療後のEBV/CMV再活性化 後方視的解析(EBV/CMV reactivation following immunosuppressive therapy with rabbit ATG for children and adolescents with aplastic anemia: A retrospective chart review)

    久保 暢大, 細貝 亮介, 渡辺 彰浩, 小川 淳, 申 将守, 高地 貴行, 笠原 靖史, 吉田 咲子, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   52 ( 4 )   313 - 313   2015年10月

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    記述言語:英語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 低ゴナドトロピン性性腺機能低下症を呈した輸血後鉄過剰症女児例

    西崎 淑美, 佐藤 英利, 小川 洋平, 長崎 啓祐, 今井 千速, 齋藤 昭彦

    日本内分泌学会雑誌   91 ( 3 )   841 - 841   2015年10月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • ニーマンピック病C型に合併した進行期肝細胞がんに対しソラフェニブ投与を行った1例

    笠原 靖史, 江村 重仁, 申 将守, 高地 貴行, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   52 ( 4 )   293 - 293   2015年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 全脳脊髄照射を要する小児脳腫瘍における術後2週間以内のG-CSF単独自家末梢血幹細胞採取

    細貝 亮介, 高地 貴行, 吉田 咲子, 岩渕 晴子, 今村 勝, 申 将守, 笠原 靖史, 齋藤 昭彦, 佐野 正和, 西山 健一, 阿部 英輔, 青山 英史, 吉村 淳一, 今井 千速

    日本小児血液・がん学会雑誌   52 ( 2 )   133 - 138   2015年8月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

    悪性脳腫瘍に対する全脳脊髄照射(CSI)では頭蓋骨及び全脊椎の骨髄組織が障害されるため、CSI後の強力な化学療法では骨髄抑制が著しく遷延し、結果的に治療全体の強度が低下することが大きな問題である。そこで我々は、CSI及び強力な化学療法を要する悪性脳腫瘍に対しG-CSF単独の末梢血幹細胞(PBSC)採取を試み、化学療法に自家末梢血幹細胞移植(aPBSCT)を併用することとした。早期にCSIを開始するため、術後2週以内の採取完了を目指した。初発未治療例6例では中央値12.6×10^6/kg(3.9-21.6×10^6/kg)のCD34陽性細胞採取が可能だったが、うち2例では複数回のaPBSCTに十分な細胞数に達しなかった。再発例の2例では少なくとも1回の移植に必要な量は採取できた。これら4例ではaPBSCT併用化学療法1コース終了後に再度PBSC採取を行い十分量が確保できた(13.7-42.1×10^6/kg)。術後2週以内のPBSC採取では白血球数が増加しやすい傾向にあったが、重篤な有害事象はみられなかった。全例で予定した複数回aPBSCTを実施でき、骨髄抑制の遷延をきたすことなく規定の間隔で化学療法を完遂できた。術後2週以内のG-CSF単独PBSC採取は安全に実施できたものの少数例の経験であり、術後早期にCSIを要する悪性脳腫瘍の集学的治療における有効性に関しては更なる検討を要する。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J06030&link_issn=&doc_id=20160106240003&doc_link_id=%2Fex9syoga%2F2015%2F005202%2F003%2F0133-0138%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fex9syoga%2F2015%2F005202%2F003%2F0133-0138%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Skin thickness in young infants and adolescents: Applications for intradermal vaccination. 査読 国際誌

    Akihiko Saitoh, Yuta Aizawa, Isamu Sato, Harunobu Hirano, Takatsugu Sakai, Masaaki Mori

    Vaccine   33 ( 29 )   3384 - 91   2015年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    As compared with standard intramuscular and subcutaneous vaccines, intradermal (ID) vaccines elicit a more potent immune response in both adults and children, with equivalent dosage or antigen dose sparing. Recently, various devices for ID injection have been developed; the length of needles ranges in 0.6-1.5 mm. However, skin thickness must be measured to determine optimal needle length for ID vaccines. Use of ID vaccines in infants and children is appealing because children require more vaccines than do adults; however, information on skin thickness in infants and children is limited. We used ultrasound echography to measure skin thickness in Japanese infants aged 2 months (n=78) and adolescents aged 13-15 years (n=82). Mean (range) deltoid and suprascapular skin thickness was 1.67 mm (1.16-2.39 mm) and 1.83 mm (1.24-2.60 mm), respectively, in infants and 1.81 mm (1.25-3.00 mm) and 2.43 mm (1.51-3.95 mm), respectively, in adolescents. Among infants who underwent re-measurement of skin thickness at age 6 months (n=11), mean deltoid skin thickness (1.84 mm) was significantly greater than at age 2 months (1.60 mm) (P<0.001). In contrast, no significant difference was observed in suprascapular skin thickness (1.79 mm vs. 1.67 mm, respectively; P=0.17). Gender was not associated with skin thickness in either age group. Skin thickness was positively correlated with body weight in adolescents (r=0.43, P<0.001 in deltoid region; r=0.30, P=0.01 in suprascapular region). In conclusion, this is the first study to evaluate skin thickness in different age groups of children, including at age 2 months. Skin thickness gradually increased from age 2 months to age 13-15 years, but no consistent trend was noted in analysis stratified by measurement site, gender, or age. These findings suggest that an appropriate length of ID device needle for infants and children is likely to be less than 1.2mm and a special device with shorter length of needle is warranted for infants and children.

    DOI: 10.1016/j.vaccine.2015.04.081

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  • Alternatively activated macrophages in the pathogenesis of chronic kidney allograft injury. 査読 国際誌

    Yohei Ikezumi, Toshiaki Suzuki, Takeshi Yamada, Hiroya Hasegawa, Utako Kaneko, Masanori Hara, Toshio Yanagihara, David J Nikolic-Paterson, Akihiko Saitoh

    Pediatric nephrology (Berlin, Germany)   30 ( 6 )   1007 - 17   2015年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Prevention of chronic kidney allograft injury (CAI) is a major goal in improving kidney allograft survival; however, the mechanisms of CAI are not clearly understood. The current study investigated whether alternatively activated M2-type macrophages are involved in the development of CAI. METHODS: A retrospective study examined kidney allograft protocol biopsies (at 1 h and at years 1, 5, and 10--a total of 41 biopsies) obtained from 13 children undergoing transplantation between 1991 and 2008 who were diagnosed with CAI: interstitial fibrosis and tubular atrophy (IF/TA) not otherwise specified (IF/TA-NOS). RESULTS: Immunostaining identified a significant increase in interstitial fibrosis with accumulation of CD68 + CD163+ M2-type macrophages. CD163+ cells were frequently localized to areas of interstitial fibrosis exhibiting collagen I deposition and accumulation of α-smooth muscle actin (SMA) + myofibroblasts. There was a significant correlation between interstitial CD163+ cells and the parameters of interstitial fibrosis (p < 0.0001), and kidney function (r =-0.82, p < 0.0001). The number of interstitial CD163+ cells at years 1 and 5 also correlated with parameters of interstitial fibrosis at years 5 and 10 respectively. Notably, urine CD163 levels correlated with interstitial CD163+ cells (r = 0.79, p < 0.01) and parameters of interstitial fibrosis (p < 0.0001). However, CD3+ T lymphocytic infiltration did not correlate with macrophage accumulation or fibrosis. In vitro, dexamethasone up-regulated expression of CD163 and cytokines (TGF-β1, FGF-2, CTGF) in human monocyte-derived macrophages, indicating a pro-fibrotic phenotype. CONCLUSIONS: Our findings identify a major population of M2-type macrophages in patients with CAI, and suggest that these M2-type macrophages might promote the development of interstitial fibrosis in IF/TA-NOS.

    DOI: 10.1007/s00467-014-3023-0

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  • Serostatus following live attenuated vaccination administered before pediatric liver transplantation. 査読 国際誌

    Takanori Funaki, Kensuke Shoji, Ippei Miyata, Seisuke Sakamoto, Mureo Kasahara, Hironori Yoshii, Isao Miyairi, Akihiko Saitoh

    Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society   21 ( 6 )   774 - 83   2015年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    After liver transplantation (LT), live attenuated vaccines (LAVs) are generally contraindicated. LAVs are recommended before LT for patients ≥ 6 months of age. However, the evidence supporting this practice is limited. Patients were enrolled before and after LT. Clinical data for patients were obtained from medical records. Serum antibody titers were evaluated at the time of enrollment and prospectively. Serum antibody titers were measured with a hemagglutination inhibition test for measles and rubella and with an enzyme-linked immunosorbent assay for varicella and mumps. Univariate and multivariate analyses were performed to investigate the factors that affect the serostatus. Serological analyses of 49 patients immunized before LT (median age, 45 months; male, 35%) were performed. Underlying diseases were biliary atresia (n = 27; 55%), metabolic diseases (n = 13; 27%), fulminant hepatic failure (n = 5; 10%), and others (n = 4; 8%). The seropositivity rate after each vaccine was 46.9% (measles), 89.4% (rubella), 67.5% (varicella), and 48.8% (mumps). Factors independently associated with seronegativity were a vaccination age < 12 months for measles (P = .002), a lower body weight for varicella (P = 0.01), and underlying diseases other than biliary atresia for mumps (P = .004). No serious adverse event was observed during the study period. The immunogenicity of LAVs before LT was high for rubella but low for the others. Before LT, further vaccination strategies are needed for patients. In addition, serological follow-up may be indicated for patients with factors associated with seronegativity.

    DOI: 10.1002/lt.24104

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  • Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells. 査読 国際誌

    Takayuki Takachi, Masahiko Takahashi, Manami Takahashi-Yoshita, Masaya Higuchi, Miki Obata, Yukio Mishima, Shujiro Okuda, Yuetsu Tanaka, Masao Matsuoka, Akihiko Saitoh, Patrick L Green, Masahiro Fujii

    Cancer science   106 ( 4 )   461 - 5   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia (ATL), which is an aggressive form of T-cell malignancy. HTLV-1 oncoproteins, Tax and HBZ, play crucial roles in the immortalization of T-cells and/or leukemogenesis by dysregulating the cellular functions in the host. Recent studies show that HTLV-1-infected T-cells have reduced expression of the BCL11B tumor suppressor protein. In the present study, we explored whether Tax and/or HBZ play a role in downregulating BCL11B in HTLV-1-infected T-cells. Lentiviral transduction of Tax in a human T-cell line repressed the expression of BCL11B at both the protein and mRNA levels, whereas the transduction of HBZ had little effect on the expression. Tax mutants with a decreased activity for the NF-κB, CREB or PDZ protein pathways still showed a reduced expression of the BCL11B protein, thereby implicating a different function of Tax in BCL11B downregulation. In addition, the HTLV-2 Tax2 protein reduced the BCL11B protein expression in T-cells. Seven HTLV-1-infected T-cell lines, including three ATL-derived cell lines, showed reduced BCL11B mRNA and protein expression relative to an uninfected T-cell line, and the greatest reductions were in the cells expressing Tax. Collectively, these results indicate that Tax is responsible for suppressing BCL11B protein expression in HTLV-1-infected T-cells; Tax-mediated repression of BCL11B is another mechanism that Tax uses to promote oncogenesis of HTLV-1-infected T-cells.

    DOI: 10.1111/cas.12618

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  • Successful detection and genotyping of rubella virus from preserved umbilical cord of patients with congenital rubella syndrome. 査読 国際誌

    Ippei Miyata, Takahiko Kubo, Isao Miyairi, Akihiko Saitoh, Noriko Morimoto

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America   60 ( 4 )   605 - 7   2015年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/cid/ciu882

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  • High rate of inducible clindamycin resistance in Staphylococcus aureus isolates--a multicenter study in Tokyo, Japan. 査読 国際誌

    Kensuke Shoji, Masayoshi Shinjoh, Yuho Horikoshi, Julian Tang, Yasushi Watanabe, Kayoko Sugita, Tomoyuki Tame, Satoshi Iwata, Isao Miyairi, Akihiko Saitoh

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   21 ( 2 )   81 - 3   2015年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The resistance of Staphylococcus aureus (S. aureus) to antibiotics is an increasing problem. Clindamycin has been used as empiric therapy for the rising incidence of community-acquired methicillin-resistant S. aureus (MRSA). As such, the local rate of inducible resistance against clindamycin is an important consideration. This multicenter study was conducted to identify the incidence of inducible clindamycin resistance of S. aureus isolates in Tokyo, the most populous city in Japan. A total of 2408 adult and pediatric samples were collected from a university hospital and two pediatric hospitals between January 2011 and December 2011. Among the 2341 samples analyzed, the incidence of inducible clindamycin resistance in erythromycin-resistant and clindamycin-susceptible/intermediate isolates was found to be 91% (n = 585), a figure much higher compared to most reports from other countries. In conclusion, we found a very high rate of inducible clindamycin resistance in macrolide-resistant S. aureus isolates in our geographic area.

    DOI: 10.1016/j.jiac.2014.10.003

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  • 新生児期のレントゲン所見による軟骨低形成症の早期診断(Criteria for radiological diagnosis of hypochondroplasia in neonates)

    齋藤 朋子, 長崎 啓祐, 西村 玄, 和田 雅樹, 入月 浩美, 高木 優樹, 長谷川 奉延, 齋藤 昭彦

    日本小児科学会雑誌   119 ( 2 )   222 - 222   2015年2月

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    記述言語:英語   出版者・発行元:(公社)日本小児科学会  

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  • Short QT syndrome in a boy diagnosed on screening for heart disease. 査読 国際誌

    Hiroshi Suzuki, Satoshi Hoshina, Junichi Ozawa, Akinori Sato, Tohru Minamino, Yoshifusa Aizawa, Akihiko Saitoh

    Pediatrics international : official journal of the Japan Pediatric Society   56 ( 5 )   774 - 6   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report on an asymptomatic 10-year-old boy who had a short QT interval (corrected QT interval, 260 ms). Short QT syndrome (SQTS) was detected in a school screening program for heart disease and the patient was subsequently diagnosed as having N588K mutation in the KCNH2 gene. Quinidine prolonged the QT interval, but not the QU interval. During treadmill exercise stress test, QT and QU intervals responded differently to heart rate changes, suggesting a mechanoelectrical hypothesis for the origin of the U wave. Although rare, attention should be paid to SQTS, which is associated with potential fatal arrhythmias.

    DOI: 10.1111/ped.12308

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  • インターフェロン、サリドマイド、プロプラノロールが無効で治療に苦慮しているびまん性肺リンパ管腫症の1例

    今村 勝, 岩渕 晴子, 吉田 咲子, 高地 貴行, 細貝 亮介, 笠原 靖史, 申 将守, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   51 ( 4 )   326 - 326   2014年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 慢性髄膜脳炎と脳梗塞を合併したX連鎖無ガンマグロブリン血症に対する脳室内免疫グロブリン治療の成功例

    笠原 靖史, 申 将守, 高地 貴行, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   51 ( 4 )   291 - 291   2014年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • Guidelines for the management and investigation of hemolytic uremic syndrome. 査読

    Takashi Igarashi, Shuichi Ito, Mayumi Sako, Akihiko Saitoh, Hiroshi Hataya, Masashi Mizuguchi, Tsuneo Morishima, Kenji Ohnishi, Naohisa Kawamura, Hirotsugu Kitayama, Akira Ashida, Shinya Kaname, Hiromichi Taneichi, Julian Tang, Makoto Ohnishi

    Clinical and experimental nephrology   18 ( 4 )   525 - 57   2014年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s10157-014-0995-9

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  • Glomerular epithelial cell phenotype in diffuse mesangial sclerosis: a report of 2 cases with markedly increased urinary podocyte excretion. 査読 国際誌

    Yohei Ikezumi, Toshiaki Suzuki, Tamaki Karasawa, Utako Kaneko, Takeshi Yamada, Hiroya Hasegawa, Michio Nagata, Akihiko Saitoh

    Human pathology   45 ( 8 )   1778 - 83   2014年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report 2 cases of diffuse mesangial sclerosis (DMS) accompanied by severe podocyte excretion in urine. Patient 1 was a 9-day-old girl with a WT1 mutation who developed Wilms tumor at 6 months of age and was subsequently diagnosed with Denys-Drash syndrome. Patient 2 was a 1-year-old boy without a WT1 abnormality but presenting with heavy proteinuria. In both patients, histological examination showed findings of DMS. Immunohistochemical staining for synaptopodin (a podocyte marker) revealed a reduced number of podocytes in the glomeruli with severe sclerosis; however, podocytes persisted in the relatively intact glomeruli. Some glomeruli were accompanied by sclerotic lesions surrounded by proliferating cells; immunofluorescence staining revealed a majority of these proliferating cells to be positive for claudin-1 (a parietal cell marker) but negative for synaptopodin. These findings suggest that podocyte loss and the consequent proliferation of parietal cells are common processes in the pathogenesis of DMS.

    DOI: 10.1016/j.humpath.2014.03.017

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  • Recent progress and concerns regarding the Japanese immunization program: addressing the "vaccine gap". 査読 国際誌

    Akihiko Saitoh, Nobuhiko Okabe

    Vaccine   32 ( 34 )   4253 - 8   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Recent progress in the Japanese immunization program has partially closed the "vaccine gap," i.e., the deficiencies in that program relative to immunization programs in other developed countries. During the last several years, seven new vaccines (12 new products, excluding influenza vaccines) have been introduced in Japan. Five of these new vaccines are produced outside Japan and four are now included as routine vaccines in the National Immunization Program, which is a new development in the licensing and financial support of imported vaccines. However, along with this progress, important concerns have arisen regarding the Japanese immunization program. A rubella epidemic among adults, in 2012-2013, resulted in more than 40 cases of congenital rubella syndrome as of March 2014. In addition, the temporary withdrawal of the active governmental recommendation for human papilloma virus vaccines, in 2013-2014, highlighted challenges in the current Japanese immunization system. Furthermore, some important vaccines - including vaccines for hepatitis B virus, mumps, varicella, and rotavirus - are still not included in the National Immunization Program and have been categorized as voluntary vaccines since their introduction. The possibility of their inclusion in the National Immunization Program remains a matter for discussion. We hope that future initiatives will further address the vaccine gap and protect Japanese children from vaccine-preventable diseases.

    DOI: 10.1016/j.vaccine.2014.06.022

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  • 当科で経験した自己免疫性好中球減少症の臨床像

    額賀 愛, 笠原 靖史, 細貝 亮介, 大石 智洋, 吉田 咲子, 岩渕 晴子, 今井 千速, 齋藤 昭彦

    日本小児科学会雑誌   118 ( 7 )   1136 - 1136   2014年7月

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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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  • Long-term follow-up study for a patient with Floating-Harbor syndrome due to a hotspot SRCAP mutation. 査読 国際誌

    Keisuke Nagasaki, Tadashi Asami, Hidetoshi Sato, Yohei Ogawa, Toru Kikuchi, Akihiko Saitoh, Tsutomu Ogata, Maki Fukami

    American journal of medical genetics. Part A   164A ( 3 )   731 - 5   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Floating-Harbor syndrome (FHS) is a rare autosomal dominant disorder characterized by short stature, skeletal malformations, speech delay, and dysmorphic facial appearance. Recently, mutations in SRCAP encoding a coactivator for cAMP-response element binding protein (CREB)-binding protein have been identified in small number of patients with FHS. Here, we report on long-term follow-up data of a male patient with a SRCAP mutation. The patient presented with mild hypothyroidism and renal hypouricemia, in addition to several FHS-compatible features including growth impairment, cognitive disability, facial dysmorphisms, and hypertension. He showed delayed bone age from infancy to 9 years of age and markedly accelerated bone age with the formation of cone-shaped epiphyses and early epiphysial fusions after the onset of puberty. His pubertal sexual development was almost age appropriate. Two-year treatment with growth hormone (GH) did not significantly improve the growth velocity. Molecular analysis identified a de novo heterozygous nonsense mutation (p.R2444X) in the last exon of SRCAP, which has been most common mutation detected in patients from other ethnic groups. These results indicate that perturbed skeletal maturation from infancy through adolescence is a characteristic feature in patients with SRCAP mutations. Furthermore, our data imply that GH therapy exerted only a marginal effect on the growth of this patient, and that renal hypouricemia may be a novel complication of FHS.

    DOI: 10.1002/ajmg.a.36314

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  • An Infant with Human Parechovirus Type 3 Infection with a Distinctive Rash on the Extremities 査読

    Kensuke Shoji, Hisako Komuro, Yoshinori Kobayashi, Tatsuhiko Shike, Takanori Funaki, Tomohiro Katsuta, Ippei Miyata, Akihiko Saitoh

    PEDIATRIC DERMATOLOGY   31 ( 2 )   258 - 259   2014年3月

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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-BLACKWELL  

    Human parechovirus type 3 (HPeV3) is known to cause sepsis-like syndrome and meningoencephalitis in neonates and young infants. We herein report a neonatal case of sepsis-like syndrome due to HPeV3 infection, diagnosed using polymerase chain reaction (PCR), with a distinctive erythematous rash present mainly on the soles and palms that helped in the diagnosis of the disease. Combining the unique characteristics of rash and confirmation by PCR at the early stage of the disease led to the diagnosis of HPeV3, distinguishing it from sepsis and other critical disease conditions, and allowing for appropriate, rapid management.

    DOI: 10.1111/j.1525-1470.2012.01819.x

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  • Clinical utility of loop-mediated isothermal amplification for rapid diagnosis of Mycoplasma pneumoniae in children. 査読 国際誌

    Yuta Aizawa, Tomohiro Oishi, Shinya Tsukano, Tetsuo Taguchi, Akihiko Saitoh

    Journal of medical microbiology   63 ( Pt 2 )   248 - 251   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Loop-mediated isothermal amplification (LAMP) is a cost-effective and rapid method for identifying Mycoplasma pneumoniae (MP). We investigated the utility of the LAMP assay in diagnosing MP pneumonia among children in a clinical setting. In this prospective study, the cause of community-acquired pneumonia was evaluated in 111 patients for whom MP was the suspected pathogen. All participants were patients at a city hospital in Japan between April 2012 and September 2012. Throat swabs for the LAMP assay were obtained at admission, and paired serum samples to measure antibody titres to MP by particle agglutination were obtained at admission and during convalescence. Overall, 45 of 111 (41 %) patients had a fourfold or greater increase in MP titres and received a diagnosis of MP pneumonia. Among them, 43 (96 %) patients (median age, 9 years) were positive on the LAMP assay and had a fourfold or greater increase in MP titres. The median interval from fever onset to collection of throat swabs was 7 days (range, 4-10 days). As compared with paired serum titres, the LAMP assay enabled quicker diagnosis of MP (median interval, 13 vs. 7 days), thereby allowing early initiation of appropriate antimicrobial therapy.

    DOI: 10.1099/jmm.0.068288-0

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  • Echovirus 3 as another enterovirus causing life-threatening neonatal fulminant hepatitis. 査読 国際誌

    Ippei Miyata, Nozomu Hanaoka, Nobuhiko Okabe, Tsuguto Fujimoto, Seisuke Sakamoto, Mureo Kasahara, Akihiko Saitoh

    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology   59 ( 2 )   132 - 4   2014年2月

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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.jcv.2013.11.015

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  • Human parechovirus-3 infection mimicking Hirschsprung-associated enterocolitis 査読

    Toshihiko Watanabe, Masataka Takahashi, Kensuke Shoji, Koji Yamada, Waka Yamada, Hideaki Tanaka, Hideo Ishihama, Ippei Miyata, Akihiko Saitoh, Yutaka Kanamori

    Journal of Pediatric Surgery Case Reports   2 ( 2 )   56 - 60   2014年

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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 Inc.  

    Human parechovirus-3 (HPeV-3) infection is being increasingly identified as an important pathogen leading to neonatal sepsis-like illness. In this case report, we present a pre-term infant with striking abdominal distention whose signs and symptoms were quite similar to those of Hirschsprung-associated enterocolitis but the patient suffered from the gastrointestinal phenotype of HPeV-3 infection.© 2014 The Authors. Published by Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.epsc.2014.01.001

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  • 偽性副甲状腺機能低下症に対する分子遺伝学的解析のアルゴリズムの作成

    長崎 啓祐, 入月 浩美, 佐藤 英利, 佐野 伸一朗, 深見 真紀, 齋藤 昭彦

    新潟県医師会報   ( 765 )   7 - 9   2013年12月

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    記述言語:日本語   出版者・発行元:新潟県医師会  

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  • [Diagnosis treatment and prevention of infectious diseases. Topics: IV. Progress in understanding of VPD (vaccine preventable diseases); 1. Recognition and progress of vaccine preventable diseases in childhood]. 査読

    Akihiko Saitoh

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   102 ( 11 )   2928 - 35   2013年11月

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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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  • The value of radiographic findings for the progression of pandemic 2009 influenza A/H1N1 virus infection. 査読 国際誌

    Takanori Funaki, Kensuke Shoji, Nobuyuki Yotani, Tomohiro Katsuta, Osamu Miyazaki, Shunsuke Nosaka, Hidekazu Masaki, Akihiko Saitoh

    BMC infectious diseases   13   516 - 516   2013年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Most illnesses caused by pandemic influenza A (H1N1) pdm09 virus (A/H1N1) infection are acute and self-limiting among children. However, in some children, disease progression is rapid and may require hospitalization and transfer to a pediatric intensive care unit (PICU). We investigated factors associated with rapid disease progression among children admitted to hospital for A/H1N1 infection, particularly findings on initial chest radiographs. METHODS: In this retrospective study, we investigated the records of children who had received a laboratory or clinical diagnosis of A/H1N1 infection and were admitted to the largest children's hospital in Japan between May 2009 and March 2010. The medical records were reviewed for age, underlying diseases, vital signs on admission, initial chest radiographic findings, and clinical outcomes. According to chest radiographic findings, patients were classified into 4 groups, as follows: [1] normal (n = 46), [2] hilar and/or peribronchial markings alone (n = 64), [3] consolidation (n = 64), and [4] other findings (n = 29). Factors associated with clinical outcomes were analyzed using logistic regression. RESULTS: Two hundreds and three patients (median 6.8 years) were enrolled in this study. Fifteen percent (31/203) of patients were admitted to PICU. Among 31 patients, 39% (12/31) of patients required mechanical ventilation (MV). When the initial chest radiographic findings were compared between patients with consolidation (n = 64) and those without consolidation (n = 139), a higher percentage of patients with consolidation were admitted to PICU (29.7% vs.8.6%, P < 0.001) and required MV (17.2% vs. 0.7%, P < 0.001). These findings remain significant when the data were analyzed with the logistic regression (P < 0.001, P < 0.001, respectively). CONCLUSIONS: Consolidation on initial chest radiographs was the most significant factor to predict clinical course of hospitalized children with the 2009 A/H1N1 infection.

    DOI: 10.1186/1471-2334-13-516

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  • 超大量メソトレキセート療法の毒性発現機序 高サイトカイン血症の介在の可能性

    笠原 靖史, 吉田 咲子, 高地 貴行, 細貝 亮介, 岩渕 晴子, 今村 勝, 川島 寛之, 生越 章, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号   55回・11回・18回   309 - 309   2013年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会  

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  • プロプラノロール点滴静注が著効した気道閉塞を伴う乳児血管腫の1例

    大田 倫美, 吉田 咲子, 笠原 靖史, 細貝 亮介, 岩渕 晴子, 今井 千速, 齋藤 昭彦

    日本小児科学会雑誌   117 ( 9 )   1501 - 1501   2013年9月

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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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  • Late development of coronary artery abnormalities could be associated with persistence of non-fever symptoms in Kawasaki disease. 査読 国際誌

    Sayaka Fukuda, Shuichi Ito, Shinji Oana, Hirokazu Sakai, Hitoshi Kato, Jun Abe, Ryuko Ito, Akihiko Saitoh, John Ichiro Takayama

    Pediatric rheumatology online journal   11 ( 1 )   28 - 28   2013年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Persistent fever after intravenous immunoglobulin (IVIG) is considered to be a major criterion of IVIG resistance in Kawasaki disease (KD), and a risk factor for the development of coronary artery abnormalities (CAA). However, the importance of persistent non-fever symptoms after defervescence has not yet been investigated. We examined the relationship between persistent non-fever symptoms and CAA in KD. METHODS: We conducted a retrospective cohort study of patients hospitalized with KD at the National Center for Child Health and Development between 1 April 2008 and 31 March 2009. Patients were divided into two groups; group A included patients who still had non-fever symptoms one month after onset of the illness and group B included patients who did not have persistent non-fever symptoms. Demographic, clinical variables were compared between the groups. RESULTS: Seventy-seven KD patients treated with IVIG were retrospectively analyzed. Patients were divided into two groups; group A included 12 (15.6%) patients and group B 65 (84.4%) patients. Demographic data, baseline laboratory data, and fever duration did not differ between the groups. In group A patients the most common persistent non-fever symptoms were lip erythema (n = 6) and bulbar conjunctivitis (n = 8). One month after onset of the illness CAA developed in seven of 77 patients (9.1%), four (33%) in group A and three (4.6%) in group B (odds ratio 10.3; 95% CI 1.9-54.8). Three patients in group A and one patient in group B developed CAA after the resolution of fever. CONCLUSIONS: Persistence of non-fever symptoms after IVIG may suggest persistence of latent inflammation, which may increase the risk of CAA. Therefore, patients with persistent non-fever symptoms may be at risk of developing CAA, even after defervescence. A prospective trial of additional IVIG for such patients should be considered.

    DOI: 10.1186/1546-0096-11-28

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  • Perinatal immunization education improves immunization rates and knowledge: a randomized controlled trial. 査読 国際誌

    Aya Saitoh, Satoko Nagata, Akihiko Saitoh, Yuki Tsukahara, Florin Vaida, Tomoyoshi Sonobe, Hajime Kamiya, Takashi Naruse, Sachiyo Murashima

    Preventive medicine   56 ( 6 )   398 - 405   2013年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: To determine if providing perinatal immunization education positively changes the immunization status of infants, influences the infant immunization knowledge, attitudes and beliefs of mothers and affects the intent to vaccinate children in Japan where immunization education is limited. METHODS: Pregnant women were recruited from three sites in Tokyo, Japan and were assigned to two intervention (pre- or postnatal education) groups and a control group. The immunization status of infants was assessed and a written survey was performed before and after the intervention. RESULTS: Among 119 study participants, 106 subjects replied to the post-survey. The intervention groups (34.3%) had higher immunization rates in infants at three months of age than the control group (8.3%) (P=0.005); however, no differences were observed between the prenatal (29.4%) and postnatal groups (38.9%) (P=0.40). The percentage of women intended to vaccinate their infants was higher in the intervention groups (61.4%) compared to the control group (33.3%) (P=0.01). The improvement in score for basic knowledge was higher in the intervention groups, particularly in the prenatal group (mean±S.D.: 3.4±1.8) compared to the control (1.9±1.9) (P=0.003). CONCLUSIONS: Perinatal immunization education improved the immunization status of infants, increased the women's knowledge on immunization and intention to vaccinate their infants.

    DOI: 10.1016/j.ypmed.2013.03.003

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  • O脚の男児から判明したX染色体優性低リン血症性くる病の一家系

    佐藤 英利, 長崎 啓祐, 小川 洋平, 菊池 透, 深見 真紀, 齋藤 昭彦

    日本内分泌学会雑誌   89 ( Suppl.Update )   55 - 57   2013年6月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

    X染色体優性低リン血症性くる病(XLH)の浸透率はほぼ100%といわれているが、女性では症状が軽いため臨床的にくる病の所見を示さず、未診断の症例が少なからず存在するものと思われる。今回、低身長・O脚を呈する男児を契機に、無症状の母親と、幼少期にO脚を指摘されていた祖母の診断に至り、XLHの原因遺伝子であるPHEX遺伝子の新規変異(Exon 1のc.2 T>C変異)をヘミ接合性に同定した1家系を経験したので、文献的考察を加えて報告した。

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  • Treatment of pyelonephritis caused by extended-spectrum β-lactamase-producing Enterobacteriaceae in children. 査読 国際誌

    Tomohiro Katsuta, Kensuke Shoji, Yasushi Watanabe, Akihiko Saitoh

    The Pediatric infectious disease journal   32 ( 4 )   417 - 9   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Fifty-four children were diagnosed as pyelonephritis caused by extended-spectrum β-lactamase-producing Enterobacteriaceae at the largest children's hospital in Japan. Although 32 (59%) patients were treated with antimicrobials that are ineffective against the organisms, 39 (72%) patients became afebrile ≤2 days and clinical outcome was excellent. Children with pyelonephritis caused by extended-spectrum β-lactamase-producing Enterobacteriaceae can be successfully treated with noncarbapenem antimicrobials.

    DOI: 10.1097/INF.0b013e318284b1e8

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  • 抗体関連型拒絶反応の克服に向けて C4d陽性の抗体関連型拒絶反応の1例

    伊藤 由美, 河野 恵美子, 吉田 一浩, 今井 直史, 山崎 裕幸, 中川 由紀, 齋藤 和英, 唐澤 環, 鈴木 俊明, 池住 洋平, 斉藤 昭彦, 高橋 公太, 成田 一衛

    今日の移植   26 ( 2 )   188 - 194   2013年4月

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    記述言語:日本語   出版者・発行元:(株)日本医学館  

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  • Detection of enteroviral RNA from preserved umbilical cord. 査読 国際誌

    Ippei Miyata, Akihiko Saitoh

    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology   56 ( 3 )   274 - 5   2013年3月

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  • Neuromuscular symptoms in a patient with familial pseudohypoparathyroidism type Ib diagnosed by methylation-specific multiplex ligation-dependent probe amplification. 査読

    Keisuke Nagasaki, Shuichi Tsuchiya, Akihiko Saitoh, Tsutomu Ogata, Maki Fukami

    Endocrine journal   60 ( 2 )   231 - 6   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pseudohypoparathyroidism type Ib (PHP-Ib) is a rare genetic disorder characterized by hypocalcemia and hyperphosphatemia due to imprinting defects in the maternally derived GNAS allele. Patients with PHP-Ib are usually identified by tetany, convulsions, and/or muscle cramps, whereas a substantial fraction of patients remain asymptomatic and are identified by familial studies. Although previous studies on patients with primary hypoparathyroidism have indicated that hypocalcemia can be associated with various neuromuscular abnormalities, such clinical features have been rarely described in patients with PHP-Ib. Here, we report a 12-year-old male patient with familial PHP-Ib and unique neuromuscular symptoms. The patient presented with general fatigue, steppage gait, and myalgia. Physical examinations revealed muscular weakness and atrophies in the lower legs, a shortening of the bilateral Achilles' tendons and absence of deep tendon reflexes. Laboratory tests showed hypocalcemia, hyperphosphatemia, elevated serum intact PTH level, and impaired responses of urinary phosphate and cyclic AMP in an Ellsworth-Howard test, in addition to an elevated serum creatine kinase level. Clinical features of the patient were significantly improved after 1 month of treatment with alfacalcidol and calcium. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and subsequent PCR analyses identified a methylation defect at exon A/B of GNAS and a microdeletion involving exons 4-6 of the GNAS neighboring gene STX16 in the patient and in his asymptomatic brother. The results suggest that various neuromuscular features probably associated with hypocalcemia can be the first symptoms of PHP-Ib, and that MS-MLPA serves as a powerful tool for screening of GNAS abnormalities in patients with atypical manifestations.

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  • Two cases of new coronary aneurysms that developed in the late period after Kawasaki disease. 査読 国際誌

    Junichi Ozawa, Hiroshi Suzuki, Satoshi Hasegawa, Fujito Numano, Hisanori Haniu, Kenichi Watanabe, Makoto Uchiyama, Akihiko Saitoh

    Pediatric cardiology   34 ( 8 )   1992 - 5   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Two cases of coronary aneurysm developed in the late period after Kawasaki disease (KD). Case 1 involved a 13-year-old boy who had aneurysms develop after a diagnosis of complete regression. Case 2 involved a 29-year-old man who had a new aneurysm develop after he was older than 20 years. Physicians need to be aware that coronary aneurysms can develop in patients with antecedent KD even after regression or in adulthood.

    DOI: 10.1007/s00246-012-0543-x

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  • インフルエンザB感染によるplastic bronchitisの1例

    大田 倫美, 吉田 咲子, 笠原 靖史, 細貝 亮介, 岩渕 晴子, 今井 千速, 齋藤 玲子, 齋藤 昭彦

    日本小児科学会雑誌   116 ( 12 )   1939 - 1939   2012年12月

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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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  • SHOX調節領域に微小欠失を同定したTurner徴候を認める女児の1例

    馬場 悠美, 長崎 啓祐, 仁田原 康利, 佐藤 英利, 小川 洋平, 菊池 透, 深見 真紀, 斉藤 昭彦

    日本内分泌学会雑誌   88 ( 3 )   1069 - 1069   2012年12月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • O脚の男児から判明したX染色体優性低リン血症性くる病の一家系

    佐藤 英利, 長崎 啓祐, 小川 洋平, 菊池 透, 深見 真紀, 齋藤 昭彦

    日本内分泌学会雑誌   88 ( 3 )   1060 - 1060   2012年12月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • 過去2年間に新潟県内で発症した発作性寒冷ヘモグロビン尿症7例の臨床的検討

    細貝 亮介, 今井 千速, 笠原 靖史, 吉田 咲子, 岩渕 晴子, 齋藤 昭彦, 渡辺 徹, 阿部 裕樹, 佐藤 紘一, 浅見 恵子, 小川 淳, 渡辺 輝浩, 申 将守, 千葉 高生, 片岡 哲, 佐藤 英利

    日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号   54回・10回・17回   254 - 254   2012年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会  

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  • 血管腫・リンパ管腫(症)に対するプロプラノロール治療の経験

    笠原 靖史, 細貝 亮介, 吉田 咲子, 岩渕 晴子, 今村 勝, 今井 千速, 齋藤 昭彦

    日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号   54回・10回・17回   418 - 418   2012年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会  

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  • Utility of gram stain of endotracheal aspirates on empiric therapy in children with hospital-acquired pneumonia. 査読 国際誌

    Chikara Ogimi, Kensuke Shoji, Tomohiro Katsuta, Yasushi Watanabe, Akihiko Saitoh

    The Journal of infection   65 ( 4 )   368 - 70   2012年10月

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  • PRKAR1A mutation affecting cAMP-mediated G protein-coupled receptor signaling in a patient with acrodysostosis and hormone resistance. 査読 国際誌

    Keisuke Nagasaki, Tomoko Iida, Hidetoshi Sato, Yohei Ogawa, Toru Kikuchi, Akihiko Saitoh, Tsutomu Ogata, Maki Fukami

    The Journal of clinical endocrinology and metabolism   97 ( 9 )   E1808-13   2012年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    CONTEXT: Acrodysostosis is a rare autosomal dominant disorder characterized by short stature, peculiar facial appearance with nasal hypoplasia, and short metacarpotarsals and phalanges with cone-shaped epiphyses. Recently, mutations of PRKAR1A and PDE4D downstream of GNAS on the cAMP-mediated G protein-coupled receptor (GPCR) signaling cascade have been identified in acrodysostosis with and without hormone resistance, although functional studies have been performed only for p.R368X of PRKAR1A. OBJECTIVE: Our objective was to report a novel PRKAR1A mutation and its functional consequence in a Japanese female patient with acrodysostosis and hormone resistance. PATIENT: This patient had acrodysostosis-compatible clinical features such as short stature and brachydactyly and mildly elevated serum PTH and TSH values. RESULTS: Although no abnormality was detected in GNAS and PDE4D, a novel de novo heterozygous missense mutation (p.T239A) was identified at the cAMP-binding domain A of PRKAR1A. Western blot analysis using primary antibodies for the phosphorylated cAMP-responsive element (CRE)-binding protein showed markedly reduced CRE-binding protein phosphorylation in the forskolin-stimulated lymphoblastoid cell lines of this patient. CRE-luciferase reporter assays indicated significantly impaired response of protein kinase A to cAMP in the HEK293 cells expressing the mutant p.T239A protein. CONCLUSIONS: The results indicate that acrodysostosis with hormone resistance is caused by a heterozygous mutation at the cAMP-binding domain A of PRKAR1A because of impaired cAMP-mediated GPCR signaling. Because GNAS, PRKAR1A, and PDE4D are involved in the GPCR signal transduction cascade and have some different characters, this would explain the phenotypic similarity and difference in patients with GNAS, PRKAR1A, and PDE4D mutations.

    DOI: 10.1210/jc.2012-1369

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  • [Diagnosis and treatment of food poisoning in childhood]. 査読

    Tomohiro Oishi, Akihiko Saitoh

    Nihon rinsho. Japanese journal of clinical medicine   70 ( 8 )   1400 - 5   2012年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    There are a few characteristics of food poisoning in childhood compared to the one in adulthood. First, it is necessary to obtain detailed history from caregivers because pediatric patients cannot tell exact food taking history and their symptoms. Second, children, especially in infants and toddlers, have higher extracelluar fluid component in their body compared to adults and have a higher chance to be dehydrated by the symptoms of food poisoning including vomiting and diarrhea. Thus, evaluation and management of dehydration is important for children. Finally, it is critical to understand the treatment indication for children with each infection causing food poisoning given the treatment can be beneficial, or not beneficial, or sometimes harmful.

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  • Current issues with the immunization program in Japan: can we fill the "vaccine gap"? 査読 国際誌

    Akihiko Saitoh, Nobuhiko Okabe

    Vaccine   30 ( 32 )   4752 - 6   2012年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The "vaccine gap" is a term which has been used in Japan to indicate that the current immunization program is behind compared to the programs in other developed countries. The current national immunization program (NIP) which was established under the Japanese Immunization Law includes only six vaccines (eight targeted diseases), and the rest of available vaccines have been categorized as voluntary vaccines, which require out-of-pocket expense in order for the patients to receive them. This has led the vaccination rates for the voluntary vaccines remaining low, and the incidence of the target diseases remaining high. In addition, there are a few domestic rules that exist for immunizations including (1) subcutaneous injection is the standard method of vaccination, (2) the thigh is not considered to be the common site of vaccination in infants, and (3) the intervals of administration of inactivated and live vaccines are strictly determined by law. Along with the "vaccine gap" and the domestic rules, some movements to improve our current NIP are underway; including increased calls to change the NIP from civilians and professionals, the establishment of a group by the representatives from 13 medical professional societies asking the government to consider the immunization policy a "national policy" and seeking the establishment of a new and reorganized national immunization technical advisory group (NITAG). In addition, the Vaccination Subcommittee of Health Sciences Council was formed in the government to reform the current Immunization Law and NIP, which established a new national program for three voluntary vaccines funded by a temporary budget. We hope these new movements will fill the "vaccine gap" and that the NITAG will help ensure that vaccine policy becomes a national policy, and will provide necessary vaccinations without out-of-pocket expense to protect children in Japan from vaccine preventable diseases.

    DOI: 10.1016/j.vaccine.2012.04.026

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  • Safety and persistence of immunological response 6 months after intramuscular vaccination with an AS03-adjuvanted H1N1 2009 influenza vaccine: an open-label, randomized trial in Japanese children aged 6 months to 17 years. 査読 国際誌

    Akihiko Saitoh, Akira Nagai, Kazuyoshi Tenjinbaru, Ping Li, David W Vaughn, François Roman, Tatsuo Kato

    Human vaccines & immunotherapeutics   8 ( 6 )   749 - 58   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This study evaluated the long-term persistence of immune response and safety of two doses of an A/California/7/2009 H1N1 pandemic influenza vaccine adjuvanted with AS03 (an α-tocopherol oil-in-water emulsion-based Adjuvant System) in Japanese children (NCT01001169). Sixty healthy subjects aged 6 mo-17 y were enrolled (1:1) into two study groups to receive 21 d apart, two doses of 1.9 µg haemagglutinin [HA]+AS03B (5.93 mg α-tocopherol) vaccine (6 mo-9 y) and 3.75 µg HA+AS03A (11.86 mg α-tocopherol) vaccine (10-17 y), respectively. Immunogenicity data (by haemagglutination inhibition [HI] and microneutralisation assays) to six months after the first vaccine dose are reported here. It was observed that following Dose 2, the HI immune response against the vaccine homologous strain induced by the two different dosages of the AS03-adjuvanted vaccine met and exceeded the US and European regulatory guidance criteria for pandemic influenza vaccines (seroprotection rate[SPR]/seroconversion rate[SCR]: 100%/100%; geometric mean fold rise GMFR: 146.8/57.1). Further, the immune response persisted for at least six months after the first vaccine dose wherein these regulatory criteria were still met (SPR: 100%/100%; SCR: 96.4%/89.7%; GMFR: 25.3/23.5). The neutralising antibody response was comparable to the HI immune response at Day 42 (vaccine response rate [VRR]: 100%/100%) and at Day 182 (VRR: 96.4%/82.8%). Overall, both vaccine dosages had a clinically acceptable safety profile. Thus, two doses of a 1.9 µg or 3.75 µg HA AS03-adjuvanted H1N1 2009 pandemic influenza vaccine in children aged 6 mo-17 y induced strong immune responses against the vaccine homologous strain that persisted for at least six months after the first vaccine dose.

    DOI: 10.4161/hv.19684

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  • Discrepancy between human T-cell lymphotropic virus type I screening test and confirmatory tests in non-endemic areas. 査読 国際誌

    Masachi Hanaoka, Takahiko Kubo, Akihiko Saitoh

    The journal of obstetrics and gynaecology research   38 ( 5 )   793 - 6   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: The purpose of this study was to examine the seroprevalence of human T-lymphotropic virus (HTLV)-I among pregnant women at our institution in Tokyo, Japan, which is a non-endemic area, and to investigate the results of Western blotting among pregnant women who had obtained positive results from a screening test. MATERIAL AND METHODS: The seroprevalence of HTLV-I was retrospectively reviewed in 11,352 pregnant women who gave birth at the National Center for Child Health and Development in Tokyo, Japan, between 2002 and 2009. For the screening test, a chemiluminescent enzyme immunoassay was performed followed by a confirmatory Western blot test. RESULTS: The overall positive rate for the screening test was 0.33% (37/11,352). Western blot testing was performed in 36 of these 37 cases. Only nine patients (25%) were positive for HTLV-I by Western blot testing, seven patients (19%) were indeterminate, and 20 patients (56%) were negative. CONCLUSIONS: In this study (carried out in a non-endemic area), the percentage of patients with a positive result from the screening test who were confirmed to be true carriers was significantly low, differing from endemic areas.

    DOI: 10.1111/j.1447-0756.2011.01786.x

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  • Identification and validation of a gene expression signature that predicts outcome in malignant glioma patients. 査読 国際誌

    Atsushi Kawaguchi, Naoki Yajima, Yoshihiro Komohara, Hiroshi Aoki, Naoto Tsuchiya, Jumpei Homma, Masakazu Sano, Manabu Natsumeda, Takeo Uzuka, Akihiko Saitoh, Hideaki Takahashi, Yuko Sakai, Hitoshi Takahashi, Yukihiko Fujii, Tatsuyuki Kakuma, Ryuya Yamanaka

    International journal of oncology   40 ( 3 )   721 - 30   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated with survival. We investigated whether genes selected using random survival forests model could be used to define subgroups of gliomas objectively. RNAs from 50 non-treated gliomas were analyzed using the GeneChip Human Genome U133 Plus 2.0 Expression array. We identified 82 genes whose expression was strongly and consistently related to patient survival. For practical purposes, a 15-gene set was also selected. Both the complete 82 gene signature and the 15 gene set subgroup indicated their significant predictivity in the 3 out of 4 independent external dataset. Our method was effective for objectively classifying gliomas, and provided a more accurate predictor of prognosis. We assessed the relationship between gene expressions and survival time by using the random survival forests model and this performance was a better classifier compared to significance analysis of microarrays.

    DOI: 10.3892/ijo.2011.1240

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  • A universal preemptive therapy for cytomegalovirus infections in children after live-donor liver transplantation. 査読 国際誌

    Akihiko Saitoh, Seisuke Sakamoto, Akinari Fukuda, Takanobu Shigeta, Toshihiko Kakiuchi, Shinya Kamiyama, Tomohiro Katsuta, Kensuke Shoji, Chikara Ogimi, Mureo Kasahara

    Transplantation   92 ( 8 )   930 - 5   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Cytomegalovirus (CMV) infection remains the most common and critical viral infection that occurs after liver transplantation (LT). The current set of guidelines recommends prophylaxis over a preemptive therapy for pediatric LT; however, the data regarding the optimal approach after LT in children are limited. METHODS: We conducted a universal preemptive therapy for CMV infection in 113 children (median: 16 months) after live-donor LT at the largest pediatric LT center in Japan between November 2005 and August 2009. CMV-pp65 antigenemia was monitored weekly regardless of the subjects' CMV serostatus after LT, and ganciclovir therapy was initiated when CMV-pp65 antigenemia was positive. RESULTS: The overall success rate of LT was 91.7%. CMV-pp65 antigenemia became positive in 37 (33%) recipients, and the positivity with their CMV serostatus was as follows: donor (D)+/recipient (R)-: 62%, D+/R+: 36%, D-/R+: 11%, and D-/R-: 8%. Among the D+/R- (n=29) and D+/R+ (n=44) recipients, 38% (n=11) and 64% (n=28) recipients were able to avoid the use of ganciclovir, respectively. Human CMV disease was documented in six (5%) recipients, and they were successfully treated with ganciclovir without any sequelae. CONCLUSIONS: A universal preemptive therapy for CMV infection after live-donor LT was successful for reducing the use of antiviral agents and for controlling CMV infection and disease in children.

    DOI: 10.1097/TP.0b013e31822d873d

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  • [Haemophilus influenzae type b vaccine]. 査読

    Tomohiro Katsuta, Akihiko Saitoh

    Nihon rinsho. Japanese journal of clinical medicine   69 ( 9 )   1589 - 93   2011年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Haemophilus influenzae type b (Hib) vaccine has been included in the national Immunization Program in more than 120 countries around the world and its effectiveness and safety have been confirmed. In Japan, Hib vaccine was recently licensed in December 2008. Because it has included in the category of voluntary vaccine and the burden of out-of-pocket expense is a major concern for caregivers, payment coverage through the local government funded by the temporal national budget has been initiated since November 2010. It is important to make an effort to fill the "vaccine gap" between Japan and other developed countries and increase a vaccine coverage rate including Hib vaccine to decrease vaccine preventable diseases in Japanese children.

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  • Complete atrioventricular block as a complication of varicella in children. 査読 国際誌

    Tomohiro Katsuta, Hitoshi Kato, Yukihiro Kaneko, Masahide Kaneko, Yasushi Misaki, Mitsutoshi Kimura, Kensuke Shoji, Hiro Nakao, Akihiko Saitoh

    The Pediatric infectious disease journal   30 ( 5 )   445 - 6   2011年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Although varicella is a benign and self-limited disease in children, serious complications can occur. We herein report a case of a 15-month-old boy who required a permanent pacemaker because of complete atrioventricular block as a complication of varicella. Universal vaccination is warranted to prevent such a potentially fatal complication in Japan where varicella is still endemic.

    DOI: 10.1097/INF.0b013e3182011286

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  • Immunogenicity of influenza vaccine in children with pediatric rheumatic diseases receiving immunosuppressive agents. 査読 国際誌

    Chikara Ogimi, Risa Tanaka, Akihiko Saitoh, Tsutomu Oh-Ishi

    The Pediatric infectious disease journal   30 ( 3 )   208 - 11   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Children with rheumatic diseases receiving immunosuppressive therapy are a high-risk group for influenza virus infection; however, few data are available regarding the efficacy and safety of influenza vaccine for those individuals. METHODS: This was a prospective study evaluating the immunogenicity and safety of influenza vaccine in 49 children (mean ± standard deviation: 12.1 ± 4.8 years, age range: 0-21 years) with pediatric rheumatic diseases including juvenile idiopathic arthritis (n = 23), systemic lupus erythematosus (n = 12), juvenile dermatomyositis (n = 6), and others (n = 8), who were receiving immunosuppressive therapies. A total of 36 healthy children were selected as a control. The influenza virus type-A and B antibody titers were measured using hemagglutinin inhibition before and after the vaccination. RESULTS: There were no significant differences in the percentage of vaccine recipients with an increase in the serum titers ≥ 4× after vaccination (H1N1, H3N2, and B strain) between the 2 groups (P = 0.49, P = 0.25, P = 0.56, respectively), demonstrating similar immunogenicity of the influenza vaccination between patients and control groups. There were no serious adverse effects related to the vaccine in either group. CONCLUSIONS: In the children with pediatric rheumatic diseases receiving immunosuppressive agents, influenza vaccination resulted in serum antibody titers similar to those in the controls without major adverse effects. Such children receiving immunosuppressive therapy are a high-risk group for influenza virus infection, therefore vaccine should be given.

    DOI: 10.1097/INF.0b013e3181f7ce44

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  • Intracellular concentrations of non-nucleoside reverse transcriptase inhibitors and its potential role on apoptosis in peripheral blood mononuclear cells 査読

    Akihiko Saitoh, Dana Dominguez, Tristan M. Stani, Steven Rossi, Edmund Capparelli, Stephen A. Specter

    Journal of Antivirals and Antiretrovirals   3 ( 2 )   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Efavirenz (EFV) and nevirapine (NVP) are non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are frequently used in combination with other antiretrovirals for the treatment of HIV-infected persons. Little information is available regarding the intracellular concentrations (ICs) of EFV and NVP in peripheral blood mononuclear cells (PBMCs) and its potential role for cellular toxicity. Methods: PBMCs from healthy adult donors were treated with or without the mean peak steady-state levels (Cmax) of EFV (12.4μM) and NVP (17.0μM) in human plasma during antiretroviral therapy multiplied by 0.5,1.0, 2.0 and 4.0. After 48 hr treatment, ICs of EFV and NVP were measured using liquid chromatoagraphy-ion trap/mass spectrometry. The degree of apoptotic cells and mitochondrial membrane potential in PBMCs were measured by flow cytometry. Results: The mean log ICs of ×1.0 Cmax NVP in PBMCs (2.00 ± 0.23 μM) were significantly lower than the one of ×1.0 Cmax EFV (2.95 ± 0.22 μM) (P &lt
    0.01). Similar significant differences of mean log ICs were observed when the concentration of NNRTIs were ×0.5 Cmax (1.62 ± 0.26 μM vs. 2.87 ±0.13 μM, p &lt
    0.01) and ×2.0 Cmax (1.99 ± 0.39 μM vs. 3.11 ± 0.21 μM, P &lt
    0.01). Furthermore, apoptotic PBMCs were lower than PBMC treated with the concentrations of NVP above the plasma Cmax observed clinically in patients as compared to those treated with comparable concentrations of EFV (P &lt
    0.01). Conclusion: These in vitro data suggest that ICs of NVP in PBMCs are significantly lower than ICs of EFV in PBMC and are also associated with less apoptotic PBMCs. The clinical relevance of this observation remains to be elucidated. © 2011 Saitoh A, et al.

    DOI: 10.4172/jaa.1000029

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  • 【小児内分泌学の進歩2010】臨床研究(肥満、糖尿病) 日本人肥満小児におけるBNPおよびNT-proBNPの検討

    菊池 透, 長崎 啓祐, 小川 洋平, 樋浦 誠, 阿部 裕樹, 田中 幸恵, 佐藤 英利, 鈴木 博, 内山 聖, 齋藤 昭彦

    ホルモンと臨床   58 ( 12 )   1077 - 1080   2010年12月

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    記述言語:日本語   出版者・発行元:(有)医学の世界社  

    肥満小児を対象にNT-proBNPとBNPと肥満の代謝異常の指標との関連を検討した。肥満小児108例を対象に、肥満度、腹囲、血圧、脈拍、体脂肪率、腹部エコーによる最大腹壁前脂肪厚(Pmax)および最小皮下脂肪厚(Smin)を測定した。男子+58.6%、女子+55.8%であり、高度肥満小児が多かった。BNP、NT-proBNPは男子が女子に比し高値傾向であった。体脂肪率、インスリン、HOMA-Rは女子が男子に比し高値であった。BNP(log変換)、NT-proBNP(log変換)と各因子との性別で補正した回帰分析で、BNPは、腹囲、Pmax、インスリン、HOMA-R、アルドステロンと負の相関、Totalアディポネクチンと正の相関があった。NT-proBNPは、Totalアディポネクチンと負の相関がみられた。

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  • Is a 6-week course of ganciclovir therapy effective for chorioretinitis in infants with congenital cytomegalovirus infection? 査読 国際誌

    Kensuke Shoji, Naoki Ito, Yushi Ito, Naoki Inoue, Shingo Adachi, Takuya Fujimaru, Tomoo Nakamura, Sachiko Nishina, Noriyuki Azuma, Akihiko Saitoh

    The Journal of pediatrics   157 ( 2 )   331 - 3   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Effective treatment for chorioretinitis caused by congenital cytomegalovirus (CMV) infection remains unknown. We report an infant with congenital CMV infection, who required a 6-month course of antiviral therapy to control his chorioretinitis. Long-term treatment may be necessary for managing congenital CMV-associated chorioretinitis.

    DOI: 10.1016/j.jpeds.2010.02.020

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  • CYP2C19 genetic variants affect nelfinavir pharmacokinetics and virologic response in HIV-1-infected children receiving highly active antiretroviral therapy. 査読 国際誌

    Akihiko Saitoh, Edmund Capparelli, Francesca Aweeka, Elizabeth Sarles, Kumud K Singh, Andrea Kovacs, Sandra K Burchett, Andrew Wiznia, Sharon Nachman, Terence Fenton, Stephen A Spector

    Journal of acquired immune deficiency syndromes (1999)   54 ( 3 )   285 - 9   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The objective of this research was to identify the impact of genetic variants of P-glycoprotein (ABCB1) and cytochrome P450 (CYP) on nelfinavir pharmacokinetics and response to highly active antiretroviral therapy (HAART) in HIV-1-infected children. METHODS: HIV-1-infected children (n = 152) from Pediatric AIDS Clinical Trial Group 366 or 377 receiving nelfinavir as a component of HAART were evaluated. Genomic DNA was assayed for ABCB1 and CYP genetic variants using real-time polymerase chain reaction Nelfinavir oral clearance (CL/F), M8 to nelfinavir ratios, CD4 T cells, and HIV-1-RNA were measured during HAART. RESULTS: Nelfinavir CL/F and M8 to nelfinavir ratios were significantly associated with the CYP2C19-G681A genotypes (P < 0.001). Furthermore, the CYP2C19-G681A genotype was related to virologic responses at week 24 (P = 0.01). A multivariate analysis demonstrated that age (P = 0.03), concomitant protease inhibitor use (P < 0.001), and the CYP2C19-G681A genotype (P < 0.001) remained significant covariates associated with nelfinavir CL/F. CONCLUSIONS: CYP2C19 genotypes altered nelfinavir pharmacokinetics and the virologic response to HAART in HIV-1-infected children. These findings suggest that CYP2C19 genotypes are important determinants of nelfinavir pharmacokinetics and virologic response in HIV-1-infected children.

    DOI: 10.1097/QAI.0b013e3181bf648a

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  • Bifidobacterium septicemia associated with postoperative probiotic therapy in a neonate with omphalocele. 査読 国際誌

    Akira Ohishi, Shigehiro Takahashi, Yushi Ito, Yoshihisa Ohishi, Keiko Tsukamoto, Yukiko Nanba, Naoki Ito, Satsuki Kakiuchi, Akihiko Saitoh, Masami Morotomi, Tomoo Nakamura

    The Journal of pediatrics   156 ( 4 )   679 - 81   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report the one case of sepsis caused by Bifidobacterium breve administered as probiotic therapy. Probiotics can be a potential cause of an invasive disease and should be used with care in vulnerable patients.

    DOI: 10.1016/j.jpeds.2009.11.041

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  • Impact of nucleoside reverse transcriptase inhibitors on mitochondrial DNA and RNA in human skeletal muscle cells. 査読 国際誌

    Akihiko Saitoh, Richard H Haas, Robert K Naviaux, Neurita G Salva, Justine K Wong, Stephen A Spector

    Antimicrobial agents and chemotherapy   52 ( 8 )   2825 - 30   2008年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We previously reported that 2',3'-dideoxyinosine (didanosine, or ddI) significantly altered mitochondrial DNA (mtDNA) in peripheral blood mononuclear cells in human immunodeficiency virus type 1 (HIV-1)-infected children who had undetectable plasma HIV-1 RNA for more than 2 years while receiving highly active antiretroviral therapy. This research examines the in vitro effects of nucleoside reverse transcriptase inhibitors (NRTIs) on mitochondria of human skeletal muscle cells (HSMCs), including myoblasts and differentiated myotubes. mtDNA, mitochondrial RNA (mtRNA), and mRNA levels for nuclear mitochondrial regulatory factors were quantified in vitro using HSMCs, including myoblasts and differentiated myotubes, treated with NRTIs singly and in combination. After 5 days of treatment, mtDNA was significantly decreased in myoblasts and myotubes treated with ddI (P < 0.001 and P = 0.01, respectively) and ddI-containing regimens (P < 0.001 and P < 0.001, respectively) compared to levels in untreated cells. mtRNA (MTCYB) was also significantly decreased in the myoblasts and myotubes treated with ddI (P = 0.004) and ddI-containing regimens (P < 0.001). Regardless of the NRTI regimens examined, NRTI combinations significantly decreased mtRNA (MTCO3) in myoblasts and myotubes (P = 0.02 and P = 0.01, respectively). No significant differences were observed for nuclear mitochondrial regulatory factor mRNA in myoblasts or myotubes when treated with NRTIs (P > 0.07). ddI and ddI-containing regimens significantly decrease mtDNA and mtRNA in HSMCs, most notably in myoblasts. These findings may be of particular importance in developing countries, where ddI is widely used for first-line treatment of HIV-infected children.

    DOI: 10.1128/AAC.00434-08

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  • Successful use of reduced-dose efavirenz in a patient with human immunodeficiency virus infection: case report and review of the literature. 査読 国際誌

    Mauro S Torno, Mallory D Witt, Akihiko Saitoh, Courtney V Fletcher

    Pharmacotherapy   28 ( 6 )   782 - 7   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Efavirenz, a nonnucleoside reverse transcriptase inhibitor, is a highly effective and widely prescribed antiretroviral agent. It is recommended as first-line treatment of human immunodeficiency virus (HIV) infection. The standard dose of efavirenz is 600 mg/day; however, adverse central nervous system effects limit its use. Few data citing use of efavirenz at lower doses have been published. We describe a 35-year-old man with HIV infection whose virologic suppression was maintained after 18 months of treatment with efavirenz 400 mg/day. Genetic testing for cytochrome P450 (CYP) 2B6 showed that the patient was a heterozygous variant; patients with this polymorphism tend to have higher plasma efavirenz concentrations and slower plasma efavirenz clearance (prolonged elimination half-lives). Therapeutic drug monitoring also supported the dose reduction in this patient. Even with the 400-mg dose, the patient's plasma trough concentrations exceeded the upper limit of the therapeutic range. However, as he remained completely asymptomatic with this dose, no further dose reduction was necessary. This case report provides evidence that reduced efavirenz doses may be effective in the treatment of HIV infection. In addition, this case demonstrates that pharmacogenetic and pharmacokinetic testing combined with therapeutic drug monitoring may be used to guide reduced-dose, efavirenz-based therapy.

    DOI: 10.1592/phco.28.6.782

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  • Clinical outcomes after an unstructured treatment interruption in children and adolescents with perinatally acquired HIV infection. 査読 国際誌

    Akihiko Saitoh, Marc Foca, Rolando M Viani, Susan Heffernan-Vacca, Florin Vaida, Jorge Lujan-Zilbermann, Patricia J Emmanuel, Jaime G Deville, Stephen A Spector

    Pediatrics   121 ( 3 )   e513-21   2008年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: An unstructured treatment interruption in children with perinatally acquired HIV infection is an issue with unresolved significance. The objective of this study was to investigate the actual prevalence and clinical outcomes of a treatment interruption in children and adolescents with perinatally acquired HIV-1 infection. METHODS: Clinical data were analyzed for 72 children and adolescents who had HIV-1 infection and stopped their medications at 4 academic centers in the United States between January 2000 and September 2004. RESULTS: Among 405 patients with perinatal HIV-1 infection, 72 (17.8%) experienced a treatment interruption during the observation period. The mean age of patients at the time of the treatment interruption was 12.8 years, and the mean length of the treatment interruption was 14 months. Medication fatigue was the most common reason for a treatment interruption. The CD4+ T-cell percentage nadir before the treatment interruption did not predict CD4+ T-cell percentage declines during the treatment interruption; however, the CD4+ T-cell percentage gain from nadir to the time of the treatment interruption predicted CD4+ T-cell percentage declines during the treatment interruption. During the median follow-up of 19 months (range: 6-48 months), 48 (67%) patients resumed antiretroviral medications. As expected, there was a continuous CD4+ T-cell percentage decrease and plasma HIV-1 RNA increase during the observation period. Overall, 7 (10%) patients were admitted to the hospital; 2 (3%) patients experienced an AIDS-defining illness. CONCLUSIONS: An unstructured treatment interruption seems to be a major issue for youth with perinatally acquired HIV-1 infection. Patients who experienced the greatest rise in CD4+ T-cell percentage on treatment had the largest CD4+ T-cell percentage decline after the treatment interruption. Close monitoring is required when a treatment interruption occurs in children and adolescents with HIV infection.

    DOI: 10.1542/peds.2007-1086

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  • Effect of Host Genetic Variation on the Pharmacokinetics and Clinical Response of Non-nucleoside Reverse Transcriptase Inhibitors. 査読 国際誌

    Akihiko Saitoh, Stephen A Spector

    Future HIV therapy   2 ( 1 )   69 - 81   2008年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been used widely for treating human immunodeficiency virus type 1 (HIV-1) infected patients as a component of highly active antiretroviral therapy (HAART) and for the prevention of mother-to-child transmission (MTCT). Cytochrome P450 (CYP) 2B6 is an important hepatic isoenzyme responsible for the metabolism of NNRTIs including efavirenz and nevirapine. Recent pharmacogenetic studies have shown that CYP2B6 genetic variants alter hepatic CYP2B6 protein expression and function, and the pharmacokinetics of several CYP2B6 substrates. In particular, the CYP2B6-G516T polymorphism in exon 4 affects the pharmacokinetics of efavirenz. Other studies have shown associations of the CYP2B6-G516T genotype with nevirapine pharmacokinetics and central nervous system adverse effects related to efavirenz use. In total, CYP2B6 genetic variants are important determinants of efavirenz and nevirapine pharmacokinetics . Further studies are needed to identify the associations of CYP2B6 genetic variants with the development of NNRTI resistant viruses.

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  • Impact of nucleoside reverse transcriptase inhibitors on mitochondria in human immunodeficiency virus type 1-infected children receiving highly active antiretroviral therapy. 査読 国際誌

    Akihiko Saitoh, Terence Fenton, Carmelita Alvero, Courtney V Fletcher, Stephen A Spector

    Antimicrobial agents and chemotherapy   51 ( 12 )   4236 - 42   2007年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mitochondrial toxicity induced by nucleoside reverse transcriptase inhibitors (NRTIs) has been reported to be responsible for various adverse effects. The relative impact of NRTIs on the mitochondria of human immunodeficiency virus (HIV) type 1 (HIV-1)-infected children receiving highly active antiretroviral therapy (HAART) is unknown. Mitochondrial DNA (mtDNA) levels were quantified longitudinally from peripheral blood mononuclear cells (PBMCs) in 31 HIV-1-infected children from Pediatric AIDS Clinical Trial Group Study 382 who were receiving HAART, including nelfinavir, efavirenz, and different NRTIs, and who had had undetectable plasma HIV-1 RNA levels for >2 years. The median mtDNA levels in PBMCs increased from 137 copies/cell at the baseline to 179 copies/cell at week 48 (P = 0.01) and 198 copies/cell at week 104 (P < 0.001). Before the initiation of HAART, children who received regimens containing didanosine had mtDNA levels persistently lower than those in children not receiving didanosine (106 versus 140 copies/cell; P = 0.008). During HAART, the median increase in the mtDNA level from the baseline to week 104 was the lowest in children who received regimens containing didanosine (+26 copies/cell) compared to those in children who received other regimens (+79 copies/cell) (P = 0.02). A multivariate analysis also demonstrated that didanosine, as part of HAART, was the only NRTI associated with the change in mtDNA levels (P = 0.007). Children receiving didanosine-containing antiretroviral regimens have the lowest mtDNA levels in PBMCs and may be at greater risk for long-term adverse effects due to mitochondrial toxicity. This may be of particular importance in resource-limited countries where didanosine is widely used for the treatment of HIV-infected children.

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  • Psychosis in a 12-year-old HIV-positive girl with an increased serum concentration of efavirenz. 査読 国際誌

    Elizabeth A Lowenhaupt, Kelly Matson, Bushra Qureishi, Akihiko Saitoh, David Pugatch

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America   45 ( 10 )   e128-30   2007年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Clearance and adverse effects of efavirenz are associated with CYP2B6-G516T polymorphism. Little is known about the prevalence of genotypes and implications for screening in children. We report (to our knowledge, for the first time in a child) the emergence of psychosis in a 12-year old white girl with an increased efavirenz concentration and heterozygous gene polymorphism of the CYP2B6-G516T.

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  • CYP2B6 genetic variants are associated with nevirapine pharmacokinetics and clinical response in HIV-1-infected children. 査読 国際誌

    Akihiko Saitoh, Elizabeth Sarles, Edmund Capparelli, Francesca Aweeka, Andrea Kovacs, Sandra K Burchett, Andrew Wiznia, Sharon Nachman, Terence Fenton, Stephen A Spector

    AIDS (London, England)   21 ( 16 )   2191 - 9   2007年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Cytochrome P450 2B6 (CYP2B6)-G516T genotype is associated with altered activity of hepatic CYP2B6 and efavirenz pharmacokinetics, but the relationship between the CYP2B6-G516T genotype and nevirapine (NVP) pharmacokinetics in plasma and cerebrospinal fluid (CSF) is limited. METHODS: In 126 children who received NVP and protease inhibitors from PACTG 366 and 377 cohorts, CYP2B6 and ATP-binding cassette, sub-family B, member 1 (ABCB1) gene polymorphisms were analyzed using real-time PCR. Plasma NVP pharmacokinetics and clinical data were collected and levels of NVP in CSF were evaluated in children with HIV-related neurologic diseases. RESULTS: NVP oral clearance in children with the CYP2B6-516-T/T genotype (homozygous variant, n = 14) was 1.6 l/h per m2, which was significantly decreased compared to 2.3 l/h per m2 in those with the -G/G (wild type, n = 49, P = 0.002) and 2.1 l/h per m2 in those with the -G/T genotype (heterozygous variants, n = 63, P = 0.008). Furthermore, children with the -T/T genotype had a significant increase in CD4+ T-cell percentage (+9.0%) compared with those with the -G/G (+3.2%, P = 0.01) and -G/T genotype (+5.0%, P = 0.04) from baseline to week 12. The same trend continued at week 24. Although ABCB1-C3435T genotypes did not affect plasma NVP pharmacokinetics (P = 0.39), the NVP CSF: plasma ratios were significantly higher in children with the ABCB1-3435-C/T or -T/T genotypes (0.62, n = 9) in comparison with those with the ABCB1-3435-C/C genotype (0.43, n = 5) (P = 0.01). CONCLUSIONS: The CYP2B6-G516T genotype alters NVP pharmacokinetics and the immunologic response to NVP-containing HAART regimens in children. These data suggest that the CYP2B6-G516T is an important genetic variant that alters the pharmacokinetics and response to HAART regimens containing NVP.

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  • Efavirenz pharmacokinetics in HIV-1-infected children are associated with CYP2B6-G516T polymorphism. 査読 国際誌

    Akihiko Saitoh, Courtney V Fletcher, Richard Brundage, Carmelita Alvero, Terrence Fenton, Karen Hsia, Stephen A Spector

    Journal of acquired immune deficiency syndromes (1999)   45 ( 3 )   280 - 5   2007年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The CYP2B6-G516T polymorphism has been shown to alter plasma efavirenz (EFV) concentrations in adults. The impact of CYP2B6-G516T polymorphisms on EFV concentrations may be different in children because of differences in liver maturation and drug dosage. METHODS: The CYP2B6-G516T polymorphisms were analyzed in 71 HIV-1-infected children receiving highly active antiretroviral therapy (HAART) containing EFV for >or=6 months. EFV pharmacokinetics, toxicity profiles, and viral resistance data were also evaluated. RESULTS: The median oral clearance (CL/F) rate was significantly lower in children with the CYP2B6-516-T/T genotype (3.0 L/h/m2, n=13) than in children with the G/T genotype (5.7 L/h/m2, n=30; P=0.02) or the G/G genotype (7.0 L/h/m2, n=31; P=0.003). In children with the CYP2B6-516-G/G genotype, which is associated with higher expression of hepatic CYP2B6, the clearance rate was significantly higher in younger children (<5 years of age) than in older children (>or=5 years of age) (9.7 L/h/m2 vs. 6.6 L/h/m2; P=0.03). No association was found between CYP2B6-G516T polymorphisms and virologic or immunologic responses, toxicity, or the development of viral resistance against EFV. CONCLUSIONS: CYP2B6-G516T polymorphisms significantly affect the CL/F rate of EFV in children. Changes in hepatic enzyme activity by age may need to be considered when evaluating the impact of genetic variants on antiretroviral pharmacokinetics in children.

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  • Mitochondrial dysfunction: prevention of HIV-1 mother-to-infant transmission outweighs fear. 査読 国際誌

    Stephen A Spector, Akihiko Saitoh

    AIDS (London, England)   20 ( 13 )   1777 - 8   2006年8月

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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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  • Association of CD4+ T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy. 査読 国際誌

    Akihiko Saitoh, Kumud K Singh, Sharsti Sandall, Christine A Powell, Terrence Fenton, Courtney V Fletcher, Karen Hsia, Stephen A Spector

    The Journal of allergy and clinical immunology   117 ( 4 )   909 - 15   2006年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: In a cohort of children receiving highly active antiretroviral therapy (HAART) with sustained plasma HIV-1 RNA < 50 copies/mL, children who reached undetectable RNA after week 8 (slow responders, median: week 20) had higher HIV-1 intracellular DNA (HIV-1 DNA) and equal or greater CD4+ T-lymphocyte counts compared with children who reached undetectable plasma HIV-1 RNA by week 8 (rapid responders) throughout HAART. OBJECTIVE: To determine whether levels of T-cell receptor excision circles (TRECs) could explain the apparent inconsistency between the quantity of HIV-1 DNA and CD4+ T-lymphocyte counts in HIV-1-infected children receiving HAART with sustained virologic suppression. METHODS: T-cell receptor excision circles and HIV-1 DNA and plasma HIV-1 RNA were quantified longitudinally by PCR in 31 children (median age, 5.6 years) with sustained undetectable plasma HIV-1 RNA for >104 weeks of HAART. RESULTS: There was a positive correlation between TREC and HIV-1 DNA during HAART, notably at weeks 48 and 80 (P < .004). During the early stage of HAART, TREC levels positively correlated with CD4+ T-lymphocyte percentages (P < .02) and naive CD4+ T-lymphocyte counts (P < .001) and percentages (P = .05). Median TREC levels were consistently equal or higher in slow responders compared with rapid responders (P < .001) despite slow responders having consistently greater quantities of HIV-1 DNA. CONCLUSION: To maintain adequate levels of CD4+ T-lymphocytes, children with high HIV-1 DNA maintain high levels of TREC while receiving HAART. Thus, a thymic control mechanism is required to maintain new CD4+ T lymphocytes in the presence of persistent virus. CLINICAL IMPLICATIONS: The TREC level is a useful marker of thymic function in HIV-infected children.

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  • Myelomeningocele in an infant with intrauterine exposure to efavirenz. 査読 国際誌

    Akihiko Saitoh, Andrew D Hull, Patricia Franklin, Stephen A Spector

    Journal of perinatology : official journal of the California Perinatal Association   25 ( 8 )   555 - 6   2005年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report a case of myelomeningocele in an infant whose mother was exposed to efavirenz during the first 16 weeks of pregnancy. Although the true risk for myelomeningocele with the use of efavirenz early in pregnancy is still unknown, the findings in humans are consistent with those observed in primates and suggest that efavirenz is a potent teratogen. Thus, we suggest that efavirenz only be prescribed for women of childbearing potential when no other comparable antiretroviral options are available.

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  • An MDR1-3435 variant is associated with higher plasma nelfinavir levels and more rapid virologic response in HIV-1 infected children. 査読 国際誌

    Akihiko Saitoh, Kumud K Singh, Christine A Powell, Terrence Fenton, Courtney V Fletcher, Richard Brundage, Stuart Starr, Stephen A Spector

    AIDS (London, England)   19 ( 4 )   371 - 80   2005年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: The multidrug-resistance transporter gene (MDR1) encoding for P-glycoprotein (P-gp) and genes encoding for isoenzymes of cytochrome P450 (CYP) have an important role in transport and metabolism of antiretroviral agents. This research examined the impact of single nucleotide polymorphisms (SNP) of MDR1 and CYP genes on nelfinavir and efavirenz pharmacokinetics and the response to highly active antiretroviral therapy (HAART) in HIV-1 infected children. METHODS: Seventy-one HIV-1-infected children from PACTG 382 receiving nelfinavir, efavirenz and one or two nucleoside reverse transcriptase inhibitors had genomic DNA from PBMC evaluated for MDR1 and CYP SNP by real-time PCR. Plasma drug concentrations, CD4 lymphocyte counts and HIV-1 RNA were measured during HAART. RESULTS: The frequencies of C/C, C/T and T/T genotypes in the MDR1-3435-C-->T polymorphisms were 44% (n = 31), 46% (n = 33) and 10% (n = 7), respectively. Ninety-one percent of children with the C/T genotype reached plasma HIV-1 RNA < 400 copies/ml by week 8 compared to 59% of children with the C/C genotype (P = 0.01). Children with the C/T genotypes had higher 8 h postdose concentration (P = 0.02) and lower clearance rate (P = 0.04) for nelfinavir compared to those with the C/C genotype. The seven children with the T/T genotype had nelfinavir pharmacokinetics and virologic response similar to those with the C/C genotype. No compensatory polymorphisms were observed between MDR1 and CYP genotypes. CONCLUSIONS: HIV-1 infected children with the MDR1-3435-C/T genotype had more rapid virologic responses to HAART at week 8 with higher plasma nelfinavir concentrations compared to those with the C/C genotype. These findings suggest that P-gp may play an important role in the pharmacokinetics and virologic response to HAART containing nelfinavir.

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  • Prediction of neurologic sequelae in childhood tuberculous meningitis: a review of 20 cases and proposal of a novel scoring system. 査読 国際誌

    Akihiko Saitoh, Alice Pong, Norman J Waecker Jr, John A D Leake, Mark P Nespeca, John S Bradley

    The Pediatric infectious disease journal   24 ( 3 )   207 - 12   2005年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Despite effective antituberculous medications, the mortality and morbidity remain high in children with tuberculous meningitis (TBM). The traditional clinical staging for TBM developed by Lincoln et al in 1960 has been widely used to predict long term neurologic sequelae (NS). In the current era of critical care medicine and corticosteroid therapy, a new scoring system is needed to predict NS more accurately in children with TBM. METHODS: We reviewed all available cases of TBM in San Diego, CA, during 1991-2001 retrospectively, and we developed a novel scoring system to predict NS in children with TBM. We assessed a tuberculous meningitis acute neurologic (TBAN) score at day 0 and on day 3 of hospitalization, to compare children who subsequently developed severe NS with those who did not. RESULTS: Among 20 children with TBM, 7 children developed severe NS and 1 child died during hospitalization. The TBAN score was higher on day 0 in those with severe NS (5.5 versus 2.0, P = 0.09), and the difference became statistically significant by day 3 of hospitalization (5.5 versus 0.0, P = 0.02). Sensitivity and specificity of the TBAN score (> or =4) on day 0 (75 and 92%) and day 3 (88 and 100%) to predict severe NS were superior to the traditional clinical staging system on day 0 (63 and 58%). CONCLUSIONS: The TBAN score is an objective marker for predicting severe NS in children with TBM.

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  • Acute disseminated encephalomyelitis associated with enteroviral infection. 査読 国際誌

    Akihiko Saitoh, Mark H Sawyer, John A D Leake

    The Pediatric infectious disease journal   23 ( 12 )   1174 - 5   2004年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A case of acute disseminated encephalomyelitis in 13-year-old boy associated with enterovirus is described. The patient had symptoms of severe headache and photophobia for 2 days. Diagnosis was made on the basis of diffuse high intensity white matter lesions in the left frontoparietal region seen on magnetic resonance imaging, and positive enterovirus polymerase chain reaction in cerebrospinal fluid. His symptoms improved substantially without specific therapy, and he recovered without neurologic sequelae.

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  • Treatment of infants coinfected with HIV-1 and cytomegalovirus with combination antiretrovirals and ganciclovir. 査読 国際誌

    Akihiko Saitoh, Rolando M Viani, Rachel D Schrier, Stephen A Spector

    The Journal of allergy and clinical immunology   114 ( 4 )   983 - 5   2004年10月

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    記述言語:英語  

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  • Longitudinal analysis of lymphocyte ratios and HIV-1 intracellular DNA levels in children. 査読 国際誌

    Akihiko Saitoh, Christine A Powell, Terence Fenton, Steven D Douglas, Stuart E Starr, Courtney V Fletcher, Stephen A Spector

    The Journal of infectious diseases   189 ( 7 )   1216 - 20   2004年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The associations between human immunodeficiency virus type 1 (HIV-1) intracellular DNA and immunological markers were analyzed longitudinally for children with sustained, undetectable RNA levels while receiving highly active antiretroviral therapy (HAART) for >2 years. When DNA levels reached a plateau at week 104 of therapy, in contrast to findings for adults, there was no correlation between the CD4(+) : CD8(+) ratio and DNA levels (r=-0.02; P=.95), and naive CD4(+)CD45RA(+) lymphocytes predominated. These data suggest that the increased proportion of naive lymphocytes found in children are less susceptible to HIV-1 infection than are the memory lymphocytes that dominate immune reconstitution in adults.

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  • Fulminant bacterial meningitis complicating sphenoid sinusitis. 査読 国際誌

    Akihiko Saitoh, Bernard Beall, Victor Nizet

    Pediatric emergency care   19 ( 6 )   415 - 7   2003年12月

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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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  • Persistence of human immunodeficiency virus (HIV) type 1 DNA in peripheral blood despite prolonged suppression of plasma HIV-1 RNA in children. 査読 国際誌

    Akihiko Saitoh, Karen Hsia, Terence Fenton, Christine A Powell, Cindy Christopherson, Courtney V Fletcher, Stuart E Starr, Stephen A Spector

    The Journal of infectious diseases   185 ( 10 )   1409 - 16   2002年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Human immunodeficiency virus (HIV) type 1 DNA in peripheral blood mononuclear cells (PBMC) was quantified in 31 children who received efavirenz, nelfinavir, and 1 or 2 nucleoside reverse-transcriptase inhibitors for > or =2 years and in whom undetectable plasma HIV-1 RNA levels (< 50 copies/mL) were sustained, to determine the usefulness of HIV-1 DNA as a marker of virus suppression. The median baseline HIV-1 DNA level was 750 copies/10(6) PBMC. After initiation of highly active antiretroviral therapy (HAART), HIV-1 DNA levels decreased gradually, reaching a plateau from week 80 through week 104 (median HIV-1 DNA level, 263 copies/10(6) PBMC). Children who had plasma HIV-1 RNA levels < 50 copies/mL after receiving HAART for 8 weeks (n=16) had persistently lower quantities of intracellular HIV-1 DNA than children whose HIV-1 RNA levels reached < 50 copies/mL after 8 weeks of HAART (n=15). The median half-life for intracellular HIV-1 DNA was 60 weeks. Thus, despite prolonged maintenance of undetectable levels of plasma HIV-1 RNA, HIV-1 DNA remains detectable in PBMC of children and may be a useful marker of further virus suppression.

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  • A case report of Stevens‐Johnson syndrome with Mycoplasma pneumoniae infection 査読

    AKIHIKO SAITOH, TATSUO OHYA, SHIGEHIKO YOSHIDA, RYOHTA HOSOYA, KOZO NISHIMURA

    Pediatrics International   37 ( 1 )   113 - 115   1995年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We encountered an 8 year old boy who suffered from Stevens‐Johnson syndrome with Mycoplasma pneumoniae infection. He had multiple erythema with vesicles in oral mucosa, and on his palms and feet, trunk and genital regions. We treated him with prednisolone (1 mg/kg per day) and antibiotics. His skin lesions improved dramatically, and a persistent fever and toxic general condition also showed dramatic improvement. Although the use of corticosteroids for Stevens‐Johnson syndrome has recently been controversial, we thought that administration of corticosteroids was an effective treatment for some selective cases of Stevens‐Johnson syndrome. The patient reported in this study had many beneficial effects in response to corticosteroid treatment. 1995 Japan Pediatric Society

    DOI: 10.1111/j.1442-200X.1995.tb03701.x

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書籍等出版物

  • ウイルスを知る

    滝川, 一, 矢冨, 裕, 深川, 雅史, 四柳, 宏, 長尾, 美紀, 川名, 敬, 石井, 健(免疫学), 齋藤, 昭彦, 石田, 直, 大曲, 貴夫, パパイヤ, 鈴木

    H.U.グループホールディングス,ニッセイエブロ  2022年7月 

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    総ページ数:193p   記述言語:日本語

    CiNii Books

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  • レジデントのための小児感染症診療マニュアル : principles & practice

    齋藤, 昭彦

    医学書院  2022年3月  ( ISBN:9784260042949

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    総ページ数:xv, 867p   記述言語:日本語

    CiNii Books

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  • 病院での感染症をどう予防するか : プロジェクトの立ち上げと現場で役立つ対策

    Saint, Sanjay, Krein, Sarah L., Stock, Robert W., 佐々木, 重喜, 齋藤, 昭彦, 徳田, 安春, 坂本, 史衣

    西村書店東京出版編集部  2017年10月  ( ISBN:9784890134793

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    総ページ数:119p   記述言語:日本語

    CiNii Books

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  • ネルソン小児感染症治療ガイド

    Bradley, John S. (John Sterling), Nelson, John D., 新潟大学小児科学教室, 齋藤, 昭彦

    医学書院  2017年1月  ( ISBN:9784260028240

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    総ページ数:xv, 295p   記述言語:日本語

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  • 感染症診療update

    岩田, 敏(予防医学), 岩本, 愛吉, 大曲, 貴夫, 齋藤, 昭彦, 竹末, 芳生, 河野, 茂, 跡見, 裕

    日本医師会,協和企画(発売)  2014年11月  ( ISBN:9784877941666

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    総ページ数:424p   記述言語:日本語

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受賞

  • 特別研究者賞

    2010年9月   アジア小児感染症学会  

    齋藤昭彦

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  • 新潟日報文化賞(学術部門)

    2023年11月   子どもたちを新興・再興感染症から守るための研究

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  • 小児医学川野賞

    2021年3月   公益財団法人川野小児医学奨学財団   新生児・早期乳児のパレコウイルス A3 感染症の病態生理の解明

    齋藤昭彦

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  • 2017年ベスト査読者賞

    2018年6月   Pediatric International(国際誌)  

    齋藤昭彦

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  • 学長教育賞

    2014年3月   新潟大学  

    齋藤昭彦

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  • 2009-2010年 特別教育賞

    2010年3月   国立成育研究センター  

    齋藤昭彦

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  • 2008-2009年 特別教育賞

    2009年3月   国立成育研究センター  

    齋藤昭彦

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  • 国際大使賞

    2009年3月   米国医療疫学学会  

    齋藤昭彦

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  • 有壬若手研究奨励賞

    2008年6月  

    齋藤昭彦

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  • ベストレジデント賞

    1993年3月  

    齋藤昭彦

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共同研究・競争的資金等の研究

  • 医療系学生のワクチンリテラシーを高める予防接種教育プログラムの開発

    研究課題/領域番号:22K10728

    2022年4月 - 2025年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    齋藤 あや, 勝田 友博, 齋藤 昭彦, 石川 洋一, 奥 裕美

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • 小児のパレコウイルスA3感染症-世界における疫学と流行・重症化因子の解明-

    研究課題/領域番号:21KK0166

    2021年10月 - 2027年3月

    制度名:科学研究費助成事業 国際共同研究加速基金(国際共同研究強化(B))

    研究種目:国際共同研究加速基金(国際共同研究強化(B))

    提供機関:日本学術振興会

    齋藤 昭彦, 渡邉 香奈子, 相澤 悠太, 泉田 亮平

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    配分額:18980000円 ( 直接経費:14600000円 、 間接経費:4380000円 )

    本研究では、パレコウイルスA3(PeVA3)の疫学を世界的規模で調査し、その遺伝子解析と流行予測を行うことを目的としている。この国際共同研究を開始する準備として、まずは、共同研究者に各国のPeV-A3流行状況を確認したが、異なる大陸5か国からは、いずれもこの2年間、流行が起こっていないことが明確となった。これまで、各国において、PeVA3は新生児、早期乳児において、2-3年おきの流行が見られていたが、COVID-19のパンデミックの影響で、感染のパターンが異なってきていることが明確となった。これは、COVID-19のパンデミックによる人流の低下、感染対策の徹底などが影響していると考えられた。
    また、今後流行が見られた際には、世界から集められた検体を用いてウイルスの遺伝子解析を実施する予定であるが、その前段階として、1997年から2021年までに新潟県で採取されたPeVA3の遺伝子解析と系統樹解析を行い、その進化の過程を解析した。その結果、過去に主流を占めていた系統のウイルスは既に消失し、近年は、新しい2つの系統のウイルスが交互に流行していることが明確になった。これらの流行した系統と患者の臨床症状、重症度には相関は見られなかった。これは、今後流行するPeV-A3の遺伝子解析を行う上で、重要な基礎的情報となるであろう。
    尚、COVID-19の流行により、海外渡航はできない状況が続き、計画通り、研究代表者、分担者の今年度の海外渡航は行わなかった。

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  • ヒトパレコウイルス3型の受容体同定と感染重症化機序の解明

    研究課題/領域番号:19K08294

    2019年4月 - 2022年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    渡邉 香奈子, 齋藤 昭彦, 樋口 雅也

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    ヒトパレコウイルス3型(HPeV-3)は、多くの場合、軽微な胃腸炎や上・下気道炎などをきたす乳幼児感染症の原因ウイルスである。しかしながら、HPeV-3が新生児あるいは早期乳児に感染すると、敗血症様症候群、脳脊髄膜炎などの重症感染症を発症し、4カ月未満児の入院率は7.5人/1,000人である。HPeV3は腸管上皮もしくは気道上皮細胞などに感染すると考えられているが、感染機構、宿主細胞域の全体像、感染の組織特異性および重症感染症を引き起こす分子機構は不明である。
    本研究ではHPeV-3のウイルス受容体を同定することによって、宿主細胞域や組織特異性を明らかにする。更に、同定した受容体を発現する動物モデルを樹立し、個体レベルでのHPeV-3感染症の分子機構を解析することにより、新生児において重症化する病態の全容解明を目指している。
    令和元年度は、HPeV-3高感受性LLC-MK2細胞から平均1.8kbフラグメントのcDNAライブラリーを作製した。また、このcDNAライブラリーの選別に用いるUnaG(緑色蛍光タンパク質)発現組換えHPeV-3(HPeV-3-UnaG)も作製した。HPeV-3-UnaGは細胞に感染して、ウイルスタンパク質の合成が始まるとEGFPが発現する組換えウイルスである。HPeV-3高感受性LLC-MK2細胞のcDNAライブラリーを1つのプールが約1,000クローンを含むプールとなるように調整し、150プールに分割した。合計約15万クローンのcDNAについてHPeV-3-UnaGを用いて一次スクリーニングを行った。150プールの中から、UnaGの緑色蛍光が観察され陽性となった2つのライブラリープールを選別した。

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  • ヒトパレコウイルス3型に対する有効な治療の検討

    研究課題/領域番号:17H04226

    2017年4月 - 2020年3月

    制度名:科学研究費助成事業 基盤研究(B)

    研究種目:基盤研究(B)

    提供機関:日本学術振興会

    齋藤 昭彦, 渡邉 香奈子, 今井 千速

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    配分額:16900000円 ( 直接経費:13000000円 、 間接経費:3900000円 )

    新生児、早期乳児に重症感染症をきたすパレコウイルスA3(PeV-A3)に対しては、特異的な治療薬が存在しない。我々は、In vitroの実験細胞を用い、抗微生物薬によるPeV-A3への効果の検討を行った。その結果、ヒト免疫グロブリンと幾つかの抗微生物薬にPeV-A3に対する抑制効果が見られた。これらの薬剤は、今後のPeV-A3感染児の治療戦略につながる可能性がある。

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  • 妊娠中のウイルス胎盤感染が児の聴力に与える影響についての研究

    研究課題/領域番号:15K10771

    2015年4月 - 2018年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    守本 倫子, 宮入 烈, 齋藤 昭彦, 中村 浩幸, 泉田 亮平, 枝吉 美奈

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    妊娠中の経胎盤感染を出生後しばらく経過してから後方視的に診断する方法はない。
    しかし我々はDNAウイルスより不安定で断片化している風疹ウイルスRNAを乾燥臍帯より抽出、RT-PCR法にて同定できる方法を確立し、感度80%・特異度100%となった。偽陰性となった検体は、症状が軽くウイルスRNA含有が少ない可能性と、RNAの断片化により検出域から外れてしまった可能性が挙げられた。本法の確立により、今後ウイルス胎盤感染を確実に診断し、将来生じうる障害の予防につなげられることが期待される。

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  • 新生児ヒトパレコウイルス3型感染症発症のメカニズム―移行抗体の役割-

    研究課題/領域番号:26461569

    2014年4月 - 2017年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    齋藤 昭彦, 相澤 悠太, 渡邉 香奈子

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    ヒトパレコウイルス3型(HPeV3)は、新生児と早期乳児に敗血症と脳髄膜炎をきたす重要な新興感染症である。我々は、1)正期産児の臍帯血、2)重篤なHPeV3関連疾患に罹患した45名の新生児と早期乳児を対象にHPeV3に対する中和抗体を測定した。その結果、1)約40%の児で、HPeV3に対する抗体価が低く、2)発症時の抗体価は低値で、その後、生後3、6か月での抗体価はすべての患者で高い値を示した。以上より、移行抗体が、重篤なHPeV3関連の疾患において重要であることが明確となった。

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  • アジアを中心としたインフルエンザウイルスのグローバルな進化と薬剤耐性株の伝播追跡

    研究課題/領域番号:25305014

    2013年4月 - 2016年3月

    制度名:科学研究費助成事業 基盤研究(B)

    研究種目:基盤研究(B)

    提供機関:日本学術振興会

    齋藤 玲子, 齋藤 昭彦, 藤井 雅寛, 菖蒲川 由郷, 長谷川 剛, 齋藤 孔良, 日比野 亮信, 近藤 大貴, 小田切 崇, 鈴木 宏, 田村 務, ダパット・クライド, ヤデナ・チョー, イーイーミン, ネイ・リン, テーテーティン, キン・イー・ウー, ラ・ラ・チョー, ロハイザ・マフッド・ハッサン, シャムスル・アズハー・シャー, グエン・レ・カン・ハン, グエン・フオン・アイン, レ・キン・マイ, ザラケット・ハッサン, ドバイボ・ガッサン

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    配分額:17680000円 ( 直接経費:13600000円 、 間接経費:4080000円 )

    ミャンマー、マレーシア、ベトナム、レバノンにおいてインフルエンザのサーベイランスを行った。3年間で合計1820件のインフルエンザ疑い検体から、456件のインフルエンザウイルスを分離した(A/H1N1pdm09 136件、A/H3N2 169件、B型 151件)。A/H1N1pdm09は、日本/ミャンマーを含めたアジアと、レバノンに代表されるヨーロッパをウイルスが双方向に行き来する傾向があり、A/H3N2は、ミャンマーで、日本やレバノンより半年早く新しい遺伝子型の株が出現していた。B型は変異が少なく伝播方向の推定が難しかった。3年間を通じ4ヶ国でノイラミニダーゼ阻害剤耐性株は検出されなかった。

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担当経験のある授業科目

  • 医学英語II

    2023年
    -
    現在
    機関名:新潟大学

  • 小児疾病治療論

    2023年
    -
    現在
    機関名:新潟大学

  • 臓器別講義・演習I

    2023年
    -
    現在
    機関名:新潟大学

  • 医学序説 I

    2022年
    -
    現在
    機関名:新潟大学

  • 臨床実習IIA(clinical clerkship)

    2022年
    -
    現在
    機関名:新潟大学

  • 医学英語I

    2021年
    -
    現在
    機関名:新潟大学

  • 医学序説 II

    2021年
    機関名:新潟大学

  • 臨床医学講義(集中)

    2020年
    -
    現在
    機関名:新潟大学

  • 臓器別講義・演習Ⅱ

    2020年
    -
    現在
    機関名:新潟大学

  • 統合臨床医学

    2020年
    -
    現在
    機関名:新潟大学

  • 医学序説 I

    2020年
    機関名:新潟大学

  • 疾病の成因と治療Ⅱ

    2014年
    -
    現在
    機関名:新潟大学

▶ 全件表示